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Probable positive effects of the photobiomodulation as an adjunctive treatment in COVID-19: A systematic review
Abstract
Background
COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea in half of the patients and acute respiratory distress syndrome (ARDS) in up to one –third of the cases. Pulmonary edema, neutrophilic infiltration, and inflammatory cytokine release are the pathologic signs of this disease. The anti-inflammatory effect of the photobiomodulation (PBM) has been confirmed in many previous studies. Therefore, this review study was conducted to evaluate the direct effect of PBM on the acute lung inflammation or ARDS and also accelerating the regeneration of the damaged tissues. The indirect effects of PBM on modulation of the immune system, increasing the blood flow and oxygenation in other tissues were also considered.
Methodology
The databases of PubMed, Cochrane library, and Google Scholar were searched to find the relevant studies. Keywords included the PBM and related terms, lung inflammation, and COVID-19 -related signs. Studies were categorized with respect to the target tissue, laser parameters, and their results.
Results
Seventeen related papers were included in this review. All of them were in animal models. They showed that the PBM could significantly decrease the pulmonary edema, neutrophil influx, and generation of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), intracellular adhesion molecule (ICAM), reactive oxygen species (ROS), isoform of nitric oxide synthase (iNOS), and macrophage inflammatory protein 2 (MIP-2)).
Conclusion
Our findings revealed that the PBM could be helpful in reducing the lung inflammation and promoting the regeneration of the damaged tissue. PBM can increase the oxygenation indirectly in order to rehabilitate the affected organs. Thus, the infra-red lasers or light-emitting diodes (LEDs) are recommended in this regard.
... 8 However, the role of PBMT in COVID-19-induced inflammation of the airway and lung remains controversial. 9 PBMT is an innovative option in this area that has been shown to have significant anti-inflammatory effects in treating pain, lymphedema, wound healing, and musculoskeletal injuries. 10 The photo-biological effects of PBMT and their interference with the immune system are very well known. ...
... 8 However, the role of PBMT in COVID-19-induced inflammation of the airway and lung remains controversial. 9 Recently, much literature evaluated PBM's impact on improving the regeneration of damaged tissues. A study by Nejatifard et al demonstrated the clinical efficacy of PBM in COVID-19 progression. ...
... A study by Nejatifard et al demonstrated the clinical efficacy of PBM in COVID-19 progression. 9 Based on their conclusion, PBM is more efficient in the early stages of COVID-19. 9 This should be remembered that interfering factors such as underlying disorders, inflammation severity, and immunodeficiency diseases influence PBM outcome. ...
Background
Different expression of cytokine genes in the body determines the type of immune response (Th1 or Th2), which can play an important role in the pathogenesis of the COVID-19 disease.
Aims
This meta-analysis was conducted to evaluate the probable effect of photobiomodulation (PBMT) therapy on the cytokine’s mRNA expression in the lung.
Methods
We systematically searched indexing databases, including PubMed/Medline, ISI web of science, Scopus, EMBASE, and Cochrane central, using standard terms without language, study region or type restrictions. Studies on using PBM in lung injury modeling with samples collected from lung tissue to observe IL-1β, TNF-α, IL-10, and IL-6 mRNA expression were included. RevMan 5.3 software was used for data analysis and standardized mean difference as effect size.
Results
Of the 438 studies found through initial searches, 17 met the inclusion criteria. The main properties of 13 articles on 384 animals included in this meta-analysis with a wide range of species include rats (n = 10) and rabbits (n = 3). The analysis revealed that PBMT reduced the mRNA expression of TNFα (SMD: −3.70, 95% CI: −6.29, −1.11, P = .005, I ² = 71%) and IL-1β (SMD: −5.85, 95% CI: −8.01, −3.69, P < .00001, I ² = 37%) significantly, but no statistically significant reduction in IL-6 (SMD: −2.89, 95% CI: −5.79, 0.01, P = .05, I ² = 88%) was observed compared with the model controls. Also, PBMT increased IL-10 mRNA expression significantly compared with the model controls (SMD: 1.04, 95% CI: 0.43, 1.64, P = .0008, I ² = 17%).
Conclusion
This meta-analysis revealed that the PBMT utilizes beneficial anti-inflammatory effects and modulation of the immune system on lung damage in animal models and clinical studies. However, animal models and clinical studies appear limited considering the evidence’s quality; therefore, large clinical trials are still required.
... This may be important in the observed decrease of neutrophils with aging [189], the impairment of neutrophils in cardiac diseases [190,191], PD [192][193][194][195] and increasingly in viral load sequelae, including the current COVID-19 pandemic [196]. A recent review supported PBMt as an adjunctive treatment of lung inflammation and for rehabilitating other affected organs by modulating neutrophil influx and inhibiting the macrophage inflammatory protein-2 and thereby reducing pulmonary edema [197]. ...
... Additionally, there are several diseases that involve abnormal neutrophil activation [205][206][207], for example, an abnormal lung response to air-borne toxins such as those found in air pollution, causing the dysfunctional activation of neutrophils [208,209], which may be modulated by PBMt. There is evidence that PBMt can modulate neutrophil activation, both by decreasing excessive neutrophil response and making the neutrophil burst more effective [197,210]. ...
Despite a significant focus on the photochemical and photoelectrical mechanisms underlying photobiomodulation (PBM), its complex functions are yet to be fully elucidated. To date, there has been limited attention to the photophysical aspects of PBM. One effect of photobiomodulation relates to the non-visual phototransduction pathway, which involves mechanotransduction and modulation to cytoskeletal structures, biophotonic signaling, and micro-oscillatory cellular interactions. Herein, we propose a number of mechanisms of PBM that do not depend on cytochrome c oxidase. These include the photophysical aspects of PBM and the interactions with biophotons and mechanotransductive processes. These hypotheses are contingent on the effect of light on ion channels and the cytoskeleton, the production of biophotons, and the properties of light and biological molecules. Specifically, the processes we review are supported by the resonant recognition model (RRM). This previous research demonstrated that protein micro-oscillations act as a signature of their function that can be activated by resonant wavelengths of light. We extend this work by exploring the local oscillatory interactions of proteins and light because they may affect global body circuits and could explain the observed effect of PBM on neuro-cortical electroencephalogram (EEG) oscillations. In particular, since dysrhythmic gamma oscillations are associated with neurodegenerative diseases and pain syndromes, including migraine with aura and fibromyalgia, we suggest that transcranial PBM should target diseases where patients are affected by impaired neural oscillations and aberrant brain wave patterns. This review also highlights examples of disorders potentially treatable with precise wavelengths of light by mimicking protein activity in other tissues, such as the liver, with, for example, Crigler-Najjar syndrome and conditions involving the dysregulation of the cytoskeleton. PBM as a novel therapeutic modality may thus behave as “precision medicine” for the treatment of various neurological diseases and other morbidities. The perspectives presented herein offer a new understanding of the photophysical effects of PBM, which is important when considering the relevance of PBM therapy (PBMt) in clinical applications, including the treatment of diseases and the optimization of health outcomes and performance.
... Recently, several studies have analyzed the possibility of employing the technique of photobiomodulation in the treatment of COVID-19 based on its potential to induce local and systemic effects, significantly decreasing pro-inflammatory cytokines, inflammatory cells, and collagen fiber deposition in the pulmonary parenchyma, enabling the reduction of mortality in patients [22][23][24][25][26][27]. The current scientific literature available contains few experimental studies on the effects of photobiomodulation on COVID-19. ...
... Photobiomodulation is useful for cellular metabolism and to proliferate or improve lung tissue, according to a report by Nejatifarda et al. [26]. They observed significant decreases in pulmonary edema, the neutrophil influx, and the generation of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), intracellular reaction molecule (ICAM), reactive oxygen species (ROS), nitric oxide synthase isoform (iNOS) and macrophage inflammatory protein 2 (MIP-2). ...
Background
COVID-19 disease is caused by SARS-CoV-2 which can trigger acute respiratory syndrome, which presents with dense alveolar and interstitial infiltrates and pulmonary edema, causing severe hypoxemia and significant alteration to pulmonary mechanics with reduced pulmonary compliance. The photobiomodulation technique alters cellular and molecular metabolism, showing promising results regarding the reduction of acute pulmonary inflammation.
Objective
To compare the photomodulation technique using near-infrared LED to conventional respiratory physiotherapy treatment in patients with COVID-19 in reversing acute conditions, reducing hospitalization time, and decreasing the need for oxygen therapy.
Methodology
The cohort was comprised of 30 patients undergoing COVID-19 treatment who were divided and allocated into two equal groups randomly: the LED group (LED), treated with infrared LED at 940 nm and conventional therapy, and the control group (CON), who received conventional treatment (antibiotic therapy for preventing superimposed bacterial infections, and physiotherapy) with LED irradiation off. Phototherapy used a vest with an array of 300 LEDs (940 nm) mounted on a 36 cm × 58 cm area and positioned in the patient's anterior thoracic and abdominal regions. The total power was 6 W, with 15 min irradiation time. Cardiopulmonary functions and blood count were monitored before and after treatment. The patients were treated daily for 7 days. Statistical analysis was conducted using a two-tailed unpaired Student's t-test at a significance level of α = 0.05.
Results
Post-treatment, the LED group showed a reduction in hospital discharge time and a statistically significant improvement for the following cardiopulmonary functions: Partial Oxygen Saturation, Tidal Volume, Maximum Inspiratory, and Expiratory Pressures, Respiratory Frequency, Heart Rate, and Systolic Blood Pressure (p < 0.05). Regarding blood count, it was observed that post-treatment, the LED group presented with significant differences in the count of leukocytes, neutrophils, and lymphocytes.
Conclusion
Photobiomodulation therapy can be used as a complement to conventional treatment of COVID-19, promoting the improvement of cardiopulmonary functions, and minimization of respiratory symptoms.
... Moreover, it increases micro and macro-circulation, thus increasing tissues' oxygen saturation. These improve cellular metabolism and promote faster regeneration or proliferation of the damaged tissue [47]. Furthermore, PBM can photo-dissociate the nitric oxide, which inhibits mitochondrial respiration, thus reversing mitochondrial inhibition [48]. ...
... On the basis of these molecular biological findings, treatment to promote muscle regeneration and energy production is hence considered. Given the ability of PBM to improve cellular metabolism and promote ATP formation [47], irradiation of the affected facial muscles and nerve branches could potentially improve the muscle regeneration and enhance the paralytic condition. Further investigations are required to compare the effects of PBM on different irradiation areas. ...
Bell’s palsy (BP) is a common condition; its incidence rate has increased during the COVID-19 pandemic. The standard treatment for facial nerve palsy includes corticosteroids alone or in combination with antiviral agents. However, the treatment is contraindicated in some patients, including hypertensive or diabetic patients. Also, the medication combination may result in inadequate recovery when complementary and alternative approaches are indicated. This chapter reviewed the literature on managing BP with different types of photobiomodulation (PBM) therapies. Fourteen papers were included. The results show that despite the different kinds of photo energy used, varying laser parameters, and the heterogeneity of patients, the outcome of PBM was similar among studies. Of interest is that acute and subacute BP respond more favorably to PBM than chronic cases. Hence, it is suggested to apply PMB as a complementary treatment in the early stage of the disease to enhance the recovery rate of BP patients. However, the risk of bias in these studies was relatively high. Therefore, further randomized, double-blind placebo-controlled studies are needed to determine the effectiveness of PBM in treating BP.
... This would be useful to combat 232 COVID-19, where the immune response is often delayed yet excessive. PBMT has significant advantages over cortico-233 steroids which have been researched for their anti-inflammatory use against COVID-19 [93], including a lack of side-234 effects and no known interactions with the underlying conditions common in COVID-19 patients. Numerous studies 235 have demonstrated that PBMT reduces pro-inflammatory cytokines and increases anti-inflammatory cytokines in in 236 vivo models [93][94][95]. ...
... PBMT has significant advantages over cortico-233 steroids which have been researched for their anti-inflammatory use against COVID-19 [93], including a lack of side-234 effects and no known interactions with the underlying conditions common in COVID-19 patients. Numerous studies 235 have demonstrated that PBMT reduces pro-inflammatory cytokines and increases anti-inflammatory cytokines in in 236 vivo models [93][94][95]. 237 PBMT also shows multiple effects on reactive oxygen and nitrogen species (RONS). It appears that PBMT may 238 decrease ROS in cells already undergoing oxidative stress, e.g. in animal disease models, but increases ROS production 239 in normal, healthy cells [96]. ...
Researchers from across the world are seeking to develop effective treatments for the ongoing coronavirus disease 2019 (COVID-19) outbreak, which arose as a major public health issue in 2019, and was declared a pandemic in early 2020. The pro-inflammatory cytokine storm, acute respiratory distress syndrome (ARDS), multiple-organ failure, neurological problems, and thrombosis have all been linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fatalities. The purpose of this review is to explore the rationale for using photobiomodulation therapy (PBMT) of the particular wavelength 1068 nm as a therapy for COVID-19, investigating the cellular and molecular mechanisms involved. Our findings illustrate the efficacy of PBMT 1068 nm for cytoprotection, nitric oxide (NO) release, inflammation changes, improved blood flow, and the regulation of heat shock proteins (Hsp70). We propose, therefore, that PBMT 1068 is a potentially effective and innovative approach for avoiding severe and critical illness in COVID-19 patients, although further clinical evidence is required.
... These benefits appear to be related on the photobiomodulation's capacity to reduce or inhibit important substances involved in pain and inflammatory processes [74], leading to an enhanced healing and improved quality of life for patients. A recent systematic review reported that photobiomodulation can significantly decrease the production of pro-inflammatory cytokines and some interleukins, reducing inflammation processes, regenerating damaged tissues [77], and balancing the immune system [76]. ...
... Although the use of photobiomodulation to treat COVID-19 positive patients is promising, further information regarding the different aspects of COVID-19 [75] and randomized clinical trials [77] are required in order to safely state their use and effectiveness. ...
Biophotonics is defined as the combination of biology and photonics (the physical science of the light). It is a general term for all techniques that deal with the interaction between biological tissues/cells and photons (light). Biophotonics offers a great variety of techniques that can facilitate the early detection of diseases and promote innovative theragnostic approaches. As the COVID-19 infection can be transmitted due to the face-to-face communication, droplets and aerosol inhalation and the exposure to saliva, blood, and other body fluids, as well as the handling of sharp instruments, dental practices are at increased risk of infection. In this paper, a literature review was performed to explore the application of Biophotonics approaches in Dentistry focusing on the COVID-19 pandemic and how they can contribute to avoid or minimize the risks of infection in a dental setting. For this, search-related papers were retrieved from PubMED, Scielo, Google Schoolar, and American Dental Association and Centers for Disease Control and Prevention databases. The body of evidence currently available showed that Biophotonics approaches can reduce microorganism load, decontaminate surfaces, air, tissues, and minimize the generation of aerosol and virus spreading by minimally invasive, time-saving, and alternative techniques in general. However, each clinical situation must be individually evaluated regarding the benefits and drawbacks of these approaches, but always pursuing less-invasive and less aerosol-generating procedures, especially during the COVID-19 pandemic.
... In pulmonary inflammation, the increased influx of neutrophils produces high levels of ROS and RNS, damaging the lung tissue ( Figure 2). PBMT can reduce ROS formation [42,43], reduce pulmonary edema, neutrophil influx, and promote lung tissue regeneration and better oxygenation to all related organs [44]. ...
... PBMT can be used as a preventive approach in high-risk, elderly, or comorbid patients receiving pre-treatment PBMT while still at an early stage of the disease [40]. In addition, PBMT can be considered a therapeutic approach in hospitalized patients before their condition worsens enough to require ICU admission [44]. ...
COVID-19 is a viral disease characterized as a pandemic by the World Health Organization in March 2020. Since then, researchers from all over the world have been looking for ways to fight this disease. Many cases of complications arise from insufficient immune responses due to low immunity, with intense release of pro-inflammatory cytokines that can damage the structure of organs such as the lung. Thus, the hypothesis arises that photobiomodulation therapy (PBMT) with the use of a low-level laser (LLLT) may be an ally approach to patients with COVID-19 since it is effective for increasing immunity, helping tissue repair, and reducing pro-inflammatory cytokines. This systematic review was performed with the use of PubMed/MEDLINE, Web of Science, Scopus and Google Scholar databases with the following keywords: “low-level laser therapy OR photobiomodulation therapy AND COVID-19”. The inclusion criteria were complete articles published from January 2020 to January 2021 in English. The exclusion criteria were other languages, editorials, reviews, brief communications, letters to the editor, comments, conference abstracts, and articles that did not provide the full text. The bibliographic search found 18 articles in the Pubmed/MEDLINE database, 118 articles on the Web of Science, 23 articles on Scopus, and 853 articles on Google Scholar. Ten articles were included for qualitative synthesis, of which four commentary articles discussed the pathogenesis and the effect of PBMT in COVID-19. Two in vitro and lab experiments showed the effect of PBMT on prevention of thrombosis and positive results in wound healing during viral infection, using the intravascular irradiation (ILIB) associated with Phthalomethyl D. Two case reports showed PBMT improved the respiratory indexes, radiological findings, and inflammatory markers in severe COVID-19 patients. One case series reported the clinical improvement after PBMT on 14 acute COVID-19 patients, rehabilitation on 24 patients, and as a preventive treatment on 70 people. One clinical trial of 30 patients with severe COVID-19 who require invasive mechanical ventilation, showed PBMT-static magnetic field was not statistically different from placebo for the length of stay in the Intensive Care Unit, but improved diaphragm muscle function and ventilation and decreased the inflammatory markers. This review suggests that PBMT may have a positive role in treatment of COVID-19. Still, the necessity for more clinical trials remains in this field and there is not sufficient research evidence regarding the effects of PBMT and COVID-19 disease, and there is a large gap.
... Mitarb. [9] veröffentlicht und beinhaltet insgesamt 17 relevante Artikel. Wichtig scheint hier anzumerken, dass es sich dabei ausschließlich um Arbeiten an Tiermodellen handelt. ...
... PBM war im Stande, die Sauerstoffversorgung indirekt zu erhöhen, um die betroffenen Organe zu regenerieren. Die Autor*innen empfehlen, Infrarotlaser oder LEDs zu verwenden [9]. ...
The number of high-ranking publications on photobiomodulation is increasing disproportionately worldwide and it is therefore easy to understand that the therapy option should also be methodically expanded and tested in the treatment of COVID-19 as a complementary method for combating pandemics. In order to ascertain the current state of knowledge on the subject, a current research on ongoing clinical research studies and the first available results was initiated. In terms of the chosen method, the research focused on the variant of a possible self-executable home treatment. Three current study designs are to be described and discussed in more detail in this overview report. The three study projects do not all meet the requirements of good scientific practice, but should be briefly presented here because they are up to date. Although the designs can be expected to provide scientifically assessable results, no scientific conclusion can currently (yet) be drawn that the three methods for the treatment of COVID-19 prove to be suitable. The reasons for this are that no results are yet available in two of the three studies and one pilot study has major formal scientific deficiencies that should be avoided in follow-up studies.
... Aimbire et al. [60], also denotes that PBM significantly reduces TNFα and Nfkβ levels compared to the control group, suggesting therapeutic potential in suppressing TNFα in various inflammatory pathologies in the clinical area. Similarly, recent systematic reviews also suggest that PBM at blue wavelengths (450, 454, and 470 nm) favor lung tissue regeneration in patients with asthma as well as pneumonia triggered by COVID-19 [63][64][65][66][67][68]. Patients treated with PBM showed rapid recovery of pulmonary status, without the need for ICU admission or mechanical ventilation after treatment [68]. ...
Although the exact mechanism of the pathogenesis of coronavirus SARS-CoV-2 (COVID-19) is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the level of inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red photobiomodulation (PBM) as an attractive therapy to downregulate the cytokine storm caused by COVID-19 in a zebrafish model. RT-qPCR analyses and protein–protein interaction prediction among SARS-CoV-2 and Danio rerio proteins showed that recombinant Spike protein (rSpike) was responsible for generating systemic inflammatory processes with significantly increased levels of pro-inflammatory (il1b, il6, tnfa, and nfkbiab), oxidative stress (romo1) and energy metabolism (slc2a1a and coa1) mRNA markers, with a pattern similar to those observed in COVID-19 cases in humans. On the other hand, PBM treatment was able to decrease the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most-impacted metabolic pathways between PBM and the rSpike treated groups were related to steroid metabolism, immune system, and lipid metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19 and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials can commence.
... LLLT is ready for clinical trials over myocardial infarction [9]. Recently, it is recommended to use as a modality to attenuate cytokine storm at multiple levels, enhance recovery, and reduce the use of ventilators in COVID-19 [1], [14] - [16]. ...
Trong những năm gần đây, việc ứng dụng phương pháp điều trị Laser công suất thấp đa bước sóng đối với một số bệnh cấp tính, mãn tính và nâng cao chất lượng điều trị đã mang lại nhiều thành tựu tích cực trong y học. Nó ngày càng phổ biến trong cả thử nghiệm thực nghiệm và thử nghiệm lâm sàng. Các thiết bị laser quang trị liệu cho các ứng dụng cụ thể đang có nhu cầu rất lớn. Trong nghiên cứu này, một thiết bị quang trị liệu đa bước sóng phát ở vùng đỏ đến vùng hồng ngoại gần, vùng cửa sổ quang trị liệu, được phát triển. Thiết bị sử dụng các mô-đun laser, cho phép dễ dàng dẫn chùm tia laser vào vùng cần được trị liệu. Để thuận tiện cho người sử dụng, thiết bị tích hợp hệ thống điều khiển kỹ thuật số (Digital control), màn hình cảm ứng dễ dàng lựa chọn các thông số như công suất, bước sóng, chế độ hoạt tối ưu với mục đích điều trị cụ thể. Bài báo này trình bày thiết kế và chế tạo hoàn chỉnh thiết bị cũng như kỹ thuật chế tạo mô-đun laser. Các thông số chính của thiết bị trị liệu laser được đưa ra, đáp ứng các thông số kỹ thuật của thiết bị quang trị liệu, phù hợp cho điều trị các vết thương hở và mãn tính dựa trên cơ chế điều biến quang sinh.
... From the studies analyzed, the authors concluded that PBM at an energy density of 6.5-7.5 J/cm 2 for red lasers and 9.5-10.5 J/cm 2 for infrared lasers could be applied to reduce inflammation in the lungs, decrease neutrophil recruiting, and modulate the balance of proinflammatory and anti-inflammatory cytokines [74]. ...
Light and lasers, as high-tech devices whose medical potential has yet to be fully discovered, have made important contributions to medicine, even in the current pandemic. The main aim of this review was to investigate how light was applied as a therapeutic tool during a crisis triggered by COVID-19. Another goal was to encourage scientists and industry to quickly design new at-home photobiomodulation therapy (PBMT) and/or antimicrobial photodynamic therapy (aPDT) easy to use systems to end this pandemic, especially for those who believe in high-tech but would never get vaccinated. This review revealed that PBMT has been successfully applied as adjunct therapy, in combination with conventional medical treatment, and as a pioneering action in SARS-CoV-2 infection, demonstrating significant improvements in airway inflammation and general clinical condition of patients, a faster recovery, avoiding intensive care unit (ICU) hospitalization, mechanical ventilation, mortality, and overcoming long-term sequelae. Application in only a limited number of cases strongly suggests the need for future randomized, placebo-controlled clinical trials to objectively determine the action and effects of PBMT in COVID-19. Implementation of unparalleled theragnostics methods and light-based techniques for disinfection of spaces, air, skin, mucosae, and textures to decrease the load of SARS-CoV-2 virus would save lives, time, and money. In this ongoing and challenging search for the seemingly intangible end of this pandemic, a non-invasive, easily accessible, safe, and side-effect-free adjuvant method appears to be PBMT, alone or in synergistic combination with aPDT, which has been shown to work in COVID-19 and opens unprecedented potential for use as home self-treatment to end the pandemic.
... In this sense, the application of non-drug therapies already consolidated that have anti-inflammatory effects as in the case of photobiomodulation, can contribute to the recovery of these patients. The photobiomodulation has been shown to be efficient and effective in the treatment of d ifferent sequelae COVID-19-related [6][7][8][9][10][11][12][13][14] . ...
It is postulated that the inflammatory process resulting from SARS‐CoV‐2 infection is the main cause of smell and taste dysfunctions in patients. In view of this, photobiomodulation, due to its anti‐inflammatory and antioxidant effects, may be a promising therapeutic modality to treat these disorders. In the present case report, we observed clinical improvement in the symptoms of anosmia and ageusia related to COVID‐19 after treatment with photobiomodulation. Due to the inflammatory nature of COVID‐19 and the anti‐inflammatory effects, photobiomodulation antioxidants already proven in the literature make it a promising therapeutic modality, especially sequela COVID‐related, including olfactory (anosmia) and taste (ageusia) dysfunction. In the present case report, the patient's olfactory and gustatory functions were re‐established after 10 treatment sessions with photobiomodulation.
... The elevated cell count in bronchoalveolar lavage, inflammatory cytokines and neutrophil numbers were reduced in PBM experiments 21 . Systematic reviews 22 23 24 25 26 and case reports 27 28 ...
BACKGROUND
There is need for non-pharmaceutical treatments for COVID-19. A home-use photobiomodulation (PBM) device was tested as Treatment in a randomized clinical trial.
METHODS
294 patients were randomized with equal allocation to Treatment or Standard of Care (Control). 199 qualified for efficacy analyses. The Treatment group self-treated for 20 minutes twice daily, for the first 5 days, and subsequently once daily for 30 days. A validated respiratory questionnaire was used, and patients were monitored remotely. The primary endpoint was the time-to-recovery (3 consecutive days of no sickness) for general sickness. The Kaplan-Meier method and the Cox Proportional Hazards model were primary methods of analyses.
RESULTS
Treatment patients with collective 0-12 days of symptoms, at moderate-to-severe level on Day 1 of Treatment, did not recover significantly faster than Control. However, for patients with 0-7 days of symptoms there was a significant mean difference of 3 days: Treatment, 18 days (95% CI, 13-20) vs. Control, 21 days (95% CI, 15-28), P=0.050. The Treatment:Control hazard ratio at 1.495 (95% CI, 0.996-2.243), P=0.054 exceeded the pre-trial target of 1.44. Treated patients exceeding 7 days symptoms duration were more tired and had lower energy. None of the patients in the Treatment group suffered death or hospitalization while the Control group had 1 death and 3 severe adverse events requiring hospitalization.
CONCLUSIONS
Patients with up to 7 days of symptoms at moderate-to-severe levels on first day of Treatment can expect faster recovery for general sickness and several respiratory symptoms. (Funded by Vielight Inc.; ClinicalTrials.gov number, NCT04418505 .)
... The need for protein during pregnancy increases for fetal growth and maintains maternal health; it is strongly recommended to consume food sources of animal protein such as fish, milk, and eggs. The need for iron during pregnancy increases as it is used to form new cells and tissues (14). ...
One of the nutritional problems in pregnant women, namely chronic energy deficiency. The lack of regular energy is the condition of pregnant women who suffer from the lack of long-lasting food (chronic) with various health disorders. Pregnant women should be pregnant to fulfill nutritional intake not to occur chronic energy deficiency (this study's purpose is the relationship between knowledge and dietary habit with chronic energy deficiency incidence in pregnant women in the Talise Public Health Center. The type of analytical research surveys using a cross-sectional approach. This research has been implemented in the puuskesmas Talise city in Palu from June until Juli 2020. The results showed that of the two independent variables, they were not related to chronic energy deficiency. The results of statistical tests for knowledge P-value = 0.775, dietary pattern P-value = 0.463. In this study, conclusions are expected to provide healthcare workers with more attention to the healthy food consumption fan that healthy during pregnancy and conduct self-examination to prevent pregnant women at risk of a shortage of chronic energy deficiency. It is recommended that mothers keep looking for information about mothers' nutritional value during pregnancy and consume food and beverages that are of adequate nutritional needs during the inevitable hamilager of less chronic energy during pregnancy.
... In this sense, the application of non-drug therapies already consolidated that have anti-inflammatory effects as in the case of photobiomodulation, can contribute to the recovery of these patients. The photobiomodulation has been shown to be efficient and effective in the treatment of d ifferent sequelae COVID-19-related [6][7][8][9][10][11][12][13][14] . ...
It is postulated that the inflammatory process resulting from SARS‐CoV‐2 infection is the main cause of smell and taste dysfunctions in patients. In view of this, photobiomodulation, due to its anti‐inflammatory and antioxidant effects, may be a promising therapeutic modality to treat these disorders. In the present case report, we observed clinical improvement in the symptoms of anosmia and ageusia related to COVID‐19 after treatment with photobiomodulation. Due to the inflammatory nature of COVID‐19 and the anti‐inflammatory effects, photobiomodulation antioxidants already proven in the literature make it a promising therapeutic modality, especially sequela COVID‐related, including olfactory (anosmia) and taste (ageusia) dysfunction. In the present case report, the patient's olfactory and gustatory functions were re‐established after 10 treatment sessions with photobiomodulation. This article is protected by copyright. All rights reserved.
... Such effect results from photon energy absorption of non-ionizing radiations at low fluences or irradiances by intracellular photoacceptors, as cytochrome c oxidase in mitochondria [8]. Photobiomodulation is the scientific base of therapeutic protocols, such as the ones for wound healing [9], bone repair [10], pain relief [11], resolution of inflammatory processes [12], skeletal muscle injury [13], and nerve regeneration [14]. Molecular processes involved in photobiomodulation have been studied, and the understanding of gene expression in cells and tissues exposed to radiations emitted from low-power lasers has been improved by evaluation of mRNA levels by RT-qPCR. ...
Gene expression evaluation in cells and biological tissues has been crucial for research in biology, medicine, biotechnology, and diagnostic. Messenger ribonucleic acid (mRNA) levels show relationship with gene expression, and they can be measured by real-time quantitative polymerase chain reaction (RT-qPCR) for the quantification of steady-state mRNA levels in cells and biological tissues. Radiations emitted from low-power lasers induce photobiomodulation, which is the base of therapeutic protocols for disease treatment. Despite that the understanding on photobiomodulation has been improved by mRNA level evaluation, laser irradiation parameters and procedures are diversified among studies, harming the comparison of RT-qPCR data. In this systematic review, data from mRNA levels reported in photobiomodulation studies were summarized regarding the process, function, and gene. Literature search was conducted for the assessment of published reports on mRNA levels evaluated by RT-qPCR in cells and biological tissues exposed to low-power lasers. Data showed that mRNA levels have been evaluated by RT-qPCR for a variety of genes related to molecular, cellular, and systemic processes after low-power violet-orange, red, and infrared laser exposure. Results from gene expression have increased the understanding of the mechanisms involved in photobiomodulation, and they can be useful to increase the efficacy and safety of clinical applications based on low-power lasers.
... Its level increases in lung inflammation. Monocyte migration may be reduced after therapy due to decrease in MCP-1 (14). On the other hand, the role of IL-10 is not clear yet. ...
Introduction. An unprecedented public health crisis has been triggered worldwide by SARS-CoV-2’s high contagiosity and it’s
mortality rates of 1-5%. Although the majority of COVID-19 cases have a good outcome, there is a small percentage that develop
severe pneumonia and citokine storm and may be in the need of mechanical ventilation.
Methods. Identifying the exact drivers of the excessive inflammation and the biomarkers that can predict a hyperinflammatory
response to SARS-CoV-2 would be extremly helpful in finding efficient anti-inflammatory interventions that may stop the
progression to acute respiratory distress syndrome (ARDS).
Results. In the search for such interventions we have identified the promising effect of low level LASER therapy (LLLT) on lung
inflammation from COVID-19 pneumonia. Due to its well known anti-inflammatory effect and modulatory activity on immune
cells, laser therapy may be able to decrease lung and systemic inflammation without affecting lung function in acute lung lesions,
relieve respiratory symptoms, normalize respiratory function and stimulate the healing process of lung tissue. The recovery time
may also be significantly shortened and all blood, immunological and radiological parameters may improve.
Conclusions. This findings need further confirmation from clinical trials but we are hopeful for their contribution on the global
battle against COVID-19 pandemic.
... Its level increases in lung inflammation. Monocyte migration may be reduced after therapy due to decrease in MCP-1 (14). On the other hand, the role of IL-10 is not clear yet. ...
Introduction. An unprecedented public health crisis has been triggered worldwide by SARS-CoV-2’s high contagiosity and it’s mortality rates of 1-5%. Although the majority of COVID-19 cases have a good outcome, there is a small percentage that develop severe pneumonia and citokine storm and may be in the need of mechanical ventilation. Methods. Identifying the exact drivers of the excessive inflammation and the biomarkers that can predict a hyperinflammatory response to SARS-CoV-2 would be extremly helpful in finding efficient anti-inflammatory interventions that may stop the progression to acute respiratory distress syndrome (ARDS). Results. In the search for such interventions we have identified the promising effect of low level LASER therapy (LLLT) on lung inflammation from COVID-19 pneumonia. Due to its well known anti-inflammatory effect and modulatory activity on immune cells, laser therapy may be able to decrease lung and systemic inflammation without affecting lung function in acute lung lesions, relieve respiratory symptoms, normalize respiratory function and stimulate the healing process of lung tissue. The recovery time may also be significantly shortened and all blood, immunological and radiological parameters may improve. Conclusions. This findings need further confirmation from clinical trials but we are hopeful for their contribution on the global battle against COVID-19 pandemic. Keywords: SARS-CoV-2, pneumonia, low LASER level therapy, anti-inflammatory effect, citokine storm
... Here we investigated the effects of NIR LED as a PBM treatment in an animal model experimental corticosteroid-resistant asthma. Several studies have investigated the use of light therapy to treat lung inflammatory diseases in animal models [13,23,24], as well as in humans [25,26]. However, NIR LEDs have not so far been investigated. ...
Corticosteroid-resistant asthma (CRA) is a severe form of disease and clinically important, since patients do not respond to mainstay corticosteroid therapies. Thus, new therapies are needed. However, a big limiting factor in the understanding of CRA is the existence of different immunological and inflammatory phenotypes, a fact that makes it difficult to reproduce experimentally. Photobiomodulation (PBM) emerges as an alternative therapy based on earlier studies. This study aims to evaluate the effect of PBM using infrared light-emitting diode (ILED) on the development of corticosteroid-resistant asthma. Therefore, groups of rats were sensitized and challenged with ovalbumin plus Freund’s adjuvant for the induction of CRA, and treated or not with ILED directly in the respiratory tract on the skin (wavelength 810 nm; power 100 mW; density energy 5 J/cm; total energy 15 J; time 150 s). Our experimental model was capable to induce neutrophilic asthma. Besides that, the corticosteroid treatment did not reverse the lung cell migration as well as the levels of leukotriene B4, and interleukins 17 and 6. The treatment with ILED reduced the lung cell migration; myeloperoxidase activity; mast cell degranulation; and the levels of leukotriene B4, thromboxane B2, prostaglandin E2, tumoral necrosis factor alpha, and interleukins 17 and 6. Still, ILED increased the level of interleukin 10. In conclusion, we showed promisor effects of ILED when irradiated directly in the respiratory tract as adjuvant treatment of corticosteroid-resistant asthma.
... As a possible solution, a noninvasive, illuminationbased therapy known as photobiomodulation therapy has been suggested as a treatment for COVID-19 [20,21]. Photobiomodulation is a proven treatment against various conditions involving resolution of underlying inflammation that include Achilles tendinopathy [22]. ...
The leading cause of mortality from COVID-19 infection is respiratory distress due to an exaggerated host immune response, resulting in hyper-inflammation and ensuing cytokine storms in the lungs. Current drug-based therapies are of limited efficacy, costly, and have potential negative side effects. By contrast, photobiomodulation therapy, which involves periodic brief exposure to red or infrared light, is a noninvasive, safe, and affordable method that is currently being used to treat a wide range of diseases with underlying inflammatory conditions. Here, we show that exposure to two 10-min, high-intensity periods per day of infrared light causes a marked reduction in the TLR-4 dependent inflammatory response pathway, which has been implicated in the onset of cytokine storms in COVID-19 patients. Infrared light exposure resulted in a significant decline in NFkB and AP1 activity as measured by the reporter gene assay; decreased expression of inflammatory marker genes IL-6, IL-8, TNF-alpha, INF-alpha, and INF-beta as determined by qPCR gene expression assay; and an 80% decline in secreted cytokine IL6 as measured by ELISA assay in cultured human cells. All of these changes occurred after only 48 hours of treatment. We suggest that an underlying cellular mechanism involving modulation of ROS may downregulate the host immune response after Infrared Light exposure, leading to decrease in inflammation. We further discuss technical considerations involving light sources and exposure conditions to put these observations into potential clinical use to treat COVID-19 induced mortality.
... The biological and clinical effects of laser therapy consist of the production of photochemical cellular reactions that activate the biomolecules responsible for restoring normal cell function, increasing the healing speed of lung parenchymal tissue through tissue regeneration in acute lung lesions, decreasing the number of proinflammatory cytokines by modulating the "cytokine storm" and the acute respiratory distress syndrome, reducing lung inflammation at molecular, cellular and tissue level, reducing pulmonary oedema, relieving lung pain, increasing lung volume and exercise capacity (Nejatifard et al., 2021;de Brito et al., 2020;Fekrazad, 2020;Cury et al., 2016;de Lima et al., 2011). ...
... It has been reported that photobiomodulation can reduce the virulence of the virus by reducing ARDS and accelerating the regeneration of damaged tissue [74][75][76]. The efficacy of photobiomodulation may be because the virus is trapped in porphyrins. ...
Although a vaccination campaign has been launched in many countries, the COVID-19 pandemic is still not under control. The main concern is the emergence of new variants of SARS-CoV-2; therefore, it is important to find new approaches to prevent or reduce the virulence and pathogenicity of the virus. Currently, the mechanism of action of SARS-CoV-2 is not fully understood. Considering the clinical effects that occur during the disease, attacking the human respiratory and hematopoietic systems, and the changes in biochemical parameters (including decreases in haemoglobin [Hb] levels and increases in serum ferritin), it is clear that iron metabolism is involved. SARS-CoV-2 induces haemolysis and interacts with Hb molecules via ACE2, CD147, CD26, and other receptors located on erythrocytes and/or blood cell precursors that produce dysfunctional Hb. A molecular docking study has reported a potential link between the virus and the beta chain of haemoglobin and attack on haem. Considering that haem is involved in miRNA processing by binding to the DCGR8-DROSHA complex, we hypothesised that the virus may check this mechanism and thwart the antiviral response.
... It is well accepted that PBM is a noninvasive treatment method which reduces inflammation and stimulates tissue regeneration and healing processes [290]. ...
In recent decades, researchers around the world have been studying intensively how micro-organisms that are present inside living organisms could affect the main processes of life, namely health and pathological conditions of mind or body. They discovered a relationship between the whole microbial colonization and the initiation and development of different medical disorders. Besides already known probiotics, novel products such as postbiotics and paraprobiotics have been developed in recent years to create new non-viable micro-organisms or bacterial-free extracts, which can provide benefits to the host with additional bioactivity to probiotics, but without the risk of side effects. The best alternatives in the use of probiotics and postbiotics to maintain the health of the intestinal microbiota and to prevent the attachment of pathogens to children and adults are highlighted and discussed as controversies and challenges. Updated knowledge of the molecular and cellular mechanisms involved in the balance between microbiota and immune system for the introspection on the gut–lung–brain axis could reveal the latest benefits and perspectives of applied photobiomics for health. Multiple interconditioning between photobiomodulation (PBM), probiotics, and the human microbiota, their effects on the human body, and their implications for the management of viral infectious diseases is essential. Coupled complex PBM and probiotic interventions can control the microbiome, improve the activity of the immune system, and save the lives of people with immune imbalances. There is an urgent need to seek and develop innovative treatments to successfully interact with the microbiota and the human immune system in the coronavirus crisis. In the near future, photobiomics and metabolomics should be applied innovatively in the SARS-CoV-2 crisis (to study and design new therapies for COVID-19 immediately), to discover how bacteria can help us through adequate energy biostimulation to combat this pandemic, so that we can find the key to the hidden code of communication between RNA viruses, bacteria, and our body.
... [34][35][36][37][38][39] Recent publications and systematic reviews provide the theory and potential mechanism of action of PBMT in fighting COVID-19. 14,18,[40][41][42][43] Our experience in treating pain, inflammation and respiratory conditions motivated this trial to use PBMT in COVID-19 patients. COVID-19 continues to claim lives while some of the patients who recover show long-term sequelae. ...
Purpose:
Evidence-based and effective treatments for COVID-19 are limited, and a new wave of infections and deaths calls for novel, easily implemented treatment strategies. Photobiomodulation therapy (PBMT) is a well-known adjunctive treatment for pain management, wound healing, lymphedema, and cellulitis. PBMT uses light to start a cascade of photochemical reactions that lead to local and systemic anti-inflammatory effects at multiple levels and that stimulate healing. Numerous empirical studies of PBMT for patients with pulmonary disease such as pneumonia, COPD and asthma suggest that PBMT is a safe and effective adjunctive treatment. Recent systematic reviews suggest that PBMT may be applied to target lung tissue in COVID-19 patients. In this preliminary study, we evaluated the effect of adjunctive PBMT on COVID-19 pneumonia and patient clinical status.
Patients and methods:
We present a small-scale clinical trial with 10 patients randomized to standard medical care or standard medical care plus adjunctive PBMT. The PBMT group received four daily sessions of near-infrared light treatment targeting the lung tissue via a Multiwave Locked System (MLS) laser. Patient outcomes were measured via blood work, chest x-rays, pulse oximetry and validated scoring tools for pneumonia.
Results:
PBMT patients showed improvement on pulmonary indices such as SMART-COP, BCRSS, RALE, and CAP (Community-Acquired Pneumonia questionnaire). PBMT-treated patients showed rapid recovery, did not require ICU admission or mechanical ventilation, and reported no long-term sequelae at 5 months after treatment. In the control group, 60% of patients were admitted to the ICU for mechanical ventilation. The control group had an overall mortality of 40%. At a 5-month follow-up, 40% of the control group experienced long-term sequelae.
Conclusion:
PBMT is a safe and effective potential treatment for COVID-19 pneumonia and improves clinical status in COVID-19 pneumonia.
... 12 In the pathophysiology of COVID-19, a non-invasive therapeutic modality able to decrease the IL-1β, IL-6, IL-8, TNFα and MCP-1 proinflammatory cytokines would reduce the fatality rate of the disease. 27,28 The complications of an overreacting immune system, particularly in populations at risk with underlying comorbidities, may also lead to critical complications, as vascular hyperpermeability and multi-organ injuries, abnormal coagulation parameters and micro-thrombosis having been described in hospitalized patients. 29 PBMT is here described using two wavelengths, 630 nm and 660 nm, from a dual RL emitter (Triwings LS ® , Biophoton) with a spectral shift of +15 nm, both wavelengths remaining in the visible spectrum, yet the second approaching the near-infrared (NIR) range. ...
PBMT using 630 + 660 nm wavelengths transcutaneously at 7 cm above chest area irradiating lungs and heart regions of patients with acute, infectious respiratory syndrome alleviated their respiratory symptoms, mitigated pulmonary inflammation and hypoxia. PBMT could prevent more severe respiratory distress requiring emergency care and reduce the strain on healthcare. This case report's clinical experience can be the basis of future research evaluating oxygen saturation levels pre‐ and post‐PBMT. PBMT using 630 + 660 nm wavelengths transcutaneously at 7 cm above chest area irradiating lungs and heart regions of patients with acute, infectious respiratory syndrome alleviated their respiratory symptoms, mitigated pulmonary inflammation and hypoxia. PBMT could prevent more severe respiratory distress requiring emergency care and reduce the strain on healthcare. This case report's clinical experience can be the basis of future research evaluating oxygen saturation levels pre‐ and post‐PBMT.
... Some recent studies have discussed an application of photomedicine called photobiomodulation therapy for management and treatment of COVID-19 disease with other therapeutic modalities such as antiviral photodynamic therapy that may be beneficial in different stages of the disease such as stifling the cytokine storm, improving cellular regeneration of the lungs, damaged tissues' oxygenation, and 1 also in viral load reduction in upper respiratory tract, blood, and even deep body tissues that are the accumulation places for viral agents (lungs etc.). [5][6][7][8] With special attention to the photobiomodulation phenomenon, it seems that this modality might be helpful for decreasing the symptoms and time of long COVID-19 with its metabolic, immunological, anti-inflammatory, and pain killing effects. I AU5 c n the respiratory system, the most important victim of the chronic symptoms, with suitable parameters of photobiomodulation in tissue regeneration field we may be able to help damaged cells both directly with direct light therapy and indirectly with systemic effects on cells and blood factors to improve conditions for cellular regeneration with better oxygenation and adequate AU4 c ATP supplementation on chronic obstructive pulmonary disease which is a chronic lung disease that resembles the chronic damages of COVID-19 disease. ...
... 12 In the pathophysiology of COVID-19, a non-invasive therapeutic modality able to decrease the IL-1β, IL-6, IL-8, TNFα and MCP-1 proinflammatory cytokines would reduce the fatality rate of the disease. 27,28 The complications of an overreacting immune system, particularly in populations at risk with underlying comorbidities, may also lead to critical complications, as vascular hyperpermeability and multi-organ injuries, abnormal coagulation parameters and micro-thrombosis having been described in hospitalized patients. 29 PBMT is here described using two wavelengths, 630 nm and 660 nm, from a dual RL emitter (Triwings LS ® , Biophoton) with a spectral shift of +15 nm, both wavelengths remaining in the visible spectrum, yet the second approaching the near-infrared (NIR) range. ...
Given the magnitude of the viral pandemic, we report the successful treatment of two early clinical cases of acute infectious respiratory syndrome addressed with Photobiomodulation and, welcome the scientific community interest in these early findings, clinical basis for further research.
Jian-Ti-Kang-Yi decoction (JTKY) is widely used in the treatment of COVID-19. However, the protective mechanisms of JTKY against pneumonia remain unknown. In this study, polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, was used to induce pneumonia in mice; the therapeutic effects of JTKY on poly(I:C)-induced pneumonia model mice were evaluated. In addition, the anti-inflammatory and anti-oxidative potentials of JTKY were also investigated. Lastly, the metabolic regulatory effects of JTKY in poly(I:C)-induced pneumonia model mice were studied using untargeted metabolomics. Our results showed that JTKY treatment decreased the wet-to-dry ratio in the lung tissue, total protein concentration, and total cell count of the bronchoalveolar lavage fluid (BALF). Hematoxylin and Eosin (HE) and Masson staining indicated that the JTKY treatment alleviated the pathological changes and decreased the fibrotic contents in the lungs. JTKY treatment also decreased the expression of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α)] and increased the levels of immunomodulatory cytokines (IL-4 and IL-10) in the BALF and serum. Flow cytometry analysis showed that the JTKY treatment lowered the ratio of CD86 ⁺ /CD206 ⁺ macrophages in the BALF, decreased inducible nitric oxide synthase (iNOS) level, and increased arginase 1 (Arg-1) level in lung. JTKY also lowered CD11b ⁺ Ly6G ⁺ neutrophils in BALF and decreased myeloperoxidase (MPO) activity in lung. Moreover, it also elevated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and decreased methane dicarboxylic aldehyde (MDA) level in lung. Untargeted metabolomic analysis showed that the JTKY treatment could affect 19 metabolites in lung, such as L-adrenaline, L-asparagine, ornithine, and alpha-ketoglutaric acid. These metabolites are associated with the synthesis and degradation of ketone bodies, butanoate, alanine, aspartate, and glutamate metabolism, and tricarboxylic acid (TCA) cycle processes. In conclusion, our study demonstrated that treatment with JTKY ameliorated poly(I:C)-induced pneumonia. The mechanism of action of JTKY may be associated with the inhibition of the inflammatory response, the reduction of oxidative stress, and the regulation of the synthesis and degradation of ketone bodies, TCA cycle, and metabolism of alanine, aspartate, glutamate, and butanoate processes in lung.
Preliminary studies also show that many of the fatalities of COVID-19 are due to over-activity of the immune system, and photobiomodulation (PBM) therapy mainly accelerates wound healing and reduces pain and inflammation. Therefore, this systematic review and meta-analysis was conducted to evaluate the probable effect of the PBM therapy on the lung inflammation or ARDS and accelerate the regeneration of the damaged tissue. We systematically searched major indexing databases, including PubMed/Medline, ISI web of science (WOS), Scopus, Embase, and Cochrane central, using standard terms without any language, study region, or type restrictions. Of the 438 studies found through initial searches, 13 met the inclusion criteria. After applying the exclusion criteria, the main properties of 13 articles on 384 animals included in this meta-analysis with a wide range of species include rat (n = 10) and rabbit (n = 3). The analysis revealed that PBM therapy reduced TNFα (SMD:-3.75, 95% CI: -4.49, -3.02, P < 0.00001, I2 = 10%), IL-1β (SMD:-4.65, 95% CI: -6.15, -3.16, P < 0.00001, I2 = 62%), and IL-6 (SMD:-4.20, 95% CI: -6.42, -1.97, P = 0.0002, I2 = 88%) significantly compared with the model controls. Hence, PBM therapy increased IL-10 significantly compared with the model controls (SMD:-4.65, 95% CI: -6.15, -3.16, P < 0.00001, I2 = 62%). PBM therapy also reduced MPO activity (SMD:-2.13, 95% CI: -3.38, -0.87, P = 0.0009, I2 = 64%) and vascular permeability (SMD:-2.59, 95% CI: -4.40, -0.77, P = 0.0052, I2 = 71%) in the lung using the Evans blue extravasation technique significantly compared with the model controls. This systematic review and meta-analysis revealed that the PBM therapy does utilize beneficial anti-inflammatory effect, modulation of the immune system, lung permeability, or bronchoalveolar lavage on lung damage in both animal models and clinical studies. However, animal model and clinical studies appear limited considering the quality of the included evidences; therefore, large clinical trials are still required.
A non-randomized 50-person case study of COVID-19 positive patients was conducted employing (for the first time) a regimen of whole-organ deep-tissue transdermal dynamic photobiomodulation (PBM) as a primary (or exclusive) therapeutic modality in the treatment of coronavirus. Therapy sessions comprised algorithmically alternating red (650 nm) and near infrared (850 nm) LEDs with average irradiance of 11 mW/cm² dynamically sequenced at multiple pulse frequencies. Delivered via 3-D bendable polymeric pads maintaining orthogonal optical incidence to body contours over 1,000 cm², a single 84-min session concurrently delivered 20 kJ to the sinuses and 15 kJ to each lung at skin temperatures below 42 °C. Therapeutic outcomes observed include significant reductions in the duration and severity of disease symptoms. Acute conditions including fever, body aches, and respiratory distress comprising paroxysmal coughing; lung congestion, dyspnea and hypoxia; sinus congestion; acute eye inflammation; and extreme malaise were eliminated in 41/50 patients within 4-days of commencing PBM treatments with 50/50 patients fully recovering within three-weeks with no supplemental oxygen requirements. SpO2 concentrations improved as much as 9 points (average 2.5 points) across the entire study population. The PBM sessions required to completely resolve COVID-19 conditions appears mono- tonically correlated to the time-to-treatment (TTTx) — the delay between the onset of a patient's symptoms and commencing PBM therapy. In contrast, acute inflammatory symptoms were resolved within 4-days irrespective of TTTx.
This article is protected by copyright. All rights reserved.
O uso de tecnologias a laser é como para as consequências da importante para a pandemia COVID-19. Além disso, a laser saúde e reabilitação, bemterapia quando combinada com a vacuoterapia ou ultrassom terapêutico parece ter seus efeitos potencializados no tratamento da dor, lesões e doenças crônicas e degenerativas. O objetivo deste estudo foi verificar os efeitos de diferentes tecnologias a laser aplicadas a saúde e reabilitação. O atual estudo trata-se de uma revisão bibliográfica realizada a partir da busca de estudos publicados até janeiro de 2021 nas bases de dados Google Scholar, Lilacs, Scielo e Pubmed. Os estudos identificados evidenciaram que o
uso de tecnologias a laser resulta em vários efeitos terapêuticos e, portanto, é considerado um importante adjuvante nas ações de cuidado à população.
COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called “cytokine storm” induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.
Introduction: High-intensity laser therapy (HILT) has been used more recently in the therapeutic protocols of pain managements. Adding therapeutic interventions to laser therapy is usual in clinical practice. This study aimed to evaluate the efficacy of HILT and beneficial effects of adding cointerventions to HILT in musculoskeletal pain management. Methods: The following databases were searched up to August 2018: Medline, PubMed, EMBASE, Cochrane, Google Scholar, Springer and ISI. The keywords of pain, HILT, high power laser therapy, laser therapy, photobiomodulation, physical therapy and rehabilitation were searched. The quality of the articles was assessed using the PEDro scale. The primary measure was pain severity expected to be reported in all studies. Effect size was calculated as standardized mean differences divided by the standard deviation of either the treatment or other group. Results: Initially 52 potential studies were found. Eighteen of these studies were excluded based on title and abstract. The full text of 34 remaining articles was screened and 15 of the studies were excluded. All included studies had high quality (PEDro ≥7). Approximately, 94% of included articles (n=18) revealed positive effects of HILT on pain. The effect sizes for HILT and placebo/comparator groups were 0.9-9.11 and 0.21-11.22 respectively. Also, the differences of effect size between two groups were between 0.03 to 5.85. Conclusion: It is early to determine that HILT may be an effective non-invasive agent in the management of musculoskeletal pain, as few studies have shown its clinical efficacy. Adding related co-interventions to HILT may enhance the beneficial effects of laser therapy. The variability of the study methods and outcomes suggests that further long-term follow-up, randomized controlled clinical trials with appropriate methodological design are needed regarding the effectiveness of HILT on pain.
Background:
A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients.
Methods:
All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.
Findings:
By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.
Interpretation:
The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies.
Funding:
Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections. Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.
Stimulated cells and cancer cells have widespread shortening of mRNA 3’-untranslated regions (3’UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates’ most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells’ migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3’UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation. U1 snRNP is a key regulator of mRNA biogenesis through its roles in splicing, and transcription and 3’-end processing. Here the authors show a tumor suppressor-like function of U1 snRNP using in vitro cell migration/invasion assays and transcriptome profiling.
Skin aging is a complex biological process induced by intrinsic and extrinsic factors which is characterized by clinical and cellular changes, especially dermal fibroblasts. It is possible that, some procedures, such as low-level laser therapy (LLLT), could decelerate this process. To test this hypothesis, this study evaluated the in vitro LLLT on dermal fibroblast cell line (HFF-1) with premature senescence H2O2-induced. HFF-1 cells were cultured in standardized conditions, and initially H2O2 exposed at different concentrations. Fibroblasts were also just exposed at different LLLT (660 nm) doses. From these curves, the lowest H2O2 concentration that induced indicators of premature senescence and the lowest LLLT doses that triggered fibroblast proliferation were used in all assays. Cellular mortality, proliferation, and the levels of oxidative, inflammatory cytokines, apoptotic markers, and of two growth signaling molecules (FGF-1 and KGF) were compared among treatments. The H2O2 at 50 μM concentration induced some fibroblast senescence markers and for LLLT, the best dose for treatment was 4 J (p < 0.001). The interaction between H2O2 at 50 μM and LLLT at 4 J showed partially reversion of the higher levels of DNA oxidation, CASP 3, CASP 8, IL-1B, IL-6, and INFy induced by H2O2 exposure. LLLT also trigger increase of IL-10 anti-inflammatory cytokine, FGF-1 and KGF levels. Cellular proliferation was also improved when fibroblasts treated with H2O2 were exposed to LLLT (p < 0.001). These results suggest that in fibroblast with some senescence characteristics H2O2-induced, the LLLT presented an important protective and proliferative action, reverting partially or totally negative effects triggering by H2O2.
Background:
It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission.
Methods:
The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality.
Discussion:
This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018.
Trial registration:
ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.
Emerging viral infections are difficult to control because heterogeneous members periodically cycle in and out of humans and zoonotic hosts, complicating the development of specific antiviral therapies and vaccines. Coronaviruses (CoVs) have a proclivity to spread rapidly into new host species causing severe disease. Severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) successively emerged, causing severe epidemic respiratory disease in immunologically naïve human populations throughout the globe. Broad-spectrum therapies capable of inhibiting CoV infections would address an immediate unmet medical need and could be invaluable in the treatment of emerging and endemic CoV infections. We show that a nucleotide prodrug, GS-5734, currently in clinical development for treatment of Ebola virus disease, can inhibit SARS-CoV and MERS-CoV replication in multiple in vitro systems, including primary human airway epithelial cell cultures with submicromolar IC50 values. GS-5734 was also effective against bat CoVs, prepandemic bat CoVs, and circulating contemporary human CoV in primary human lung cells, thus demonstrating broad-spectrum anti-CoV activity. In a mouse model of SARS-CoV pathogenesis, prophylactic and early therapeutic administration of GS-5734 significantly reduced lung viral load and improved clinical signs of disease as well as respiratory function. These data provide substantive evidence that GS-5734 may prove effective against endemic MERS-CoV in the Middle East, circulating human CoV, and, possibly most importantly, emerging CoV of the future.
Photobiomodulation also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infrared region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential, and adenosine triphosphate production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium (Ca2+) to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO, and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, and antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.
Objective:
This study was conducted to investigate the effects of low-level laser (LLL) doses on human red blood cell volume. The effects of exposure to a diode pump solid state (DPSS) (λ = 405 nm) laser were observed.
Background data:
The response of human blood to LLL irradiation gives important information about the mechanism of interaction of laser light with living organisms. Materials and methods Blood samples were collected into ethylenediaminetetraacetic acid (EDTA)-containing tubes, and each sample was divided into two equal aliquots, one to serve as control and the other for irradiation. The aliquot was subjected to laser irradiation for 20, 30, 40, or 50 min at a fixed power density of 0.03 W/cm(2). Mean cell volume (MCV) and red blood cell (RBC) counts were measured immediately after irradiation using a computerized hemtoanalyzer.
Results:
Significant decrease in RBC volume (p < 0.05, p < 0.0001, p < 0.0001, and p < 0.05, respectively) was induced with variation in laser doses.The highest response was observed with an exposure time of 40 min. This result was reproduced in RBCs suspended in a buffered NaCl solution. In contrast to this finding, laser-induced RBC volume change was completely abolished by suspending RBCs in a solution containing a higher concentration of EDTA.
Conclusions:
It was suggested that LLL can reduce RBC volume possibly because of the increased free intracellular Ca(+2) concentrations, which activate Ca(+2)-dependent K(+) channels with consequent K(+) ion efflux and cell shrinkage.
Lung diseases constitute an important public health problem and its growing level of concern has led to efforts for the development of new therapies, particularly for the control of lung inflammation. Low Level Laser Therapy (LLLT) has been highlighted as a non-invasive therapy with few side effects, but its mechanisms need to be better understood and explored. Considering that pollution causes several harmful effects on human health, including lung inflammation, in this study, we have used formaldehyde (FA), an environmental and occupational pollutant, for the induction of neutrophilic lung inflammation. Our objective was to investigate the local and systemic effects of LLLT after FA exposure. Male Wistar rats were exposed to FA (1%) or vehicle (distillated water) during 3 consecutive days and treated or not with LLLT (1 and 5 hours after each FA exposure). Non-manipulated rats were used as control. 24 h after the last FA exposure, we analyzed the local and systemic effects of LLLT. The treatment with LLLT reduced the development of neutrophilic lung inflammation induced by FA, as observed by the reduced number of leukocytes, mast cells degranulated, and a decreased myeloperoxidase activity in the lung. Moreover, LLLT also reduced the microvascular lung permeability in the parenchyma and the intrapulmonary bronchi. Alterations on the profile of inflammatory cytokines were evidenced by the reduced levels of IL-6 and TNF-α and the elevated levels of IL-10 in the lung. Together, our results showed that LLLT abolishes FA-induced neutrophilic lung inflammation by a reduction of the inflammatory cytokines and mast cell degranulation. This study may provide important information about the mechanisms of LLLT in lung inflammation induced by a pollutant.
Intestinal ischemia and reperfusion (i-I/R) is an insult associated with acute respiratory distress syndrome (ARDS). Herein we evaluate the dose-response effect of low-level laser therapy (LLLT) on lung inflammation induced by i-I/R.
Mice were subjected to mesenteric artery occlusion (45 min) and killed after clamp release and intestinal reperfusion (2h). Increasing doses (1, 3, 5 and 7,5 J/cm(2)) of laser irradiation (660 nm) was carried out on the mice skin over the upper bronchus for 5 min after initiating reperfusion. Neutrophils activation was determined by myeloperoxidase (MPO) activity. The mRNA expression and protein concentration of inflammatory mediators IL-1β, IL-6, TNF and IL-10 in lung were measured by RT-PCR and ELISA, respectively.
With exception of 1J/cm(2), LLLT reduced MPO activity as well as IL-1β levels in the lungs from inflamed mice. LLLT was also markedly effective in reducing both IL-6 and TNF expression and levels in the lungs from mice submitted to i-I/R in all laser doses studied. Otherwise, LLLT significantly increased the protein levels of IL-10 in inflamed mice by i-I/R; however only in the dose of 1J/cm(2).
We conclude that the LLLT is able to control the neutrophils activation and proinflammatorycytokines release into the lungs in a model of i-I/R in mice.
Asthma is a complex chronic inflammatory disease of the airways that involves the activation of many inflammatory and other types of cells. We investigated the effect of low-level laser therapy (LLLT) on allergic asthma in rats and compared its effect with that of the glucocorticoid budesonide. Asthma was induced by challenge and repeated exposure to ovalbumin. Asthmatic rats were then treated with LLLT or budesonide suspension. LLLT at 8 J/cm(2) once daily for 21 days could relieve pathological damage and airway inflammation in asthmatic rats. LLLT could decrease the total numbers of cells and eosinophils in bronchoalveolar lavage fluid. LLLT could reduce levels of IL-4 and increase IFN-γ levels in bronchoalveolar lavage fluid and serum, meanwhile reduce serum IgE levels. Flow cytometry assay showed that LLLT can regulate the Th1/Th2 imbalance of asthmatic rats. LLLT had a similar effect to that of budesonide. These findings suggest that the mechanism of LLLT treatment of asthma is by adjustment of Th1/Th2 imbalance. Thus, LLLT could take over some of the effects of budesonide for the treatment of asthma, thereby reducing some of the side effects of budesonide.
Acute respiratory distress syndrome (ARDS) due to sepsis has a high mortality rate with limited treatment options. High density lipoprotein (HDL) exerts innate protective effects in systemic inflammation. However, its role in ARDS has not been well studied. Peptides such as L-4F mimic the secondary structural features and functions of apolipoprotein (apo)A-I, the major protein component of HDL. We set out to measure changes in HDL in sepsis-mediated ARDS patients, and to study the potential of L-4F to prevent sepsis-mediated ARDS in a rodent model of lipopolysaccharide (LPS)-mediated acute lung injury, and a combination of primary human leukocytes and human ARDS serum. We also analyzed serum from non-lung disease intubated patients (controls) and sepsis-mediated ARDS patients. Compared to controls, ARDS demonstrates increased serum endotoxin and IL-6 levels, and decreased HDL, apoA-I and activity of anti-oxidant HDL-associated paraoxanase-1. L-4F inhibits the activation of isolated human leukocytes and neutrophils by ARDS serum and LPS in vitro. Further, L-4F decreased endotoxin activity and preserved anti-oxidant properties of HDL both in vitro and in vivo. In a rat model of severe endotoxemia, L-4F significantly decreased mortality and reduces lung and liver injury, even when administered 1 hour post LPS. Our study suggests the protective role of the apoA-I mimetic peptide L-4F in ARDS and gram-negative endotoxemia and warrant further clinical evaluation. The main protective mechanisms of L-4F are due to direct inhibition of endotoxin activity and preservation of HDL anti-oxidant activity.
Introduction
The acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice.
Methods
A study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood. Six experimental groups were designated as: 1) endotoxin alone, 2) endotoxin + total fresh whole bone marrow nuclear cells (BMC), 3) endotoxin + non-hematopoietic bone marrow cells (CD45 neg), 4) endotoxin + hematopoietic bone marrow cells (CD45 positive), 5) endotoxin + buffy coat and 6) endotoxin + in vitro expanded swine CD45 negative adherent allogeneic bone marrow cells (cultured CD45neg). We measured at different levels the biological consequences of the infusion of the different subsets of cells. The measured parameters were: pulmonary vascular resistance (PVR), gas exchange (PO2), lung edema (lung wet/dry weight), gene expression and serum concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6.
Results
Infusion of freshly purified autologous total BMCs, as well as non-hematopoietic CD45(-) bone marrow cells significantly reduced endotoxin-induced pulmonary hypertension and hypoxemia and reduced the lung edema. Also, in the groups that received BMCs and cultured CD45neg we observed a decrease in the levels of IL-1β and TNF-α in plasma. Infusion of hematopoietic CD45(+) bone marrow cells or peripheral blood buffy coat cells did not protect against LPS-induced lung injury.
Conclusions
We conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating the inflammatory response, mechanisms that do not involve engraftment or trans-differentiation of the cells. These observations may have important implications for the design of future cell therapies for ARDS.
Author Summary
Invasive infections caused by the human pathogen Staphylococcus aureus result in more deaths annually than infections caused by any other single infectious agent in the United States. Although neutrophil recruitment and abscess formation is crucial for effective host defense against this pathogen, how neutrophils sense and mount an inflammatory response are not completely clear. Using gene expression analysis and in vivo bioluminescence and fluorescence imaging, we found that neutrophil recruitment during a S. aureus cutaneous infection is functionally and temporally linked to IL-1β/IL-1R activation. Surprisingly, neutrophils themselves were determined to be the most abundant cell type that produced IL-1β during infection. Further, neutrophil-derived IL-1β, in the absence of other cellular sources of IL-1β, was sufficient for neutrophil recruitment, abscess formation, and bacterial clearance. Finally, mouse neutrophils produced IL-1β in direct response to live S. aureus in vitro. These findings expand our understanding of the acute neutrophil response to infection in which early recruited neutrophils serve as a source of IL-1β that is essential for amplifying and sustaining the neutrophilic response to promote abscess formation and bacterial clearance. Therapies aimed at promoting IL-1β production by neutrophils may be an effective immunotherapeutic strategy to control S. aureus infections.
Paeonol is an active component of Moutan Cortex Radicis and is widely used as an analgesic, antipyretic, and anti-inflammatory agent in traditional Chinese medicine. We wanted to determine the role of paeonol in treating adult respiratory distress syndrome (ARDS). We established an acute lung injury (ALI) model in Sprague-Dawley rats, which was similar to ARDS in humans, using intratracheal administration of lipopolysaccharide (LPS). The intraperitoneal administration of paeonol successfully reduced histopathological scores and attenuated myeloperoxidase-reactive cells as an index of polymorphonuclear neutrophils infiltration and also reduces inducible nitric oxide synthase expression in the lung tissue, at 16 h after LPS administration. In addition, paeonol reduced proinflammatory cytokines in bronchoalveolar lavage fluid, including tumor-necrosis factor-α, interleukin-1β, interleukin-6, and plasminogen-activated inhibition factor-1. These results indicated that paeonol successfully attenuates inflammatory and coagulation reactions to protect against ALI.
The aim of this work is to review the available literature on the details of low-level laser therapy (LLLT) use for the enhancement of the proliferation of various cultured cell lines including stem cells. A cell culture is one of the most useful techniques in science, particularly in the production of viral vaccines and hybrid cell lines. However, the growth rate of some of the much-needed mammalian cells is slow. LLLT can enhance the proliferation rate of various cell lines. Literature review from 1923 to 2010. By investigating the outcome of LLLT on cell cultures, many articles report that it produces higher rates of ATP, RNA, and DNA synthesis in stem cells and other cell lines. Thus, LLLT improves the proliferation of the cells without causing any cytotoxic effects. Mainly, helium neon and gallium-aluminum-arsenide (Ga-Al-As) lasers are used for LLLT on cultured cells. The results of LLLT also vary according to the applied energy density and wavelengths to which the target cells are subjected. This review suggests that an energy density value of 0.5 to 4.0 J/cm(2) and a visible spectrum ranging from 600 to 700 nm of LLLT are very helpful in enhancing the proliferation rate of various cell lines. With the appropriate use of LLLT, the proliferation rate of cultured cells, including stem cells, can be increased, which would be very useful in tissue engineering and regenerative medicine.
The aim of this work was to investigate if the low-level laser therapy (LLLT) on acute lung inflammation (ALI) induced by lipopolysaccharide (LPS) is linked to tumor necrosis factor (TNF) in alveolar macrophages (AM) from bronchoalveolar lavage fluid (BALF) of mice. LLLT has been reported to actuate positively for relieving the late and early symptoms of airway and lung inflammation. It is not known if the increased TNF mRNA expression and dysfunction of cAMP generation observed in ALI can be influenced by LLLT. For in vivo studies, Balb/c mice (n = 5 for group) received LPS inhalation or TNF intra nasal instillation and 3 h after LPS or TNF-α, leukocytes in BALF were analyzed. LLLT administered perpendicularly to a point in the middle of the dissected bronchi with a wavelength of 660 nm and a dose of 4.5 J/cm(2). The mice were irradiated 15 min after ALI induction. In vitro AM from mice were cultured for analyses of TNF mRNA expression and protein and adenosine3':5'-cyclic monophosphate (cAMP) levels. One hour after LPS, the TNF and cAMP levels in AM were measured by ELISA. RT-PCR was used to measure TNF mRNA in AM. The LLLT was inefficient in potentiating the rolipram effect in presence of a TNF synthesis inhibitor. LLLT attenuated the neutrophil influx and TNF in BALF. In AM, the laser increased the cAMP and reduced the TNF-α mRNA. LLLT increases indirectly the cAMP in AM by a TNF-dependent mechanism.
The aim of this work was to investigate the low-level laser therapy (LLLT) effect on alveolar macrophages (AM) activated by oxidative stress and lipopolysaccharide (LPS).
LLLT has been reported to actuate positively relieving the late and early symptoms of airway and lung inflammation. It is not known if the increased MIP-2 mRNA expression and intracellular reactive oxygen species (ROS) generation observed in acute lung inflammation (ALI) can be influenced by LLLT.
Rat AM cell line (AMJ2-C11) was cultured with LPS or H(2)O(2) and laser irradiated. MIP-2 mRNA and ROS production in the AM were evaluated by Real Time-PCR and the 2',7'-dichlorofluorescin diacetate (DCFH-DA) respectively. The NF-κB protein in the AM was measured by the enzyme linked immunoassay method. To investigate the antioxidant effect of laser, the AM were prebathed with N-acetylcysteine (NAC) and then irradiated with laser. LLLT was also studied in the presence of an inhibitor of NF-κB (BMS 205820). In addition, the effect of LLLT on NF-κB protein was investigated.
LLLT attenuated the MIP-2 mRNA expression and intracellular ROS generation after LPS or H(2)O(2). When the AM were pretreated with NAC, the laser effect was potentiated. BMS 205820 suppresses the effect of LLLT on MIP-2 mRNA expression and ROS generation, stimulated by LPS or H(2)O(2). On NF-κB transcription factor, both the LLLT and NAC reduced this protein in the AM exposed to LPS or H(2)O(2). The synergistic effect between LLLT and NAC on the reduction the NF-κB was also evidenced.
Results indicate that there is a synergistic action of LLLT with NAC on MIP-2 mRNA expression from LPS- or H(2)O(2)-stimulated AM, and that both ROS intracellular generation and NF-kB signaling seem to be involved.
Inflammatory cytokines have been related to the development of adult respiratory distress syndrome (ARDS), shock, and multiple organ dysfunction syndrome (MODS). We tested the hypothesis that unfavorable outcome in patients with ARDS is related to the presence of a persistent inflammatory response. For this purpose, we evaluated the behavior of inflammatory cytokines during progression of ARDS and the relationship of plasma inflammatory cytokines with clinical variables and outcome.
We prospectively studied 27 consecutive patients with severe medical ARDS. Plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukins (ILs) 1 beta, 2, 4, 6, and 8 were measured (enzyme-linked immunosorbent assay [ELISA] method) on days 1, 2, 3, 5, 7, 10, and 12 of ARDS and every third day thereafter while patients were receiving mechanical ventilation. Subgroups of patients were identified based on outcome, cause of ARDS, presence or absence of sepsis, shock, and MODS at the time ARDS developed. Subgroups were compared for levels of plasma inflammatory cytokines on day 1 of ARDS and over time.
Of the 27 patients, 13 survived ICU admission and 14 died (a mortality rate of 52%). Overall mortality was higher in patients with sepsis (86 vs 38%, p < 0.02). The mean initial plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 were significantly higher in nonsurvivors (p < 0.0001) and in those patients with sepsis (p < 0.0001). Plasma levels of IL-1 beta (p < 0.01) and IL-6 (p = 0.03) were more strongly associated with patient outcome than cause of ARDS (p = 0.8), lung injury score (LIS), APACHE II score, sepsis (p = 0.16), shock, or MODS score. Plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 remained significantly elevated over time (p < 0.0001) in those who died. Although it was the best early predictor of death (p < 0.001), plasma IL-2 > 200 pg/mL lost its usefulness after the first 48 h. A plasma IL-1 beta or IL-6 level > 400 pg/mL on any day in the first week of ARDS was associated with a low likelihood of survival.
Our findings indicate that unfavorable outcome in acute lung injury is related to the degree of inflammatory response at the onset and during the course of ARDS. Patients with higher plasma levels of TNF-alpha, IL-1 beta, IL-6, and IL-8 on day 1 of ARDS had persistent elevation of these inflammatory cytokines over time and died. Survivors had lesser elevations of plasma inflammatory cytokines on day 1 of ARDS and a rapid reduction over time. Plasma IL-1 beta and IL-6 levels were consistent and efficient predictors of outcome.
Background
The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries with cases reported worldwide. This novel Coronavirus Disease (COVID-19) is associated with a respiratory illness that may cause severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which have not been completely understood to date.
Objectives
We provide a review of the differences in terms of pathogenesis, epidemiology and clinical features between COVID-19, SARS and MERS.
Sources
The most recent literature in English language regarding COVID-19 has been reviewed and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics.
Content
COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than SARS (9.5%) and much lower than MERS (34.4%). It cannot be excluded that because of the COVID-19 less severe clinical picture it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2-2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7-1.9) and higher than MERS (<1),. The gastrointestinal route of transmission of SARS-CoV-2, which has been also assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs to be further investigated.
Implications
There is still much more to know about COVID-19, especially as concerns mortality and capacity of spreading on a pandemic level. Nonetheless, all of the lessons we learned in the past from SARS and MERS epidemics are the best cultural weapons to face this new global threat.
The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.
Background
Stem cells have attracted the researchers increasing interest, due to their applications in regenerative medicine. Their self-renewal, capacity for multipotent differentiation, and immunomodulatory properties make them unique to significantly contribute in tissue repair and regeneration applications. Recently, cells have shown increased proliferation when irradiated with low level laser therapy or Photobiomodulation therapy (PBMT), which induces the activation of intracellular and extracellular chromophores and the initiation of cellular signaling. The purpose of this study was to evaluate this phenomenon in the literature.
Method
The literature investigated the articles written in English in four electronic data bases of PubMed, Scopus, Google scholar and Cochrane up to April 2019. Stem cell was searched by combining the search keyword of "low level laser therapy" OR "low power laser therapy" OR "low intensity laser therapy" OR "photobiomodulation therapy" OR "photo biostimulation therapy" OR "LED". In total, 46 articles had eligibility to be evaluated.
Results
Studies demonstrated that red to near-infrared light is absorbed by the mitochondrial respiratory chain. Mitochondria are the significant sources of reactive oxygen species (ROS). Mitochondria play an important role in metabolism, energy generation, and are also involved in mediating the effects induced by PBMT. PBMT may result in the increased production of (ROS), nitric oxide (NO), adenosine triphosphate (ATP), and cyclic adenosine monophosphate (cAMP). These changes in turn initiate cell proliferation and induce the signal cascade effect.
Conclusion
The findings of this review suggest that PBMT -based regenerative medicine could be a useful tool for future advances in tissue engineering and cell therapy.
Glucocorticoids (GC) in all its various forms and formulations are likely one of the most commonly used pharmacologic agents in medicine. Their use can be profoundly therapeutic but are also associated with a myriad of acute and chronic side effects. It is fairly well-accepted in the medical community that GC can be life-saving when used in critically ill patients with severe exacerbations of asthma and chronic obstructive pulmonary disease, HIV-associated pneumocystosis, and systemic vasculitides.
However, the adjunctive role of GC is much more controversial in acute respiratory distress syndrome (ARDS), septic shock, community-acquired pneumonia, and several other serious medical conditions. Despite such controversies, GC should at least be considered for patients with fulminant manifestations of the following conditions as there is equipoise to indicate that GC may improve outcome with acceptable risks: (i) severe ARDS with refractory hypoxemia despite one to two weeks of state-of-the-art management, (ii) recalcitrant, vasopressor-dependent septic shock, (iii) non-influenza, severe community-acquired pneumonia, and (iv) severe alcoholic hepatitis.
The bases for these controversies is likely due to both host factors (e.g., differences in GC resistance and susceptibility to adverse effects) and different phenotypes of any one disease state; e.g., different pathogenesis and pathogens under the rubric of “sepsis.” Elucidation of better biomarkers to determine the underlying pathogenic phenotype will significantly advance our understanding and prediction of which critically ill patients will benefit from GC and who would experience a deleterious effect from its use.
Objective: This study represents a viable assessment of the effect of the low-level laser (LLL) of 635 nm and ultraviolet (UV) of 265 nm on biophysical properties of blood.
Materials and methods: Blood samples were divided into two main groups: one for irradiation by LLL and the other for irradiation by UV. Each group was divided into three aliquots. First aliquot: whole blood was exposed to radiation. The second aliquot: erythrocytes were exposed to radiation and resuspended in autologous plasma. The third aliquot: plasma was exposed to radiation, and erythrocytes were resuspended in it. The following parameters were measured after irradiation by LLL and UV for all aliquots: whole blood viscosity, microscopic aggregation index, deformation index, and Zeta potential.
Results: A decrease in whole blood viscosity due to irradiation by LLL was observed. To the contrary, an increase in whole blood viscosity due to irradiation by UV was detected. A significant reduction in erythrocytes' aggregation was observed as a result of LLL and UV radiation. Erythrocytes' deformability was strongly affected by UV radiation, while there was no significant effect from LLL. Another noticeable change observed was an increase in Zeta potential due to UV and a decrease in Zeta potential values, as a result of LLL irradiation.
Conclusions: It can be concluded from this study that LLL and UV can be used to change some biological processes, as well as cellular properties.
Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are defined as a pulmonary inflammation, could occur from sepsis and leads to pulmonary permeability and alveolar edema making it a life-threatening disease. Photobiomodulation (PBM) properties have been widely described in the literature in several inflammatory diseases; although the mechanisms of action are not always clear, this could be a possible treatment for ARDS/ALI. Thus, the aim of this study was to evaluate the mRNA levels from Caspase-3 and BCL-2 genes and DNA fragmentation in lung tissue from Wistar rats affected by ALI and submitted to photobiomodulation by exposure to low power infrared laser (808nm; 100mW; 3.571W/cm²; four points per lung). Adult male Wistar rats were randomized into 6 groups (n=5, for each group): control, PBM10 (10J/cm², 2J and 2 seconds), PBM20 (20J/cm², 5J and 5 seconds), ALI, ALI+PBM10 and ALI+PBM20. ALI was induced by intraperitoneal Escherichia coli lipopolysaccharide injection. Lung samples were collected and divided for mRNA expression of Caspase-3 and Bcl-2 and DNA fragmentation quantifications. Data show that Caspase-3 mRNA levels are reduced and Bcl-2 mRNA levels increased in ALI after low power infrared laser exposure when compared to non-exposed ALI group. DNA fragmentation was increased in inflammatory infiltrate cells and reduced in alveolar cell. Our research shows that photobiomodulation can alter mRNA relative levels from genes involved in apoptotic process and DNA fragmentation in inflammatory and alveolar cells after lipopolysaccharide-induced acute lung injury. Also, inflammatory cell apoptosis is part of the photobiomodulation effects induced by exposure to low power infrared laser.
Endogenous glucocorticoids are crucial to various physiological processes, including metabolism, development and inflammation. Since 1948, synthetic glucocorticoids have been used to treat various immune-related disorders. The mechanisms that underlie the immunosuppressive properties of these hormones have been intensely scrutinized, and it is widely appreciated that glucocorticoids have pleiotropic effects on the immune system. However, a clear picture of the cellular and molecular basis of glucocorticoid action has remained elusive. In this Review, we distil several decades of intense (and often conflicting) research that defines the interface between the endocrine stress response and the immune system.
Introduction The acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice. Methods A study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood. Six experimental groups were designated as: 1) endotoxin alone, 2) endotoxin + total fresh whole bone marrow nuclear cells (BMC), 3) endotoxin + non-hematopoietic bone marrow cells (CD45 neg), 4) endotoxin + hematopoietic bone marrow cells (CD45 positive), 5) endotoxin + buffy coat and 6) endotoxin + in vitro expanded swine CD45 negative adherent allogeneic bone marrow cells (cultured CD45neg). We measured at different levels the biological consequences of the infusion of the different subsets of cells. The measured parameters were: pulmonary vascular resistance (PVR), gas exchange (PO2), lung edema (lung wet/dry weight), gene expression and serum concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6. Results Infusion of freshly purified autologous total BMCs, as well as non-hematopoietic CD45(-) bone marrow cells significantly reduced endotoxin-induced pulmonary hypertension and hypoxemia and reduced the lung edema. Also, in the groups that received BMCs and cultured CD45neg we observed a decrease in the levels of IL-1β and TNF-α in plasma. Infusion of hematopoietic CD45(+) bone marrow cells or peripheral blood buffy coat cells did not protect against LPS-induced lung injury. Conclusions We conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating the inflammatory response, mechanisms that do not involve engraftment or trans-differentiation of the cells. These observations may have important implications for the design of future cell therapies for ARDS.
Objective:
The purpose of this study was to review available literature about the effect of photobiomodulation (PBM) on mesenchymal stem cells (MSCs).
Background data:
The effects of coherent and noncoherent light sources such as low-level lasers and light-emitting diodes (LEDs) on cells and tissues, known as PBM, form the basis of photomedicine. This treatment technique effects cell function, proliferation, and migration, and plays an important role in tissue regeneration. Stem cells have been found to be helpful elements in tissue regeneration, and the combination of stem cell therapy and laser therapy appears to positively affect treatment results.
Materials and methods:
An electronic search in PubMed was conducted of publications from the previous 12 years. English language articles related to the subject were found using selected key words. The full texts of potentially suitable articles were assessed according to inclusion and exclusion criteria.
Results:
After evaluation, 30 articles were deemed relevant according to the inclusion criteria. The energy density of the laser was 0.7-9 J/cm(2). The power used for visible light was 30-110 mW and that used for infrared light was 50-800 mW. Nearly all studies showed that low-level laser therapy had a positive effect on cell proliferation. Similar outcomes were found for LED; however, some studies suggest that the laser alone is not effective, and should be used as an adjunct tool.
Conclusions:
PBM has positive effects on MSCs. This review concluded that doses of 0.7-4 J/cm(2) and wavelengths of 600-700 nm are appropriate for light therapy. The results were dependent upon different parameters; therefore, optimization of parameters used in light therapy to obtain favorable results is required to provide more accurate comparison.
We previously showed that near-infrared laser photobiomodulation (PBM) (810 nm, CW, 18 J/cm(2) , 25 mW/cm(2) ) delivered to the mouse daily for 3-days after a controlled cortical impact traumatic brain injury (TBI) gave a significant improvement in neurological/cognitive function. However the same parameters delivered 14X daily gave significantly less benefit. This biphasic dose response intrigued us, and we decided to follow the mice that received 3X or 14X laser treatments out to 56-days post-TBI. We found the 14X group showed worse neurological function than the no-treatment TBI group at 2-weeks, but started to improve steadily during the next 6-weeks, and by 56-days were significantly better than the no-treatment TBI mice, but still worse than the 3X mice. A marker of activated glial cells (GFAP) was significantly increased in the brain regions (compared to both untreated TBI and 3X groups) at 4-weeks in the 14X group, but the GFAP had fallen to low levels in both 3X and 14X groups by 8-weeks. We conclude that an excessive number of laser-treatments delivered to mice can temporarily inhibit the process of brain repair stimulated by tPBM, but then the inhibitory effect ceases, and brain repair can resume. The mechanism may be temporary induction of reactive gliosis.
This study investigated cytochemical changes of calcium ion dependent adenosine triphosphatase (Ca2+-ATPase) activity in rat saphenous artery following irradiation of low reactive level laser (GaAlAs diode laseer). Three experimental groups of animals were used: group 1 received a single 15 s irradiation, group 2 for 2 days, twice per day, 15 s per irradiation, and group 3 for 4 days, twice per day, 15 s per irradiation. A fourth group was unirradiated, and acted as the control group. Irradiation for 4 days (irradiation was performed twice per day) induced intensification f Ca2+-ATPase activity in endothelial and smooth muscle cells. Noticeable finding was indicated in the caveolae and vesicles of the abluminal side of the endothelial cell. After irradiation, the numbr of caveolae and vesicles increased, in addition to intensification of the Ca2+-ATPase activity. These findings suggested that intensification of Ca2+-ATPase activity in low reactive level laser-treated saphenous artery may be associated with increase of vascular permeability in endothelial cells and vasodilation by active Ca2+ extrusion.
Low-level laser therapy (LLLT) is growing rapidly as an accredited anti-inflammatory therapy. However, its effects in models of inflammatory lung diseases are unknown. Therefore, this study investigated the effects of LLLT in two models of LPS-induced acute respiratory distress (ARDS). Intratracheal(i.t) LPS (10ug/mouse) and intraperitoneal (i.p) LPS (100ug/mouse) were used. LLLT consisted of (laser at 830nm, 3J/cm², 35mW, 80 seconds per point 3 points per application) in direct contact with the skin, beginning one hour after LPS administration, repeated consecutively for three times. BALB/c male mice were divided into control (n=6), LPS i.t (n=7), LPS i.p (n=7), LPS i.t. + LLLT (n=9), LPS i.p. + LLLT (n=9). Twenty-four hours after LPS administration, the animals were euthanized for evaluation of pulmonary inflammation by: Total and differential cell counts in bronchoalveolar lavage (BAL), analysis of cytokines levels in BAL and in serum (IL-1beta, IL-6, KC, and TNF-alpha) and through the quantitative analysis of the number of neutrophils in the lung parenchyma. The results showed that LLLT significantly reduced the levels LPS i.t. and LPS i.p. induce ARDS as demonstrated by reduced number of total cells (p<0.001) and neutrophils (p<0.001) in the BAL, reduced levels of IL-1beta, IL-6, KC, and TNF-alpha in BAL and in serum (p<0.001), beyond the number of neutrophils in the lung parenchyma (p<0.001). On the other hand, LLLT have not increased IL-10 levels. We conclude that low-level laser therapy at 830nm is effective in reducing pulmonary and systemic inflammation in models of LPS-induced ARDS independent of the etiology of the disease.
Low level laser therapy (LLLT) is a known anti-inflammatory therapy. Herein we studied the effect of LLLT on lung permeability and the IL-1beta level in LPS-induced pulmonary inflammation. STUDY DESIGN/METHODOLOGY: Rats were divided into 12 groups (n = 7 for each group). Lung permeability was measured by quantifying extravasated albumin concentration in lung homogenate, inflammatory cells influx was determined by myeloperoxidase activity, IL-1beta in BAL was determined by ELISA and IL-1beta mRNA expression in trachea was evaluated by RT-PCR. The rats were irradiated on the skin over the upper bronchus at the site of tracheotomy after LPS.
LLLT attenuated lung permeability. In addition, there was reduced neutrophil influx, myeloperoxidase activity and both IL-1beta in BAL and IL-1beta mRNA expression in trachea obtained from animals subjected to LPS-induced inflammation.
LLLT reduced the lung permeability by a mechanism in which the IL-1beta seems to have an important role.
The present study aimed to investigate the effects low level laser therapy (LLLT) in a LPS-induced pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS) in BALB/c mice. Laser (830nm laser, 9J/cm(2), 35mW, 80s per point, 3 points per application) was applied in direct contact with skin, 1h after LPS administration. Mice were distributed in control (n=6; PBS), ARDS IT (n=7; LPS orotracheally 10μg/mouse), ARDS IP (n=7; LPS intra-peritoneally 100μg/mouse), ARDS IT+Laser (n=9; LPS intra-tracheally 10μg/mouse), ARDS IP+Laser (n=9; LPS intra-peritoneally 100μg/mouse). Twenty-four hours after last LPS administration, mice were studied for pulmonary inflammation by total and differential cell count in bronchoalveolar lavage (BAL), cytokines (IL-1beta, IL-6, KC and TNF-alpha) levels in BAL fluid and also by quantitative analysis of neutrophils number in the lung parenchyma. LLLT significantly reduced pulmonary and extrapulmonary inflammation in LPS-induced ARDS, as demonstrated by reduced number of total cells (p<0.001) and neutrophils (p<0.001) in BAL, reduced levels of IL-1beta, IL-6, KC and TNF-alpha in BAL fluid and in serum (p<0.001), as well as the number of neutrophils in lung parenchyma (p<0.001). LLLT is effective to reduce pulmonary inflammation in both pulmonary and extrapulmonary model of LPS-induced ARDS.
The aim of the study was to confirm the analgesic effect of low-power laser radiation with a tail-immersion test and check if nitric oxide is involved in laser radiation-induced analgesia in rats. The experiment was performed on male Wistar rats. On the day of experiment the scull of rats was exposed to IR laser radiation for 10 min and antinociceptive effect was determined by means of tail immersion test. The experiments were also performed on 1-NAME and methylene blue pretreated rates, in which both chemicals were administered into right lateral brain ventricle. The results were compared to the ones obtained in the control group in which sham irradiation was made. It was observed that 10 min. exposure to low-power IR laser radiation induced only transient distinct antinociceptive effect in rats. This effect was prevented by ICV. injection of 1-NAME, an inhibitor of nitric oxide synthase and methylene blue, an inhibitor of soluble guanylate cyclase. It seems that nitric oxide is involved in mechanism of low-power laser radiation- induced analgesia.
Acute respiratory distress syndrome (ARDS) is a medical emergency, which may be precipitated by an acute injury to the lung. The injury can also follow direct chest trauma from aspiration of gastric contents or inhalation of toxic gasses. ARDS is not itself a specific disease but a syndrome - a group of symptoms and signs that make up one of the most important forms of respiratory failure.ARDS is devastating because it can develop quite suddenly in persons whose lungs had been perfectly normal - it kills at least 60% of its victims. The fundamental problem is the sudden appearance of large amounts of fluid in the lung preventing blood from entering the alveoli and decreasing oxygen extraction resulting in hypoxemia.The tragic feature of ARDS is that it drowns its victim. The appearance of fluid in the lungs a lethal situation - is from neuro-inflammation.Important to keep in mind when treating ARDS are: a) Inflammation and Inflammatory exudates Gap Formation, b) Interstitial and Alveolar Inflammation, c) Inflammation and the Nervous System, d) Cholinergic anti-inflammatory pathway.Neuro-inflammation can be relieved by stimulation of the vagus nerve. Low-level laser therapy, a simple modality with few undesirable side effects, is used to relieve respiratory distress
It is unknown if the oxidative stress can be regulated by low- level laser therapy (LLLT) in lung inflammation induced by intestinal reperfusion (i-I/R). A study was developed in which rats were irradiated (660 nm, 30 mW, 5.4 J) on the skin over the bronchus and euthanized 2 h after the initial of intestinal reperfusion. Lung edema and BALF neutrophils were measured by the Evans blue extravasation and myeloperoxidase (MPO) activity, respectively. Lung histology was used for analyzing the injury score. Reactive oxygen species (ROS) was measured by fluorescence. Both expression adhesion molecule (ICAM-1) and peroxisome-proliferator-activated receptor-y (PPARy) were measured by RT-PCR. The lung immunohistochemical localization of ICAM-1 was visualized as a brown stain. Both lung HSP 70 and glutathione protein were evaluated by ELISA. LLLT reduced neatly the edema, neutrophils influx, MPO activity and ICAM-1 mRNA expression. LLLT also reduced the ROS formation and oppositely increased GSH concentration in lung from i-I/R groups. Both HSP 70 and PPARy expression also were elevated after laser irradiation. Results indicate that laser effect in attenuating the acute lung inflammation is driven to restore the balance between the pro- and anti-oxidants mediators rising of PPARy expression and consequently the HSP 70 production. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.
Background and Objective
It is unknown if pro- and anti-inflammatory mediators in acute lung inflammation induced by intestinal ischemia and reperfusion (i-I/R) can be modulated by low-level laser therapy (LLLT).Study Design/Material and MethodsA controlled ex vivo study was developed in which rats were irradiated (660 nm, 30 mW, 0.08 cm2 of spot size) on the skin over the right upper bronchus 1 hour post-mesenteric artery occlusion and euthanized 4 hours later. For pretreatment with anti-tumor necrosis factor (TNF) or IL-10 antibodies, the rats received either one of the agents 15 minutes before the beginning of reperfusion.Methods
Lung edema was measured by the Evans blue extravasation and pulmonary neutrophils influx was determined by myeloperoxidase (MPO) activity. Both TNF and IL-10 expression and protein in lung were evaluated by RT-PCR and ELISA, respectively.ResultsLLLT reduced the edema (80.1 ± 41.8 µg g−1 dry weight), neutrophils influx (0.83 ± 0.02 × 106 cells ml−1), MPO activity (2.91 ± 0.60), and TNF (153.0 ± 21.0 pg mg−1 tissue) in lung when compared with respective control groups. Surprisingly, the LLLT increased the IL-10 (0.65 ± 0.13) in lung from animals subjected to i-I/R. Moreover, LLLT (0.32 ± 0.07 pg ml−1) reduced the TNF-α level in RPAECs when compared with i-I/R group. The presence of anti-TNF or IL-10 antibodies did not alter the LLLT effect on IL-10 (465.1 ± 21.0 pg mg−1 tissue) or TNF (223.5 ± 21.0 pg mg−1 tissue) in lung from animals submitted to i-I/R.Conclusion
The results indicate that the LLLT attenuates the i-I/R-induced acute lung inflammation which favor the IL-10 production and reduce TNF generation. Lasers Surg. Med. 43:410–420, 2011. © 2011 Wiley-Liss, Inc.
Intestinal ischemia and reperfusion (i-I/R) is an insult associated with acute respiratory distress syndrome (ARDS). It is not known if pro- and anti-inflammatory mediators in ARDS induced by i-I/R can be controlled by low-level laser therapy (LLLT). This study was designed to evaluate the effect of LLLT on tracheal cholinergic reactivity dysfunction and the release of inflammatory mediators from the lung after i-I/R. Anesthetized rats were subjected to superior mesenteric artery occlusion (45 min) and killed after clamp release and preestablished periods of intestinal reperfusion (30 min, 2 or 4 h). The LLLT (660 nm, 7.5 J/cm(2)) was carried out by irradiating the rats on the skin over the right upper bronchus for 15 and 30 min after initiating reperfusion and then euthanizing them 30 min, 2, or 4 h later. Lung edema was measured by the Evans blue extravasation technique, and pulmonary neutrophils were determined by myeloperoxidase (MPO) activity. Pulmonary tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), intercellular adhesion molecule-1 (ICAM-1), and isoform of NO synthase (iNOS) mRNA expression were analyzed by real-time PCR. TNF-α, IL-10, and iNOS proteins in the lung were measured by the enzyme-linked immunoassay technique. LLLT (660 nm, 7.5 J/cm(2)) restored the tracheal hyperresponsiveness and hyporesponsiveness in all the periods after intestinal reperfusion. Although LLLT reduced edema and MPO activity, it did not do so in all the postreperfusion periods. It was also observed with the ICAM-1 expression. In addition to reducing both TNF-α and iNOS, LLLT increased IL-10 in the lungs of animals subjected to i-I/R. The results indicate that LLLT can control the lung's inflammatory response and the airway reactivity dysfunction by simultaneously reducing both TNF-α and iNOS.
MitochondriaLaserTransmembrane proton gradientMembrane potentialATP synthesisOxygen uptake
Phototherapy with low intensity laser irradiation has shown to be effective in promoting the proliferation of different cells. The aim of this in vitro study was to evaluate the potential effect of laser phototherapy (660 nm) on human dental pulp stem cell (hDPSC) proliferation.
The hDPSC cell strain was used. Cells cultured under nutritional deficit (10% FBS) were either irradiated or not (control) using two different power settings (20 mW/6 seconds to 40 mW/3 seconds), with an InGaAIP diode laser. The cell growth was indirectly assessed by measuring the cell mitochondrial activity through the MTT reduction-based cytotoxicity assay.
The group irradiated with the 20 mW setting presented significantly higher MTT activity at 72 hours than the other two groups (negative control--10% FBS--and lased 40 mW with 3 seconds exposure time). After 24 hours of the first irradiation, cultures grown under nutritional deficit (10% FBS) and irradiated presented significantly higher viable cells than the non-irradiated cultures grown under the same nutritional conditions.
Under the conditions of this study it was possible to conclude that the cell strain hDPSC responds positively to laser phototherapy by improving the cell growth when cultured under nutritional deficit conditions. Thus, the association of laser phototherapy and hDPSC cells could be of importance for future tissue engineering and regenerative medicine. Moreover, it opens the possibility of using laser phototherapy for improving the cell growth of other types of stem cells.
It has been suggested that low intensity laser therapy (LILT) acts on pulmonary inflammation. Thus, we investigate in this work if LILT (650nm, 2.5mW, 31.2mW/cm(2), 1.3J/cm(2), laser spot size of 0.08cm(2) and irradiation time of 42s) can attenuate edema, neutrophil recruitment and inflammatory mediators in acute lung inflammation. Thirty-five male Wistar rats (n=7 per group) were distributed in the following experimental groups: control, laser, LPS, LPS+laser and dexamethasone+LPS. Airway inflammation was measured 4h post-LPS challenge. Pulmonary microvascular leakage was used for measuring pulmonary edema. Bronchoalveolar lavage fluid (BALF) cellularity and myeloperoxidase (MPO) were used for measuring neutrophil recruitment and activation. RT-PCR was performed in lung tissue to assess mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin (IL-10), cytokine-induced neutrophil chemoattractant-1 (CINC-1), macrophage inflammatory protein-2 (MIP-2) and intercellular adhesion molecule-1 (ICAM-1). Protein levels in both BALF and lung were determined by ELISA. LILT inhibited pulmonary edema and endothelial cytoskeleton damage, as well as neutrophil influx and activation. Similarly, the LILT reduced the TNF-α and IL-1β, in lung and BALF. LILT prevented lung ICAM-1 up-regulation. The rise of CINC-1 and MIP-2 protein levels in both lung and BALF, and the lung mRNA expressions for IL-10, were unaffected. Data suggest that the LILT effect is due to the inhibition of ICAM-1 via the inhibition of TNF-α and IL-1β.
It is unknown if the decreased ability to relax airways smooth muscles in asthma and other inflammatory disorders, such as acute respiratory distress syndrome (ARDS), can be influenced by low level laser therapy (LLLT) irradiation. In this context, the present work was developed in order to investigate if LLLT could reduce dysfunction in inflamed bronchi smooth muscles (BSM) in rats.
A controlled ex vivo study was developed where bronchi from Wistar rat were dissected and mounted in an organ bath apparatus with or without a TNF-alpha.
LLLT administered perpendicularly to a point in the middle of the dissected bronchi with a wavelength of 655 nm and a dose of 2.6 J/cm(2), partially decreased BSM hyperreactivity to cholinergic agonist, restored BSM relaxation to isoproterenol and reduced the TNF-alpha mRNA expression. An NF-kappaB antagonist (BMS205820) blocked the LLLT effect on dysfunction in inflamed BSM.
The results obtained in this work indicate that the LLLT effect on alterations in responsiveness of airway smooth muscles observed in TNF-alpha-induced experimental acute lung inflammation seems to be dependent of NF-kappaB activation.
The aim of this randomized controlled clinical trial was to determine the anxiety levels of patients with recurrent aphthous stomatitis (RAS) prior to therapy with the Nd:YAG laser or medication, and to compare the effects of these different treatment methods on the degree of post-treatment pain, discomfort, and functional complications (eating and speech) experienced.
Twenty patients with RAS-related oral problems were included in the study. Levels of pre- and post-treatment pain and functional complications were assessed at patient visits on days 1, 4, and 7.
The results indicated that patients treated with the Nd:YAG laser had less post-treatment pain and fewer functional complications, and reported immediate relief of pain and faster healing (p +/- 0.05). However, only after 5 d was there a significant reduction in the pain levels of the patients treated with medication.
Our results suggest that the Nd:YAG laser has better patient acceptance, shorter treatment time, and lower rates of pain and post-treatment adverse events among patients with RAS.
The effects of laser light on the immune system have not been extensively characterized. Low-power laser sources, such as the helium-neon (He-Ne) laser with a wavelength of 632.8 nm, have been found to produce photobiological effects with evidence of interference with immunological functions. We have investigated the effects of He-Ne laser irradiation on Ficoll-Hypaque-isolated human peripheral blood mononuclear cells (PBMC). Cultured cells were irradiated for various times at two selected intensities and then stimulated with different mitogens. The rate of incorporation of 3H-thymidine into the DNA of stimulated cells decreased with increasing energy density. The levels of interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in supernatants of the cultures were determined (irradiated either before or after stimulation). When stimulating cells after irradiation, significantly increased levels of all cytokines were detected after 30 min of irradiation (18.9 J cm-2), whereas after 60 min of irradiation (37.8 J cm-2) cytokine levels were found to be significantly decreased.
Interferon-gamma (IFN-gamma) is an important cytokine involved in the regulation of allergen-induced immune responses. We examined the role of IFN-gamma in a Brown-Norway rat model of bronchial hyperresponsiveness (BHR) and airway eosinophilia, and its effects on the mRNA expression of T helper type 1 (Th1)/Th2 cytokine. Ovalbumin (OA)-sensitized animals were given either exogenous IFN-gamma (105 U/rat over 3 days, intraperitoneally) or anti-IFN-gamma blocking antibody (DB-1 0.3 mg/rat, intravenously) prior to exposure to OA aerosol and were studied 18-24 hr later. In sensitized animals, OA induced significant BHR, accumulation of eosinophils, T lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid, and also increased eosinophils and CD8+ T cells in the airways. Exogenous IFN-gamma attenuated allergen-induced BHR (P<0.02, compared with sham-treated animals) together with a significant reduction in eosinophil and neutrophil numbers in BAL fluid (P<0. 005), and eosinophils and CD8+ T cells in airways (P<0.05). By contrast, anti-IFN-gamma antibody increased airway CD4+ T cells and BHR. Using reverse transcriptase-polymerase chain reaction, significant increases in Th2 [interleukin-4 (IL-4), IL-5 and IL-10], and IFN-gamma cytokine mRNA were found in the lungs of sensitized and OA-exposed animals, while exogenous IFN-gamma significantly suppressed IL-4, IL-5 and IL-10 mRNA expression, and anti-IFN-gamma antibody increased IL-4 and IL-5 mRNA expression. These results indicate that Th1 effects, such as those mediated by IFN-gamma, play a down-regulatory role to suppress the Th2 responses associated with allergen-induced BHR and eosinophilic inflammation.