Dose-Response is an open access peer-reviewed online journal publishing original findings and commentaries on the occurrence of dose-response relationships across a broad range of disciplines, including physiology, biochemistry, molecular biology, toxicology, radiation biology, pharmacology, medicine, experimental psychology, plant biology, as well as environmental and related sciences.
Adenomyosis is a uterine condition in which endometrial glands and stroma are commonly pathologically observed in the myometrium. In this study, we sought to determine the effect of resveratrol on the progression of adenomyosis. Adenomyosis was induced in mice given tamoxifen neonatally. All mice were subjected to body weight measurement and hotplate testing every four weeks beginning four weeks after birth. All mice with adenomyosis were randomly separated into 3 groups at 16 weeks: untreated, low-dose resveratrol (25 mg/kg), and high-dose resveratrol (50 mg/kg). After 3 weeks of treatment, final hotplate test and body weight measurement were performed, and the uterine horn blood samples were collected. Adenomyosis in mice caused body weight loss and uterine weight gain, reduced hotplate latency, and progression of endometrial fibrosis. The underlying biological process could be coupled with the overexpression of many cells' proliferation and immune-regulation-related genes. Resveratrol treatment could slow the progression of adenomyosis by enhancing hotplate latency, lowering endometrial fibrosis, and restoring cell proliferation- and immune-regulation-associated gene expression levels in endometrium and plasma. However, resveratrol treatment also reduced the body weight and uterine weight. In conclusion, Resveratrol might be a potential compound for treating patients with adenomyosis.
The therapeutic potential of Haloxylon griffithii found in northern region of Balochistan, so far has been neglected.
The current study was aimed to assess the phytochemicals and pharmacological potential of fractions isolated from H griffithii.
During phytochemicals analysis of H griffithii using GC/MS showed various bioactive compounds like alkaloids, flavonoids, terpenoids, tannins, saponins, and carboxylic acids. In vitro antioxidant activity of H griffithii was determined by 2, 2’- diphenyl-1-picrylhydrazyl (DPPH) assay. Disc diffusion method was used to evaluate the antimicrobial activity.
The quantitative analysis of ethyl acetate showed highest total flavonoid contents (1.19 ± .05) while ethanol with lowest value (.52 ± .01). The total phenolic contents in ethyle acetate was 1.50 ± .42, whereas ethanol showed lowest value (.77 ± .02). Ethanol exhibited excellent (88.68 ± 3.0) free radical scavenging potential measured by 1,1-diphenyl-2-picryl-hydrazyl radical scavenging assay. For antimicrobial activity, different bacterial and fungal strains like B subtilis, S aureus, E coli, S typhi, C albicans, and A. niger were selected . The essential oil showed maximum % inhibition diameter (9 mm) against B. Subtillus and (5 mm) against C albicans, respectively . The ethyl acetate presented % inhibition diameter (9 mm) against S aureus and (6 mm) against A niger. Anti-urease activity also showed positive response.
The presence of high (%) bioactive compounds with great therapeutic potential suggest that H griffithii can be used as natural alternative of synthetic drugs without side effects.
Herd immunity against measles is essential to interrupt measles transmission, and this can only be attained by reaching at least 95% coverage for each of the 2 doses of measles vaccine provided in infancy and early childhood age group. It is important to provide everyone with 2 doses of the measles vaccine in order to effectively safeguard the population. Despite this, little is known about the second dosage of the measles vaccine utilization status and the factors that affect it. Therefore, this study aimed to assess second dose of measles vaccination utilization and its associated factors among children aged 24–35 months in Jabitehnan district, 2020.
A community-based cross-sectional study design was conducted at Jabitehnan District, Northwest Ethiopia, from September 1st, 2020 to October 1st, 2020. Systematic random sampling technique was used to select 845 mothers/caregivers who had children aged 24–35 months. Both bi-variable and multivariable logistic regression was fitted to identify the determinant factors of second dose measles vaccination utilization. Finally, the statistical significant variables were declared by using 95% CI and P value less than .05 in the multivariable logistic regression analysis. The Hosmer and Lemeshow test was used to check the model’s fit to the data, and the variance inflation factor was used to assess multi-collinearity.
The overall second dose of measles vaccination utilization was 48.1%, (95% CI: 44.7-51.6). Mothers with primary school education (AOR = 1.91, 95% CI: 1.15-3.17), information about MCV2 (AOR = 6.53, 95% CI: 4.22-10.08), distance from vaccination site (AOR = 3.56, 95% CI: 2.46-5.14), knowledge about immunization (AOR = 1.935, 95% CI: 1.29-2.90), and favorable attitude about immunization (AOR = 5.19, 95% CI: 3.25-8.29) were significantly associated factors with second dose of measles vaccination utilization.
Second dose measles vaccination utilization in the district was lower than the national target. Maternal education, distances from vaccination site, information about MCV2, and knowledge about immunization were significantly associated variables with second dose measles vaccination utilization. Therefore, in order to increase the utilization of the second dose of the measles vaccine, improved health education and service expansion to difficult-to-reach areas are required.
Acanthopanacis Cortex (AC) is a valuable Chinese medicine, which exerts beneficial effects on anti-fatigue, anti-stress, and inflammatory modulation in the periphery. However, the central nervous system (CNS) function of AC has not been clearly illustrated. As communication between the peripheral immune system and the CNS converges, it promotes a heightened neuroinflammatory environment that contributes to depression. We investigated the effect of AC against depression through neuroinflammatory modulation.
Network pharmacology was used to screen for target compounds and pathways. Mice with CMS-induced depression were used to evaluate the efficacy of AC against depression. Behavioral studies and detection of neurotransmitters, neurotrophic factors, and pro-inflammatory cytokines were performed. The IL-17 signaling cascade was involved to further investigate the underlying mechanism of AC against depression.
Twenty-five components were screened by network pharmacology and the IL-17 mediated signaling pathway was associated with the antidepressant action of AC. This herb had a beneficial effect on CMS-induced depressive mice, including improvements in depressive behavior, modulation of neurotransmitter levels, neurotrophic factors, and pro-inflammatory cytokines.
Our results revealed that AC exhibits effects on anti-depression and one of the mechanisms was mediated by neuroinflammatory modulation.
The use of doxorubicin (DOX) as an anthraquinone antineoplastic agent is limited due to its cardiotoxicity. Our previous study suggested that low-dose radiation (LDR) could mitigate the cardiotoxicity induced by DOX via suppressing oxidative stress and cell apoptosis. However, the molecular targets and protective mechanism of LDR are not understood. In the present study, we sought to investigate the mechanisms underlying LDR’s cardioprotection. Balb/c mice were randomly divided into four groups: Control group (no treatment), DOX group, LDR group (75 mGy), and LDR-72 h-DOX group (LDR pretreatment followed by intraperitoneal injection of DOX). Electron microscopy, PCR, and Western blot analyses indicated that LDR pretreatment mitigated changes in mitochondrial morphology caused by DOX, upregulated activity of mitochondrial complexes, and restored ATP levels in cardiomyocytes that were decreased by DOX. Whole genome microarray and PCR analyses showed that mitochondrial-related genes were altered by LDR pretreatment. Thus, our study showed that LDR can protect cardiomyocytes against DOX through improving mitochondrial function and increasing ATP production. This research could inform DOX chemotherapy strategies and provide new insight into the molecule mechanisms underlying the cardioprotective effects of LDR.
Esketamine, the right-handed optical isomer of racemic ketamine, has recently become widely used for anesthesia and analgesia as a replacement for racemic ketamine. However, there are limited studies comparing the anesthetic and analgesic effects of esketamine and racemic ketamine in mice. This research was conducted to analyze the dose-dependent anesthetic and analgesic efficacy of esketamine in mice and to compare its potency with that of the racemate. We tested the anesthetic effects of different doses of esketamine and compared its potency with that of the racemate using righting reflex tests. Then, the acetic acid-induced pain model and formalin-induced pain model were used to investigate the analgesic effect. Compared with racemic ketamine, an equivalent dose of esketamine at 100 mg/kg was required to induce stable anesthesia. In contrast, 5 mg/kg esketamine was sufficient to provide analgesic effects similar to those of 10 mg/kg ketamine. Together, esketamine had a similar potency to racemic ketamine for anesthesia and a stronger potency for analgesia in mice.
Ulcerative colitis (UC) is an inflammatory bowel disease involving chronic and recurring colon inflammation. Current management protocols are limited by adverse effects or short-term symptomatic relief. We aimed to investigate the possible therapeutic prospect of low dose gamma (γ) irradiation or apigenin treatment in acetic acid-induced UC in rats. Induction of UC was carried out by installation of acetic acid intra-rectally. One hour post-induction, rats received a sole dose of γ-radiation (0.5 Gray) or were treated with apigenin (3 mg/kg/day, peroral) for 7 successive days. Antioxidant and anti-inflammatory effects of both agents were assessed via determination of colon malondialdehyde (MDA), reduced glutathione (GSH), total nitrate/nitrite (NOx), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), and interleukin-1beta (IL-1β) contents as well as myeloperoxidase (MPO) activity. Body weight (BW), colon weight/length (W/L) ratio, disease activity index (DAI), and histopathological changes were evaluated. Gamma irradiation and apigenin significantly ameliorated the acetic acid-induced biochemical and histopathological changes. Both therapeutic approaches significantly restored colon contents of the investigated biomarkers. They modulated BW, colon W/L ratio and DAI. This study proposes low dose γ-irradiation as a new therapeutic candidate for the management of UC. We also concluded that apigenin exhibited therapeutic benefits in UC management.
Magnesium is an antagonist of the N-methyl-D-aspartate receptor. This study aimed to investigate the anti-edematous effect of magnesium sulfate (MS) in different protocols of use and the possible mechanism of its action.
In a rat model of carrageenan-induced paw inflammation, the anti-edematous activity of MS was assessed with a plethysmometer. The effects of the nonselective inhibitor (L-NAME), selective inhibitor of neuronal (L-NPA) and inducible (SMT) nitric oxide synthase on the effects of MS were evaluated.
MS administered systemically before or after inflammation reduced edema by 30% (5 mg/kg, P < .05) and 55% (30 mg/kg, P < .05). MS administered locally (.5 mg/paw, P < .05) significantly prevented the development of inflammatory edema by 60%. L-NAME, intraperitoneally administered before MS, potentiated (5 mg/kg, P < .05) or reduced (3 mg/kg, P < .05), while in the highest tested dose L-NPA (2 mg/kg, P < .01) and SMT (.015 mg/kg, P < .01) reduced the anti-edematous effect of MS.
Magnesium is a more effective anti-edematous drug in therapy than for preventing inflammatory edema. The effect of MS is achieved after systemic and local peripheral administration and when MS is administered as a single drug in a single dose. This effect is mediated at least in part via the production of nitric oxide.
This study focusses on the fabrication of nano-carriers for delivery of ciprofloxacin through the nanoprecipitation process. This was done to examine the release of drug at the pH of stomach to find out the antibacterial action of ciprofloxacin loaded nanoparticles (NPs). Prepared NPs were characterized by Fourier Transform Infra-Red (FTIR) spectroscopy, Scanning Electron Microscopy (SEM), and particle size analyzer (PSA) techniques. Drug yield, loading, and sustained release was studied as function of time (up to 8 h). Antibacterial activity of ciprofloxacin loaded NPs were also determined against different gram-positive and gram-negative bacteria. Results revealed that nanoprecipitation is a suitable method for encapsulation of ciprofloxacin in poly(lactic-co-glycolic acid) PLGA NPs. The drug yield and drug loading were found to be 60%. The size range of NPs observed by PSA was in the range of 5.03–6.60 nm. It can be concluded that nanoformulation of ciprofloxacin loaded PLGA NPs can be used in stomach for longer period of time to enhance the bioavailability of the drug.
Gout is a metabolic arthritis that originates from increased accumulation of monosodium urate (MSU) crystals in joints. This work aimed to evaluate the antioxidant and anti-inflammatory activities of the hydromethanolic extract of Gnidia kraussiana (HEGK) using model of Gouty arthritis on mice. The total polyphenol, flavonoid, tannin content and the antioxidant activity of HEGK were also evaluated. MSU-injected mice were treated daily for 3 days with HEGK (25, 50 and 100 mg/kg). Indomethacin and colchicin were used as reference drugs. Paw oedema and body temperature were measured at different time intervals post-injection. Malondialdehyde, acid phosphatase, β-Galactosidase, catalase, superoxide dismutase and glutathione levels were evaluated. HEGK is rich in polyphenol (129.93 mg/100 g), flavonoid (67.78 mg/100 g) and tannin conferring it a high antioxidant activity. Acute oral toxicity of HEGK resulted in LD50 greater than 2000 mg/kg. Oral administration of HEGK induced a significant decrease in the oedema of legs injected with urate crystals and reduced the release of acid phosphatase and β-Galactosidase. A model of oxidative damage was successfully established, revealing a significant increase in malondialdehyde and inhibition of antioxidants, including superoxide dismutase, catalase and glutathione activity. Thus, HEGK can actively inhibit the effect of inflammatory mediators in gouty arthritis.
Obesity, a chronic metabolic condition, is an increase in fat mass and blood lipid levels mainly causing atherosclerosis and hypertension, which further lead to cardiovascular complications. The objective of the study was to investigate the crude extract of Caralluma edulis (CE.Cr) for its potential against high-fat diet (HFD)-induced obesity and its related complications. Hyperlipidemia was induced in Wistar albino rats with HFD (1% cholesterol + 0.5% cholic acid) for 28 days. Treatment groups were administered with different doses of CE.Cr (100, 300 and 500 mg/Kg, p.o.) and the standard group received atorvastatin. At the end of study, sera were analyzed for biochemical markers and the aorta was dissected for microscopic examination. Antioxidant potential was evaluated and high-performance liquid chromatography (HPLC) analysis was performed. The hypotensive potential of CE.Cr was evaluated through an invasive technique. HPLC analysis of CE.Cr showed the presence of chlorogenic acid, caffeic acid, apigenin and naringenin. Histological examination of the aorta section showed anti-atherosclerotic effects which were also evident from decrease in serum total cholesterol, triglycerides and low-density lipoproteins levels. CE.Cr decreased mean arterial blood pressure and evoked significant hypotensive effects. The crude extract of C. edulis showed anti-obesity, antihypertensive, anti-atherosclerotic and antioxidant potential.
We had previously demonstrated on various stable cell cultures exposed to chemically different nanoparticles when assessing their cytotoxicity by different outcomes, dose-response relationships may be either monotonic or non-monotonic falling within an extended understanding of the hormesis paradigm. Presently, on human fibroblasts exposed to the copper-oxide and/or selenium-oxide nanoparticles, we assessed their cytotoxic effect by the inhibition of oxygen uptake against modulating the respiratory function of mitochondria (oligomycin, followed by carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone, and, finally, rotenone with antimycin A). It is hypothesized that a given type of this relationship is closely associated with the mitochondrial respiratory function. However, in only one case, this hypothesis was confirmed by finding that the monotonic dose-response relationship transformed into a non-monotonic one of the hormesis type under exposure to SeO-NP with the mitochondrial respiratory function fully inhibited by the effect of rotenone + antimycin А. In all other variants of the experiment, the shape of this relationship did not depend on the addition of the above agents to the cell culture. Neither did the effect of these modulators change the pattern of combined action of CuO-NP and SeO-NP, which was additive in all cases.
The current system of radiological protection relies on the linear no-threshold (LNT) hypothesis of cancer risk due to humans being exposed to ionizing radiation (IR). Under this tenet, effects of low doses (i.e. of those not exceeding 100 mGy or 0.1 mGy/min. of X- or γ-rays for acute and chronic exposures, respectively) are evaluated by downward linear extrapolation from regions of higher doses and dose rates where harmful effects are actually observed. However, evidence accumulated over many years clearly indicates that exposure of humans to low doses of radiation does not cause any harm and often promotes health. In this review, we discuss results of some epidemiological analyses, clinical trials and controlled experimental animal studies. Epidemiological data indicate the presence of a threshold and departure from linearity at the lowest dose ranges. Experimental studies clearly demonstrate the qualitative difference between biological mechanisms and effects at low and at higher doses of IR. We also discuss the genesis and the likely reasons for the persistence of the LNT tenet, despite its scientific implausibility and deleterious social consequences. It is high time to replace the LNT paradigm by a scientifically based dose-effect relationship where realistic quantitative hormetic or threshold models are exploited.
Colorectal cancer is considered the second most deadly cancer in the world. Studies have indicated that diet can prevent the risk of developing colorectal cancer. Recently, there has been an increasing interest in polyphenols due to their plausible effect on cancer prevention and treatment. p-Coumaric acid (p-CouA), a phenolic compound, is a cinnamic acid derivative found in several fruits, vegetables, and herbs. A growing body of evidence suggests that p-CouA may be an effective agent for preventing and managing colorectal cancer. In this current review, we briefly highlight the bioavailability of p-CouA. We also provide an up-to-date overview of molecular mechanisms underlying its anticancer effects, focusing on anti-inflammatory and antioxidant potentials, apoptosis induction, and cell cycle blockade. Finally, we discuss the impact of p-CouA on clonogenicity and multidrug resistance of colorectal cancer cells.
Acute ischemic stroke is a current major disabling and killer disease worldwide. We aimed to investigate the protective effect and mechanism of diammonium glycyrrhizinate in alleviating acute ischemic stroke.
Ninety male Sprague Dawley (SD) rats (weighing 250–300 g) were randomly allocated into three groups: sham operation group (sham group), diammonium glycyrrhizinate group (DG group) and model group (model group) each with 30 individuals. A rat model of focal CIR injury was established by reversible middle cerebral artery occlusion.
Zea-Longa scores for the rats in the DG group and model group were 7-fold and 8-fold higher than those of the sham group 2 h post-surgery (2.90 ± 0.99 vs. 0.30 ± 0.53, P < .05; 2.80 ± 0.61 vs. 0.30 ± 0.53, P < .05, respectively). Three days after model establishment, the scores of DG group were 26.92% lower compared with those of the model group (1.90 ± 0.76 vs. 2.60 ± 0.62, P < .05). In addition, compared with the sham group, the number of Nissl bodies and Akt-positive cells in were 27.35% and 30.42% lower in the hippocampus of the DG group (Nissl bodies: 83.40 ± 7.01 vs. 115.60 ± 11.97, p < 0.05; Akt-positive cells: 94.70 ± 8.23 vs. 136.10 ± 10.37, P < .05) and 58.65% and 57.31% lower in the model group (Nissl bodies: 47.80 ± 4.91 vs. 115.60 ± 11.97, P < .05; Akt-positive cells: 58.10 ± 4.98 vs. 136.10 ± 10.37, P < 0.05), respectively. However, the number of Nissl bodies and Akt-positive cells in the hippocampus of DG group were 74.48% and 62.9% higher compared with the model group, respectively (Nissl bodies: 83.40 ± 7.01 vs. 47.80 ± 4, P < 0.05; Akt-positive cells: 94.70 ± 8.23 vs. 58.10 ± 4.98, P < .05). In addition, compared with the sham group, the number of caspase-3-positive cells, the expression level of p38 mitogen-activated protein kinase (MAPK) and the expression of matrix metallopeptidase 9 (MMP-9) were 2-fold, 34.38%, 64.78% higher in the DG group (caspase-3-positive cells: 78.70 ± 6.52 vs. 27.10 ±3.00, P < .05; p-38MAPK: 0.43 ± 0.15 vs. 0.32 ± 0.10, P < .05; MMP-9: 14.83 ± 1.18 vs. 9.00 ± 2.05, P < .05, respectively), and more than 3-fold, 1-fold and 1-fold higher in model group (caspase-3-positive cells: 121.10 ± 11.04 vs. 27.10 ± 3.00, P < .05; p-38MAPK: 0.70 ± 0.12 vs. 0.32 ± 0.10, P < .05; MMP-9: 19.00 ± 1.90 vs. 9.00 ± 2.05, P < .05), respectively. However, the number of caspase-3-positive cells and the expression levels of p-38MAPK and MMP-9 were 35.01%, 38.57% and 28.12% lower in DG group compared with the model group (caspase-3-positive cells: 78.70 ± 6.52 vs. 121.10 ± 11.04, P < .05; p-38MAPK: 0.43 ± 0.15 vs. 0.70 ± 0.12, P < .05; MMP-9: 14.83 ± 1.18 vs. 19.00 ± 1.90, P < .05).
Our study showed that diammonium glycyrrhizinate at 20 mg/kg/day had a protective effect on cerebral ischemia-reperfusion injury in rats by promoting formation of Nissl bodies and increasing protein expression of Akt while decreasing that of caspase-3, p38 MAPK and MMP-9, either directly or indirectly, by inhibiting apoptosis and reducing neuroinflammation. All these mechanisms resulted in improved overall neurological function.
Hyperbaric Oxygen Therapy (HBOT) has definitive therapeutic effects on spinal cord injury (SCI), but its mechanism of action is still unclear. Here, we’ve conducted a systemic proteomic analysis to identify differentially expressed proteins (DEPs) between SCI rats and HBOT + SCI rats. The function clustering analysis showed that the top enriched pathways of DEPs include oxygen transport activity, oxygen binding, and regulation of T cell proliferation. The results of functional and signal pathway analyses indicated that metabolic pathways, thermogenesis, LXR/RXR activation, acute phase response signaling, and the intrinsic prothrombin pathway in the SCI + HBOT group was higher than SCI group.
This review article describes our simplified biophysical model for the response of a group of cells to ionizing radiation. The model, which is a product of 10 years of studies, acts as (a) a comprehensive stochastic approach based on the Monte Carlo simulation with a probability tree and (b) the thereof derived detailed deterministic models describing the selected biophysical and radiobiological phenomena in an analytical manner. Specifically, the presented model describes effects such as the risk of neoplastic transformation of cells relative to the absorbed radiation dose, the dynamics of tumor development, the priming dose effect (also called the Raper-Yonezawa effect) based on the introduced adaptive response approach, and the bystander effect. The model is also modifiable depending on users' potential needs.
The liver is the organ by which the majority of substances are metabolized, including psychotropic drugs. Lithium (Li) used as drug for many neurological disorders such as bipolar disorders.
This study aims to assess lithium toxicity and to evaluate the hepatic-protective properties of a grape skin seed and extract (GSSE).
Materials and methods
Twenty-four male Wistar rats were exposed for 30 days to either various lithium concentrations, GSSE alone, or lithium supplemented with GSSE. The proteomic analysis revealed alterations of liver protein profiles after lithium treatments that were successfully identified by mass spectrometry.
Lithium treatment induced an oxidative damage by the alteration of antioxidant enzymes activities such as superoxide dismutase, CAT, and Gpx. The regulated proteins are mainly involved in the respiratory electron transport chain, detoxification processes, ribosomal stress pathway, glycolysis, and cytoskeleton. Proteins were differentially expressed in a dose-dependent manner. Interestingly, GSSE reversed the situation and restored the level of liver proteins whose abundance was modified after lithium treatment, arguing for its protective activity.
Our data demonstrated the ability of proteomic analysis to underline the toxicity mechanisms of lithium in animal models. Based on these results, GSSE may be envisaged as a nutritional supplement to weaken the liver toxicity of lithium.
Ethanol extracts of Cnidii Fructus, the dried fruits of Cnidium monnieri (L.) Cusson, have been externally applied in the treatment of Trichomonas vaginalis. However, the precise identity of the major constituents responsible for activity against T. vaginalis is unknown, but there is probability they are coumarin derivatives. In this study, the anti- Trichomonas activity of 4 major coumarin derivative constituents of Cnidii Fructus, namely, osthole, xanthotoxin, isopimpinellin, and bergapten, was characterized in terms of the resulting kinetics of growth and morphology of T. vaginalis upon treatment. The results demonstrated that osthole and xanthotoxol had significant trichomonacidal ability, while isopimpinellin and bergapten displayed low or no inhibitory efficacy toward T. vaginalis parasites. Our study suggests that the coumarin derivatives osthole and xanthotoxol can be potentially used as a basis for the development and design of new drugs for application in alternative or synergistic therapy against T. vaginalis.
The volatiles chemical composition and biological attributes of coriander (Coriandrum sativum L.) leaves essential oil obtained by two extraction techniques namely supercritical fluid extraction and hydro-distillation is appraised. The coriander essential oil yield (.12%) by hydro-distillation was slightly higher than that of supercritical fluid extraction (.09%). The physico-chemical variables of the essential oil obtained from both the techniques varied in significantly (P < .05). GC-MS analysis identified 23 different components in supercritical fluid extracted oil and 18 components in hydro-distilled essential oil having linalool as major component (51.32% and 61.78%, respectively) followed by phytol (12.71%). The oil recovered by supercritical fluid extraction exhibited greater DPPH radical scavenging activity as well as reducing power as compared to the essential oil obtained by hydro-distillation technique along with a stronger biofilm inhibition and least hemolysis. The results of antimicrobial activity revealed that super critical fluid extracted essential oil has potent antifungal and antibacterial activity against P. multocida and A alternata, whereas hydro-distilled essential oil displayed better antimicrobial potential against E coli and A niger. Overall, these results depict that supercritical fluid extraction is superior than hydro-distillation with regard to isolation of better-quality coriander essential oil for nutra-pharmaceutical developments.
Xanthohumol (XN) is the major prenylated chalcone of the female inflorescences (cone) of the hop plant ( Humulus lupulus). It is also a constituent of beer, the major dietary source of prenylated flavonoids. It has shown strong antitumorigenic activity towards various types of cancer cells. In the present study, we show the impact on human hepatocarcinoma cell line HepG2 cell and potential adverse effects on rat primary hepatocytes. Cell growth/viability assay (MTT) demonstrated that HepG2 cells are highly sensitive to XN at a concentration range of 25-100 μM. The primary mode of tumor cell destruction was apoptosis as demonstrated by the binding of Annexin Ⅴ-FITC, we show that XN at a concentration of 25 μM induced apoptosis in HepG2. Further evidence that XN kills HepG2 by inducing apoptosis was provided by the impact of XN on the cleavage of PARP-1 and caspases-3. In contrast, XN concentrations up to 100 μM did not affect viability of primary rat hepatocytes in vitro, meanwhile, XN did not induce the apoptosis of primary rat hepatocytes in vitro . In summary, our data provide a rationale for clinical evaluation of XN for the treatment of liver cancer.
Neurodegenerative diseases have increased worldwide in recent years. Their relationship with oxidative stress has motivated the research to find therapies and medications capable of suppressing oxidative damage and therefore slowing the progression of these diseases. Glutathione (GSH) is the most important cellular antioxidant in living beings and is responsible for regulating the cellular redox state. However, GSH cannot be administered by any route of administration, so molecules that increase its levels by activating Nrf2-ARE signaling pathway are explored; since Nrf2 regulates the main genes involved in GSH de novo synthesis and recycling. Astrocytes are the most important cell-type in the antioxidant cell response and are responsible for providing GSH and other substrates for neurons to have an efficient antioxidant response. Methotrexate (MTX) is an anti-inflammatory agent that has different cellular effects when administered at low or high concentrations. So in this study, we used MTX different concentrations and exposure times to induce a hormetic antioxidant response in rat primary astrocytes. Our results showed that 20 nM MTX pre-conditioning for 12 h augmented the GSH/GSSG ratio and protected cellular viability against a toxic MTX and H 2 O 2 insult, which was abrogated when Nrf2 was inhibited by brusatol. Hence, MTX subsequent studies as a drug to counteract the progression of some stress-associated neurodegenerative diseases are suggested.
Radiation-induced esophageal injury remains a limitation for the process of radiotherapy for lung and esophageal cancer patients. Esophageal epithelial cells are extremely sensitive to irradiation, nevertheless, factors involved in the radiosensitivity of esophageal epithelial cells are still unknown. Terminal uridyl transferase 4 (TUT4) could modify the sequence of miRNAs, which affect their regulation on miRNA targets and function. In this study, we used transcriptome sequencing technology to identify mRNAs that were differentially expressed before and after radiotherapy in esophageal epithelial cells. We further explored the mRNA expression profiles between wild-type and TUT4 knockout esophageal epithelial cells. Volcano and heatmap plots unsupervised hierarchical clustering analysis were performed to classify the samples. Enrichment analysis on Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathways was performed. We annotated differential genes from metabolism, genetic information processing, environmental information processing, cellular processes, and organismal systems human diseases. The aberrantly expressed genes are significantly enriched in irradiation-related biological processes, such as DNA replication, ferroptosis, and cell cycle. Moreover, we explored the distribution of transcription factor family and its target genes in differential genes. These mRNAs might serve as therapeutic targets in TUT4-related radiation-induced esophageal injury.
Quorum sensing (QS) is a major controller of virulence and biofilm formation in pathogenic bacteria. The aim of the research was to screen novel synthetic compounds (18) from 2 series (Pyrazole and Diene dione) for quorum sensing and biofilm inhibitory potential against resistant pathogens isolated from patients with chronic sinusitis. Most of the compounds have documented zone of inhibition against Gram positive strains Staphylococcus aureus, Enterococcus faecalis and moderate activity against Gram negative Klebseilla pneumoniae and Proteus mirabilis in comparison with standard antibiotic. Compounds Q1 and Q7 have given the maximum zone of inhibition 18 and 20 mm with MICs 0.312 mg/mL and .156 mg/mL against S aureus and E faecalis, respectively. Some compounds were equally potent at inhibiting the formation of biofilm which later established by phase contrast microscopy. Regarding quorum sensing inhibition, the tested concentration of synthetic compound UA3 0.313 mg/mL inhibited violacein production without decreasing Chromobacterium pseudoviolaceum count which was significantly lower than determined MIC’s. It was depicted from the results that selected compounds exhibited low level of cytotoxicity toward human red blood cells. Hence, these findings revealed that most novel compounds were effective antibacterial, whereas compound UA3 has shared significant anti-quorum sensing potential against Chromobacterium pseudoviolaceum.
Tartaric acid is capable of balancing blood pressure. It is the main constituent of antihypertensive agents (grapes and wine) and has not been scientifically explored as an antihypertensive remedy. This study aimed to investigate the antihypertensive effect of a low-dose tartaric acid in vivo and explore underlying mechanisms in vitro. Intravenous administration of tartaric acid at the dose of 50 µg/kg caused a % fall in mean arterial pressure (MAP) in normotensive and hypertensive rats [51.5 ± 1.7 and 63.5 ± 2.9% mmHg]. This hypotensive effect was partially inhibited by atropine (1 mg/kg) and L -NAME (100 µg/kg) pretreatment. In hypertensive rats, oral administration of tartaric acid (.1, .5, 1, 5, and 10 mg/kg) for 2 weeks resulted in 65 ± 7.3 mmHg MAP at 10 mg/kg. This antihypertensive effect was comparable to the orally administered verapamil (10 mg/kg) for 2 weeks which caused a decrease in MAP 60.4 ± 3.8 mmHg. Tartaric acid relaxed phenylephrine (PE) and High K ⁺ -induced contractions with EC 50 values of .157 (.043-.2) and 1.93 (.07-2) µg/mL in vitro. This endothelium-dependent relaxation was inhibited with atropine (1 µM) and L -NAME (10 µM) pretreatment. Tartaric acid also suppressed phenylephrine contractions in Ca ⁺² free/EGTA medium and on voltage-dependent calcium channels, causing the concentration–response curves toward right. Tartaric acid induced negative inotropic and chronotropic effects with EC 50 values of .26 (.14-.4) and .60 (.2-.8) in rat atria. It showed its effect by complete blockade against atropine and partially in propranolol pretreatment. These findings provide scientific basis to low-dose tartaric acid as an antihypertensive and vasodilatory remedy through muscarinic receptor-linked nitric oxide (NO) pathway and Ca ⁺² channel antagonist.
The C-reactive protein is generally considered a marker of inflammation, and it is widely used in clinical practice as a minimally invasive index of any ongoing inflammatory response. Alpha-lipoic acid (ALA) supplementation can be beneficial for human health, especially in the sense of its anti-inflammatory action. The aim of this meta-analysis was to, based on the currently available highest level of evidence (prospective, randomized, double-blind, and placebo-controlled data), investigate the effect of ALA supplementation on CRP levels. Prospective, randomized, double-blind, and placebo-controlled clinical trials were extracted after a systematic search of PubMed, the Cochrane Library, the Web of Science, EMBASE, and the Scopus databases. A random effect model was used in this meta-analysis to investigate the influence of ALA on the blood CRP level. The subgroup analysis and meta-regression were used to identify the source of heterogeneity. This meta-analysis provided evidence of the positive effect of ALA on the reduction of the blood CRP level. The subgroup analysis and meta-regression results indicated that ALA can reduce the CRP level when administrated at a 600 mg dose, and not in higher or lower doses. Also, a shorter duration of study positively correlates with the reduction of CRP after ALA supplementation.
Disruption of quorum sensing pathway of pathogenic microbes is considered as novel approach to fight against infectious diseases. The current study was planned to evaluate the antibiofilm and quorum sensing inhibitory potential of Lagerstroemia speciosa. Antibacterial and antibiofilm potential of L. speciosa extracts was determined through agar well diffusion and crystal violet assay against sinusitis isolates, that is, Staphylococcus aureus, Enterococcus faecalis, Proteus mirabilis, and Klebsiella pneumoniae, while quorum sensing inhibition efficacy of L. speciosa extracts was determined through violacein inhibition assay using Chromobacterium pseudoviolaceum as bacterial model . The methanolic extract of L. speciosa presented the highest antimicrobial activity against E. faecalis and antibiofilm activity against K. pneumoniae (77.42 ± 1.51%) , while n-hexane extract was found to be least active against all tested bacterial strains . Quorum sensing inhibition activity of L. speciosa extracts against C. pseudoviolaceum showed significant dose-dependent inhibition in violacein production by different concentrations of methanolic extract. Furthermore, none of the extracts of L. speciosa showed any hemolytic activity against human RBCs and hold considerable thrombolytic potential in comparison to streptokinase (75.9 ± .46%). In conclusion, findings suggest that L. speciosa leaves are excellent source of phytochemicals with potent antibiofilm and quorum sensing inhibition potential.
The current study aims to isolate, purify, and characterize the trypsin inhibitor protein from seeds of soya beans, scientifically known as Glycine max. Its seeds were ground, and the powder was soaked several times using n-hexane. It was added to phosphate buffer saline (PBS) followed by filtration and centrifugation of the PBS dissolved extract. The supernatant was subjected to ammonium sulfate precipitation and about six fractions, 30% to 80% were prepared. The centrifuged pellets obtained from each fraction were dialyzed and run on SDS-PAGE. The trypsin inhibitor protein was precipitated and characterized in 30% pellet and molecular weight was 21.5 kDa compared to protein ladder (ThermoFisher 10-170 kDa). GC-MS analysis revealed the steroid derivatives such as stigmasterol, campesterol, beta-sitosterol, and gamma-tocopherol. Glycine max trypsin inhibitor could be used as a plant-derived drug to overcome the over-activation of trypsin without its real substrate (proteins) becoming activated and start auto digestion leading to pancreatitis. Keywords Bowman-Birk trypsin inhibitor, Kunitz trypsin inhibitor, soybean trypsin inhibitor and antioxidant activity
Leukemia accounts for a large number of deaths, worldwide, every year. Treating this ailment is always a challenging job. Recently, oncogenic miRNA leading to apoptosis are highly promising targets of many natural products. In this study, Garmultin-A (GA), isolated from the bark of Garcinia multiflora, was elucidated for its anti-leukemic effect in CB3 cells.
The effect of the compound on CB3 cell viability was detected by MTT assay and apoptosis by FITC Annexin V/PI and Hochest 33258 staining. The western blot analysis assessed the BAX, BCL2, cMYC, pERK, and PARP-1 protein levels. Autodock analysis predicted the ligand-protein interactions. q-RT-PCR quantified the miR-17-5p expression. Luciferase assay confirmed the interaction between PARP-1 and miR-17-5p.
We uncover that GA leads to apoptosis by inducing overexpression of miR-17-5p and significantly downregulate PARP-1 protein levels in CB3 cells. The overexpression of miR-17-5p promotes apoptosis, and the miR-17-5p antagomirs restore GA-triggered apoptosis. Notably, we disclose that PARP-1 is a direct target of miR-17-5p. Increased pro-apoptotic and reduced anti-apoptosis protein levels were also observed in GA-treated CB3 cells.
These results provide critical insights that GA could induce apoptosis in CB3 cells through targeting miR-17-5p by attenuating PARP-1. Thus, GA could act as a novel therapeutic agent for erythroleukemia.
Extensive studies on evaluation of effectiveness/toxicity of different oral doses of iodine have not been explored yet. An open-labeled phase I clinical studies were conducted using iodine complex based research compound called Renessans. Study groups were observed for development of any adverse/serious adverse events and alteration in laboratory values of vital organs, TSH and T4 hormones before and after the administration of the products. Out of 31 consented individuals, 24 healthy individuals participated in the study. Rate of occurrence of mild Adverse Events (AEs) in group A was 8.3% while in Group B it was 33.33% but these Adverse Events were self-resolving. After completion of study treatment blood serum iodine was reported to 3522.88 µg/l while mean urine iodine concentration (MUIC) was greater than 2000 µg/l. Hormonal and vital organ's testing revealed that all parameters of TSH and T4, LFT, CBC, RFT remained unaltered except from ALT-SGPT (P-value = .006) and AST-SGOT (P-value = .02). From all of these findings, it can be inferred that the use of Renessans formulations did not pose any sort of risk to human body and can be considered safe through this pilot study.
Bleomycin is an effective chemotherapeutic agent with main side effects including lung fibrosis which limited its clinical use. The aim of this study is to evaluate the protective effect of grape seed and skin extract (GSSE) against bleomycin-induced oxidative damage and inflammation in rat lung, by assessing respiratory index (RI), oxidative and nitrosative stress (SOD and XO activity, NO), fibrotic mediators (hydroxyproline and collagen), apoptosis (cytochrome C and LDH), inflammation (IL-6, TNF-α and TGF-β1), and histological disturbances.
Rats were pre-treated during three weeks with vehicle [ethanol 10% control] or GSSE (4 g/kg) and then administered with a single dose of bleo (15 mg/kg bw) at the 7th day.Results: Bleo disturbed lung function through the accumulation of hydroxyproline and collagen, decreased SOD activity but increased XO activity as well as GSH and NO levels. Bleo also increased the pro-inflammatory cytokines IL-6, TNF-α, and TGF-β1, and pro-apoptotic cytochrome C factor and induced severe histological alterations of lung parenchyma. Interestingly GSSE pre-treatment efficiently counteracted most of the bleo-induced lung tissue damages.
Data suggest that GSSE exerts anti-oxidant, ant-inflammatory, and anti-fibrosis properties that could find potential application in the protection against bleo-induced lung fibrosis.
Inorganic nanoparticles are representing an emerging paradigm in molecular imaging probe design. We have determined
lanthanum oxide nanoparticles (La2O3 NPs)-induced toxicity on human livers cells for 48 hrs. Before exposure to La2O3 NPs,
the size and shape of NPs were confirmed by transmission electron microscope. It was found at 32 ±1.6 nm with a sheet-like
morphological structure. The viability of CHANG and HuH-7 cells was reduced as the concentration of La2O3 NPs increased.
HuH-7 cells were more sensitive than CHANG cells to La2O3 NPs. We observed production of intracellular ROS in HuH-7
cells was more than CHANG cells and the LPO level was more in CHANG cells than in HuH-7 cells at 50 μg/ml of La2O3 NPs.
Glutathione was decreased and catalase was increased at 50 μg/ml of La2O3 NPs. More apoptotic and necrotic cells were
observed at 300 μg/ml in HuH-7 cells FACS. DNA damage was observed by the SGCE test and more DNA damage was found in
CHANG cells than HuH-7 cells at 300 μg/ml La2O3 NPs over 48 hrs. Thus, study warrants the application of La2O3 NPs in daily
life and provides vital information about the toxicity of La2O3 NPs.
Transfer RNA-derived small RNAs (tsRNAs) are a novel type of non-coding RNA with various regulatory functions. They are associated with oxidative stress in various diseases, but their potential functions in radiation-induced lung injury (RILI) remain uncertain.
To explore the role of tsRNAs in RILI, we used X-rays to irradiate human bronchial epithelial cells and examined the expression profile of altered tsRNAs by RNA sequencing and bioinformatics analysis. Sequencing results were verified by qRT-PCR. tsRNA functions were explored using several methods, including CCK-8, reactive oxygen species (ROS) assays, cell transfection, and western blotting.
Eighty-six differentially expressed tRNA-derived fragments (tRFs) were identified: 64 were upregulated, and 22 were downregulated. Among them, the regulation of tRF-Gly-GCC, associated with oxidative stress, may be mediated by the inhibition of cell proliferation, promotion of ROS production, and apoptosis in the occurrence and development of RILI. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the underlying molecular mechanism may involve the PI3K/AKT and the FOXO1 signaling pathways.
Our findings provide new insights into the molecular mechanisms underpinning RILI, advancing the clinical prevention and treatment of this disease.
Professor Ludwik Dobrzyński, an eminent scientist and popularizer of science, passed away on January 11, 2022, in his home in Warsaw, Poland, just before his 81st birthday. He was a specialist in solid-state physics. Later in his career, Ludwik also became interested in the effects of small doses of ionizing radiation on health. Professor Dobrzyński was one of the most outstanding physicists at the Polish Institute of Nuclear Research (IBJ), later transformed into the National Centre for Nuclear Research (NCBJ) at Świerk near Warsaw. He was also a well-recognized personality among the international low-dose radiation research community.
To examine the effect of blood flow restriction resistance training under different external loads on the muscle strength and vertical jumping performance in volleyball players.
18 well-trained collegiate male volleyball players were randomly divided into 3 groups: high-load resistance training group (HL-RT, 70% 1RM, n = 6), low-load blood flow restriction resistance training group (LL-BFR-RT, 30% 1RM, 50% arterial occlusion, n = 6), and high-load blood flow restriction resistance training group (HL-BFR-RT, 70% 1RM, 50% arterial occlusion, n = 6). Participants performed leg half-squat exercise 3 times per week for 8 weeks. Measurements of Isokinetic peak torque of knee extension and flexion, 1RM leg half-squat, squat jump, and 3 footed take-off were obtained before and after training. A two-way repeated-measures analysis of variance was used to examine differences among the 3 groups and between the 2 testing time (pre-test vs post-test).
(1) The HL-RT group was significantly greater in muscle strength than that in the LL-BFR-RT group ( P < .05), but no improvement in vertical jumping performance ( P >.05). (2) Improvement in muscle strength and vertical jumping performance was significantly greater in the HL-BFR-RT group than that in the LL-BFR-RT group ( P <.05). (3) The HL-BFR-RT group had greater but not significant improvement in muscle strength and vertical jumping performance than that in the HL-RT group.
Although increases in muscle strength were observed between training groups, HL-BFR-RT increased not only muscle strength but vertical jumping performance to a greater extent compared to LL-BFR-RT and HL-RT.
This paper provides an assessment of hormetic dose responses in epidermal stem cells (EpSCs) in animal models and humans, with emphasis on cell proliferation and differentiation and application to wound healing and aging processes. Hormetic dose responses were induced by several agents, including dietary supplements (eg, luteolin, quercetin), pharmaceuticals (eg, nitric oxide), endogenous agents (eg, growth/differentiation factor 5), and via diverse chemical means to sustain steaminess features to retard aging and disease onset. While hormetic dose responses have been extensively reported in a broad spectrum of stem cells, this area has only been explored to a limited extent in EpSCs, principally within the past 5 years. Nonetheless, these findings provide the first integrated assessment of hormesis and EpSC biology within the context of enhancing key functions such as cell proliferation and differentiation and resilience to inflammatory stresses. This paper assesses putative mechanisms of hormetic responses in EpSCs and potential therapeutic applications to prevent dermatological injury and disease.
Magnesium oxide (MgO) and manganese oxide (MnO) have been reported to be effective against Diabetes Mellitus (DM). However, their nanoparticulate form has not been evaluated for antidiabetic effect. MgO and MnO nanoparticles (15–35 nm) were synthesized and subsequently characterized by ultraviolet-visible spectroscopy (UV-VIS), zeta sizer, and scanning electron microscopy. 6–7 weeks old rats weighing 200–220 mg were divided into 07 equal groups (n = 8), namely, negative control (NC), positive control (PC), standard control (Std-C), MgO high dose group (MgO-300) and low dose group (MgO-150), and MnO nanoparticle high dose (MnO-30) and low dose group (MnO-15). Diabetes was chemically induced (streptozotocin 60 mg/kg B.W) in all groups except the NC. Animals were given CMD and water was ad libitum. Nanoparticles were supplemented for 30 days after the successful induction of diabetes. Blood and tissue samples were collected after the 30 th day of the trial. The mean serum glucose, insulin, and glucagon levels were improved maximally in the MgO-300 group followed by MgO-150 and MnO-30 groups. Whereas the MnO-15 group fails to show any substantial improvement in the levels of glucose, insulin, and glucagon as compared to the positive control group. Interesting the serum triiodothyronine, thyroxine, and thyroid-stimulating hormone levels were markedly improved in all the nanoparticle treatment groups and were found to be similar to the standard control group. These results highlight the modulatory properties of MgO and MnO nanoparticles and merit further studies delineating the molecular mechanisms through which these nanoparticles induce antidiabetic effects.
Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs. Flavonols, flavanones, flavones, stilbenes, diferuloylmethanes, tannins, protoalkaloids, flavans, hyperforin and terpenes, reduce plasma concentration of cyclosporine, simvastatin, celiprolol, midazolam, saquinavir, buspirone, everolimus, nadolol, tamoxifen, alprazolam, verapamil, quazepam, digoxin, fexofenadine, theophylline, indinavir, clopidogrel. Anthocyanins, flavonols, flavones, flavanones, flavonoid glycosides, stilbenes, diferuloylmethanes, catechin, hyperforin, alkaloids, terpenes, tannins and protoalkaloids increase of plasma concentration of buspirone, losartan, diltiazem, felodipine, midazolam, cyclosporine, triazolam, verapamil, carbamazepine, diltiazem, aripiprazole, tamoxifen, doxorubicin, paclitaxel, nicardipine. Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose. Therefore, it is important for the clinician to consider these interactions to obtain a better therapeutic effect.
Adult T-cell leukemia/lymphoma (ATLL) is a blood neoplasm with specific geographic distribution. Although radiotherapy is a palliative treatment that provides long-term local control, single use of radiation leads to complications for patients. To introduce a novel multimodal approach against ATLL, we investigated combinatorial effects of 7-geranyloxycoumarin and radiation in vitro.
Viability of MT-2 cells was determined by resazurin assay upon administration of 7-geranyloxycoumarin alone and followed by radiation. Then, apoptosis was detected by annexin V and propidium iodide, and the expression of candidate genes was analyzed by qPCR.
Findings revealed significant (P<.0001) improvement in radiation effects upon 7-geranyloxycoumarin pretreatment, most notably when cells were pretreated with 5 µg/ml 7-geranyloxycoumarin for 96 h, exposed to 6 Gy radiation and recovered for 48 h. These results were confirmed by flow cytometry, as the percentage of early and late apoptotic cells was increased after combinatorial treatment. In addition, significant (P< .0001) changes in CD44, c-MYC, cFLIPL, BMI-1, NF-κB ( Rel A), and P53 expression was induced by 7-geranyloxycoumarin and radiation.
Current research indicated, for the first time, that combinatorial use of 7-geranyloxycoumarin and ionizing radiation could be considered as an effective therapeutic modality for ATLL.
The liver and kidneys are the vital organs of the body and perform important life-sustaining functions in the body. Synthetic drugs used in the treatment of liver and kidney diseases are sometimes inadequate and can lead to serious side effects. Medicinal herbs and plants were used to combat diseases for a long time and combination therapy is preferred over single plant therapy. In the current study, the Asparagus racemosus, Mucuna pruriens, Anacyclus pyrethrum, and Tribulus terrestris polyherbal preparation (PHP) was selected to evaluate its hepatoprotective, antioxidant, and anti-nephrotoxic potential. The methanolic extract of PHP was prepared following standard protocols. Fifty-six albino rats were divided into 7 groups (n = 8). The negative control (NC) having the healthy rats and the remaining 6 groups were induced liver toxicity by intraperitoneally injecting 0.5 mL/kg of 50% CCl 4 in olive oil. Group 2 was positive control and group 3 and 4 received silymarin standard drug at the dose of 100 and 200 mg/kg body weight. Groups 5, 6, and 7 (PHP-1, PHP-2, PHP-3) were the liver-damaged rats receiving the PHP at a dose of 50, 100, and 150 mg/kg body weight. Blood samples were collected at 21 of the trial, to evaluate oxidative stress, hepatoprotective and anti-nephrotoxic potential. Results of liver function tests revealed significant (P < .05) hepatoprotective activities of PHP after intoxication with CCl 4 of albino rats as compared to standard groups. Moreover, results of renal functions also showed that PHP has a significant (P < .05) restoring the capacity of blood urea, creatinine, and uric acid in intoxicated rats as compared with the control group. The PHP also reduced the oxidative stress in the treatment groups by increasing the total antioxidant capacity and reducing the total oxidative status. It can be concluded that selected medicinal plants have a potential role in the management of liver and kidney disorders. So, by running the clinical trial on a large scale and by isolating the phytochemical constituents responsible for hepatoprotective and nephroprotective activities, locally prepared drugs could be developed to manage liver and renal disorders.
Accidental radiation exposure is a threat to human health that necessitates effective clinical diagnosis. Suitable biomarkers are urgently needed for early assessment of exposure dose. Existing technologies being used to assess the extent of radiation have notable limitations. As a radiation biomarker, miRNA has the advantages of simple detection and high throughput. In this study, we screened for miRNAs with dose and time dependent responses in peripheral blood leukocytes via miRNA sequencing in establishing the animal model of acute radiation injury. Four radiation-sensitive and stably expressed miRNAs were selected out in the 24 h group of leukocyte miRNAs: mmu-miR-130b-5p, mmu-miR-148b-5p, mmu-miR-184-3p, mmu-miR-26a-2-3p, and five were screened in the 48 h group of leukocyte miRNAs: mmu-miR-130b-5p, mmu-miR-423-5p, mmu-miR-676-3p, mmu-miR-150-5p, mmu-miR-342-3p.The correlation curves between their expression and irradiation dose were plotted. Then, the results were validated by RT-qPCR in mouse peripheral blood. As a result, mmu-miR-150-5p and mmu-miR-342-3p showed the highest correlation at 48h after irradiation, and mmu-miR-130b-5p showed good correlation at both 24 h and 48 h after irradiation. In a conclusion, the miRNAs that are sensitive to ionizing radiation with dose dependent effects were selected out, which have the potential of forming a rapid assessment scheme for acute radiation injury.
Ginger ( Zingiber officinale) rhizomes are commonly used in foods and employed for many ailments including gastrointestinal disorders. Our main objective was to evaluate the effect of Zingiber officinale aqueous extract (ZOAE) on gastrointestinal (GI) physiological motility and colonic dysmotility. Thereby, Wistar rats were given loperamide (LP, 3 mg/kg, b.w.) and ZOAE (75, 150, and 300 mg/kg, b.w.) or yohimbine (YOH, 2 mg/kg, b.w.). ZOAE-action on intestinal secretion was assessed using Ussing chamber technique and intestinal motility with isometric transducer. GI-transit (GIT) and gastric emptying (GE) were evaluated with the charcoal meal test and the red phenol methods. ZOAE-bioactive components were analyzed by liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS). Constipation was induced with LP and the different indicators such as stool composition, GIT, oxidative stress biological parameters, and colonic mucosa histological alteration were performed. Anti-constipation effect of ZOAE was confirmed on stool composition, GIT (53.42% to 85.57%), GE (55.47% to 98.88%), and re-established oxidative balance. ZOAE induces an amplitude increase of spontaneous intestinal contraction with EC50 of 10.52 μg/mL. No effect of ZOAE was observed on electrogenic transport of intestinal fluid. These findings suggest that ZOAE-bioactive candidates might exert an anti-constipation action and spontaneous intestinal contraction modulation.
Thrombosis is a major disorder which is an outcome of an imbalance in the hemostatic system that develop undesirable blood clot and hinder blood circulation.
The current study was designed to verify the potential of aqueous methanolic crude extract of Asphodelus tenuifolius Cav . (At.Cr), used traditionally as remedy in circulatory problems.
Antioxidant activity, FTIR, and HPLC analysis were performed. In-vitro clot lysis assay was performed on human blood samples, and in-vivo acute pulmonary thromboembolism model was developed by administering the mixture of collagen and epinephrine in tail vein of mice. Carrageenan-induced thrombosis and FeCl 3 -induced carotid arterial thrombosis models were developed in rats.
At.Cr demonstrated significant increase in lysis of human blood clot. Bleeding and clotting times were increased dose-dependently. Lungs histology showed clear alveolar spaces with decreased red blood cells congestion. Reduction in infarcted tail length, augmentation in prothrombin time, and activated partial thromboplastin time with decrease in platelet count were observed. At.Cr also prolonged the arterial occlusion time and reduced the weight of thrombus and TXB 2 levels dose-dependently.
The results demonstrated the antithrombotic and thrombolytic potential of At.Cr due to activation of coagulation factors through extrinsic and intrinsic pathways.
Chronic kidney disease (CKD) is an important factor that contributes to the increase of all-cause morbidity and mortality in the group of non-communicable diseases, and it is also recognized as a strong and independent risk factor that contributes to cardiovascular disease (CVD). CVDs are a consequence of the action of a large number of risk factors among which are traditional and non-traditional. These risk factors have been the subject of a large number of studies which partially explained the unfavorable cardiovascular (CV) outcome of CKD patients. Therefore, valid studies about clinical and biohumoral predictors are of particular importance, especially in the early stages of renal disease, that is, in patients with creatinine clearance below 60 ml/min/1.73 m ² when preventive measures are most effective. Among potential predictors of adverse CV outcome are biomarkers of inflammation (Interleukin-18—IL-18), oxidative stress (ischemia-modified albumin—IMA; superoxide dismutase—SOD), acute kidney injury (kidney injury molecule -1—KIM-1; neutrophil gelatinase–associated lipocalin—NGAL), and microribonucleic acids (specific microRNA-133a). In this review, we tried to confirm the relationship between risk factors of CKD and CVD and newer, less frequently examined biomarkers with the occurrence of incidental CV events in renal patients.
To determine whether the width of the shoulder and the size of the bystander effect are correlated using clonal lineages derived from a cultured cell line.
HCT 116 (p53 wildtype) cells were grown at cloning density and individual viable colonies were picked off and grown to establish a series of cell lines from both unirradiated and irradiated progenitors. These cell lines were then irradiated to generate full survival curves. Highly variant clones were then tested to determine the level of the bystander effect using a medium transfer protocol.
The multi-target model gave the best fit in these experiments and size of the shoulder n is assessed in terms of radiosensitivity. The parent cell line has an n value of 1.1 while the most variant clones have n values of 0.88 (Clone G) and 5.5 (Clone A). Clonal lines subject to irradiation prior to isolation differed in bystander signal strength in comparison to clonal lines which were not initially irradiated ( P = .055).
Based on these experiments we suggest there may be a link between shoulder size of a mammalian cell line and the strength of a bystander effect produced in vitro. This may have implications for radiotherapy related to out-of-field effects.
The aims and objectives of the study were to evaluate the antiParkinson’s (PD) potential of B cernua (BCE). B cernua (Poir.) Müll. Arg. (B cernua) is a member of the Phyllanthaceae family. HPLC revealed the presence of various phytochemicals. Study was conducted for 40 days. After PD induction by paraquat behavioural studies were carried out. Biochemical parameters such as DPPH, NO-scavenging, Ferrous reducing power, MDA, GSH, CAT, SOD, acetylcholinesterase (AChE), neurotransmitter estimation and TNF-α and IL-6 levels were determined. DPPH, NO-scavenging and Ferrous reducing power assays showed 78.02%, 48.05% and 71.45% inhibitions, respectively. There was significant improvement in motor functions and coordination in a dose-dependent manner (50 < 250 < 500 mg/kg) in PD rat model. Biochemical markers; SOD, CAT, GPx and GSH showed significant restoration ( P < .001) while MDA showed significant decrease ( P < .05). The AChE level was significantly reduced ( P < .05) at 500 mg/kg while neurotransmitters were significantly improved ( P < .001) in a dose-dependent fashion. The ELISA results showed significant ( P < .001) down-regulation of IL-6 and TNF-α level. In conclusion, it is suggested that BCE has the potential to reduce the symptoms of PD.
Present research work evaluates variation in volatile chemicals profile and biological activities of essential oil (EO) obtained from the leaves of eucalyptus ( Eucalyptus camaldulensis Dehnh.) using hydro-distillation (HD) and supercritical fluid extraction (SFE). The yield (1.32%) of volatile oil by HD was higher than the yield (.52%) of the SFE method ( P < .05). The results of physical factors like density, color, refractive index, and solubility of the EOs produced by both the methods showed insignificant variations. Gas chromatography - mass spectrometry (GC-MS) compositional analysis showed that eucalyptol (31.10% and 30.43%) and α-pinene (11.02% and 10.35%) were the main constituents detected in SFE and HD extracted Eucalyptus camaldulensis EO, respectively. Antioxidant activity-related parameters, such as reducing ability and DPPH free radical scavenging capability exhibited by EO obtained via SFE were noted to be better than hydro-distilled EO. Supercritical fluid extracted and hydro-distilled essential oils demonstrated a considerable but variable antimicrobial potential against selected bacterial and fungal strains. Interestingly, oil extracted by SFE showed relatively higher hemolytic activity and biofilm inhibition potential. The variation in biological activities of tested EOs can be linked to the difference in the volatile bioactives composition due to different isolation techniques. In conclusion, the EO obtained from Eucalyptus leaves by the SFE method can be explored as a potential antioxidant and antimicrobial agent in the functional food and nutra-pharmaceutical sector.