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The relationship between Nrf2 and NF-κB. CBP – CREB binding protein; COX-2 – cyclooxygenase-2; Gai2 – inhibitory G protein; HO-1 – heme oxgenase-1; IκB – inhibitory protein of NF-κB; IL-8 – interleukin 8; Keap1 – Kelch-like ECHassociated protein; NF-κB – nuclear factor-κB; Nrf2 – nuclear factor-erythroid 2 (NF-E2)-related factor 2; P – phosphorylation; PI3K – phosphatidylinositol 3-kinase; ROS – reactive oxygen species.
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Nrf2 and NF-κB transcription factors act in wound healing via their anti-inflammatory and anti-oxidant effects or through the immune response. Studying this process is a matter of some importance given the high cost of wound treatment. A major contribution in this regard is being made by models that enable investigation of the involvement of multip...
Citations
... Because of its capacity to scavenge free radicals, cerium oxide nanoparticles (CNP) can be used as a therapeutic treatment for oxidative stress. In diabetic wounds, miR-146a inhibits interlukin-1 receptor associated kinase 1 (IRAK1) and tumor necrosis factor receptor associated kinase 6 (TRAF6) (Ambrozova et al. 2017). ...
Various scientists and researchers from prestigious institutions have turned their research to achieve sustainability goals in almost every field, especially materials. The fabrication of new synthetic and natural renewable biomaterials is the fastest-growing field in biomedical applications. In well-known biomedical applications such as tissue engineering, implants, and drug delivery systems, renewable materials now have new opportunities due to the improvement of their bioactivity, compatibility, and mechanical properties. One example is skin tissue engineering which has arisen as an alternative and successful method to restore completely functioning tissue using novel biomaterials or engineered scaffolding. The design of advanced biomaterials with regulated physical, chemical, electrical, and biological properties would also promote functional tissues. Both natural and synthetic biomaterials used in tissue engineering provisionally support and mass transfer to promote system while also regulating regenerated tissue size and shape.KeywordsRenewable biomaterialsNatural biomaterialsSynthetic biomaterialsSustainable designNanomaterialsDrug deliveryWound healing
... Because of its capacity to scavenge free radicals, cerium oxide nanoparticles (CNP) can be used as a therapeutic treatment for oxidative stress. In diabetic wounds, miR-146a inhibits interlukin-1 receptor associated kinase 1 (IRAK1) and tumor necrosis factor receptor associated kinase 6 (TRAF6) (Ambrozova et al. 2017). ...
A wide range of biomaterials, both of natural and synthetic origin, have been studied for utilization in biomedical applications. The tremendous growth in science and technology of material science and biomedical engineering has enabled the influx of different kinds of materials, either obtained from natural sources or chemically synthesized, through various fabrications and bioprocessing techniques to be used in patient care. The progress in this field also raises many concerns and challenges from the ethical and legal aspects that need to be addressed to ensure its sustainability. This chapter discusses the ethical and regulatory factors including but not limited to the responsible and efficient use of resources, green synthesis, waste management, impact on the economy, society, and environment, and the legislation on a sustainable design approach that needs to be considered to ensure the sustainability of the materials and also its utilization in the biomedical field in the future.KeywordsSustainabilityRegenerative medicineGreen synthesisCircular economyWaste reductionBiomaterialBiodegradable
... Subsequently, the downstream mechanism of SIM was investigated. Nrf2 acts as a key transcription factor in regulating cellular responses to oxidative stress and inflammation (29). In another way, a summary review revealed that Nrf2 was a pro-survival factor and a main regulator of cytoprotective mechanisms, while Nrf2-ARE signaling could modulate cellular response under oxidative stress (30). ...
Objectives:
Increased oxidative stress and inflammatory response are risk factors for kidney and cardiovascular diseases in patients with hyperuricemia. Uric acid (UA) has been reported to cause inflammation and oxidative damage in cells by inhibiting the nuclear factor E2-related factor 2 (Nrf2) pathway. Notably, Simvastatin (SIM) can regulate the Nrf2 pathway, but whether SIM can regulate inflammatory response and oxidative stress in vascular endothelial cells induced by high UA via this pathway has not been clarified.
Materials and methods:
To demonstrate this speculation, cell activity, as well as apoptosis, was estimated employing CCK-8 and TUNEL, respectively. Indicators of oxidative stress and inflammation were assessed by related kits and western blotting. Subsequently, the effects of SIM on signaling pathways were examined using western blotting.
Results:
The result showed that after UA exposure, oxidative stress was activated and inflammation was increased, and SIM could reverse this trend. Meanwhile, SIM could inhibit high UA-induced apoptosis. In addition, western blotting results showed that SIM reversed the down-regulation of the expression of Nrf2 pathway-related proteins caused by high UA.
Conclusion:
SIM alleviated the inflammatory response as well as inhibiting oxidative stress through the Nrf2 pathway, thereby attenuating high UA-induced vascular endothelial cell injury.
... However, excessive or prolonged activation of NF-kB signaling can lead to chronic inflammation and delay wound healing. Therefore, the proper regulation of NF-kB signaling is crucial for optimal wound healing [61]. QCN exhibits antiaging properties on middle-aged keratinocytes and supports regeneration of terminally senescent cells. ...
Quercetin is a well-known plant flavanol that exhibits multiple biological activities, including antioxidant, anti-inflammatory and anticancer activities. The role of quercetin in wound healing has been widely explored by a range of researchers in different models. However, the physicochemical properties, such as solubility and permeability, of this compound are low, which ultimately limits its bioavailability on the target site. To overcome these limitations for successful therapy, scientists have developed a range of nanoformulations that provide effective therapeutic potential. In this review, the broad mechanism of quercetin for acute and chronic wounds is covered. A compilation of recent advances on the horizon of wound healing via quercetin is incorporated with several advanced nanoformulations.
... The anti-inflammatory and antioxidant response of NF-κB plays an important role in wound healing and tissue repair. Moreover, NF-κB activates the migration of cells, proliferation, modulates the expression of matrix metalloproteinases (MMPs), and activates the secretion of growth factors and cytokines for improved wound healing [137]. It was observed that LPS considerably raised the phosphorylation of NF-κB and inhibited Iκ-B phosphorylation which in turn inhibited NF-κB nuclear translocation and transcriptional activity, ultimately reducing the release of inflammatory mediators and cytokines. ...
The therapeutic benefits of phytochemicals in the treatment of various illnesses and disorders are well documented. They show significant promise for the discovery and creation of novel medications for treating a variety of human diseases. Numerous phytoconstituents have shown antibiotic, antioxidant, and wound-healing effects in the conventional system. Traditional medicines based on alkaloids, phenolics, tannins, saponins, terpenes, steroids, flavonoids, glycosides, and phytosterols have been in use for a long time and are crucial as alternative treatments. These phytochemical elements are crucial for scavenging free radicals, capturing reactive carbonyl species, changing protein glycation sites, inactivating carbohydrate hydrolases, fighting pathological conditions, and accelerating the healing of wounds. In this review, 221 research papers have been reviewed. This research sought to provide an update on the types and methods of formation of methylglyoxal-advanced glycation end products (MGO-AGEs) and molecular pathways induced by AGEs during the progression of the chronic complications of diabetes and associated diseases as well as to discuss the role of phytoconstituents in MGO scavenging and AGEs breaking. The development and commercialization of functional foods using these natural compounds can provide potential health benefits.
... The total level of SOD (Cu/Zn/Mn-SOD) increases in the endometrium from the proliferative phase to the mid-secretory phase and decreases in the late-secretory phase, and on the contrary, lipid peroxidation increases as a physiological action of ROS [23]. Non-enzymatic antioxidants, mainly taken in food or endogenous biosynthesis, include polyphenols (quercetin, resveratrol, baicalin), carotenoids (β-carotene, lycopene, lutein), low-molecular-weight antioxidants (glutathione, uric acid), trace elements (zinc and selenium), vitamins (A, E, C, B9), and others (L-carnitine, melatonin, acetylcysteine) [35,36]. The level of endogenous antioxidants is mostly stable and these molecules are only activated as necessary [37]. ...
Oxidative stress (OS) has an important role in female reproduction, whether it is ovulation, endometrium decidualization, menstruation, oocyte fertilization, or development andimplantation of an embryo in the uterus. The menstrual cycle is regulated by the physiological concentration of reactive forms of oxygen and nitrogen as redox signal molecules, which trigger and regulate the length of individual phases of the menstrual cycle. It has been suggested that the decline in female fertility is modulated by pathological OS. The pathological excess of OS compared to antioxidants triggers many disorders of female reproduction which could lead to gynecological diseases and to infertility. Therefore, antioxidants are crucial for proper female reproductive function. They play a part in the metabolism of oocytes; in endometrium maturation via the activation of antioxidant signaling pathways Nrf2 and NF-κB; and in the hormonal regulation of vascular action. Antioxidants can directly scavenge radicals and act as a cofactor of highly valuable enzymes of cell differentiation and development, or enhance the activity of antioxidant enzymes. Compensation for low levels of antioxidants through their supplementation can improve fertility. This review considers the role of selected vitamins, flavonoids, peptides, and trace elements with antioxidant effects in female reproduction mechanisms.
... The Hippo pathway is an evolutionarily conserved signaling mechanism that holds important functions in tissue regeneration, immunological regulation, epithelial homeostasis, organ development, and wound healing. Many of these functions are carried out by the transcriptional effectors YAP and TAZ, which regulate the TEAD family of transcription factors to control gene expression [114]. According to previously published research, it has been found that there is an interaction between the YAP/TAZ (Hippo pathway) and TGF-1/Smad signaling pathways during the healing process, which suggests that the findings might have pleiotropic effects that affect collagen production, cell growth, and wound healing [115]. ...
Wounds are considered to be a serious problem that affects the healthcare sector in many countries, primarily due to diabetes and obesity. Wounds become worse because of unhealthy lifestyles and habits. Wound healing is a complicated physiological process that is essential for restoring the epithelial barrier after an injury. Numerous studies have reported that flavonoids possess wound-healing properties due to their well-acclaimed anti-inflammatory, angiogenesis, re-epithelialization, and antioxidant effects. They have been shown to be able to act on the wound-healing process via expression of biomarkers respective to the pathways that mainly include Wnt/β-catenin, Hippo, Transforming Growth Factor-beta (TGF-β), Hedgehog, c-Jun N-Terminal Kinase (JNK), NF-E2-related factor 2/antioxidant responsive element (Nrf2/ARE), Nuclear Factor Kappa B (NF-κB), MAPK/ERK, Ras/Raf/MEK/ERK, phosphatidylinositol 3-kinase (PI3K)/Akt, Nitric oxide (NO) pathways, etc. Hence, we have compiled existing evidence on the manipulation of flavonoids towards achieving skin wound healing, together with current limitations and future perspectives in support of these polyphenolic compounds as safe wound-healing agents, in this review.
... Our previous study showed that elevated ROS levels in a high-glucose environment contribute to the increase in IL-8 production from keratinocytes, and neutrophil infiltration results in impaired wound healing in a diabetic rat model [49]. ROS can upregulate MMP-9 through the activation of nuclear factor kappa beta (NF-κB) in human keratinocytes, leading to the impairment of keratinocyte migration [50,51]. In addition, the mitochondria, a main source of ROS production, can generate huge amounts of ROS in a high glucose environment, followed by the hampering of the antioxidant ability of the cell and resulting in mitochondria damage [52,53]. ...
Diabetes mellitus (DM) is an important cause of chronic wounds and non-traumatic amputation. The prevalence and number of cases of diabetic mellitus are increasing worldwide. Keratinocytes, the outermost layer of the epidermis, play an important role in wound healing. A high glucose environment may disrupt the physiologic functions of keratinocytes, resulting in prolonged inflammation, impaired proliferation, and the migration of keratinocytes and impaired angiogenesis. This review provides an overview of keratinocyte dysfunctions in a high glucose environment. Effective and safe therapeutic approaches for promoting diabetic wound healing can be developed if molecular mechanisms responsible for keratinocyte dysfunction in high glucose environments are elucidated.
... NF-kB also has a role in the regulation of homeostasis in response to inflammatory stimuli, expressing cytokines [62], cell adhesion molecules, and growth factors during healing [70]. NF-kB acts primarily through activation of the canonical IkB/NF-kB signaling pathway [71,72]. ...
Wound healing is characterized by a systemic and complex process of cellular and molecular activities. Dipotassium Glycyrrhizinate (DPG), a side product derived from glycyrrhizic acid, has several biological effects, such as being antiallergic, antioxidant, antibacterial, antiviral, gastroprotective, antitumoral, and anti-inflammatory. This study aimed to evaluate the anti-inflammatory effect of topical DPG on the healing of cutaneous wounds by secondary intention in an in vivo experimental model. Twenty-four male Wistar rats were used in the experiment, and were randomly divided into six groups of four. Circular excisions were performed and topically treated for 14 days after wound induction. Macroscopic and histopathological analyses were performed. Gene expression was evaluated by real-time qPCR. Our results showed that treatment with DPG caused a decrease in the inflammatory exudate as well as an absence of active hyperemia. Increases in granulation tissue, tissue reepithelization, and total collagen were also observed. Furthermore, DPG treatment reduced the expression of pro-inflammatory cytokines (Tnf-α, Cox-2, Il-8, Irak-2, Nf-kB, and Il-1) while increasing the expression of Il-10, demonstrating anti-inflammatory effects across all three treatment periods. Based on our results, we conclude that DPG attenuates the inflammatory process by promoting skin wound healing through the modulation of distinct mechanisms and signaling pathways, including anti-inflammatory ones. This involves modulation of the expression of pro- and anti-inflammatory cytokine expression; promotion of new granulation tissue; angiogenesis; and tissue re-epithelialization, all of which contribute to tissue remodeling.
... The rate of wound contraction was increased due to rapid wound contraction, epithelialization, and collagenization [52]. In addition, IL-1b contributes to re-epithelialization, angiogenesis, and collagen synthesis [53]. ...
Wound care has become increasingly important over the years. Various synthetic products for wound care treatment have been reported to cause toxic side effects and therefore natural products are in significant demand as they have minimal side effects. The presence of bioactive compounds in medicinal mushrooms contributes to various biological activities which assist in the early inflammatory phase, keratinocyte proliferation, and its migration enhancement which are pertinent to wound rehabilitation. Lignosus rhinocerus (tiger milk mushroom) can reduce the inflammation phase in wound healing by fighting off bacterial infection and modulating pro-inflammatory cytokines expression in the early stage to avoid prolonged inflammation and tissue damage. The antibacterial, immunomodulating, and anti-inflammatory activities exhibited by most macrofungi play a key role in enhancing wound healing. Several antibacterial and antifungal compounds sourced from traditional botanicals/products may prevent further complications and reoccurrence of injury to a wounded site. Scientific studies are actively underway to ascertain the potential use of macrofungi as a wound healing agent.
