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Human TNF-α levels in WS1 fibroblasts receiving no irradiation (0 J/cm²) or irradiation (5 J/cm²) at 660 nm at (a) 0 h, (b) 24 h, and (c) 48 h postirradiation. Results are represented as the mean±standard deviation. ∗P≤0.05; ∗∗P≤0.01; ∗∗∗P≤0.001.
Source publication
Chemicals and signaling molecules released by injured cells at the beginning of wound healing prompt inflammation. In diabetes, prolonged inflammation is one of the probable causes for delayed wound healing. Increased levels of cyclooxygenase-2 (cox-2), interleukin–6 (IL-6), and tumour necrosis factor-alpha (TNF-α) are associated with the inflammat...
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Citations
... Transcranial photobiomodulation (t-PBM) is a noninvasive, lowcost, emerging therapy that utilizes low-level light to modulate brain activity (Hamblin, 2016;Lopes Martins et al., 2021) and has been demonstrated to have anti-inflammatory effects, as shown by various animal and human models (Bathini et al., 2022;De Marchi et al., 2021;Dos Santos Cardoso et al., 2022;Esteves et al., 2022;Hamblin, 2017;Lima et al., 2014;Lu et al., 2017;Shaikh-Kader et al., 2021;Zheng et al., 2021). When applied to the scalp, nearinfrared (NIR) light, the main light source for t-PBM, increases cerebral blood flow, oxygenation, and metabolism, which enhances neuronal plasticity and promotes neuroprotection (Henderson & Morries, 2015;Nawashiro et al., 2012;Salgado et al., 2015;Tian et al., 2016). ...
... The presumptive mechanism of action of t-PBM involves the absorption of photons by chromophores in the mitochondria, specifically cytochrome c oxidase (CCO), which is a component of the mitochondrial respiratory chain (Oron et al., 2007). Research has suggested that the above-mentioned mechanisms of t-PBM may impact the pathophysiology of neuropsychiatric disorders via (1) modulation of oxidative stress (de Freitas & Hamblin, 2016;Molendijk et al., 2014;Rizzi et al., 2006); (2) downregulation of immune cell alterations and the NLRP3 inflammasome complex (Choi et al., 2012;de Barros Silva et al., 2022;de Brito et al., 2022;Guo et al., 2021;Li, Liang, et al., 2020;Ryu et al., 2022;Wu et al., 2022); (3) reduction of proinflammatory cytokines levels such as TNFα, CRP, IL-1β, and IL-6 (De Marchi et al., 2021;Esteves et al., 2022;Lima et al., 2014;Lu et al., 2017;Shaikh-Kader et al., 2021;Zheng et al., 2021); (4) deactivation of neurotoxic microglia (Choi et al., 2012;Ketz et al., 2017;Lu et al., 2017;Tao et al., 2021;Wang et al., 2021), and (5) increase of BDNF gene expression (Heo et al., 2019;Yan et al., 2017). ...
... 1. t-PBM could balance the alterations in peripheral immune cell populations observed in OCD, such as dysregulation of Th17, Treg, monocytes, and the NLRP3 inflammasome complex (Choi et al., 2012;de Barros Silva et al., 2022;de Brito et al., 2022;Guo et al., 2021;Li, Liang, et al., 2020;Ryu et al., 2022;Wu et al., 2022); 2. t-PBM could decrease the levels of peripheral cytokines that are elevated in OCD, including TNFα, CRP, IL-1β, and IL-6 (De Marchi et al., 2021;Esteves et al., 2022;Lima et al., 2014;Lu et al., 2017;Shaikh-Kader et al., 2021;Zheng et al., 2021); ...
Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric disorder that affects about 2%-3% of the global population. Despite the availability of several treatments , many patients with OCD do not respond adequately, highlighting the need for new therapeutic approaches. Recent studies have associated various inflammatory processes with the pathogenesis of OCD, including alterations in peripheral immune cells, alterations in cytokine levels, and neuroinflammation. These findings suggest that inflammation could be a promising target for intervention. Transcranial photobio-modulation (t-PBM) with near-infrared light is a noninvasive neuromodulation technique that has shown potential for several neuropsychiatric disorders. However, its efficacy in OCD remains to be fully explored. This study aimed to review the literature on inflammation in OCD, detailing associations with T-cell populations, monocytes, NLRP3 inflammasome components, microglial activation, and elevated proinflamma-tory cytokines such as TNF-α, CRP, IL-1β, and IL-6. We also examined the hypothesis-based potential of t-PBM in targeting these inflammatory pathways of OCD, focusing on mechanisms such as modulation of oxidative stress, regulation of immune cell function, reduction of proinflammatory cytokine levels, deactivation of neurotoxic microglia, and upregulation of BDNF gene expression. Our review suggests that t-PBM could be a promising, noninvasive intervention for OCD, with the potential to modulate underlying inflammatory processes. Future research should focus on rand-omized clinical trials to assess t-PBM's efficacy and optimal treatment parameters in OCD. Biomarker analyses and neuroimaging studies will be important in understanding the relationship between inflammatory modulation and OCD symptom improvement following t-PBM sessions.
... It has long been understood that by imitating the scarless wound healing process of foetal system, adequate inhibition or control of inflammatory response will be useful for reducing scars 220 . For an instance, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-a), pro-inflammatory cytokines that are primarily released by M1 macrophages, can interfere with one or more phases of the wound healing process and cause prolonged inflammation that results in additional tissue damage, including tissue fibrosis 221 . M2 macrophages, however, support tissue regeneration through antiinflammation, immunological regulation, and tissue remodelling 222,223 . ...
The objective of this review is to provide an up-to-date and all-encompassing primal account and recent advancements in the domain of interactive wound dressings. Appreciating the gap between obtained and...
... Red LED was also able to increase BDNF expression in mouse hippocampal organotypic slices [83], and lowpower red laser increased BNDF expression in cultures of neural stem cells from the mouse hippocampus [84]. It was reported that low-power laser and LED decreased pro-inflammatory interleukin (IL) levels, such as IL-6 levels, in diabetic fibroblast cell models after red laser exposure [85], and low-power infrared laser decreased the immunoexpression of IL-1β in an experimental model of COVID-19 infection [86]. In addition, radiation from such light sources was able to increase anti-inflammatory interleukin levels, as IL-10 levels were increased in individuals with relapsing-remitting multiple sclerosis after sublingual exposure to a low-power infrared (808 nm) laser [87], and low-power red (635 nm) increased IL-10 expression in the mouse hippocampus of Alzheimer's disease models [84]. ...
Since the reporting of Endre Mester’s results, researchers have investigated the biological effects induced by non-ionizing radiation emitted from low-power lasers. Recently, owing to the use of light-emitting diodes (LEDs), the term photobiomodulation (PBM) has been used. However, the molecular, cellular, and systemic effects involved in PBM are still under investigation, and a better understanding of these effects could improve clinical safety and efficacy. Our aim was to review the molecular, cellular, and systemic effects involved in PBM to elucidate the levels of biological complexity. PBM occurs as a consequence of photon-photoacceptor interactions, which lead to the production of trigger molecules capable of inducing signaling, effector molecules, and transcription factors, which feature it at the molecular level. These molecules and factors are responsible for cellular effects, such as cell proliferation, migration, differentiation, and apoptosis, which feature PBM at the cellular level. Finally, molecular and cellular effects are responsible for systemic effects, such as modulation of the inflammatory process, promotion of tissue repair and wound healing, reduction of edema and pain, and improvement of muscle performance, which features PBM at the systemic level.
... This might be due to the fact that under diabetic conditions the excess generation of free radicals and inflammatory cytokines blocks the activation of PI3K that directly inhibits the activation of AKT and finally results in poor cell proliferation/migration followed by cell death. Previous studies from our lab reported that irradiation with 660 or 830 nm dramatically inhibits pro-inflammatory cytokines and generation of free radicals [36,37] and this course of action might be due to activation of the PI3K/AKT signaling pathway, which is now confirmed in this present study. The major reason behind this action might be due to the ability of PBM in activating and up-regulating the PI3K/AKT signaling pathway and the downstream effect of this AKT activation is the inhibition of FoxO1 in order to inhibit apoptosis and cell death. ...
Prolonged inflammation and impaired redox balance are important causes of delayed wound healing. Photobiomodulation (PBM) enhances delayed wound healing by modulating various cellular signaling pathways involved in the wound healing process. This study aimed to reveal the mechanisms of action of PBM in accelerating wound healing in a diabetic adipose derived stem cell (ADSC)-fibroblast co-culture cell model. ADSC-fibroblast co-culture cells were divided into normal (N), normal wounded (NW), diabetic (D) and diabetic wounded (DW) groups and were irradiated (wavelength: 660 or 830 nm; energy density: 5 J/cm²). Unirradiated cells (0 J/cm²) served as controls. Wound closure/migration was recorded in NW and DW groups using light microscopy. Signaling pathway proteins (PI3 kinase, AKT and FoxO1) modulated by PBM were evaluated by immunofluorescence and western blotting. ELISA was used to measure the levels of antioxidants (HMOX1, SOD and CAT). PBM treatment effectively enhanced cell migration and wound closure in irradiated groups. Furthermore, PBM elevated PI3 kinase and AKT signaling proteins that in turn elevated antioxidant levels. These results demonstrate that PBM at 660 and 830 nm increases migration of co-culture cells and is mediated at least in part through the activation/regulation of the PI3K/AKT/FoxO1 signaling pathway. PBM could be a promising therapeutic approach which can be used in chronic wound treatment.
... AgNPs exhibited a promising wound healing potential for the infected rat wounds, as they induced complete epithelization and decreased the TNF-α immunostaining. TNF-α usually increases in non-healing wounds due to oxidative stress and inflammation [47]. Furthermore, the synthesis of collagen fibers was significantly higher in the case of treatment with AgNPs. ...
Candida albicans is a major human opportunistic pathogen causing infections, which range from cutaneous to invasive systemic infections. Herein, the antifungal and anti-biofilm potential of silver nanoparticles (AgNPs) green synthesized in the presence of Encephalartos laurentianus leaf extract (ELLE) were investigated. The bioactive chemicals of ELLE, including phenolics, flavonoids, and glycosides were identified and quantified for the first time. AgNPs showed minimum inhibitory concentration (MIC) values against C. albicans clinical isolates ranging from 8 to 256 µg/mL. In addition, AgNPs significantly decreased biofilm formation. The impact of AgNPs on the expression of the genes encoding biofilm formation was assessed using qRT-PCR. AgNPs had a beneficial role in the macroscopic wound healing, and they resulted in complete epithelization without any granulation tissue or inflammation. Treatment with AgNPs resulted in negative immunostaining of tumor necrosis factor-α. The levels of the inflammation markers, interleukin-6 and interleukin-1β, significantly decreased (p < 0.05) in the AgNPs-treated group. There was also a pronounced increase in the gene expression of fibronectin and platelet-derived growth factor in the wound tissues. Thus, AgNPs synthesized using ELLE may be a promising antifungal and wound healing agent.
... Shaikh-Kader et al. evaluated the effects of PBM (660 nm, 5 J/cm 2 ) on some proinflammatory cytokines levels, including IL-6, in fibroblast cell culture models. They concluded that PBM at 660 nm may reduce oxidative stress by reducing IL-6 levels in models of diabetic cells [41]. Rajendran et al. investigated the effect of PBM (660 nm, 5 J/cm 2 , and 11.2 mW/cm 2 ; and 830 nm, 5 J/cm 2 , 10.3 mW/cm 2 ) on antioxidant enzymes in ADSs in vitro. ...
The single and associated impressions of photobiomodulation (PBM) and adipose-derived stem cells (ADS) on stereological parameters (SP), and gene expression (GE) of some antioxidant and oxidative stressors of repairing injured skin at inflammation and proliferation steps (days 4 and 8) of a delayed healing, ischemic, and infected wound model (DHIIWM) were examined in type one diabetic (DM1) rats. DM1 was induced by administration of streptozotocin (40 mg/kg) in 48 rats. The DHIIWM was infected by methicillin-resistant Staphylococcus aureus (MRSA). The study comprised 4 groups (each, n = 6): Group 1 was the control group (CG). Group 2 received allograft human (h) ADSs transplanted into the wound. In group 3, PBM (890 nm, 80 Hz, 0.2 J/cm2) was emitted, and in group 4, a combination of PBM+ADS was used. At both studied time points, PBM+ADS, PBM, and ADS significantly decreased inflammatory cell count (p < 0.05) and increased granulation tissue formation compared to CG (p < 0.05). Similarly, there were lower inflammatory cells, as well as higher granulation tissue in the PBM+ADS compared to those of alone PBM and ADS (all, p < 0.001). At both studied time points, the GE of catalase (CAT) and superoxide dismutase (SOD) was remarkably higher in all treatment groups than in CG (p < 0.05). Concomitantly, the outcomes of the PBM+ADS group were higher than the single effects of PBM and ADS (p < 0.05). On day 8, the GE of NADPH oxidase (NOX) 1 and NOX4 was substantially less in the PBM+ADS than in the other groups (p < 0.05). PBM+ADS, PBM, and ADS treatments significantly accelerated the inflammatory and proliferative stages of wound healing in a DIIWHM with MRSA in DM1 rats by decreasing the inflammatory response, and NOX1 and 4 as well; and also increasing granulation tissue formation and SOD and CAT. The associated treatment of PBM+ADS was more effective than the individual impacts of alone PBM and ADS because of the additive anti-inflammatory and proliferative effects of PBM plus ADS treatments.
... TNF-α and COX-2 immunostaining was carried out and examined using a light microscope, as shown in Figs. 10 and 11. TNF-α and COX-2 levels usually increase in non-healing wounds as they have a role in inflammation and oxidative stress (Shaikh-Kader et al., 2021). Hence, we carried out immunohistochemical studies to investigate the levels of these markers in the wound tissues. ...
Nanofibers (NFs) provide versatile advantages like their great flexibility and similarity with extracellular matrix (ECM) which qualify them to be the unique model of a wound dressing. NFs could create mats of polymeric matrix loaded with an active agent enhancing its solubility and stability. In our study, Gentiopicroside (GPS) and Thymoquinone (TQ) loaded in NFs polymeric mats composed of coblended polyvinyl pyrrolidine (PVP) and methyl ether Polyethylene glycol (m-PEG) were fabricated via electrospinning technique. A morphological study using Scanning Electron Microscopy (SEM) was performed for all formulae as well as in vitro release study using High-performance Liquid chromatography (HPLC) for sample analysis. The optimized formula (F3) was chosen for further assays using Fourier-Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC). Study of the antibacterial effect, and in vivo healing action for diabetic infected wounds to quantify Tumor necrosis factor-alpha and Cyclooxygenase-2 were also investigated. F3 achieved the highest % cumulative release (99.79±6.47 for GPS and 96.89±6.87 for TQ) at 60 minutes, and a smaller diameter (200 nm) showing significant anti-bacterial effects with well-organized skin architecture demonstrating great healing signs. Our results revealed that m-PEG/PVP NFs mats loaded with GPS and TQ could be considered an optimal wound care dressing.
... In the case of fibroblasts and keratinocytes, it was determined that the application of the low intensity laser at 3200 Hz results in a significant reduction of the negative effect on cell viability after 48 h or 72 h, respectively. This protective effect could be based on a published reduction of the pro-inflammatory mediators cyclooxygenase 2 (Cox2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) [37,42], which was assigned to be potential laser-induced mechanisms, triggering the positive effects on viability and proliferation of fibroblasts, evaluated in this study. As physiologically expected, the monocytes THP-1 responded to TNF-α application with a significant and time-independent enhancement of their metabolic activity, which was not interfered by laser treatment. ...
Objectives
Treating infected or chronic wounds burdened with biofilms still is a major challenge in medical care. Healing-stimulating factors lose their efficacy due to bacterial degradation, and antimicrobial substances negatively affect dermal cells. Therefore, alternative treatment approaches like the pulsed low intensity laser therapy (LILT) require consideration.
Methods
The effect of pulsed LILT (904 nm, in three frequencies) on relevant human cells of the wound healing process (fibroblasts (BJ), keratinocytes (HaCaT), endothelial cells (HMEC), monocytes (THP-1)) were investigated in in-vitro and ex-vivo wound models with respect to viability, proliferation and migration. Antimicrobial efficacy of the most efficient frequency in cell biological analyses of LILT (3200 Hz) was determined in a human biofilm model (lhBIOM). Quantification of bacterial load was evaluated by suspension method and qualitative visualization was performed by scanning electron microscopy (SEM).
Results
Pulsed LILT at 904 nm at 3200 Hz ± 50% showed the most positive effects on metabolic activity and proliferation of human wound cells in vitro (after 72 h – BJ: BPT 0.97 ± 0.05 vs. 0.75 ± 0.04 (p = 0.0283); HaCaT: BPT 0.79 ± 0.04 vs. 0.59 ± 0.02 (p = 0.0106); HMEC: 0.74 ± 0.02 vs. 0.52 ± 0.04 (p = 0.009); THP-1: 0.58 ± 0.01 vs. 0.64 ± 0.01 (p > 0.05) and ex vivo. Interestingly, re-epithelialization was stimulated in a frequency-independent manner. The inhibition of metabolic activity after TNF-α application was abolished after laser treatment. No impact of LILT on monocytes was detected. Likewise, the tested LILT regimens showed no growth rate reducing effects on three bacterial strains (after 72 h - PA: -1.03%; SA: -0.02%; EF: −1,89%) and one fungal (−2.06%) biofilm producing species compared to the respective untreated control. Accordingly, no significant morphological changes of the biofilms were observed after LILT treatment in the SEM.
Conclusions
Frequent application of LILT (904 nm, 3200 Hz) seems to be beneficial for the metabolism of human dermal cells during wound healing. Considering this, the lack of disturbance of the behavior of the immune cells and no growth-inducing effect on bacteria and fungi in the biofilm can be assigned as rather positive. Based on this combined mode of action, LILT may be an option for hard to heal wounds infected with persistent biofilms.
... Існують дані, що еритроцити пацієнтів за ЦД мають підвищену адгезію до ендотеліальних клітин.Крім того, зміни, що відбуваються за ЦД у внутрішньоклітинному окисновідновному стані та передачі сигналів NO в еритроцитах, сприяють посиленню оксидативно-нітративного стресу в судинах, що викликає згубний вплив на судинну та серцеву функцію та сприяє розбитку подальших ускладнень, які характерні за ЦД[77].1.6. Ефекти впливу фотобіомодуляційної терапіїРВМТ викликає загоєння ран[1,2], зменшує біль та знижує запалення за ЦД[109]. Найчастіше для РВМТ застосовують довжину хвилі, що становить 630-660 нм. ...
Відповідно до статистики Міжнародної діабетичної федерації (IDF) станом на 2021 рік, приблизно 6,7 мільйона людей померло внаслідок цукрового діабету та його ускладнень. Таким чином, дослідження впливу фотобіомодуляційної терапії на щурів із цукровим діабетом є життєво важливими для практичного застосування цієї мінімально інвазивної та економічно вигідної допоміжної терапії. Метою та завданням магістерської роботи було дослідження впливу фотобіомодуляційної терапії на енергозабезпечення лейкоцитів, а також на розвиток оксидативно-нітративного стресу в крові щурів у нормі та за експериментального цукрового діабету. Було виявлено, що фотобіомодуляційна терапія із застосуванням червоних світлодіодів позитивно впливає на енергопостачання та функціонування лейкоцитів за цукрового діабету, покращує транспорт глюкози та вироблення АТФ, нормалізує активність мієлопероксидази, знижує деякі біомаркери оксидативно-нітративного стресу. Крім того, фотобіомодуляційна терапія викликає зниження маркерів нітративного стресу та зниження вмісту метгемоглобіну в еритроцитах, що покращує постачання тканин киснем. На основі літературних джерел, а також інформації, отриманої у результаті досліджень, створені гіпотетичні схеми впливу фотобіомодуляційної терапії на поглинання глюкози полегшеною дифузією транспортерами родини GLUT (GLUT1, GLUT3, GLUT4) та Na+-залежним ко-транспортером глюкози SGLT1, а також схема впливу терапії на перетворення форм нітрогену та гемоглобіну в еритроцитах щурів із цукровим діабетом.
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... High risk of wound infection and healing failure was found in diabetes, and the abnormal function of fibroblasts was assumed as a major issue contributing to the delayed wound healing [9][10][11]. Noticeably, fibroblasts exert an important role in wound inflammatory response by release of various antibacterial regulators, providing a robust defense of skin against infections [12][13][14]. Diabetes patients are susceptible to infections due to the dysregulated function of the T cells, leading to the overactivated tissue inflammation. In this bioinformatic research, functional enrichment analysis was performed, and the systematic results suggested that the highest p value was the MAPK signaling pathway among DEGs in fibroblasts. ...
Fibroblasts are the essential cell type of skin, highly involved in the wound regeneration process. In this study, we sought to screen out the novel genes which act important roles in diabetic fibroblasts through bioinformatic methods. A total of 811 and 490 differentially expressed genes (DEGs) between diabetic and normal fibroblasts were screened out in GSE49566 and GSE78891, respectively. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in type 2 diabetes were retrieved from miRWalk. Consequently, the integrated bioinformatic analyses revealed the shared KEGG pathways between DEG-identified and diabetes-related pathways were functionally enriched in the MAPK signaling pathway, and the MAPKAPK3, HSPA2, TGFBR1, and p53 signaling pathways were involved. Finally, ETV4 and NPE2 were identified as the targeted transcript factors of MAPKAPK3, HSPA2, and TGFBR1. Our findings may throw novel sight in elucidating the molecular mechanisms of fibroblast pathologies in patients with diabetic wounds and targeting new factors to advance diabetic wound treatment in clinic.
