Photobiomodulation and conditioned medium of adipose-derived stem cells for enhancing wound healing in rats with diabetes: an investigation on the proliferation phase.

This investigation tried to evaluate the combined and solo effects of photobiomodulation (PBM) and conditioned medium derived from human adipose tissue-derived stem cells (h-ASC-CM) on the inflammatory and proliferative phases of an ischemic infected delayed healing wound model (IIDHWM) in rats with type I diabetes mellitus (TIDM). The present investigation consisted of four groups: group 1 served as the control, group 2 treated with h-ASC-CM, group 3 underwent PBM treatment, and group 4 received a combination of h-ASC-CM and PBM. Clinical and laboratory assessments were conducted on days 4 and 8. All treatment groups exhibited significantly higher wound strength than the group 1 (p = 0.000). Groups 4 and 3 demonstrated significantly greater wound strength than group 2 (p = 0.000). Additionally, all therapeutic groups showed reduced methicillin -resistant Staphylococcus aureus (MRSA) in comparison with group 1 (p = 0.000). While inflammatory reactions, including neutrophil and macrophage counts, were significantly lower in all therapeutic groups rather than group 1 on days 4 and 8 (p < 0.01), groups 4 and 3 exhibited superior results compared to group 2 (p < 0.01). Furthermore, proliferative activities, including fibroblast and new vessel counts, as well as the measurement of new epidermal and dermal layers, were significantly increased in all treatment groups on 4 and 8 days after the surgery (p < 0.001). At the same times, groups 4 and 3 displayed significantly higher proliferative activities compared to group 2 (p < 0.001). The treatment groups exhibited significantly higher mast cell counts and degranulation phenotypes in comparison with the group 1 on day 4 (p < 0.05). The treatment groups showed significantly lower mast cell counts and degranulation phenotypes than group 1 on day 8 (p < 0.05).The combined and individual application of h-ASC-CM and PBM remarkably could accelerate the proliferation phase of wound healing in the IIDHWM for TIDM in rats, as indicated by improved MRSA control, wound strength, and stereological evaluation. Furthermore, the combination of h-ASC-CM and PBM demonstrated better outcomes compared to the individual application of either h-ASC-CM or PBM alone.

Role of anti-tumor necrosis factor-alpha agents in treatment of sarcoidosis: A meta-analysis.

IMPORTANCE: Anti-tumor necrosis factor-alpha agent (anti-TNF-α) is considered an effective third-line therapy for refractory sarcoidosis,studies observing the efficacy of anti-TNF-α agents show conflicting results. OBJECTIVE: We performed an up-to-date systemic meta-analysis to determine effectiveness and further elucidate the role of anti-TNF-α in the treatment of sarcoidosis. DATA SOURCES: A systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting the therapeutic effects of anti-TNF drugs on patients with pulmonary and extra-pulmonary sarcoidosis, published up to April 10, 2022. The study was registered in the international prospective register of systematic reviews (PROSPERO) under ID: CRD42022364614. STUDY SELECTION: Clinical trials written reporting the therapeutic effects of anti-TNF drugs on patients with pulmonary and extra-pulmonary sarcoidosis were included. DATA EXTRACTION AND SYNTHESIS: Statistical analyses were performed with Comprehensive Meta-Analysis software, and the random-effects model was used. The combined overall treatment success was determined for patients with pulmonary and extrapulmonary sarcoidosis. MAIN OUTCOMES AND MEASURES: Overall treatment success rate wasdefined as no disease progression or improvement in symptoms. RESULTS: Eight clinical trial articles were included in the meta-analysis; four used Infliximab, two Etanercept, one Adalimumab, and one Ustekinumab and Golimumab. The mean age of participants was 48.5 years. The duration of drug therapy ranged from 14 to 45 weeks. We found a combined overall treatment success rate, defined as no disease progression or improvement in symptoms, of 69.9% (95% CI 35.0-90.9, I2: 70%) in the pulmonary sarcoidosis group and 74.5% (95% CI 36.3-93.7, I2: 90%) in the extrapulmonary sarcoidosis group. There was no evidence of publication bias in either group. CONCLUSION AND RELEVANCE: Treatment of refractory sarcoidosis with anti-TNF-α agents was effective in both pulmonary and extrapulmonary sarcoidosis, with a slightly higher efficacy seen in extrapulmonary sarcoidosis. Further randomized controlled trials should be conducted to determine the effects of anti-TNF-α agents as a part of the management strategy of sarcoidosis. Patients with pulmonary sarcoidosis should be studied separately from patients with extrapulmonary sarcoidosis to adjust for confounding results.

Impact of photobiomodulation on macrophages and their polarization during diabetic wound healing: a systematic review.

This review aims to providing essential information and the current knowledge about the potential role of macrophages, especially their M2 subtypes in different diabetic wounds both in clinical and pre-clinical models under the influence of photobiomodulation (PBM). The long-term goal is to advance the macrophage-based therapies to accelerate healing of diabetic foot ulcers. We reviewed all databases provided by PubMed, Google Scholar, Scopus, Web of Science, and Cochrane precisely from their dates of inception to 25/10/2021. The keywords of Diabetes mellitus diseases, wound healing, macrophage, and photobiomodulation or low-level laser therapy were used in this systematic review.A total of 438 articles were initially identified in pubmed.ncbi.nlm.nih.gov (15 articles), Google scholar (398 articles), Scopus (18 articles), and Web of Science (7 articles). Four hundred sixteen articles that remained after duplicate studies (22 articles) were excluded. After screening abstracts and full texts, 14 articles were included in our analysis. Among them, 4 articles were about the effect of PBM on macrophages in type 2 diabetes and also found 10 articles about the impact of PBM on macrophages in type 1 diabetes. The obtained data from most of the reviewed studies affirmed that the PBM alone or combined with other agents (e.g., stem cells) could moderate the inflammatory response and accelerate the wound healing process in pre-clinical diabetic wound models. However, only very few studies conducted the detailed functions of polarized macrophages and M2 subtypes in wound healing of diabetic models under the influence of PBM. Further pre-clinical and clinical investigations are still needed to investigate the role of M2 macrophages, especially its M2c subtype, in the healing processes of diabetic foot ulcers in clinical and preclinical settings.