Search

Background: Wound healing is a complex biological process that can be impaired in individuals with diabetes. Diabetic wounds are a serious complication of diabetes that require promoting diagnosis and effective treatment. FGF-21, a member of the endocrine FGF factors family, has caught the spotlight in the treatment of diabetes for its beneficial effects on accelerating human glucose uptake and fat catabolism. However, the therapeutic efficacy of FGF-21 in promoting diabetic wounds remains unknown. This study aims to evaluate the therapeutic potential of FGF-21 in promoting diabetic wound healing. Methods: we investigated the effects of FGF-21 on wound healing related-cells under high-glucose conditions using various assays such as CCK8, scratch assay, flow cytometry analysis, endothelial tube-formation assay, and transmission electron microscopy. Furthermore, we used db/db mice to verify the healing-promoting therapeutic effects of FGF-21 on diabetic wounds. We also conducted qRT-PCR, Western blot, and immunofluorescence staining analyses to elucidate the underlying mechanism. Result: Our results indicate that FGF-21 treatment restored hyperglycemic damage on endothelial cell proliferation, migration, and tube-forming ability. It also reduced endothelial cell death rates under high-glucose conditions. TEM analysis showed that FGF-21 treatment effectively restored mitochondrial damage and morphological changes in endothelial cells caused by glucose. Additionally, qRT-PCR and Western blot analysis indicated that FGF-21 treatment restored inflammatory responses caused by hyperglycemic damage. Animal experiments confirmed these findings, suggesting that FGF-21 may be a promising candidate for the treatment of non-healing diabetic wounds due to its effectiveness in stimulating angiogenesis and anti-inflammatory function. Conclusion: Our study provides evidence that FGF-21 is an essential regulator of wound-related cells under high-glucose conditions and has the potential to be a novel therapeutic target for accelerating diabetic wound healing.

Analysis of liver biopsy specimens showed that SARS-CoV-2 might have led to liver damage. This study aimed to evaluate the role of selected hepatokines and myokines in the development and progression of COVID-19. Seventy patients with laboratory-confirmed COVID-19 and 20 healthy volunteers were enrolled in the study. Irisin, pentraxin 3, fetuin-A, and FGF-21 serum concentrations and biochemical parameters were assessed using an immunoenzymatic method with commercially available enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) kits. Serum fetuin-A concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers. The serum concentration of FGF-21 was significantly increased in obese COVID-19 patients compared to overweight ones. Moreover, the FGF-21 level was higher in COVID-19 patients diagnosed with metabolic syndrome than in patients without metabolic syndrome. PTX3 concentration was higher in COVID-19 patients with higher HOMA-IR values than those with lower HOMA-IR values. COVID-19 patients with HOMA-IR ≤ 3 and >3 had significantly lower fetuin-A levels than the control group. Irisin concentration was significantly decreased in the HOMA-IR ≤ 3 COVID-19 subgroup when comparing with the control group. Lower levels of fetuin-A observed in COVID-19 patients despite higher HOMA-IR, CRP, and ferritin levels, pneumonia, patients requiring ICU care suggests that fetuin-A deficiency predisposes to more severe COVID-19 course. Upregulated pentraxin 3 may be used as a potential predictor of COVID-19 severity.

Objective: The purpose of this study was to investigate the effects of a long-term weight loss therapy in two groups (insulin resistance [IR] and non-insulin resistance [non-IR]) of obese adolescents based on metabolic profile, biomarkers of inflammation, and fibroblast growth factor-21 (FGF-21) concentrations. Methods: Obese adolescents (15–19 years) were randomised into two groups (IR=8 and non-IR=9) and monitored through clinical, exercise training, nutritional, and psychological counselling over 1 year. Measurements of inflammatory biomarkers and FGF-21 were performed. The effects of therapy were verified by two-way ANOVA and post hoc analyses were performed (α ≤5%). Results: A reduction in body mass, visceral fat, and an increase in adiponectin in both groups was found. Only the non-IR group demonstrated improved BMI, body fat mass, lean body mass, and waist circumference. Indeed, in the non-IR group, FGF-21 presence was positively correlated with high-density lipoprotein cholesterol and lean body mass and inversely correlated with plasminogen activator inhibitor-1 and triglycerides. In the IR group, there was a reduction in FGF-21 concentration, adiponectin/leptin ratio, insulin, total cholesterol, low-density lipoprotein cholesterol, and plasminogen activator inhibitor-1. FGF-21 was negatively correlated with delta-triglycerides, waist circumference, and low-density lipoprotein cholesterol. The IR prevalence reduced from 47% to 23.5% in the studied population. Conclusions: Although the multicomponent clinical approach improves, in both analysed groups and in both metabolic and inflammatory states, the presence of IR resulted in a reduction in both FGF-21 concentration and adiponectin/leptin ratio. Additionally, in the IR group, FGF-21 was negatively correlated with proinflammatory markers, and in the non-IR group it was positively associated with high-density lipoprotein, suggesting its role in the control of inflammation counteracting IR. In this way, we suggest that IR can impair the anti-inflammatory effects of FGF-21. It will be helpful if these results can be confirmed in a large cohort, underlying physiological mechanisms to explore how these results can help in setting up more prospective studies.