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Diabetic wounds, marked by poor regeneration, chronic inflammation, and oxidative stress, pose a major challenge in diabetes. Esculin, a natural coumarin with antioxidant and anti-inflammatory effects, shows promise for wound healing. This study investigated the histopathological, biochemical, and molecular effects of topical esculin on full-thickness wounds in streptozotocin-induced diabetic rats. Excisional wounds were created on 60 Sprague-Dawley rats, assigned to four groups: normal control, diabetic control, esculin ointment 5% and 10%. Tissue samples were collected on days 7, 14, and 21 for histopathological, molecular, and biochemical analysis. Esculin treatment significantly accelerated wound closure and improved re-epithelialization and granulation tissue formation. Histological analysis revealed a decrease in lymphocyte infiltration, increased fibroblast proliferation and neovascularization at the earlier stages, and a higher number of fibrocytes and more organized collagen deposition at later stages of wound healing. Biochemically, esculin significantly elevated antioxidant enzyme activities and reduced oxidative stress markers, indicating restoration of redox balance. Moreover, esculin downregulated the pro-inflammatory cytokine IL-1β and upregulated bFGF, VEG), and TGF-β1, thereby supporting fibroblast activity, angiogenesis, and extracellular matrix remodeling. Collectively, these findings highlight the multifaceted role of esculin in promoting wound healing under diabetic conditions, supporting its potential as a promising adjunct therapy for managing chronic wounds.

Today, probiotics are considered to be living microorganisms whose consumption has a certain number of beneficial effects on the consumer. The present study aimed to investigate the effect of a new probiotic extract ( Lactobacillus delbrueckii subsp. lactis KUMS Y33) on the differentiation process of human adipose-derived stem cells (hADSCs) into adipocytes and osteocytes and, as a result, clarify its role in the prevention and treatment of bone age disease. Several bacteria were isolated from traditional yogurt. They were evaluated to characterize the probiotic’s activity. Then, the isolated hADSCs were treated with the probiotic extract, and then osteogenesis and adipogenesis were induced. To evaluate the differentiation process, oil red O and alizarin red staining, a triglyceride content assay, an alkaline phosphatase (ALP) activity assay, as well as real-time PCR and western blot analysis of osteocyte- and adipocyte-specific genes, were performed. Ultimately, the new strain was sequenced and registered on NBCI. In the probiotic-treated group, the triglyceride content and the gene expression and protein levels of C/EBP-α and PPAR-γ2 (adipocyte-specific markers) were significantly decreased compared to the control group ( P  <  0.05 ), indicating an inhibited adipogenesis process. Furthermore, the probiotic extract caused a significant increase in the ALP activity, the expression levels of RUNX2 and osteocalcin, and the protein levels of collagen I and FGF-23 (osteocyte-specific markers) in comparison to the control group ( P  <  0.05 ), indicating an enhanced osteogenesis process. According to the results of the present study, the probiotic extract inhibits adipogenesis and significantly increases osteogenesis, suggesting a positive role in the prevention and treatment of osteoporosis and opening a new aspect for future in-vivo study.

Background Multiple sclerosis (MS) is a chronic neuroinflammatory disorder marked by demyelination and axonal damage, where oxidative stress and cytokine-mediated inflammation are key pathological factors. Spirulina, a microalga rich in phycocyanin, phenolic compounds, and omega-3 fatty acids, exhibits potent antioxidant and anti-inflammatory properties, potentially targeting these pathways. This study investigated spirulina’s impact on inflammatory biomarkers and quality of life in relapsing-remitting MS (RRMS) patients. Methods A triple-blind, placebo-controlled trial randomized 80 RRMS patients (EDSS 0–6) to receive 1 g/day spirulina ( n  = 40) or placebo ( n  = 40) for 12 weeks. Sixteen participants (20%) withdrew. Primary analysis followed the intention-to-treat (ITT) principle ( N  = 80) using baseline-observation-carried-forward for missing data. Serum IL-1β and IL-6 (primary outcomes) were measured by ELISA. Quality of life (MSQoL-54) and anthropometric measures were secondary outcomes. Results A linear mixed-effects model revealed that spirulina supplementation significantly reduced serum IL-1β (Estimate = − 1.07 ± 0.14, p  < 0.001) and IL-6 levels (Estimate = − 2.66 ± 0.26, p  < 0.001) compared to placebo. Significant improvements were also observed in health perception (Estimate = − 0.49 ± 0.12, p  < 0.001), physical function (–0.37 ± 0.11, p  < 0.001), role limitation–physical (–0.36 ± 0.16, p  = 0.030), energy (–0.64 ± 0.15, p  < 0.001), and sexual function (–1.31 ± 0.29, p  < 0.001). No significant effects were found for emotional wellbeing, health distress, social function, cognitive function, sexual satisfaction, overall quality of life, or total mental health. Anthropometric analysis showed a significant weight reduction in the spirulina group versus placebo (–2.85 ± 1.13 kg, p  = 0.015), while BMI reduction was borderline significant (–0.78 ± 0.41, p  = 0.060). No significant changes were observed in waist circumference, waist-to-hip ratio, energy intake, or physical activity. Conclusion Spirulina supplementation significantly reduced pro-inflammatory markers and improved multiple physical and cognitive quality of life domains in patients with RRMS. Spirulina shows promise as a safe adjunct therapy in MS management, but larger trials with longer follow-up are warranted to confirm these findings and explore its clinical utility alongside DMTs. Trial registration The trial is registered with the Iranian Registry of Clinical Trials (ID IRCT2024124060794N1), with registration completed on 4 February 2024. Informed consent will be secured from each participant or their legal guardian.

This study aimed to assess the efficacy of ezetimibe in combination with metformin versus metformin alone in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus. Patients were randomly divided into two groups: one receiving ezetimibe and metformin (Met + EZY) and the other receiving metformin alone (Met group) for six months. Parameters were measured at baseline (T1), after three months (T2), and after six months (T3). The findings indicated that insulin levels and HOMA-IR exhibited a significant decrease from T1 to T2 in the Met + EZY group ( p  < 0.05). Malondialdehyde (MDA) and triglycerides levels also demonstrated significant decreases from T1 to T2 in the Met + EZY group ( p  < 0.05). The expression of peroxisome proliferator-activated receptor gamma ( PPAR-γ ) and adiponectin ( ADIPO ) showed a significant increase from T1 to T2 in the Met + EZY group ( p  < 0.01). Additionally, ADIPO expression showed a significant increase from T1 to T3 ( p  < 0.001) in both groups. When comparing the two treatment groups, PPAR-γ and ADIPO expression were significantly higher in the Met + EZY group during T2 and T3 compared to the Met group ( p  < 0.001). Combination therapy appears to be more effective than metformin treatment alone and should be used cautiously.

Methotrexate (MTX), as a folic acid antagonist, is an effective drug in treating a wide range of malignancies and autoimmune diseases. However, the clinical use of MTX has been limited due to its side effects, the most common of which is hepatotoxicity. In this study, rats were randomly divided into six groups: three treatment groups received methotrexate and different doses of astaxanthin (AX) for 14 days. At the end of the study, blood samples were collected to determine serum levels of ALT, AST, ALP, and LDH. Also, liver tissues were isolated to evaluate antioxidant enzymes and markers of oxidative stress, histopathological damage, and expression of NF-E2-related transcription factor (Nrf2) and Heme oxygenase-1 (HO-1) genes. The results showed that administration of MTX significantly increased the levels of ALT, AST, ALP, and LDH in the blood, markers of oxidative stress, and histopathological damage in liver tissue and significantly reduced the levels of antioxidant enzymes and the expression of Nrf2 and HO-1 genes. On the other hand, treatment with AX decreased blood levels of ALT, AST, ALP, and LDH and oxidative stress markers and remarkably raises the activity of antioxidant enzymes and expression of Nrf2 and HO-1 genes in liver tissue. In addition, histopathological lesions were improved with AX administration. The findings of this study indicated that AX may be useful for the prevention of MTX-induced hepatotoxicity by improving oxidative and inflammatory changes.

Multiple sclerosis (MS) is a chronic neuroinflammatory disorder marked by demyelination and axonal damage, where oxidative stress and cytokine-mediated inflammation are key pathological factors. Spirulina, a microalga rich in phycocyanin, phenolic compounds, and omega-3 fatty acids, exhibits potent antioxidant and anti-inflammatory properties, potentially targeting these pathways. This study investigated spirulina's impact on inflammatory biomarkers and quality of life in relapsing-remitting MS (RRMS) patients. A triple-blind, placebo-controlled trial randomized 80 RRMS patients (EDSS 0-6) to receive 1 g/day spirulina (n = 40) or placebo (n = 40) for 12 weeks. Sixteen participants (20%) withdrew. Primary analysis followed the intention-to-treat (ITT) principle (N = 80) using baseline-observation-carried-forward for missing data. Serum IL-1[beta] and IL-6 (primary outcomes) were measured by ELISA. Quality of life (MSQoL-54) and anthropometric measures were secondary outcomes. A linear mixed-effects model revealed that spirulina supplementation significantly reduced serum IL-1[beta] (Estimate = - 1.07 ± 0.14, p < 0.001) and IL-6 levels (Estimate = - 2.66 ± 0.26, p < 0.001) compared to placebo. Significant improvements were also observed in health perception (Estimate = - 0.49 ± 0.12, p < 0.001), physical function (-0.37 ± 0.11, p < 0.001), role limitation-physical (-0.36 ± 0.16, p = 0.030), energy (-0.64 ± 0.15, p < 0.001), and sexual function (-1.31 ± 0.29, p < 0.001). No significant effects were found for emotional wellbeing, health distress, social function, cognitive function, sexual satisfaction, overall quality of life, or total mental health. Anthropometric analysis showed a significant weight reduction in the spirulina group versus placebo (-2.85 ± 1.13 kg, p = 0.015), while BMI reduction was borderline significant (-0.78 ± 0.41, p = 0.060). No significant changes were observed in waist circumference, waist-to-hip ratio, energy intake, or physical activity. Spirulina supplementation significantly reduced pro-inflammatory markers and improved multiple physical and cognitive quality of life domains in patients with RRMS. Spirulina shows promise as a safe adjunct therapy in MS management, but larger trials with longer follow-up are warranted to confirm these findings and explore its clinical utility alongside DMTs.

Differentiation process of mesenchymal stem cells (MSCs) into adipocyte is involved in obesity. Multiple factors such as Ca2+ play important roles in different stages of this process. Because of the complicated roles of Ca2+ in adipogenesis, the aim of present investigation was to study the influx and efflux of Ca2+ into and out of the cells during adipogenesis. Adipose-derived MSCs were used to differentiate into adipocytes. MSCs were exposed to 2.5 mM Ca2+ or 1.8 mM Ca2+ plus calcium ionophore, A23187, for 3 days. Lipid staining, triglycerides (TG) content, and glyceraldehyde phosphate dehydrogenase (GAPDH) activity were evaluated to confirm the efficiency of the differentiation. Gene expression of GLUT4, PPARγ2, RAR-α, and calreticulin, as well as the protein levels of GLUT4 and PPARγ2 were determined. Ca2+ and in particular Ca2+ plus A23187 significantly lowered the efficiency of differentiation accompanied by decrease in intracellular TG deposits, GAPDH activity and alleviation of gene, and protein levels of GLUT4 and PPARγ2. While calreticulin and RAR-α were remarkably upregulated in A23187 group. This study showed the inhibitory effects of calcium in adipogenesis. Additionally, it indicated the greater inhibitory effect of calreticulin and RAR-α in controlling adipogenesis by higher levels of calcium.

Adipose tissue is one of the most important endocrine organs that liberates many metabolic mediators such as hormones, cytokines, and chemokines. Different types of fatty acids have key roles in adipogenesis. The aim of this study was to evaluate the effects of two essential fatty acids, including Arachidonic acid (AA) and Eicosapentaenoic acid (EPA), on the process of adipogenicity in human Adipose-Derived Stem Cells (hADSCs). After immunophenotyping of hADSCs by flowcytometry, they were differentiated into adipocytes and simultaneously exposed to 30 μM and 60 μM of AA and 25 μM and 50 μM of EPA. Further, along with the MTS assay, the activity of glycalaldehyde-3-phosphate dehydrogenase (GAPDH) was also measured. In addition, expression of lipid markers including peroxisome proliferator-activated receptor γ2 (PPARγ2) and glucose transporter 4 (GLUT4) was evaluated, and the neutral lipid contents were determined using Oil red O staining. MTS evaluation showed a significant decrease in proliferation in all treatment groups compared to the control group. Based on oil red O staining, fat droplets in the AA treatment groups were higher than in controls. The expression of PPARγ2 and GLUT4 genes and proteins increased in almost all AA and EPA groups compared to control. In addition, GAPDH activity was higher in AA groups than in the control group. In general, while different concentrations of EPA did not increase the adipogenic process compared to the control group, stimulation of differentiation to adipocytes was largely determined by the AA. The result indicates a positive effect of omega-6 versus omega-3 in stimulating the pathways of adipogenesis.