Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, progressive joint destruction, and systemic complications. Although genetic susceptibility and environmental factors contribute to disease development, the precise mechanisms underlying RA pathogenesis remain incompletely understood. Increasing evidence suggests that the gut microbiota plays a critical role in regulating host immune responses and maintaining immune homeostasis. Alterations in the composition and function of gut microbial communities (dysbiosis) have been associated with immune dysregulation and the development of autoimmune diseases, including RA. Recent studies indicate that modulation of the gut microbiome through probiotics, prebiotics, dietary interventions, and microbiota-targeted therapies may alleviate inflammation and improve clinical outcomes in RA patients. This review summarizes the current understanding of RA pathogenesis, highlights the role of gut microbiota in immune regulation, and discusses the therapeutic potential of microbiome-based interventions in the management of RA.

Objectives: Sciatic nerve injury is a neurological disorder that leads to muscle wasting and sensory-motor dysfunction. This study aimed to investigate the effects of combined lithium and resistance training intervention on histological, behavioral and molecular indices in rats modeled with sciatic nerve injury.

Methods: In this study, 25 rats were randomly divided into five groups: sham, model (sciatic nerve injury), model + lithium (10 mg/kg, intraperitoneally for 5 days), model + resistance training (6 weeks) and model + lithium + resistance training. Interventions began 24 hours after injury. At the end of the 6-week period, the soleus muscle tissue was examined for histopathology and muscle fiber diameter. The behavioral response of the animals was assessed by hot plate test and the expression levels of Wnt and β-catenin genes in the cerebrospinal fluid were assessed by Real-time PCR.

Results: The findings showed that the model group had a significant decrease in muscle fiber diameter and a significant increase in reaction time in the hot plate test compared to the sham group. Also, the expression of Wnt and β-catenin genes in the model group increased significantly. In contrast, the treatment groups, especially the combination group (lithium + resistance training), showed a significant improvement in muscle fiber diameter, a decrease in reaction time in the behavioral test and a decrease in the expression of Wnt and β-catenin genes compared to the model group (p<0.05).

Conclusion: The results of this study suggest that combined lithium and resistance training therapy can improve muscle tissue structure and reduce sensory-motor disorders caused by sciatic nerve injury by reducing Wnt/β-catenin pathway activity. This combined approach can be considered as a promising therapeutic strategy for managing complications caused by peripheral nerve injuries.

Objectives: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in patients with type 2 diabetes mellitus (T2DM), involving complex metabolic, inflammatory, and hormonal dysregulation. This study investigated the circulating levels and interrelationships between Irisin, Amylin, SIRT1, vitamin D3 (Vit-D3), vitamin B3 (Vit-B3), and serum amyloid A (SAA) among healthy controls, patients withT2DM, and DN patients.

Methods: In this case-control study, 150 male participants (50 per group; aged 40–65 years) were enrolled and matched for age and BMI. Fasting samples were used to measure routine biochemical parameters, HOMA-IR, HbA1c, and specific markers (Irisin, Amylin, SIRT1, SAA, Vit-B3 via ELISA; Vit-D3 via CLIA).

Results: Both diabetic groups had elevated FBS, HbA1c, insulin, HOMA-IR, and BMI versus controls. DN group exhibited marked renal impairment (higher urea, creatinine, microalbumin; lower eGFR). Vit-D3 and Vit-B3 were significantly lower in patients with T2DM and DN, with a further reduction in Vit-B3 in DN. Serum amyloid A levels were unexpectedly lower in diabetic groups. The order of amylin levels was: control > T2DM > DN, while Irisin and SIRT1 were in the opposite order. The association between Irisin and SIRT1 was weak in DN group. Amylin-SIRT1 was negative in T2DM and positive in DN groups. Vit-B3 correlated positively with SIRT1 only in DN group. Serum amyloid A was negatively correlated with SIRT1 in diabetic groups. This parameter correlated with HbA1c in DN group.

Conclusions: These findings highlight potential compensatory roles of Irisin-SIRT1, niacin-NAD+ dependency, and atypical serum amyloid A regulation, suggesting novel biomarkers and therapeutic avenues (e.g., NAD+ precursors, SIRT1 modulation) for diabetic kidney disease.

Objectives: COVID-19 is a disease associated with biochemical disruptions. This study aimed to evaluate changes in biochemical parameters in COVID-19 patients and to identify clinically applicable biomarkers for disease prognosis and severity assessment.

Methods: This study enrolled 155 hospitalized COVID-19 patients classified as mild (n=35), moderate (n=40), severe (n=35), or critical (n=45), along with 40 healthy controls. Serum levels of blood glucose (BG), blood urea nitrogen (BUN), creatinine (Cr), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T‑Bil), direct bilirubin (D‑Bil), lactate dehydrogenase (LDH), high‑sensitivity C‑reactive protein (hs‑CRP), and electrolytes (Na⁺, K⁺) were measured. Logistic regression was performed to assess disease severity. Receiver operating characteristic (ROC) curve analyses were conducted to identify independent predictors and optimal cut‑off values for prognosis (patients vs. controls) and severity (mild vs. moderate, severe, and critical groups).

Results: All hepatic, renal, and glycemic parameters, as well as LDH and hs‑CRP, were elevated across all patient groups compared to controls (P < 0.001). Adjusted logistic regression identified hs‑CRP (odds ratio (OR) = 25.76), D‑Bil (OR = 4.56), Cr (OR = 3.17), and LDH (OR = 1.26) as the strongest independent predictors of increased infection severity. ROC analysis determined LDH as the best biomarker for disease prognosis (AUC = 97.72%, cut‑off > 317 U/L) and D‑Bil for disease severity (AUC = 72.81%, cut‑off > 0.23 mg/dL).

Conclusion: LDH and D‑Bil represent the most clinically useful biomarkers for COVID‑19 prognosis and severity detection, respectively. These results advocate for their routine integration into standard biochemical surveillance to facilitate early risk assessment; however, broader prospective investigations with larger cohorts are essential to confirm their generalizability.

Objective: Diabetic nephropathy (DN) is a major complication of type 2 diabetes mellitus (T2DM). This study aims to evaluate the association of the uric acid-to-high-density lipoprotein cholesterol ratio (UHR) with biochemical parameters in patients with and without DN.

Methods: In this comparative cross-sectional study, 120 patients with T2DM (60 with DN and 60 without DN) were enrolled. Clinical, biochemical, lipid, renal, inflammatory, and hematological parameters were measured. Correlations between UHR and glycemic indices were analyzed, and receiver operating characteristic (ROC) analysis was performed.

Results: Patients with DN had higher triglyceride and creatinine levels, lower high-density lipoprotein cholesterol (HDL-C) levels, and borderline higher UHR (P=0.05) than those without DN. No significant differences were found for HbA1c, fasting blood glucose, postprandial glucose, mean plasma glucose, triglyceride-glucose index, or serum uric acid. UHR was not significantly correlated with any glycemic index (all P>0.05). ROC analysis showed poor discriminatory performance of UHR for DN (AUC=0.452, P=0.475).

Conclusion: Although UHR was borderline elevated in patients with DN, it was not associated with glycemic indices and showed poor diagnostic performance. These findings suggest that UHR has limited utility as an independent biomarker of diabetic nephropathy in T2DM.

Objectives: Methotrexate (MTX) is an effective chemotherapeutic and immunosuppressive agent; however, its clinical use is limited due to nephrotoxicity associated with oxidative stress. This study aims to evaluate the protective effects of silymarin, citral, and thymoquinone against MTX-induced renal injury in rats.

Methods: Forty-eight adult male Sprague–Dawley rats were randomly assigned into six groups (n=8): healthy control, cosolvent control (DMSO), MTX-only, MTX+citral (30 mg/kg), MTX+silymarin (50 mg/kg), and MTX+thymoquinone (10 mg/kg). Treatments were administered intraperitoneally for 10 consecutive days. Methotrexate (20 mg/kg, i.p.) was administered to all groups except the healthy control. Serum urea and creatinine levels were measured, while renal tissues were evaluated for total antioxidant capacity (TAC), malondialdehyde (MDA), and histopathological alterations.

Results: MTX administration significantly increased serum urea, creatinine, and renal MDA levels while decreasing TAC compared with the healthy control group. Silymarin significantly reduced serum urea and creatinine levels and restored TAC compared with the MTX group (p<0.05). Thymoquinone significantly improved TAC and reduced MDA levels (p<0.05), although its effects on serum renal biomarkers were not statistically significant. Citral significantly decreased MDA levels (p<0.01) but showed limited effects on TAC and renal function markers. Histopathological examination demonstrated vascular and glomerular congestion with hemorrhage in the MTX group, whereas treatment groups exhibited varying degrees of structural preservation, with silymarin showing the greatest improvement.

Conclusions: Oxidative stress plays a major role in MTX-induced nephrotoxicity. Among the tested compounds, silymarin demonstrated the most consistent nephroprotective effects, while thymoquinone and citral provided partial antioxidant and histological protection. These findings support the potential use of natural antioxidants as adjunctive strategies against MTX-induced renal injury.

Objective: Precocious puberty is a significant pediatric endocrine disorder with potential long-term physical and psychosocial consequences, including short stature, obesity, and increased risk of certain malignancies. Vitamin D (vitD) has been proposed to play a role in reproductive maturation. However, the evidence regarding its association with precocious puberty remains inconsistent across populations. This study aimed to investigate the relationship between serum vitD levels and idiopathic central precocious puberty (ICPP) in Iranian girls.

Methods: This case-control study included 81 girls diagnosed with central precocious puberty and 51 healthy girls as controls. Demographic, anthropometric, and laboratory data (including age, weight, height, and serum levels of estradiol, LH, FSH, TSH, T4, and 25-hydroxyvitamin D) were extracted from clinical records. BMI z-scores, weight-for-age z-scores, and weight-for-height z-scores were calculated using standardized tools. Serum vitD levels were compared between groups, and correlations with anthropometric and biochemical parameters were assessed using appropriate statistical tests.

Results: Median serum vitD levels were significantly lower in the case group than in controls (27.05 vs. 41.00 ng/mL; P = 0.0006). BMI z-score and weight-for-age z-score were significantly higher in girls with precocious puberty (P < 0.0001). Cases showed a larger discrepancy between bone age and chronological age (P < 0.0001). Serum vitD showed significant inverse correlations with BMI z-score (r = −0.236, P = 0.035) and weight-for-height z-score (r=−0.605, P=0.028), and a significant positive correlation with T4 (r = 0.317, P = 0.010). No significant correlations were observed between vitD and reproductive hormones, including estradiol, LH, or FSH.

Conclusion: Serum vitD levels are significantly lower in Iranian girls with ICPP compared to healthy controls. These findings suggest that vitD may influence pubertal development; therefore, routine assessment of vitD status in girls presenting with precocious puberty may be clinically warranted, particularly in populations with a high background prevalence of deficiency.