Steatosis extends beyond the liver to the pancreas, heart, and skeletal muscle, yet prevailing definitions remain narrowly organ-focused. This narrative review introduces the Metabolic Steatotic Axis (MSA) as a framework that captures the dynamic, bidirectional interactions among these organs, driving systemic metabolic dysfunction. We synthesize evidence linking lipotoxicity, inflammatory signaling, and endocrine cross-talk into a self-amplifying network accelerating insulin resistance, β-cell failure, and cardiometabolic risk. The MSA concept provides a rationale for axis-based staging systems and composite biomarker panels to quantify cumulative disease burden better and refine risk stratification. We highlight phenotypic heterogeneity within MSA stages, the possible hierarchy of organ vulnerability, and the implications for prognosis and therapy. Viewing pharmacological and lifestyle interventions through the MSA lens reframes them as systemic modulators rather than organ-specific treatments, underscoring the need for multi-organ endpoints in clinical trials. Finally, we outline priorities for longitudinal imaging, multi-omics integration, and global harmonization to translate the MSA from a conceptual construct to a clinically actionable paradigm. By unifying fragmented observations into a systemic model, the MSA has the potential to reshape disease classification, therapeutic strategies, and precision medicine in metabolic disorders.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of cartilage, as well as by extra-articular manifestations. Rheumatoid nephropathy is a common complication of RA and its principal target is the renal corpuscle. Vitamin D and its analogs exert immunomodulatory actions throughout the body due to the widespread of their receptors. Our study aimed to compare the effects of cholecalciferol (vitamin D3) and alfacalcidol on renal corpuscle changes in pristane-induced RA model following a 28-day treatment, using geometric morphometrics. Forty female Wistar rats (190–210 g; 12–13 weeks old) were randomly assigned to four groups: the control (Cont) group (n = 10) received saline i.c., the PIA group (n = 10) was administered pristane i.c., PIA-ALF group (n = 10) was administered pristane i.c. and alfacalcidol orally, and the PIA-CH group (n = 10) was injected i.c. with pristane and received cholecalciferol orally. Pristane administration was used for RA induction. At the end of the experiment, the left kidneys were removed and processed by standard histological procedures for geometric morphometric analysis. Geometric morphometric analysis demonstrated that, compared with the control group, the architecture of the renal corpuscles was altered in the PIA (p < 0.0001) and PIA-CH (p = 0.0065) groups. In contrast, no statistically significant differences were observed in the PIA-ALF group (p = 0.3011). Geometric morphometric analysis demonstrated that alfacalcidol, but not cholecalciferol, exertedaprotective effect on the renal corpuscle architecture in pristane-induced rheumatoid arthritis in rats.

Abstract.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes, obesity and cardiorenal disease. Beyond their established glycaemic and weight-lowering effects, both drug classes consistently lower blood pressure (BP), a benefit that remains relatively underrecognized. This review provides an integrated synthesis of trial evidence, real-world data and meta-analyses examining the antihypertensive effects of SGLT2is and GLP-1 RAs. Across cardiovascular, heart failure, renal and obesity trials, modest but clinically meaningful BP reductions have been observed in diverse populations, including individuals without diabetes. These effects appear largely independent of glycaemic control and offer additive value in high-risk patients with overlapping comorbidities. The totality of evidence supports the strategic incorporation of these agents into future antihypertensive frameworks, warranting further investigation in dedicated blood pressure-focused trials.

Introduction: Polycystic ovary syndrome (PCOS) represents a state of androgen-driven metabolic dysregulation where visceral adiposity and inflammation critically define cardiometabolic risk. Visceral adiposity is not a bystander in PCOS; it is an active endocrine organ driving insulin resistance, low-grade inflammation, and androgen persistence. Interventions that reverse adipocyte hypertrophy and inflammatory signaling may therefore alter the metabolic trajectory of PCOS. Beyond its chronobiotic role, melatonin exerts profound metabolic actions via MT1/MT2 receptors in adipose tissue, modulating oxidative stress and inflammatory gene expression. Yet its direct impact on androgen-induced visceral adiposity remains unclear. Aim: The present study aimed to evaluate the effects of melatonin, metformin, and their combination on visceral fat accumulation in a testosterone-induced PCOS rat model. Material and methods: Thirty prepubertal female Wistar rats were randomized into five groups (n=6): control, PCOS (testosterone 20 mg/kg/day), PCOS+metformin (500 mg/kg/day), PCOS+melatonin (2 mg/kg/day), and PCOS+melatonin+metformin. Treatments lasted 36 days. Estrous cyclicity was monitored by daily vaginal cytology, and somatometric parameters were recorded weekly. On day 36, serum, ovaries, and visceral fat were collected for biochemical and histological analysis. Results: Vaginal smear changes and ovarian pathological alteration due to prolonged testosterone exposure confirmed the successful induction of the PCOS model. Measures of central adiposity, including abdominal circumference and the TC/AC ratio, were significantly higher in the PCOS model than in controls (p < 0.001). Abdominal circumference (AC) increase was greatest in the PCOS model (p < 0.001), while all treatment groups showed significant reductions, most notably in the melatonin + metformin group, followed by melatonin monotherapy and then metformin (all p < 0.001 vs. PCOS). Melatonin was more effective than metformin (p=0.029). AC/TC reduction was greatest in the combined treatment group (p < 0.05). Total weight gain among groups did not reach statistical significance. While total visceral fat weight did not differ among groups, histology revealed a marked reduction in adipocyte number in treated animals, most pronounced in the melatonin group (p < 0.033). Conclusion: Our findings identify melatonin as a metabolic modulator of androgen-driven adiposity, supporting its potential as an adjunctive therapy targeting visceral fat and inflammation in PCOS

Small intestinal bacterial overgrowth (SIBO) is a major yet underrecognized driver of gastrointestinal morbidity in systemic sclerosis (SSc). Disordered motility, fibrosis, and dysbiosis promote microbial stasis, malabsorption, and malnutrition, contributing substantially to impaired quality of life and survival. Diagnostic accuracy remains limited: jejunal aspirate culture is invasive, whereas breath testing offers only moderate sensitivity and specificity. Empirical antibiotic therapy yields transient symptom relief, but recurrence is common, and evidence guiding optimal eradication strategies is sparse. Adjunctive measures, including probiotics, prokinetics, and dietary interventions, remain variably applied, with heterogeneous outcomes across studies. Novel microbiome-targeted, neuromodulatory, and antifibrotic therapies are emerging as promising mechanism-based options. Bearing this in mind, this narrative review aims to consolidate current knowledge on SIBO eradication in SSc. We first outline the pathophysiological rationale and clinical relevance of bacterial overgrowth. We then synthesize available evidence for treatment strategies, appraise barriers to durable remission, and discuss implications for multidisciplinary management. Finally, we highlight emerging approaches, including microbiome-directed therapies, novel prokinetics, and antifibrotic interventions, and define priorities for future clinical research.

Spinal muscular atrophy (SMA) has transitioned from a uniformly fatal disease to a treatable condition, yet incomplete neuromuscular recovery underscores the limits of current SMN-restorative therapies. Emerging data implicate disrupted axon-to-muscle exosomal signaling as an important, overlooked driver of residual dysfunction. Exosomes, nanovesicles mediating bidirectional neuronal-muscular communication, carry synaptic organizers, trophic factors, and microRNAs essential for neuromuscular junction integrity. SMN deficiency alters exosomal biogenesis and cargo, leading to loss of agrin-MuSK signaling, impaired β-actin transport, and muscle atrophy. Comparative insights from amyotrophic lateral sclerosis and muscular dystrophy reveal that stem-cell-derived or engineered exosomes restore synaptic stability, enhance regeneration, and cross biological barriers safely. Thus, we speculate herein on a translational model integrating exosome-based therapies with existing genetic interventions to achieve durable, systems-level recovery in SMA. Exosomal profiling may further yield minimally invasive biomarkers for disease monitoring and treatment optimization, establishing vesicle-mediated communication as a novel therapeutic axis in neuromuscular medicine.

This article introduces a mechanistic framework to reclassify suboptimal responses to GLP-1 receptor agonists. It defines three mechanistic subtypes of incretin resistance—receptor-level, post-receptor, and secretory—highlighting their distinct pathways and therapeutic implications. This model promotes personalized care by moving beyond the oversimplified ‘non-responder’ classification.

Pain remains one of the most burdensome symptoms in rheumatoid arthritis (RA), often persisting despite inflammatory remission and profoundly impairing quality of life. This review aimed to evaluate the clinical efficacy and mechanistic pathways by which Janus kinase (JAK) inhibitors alleviate RA-related pain. Evidence from randomized clinical trials demonstrates that JAK inhibitors have demonstrated rapid and significant pain relief, often exceeding that of methotrexate or biologic DMARDs. Improvements in patient-reported pain scores seem to typically emerge within 1–2 weeks and are sustained over time. Beyond anti-inflammatory effects, JAK inhibitors modulate central sensitization and nociceptive signaling by attenuating IL-6 and GM-CSF activity, reducing astrocyte and microglial activation, and downregulating nociceptor excitability in dorsal root ganglia and spinal pathways. Preclinical models further suggest that JAK inhibition interrupts neuroimmune feedback loops critical to chronic pain maintenance. Comparative and network meta-analyses consistently position JAK inhibitors among the most effective agents for pain control in RA. However, individual variability in response, partly due to differential JAK-STAT activation and cytokine receptor uncoupling, underscores the need for biomarker-guided treatment approaches. JAK inhibitors represent a mechanistically distinct and clinically impactful class of therapies that target both inflammatory and non-inflammatory pain in RA. Their integration into personalized pain management strategies offers a promising path to address one of RA’s most persistent unmet needs.