Ischemic stroke (IS) is a leading cause of mortality worldwide, responsible for approximately 55% of all neurological disabilities. Proper brain function requires continuous energy supply, primarily generated by mitochondria. Cerebral ischemia impairs the functioning of mitochondrial electron transport chain, reducing adenosine triphosphate production and increasing reactive oxygen species. Inflammation also plays a critical role throughout all stroke phases. YKL-40, a pro-inflammatory glycoprotein, serves as a biomarker of macrophage and microglial activation, while YKL-39 regulates autoimmunity, tissue remodeling, and exhibits monocyte chemotactic and pro-angiogenic activity. This study aims to investigate mitochondrial bioenergetics, oxidative stress, and inflammation in IS patients before and after thrombolysis. Bioenergetic parameters were assessed using Mito Stress Test on an Agilent Seahorse analyzer, and YKL-39, YKL-40 and 4-HNE plasma levels via ELISA. Pre-thrombolytic IS patients demonstrated significantly reduced basal respiration and spare respiratory capacity, along with lower plasma YKL-40 levels. In contrast, they exhibited higher plasma YKL-39 concentrations and increased oxidative stress marker 4-hydroxy-2-nonenal compared to post-thrombolytic patients. These findings highlight novel associations between mitochondrial dysfunction, oxidative stress, and inflammation in IS, and suggest that parameters reflecting these processes may serve as potential biomarkers for evaluating disease severity and predicting outcomes.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated by inflammation of the synovial tissue and autoantibody production. Oxidative stress and free radicals are known to be indirectly implicated in joint damage and cartilage destruction in RA. Several studies describe the presence of mitochondrial dysfunction in RA, but few of them follow the dynamics in energy parameters after therapy. The aim of our investigation is to evaluate the direct effect of JAK inhibitors on cellular metabolism (and under induced oxidative stress) in RA patients. Ten newly diagnosed RA patients were included in the study. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated before and 6 months after therapy with JAK inhibitors. A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in PBMCs. Sonographic examination, DAS28 and conventional clinical laboratory parameters were determined also prior and post therapy. A significant decrease in proton leak after therapy with JAK inhibitors was found. The increased production of ATP indicates improvement of cellular bioenergetics status. These findings could be related to the catalytic action of JAK inhibitors on oxidative phosphorylation which corresponds to the amelioration of clinical and ultra-sonographic parameters after treatment. Our study is the first to establish the dynamics of mitochondrial parameters in PBMCs from RA patients before and after in vivo therapy with JAK inhibitors.

Introduction: Adipose tissue is immunologically and hormonally active, and these effects are mediated largely by adipocytokines. Thyroid hormones regulate metabolism and organ function, and Hashimoto’s thyroiditis (HT) is the most common autoimmune disease affecting thyroid function. Aim: To evaluate the levels of the adipocytokines leptin and adiponectin in patients with autoimmune HT, and to perform a comparative intragroup analysis in patients with different stages of gland functional activity, and in a control group. Materials and methods: Ninety-five patients with HT and 21 healthy controls were enrolled in the study. Venous blood was taken without anticoagulants after at least 12 hours of fasting, and serum samples were frozen at −70°C until analysis. Serum levels of leptin and adiponectin were determined by an enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of leptin in HT patients were higher than those in the control group (4.5±5.2 ng/mL vs. 1.9±1.3 ng/mL). The hypothyroid patient’s group showed significantly higher levels of leptin than those of the healthy controls (5.1±5.2 ng/mL vs. 1.9±1.3 ng/mL), (p=0.031). Leptin levels correlated positively with body mass index (r=0.533, p<0.001), triglycerides (r=0.223, p=0.033), and immunoreactive insulin (r=0.488, p<0.001) levels. Serum adiponectin concentrations were higher in euthyroid HT patients than in the other groups, but the difference was not statistically significant (p=0.68). We found a positive correlation between adiponectin and HDL cholesterol levels (r=0.442, p<0.001), and negative with body mass index (r=−0.217, p=0.03), and immunoreactive insulin (r=−0.341, p=0.002). Conclusions: The results of this study suggest that leptin has a stronger effect than adiponectin in Hashimoto’s thyroiditis, which can be used to develop new therapeutic agents that modify its effect in the organism.

Rheumatoid arthritis (RA) is an inflammatory joint disease characterized by persistent synovitis and inflammation. The exact mechanism of mitochondrial function in the presence of inflammation and dysregulation of autophagic processes in the pathogenesis of RA is still unclear. The aim of our study is to determine mitochondrial function, gene and protein levels of biomolecules related to inflammation (YKL-40) and autophagy (LAMPs) and to search a connection between them in the RA context. Twenty newly diagnosed RA patients and ten healthy individuals were included in the study. Disease severity was assessed by ultrasonography. Conventional clinico-laboratory parameters, immunological markers and protein levels of LAMPs and YKL-40 were examined in plasma. Gene expression analysis for the quantitative measurement of LAMPs and YKL-40 were conducted in white blood cells (WBC). A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in peripheral blood mononuclear cells (PBMCs). Increase in spare respiratory capacity in PBMCs of RA patients was detected. Decreased LAMPs plasma protein levels and increased protein levels of YKL-40 in RA patients compared to healthy individuals were measured. No significant differences were found in gene expressions. Correlations between mitochondrial, ultrasonographic and protein levels of the biomarkers related with inflammation and autophagy were established. New data on mitochondrial dysfunction in RA patients and links to inflammation and mitophagy are reported. The relationship between dysregulation of mitophagy and joint diseases deserves to be thoroughly investigated as it would be a promising therapeutic approach.

Mitochondria are increasingly recognized as multifunctional organelles that integrate metabolic, redox, immune, and cell fate signaling, thereby maintaining cellular and tissue homeostasis under physiological conditions. Beyond their classical role in ATP production, mitochondria act as central regulatory hubs coordinating adaptive responses to metabolic demands and environmental stress. These functions are sustained through tightly regulated quality control mechanisms, including mitochondrial biogenesis, dynamic fusion–fission remodeling, redox signaling, and selective removal of damaged organelles via mitophagy. Disruption of these processes compromises cellular resilience and contributes to disease initiation and progression. This review summarizes and critically evaluates current evidence on mitochondrial function in health and its dysregulation in pathological conditions, with a particular focus on rheumatoid arthritis (RA), ischemic stroke (IS), and autism spectrum disorder (ASD). Despite their distinct clinical manifestations, these disorders share convergent mitochondrial abnormalities, including metabolic reprogramming toward glycolysis, excessive or persistent reactive oxygen species production, impaired mitophagy, mitochondrial DNA-driven innate immune activation, and hypoxia-related stress. In RA, mitochondrial dysfunction sustains chronic inflammation and joint destruction; in IS, acute mitochondrial failure and reperfusion-associated oxidative stress drive neuronal injury; and in ASD, mitochondrial metabolic inflexibility and defective quality control contribute to chronic low-grade inflammation and neurodevelopmental vulnerability. A variety of methods for the assessment of mitochondrial function are available to study these pathological conditions. Collectively, these findings position mitochondrial dysfunction as a unifying pathogenic mechanism linking inflammatory, neurodegenerative, and neurodevelopmental processes. Targeting mitochondrial metabolism, redox balance, and quality control pathways therefore represents a promising cross-disease therapeutic strategy.

Rheumatoid arthritis (RA) is an autoimmune disease affecting the synovium. Mitochondrial dysfunction is considered a critical factor in the pathogenesis of RA. The aim of the study was to determine the effect of methotrexate and tofacitinib on mitochondrial function and oxidative stress in an in vitro study on the model synovial cell line SW982. TNF-alpha-stimulated SW982 cells, as well as control untreated cells, were incubated with methotrexate and tofacitinib. A metabolic test was performed to assess mitochondrial function. The oxidative stress generated after the application of the therapeutics was determined by a chromatographic analysis. The results obtained showed an increase in ATP levels (p < 0.0001) and a decrease in proton leak (p < 0.0003) after treatment with tofacitinib. The opposite trend was observed—reduced ATP production (p < 0.0096) and increased levels of proton leak (p < 0.0001)—after treatment with methotrexate. A two-fold increase in 8-ISOPGF2A was measured in comparison to TNF-alpha-stimulated and untreated cells. The dynamics of mitochondrial activity and oxidative stress were monitored in a certified RA model cell line after the administration of two different therapeutics. Methotrexate was found to induce mitochondrial dysfunction and oxidative stress in vitro, while tofacitinib partially improved mitochondrial parameters.