The heart’s relentless contractile activity depends critically on mitochondrial function to meet its extraordinary bioenergetic demands. Mitochondria, through oxidative phosphorylation, not only supply ATP but also regulate metabolism, calcium homeostasis, and apoptotic signaling, ensuring cardiomyocyte viability and cardiac function. Mitochondrial dysfunction is a hallmark of cardiomyopathies and heart failure, characterized by impaired oxidative phosphorylation, excessive production of reactive oxygen species (ROS), dysregulated calcium handling, and disturbances in mitochondrial dynamics and mitophagy. These defects culminate in energetic insufficiency, cellular injury, and cardiomyocyte death, driving heart disease progression. Diverse cardiomyopathy phenotypes exhibit distinct mitochondrial pathologies, from acute ischemia-induced mitochondrial collapse to chronic remodeling seen in dilated, hypertrophic, restrictive, and primary mitochondrial cardiomyopathies. Mitochondria also orchestrate cell death and inflammatory pathways that worsen cardiac dysfunction. Therapeutic strategies targeting mitochondrial dysfunction, including antioxidants, modulators of mitochondrial biogenesis, metabolic therapies, and innovative approaches such as mitochondrial transplantation, show promise but face challenges in clinical translation. Advances in biomarker discovery and personalized medicine approaches hold promise for optimizing mitochondrial-targeted therapies. Unlike previous reviews that examined these pathways or interventions individually, this work summarizes insights into mechanisms with emerging therapeutic strategies, such as SGLT2 inhibition in HFpEF, NAD+ repletion, mitochondrial transplantation, and biomarker-driven precision medicine, into a unified synthesis. This framework underscores the novel contribution of linking basic mitochondrial biology to translational and clinical opportunities in cardiomyopathy and heart failure. This review synthesizes the current understanding of mitochondrial biology in cardiac health and disease, delineates the molecular mechanisms underpinning mitochondrial dysfunction in cardiomyopathy and heart failure, and explores emerging therapeutic avenues aimed at restoring mitochondrial integrity and improving clinical outcomes in cardiac patients.

Simple Summary Advanced gastric cancer is generally associated with a poor prognosis. Stroma AReactive Invasive Front Area (SARIFA) is a recently recognized aggressive histological feature, defined as five tumor cells in direct contact with adipocytes within perigastric, submucosal, or perivascular adipose tissue. The aim of our retrospective study was to evaluate the correlation of SARIFA with pathohistological variables and its impact on overall survival. A cohort of 102 Croatian patients with locally advanced gastric cancer was analyzed, and a significant association between SARIFA and nodal metastases as well as perineural invasion was observed. Patients with both lymphovascular invasion and SARIFA had a significantly higher proportion of affected lymph nodes. They also exhibited a shorter, though not statistically significant, overall survival compared with patients with one or neither of these factors (median 9.2 vs. 16.1 months). A positive SARIFA status may serve as a biomarker of invasiveness and an additional prognostic risk factor. Abstract Background/Objectives: Advanced gastric cancer usually has an unfavorable prognosis. Stroma AReactive Invasion Front Area (SARIFA) is a newly recognized biomarker of aggressiveness, easily recognized as five tumor cells in direct contact with adipocytes in perigastric, submucosal, and perivascular adipose tissue. We investigated this phenomenon and correlated it with other pathohistological variables. Material and Methods: The sample includes 102 Croatian patients with locally advanced gastric cancer, who underwent total gastrectomy/lymphadenectomy between 2012–2018 and in 2023 at University Hospital Split, Croatia, and had pathological stage pT3 or pT4. Representative histological specimens were analyzed for SARIFA, and results were compared with other variables and overall survival. External validation and gene expression analysis of CD36 and FABP4 were performed using the TCGA-STAD cohort. Results: SARIFA was significantly associated with positive pN status (p = 0.009) and perineural invasion (p = 0.043). Patients with SARIFA had a more than fivefold increased risk of nodal involvement (OR = 6.35; 95% CI: 1.35–29.84; p = 0.019). Lymphovascular invasion (LVI) was associated with nodal disease (OR = 4.39; 95% CI: 1.194–16.143; p = 0.026), and SARIFA was marginally associated (OR = 4.886; 95% CI: 0.985–24.241; p = 0.052). Patients who had both LVI and SARIFA had a higher proportion of affected lymph nodes (p = 0.009). SARIFA status did not significantly affect overall survival. Gene expression analysis showed a significant increase in CD36 expression, while FABP4 expression was elevated but not statistically significant, in SARIFA-positive cases. Conclusions: SARIFA could be used as a marker for invasiveness and further investigated due to its predictive potential.

Background/Objectives: Hip osteoarthritis (HOA) is a progressive joint disease characterized by cartilage loss, subchondral bone changes, and synovial inflammation. While tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and transforming growth factor-beta 1 (TGF-β1) are recognized as key mediators of joint pathology, their compartment-specific expression in the human hip synovium remains insufficiently characterized. Therefore, we aimed to investigate their localization and expression in the intimal and subintimal compartments of synovial tissue in patients with HOA compared to controls (CTRL). Methods: Synovial membrane samples were obtained from 19 patients with primary HOA undergoing total hip arthroplasty and 10 CTRL subjects undergoing arthroplasty for acute femoral neck fracture without HOA. Specimens were processed for hematoxylin and eosin (H&E) and immunofluorescence staining. Expression of TNFR1, IL-6, and TGF-β1 was quantified in the intima and subintima using ImageJ analysis. Group differences were assessed using two-way Analysis of variance (ANOVA) with Tukey’s test when assumptions were met; for heteroscedastic outcomes we applied Brown–Forsythe ANOVA with Dunnett’s T3 multiple comparisons. Results: Histological analysis confirmed synovitis in HOA samples, with intimal hyperplasia and mononuclear infiltration. IL-6 was significantly upregulated in the intima of HOA synovium compared with CTRLs, while subintimal expression remained unchanged. In contrast, TGF-β1 expression was reduced in the HOA intima, eliminating the normal intima–subintima gradient. For TNFR1, the within-HOA contrast (int > sub) was significant, whereas the intimal HOA vs. CTRL comparison showed a non-significant trend. Transcriptomic analysis supported IL-6 upregulation, while TNFR1 and TGF-β1 did not reach statistical significance at the mRNA level in an orthogonal, non-hip (knee-predominant) dataset. Conclusions: These findings demonstrate compartment-specific cytokine dysregulation in HOA, with increased intimal TNFR1 and IL-6 alongside reduced intimal TGF-β1. The synovial lining emerges as a dominant site of inflammatory signaling, underscoring its importance in disease progression.

The kidney’s intricate physiology relies on finely tuned gene regulatory networks that coordinate cellular responses to metabolic, inflammatory, and fibrotic stress. Beyond protein-coding transcripts, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators of renal biology. By modulating transcriptional, post-transcriptional, and epigenetic pathways, ncRNAs govern podocyte integrity, tubular adaptation, intercellular signaling, and immune activation. Dysregulation of these networks is now recognized as a hallmark of major kidney diseases, ranging from diabetic nephropathy and acute kidney injury to chronic kidney disease, glomerulopathies, and polycystic kidney disease. Mechanistic studies have revealed how pathogenic ncRNAs drive apoptosis, inflammation, fibrosis, and cystic remodeling, while protective ncRNAs mitigate these processes, highlighting their dual roles as both disease mediators and therapeutic targets. The exceptional stability of ncRNAs in urine, plasma, and exosomes further positions them as minimally invasive biomarkers with diagnostic and prognostic value. Translational advances include anti-miR and mimic-based therapies (e.g., lademirsen targeting miR-21, miR-29 mimics, anti-miR-17 oligonucleotides), alongside lncRNA silencing strategies, although challenges in delivery, safety, and redundancy remain significant. This review integrates molecular mechanisms with translational perspectives, providing a comprehensive synthesis of how ncRNAs shape renal pathophysiology. By bridging mechanistic insights with emerging diagnostic and therapeutic applications, we highlight the potential of ncRNAs to transform nephrology, paving the way for biomarker-driven precision medicine and novel interventions aimed at intercepting kidney injury at its regulatory roots. In clinical terms, ncRNA-based biomarkers and therapeutics promise earlier detection, more precise risk stratification, and individualized treatment selection within precision nephrology.

Background/Objectives: Postural orthostatic tachycardia syndrome (POTS) is a form of dysautonomia characterized by excessive tachycardia during orthostatic stress. It is frequently observed in patients with syncope, Chronic Fatigue Syndrome (CFS), and post-COVID-19 syndrome (PCS), yet the underlying mechanisms may differ across these conditions. This study aimed to assess autonomic nervous system (ANS) function in patients with syncope, CFS of insidious onset, and CFS post-COVID-19 who presented with POTS, and to compare them with age- and sex-matched patients without POTS. Methods: In this retrospective cross-sectional study, 138 patients over 18 years of age were included following head-up tilt testing (HUTT). Patients were divided into six groups: syncope with and without POTS, CFS with insidious onset with and without POTS, and CFS post-COVID-19 with and without POTS. All participants underwent HUTT, cardiovascular reflex testing (CART) by Ewing, five-minute resting ECG with short-term Heart Rate Variability (HRV) analysis, and 24 h Holter ECG monitoring. Results: The prevalence of POTS across groups ranged from 5% to 7%. Female predominance was consistent across all subgroups. In syncope with POTS, hypertensive responses during HUTT, lower rates of normal Valsalva maneuver results, and reduced HF values in short-term HRV suggested baroreceptor dysfunction with sympathetic overdrive. In both CFS subgroups with POTS, CART revealed higher rates of definite parasympathetic dysfunction, along with more frequent extreme blood pressure variation during HUTT and reduced vagally mediated HRV parameters (rMSSD, pNN50). Across groups, no significant differences were observed with regard to long-term HRV across groups. Conclusions: Distinct autonomic profiles were identified in POTS patients depending on the underlying condition. Syncope-related POTS was associated with baroreceptor dysfunction and sympathetic predominance, whereas CFS-related POTS was characterized by parasympathetic impairment and impaired short-term baroreflex regulation. Evaluating dysautonomia patterns across disease contexts may inform tailored therapeutic strategies and improve management of patients with POTS.

Background and Clinical Significance: Concomitant severe aortic stenosis (AS) and abdominal aortic aneurysm (AAA) in elderly patients presents a significant therapeutic challenge. While transcatheter aortic valve replacement (TAVR) and endovascular aneurysm repair (EVAR) have become established minimally invasive treatments for high-risk patients, simultaneous management of both conditions remains rare. Case Presentation: We report the first documented case in Serbia of a simultaneous TAVR and EVAR in a 75-year-old male with severe symptomatic AS and AAA. The patient had a history of hypertension, diabetes mellitus, atrial fibrillation, prior radiofrequency pulmonary vein ablation, and pacemaker implantation. Echocardiography demonstrated severe AS with a transvalvular gradient of 116/61 mmHg, an aortic valve area of 0.6 cm2, and a left ventricular ejection fraction of 30–35%. Coronary angiography revealed 50–60% stenosis of the right coronary artery. Following evaluation by a multidisciplinary Heart and Vascular Team, a combined procedure was performed under general anesthesia via bilateral femoral access. TAVR with a Medtronic Evolut R valve was successfully deployed, followed by EVAR with satisfactory stent graft positioning and angiographic results. The patient’s postoperative course was uneventful, and he was discharged on the ninth day. At six-month follow-up, echocardiography showed optimal valve function, and CT identified a type II endoleak, which was managed conservatively. Conclusions: This case demonstrates the feasibility and safety of simultaneous TAVR and EVAR in a high-risk elderly patient, emphasizing the importance of careful preoperative planning and a coordinated multidisciplinary approach. Further studies are warranted to establish standardized guidelines for the management of patients with coexisting severe AS and AAA.

Background The aim of this study was to examine the prevalence of malnutrition and its association with the frequency of falls and respiratory infections among older adults residing in Croatian nursing homes. Materials and methods The study included 148 participants, 112 (75.7%) women and 36 (24.3%) men, aged 65 years and older, living in the nursing homes in Rijeka and Opatija. The Mini Nutritional Assessment-Short Form (MNA-SF) and data from the medical records were used for data collection. Results The study showed that seven (4.7%) of the older adults living in nursing homes were malnourished, while 53 (35.8%) were at risk of malnutrition. It was found that participants with malnutrition and nutritional risk were more likely to develop respiratory infections (r=-0.37). No correlation was found between malnutrition and the frequency of falls in older adults (r=0.01). Conclusion Malnutrition and the risk of malnutrition are common problems in older adults in nursing homes, requiring regular monitoring and timely intervention. The results confirmed the association between malnutrition and respiratory tract infections, while also highlighting the possibility of co-occurrence of obesity and malnutrition, which is often overlooked.

Simple Summary African swine fever is a deadly viral disease of pigs and wild boar that causes major losses for farmers and threatens food security. The disease does not affect people, but its rapid spread and high fatality in pigs make it one of the most serious challenges for animal health in Europe. Since 2019, the disease has been present in Serbia, and in 2023, it was first reported in Bosnia and Herzegovina. In this study, we examined virus samples collected from pigs and wild boar during outbreaks between 2023 and 2025 to better understand how the virus is spreading in the region. By looking at several important parts of the virus genome, we found that all the samples belonged to the same group, known as cluster 19. This shows that the same type of virus has been circulating for several years without major changes. The results suggest that the disease is being maintained locally, mainly through contact between wild boar and pigs kept on small farms with little or no protection. The discovery of the same virus type in Bosnia and Herzegovina highlights that the disease crosses borders, making regional cooperation and continued monitoring essential for controlling its spread.

Synthetic herbicides have adverse effects on the environment and human health. Understanding allelopathic intera c tions can provide alternatives for weed control without using these synthetic chemicals. This study investigated the impact of three concentrations (10, 20, and 30 μg/m L ) of Salvia sclarea essential oil (EO) on the Matricaria chamomilla , Leuca n themum vulgare , and Trifolium repens germination process, as well as its toxicological and antimicrobi al profile. Our results showed that S. sclarea EO, particularly at higher concentrations, affected the germination and growth parameters of the tested species, with T. repens being the most sensitive. A statistically significant increase in the value of the mitotic index was observed for all three tested concentrations of S. sclarea EO compared to the control group. A significant i n crease in the number of acentric fragments at between 10 and 30 µg/m L of S. sclarea EO compared to the control group, as well as an increase in the frequency of aneuploidy at between 10 µg/m L of S. sclarea EO compared to the control was detected. Minimum inhibitory concentration of EO was 500 μ L /m L for all tested bacteria. Impact on the bacterial biofilm formation was species-specific and concentration dependent. Our findings suggest that S. sclarea EO possesses certain allelopathic, proliferative, genotoxic, and antibacterial potential.