microRNA-27a is a promising candidate for miRNA mimic therapy to combat obesity, but its clinical application is hindered by enzymatic degradation and low membrane permeability. To address these challenges, we developed cationic nanostructured lipid carriers (cNLCs) via high-pressure homogenization as non-viral carriers for miRNA-27a. However, the formation of a protein corona in biologically-relevant media altered the particle size and surface charge, significantly reducing cellular uptake. To mitigate this issue, we hypothesized that coating miRNA/cNLC complexes with human serum albumin (HSA) will prevent protein corona formation and enhance cellular uptake. The HSA-coated miRNA/cNLC complexes, termed albuplexes, were characterized for particle size, zeta potential, morphology, and stability in various media. The integrity of the HSA coat was assessed using circular dichroism and UV/Vis spectroscopy. We also evaluated the biocompatibility and cellular uptake of albuplexes in 3T3-L1 cells. The biological effects of miRNA-27a on adipocyte development were analyzed through light microscopy and absorbance measurements of Oil-red-O dye in lipid droplets. Results indicated that albuplexes possess favourable physicochemical properties and enhanced stability in serum. Notably, albuplexes were rapidly taken up by 3T3-L cells via endocytosis, although 20 % HSA in the culture medium completely inhibited uptake. Furthermore, albuplexes exhibited an anti-adipogenic effect by reducing the lipid droplet accumulation, suggesting their potential as a therapeutic strategy for miRNA replacement in obesity treatment.

Three novel unsymmetrically substituted 2,2'-bipyridine ligands were prepared by introducing a 2-hydroxyphenyl group at the 6-position and either a 4-methoxyphenyl, 3,4-dimethoxyphenyl or 3,4-methylenedioxyphenyl group at the 4-position, using a modified Kröhnke protocol. Their corresponding rhenium(I) tricarbonyl iodido complexes, fac-[Re(L)(CO)3I], 1-3, were synthesized and comprehensively characterized by single-crystal X-ray diffraction (SCXRD), 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, cyclic voltammetry (CV), high-resolution mass spectrometry (HRMS), and elemental analysis. The common 6-(2-hydroxyphenyl) moiety predominantly influences the spectroscopic and redox properties of the complexes. SCXRD confirms the facial arrangement of the fac-[Re(CO)3N2I] core in all three cases, although solid-state conformational isomerism was observed only in complex 1. In contrast, two NMR-distinguishable isomers are observed in solution for all three complexes. The cytotoxicity of 1-3 was evaluated by MTT assay after 48 h of continuous exposure in several human tumor cell lines (HeLa, PANC-1, MDA-MB-231, A549) and in non-malignant human lung fibroblasts (MRC-5). Notably, all three complexes displayed low-micromolar IC50 values comparable to cisplatin, with the highest activity observed in HeLa cells (5.11-7.45 μM). However, significant activity was also recorded in MRC-5 cells (IC50 = 8.19-8.95 μM), suggesting higher overall toxicity and weaker selectivity compared to cisplatin. Analysis in HeLa cells using bright-field microscopy confirmed a substantial antiproliferative effect.

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.

Dexketoprofen/tramadol is a fixed-dose multimodal combination analgesic that significantly controls multiple acute pain states, and may have an important clinical application in providing pain control adequate to prevent the transition from acute to chronic postsurgical and low back pain. A consensus is needed to quantify and define the actual burden of postsurgical pain (PSP) and low back pain (LBP), which can support efforts toward effective approaches to manage potential pain chronification. This study utilized a modified Delphi approach. A Scientific Committee set forth 28 statements on six themes about the burden of acute PSP and LBP, their potential transition to chronic pain, their pathophysiology, therapeutic approaches to stop this transition, and the role of multimodal analgesia in this context, specifically a fixed-dose combination oral product of dexketoprofen/tramadol. An international panel of healthcare professionals from various regions and relevant medical specialties participated in a Delphi study and were surveyed for consensus on a 5-point Likert scale with consensus defined as > 70% concordance. A round of online voting lasting 3 months and using an online survey platform was permitted for each participant. A total of 100 experts completed the Delphi survey. All the 28 proposed statements reached consensus > 70% in the first round of voting. A fixed-dose combination product, specifically dexketoprofen/tramadol was recognized as a multimodal analgesic which could effectively relieve acute pain and act to prevent its transition to chronic pain. The high global burden of chronic PSP (CPSP) and chronic LBP (CLBP) was identified as well. Healthcare professionals who deal with pain recognize the burden of acute pain, the risks of acute pain transitioning to chronic pain, and inspire to avert the transition by providing effective multimodal control of acute pain. The role of fixed-dose combination analgesics, in particular dexketoprofen/tramadol, was recognized by consensus as an efficacious and safe therapy option for these acute pain syndromes. 7KDL7wDHZ5GDvGppW1iD89 A Video Abstract is available for this article. To view, please see the online version of the manuscript or follow the ‘Digital Features’ link. A Video Abstract for The Role of Dexketoprofen/Tramadol in Multimodal Therapy to Prevent Acute Postsurgical and Acute Low Back Pain from Developing into Chronic Pain: A Delphi Consensus Study (MP4 112565 KB) A Video Abstract is available for this article. To view, please see the online version of the manuscript or follow the ‘Digital Features’ link. A Video Abstract for The Role of Dexketoprofen/Tramadol in Multimodal Therapy to Prevent Acute Postsurgical and Acute Low Back Pain from Developing into Chronic Pain: A Delphi Consensus Study (MP4 112565 KB)

Bacterial cell poles play a fundamental role in several cellular processes, such as cell cycle, chemotaxis, cell differentiation, development, growth, and structure of the bacterial cell, as well as protein localization. Using a set of bioinformatics tools, we evaluated the probability of 19 bacterial cell pole-related proteins to be disordered and undergo spontaneous liquid-liquid phase separation (LLPS). Our analysis revealed that11 cell pole-related proteins are predicted to be highly disordered, 7 proteins are moderately disordered, and only one protein is expected to be highly ordered. Furthermore, this intrinsic disorder propensity is mostly evolutionary conserved. Most of the analyzed 19 cell pole-related proteins were found to be associated with the LLPS process, with TipN, PopZ, and PBP2A being capable of spontaneous phase separation, RacA, Noc, PBP1A/1B, ParB, PBP3, PBP2B, FtsZ, MipZ, MinD, and MreB being expected to potentially serve as droplet clients, and with the remaining proteins (DivIVA, ComN, Maf, PBP4, MinC, and MinJ) being predicted to be unrelated to LLPS. The results suggested that FtsZ, DivIVA, and MiPZ serve as the main regulatory proteins, being well-known for their role in forming the septum and chromosomal segregation. Furthermore, PopZ and TipN proteins contribute to high stress resistance. Clarifying the function and effects of each mechanism gives insight into the organization of bacterial cells and some strategies for antimicrobial targets.

In heart failure, hyperuricemia is common, and higher serum uric acid levels are associated with poorer clinical outcomes. Additionally, hyperuricemia can cause gout, which is difficult to manage and can prolong hospitalization in patients with heart failure. In this context, agents that lower UA have even been investigated as potential treatments for heart failure because of their potential effect on SUA. Among patients with chronic heart failure, our study aimed to determine whether SGLT2 inhibitor empagliflozin influences SUA levels and whether empagliflozin has therapeutic efficacy related to SUA, particularly their effect on reducing mortality, preventing hospitalization, and improving clinical status. In 164 patients, the association between SUA and cardiovascular death or hospitalization for worsening HF and all-cause mortality was investigated. The treatment effect of empagliflozin was studied in relation to SUA as continuous variable, to clinical hyperuricemia (SUA >5.7 mg/dL for women, >7.0 mg/dL for men). Hyperuricemia was prevalent in 61% of patients with no sex differences. Elevated SUA (mean SUA 9.42 ± 1.53 mg/dL) was associated with advanced severity of HF and with worst outcome [composite outcome, hazard ratio (HR) 1.67 (95% confidence interval, CI 1.26–2.14); cardiovascular mortality, HR 1.96 (95% CI 1.32–2.89); all-cause mortality, HR 1.8 (95% CI 1.31–2.44). The reduction of SUA after initiating therapy with empagliflozin was observed rapidly (i.e. at 4 weeks) and was maintained throughout the follow-up period. The beneficial effect of empagliflozin on the primary endpoint was independent of baseline SUA [HR 0.78 (95% CI 0.69–0.90), P < 0.001) and of the change in SUA at 4 weeks [HR 0.84 (95% CI 0.71–0.94), P = 0.014]. Hyperuricemia is common in HF and is a strong indicator of advanced disease severity and increased mortality. The administration of empagliflozin resulted in rapid and sustained reductions in SUA levels and hyperuricemia-related clinical events. The benefit of empagliflozin on the primary outcome was observed independently of SUA. Patients with elevated SUA levels experienced a significant reduction in cardiovascular mortality and all-cause mortality, whereas patients with lower SUA levels did not experience this reduction. Empagliflozin was most effective in lowering SUA levels in patients with the highest SUA levels at baseline who also showed the highest mortality risks.Treatment effect of empagliflozin  Cumulative incidence of hyperur. events

Per- and polyfluoroalkyl substances (PFAS) are of increasing concern due to their environmental persistence, bioaccumulative nature, and association with adverse health outcomes. The growing need for large-scale monitoring and long-term exposure assessment studies necessitates the development of high-throughput, sustainable analytical methodologies. In this work, a solid-phase microextraction-microfluidic open interface-mass spectrometry (SPME-MOI-MS) platform was developed for the rapid screening of 18 PFAS compounds in human plasma. By bypassing the liquid chromatography separation, the method achieves high-throughput performance with an average analysis time of 3.7 min per sample. A novel SPME coating, comprising hydrophilic-lipophilic balanced mixed-mode weak anion exchange sorbent (HLB-WAX) particles embedded in a polyacrylonitrile (PAN) binder, enabled efficient extraction and effective cleanup of complex biological matrices, facilitating direct MS analysis. The method demonstrated excellent linearity (1-100 ng/mL) and low limits of detection (0.11-0.86 ng/mL) across target PFAS compounds. For practical application, PFOA and PFNA were detected in human plasma samples during these initial investigations, demonstrating the potential of the SPME-MOI-MS approach for large-scale PFAS biomonitoring and exposure assessment.

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.

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.