Aging-induced endothelial dysfunction is a core driver of age-related cardiovascular diseases (CVDs). In 20-month-old naturally aged mice, 12-week soybean polysaccharide (SP) supplementation restored endothelium-dependent relaxation, reduced aortic reactive oxygen species and VCAM-1 in the aortic endothelium, and attenuated colon senescence, improved gut barrier integrity, and reduced systemic inflammation, as shown by decreased serum LPS, IL-1β, TNF-α, and fecal and serum TMA/TMAO levels. SP enriched butyrate-producing gut bacteria, including Lachnospiraceae_NK4A136_group, and increased gut and serum butyrate, consistent with enhanced microbial short-chain fatty acid biosynthesis capacity predicted by PICRUSt2. Direct butyrate supplementation reproduced these vascular and colonic benefits. It activated PPARγ signaling and downregulated p21, ICAM-1, VCAM-1, and p16, whereas PPARα and PPARδ remained unchanged. These findings support a gut microbiota-butyrate-PPARγ/p21 axis through which SP protects against aging-related endothelial dysfunction, providing a nutritional basis for targeting the gut-vascular axis in cardiovascular aging.

Experimental myocardial infarction (MI) is commonly modeled in animals through transient occlusion of the left anterior descending (LAD) coronary artery or, at the cellular level, by hypoxia-reoxygenation protocols. As an alternative organ-level model of ischemia, the Langendorff-perfused heart has remained a cornerstone tool for investigating the effects of physiological perturbations and pharmacological interventions on cardioprotection. Here, we present the basic methodology and fundamental rules required for establishing a regional myocardial ischemia/reperfusion model in the isolated mouse heart. In brief, following cardioplegic arrest, the LAD was ligated after a brief flush with ice-cold PBS. The heart was then mounted on a Langendorff apparatus and perfused with a nutrient-rich oxygenated buffer at 37°C under a constant perfusion pressure of 110 cmH₂O. The length of myocardial ischemia was induced for 30, 45, 60, 90 and 120 min followed by 90 min of reperfusion. Cardiomyocyte viability and infarct size were assessed by using microscopic 2,3,5-triphenyltetrazolium chloride (TTC) staining approach. We demonstrated that the ex vivo MI model reliably yielded reproducible myocardial injury, characterized by a progressive loss of viable cardiomyocytes within the infarct region as ischemic duration extended. In addition, at least 30 min of reperfusion was required to achieve clear TTC-based delineation of the infarcted myocardium. This approach bypasses systemic variables, thereby allowing researchers to evaluate directly cardiac effects in the absence of extrinsic regulatory influences, such as circulating humoral factors and immune cell infiltration, that may confound MI progression, and to test localized pharmaceutical interventions. Thus, the ex vivo MI model represents a useful platform for investigating cardioprotective mechanisms that act directly on cardiomyocytes.

Primary percutaneous coronary intervention (pPCI) restores epicardial coronary flow in ST-segment elevation myocardial infarction (STEMI), but microvascular and tissue-level reperfusion may remain impaired. Cardiovascular magnetic resonance (CMR)-defined microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH) both mark severe reperfusion injury but reflect distinct tissue processes. This structured narrative review synthesizes evidence on MVO mechanisms, multimodal phenotypes, and interventions. Available evidence implicates interacting contributions from distal embolization, endothelial barrier and vasomotor dysfunction, pericyte-mediated capillary constriction, immunothrombosis, and tissue edema. IMH reflects more extensive microvascular destruction with erythrocyte extravasation. Angiography, electrocardiography, invasive physiology, angiography-derived indices, echocardiography, and CMR assess different pathophysiologic levels. Discordance between modalities is therefore not necessarily contradictory. Across trials, improvements in surrogate endpoints have often not translated into long-term clinical benefit, partly because of mechanistic heterogeneity and misaligned treatment timing and endpoints. A conceptual, reperfusion-centered T- to T5 research framework is proposed for serial within-patient assessment. It links early physiology, inflammatory and thrombotic biomarkers, acute-phase CMR, and long-term remodeling. Future trials should align mechanistic enrichment, intervention timing, and endpoint selection to establish a continuous evidence chain from target engagement to clinical outcomes.

The objective of this study was to test the hypothesis that supplementation with a combination of prebiotics (inulin and yeast extract), essential oils, and an acidifier (lactic acid) could mitigate the negative impacts of F18⁺ Escherichia coli (E. coli) on intestinal health and growth performance of nursery pigs. Thirty-six nursery pigs (6.8 ± 0.3 kg) weaned at 21 d of age were assigned to 3 treatments in a randomized complete block design with initial body weight and sex as blocks. Pigs were fed for 28 d in 3 phases (d 0 to 10, 10 to 22, and 22 to 28, respectively). Treatments were NC (basal diet, no challenge), PC (basal diet, challenged with F18⁺ E. coli), and POA (basal diet supplemented with a combined mixture of inulin, yeast extract, essential oils, and lactic acid at 0.1%, challenged with F18⁺ E. coli). On d 7 and 8, pigs in the PC and POA were orally inoculated with F18⁺ E. coli with a total dose of 1.1 × 1010 CFU/pig. On d 28, pigs were euthanized to collect jejunal tissue and mucosa. Data were analyzed using preplanned contrasts (NC vs. PC and PC vs. POA) in the MIXED procedure of SAS. The PC increased (P < 0.05) the expression of interferon-γ in the jejunum compared with the NC, whereas the POA decreased (P < 0.05) it compared with the PC. The PC tended to reduce (P = 0.051) the expression of occludin in the jejunum compared with the NC, whereas the POA increased (P < 0.05) occludin compared with the PC. The PC tended to increase interleukin-6 (P = 0.064) and interleukin-8 (P = 0.080) and increased (P < 0.05) protein carbonyl in the jejunal mucosa compared with the NC, whereas the POA reduced (P < 0.05) tumor necrosis factor-α, interleukin-6, and protein carbonyl compared with the PC. The PC reduced (P < 0.05) jejunal villus height, whereas the POA increased (P < 0.05) it compared with the PC. The PC reduced (P < 0.05) overall average daily gain and gain:feed compared with the NC. The POA tended to reduce (P = 0.059) overall average daily feed intake compared with the PC without compromising average daily gain or gain:feed, suggesting that the reduction in feed intake did not negatively affect growth performance. In conclusion, supplementation with a combination of inulin, yeast extract, essential oils, and lactic acid reduced intestinal inflammation and oxidative damage, and improved intestinal integrity and morphology in F18+  E. coli challenged pigs, whereas growth performance remained unaffected.

Noninfectious scleritis represents a spectrum of potentially vision-threatening inflammatory disorders frequently associated with systemic immune-mediated disease. Therapy is decided based on the location, severity, and presence of ocular complications and systemic associated diseases. Starting with nonsteroidal anti-inflammatory drugs to oral corticosteroids, the therapeutic armamentarium has widened to include oral immunomodulator therapy. Over the last decade, advances in immunology and targeted therapeutics have substantially altered management paradigms, particularly for refractory and necrotizing disease. This review provides an updated, clinically focused synthesis of contemporary management strategies in noninfectious scleritis, with particular emphasis on biologic agents, small-molecule therapies, and emerging targeted treatments. We first discuss the management which includes the existing large-body of evidence supporting systemic corticosteroids and conventional immunosuppressive therapy. We further review second-line therapies which include biological agents such as tumor necrosis factor-α inhibitors, interleukin-6 blockade, and B-cell-directed therapy. Newer agents such as Janus kinase inhibitors are reviewed in the context of early clinical experience and evolving safety data. The role of local therapies, surgical intervention as an adjunct to systemic immunomodulation, and management of common complications are also addressed. Finally, we highlight strategies for long-term monitoring, prognostic factors, and future directions, emphasizing the need for prospective trials and precision-based approaches. This review is intended for clinicians managing complex scleritis and aims to inform evidence-based, individualized care in contemporary practice.

The present study aimed to clarify the relationship between polymorphisms present in the interleukin-6 (IL-6) gene (rs1800795 and rs1800797) and the susceptibility to chronic kidney disease (CKD), while concurrently examining critical biochemical markers (urea, creatinine, albumin, calcium, phosphate and glucose) alongside the levels of immunological factors [IL-6, tumor necrosis factor-α (TNF-α) and antinuclear antibodies (ANAs)]. A detailed investigation was carried out on a group of 51 subjects (22 male and 29 female subjects) who were 40-60 years old. The serum concentrations of IL-6, TNF-α and ANA were quantitatively evaluated using enzyme-linked immunosorbent assays, whereas the levels of various biochemical markers were determined by the Cobas 6000 analytical system. Genomic DNA was isolated and the IL-6 single nucleotide polymorphisms were genotyped by employing the PCR-restriction fragment length polymorphism methodology. The analysis of body weight showed notable differences between the male and female participants; however, other chemical markers did not indicate any sex-related variations. The correlation analyses illustrated moderate statistically significant relationships between albumin and calcium, together with an association between urea and phosphate, while the levels of IL-6, TNF-α and ANA portrayed a non-significant fluctuation. Analysis of the IL-6 gene showed that carriage of the rs1800795 C allele was associated with increased susceptibility to CKD, whereas rs1800797 was not significantly associated with CKD. Integrating genetic, immunological and biochemical data may improve understanding of CKD susceptibility, although validation in larger cohorts is required.

Intra-articular osteoid osteoma is an uncommon benign osteoblastic tumor that frequently presents with atypical clinical and radiographic findings, often delaying diagnosis. Lesions involving the talus are challenging because marrow edema and synovitis may obscure the characteristic nidus on magnetic resonance imaging (MRI), mimicking other pathologic processes. We present the case of a young male with a greater than 2-year history of atraumatic ankle pain and diffuse talar marrow edema on MRI, initially interpreted as osteonecrosis. He underwent ankle arthroscopy and talar core decompression, with minimal improvement. Repeat MRI demonstrated an evolving dorsolateral talar neck lesion, raising concern for osteoid osteoma and prompting excision. Histopathology demonstrated osteoid osteoma. At 6-month follow-up, he reported full pain resolution and unrestricted activity. This case highlights that intra-articular osteoid osteoma of the talus should be considered in young patients with persistent atraumatic ankle pain and diffuse marrow edema when the clinical course becomes discordant with avascular necrosis.

Natural killer (NK) cells are essential components of innate immunity and play a pivotal role in tumor surveillance through direct cytotoxicity and immune regulation. In recent years, NK-cell-derived extracellular vesicles (NK-EVs) have emerged as a promising cell-free therapeutic modality that preserves key antitumor functions of parental NK cells while overcoming several limitations associated with cell-based immunotherapy. As biologically derived nanovesicles, NK-EVs combine nanoscale delivery properties with a cell-free formulation format and generally low immunogenicity. However, although selected preclinical studies suggest tumor-interacting or target-cell-recognition properties, a broadly applicable intrinsic tumor-targeting capacity-and, in particular, intrinsic blood-brain barrier (BBB) penetration-has not been established for native NK-EVs. This review systematically summarizes the biological characteristics, biogenesis pathways, and molecular cargo of NK-EVs, with particular emphasis on their antitumor mechanisms. Current evidence supports perforin/granzyme-mediated cytotoxicity and Fas/Fas ligand (FasL) signaling as the most established mechanisms of NK-EVs-mediated tumor killing, whereas miRNA-mediated regulation and tumor microenvironment remodeling represent emerging functional pathways requiring further validation. By contrast, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-death receptor 4/5 (DR4/DR5) signaling remains putative because direct NK-EVs-specific causal evidence is limited. Functionally investigated miRNAs and tumor-microenvironment effects represent context-dependent or emerging pathways whose generalizability across NK-cell sources and preparation conditions requires further validation. Importantly, recent advances in engineering strategies-including parental-cell priming, cargo loading, antigen-recognition engineering, tissue/barrier-targeting modification, biomimetic nanovesicle construction, and formulation-based stabilization. These approaches can alter cargo composition, recipient-cell recognition, or tissue-specific delivery through distinct mechanisms. Improvements achieved by engineered composite platforms should therefore not be conflated with intrinsic properties of native NK-EVs. Nevertheless, major translational challenges remain, including scalable manufacturing, purification and characterization standardization, mechanism-linked potency testing, biodistribution uncertainty, batch comparability, and product-specific regulatory considerations. Overall, NK-EVs should be viewed not only as potential cell-free therapeutic tools but also as specialized mediators of tumor-immune communication that integrate cytotoxic protein transfer, receptor-mediated signaling, RNA-based regulation, and microenvironmental crosstalk.