Search Results (55,484)

CLEC3B (C-type lectin domain family 3 member B), also known as tetranectin (TN), is a secreted trimeric protein containing a C-type lectin-like domain (CTLD). Located on chromosome 3p21.31. CLEC3B maintains organismal homeostasis through roles in immune regulation, angiogenesis, and musculoskeletal biology. Genetic studies demonstrate that CLEC3B deficiency impairs tissue repair, bone mineralization, and fibrinolytic balance. Altered CLEC3B expression is linked to cardiovascular disease progression, autoimmune susceptibility, and cancer prognosis. This review synthesizes CLEC3B’s biological functions and evaluates its translational potential: circulating CLEC3B as a prognostic and diagnostic biomarker; tissue-resident CLEC3B as a predictive marker for therapeutic response; and CLEC3B-related pathways as candidate therapeutic targets for potential amenable to replacement or inhibition strategies. We identify critical research gaps to guide future investigations, including limited structural data, ambiguous glycan specificity, incomplete proteolytic network mapping, and lack of validated disease models. Collectively, these gaps currently preclude definitive therapeutic claims. Full article

Objective: Malignant middle cerebral artery infarction is associated with high mortality despite decompressive craniectomy. Reliable biomarkers predicting early outcome remain limited. The aim of this study was to evaluate the prognostic significance of inflammatory biomarkers, particularly the systemic immune–inflammation index (SII), for predicting in-hospital mortality in patients undergoing decompressive craniectomy for malignant middle cerebral artery infarction. Methods: This retrospective study included 31 patients who underwent decompressive craniectomy for malignant MCA infarction between 2014 and 2024. Demographic, clinical, radiological, and laboratory variables were analyzed. Results: Overall in-hospital mortality was 61.3%. Non-survivors had significantly higher SII, neutrophil count, neutrophil-to-lymphocyte ratio, serum creatinine, and higher prevalence of hypertension and anticoagulant therapy. ROC analysis showed that SII had the highest predictive performance (AUC = 0.833). Multivariate analysis identified age, serum creatinine, NLR, SII, hypertension, and anticoagulant therapy as independent predictors of mortality. Patients aged ≥65 years had significantly higher in-hospital mortality than younger patients. Conclusions: Elevated SII is a strong independent predictor of early mortality after decompressive craniectomy and may serve as a simple and clinically applicable biomarker for risk stratification. Full article

Hepcidin, a 25-amino-acid peptide hormone produced primarily by hepatocytes, is the master regulator of systemic iron homeostasis. By binding the cellular iron exporter ferroportin and inducing its internalization and lysosomal degradation, hepcidin restricts iron entry into plasma from enterocytes, macrophages, and hepatocytes. Its transcription is governed by an intricate molecular network that integrates iron status, erythropoietic demand, oxygen tension, and inflammation, with the BMP–HJV–ALK2/SMAD axis acting as the canonical activating pathway and erythroferrone (ERFE) and matriptase-2 (TMPRSS6) as physiological suppressors. Dysregulation of hepcidin underpins a wide spectrum of human diseases: insufficient hepcidin drives hereditary hemochromatosis and the iron overload of congenital and acquired ineffective erythropoiesis diseases and other ineffective erythropoiesis syndromes, whereas excessive or inappropriate hepcidin contributes to anemia of inflammation, anemia of chronic kidney disease, iron-restricted erythropoiesis in cancer, the iron-restrictive anemia of myelofibrosis, and pathogen-restrictive nutritional immunity. Within the myeloproliferative neoplasm spectrum, the divergent hepcidin patterns observed in polycythemia vera (suppressed) and myelofibrosis (inappropriately elevated through dual BMP/ACVR1/SMAD and IL-6/STAT3 hyperactivation) exemplify the clinical relevance of this axis and underpin two opposite pharmacologic strategies. Over the past decade, hepcidin pathway pharmacology has matured from proof-of-concept to regulatory milestones, shifting perspectives on several diseases and markedly improving clinical approaches. Full article

Microglia, the resident innate immune cells of the central nervous system, are central players in brain development, healthy aging, and degenerative pathology, including Alzheimer’s disease (AD). Aging is a major risk factor for AD, and various studies have identified alterations in microglial molecular signatures and morphological patterns that overlap with microglial states during aging. However, the mechanisms underlying the divergence of aging trajectories toward disease remain unclear. Thus, understanding the molecular changes in microglia during aging and AD pathology is crucial to elucidating the mechanisms that drive disease progression. In this review, we examine current advances in understanding the phenotypic alterations in human microglia, highlighting gene signatures and morphological changes that may aid in defining microglia’s molecular and functional programs in healthy aging and over the course of AD. We further explore the roles of oxidative stress and cellular senescence in driving the development of a chronic reactive state in microglia during aging, which may also contribute to the complex process underlying the onset and progression of AD pathology. This review highlights the advancements in therapeutic strategies focused on targeting pertinent pathological microglial changes during aging and in disease to mitigate the AD neurodegenerative process. Full article

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are critical modulators of male reproductive health, influencing sperm function, hormonal regulation, and overall fertility. While physiological levels of ROS and RNS are essential for processes such as sperm capacitation and acrosome reaction, their overproduction leads to oxidative and nitrosative stress, contributing to male infertility. Excessive ROS and RNS can damage sperm DNA, proteins, and lipids, impairing motility, viability, and fertilizing capacity. Moreover, these reactive species disrupt the hypothalamic-pituitary-gonadal (HPG) axis, leading to hormonal imbalances that further compromise reproductive function. Environmental factors, lifestyle choices, and underlying health conditions exacerbate the production of ROS and RNS, highlighting the need for preventive and therapeutic strategies. Clinically, ROS- and RNS-mediated redox imbalance has been implicated in several male reproductive disorders, including varicocele, genital tract infection and inflammation, obesity, diabetes and other metabolic disorders, and toxicant-related reproductive dysfunction. Antioxidant supplementation has shown promise in mitigating oxidative stress; however, its efficacy varies, and further research is necessary to establish standardized treatment protocols. These findings underscore the clinical relevance of integrating oxidative stress assessment with conventional semen analysis to improve risk stratification and guide targeted interventions in male infertility. This review synthesizes current knowledge on the molecular mechanisms by which ROS and RNS affect male reproduction and discusses potential clinical interventions to address oxidative and nitrosative stress in male infertility. Full article

This study investigates the phytochemical and pharmacological profiles of Crinum asiaticum L. var. anomalum Baker from Vietnam. Phytochemical screening identified diverse secondary metabolites, including polyphenols, flavonoids, and alkaloids. Gas chromatography–mass spectrometry analysis of the n-hexane fractions revealed 19 major compounds. While all extracts showed moderate antioxidant activity, the chloroform fraction exhibited superior antidiabetic potential via α-amylase inhibition (IC₅₀ = 83.13 ± 6.67 µg/mL). Furthermore, at non-cytotoxic concentrations (3.13 to 50 µg/mL), this fraction effectively rescued mouse β-TC6 insulinoma cells from thapsigargin. In anti-inflammatory assays, the n-hexane fraction significantly suppressed nitric oxide production in RAW 264.7 macrophages (IC₅₀ = 53.12 ± 1.63 µg/mL). Notably, the extracts displayed remarkable selective anticancer activity, particularly the chloroform fraction against HeLa cervical and HepG2/Huh-7 hepatoma cell lines. In silico ADMET and Lipinski’s Rule of Five analyses confirmed that the key bioactive constituents possess favorable pharmacokinetic profiles and drug-likeness. These findings demonstrate C. asiaticum L. var. anomalum Baker as a promising natural source for developing multitarget therapeutic agents against inflammation, diabetes, and cancer. Full article

Swine Inflammation and Necrosis Syndrome (SINS) is a widespread condition in pigs and has been proposed as an early-life animal-based measure (ABM) for assessing health and welfare. However, its prognostic value for later-life outcomes under commercial conditions remains poorly understood. This study investigated the prevalence, progression, and predictive relevance of SINS in two organic pig farms in the Netherlands. Clinical SINS signs were assessed in suckling and weaned piglets and related to hematological parameters at weaning (35 weaned piglets) as well as tail integrity at slaughter. SINS lesions were highly prevalent in suckling piglets (approximately 80%) but markedly decreased after weaning. Lesion prevalence and severity differed substantially between farms and showed clear age-dependent patterns, peaking between days 3 and 5 of life. Higher SINS scores in suckling piglets were associated with systemic hematological alterations at weaning, including increased monocyte proportions, reduced platelet counts, and altered red blood cell indices. Importantly, early-life SINS was significantly associated with later tail integrity. Pigs with higher SINS scores showed a lower probability of intact tails at slaughter and subsequently a higher prevalence of tail lesions. These findings suggest that SINS may have potential as an early-life indicator of later tail outcomes; however, this hypothesis requires validation in larger studies involving a greater number of farms and production systems. Full article

Background: Oxidative stress is pivotal in pulmonary hypertension. The uric acid-to-albumin ratio (UAR) is a readily available composite biomarker reflecting oxidative stress, inflammation and nutritional status. However, its clinical value for short-term risk stratification in PH remains unclear. Objective: This study aimed to evaluate the association of UAR with in-hospital mortality, clinically recorded PH severity grades, and selected cardiac structural and functional indicators in hospitalized patients with PH. Methods: This single-center retrospective cohort study included 8763 PH patients. Patients were stratified by UAR quartiles. Ordinal logistic regression, multivariable logistic regression, and linear regression were used to assess associations of UAR with clinically recorded PH severity grades, in-hospital mortality, left ventricular ejection fraction (LVEF), and right ventricular internal diameter (RVID). Restricted cubic spline analyses, subgroup analyses, receiver operating characteristic curve analyses, and incremental prediction analyses using C-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were also performed. Results: In-hospital mortality increased stepwise across UAR quartiles (0.5% vs. 1.0% vs. 1.8% vs. 2.8%, p < 0.001). In the fully adjusted model, each 1-unit increase in UAR was associated with higher odds of a more severe clinically recorded PH grade (OR = 1.11, 95% CI: 1.09–1.13, p < 0.001) and higher odds of in-hospital mortality (OR = 1.09, 95% CI: 1.04–1.14, p < 0.001). Higher UAR was also associated with lower LVEF (β = −0.53, 95% CI: −0.58 to −0.47, p < 0.001) and greater RVID (β = 0.18, 95% CI: 0.15–0.22, p < 0.001). Adding UAR to a model containing routinely available clinical, laboratory, and echocardiographic variables improved the C-statistic from 0.6922 to 0.7230, with significant improvements in NRI and IDI. Conclusions: UAR was independently associated with in-hospital mortality, clinically recorded PH severity, LVEF, and RVID, and provided incremental prognostic information. UAR may serve as a low-cost, routinely available, complementary biomarker for short-term in-hospital risk stratification in patients with PH. Full article

Imiquimod-induced skin inflammation is the most widely used psoriasis mouse model. Although p38 mitogen-activated protein kinase reportedly plays a role in the pathogenesis of psoriatic inflammation, the purpose of one of its upstream activators, apoptosis signal-regulating kinase 1 (ASK1), remains unclear. This study investigated the role of ASK1 and its molecular mechanism in the imiquimod-induced psoriasis model. Compared to wild-type mice, the ASK1 knockout (KO) mouse skin lesion showed a higher clinical score and a thicker epidermis. The mRNA expression of pro-inflammatory cytokines, such as IL-17 and TNF-α, was also higher. Notably, the expression of aryl hydrocarbon receptor (AhR), a sensor for xenobiotic chemicals that is expressed in the skin to strengthen the skin barrier and accelerate terminal differentiation of the epidermis—as well as its downstream molecule CYP1A1, but not NRF2—was increased in the ASK1 KO psoriatic skin lesion. Immunoprecipitation analysis, followed by Western blotting, revealed that ASK1 interacts with AhR in cells transfected with their respective expression vectors, potentially leading to reduced AhR expression. These results suggest that ASK1 negatively regulates the development of the imiquimod-induced mouse psoriasis model by interacting with AhR and presumably antagonizing the AhR-CYP1A1 axis. Full article

Stroke remains one of the leading causes of long-term disability and death worldwide. Growing evidence suggests that both stroke onset and severity exhibit strong circadian patterns. This blood–brain interface (BBI), which regulates bidirectional communication between the peripheral circulation and the central nervous system, plays a critical role in cerebrovascular injury. Aging further exacerbates these processes by dampening the molecular clock function and increasing inflammatory activation. In this review, we examine the circadian regulation of the BBI, aging, and its implications in stroke vulnerability. Understanding how circadian biology modulates neurovascular function may reveal novel therapeutic targets and time-of-day-dependent approaches for stroke prevention and treatment. Full article

Background/Objectives: Inflammation plays a central role in the pathophysiology of ST-elevation myocardial infarction (STEMI) and may influence myocardial injury, ventricular dysfunction and clinical outcomes. Simple inflammatory biomarkers derived from routine laboratory tests have been proposed as potential prognostic indicators in patients undergoing primary percutaneous coronary intervention (PCI). Objective: This study aimed to evaluate the association between admission inflammatory biomarkers, echocardiographic markers of ventricular dysfunction and in-hospital mortality in patients with STEMI treated with primary PCI. Methods: We conducted a retrospective observational study including 600 consecutive patients admitted with STEMI and treated with primary PCI between January 2021 and August 2025. Inflammatory biomarkers measured at admission included C-reactive protein (CRP); neutrophil-to-lymphocyte ratio (NLR); platelet-to-lymphocyte ratio (PLR); systemic immune-inflammation index (SII) and C-reactive protein-to-lymphocyte ratio (CLR). Echocardiographic parameters and clinical outcomes were recorded. Multivariable logistic regression analysis was performed to identify independent predictors of in-hospital mortality. Results: In-hospital mortality occurred in 54 patients (9.0%). Patients with reduced left ventricular ejection fraction (LVEF ≤ 40%) had significantly higher CRP and CLR levels (p < 0.01). Inflammatory biomarkers were associated with markers of ventricular dysfunction but were not independent predictors of mortality. Age, LVEF < 40% and the number of residual coronary lesions independently predicted in-hospital death. Conclusions: In STEMI patients undergoing primary PCI, early mortality is mainly determined by age; ventricular dysfunction and residual coronary disease burden, while inflammatory biomarkers primarily reflect the severity of myocardial injury rather than independently predicting short-term mortality. Full article

High-glucose exposure impairs intestinal metabolic homeostasis and barrier integrity in fish, but the transcriptional responses associated with high-glucose adaptation in fish intestinal epithelial cells remain incompletely understood. This study investigated whether exogenous 5-methylcytosine (5MC) alleviates high-glucose-induced metabolic and epithelial stress in grass carp (Ctenopharyngodon Idella) intestinal epithelial cells and whether these responses are associated with changes in DNA methyltransferase 3 beta (dnmt3b) expression and Caudal type homeobox 1b (cdx1b)/Sodium-glucose cotransporter 1 (sglt1)-related transcriptional responses. As exploratory in silico information, molecular docking predicted candidate complex conformations of DNMT3B with CDX1B and SGLT1, with binding energies of −37.2 and −25.9 kcal/mol, respectively. Functionally, dnmt3b knockdown significantly reduced dnmt3b, Interleukin 6 (il6), and Nuclear factor kappa B (nfκb) expression, while increasing cdx1b, sglt1, Solute carrier family 2 member 3a (slc2a3a), 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4a (pfkfb4a), and Amine oxidase copper containing 1 (aoc1) expression (p < 0.05). CDX2/CDX1B-like immunoreactive protein and SGLT1 protein levels were also increased after dnmt3b knockdown (p < 0.05). Under high-glucose stress, exogenous 5MC exerted concentration-dependent effects. Specifically, 6 mM 5MC significantly reduced residual extracellular glucose, lactate dehydrogenase and diamine oxidase activities, and malondialdehyde content, while increasing glutathione content, cell viability, and cell migration (p < 0.05). These effects remained detectable after replacement with high-glucose medium for an additional 12 h. By contrast, 24 mM 5MC markedly increased lactate dehydrogenase activity and reduced cell viability, suggesting potential cytotoxicity (p < 0.05). S-adenosylmethionine (SAM) levels were significantly lower in the NC and 6 mM groups than in the HG, 12 mM, and 24 mM groups, suggesting changes in SAM-related one-carbon metabolic status rather than direct evidence of altered DNA methylation (p < 0.05). Exogenous 5MC, particularly at 6 mM, alleviated high-glucose-induced metabolic and epithelial stress in grass carp intestinal epithelial cells. These effects were accompanied by changes in several glucose metabolism- and inflammation-related genes. However, the cellular uptake, metabolic fate, DNA incorporation, methylation consequences, and causal roles of these gene-expression changes remain to be further verified. Full article

Background and Objectives: The aim of this study is to evaluate the effects of oridonin on a cisplatin-induced ovarian injury rat model. Materials and Methods: Thirty female rats were divided into three groups. Group 1: control; group 2: cisplatin; group 3: cisplatin plus oridonin group. In groups 2 and 3, the rats were injected with 2.5 mg/kg (twice weekly) cisplatin intraperitoneally (i.p.) for 4 weeks. In Group 3, rats received oridonin (10 mg/kg/day, i.p.). At the end of the study, the ovaries were removed in all groups. Histopathologic analysis and follicle counting were performed. Plasma anti-Müllerian hormone (AMH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels were measured, while ovarian transforming growth factor-beta 1 (TGF-β1), SMAD family member 3 (SMAD3), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels were evaluated. Results: Oridonin alleviated cisplatin-induced histopathological changes in the ovarian tissue. The numbers of primordial, primary, secondary, and tertiary follicles were significantly decreased, while ovarian fibrosis was significantly increased in Group 2 compared with Group 1 (p < 0.05). Co-treatment with oridonin statistically significantly increased follicle counts at all developmental stages and markedly reduced ovarian fibrosis in group 2 compared with group 3. Compared with Group 1, AMH decreased, whereas MDA, TNF-α, TGF-β1, SMAD3, and TIMP-1 increased in Group 2 (p < 0.001); these alterations were markedly attenuated in Group 3. Conclusions: These findings suggest that oridonin may exert protective effects against cisplatin-induced ovarian injury. Full article

Background/Objectives: Chronic kidney disease (CKD) is associated with numerous oral manifestations that may negatively affect quality of life, nutrition, and overall health. This narrative review aimed to summarize current evidence regarding oral manifestations of CKD and kidney transplantation, examine their proposed underlying mechanisms, and discuss implications for dental management. Methods: A structured literature search of PubMed/MEDLINE was conducted for English-language publications from January 2000 to March 2026. Original studies, systematic reviews, meta-analyses, clinical guidelines, and relevant narrative reviews were included. Additional references were identified through manual screening of bibliographies. Results: Oral manifestations associated with CKD include xerostomia, periodontal disease, oral infections, anemia-related mucosal pallor, developmental enamel defects, and medication-related gingival overgrowth. Kidney transplant recipients are additionally at risk of opportunistic infections and oral malignancies related to long-term immunosuppressive therapy. While oral diseases, particularly periodontal disease and oral infections, may contribute to systemic inflammation, much of the available evidence remains observational. Similarly, many recommendations for dental management are based on expert consensus and clinical experience rather than high-quality interventional studies. Conclusions: Oral complications are common throughout the CKD continuum and warrant regular assessment and preventive care. Multidisciplinary collaboration is essential, while further prospective studies are needed to strengthen the evidence base for clinical management. Full article

Bisphenol A (BPA) is a common industrial chemical primarily used in the manufacture of plastics, and it has been found in more than 90% of people worldwide. As an endocrine disruptor, BPA can impair reproduction, development, immunity, metabolism, and cognition; it also disturbs immune balance and thus fosters chronic inflammation. A number of population-based studies have indicated a link between environmental BPA exposure and atopic dermatitis (AD). Nevertheless, the detailed molecular pathways connecting BPA to AD remain poorly understood. AD is the leading chronic recurrent inflammatory skin disorder, characterized by severe itching and repeated eczema-like lesions. Its prevalence is roughly 13% among children and 5% among adults, and its global incidence continues to rise, imposing heavy health and economic burdens on societies. To clarify whether and how BPA may promote or worsen AD, we carried out a comprehensive computational study that integrated network toxicology, transcriptomic data, machine learning, molecular docking, and molecular dynamics simulations. From the CTD, ChEMBL, and SwissTargetPrediction databases, we collected 5701 potential BPA targets; from GeneCards and OMIM, we obtained 3270 genes linked to AD. The overlap between these two gene sets gave a group of common candidate genes. Enrichment analyses using GO and KEGG showed that these common genes were significantly overrepresented in the PI3K-Akt signaling pathway, Th17 cell differentiation, and the JAK-STAT signaling pathway—all central to immune and inflammatory regulation. We then built a protein–protein interaction (PPI) network by submitting the common genes to the STRING database and employed Cytoscape to extract hub genes from that network. By integrating human AD transcriptomic profiles with the hub genes and applying two machine learning techniques (LASSO and SVM), we identified six core toxic targets of BPA in AD: TIGIT, JAK3, IL22, S100A8, CCL2, and FCER1G. These six targets fall into two main functional categories: immune dysregulation and inflammatory cell infiltration. Subsequent molecular docking and molecular dynamics simulation experiments confirmed that BPA binds well to all six targets and can form stable complexes with them. Collectively, our findings offer a preliminary experimental foundation for future investigations into the pathogenesis of BPA-induced AD and provide important molecular evidence for understanding how environment–gene interactions contribute to complex inflammatory skin diseases such as AD. Full article