Search Results (1,453)

To further investigate the role of PKCλ/ι in Schistosoma japonicum-induced hepatic fibrosis, we employed a CD4⁺ T-cell-specific PKCλ/ι conditional knockout (KOSJ) mouse model, with wild-type (WTSJ) mice used as controls. Transcriptomic profiling of hepatic mRNA was used to reveal the immune regulatory mechanisms underlying the role of PKCλ/ι in the hepatic fibrosis caused by S. japonicum infection. Flow cytometry, RT–qPCR and ELISA were used to analyze the effects of PKCλ/ι on Tfh and Tfr cells, and single-cell RNA sequencing was used to elucidate the interactions between Tfr and B cells. The results showed that PKCλ/ι deficiency led to altered BCR signaling gene expression, reduced germinal center activity, and decreased anti-SEA antibody levels. Tfh cells and key factors including IL-21, CXCR5, and ICOS were downregulated, while Tfr cells and IL-10⁺ B cells increased. Additionally, hepatic neutrophils decreased and Treg/Tfr ratios rose, with enhanced IL-10-mediated cellular crosstalk. These findings indicate that PKCλ/ι deficiency attenuates liver fibrosis by inhibiting Tfh differentiation, promoting Tfr function, and activating IL-10-producing Breg cells, suggesting its potential as a therapeutic target. Full article

Colchicine, a natural alkaloid, has emerged as a promising anti-inflammatory therapy with applications in cardiovascular diseases, dermatological conditions, and COVID-19 management. Its mechanisms, including the modulation of neutrophil activity, the inhibition of the NLRP3 inflammasome, and the mitigation of cytokine storms, have expanded its therapeutic potential beyond traditional uses. This review synthesizes current evidence on colchicine’s clinical applications and mechanisms of action. In cardiovascular medicine, colchicine has been shown to reduce risks of pericarditis, coronary artery disease and atrial fibrillation. In dermatology, most evidence derives from small-scale studies, case series, and retrospective analyses, suggesting potential benefits in conditions such as leukocytoclastic vasculitis, cutaneous amyloidosis, and pemphigus, although these findings require confirmation through randomized controlled trials (RCTs). Emerging studies also indicate a potential role for colchicine in improving outcomes in severe COVID-19. Overall, colchicine demonstrates broad therapeutic utility, warranting further research to clarify its effectiveness across diverse clinical settings. Full article

Background: Sarcoidosis is a systemic granulomatous disease with a highly variable clinical course, and distinguishing it from other diseases and predicting its prognosis can be challenging. In recent years, hematological and biochemical parameters have been investigated as potential biomarkers for assessing inflammation and predicting disease prognosis. This study aimed to evaluate the prognostic value of the lactate dehydrogenase-to-albumin ratio (LAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR). Methods: This retrospective, single-center study included 369 newly diagnosed patients with sarcoidosis who were admitted between January 2020 and October 2024. Sarcoidosis was diagnosed based on current ERS, ATS, and WASOG guidelines. At the 6-month follow-up, patients’ clinical courses were classified as regression, stable, or progression based on clinical, radiological, and pulmonary function tests. The predictive values of various hematological and biochemical parameters were analyzed using statistical methods, including binary logistic regression analysis and ROC analysis. Results: A total of 369 patients were included in the study. At the 6-month follow-up, 63.4% of patients showed regression, 21.4% had a stable course, and 15.2% showed progression. The progression group had a significantly higher LAR (5.26 [4.21–7.76]) compared to the stable/regression group (4.59 [3.82–5.86]) (p = 0.033). Additionally, baseline FVC% (OR, 0.97; p = 0.036) and the presence of dyspnea (OR, 3.08; p = 0.03) were identified as independent risk factors for disease progression. No significant associations were found between NLR, PLR, LMR, and serum ACE levels and the clinical course. The cutoff value of LAR for predicting disease progression was 4.87 (AUC: 0.605), with a sensitivity of 58.8% and specificity of 59.7%. Conclusions: Our study, which is the first to evaluate the prognostic value of LAR in sarcoidosis, identified this parameter as a significant indicator for the clinical course. The finding of significantly higher LAR levels in patients with disease progression suggests its potential as a prognostic biomarker. These results may help guide treatment and follow-up strategies, although further large-scale prospective studies are needed for validation. Full article

Background: Coronary collateral circulation (CCC) plays a crucial protective role in patients with chronic total occlusion (CTO), mitigating ischemia and improving long-term outcomes. However, the degree of collateral vessel development varies substantially among individuals. Systemic inflammatory and nutritional status may influence this variability. The Naples Prognostic Score (NPS) is a composite index reflecting these parameters, yet its relationship with CCC remains incompletely defined. Methods: We retrospectively analyzed 324 patients with angiographically confirmed CTO at Selçuk University Faculty of Medicine between 2014 and 2025. Coronary collaterals were graded using the Rentrop classification, and patients were categorized as having poor (grades 0–1) or good (grades 2–3) collaterals. The NPS was calculated using serum albumin, cholesterol, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Baseline clinical and laboratory data were compared between groups. Univariate and multiple binary logistic regression analyses were performed to identify independent predictors of collateral development. Results: Of the 324 patients, 208 (64.2%) had poor and 116 (35.8%) had good collateral circulation. Patients with good collaterals had higher body mass index, HDL Cholesterol (HDL-C), and triglyceride levels, and significantly lower NPS values compared with those with poor collaterals (p < 0.05 for all). In multiple binary logistic regression analysis, HDL-C (OR 1.035; 95% CI 1.008–1.063; p = 0.011) and NPS (OR 0.226; 95% CI 0.130–0.393; p < 0.001) emerged as independent predictors of well-developed collaterals. Conclusions: Both NPS and HDL-C are independently associated with the degree of coronary collateral circulation in CTO patients. These findings highlight the interplay between systemic inflammation, nutritional status, lipid metabolism, and vascular adaptation. As simple and routinely available measures, NPS and HDL-C may serve as practical tools for risk stratification and identifying patients at risk of inadequate collateral formation. Prospective studies with functional assessments of collateral flow are warranted to confirm these associations and explore potential therapeutic interventions. Full article

Clinical studies have linked glyphosate exposure to substantial morbidity, with acute kidney injury occurring in some cases. Although the toxic effects of glyphosate-based herbicides (GBHs) have been reported in several studies, their molecular impact on renal function remains poorly understood. Given the kidney’s critical role in excretion, it is particularly susceptible to damage from xenobiotic exposure. In this study, we aim to identify N-glycomics and proteomics change in the kidney following chronic GBH exposure, to better understand the mechanisms behind glyphosate-induced kidney damage. Kidney tissues from female and male rats were analyzed using liquid chromatography–tandem mass spectrometry. The results revealed notable changes in the N-glycan composition, particularly in the fucosylated and sialofucosylated N-glycan types. The proteomic analysis revealed the activation of immune signaling and inflammatory pathways, including neutrophil degranulation, integrin signaling, and MHC class I antigen presentation. Transcription regulators, such as IL-6, STAT3, and NFE2L2, were upregulated, indicating a coordinated inflammatory and oxidative stress response. Sex-specific differences were apparent, with female rats exhibiting more pronounced alterations in both the N-glycan and protein expression profiles, suggesting a higher susceptibility to GBH-induced nephrotoxicity. These findings provide new evidence that chronic GBH exposure may trigger immune activation, inflammation, and potentially carcinogenic processes in the kidney. Full article

Introduction: Sepsis-induced cardiac dysfunction (SICD) is a transient cardiac disfunction, with variable described prevalence and uncertain prognostic. This study aimed to characterize the laboratory and microbiological findings in critically ill patients with sepsis who developed left ventricular (LV) or biventricular systolic dysfunction. Methods: Patients who required intensive care unit hospitalization for sepsis were screened retrospectively. Only patients with positive cultures and echocardiography performed within 24 h from admission were included. The exclusion criteria were infective endocarditis, acute coronary syndrome, history of cardiomyopathy, severe valve disease, end-stage organ or oncological disease. Cardiac function was appreciated on transthoracic echocardiography, using LV ejection fraction for the left ventricle and tricuspid annular plane systolic excursion (TAPSE) for the right ventricle. SICD was confirmed if the systolic dysfunction found upon admission was reversible within 7–10 days. Results: A total of 100 patients with positive cultures were included. The median age was 73 and 55% were male. SICD was diagnosed in 14% of patients. Patients with SICD were more likely to develop septic shock and had longer hospital and intensive care unit stay. In-hospital mortality was 44% with no significant difference between SICD and non-SICD patients. Laboratory markers upon hospital admission showed that SICD patients had significantly higher values of lactate and transaminases. Cardiac (troponin and NT-proBNP) and inflammation markers (leukocytes, neutrophils, NLR, C-reactive protein, procalcitonin) had higher values in patients with SICD but the difference did not reach statistical significance. Streptococcal infections and polymicrobial cultures were risk factors for developing SICD. Higher rates of infections with Enterobacterales were seen in the SICD group but the difference was not significant. Conclusions: SICD patients had higher lactate, inflammation, and cardiac biomarkers levels upon admission and significantly higher rates of streptococcal infections and polymicrobial cultures. Full article

Neutrophils are among the first cells to be recruited to the lungs during Chlamydia pneumoniae infection in mouse models; however, their regulatory functions are not yet fully understood. This study examined the mechanisms and significance of IL-10-producing neutrophils throughout C. pneumoniae pulmonary infection in C57BL/6 mice. Our findings revealed that infection with C. pneumoniae induces IL-10 secretion in bone marrow-derived neutrophils, depending on Toll-like receptor 2 (TLR2) activation. This process involves TLR2-dependent mitochondrial reactive oxygen species (ROS) production, which triggers the endoplasmic reticulum (ER) stress pathway, including IRE1α and subsequent Xbp1 splicing. Inhibition of this pathway or depletion of neutrophils (using the 1A8 monoclonal antibody) significantly reduces IL-10 levels in bronchoalveolar lavage fluid (BALF) in vivo. Conversely, the absence of IL-10-producing neutrophils, whether through depletion or TLR2 deficiency, leads to increased IL-12p70 and IFN-γ-positive NK cells, along with decreased regulatory T cells and M2-like macrophages. This results in a lower bacterial burden in the lungs but causes more severe pulmonary damage and decreased survival rates. These findings highlight that IL-10 produced by neutrophils via the TLR2-mitochondrial ROS–ER stress pathway is essential for modulating pulmonary immune responses and maintaining immune homeostasis during C. pneumoniae infection, thereby preventing excessive inflammation and tissue damage. Full article

Sugarcane wax-derived policosanol (POL) is well recognized for its multifaceted biological activities, particularly in dyslipidemia management, whereas sugar cane extract powder (SEP), prepared from whole sugar juice blended with supplementary components, has not been thoroughly investigated for its biological activities and potential toxicities. Herein, the comparative dietary effect of four distinct SEPs (SEP-1 to SEP-4) and Cuban sugarcane wax extracted POL were examined to prevent the pathological events in high-cholesterol diet (HCD)-induced hyperlipidemic zebrafish. Among the SEPs, a 14-week intake of SEP-2 emerged with the least zebrafish survival probability (0.75, log-rank: χ² = 14.1, p = 0.015), while the POL supplemented group showed the utmost survival probability. A significant change in body weight and morphometric parameters was observed in the SEP-2 supplemented group compared to the HCD group, while non-significant changes had appeared in POL, SEP-1, SEP-3, and SEP-4 supplemented groups. The HCD elevated total cholesterol (TC) and triglyceride (TG) levels were significantly minimized by the supplementation of POL, SEP-1, and SEP-2. However, an augmented HDL-C level was only noticed in POL-supplemented zebrafish. Likewise, only the POL-supplemented group showed a reduction in blood glucose, malondialdehyde (MDA), AST, and ALT levels, and an elevation in sulfhydryl content, paraoxonase (PON), and ferric ion reduction (FRA) activity. Also, plasma from the POL-supplemented group showed the highest antioxidant activity and protected zebrafish embryos from carboxymethyllysine (CML)-induced toxicity and developmental deformities. POL effectively mitigated HCD-triggered hepatic neutrophil infiltration, steatosis, and the production of interleukin (IL)-6 and inhibited cellular senescence in the kidney and minimized the ROS generation and apoptosis in the brain. Additionally, POL substantially elevated spermatozoa count in the testis and safeguarded ovaries from HCD-generated ROS and senescence. The SEP products (SEP-1, SEP-3, and SEP-4) showed almost non-significant protective effect; however, SEP-2 exhibited an additive effect on the adversity posed by HCD in various organs and biochemical parameters. The multivariate examination, employing principal component analysis (PCA) and hierarchical cluster analysis (HCA), demonstrates the positive impact of POL on the HCD-induced pathological events in zebrafish, which are notably diverse, with the effect mediated by SEPs. The comparative study concludes that POL has a functional superiority over SEPs in mitigating adverse events in hyperlipidemic zebrafish. Full article

Postpartum uterine diseases such as metritis and endometritis impair reproductive performance and cause substantial economic losses in dairy cows worldwide. The multifactorial etiology, involving polymicrobial infections and complex host immune responses, poses diagnostic and therapeutic challenges. Traditional treatments rely on antibiotics, e.g., cephalosporins like ceftiofur and cephapirin, with broad-spectrum efficacy. However, emerging antimicrobial resistance, biofilm formation by pathogens such as Trueperella pyogenes, Fusobacterium necrophorum, and Escherichia coli, and bacterial virulence factors have reduced effectiveness of conventional therapies. Advances in systems biology, particularly proteomics, metabolomics, and microRNA (miRNA) profiling, have provided unprecedented insights into the molecular mechanisms underpinning uterine disease pathophysiology. Proteomic analyses reveal dynamic changes in inflammatory proteins and immune pathways, whereas metabolomics highlight shifts in energy metabolism and bacterial–host interactions. Furthermore, miRNAs have critical roles in post-transcriptional gene regulation affecting immune modulation, inflammation, and tissue repair, and also in modulating neutrophil function and inflammatory signaling. Uterine inflammation not only disrupts local tissue homeostasis but also compromises early embryo development by altering endometrial receptivity, cytokine milieu, and oocyte quality. Integration of multi-omics approaches, combined with improved diagnostics and adjunct therapies—including micronutrient supplementation and immunomodulators—offers promising avenues for enhancing disease management and fertility in dairy herds. This review synthesizes current knowledge on proteomics, metabolomics, and miRNAs in postpartum uterine diseases and highlights future directions for research and clinical applications. Full article

The compatible solute ectoine is known to attenuate inflammatory effects in the airways after exposure to combustion-derived nanoparticles. Pro-inflammatory signaling in epithelial cells, as well as antiapoptotic mechanisms in neutrophilic granulocytes, both triggered by particles, are reduced by this substance. Here we investigated the preventive potential in airway inflammation of additional compounds originating from the ectoine metabolism, Nγ-acetyl-L-2,4-diaminobutyric acid (NADA), and 5-hydroxyectoine in a mouse model and in human neutrophilic granulocytes. Furthermore, effects of these molecules on the reduction in cystic fibrosis transmembrane conductance regulator (CFTR), as an additional pathogenic endpoint of nanoparticle exposure, were investigated. All three solutes exhibited beneficial effects at the level of inflammatory cells in lung lavages from exposed mice. The decrease in CFTR in lung tissue of exposed mice was mitigated by the substances. In primary human neutrophils and in neutrophilic differentiated HL-60 cells, the delay of apoptosis rates after particle exposure was effectively abolished. The decline in CFTR from the cytoplasmic membrane in neutrophilic cells was also counteracted by the compatible solutes. The data identify both NADA and 5-hydroxyectoine as additional substances for molecular prevention of airway effects of environmental particles. Furthermore, the reduction in CFTR might be a relevant finding for patients suffering from impaired function of this ion channel. Full article

Medicinal plants remain central to traditional healthcare, yet their increasing integration into modern pharmacology necessitates robust toxicological evaluation. Origanum majorana L. (sweet marjoram), widely used in culinary and folk medicine, contains diverse secondary metabolites with both therapeutic and potential genotoxic activities. Despite its popularity, systematic in vivo and in vitro safety assessments remain limited. This study aimed to comprehensively evaluate the acute oral toxicity, cytotoxicity, and genotoxicity of O. majorana methanolic extract, providing baseline toxicological data to support its safe traditional use and potential pharmaceutical applications. The methanol extract of O. majorana leaves was tested in NIH-3T3 fibroblasts for cytotoxicity and genotoxicity. In vivo acute oral toxicity was assessed in rats according to OECD Guideline 420, with animals monitored over 14 days for clinical signs, hematological and biochemical alterations, and histopathological changes. The extract preserved fibroblast viability above 90% across all tested concentrations (10–200 µg/mL), indicating absence of cytotoxicity. However, comet and micronucleus assays revealed dose-dependent DNA damage, suggesting genotoxic potential at higher exposures. In vivo, no mortality or overt systemic toxicity was observed at doses up to 2000 mg/kg. Hematological analyses showed immunomodulatory shifts (increased neutrophils and monocytes, reduced eosinophils), while biochemical profiles indicated hepatoprotective and cardioprotective effects, with reduced ALT, AST, and LDH levels. Histopathological evaluation revealed only mild, focal changes consistent with adaptive rather than irreversible responses. O. majorana extract demonstrates a favorable acute safety profile with preserved hepatic and renal function, hematological modulation, and absence of in vitro cytotoxicity. Nevertheless, dose-dependent genotoxicity warrants caution for concentrated formulations. According to GHS classification, the extract aligns with Category 5 (acute oral toxicity, lowest hazard) and Category 2 (germ cell mutagenicity). These findings underscore the importance of dose management and further long-term genotoxicity studies before translational applications in nutraceutical or biomedical fields. Full article

Background/Objectives: Chronic kidney disease (CKD) progression is strongly influenced by systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR), derived from routine blood counts, reflects the balance between innate and adaptive immunity and has been proposed as a marker of adverse renal outcomes. We hypothesized that elevated baseline NLR is associated with reduced kidney function and increased risk of progression to end-stage kidney disease (ESKD) in adults with non-dialysis CKD. Methods: Following PRISMA guidelines, we systematically searched MEDLINE, Embase, and Scopus for studies enrolling adults with CKD stages 1–4 that reported renal outcomes according to baseline NLR. The primary outcome was progression to ESKD or renal replacement therapy (RRT) initiation. Results: Six eligible studies were identified, of which four provided sufficient data for meta-analysis. Across cohorts, elevated baseline NLR was consistently associated with adverse renal outcomes. In pooled analyses, high NLR nearly doubled the risk of ESKD or RRT (RR 1.96, 95% CI 1.30–2.97). Leave-one-out sensitivity analysis strengthened the association while reducing heterogeneity. For kidney function, higher NLR was associated with lower baseline eGFR (SMD −1.59, 95% CI −2.38 to −0.80). Conclusions: Elevated NLR is a robust prognostic marker of renal function decline and progression to ESKD or RRT in non-dialysis CKD. As a simple and inexpensive biomarker, NLR offers additional predictive value beyond eGFR and albuminuria. Incorporating NLR into risk models may refine stratification, guide follow-up, and enable earlier therapeutic optimization. Prospective large studies are warranted to establish thresholds and validate its role in clinical practice. Full article

Acute kidney injury (AKI) is a frequent and severe complication in trauma patients, affecting up to 28% of intensive care unit (ICU) admissions and contributing significantly to morbidity, mortality, and long-term renal impairment. Trauma-related AKI (TRAKI) arises from diverse mechanisms, including hemorrhagic shock, ischemia–reperfusion injury, systemic inflammation, rhabdomyolysis, nephrotoxicity, and complex organ crosstalk involving the brain, lungs, and abdomen. Pathophysiologically, TRAKI involves early disruption of the glomerular filtration barrier, tubular epithelial injury, and renal microvascular dysfunction. Inflammatory cascades, oxidative stress, immune thrombosis, and maladaptive repair mechanisms mediate these injuries. Trauma-related rhabdomyolysis and exposure to contrast agents or nephrotoxic drugs further exacerbate renal stress, particularly in patients with pre-existing comorbidities. Traditional markers such as serum creatinine (sCr) are late indicators of kidney damage and lack specificity. Emerging structural and stress response biomarkers—such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), C-C motif chemokine ligand 14 (CCL14), Dickkopf-3 (DKK3), and the U.S. Food and Drug Administration (FDA)-approved tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein 7 (TIMP-2 × IGFBP-7)—allow earlier detection of subclinical AKI and better predict progression and the need for renal replacement therapy. Together, functional indices like urinary sodium and fractional potassium excretion reflect early microcirculatory stress and add clinical value. In parallel, risk stratification tools, including the Renal Angina Index (RAI), the McMahon score, and the Haines model, enable the early identification of high-risk patients and help tailor nephroprotective strategies. Together, these biomarkers and risk models shift from passive AKI recognition to proactive, personalized management. A new paradigm that integrates biomarker-guided diagnostics and dynamic clinical scoring into trauma care promises to reduce AKI burden and improve renal outcomes in this critically ill population. Full article

Chronic kidney disease (CKD) poses a global burden affecting over 10% of the adult population worldwide. Acute kidney injury (AKI) is an important cause of CKD, especially following severe and repeated episodes. However, the processes underpinning progressive and chronic renal deterioration after AKI are only incompletely understood. Thus, models reproducing this scenario are needed to study the pathophysiological mechanisms involved and identify biomarkers and molecular targets for diagnostic and therapeutic purposes. In this study, we developed a rat model of 3 serial AKIs leading to CKD, in which renal function, kidney structure and fibrosis, and urinary injury biomarkers were studied over a period of 9 months, alongside a traditional model of CKD caused by renal mass reduction. Our results show that consecutive AKIs eventually develop key features of CKD including progressive fibrosis and albuminuria. Renal injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), and retinol binding protein 4 (RBP4) show distinct evolution patterns suggestive of specific but undetermined damages with different time courses. The chronic evolution of renal tissue degeneration and dysfunction following serial AKIs closely resembles those observed after extensive renal mass reduction, which indicates chronic degeneration. Finally, a clear dissociation in the evolution of interstitial fibrosis (progressively increasing) and of glomerular filtration (mainly stable) was observed in both models. This questions the consuetudinary paradigm ascribing an etiological role to fibrosis in progressive renal dysfunction. Full article

Background: Studying the genetic characteristics and molecular mechanisms of immune regulation in horses is of great significance for protecting their genetic resources, improving breeding strategies, and enhancing their disease resistance, thereby ensuring their healthy performance in both sports and production. Aims/objectives: This study investigates the genetic characteristics and molecular mechanisms underlying immune regulation in Yili horses, comparing them with Thoroughbreds and Kazakh horses. Methods: Blood samples from each breed were analyzed for physiological, biochemical, and immune indices alongside transcriptome sequencing to identify differentially expressed genes (DEGs). Results: The results revealed significant differences in neutrophil counts, monocytes, red blood cell parameters, glucose levels, and immunoglobulins (IgA, IgG, IgM) among breeds. Yili horses exhibited intermediate values for most parameters, aligning more closely with Thoroughbreds. Transcriptomic analysis identified 3574 DEGs, enriched in immune-related pathways such as platelet activation, antigen processing, and cytokine signaling. Key genes, including TNFRSF14, IFIT3, and IL21R, correlated with immune traits, highlighting hybrid vigor in Yili horses. Functional enrichment underscored pathways like IL-17 signaling and NF-κB regulation, linking genetic differences to immune adaptability. Conclusions: These findings provide molecular insights into breed-specific immune traits, supporting strategies to enhance disease resilience in Yili horses while preserving their athletic performance. This study underscores the importance of integrating transcriptomic and phenotypic data for informed breeding practices in equine conservation and improvement. Full article