Search Results (72,368)

Background: Myocardial ischemia–reperfusion during cardiac surgery is associated with complex metabolic alterations that reflect both myocardial injury and recovery. This prospective study aimed to characterize intraoperative lactate, pH, and bicarbonate dynamics in paired coronary sinus (CS) and peripheral blood samples and to explore whether these responses could be integrated into a composite marker of reperfusion-related metabolic burden (RMB). Methods: We prospectively studied 101 patients undergoing cardiac surgery with cardiopulmonary bypass. Simultaneous blood samples from the CS and peripheral circulation were obtained before aortic cross-clamping (T0), immediately after declamping (T1), and 10 min after reperfusion (T2). Temporal changes and transmyocardial gradients of lactate, pH, and bicarbonate were analyzed. RMB was calculated from standardized changes in these variables. As an exploratory analysis, associations with in-hospital mortality were evaluated using receiver operating characteristic (ROC) analysis. Results: Significant temporal variations in metabolic parameters were observed, with the most pronounced transmyocardial disturbances occurring at aortic declamping. Lactate demonstrated the largest gradient during early reperfusion, accompanied by transient acidosis and bicarbonate consumption. The RMB framework integrated these coordinated metabolic responses into a single measure of reperfusion stress. In exploratory outcome analyses, higher RMB values were observed among non-survivors, with the largest observed AUC for peripheral RMB measured 10 min after reperfusion (AUC 0.87). However, these estimates were based on only seven deaths and should be considered hypothesis-generating. Conclusions: Paired CS and peripheral sampling revealed dynamic metabolic adaptations during myocardial ischemia–reperfusion. The exploratory RMB framework integrates coordinated metabolic changes into a single descriptive measure of reperfusion-related stress. Its observed associations with in-hospital mortality remain preliminary and require confirmation through external validation and evaluation in larger independent prospective cohorts. Full article

Antimicrobial proteinaceous postbiotic substances (PS) and/or bacteriocins can beneficially influence animal health, as previously shown with enterocins from non-autochthonous enterococcal strains. Therefore, the effectiveness of PS 412, produced by our beneficial autochthonous strain Enterococcus faecium EF 412, was assessed in horses. In the pilot experiment, PS 412 was administered to 12 horses of various ages and breeds for 21 days via a small feed ball. Sampling was performed on days 0/1, 21, and 42 (after a 3-week cessation of PS 412). The horses served as their own controls. Although the number of horses was limited, the microbiological analysis showed significant decreases in enterococci, other lactic acid bacteria, and campylobacters (p < 0.05; p < 0.001). Staphylococci decreased slightly. Coliforms, aeromonads (p < 0.001), and pseudomonads also decreased. In next-generation sequencing at the phylum level, 15 phyla were detected at higher abundance, with Bacteroidota (35.38%) and Bacillota (32.25%) the most abundant. After PS 412 (activity 51,200 AU/mL), the relative abundance of several phyla decreased. On day 21, phagocytic activity was higher (69.00 ± 3.91%). The metabolic profiles and hematologic values were mostly within the reference range. Although continued testing is necessary, postbiotics appear to be a tool for supporting equine health. Full article

Background/Objectives: Methylglyoxal-derived hydroimidazolone-1 (MG-H1), an advanced glycation end product, has implications in the pathogenesis of diabetic kidney disease (DKD). Although liquid chromatography–mass spectrometry is the current gold standard for quantifying MG-H1, its overall complexity limits its utility. We developed an ELISA to measure MG-H1 using a specific monoclonal antibody. Methods: Competitive ELISA was used to quantify total, high-molecular-weight (HMW), and low-molecular-weight (LMW) MG-H1 in serum. The assay’s specificity was validated against structurally related compounds. Spike-and-recovery experiments were conducted to assess accuracy and precision. Serum samples from healthy controls, diabetic patients without kidney disease, and patients with DKD were analyzed (n = 10, 23, and 19, respectively). MG-H1’s correlation with renal biomarkers and diagnostic performance was assessed using receiver operating characteristic analyses. Results: The ELISA exhibited preferential reactivity toward MG-H1 compared with structurally related compounds. Spike-and-recovery experiments resulted in recovery rates ranging 108–119%. MG-H1 levels were increased in patients with DKD, although the magnitude of the changes varied among the MG-H1 forms. All MG-H1 forms correlated positively with serum creatinine and blood urea nitrogen, and negatively with estimated glomerular filtration rate. No significant correlations were observed with glycoalbumin, and only a modest association was observed between LMW MG-H1 and HbA1c. Exploratory ROC analyses suggested that all MG-H1 forms could discriminate DKD from DM, with total and HMW MG-H1 showing performance comparable to that of conventional renal function markers. Conclusions: This competitive ELISA enables high-throughput quantification of MG-H1 in serum and demonstrates analytical feasibility; further multicenter validation is required before clinical implementation. Full article

Major depressive disorder (MDD) is a heterogeneous psychiatric disorder characterized by impaired mood, neuroplasticity, neuroinflammation, and dysregulated stress response systems. Chronic stress can induce epigenetic changes leading to depression. Evidence suggests that histone acetylation and deacetylation are epigenetic processes involved in changes in gene expression. Histone deacetylases (HDACs) modulate chromatin structure and transcription, and their dysregulation is associated with stress susceptibility, decreased brain-derived neurotrophic factor (BDNF) signaling, impaired synaptic plasticity, and inflammatory activation. HDAC isoforms HDAC3 and HDAC6 have emerged as epigenetic regulators in stress-induced depression. HDAC3 is a transcriptional regulator involved in neuroplasticity-related gene expression, inflammatory signaling, and glucocorticoid receptor-mediated stress responses. In contrast, HDAC6 is cytoplasmic and regulates non-histone substrates involved in microtubule dynamics, synaptic function, protein trafficking, and the regulation of the hypothalamic–pituitary–adrenal axis (HPA axis). Preclinical studies show that HDAC3 or HDAC6 inhibition can exert antidepressant-like effects by promoting neuroplasticity, reducing neuroinflammation, and restoring stress-related signaling. Dual targeting is an interesting therapeutic approach because both regulate complementary mechanisms. However, clinical translation is limited by poor blood–brain barrier penetration, systemic toxicity, insufficient isoform selectivity, and a lack of clinical evidence. This review summarizes the roles and mechanisms of HDAC3 and HDAC6, the rationale for dual targeting, translational limitations, and future therapeutic perspectives. Full article

Background/Objectives: Dietary inflammation may influence cardiometabolic health, yet the gut mycobiome and bacterial–fungal interactions remain unclear. Building upon our earlier findings and data from the TALENTs trial (Targeting Aging and Longevity with Exogenous Nucleotides) baseline data, we explored gut fungal profiles and bacterial–fungal co-occurrence patterns in relation to the Dietary Inflammatory Index (DII) and Life’s Essential 8 (LE8) in older adults. Methods: We enrolled 301 community residents aged 60–70 years, with 285 providing qualified fungal internal transcribed spacer (ITS) sequencing data. DII scores were derived from 3-day dietary records to reflect dietary inflammatory risk, and LE8 (integrating health behaviors including physical activity and metabolic health factors including BMI, blood lipids, blood pressure, and blood glucose) was used to assess cardiovascular health; LE8_non-diet was applied as a sensitivity measure. Fungal diversity, genus-level taxa, ecological guilds, and bacterial–fungal associations were analyzed using diversity indices, ZINB/Hurdle models, bootstrap, E-values, DIABLO analysis, and network construction. Results: DII showed an inverse correlation with LE8_non-diet (r = −0.130, p = 0.024). Fungal alpha and beta diversity did not differ significantly across DII-defined groups. Conversely, better cardiovascular status was linked to higher fungal richness, with significantly elevated Chao1 and ACE indices in the high-CVH group (both p < 0.05). Additionally, integrated ZINB, Hurdle, and stability analyses jointly pinpointed four candidate fungal genera that correlated with both DII and LE8. Both ZINB and DIABLO analyses consistently indicated that antagonistic interactions dominated gut bacterial–fungal associations (89.9% vs. 63.8% of negative associations, respectively), with DIABLO further revealing synchronized community-level co-variation between the two kingdoms (r = 0.325, p < 0.01). FUNGuild prediction further revealed saprotrophic guilds enriched in the high-CVH group and host-associated guilds in the low-CVH group, with similar patterns across DII-defined groups. Conclusions: This cross-sectional study reveals gut mycobiome profiles and potential bacterial–fungal co-occurrence patterns among older adults stratified by dietary inflammatory potential and cardiovascular health status, generating testable hypotheses for subsequent nutritional and metabolic research integrating lifestyle behaviors and functional health outcomes. Full article

Background/objectives: Multidrug-resistant and extensively drug-resistant Gram-negative pathogens are a major cause of severe ocular infections, yet treatment options are increasingly compromised by escalating antibiotic resistance. Membrane-active peptides (colistin and Mel4) offer the potential to restore antibiotic susceptibility. This study investigated the efficacy of peptide- and colistin-based adjuvant strategies in enhancing the activity of conventional antibiotics. Methods: Antibacterial activity was assessed using MIC/MBC testing, checkerboard assays, time–kill kinetics, and biofilm disruption studies, supported by confocal microscopy. Toxicity was assessed using L929 fibroblasts and red blood cells. A mechanistic study was performed with a membrane permeability assay. Results: Clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae showed high resistance to six antibiotic classes (up to MICs > 2048 mg/L), while polymyxin B and colistin remained active (MIC ≤ 2 mg/L). Mel4 displayed variable activity (MIC 7.8–500 mg/L). A total of 102 antibiotic–antibiotic, antibiotic–Mel4, and antibiotic–colistin combination tests were performed, of which 45 showed synergistic interactions. Combining traditional antimicrobials with either colistin or Mel4 restored antibiotic susceptibility, reducing MICs up to 2048-fold. Aminoglycoside–colistin combinations significantly lowered MICs, especially against K. pneumoniae. Time–kill assays confirmed rapid bactericidal effects (>3 log10 reduction in 3 h). The ciprofloxacin–Mel4 combination effectively disrupted biofilms (62–92%) with low toxicity and high cell viability. Membrane permeability assays showed that ciprofloxacin has limited activity, whereas both Mel4 and the ciprofloxacin–Mel4 combination showed enhanced activity across concentration gradients and over time. Conclusions: Membrane-active antimicrobials, colistin and Mel4, enhance conventional antibiotics against multidrug- and extensively drug-resistant ocular Gram-negative pathogens by restoring susceptibility, accelerating bactericidal effects, and disrupting biofilms. With low toxicity, these combinations represent promising therapeutic strategies for severe multidrug-resistant ocular infections. Full article

Pestivirus infections, including those caused by Border disease virus (BDV), are associated with reproductive disorders, neonatal losses, and persistent infections in sheep, potentially resulting in substantial economic losses. This study aimed to determine the animal- and herd-level pestivirus seroprevalence among sheep in Konya Province, Türkiye, to investigate evidence of current infection, and to identify factors associated with seropositivity. Serum and whole-blood samples were collected from 280 sheep in 16 herds. Serum samples were tested for pestivirus antibodies by competitive ELISA, while whole-blood samples were examined for pestiviral antigen and RNA by antigen ELISA and real-time RT-PCR, respectively. Epidemiological associations were evaluated using generalized estimating equations (GEE), with herd included as the clustering variable. Pestivirus antibodies were detected in 168 of 280 sheep, corresponding to an animal-level pestivirus seroprevalence of 60.00% (95% confidence interval (CI): 54.16–65.57). At the herd level, 14 of 16 herds (87.5%) had at least one seropositive animal, while herd-specific antibody seropositivity ranged from 0% to 82.76%. Four animals were antigen-reactive at the initial sampling, and one remained so at the 15-day retest; however, all samples were negative by real-time RT-PCR. Therefore, persistent infection could not be confirmed. In the multivariable GEE model, animal age, herd disease history, and the introduction of new animals into the herd were significantly associated with pestivirus seropositivity. Together with previous studies from Türkiye, our findings indicate that pestivirus exposure remains common in sheep populations and warrants continued regional surveillance. Serological screening should therefore be complemented by direct detection methods, including antigen ELISA and real-time RT-PCR, when investigating current or persistent pestivirus infection. Informing herd owners about pestivirus infections and appropriate biosecurity measures may also contribute to reducing their potential impact on animal health and production. Full article

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with malignancy. Biomarkers of hypercoagulability and thromboinflammation may improve risk stratification and support personalised thromboprophylaxis, but evidence remains heterogeneous, particularly in cervical cancer. A systematic review was conducted according to PRISMA 2020. PubMed/MEDLINE, Scopus, Embase, and Web of Science were searched for studies published between January 2009 and March 2025 evaluating biological, molecular, genetic, and imaging biomarkers associated with hypercoagulability and thromboinflammation in women withcervical cancer. Evidence from breast cancer and broader CAT studies was incorporated to provide translational context. Owing to substantial methodological heterogeneity, findings were synthesised qualitatively. Twenty-five cervical cancer studies met eligibility criteria. D-dimer was the most extensively investigated biomarker and was consistently associated with VTE risk, although specificity was limited. Biomarkers of thrombin generation and fibrinolytic activation, including thrombin–antithrombin complexes, prothrombin fragment 1+2, and plasmin–α2-antiplasmin complex, demonstrated greater mechanistic specificity. Multimarker panels integrating coagulation, fibrinolysis, endothelial injury, platelet activation, and inflammation showed superior predictive performance compared with single biomarkers. Emerging biomarkers, including circulating tumour DNA, extracellular vesicles, and microRNAs, further supported tumour-driven thromboinflammation. SERPINE1 and F2 gene variants were associated with thrombotic risk and adverse prognosis. Current evidence supports further evaluation of integrated multimodal biomarker strategies for CAT risk assessment, but prospective, standardised, tumour-specific studies are required before biomarker-guided approaches can be implemented in clinical practice. Full article

The renin–angiotensin system (RAS) and vasopressin system (VAS) play an essential role in the regulation of multiple vital body functions. A survey of the literature provides evidence that the central and systemic RAS and VAS are activated during pregnancy and cooperate in the regulation of blood circulation and in the exchange of substrates and metabolites between the mother and fetus. The present review is focused on the engagement of the RAS and VAS in the regulation of blood circulation in healthy pregnant women and fetuses and in gestations complicated by cardiovascular, metabolic and psychogenic diseases. The presence of several components of the RAS and VAS, such as renin, angiotensin-converting enzymes (ACE1, ACE2), angiotensins [Ang II, Ang-(1–7)], angiotensin receptors (AT1R, AT2R), and AVP receptors (V1aR), in the placenta and the myometrium allows us to assume that the RAS and VAS play a prominent role in function of the maternal–placental–fetal unit. Gestation is also associated with the activation of components of the RAS and VAS in appropriate regions of the central nervous system that are involved in the regulation of blood pressure. Experimental studies suggest that the RAS and VAS participate in the autonomic control of blood circulation and in the regulation of emotional aspects of pregnancy and maternity. Abnormal functioning of the RAS and/or VAS was found in eclampsia, metabolic diseases (diabetes mellitus) and psychogenic disorders (anxiety, stress, and depression). Some of these abnormalities may have an immunological or genetic background. In eclampsia, the presence of specific agonistic angiotensin receptor autoantibodies (AT1-AA) and altered genotypes of AGT, ACE2, AT1R, and AT2R were reported. Polymorphism of the AVP promoter was also described. Inappropriate pharmacotherapy or toxic environmental pollution may disturb the regulation of the cardiovascular system of the mother and fetus by the RAS and VAS during gestation. Further studies are necessary to better recognize the mechanisms of action of the RAS and VAS in healthy and pathological pregnancies. Full article

We propose an entropy-stable numerical scheme for an augmented one-dimensional blood flow model by constructing an explicit diffusion operator independent of the reconstruction method used for the scaled entropy variables. The diffusion term plays an important role in entropy-stable schemes, i.e., schemes satisfying a discrete entropy inequality. In general, the diffusion operator involves a diffusion matrix that depends on the scaled right eigenvectors and on the reconstruction of the scaled variables. We derive a simple, explicit expression for this operator that avoids computing the full set of scaled eigenvectors. The performance of the scheme is assessed through numerical experiments, focusing on Riemann problems, which confirm its ability to capture shock waves accurately and provide numerical evidence of entropy decay for non-smooth solutions. Full article

Cryptosporidiosis is a significant zoonotic disease caused by Cryptosporidium species, primarily Cryptosporidium parvum, leading to serious economic losses in neonatal calves; the absence of an approved vaccine or fully effective treatment necessitates alternative therapeutic approaches. This study evaluated the therapeutic efficacy of albendazole (20 mg/kg, orally, 5 days) in naturally infected neonatal calves, comparing it to paromomycin (100 mg/kg, orally, 5 days) and an albendazole + paromomycin combination. Forty-eight Simmental calves (36 naturally infected, mean age of 14 days, and 12 healthy controls) were included. Infection was confirmed by rapid immunochromatographic tests, carbol fuchsin staining, nested PCR, and RFLP, identifying C. parvum as the causative agent. Fecal and blood samples were collected on days 0, 3, 7, 10, 20, and 30, alongside clinical evaluations and live weight measurements. Oocyst shedding declined significantly over the study period in all three treatment groups, with the paromomycin and albendazole + paromomycin groups showing a numerically earlier decline than the albendazole group; however, no statistically significant differences among the three treatment groups were detected at any individual sampling day. Fecal scores paralleled oocyst shedding patterns. No significant differences were detected among treatment groups in hematological, biochemical, or hepatorenal safety parameters. Albendazole demonstrated efficacy in reducing oocyst shedding in Cryptosporidium infection, suggesting it may serve as a viable alternative treatment option in field conditions. Full article

Rare earth elements (REEs) are increasingly recognized as modulators of male reproductive health. This review presents the first comprehensive and critical analysis of the detrimental and potentially beneficial effects of REEs on male vertebrate reproductive function. In vivo and in vitro studies show that elements, particularly Gadolinium, Lanthanum, and Yttrium, share a toxicological profile characterized by oxidative stress, inflammation, mitochondrial dysfunction, endocrine disruption, and impairment of the blood–testis barrier. These mechanisms converge on both somatic and germ cell populations, ultimately compromising spermatogenesis and hormonal balance. Limited epidemiological data in humans are consistent with experimental findings, indicating inverse associations between seminal REE levels and sperm quality. CeO₂ nanoparticles represent an exception, showing dose-dependent duality: although some murine studies describe toxic effects, a broader and more consistent body of evidence indicates their protective action by restoring testicular homeostasis in diabetic models, in rats exposed to pesticides, pharmacological agents or irradiation, and in in vitro-treated spermatozoa. Preliminary data on Yttrium (YO) and Gadolinium (GdVO₄) nanoparticles similarly point to protective effects under pathological conditions, whereas Neodymium and Samarium show reproductive toxicity, including hormonal disruption and impaired sperm quality. Overall, REEs cannot be considered a homogeneous class: some pose reproductive hazards, others show potential biomedical utility. A systematic, mechanistic research framework is needed to resolve these dualities. It should contextualise reproductive risks in relation to the growing environmental and occupational exposure to REEs, while simultaneously exploring the biomedical potential of those elements that exhibit protective profiles. Full article

A healthy 65-year-old postmenopausal woman with a 15-year history of copper intrauterine device use presented to the emergency room with several days of lower abdominal pain and diarrhea. Laboratory testing revealed leukocytosis (white blood cell count, 26.15 × 10³/µL) and elevated C-reactive protein (19.81 mg/dL). Contrast-enhanced computed tomography demonstrated multiple cystic and heterogeneous abdominopelvic lesions, including extension across the abdominal wall fascia and muscles, with involvement of the uterus and urinary bladder, raising suspicion for advanced gynecologic malignancy with peritoneal dissemination. Tumor markers were within normal limits. Persistent lower abdominal pain and inflammatory markers without fever and negative blood culture after a week of empirical antibiotics (Flomoxef Sodium 2000 mg) prompted exploratory laparotomy to evaluate for possible ovarian malignancy or abscess. Total hysterectomy, right salpingo-oophorectomy, partial excision of the abdominal abscess, and drainage of the left ovarian abscess were performed. Histopathology later confirmed the diagnosis of diffuse pelvic actinomycosis. The patient recovered after surgical drainage and antibiotics penicillin G for 4 weeks, followed by doxycycline (200 mg) twice daily for 3 months. This case highlights the important radiologic features of pelvic actinomycosis mimicking gynecologic malignancy, particularly in women with prolonged intrauterine device use and the management in refractory pelvic actinomycosis. Full article

Lead (Pb) is a widespread environmental pollutant that induces systemic toxicity in aquatic organisms primarily through oxidative stress, hematological disruption, and immune dysfunction. This study investigated the protective effects of ellagic acid (EA) against Pb-induced toxicity in common carp (Cyprinus carpio) using a multi-biomarker approach and molecular docking. Fish were assigned to six experimental groups: control, EA-treated, Pb-I, Pb-I + EA, Pb-II, and Pb-II + EA. Fish in the Pb-I and Pb-II groups were exposed to 2.5 and 5 mg/L Pb, respectively, while EA was administered via diet at 100 mg/kg for 14 days. At the end of the exposure period, hematological indices, innate immune parameters, and oxidative stress biomarkers were assessed in blood, liver, kidney, and gill tissues. Pb exposure caused marked hematological impairment, suppressed immune responses, increased malondialdehyde levels, and disrupted antioxidant defense by reducing SOD, CAT, GSH-Px, and GSH levels while increasing GST activity. In contrast, dietary EA supplementation significantly mitigated Pb-induced alterations, improved hematological and immunological responses, reduced lipid peroxidation, restored antioxidant capacity, and normalized GST activity to control levels. Molecular docking analyses further showed that EA interacts with hemoglobin and immunoglobulin M, supporting its potential role in preserving oxygen transport and immune functions under Pb-induced stress. Overall, the findings demonstrate that Pb-induced toxicity involves coordinated disruption of redox homeostasis and immune function, whereas EA exerts a multi-target protective effect through biochemical and molecular mechanisms. This study provides mechanistic insight into chemical–biological interactions and supports the potential application of natural bioactive compounds in mitigating heavy metal-induced toxicity. Full article

Background/Objectives: Diabetic macular edema is caused by disruptions in the blood–retinal barrier, resulting in leakage and inflammation, appearing in optical coherence tomography as retinal fluid, hard exudates, and hyper-reflective foci. This study aimed to assess volumetric changes in hyper-reflective foci and hard exudates in faricimab-treated diabetic macular edema in real-world practice. Methods: This retrospective longitudinal study included forty-four eyes with faricimab-treated diabetic macular edema and follow-up of ≥40 weeks. Optical coherence tomography scans were analyzed at baseline, post-loading, 6 months and 1 year. Hyper-reflective foci and hard exudates were quantified across macular subfields using a machine-learning algorithm with manual correction. Outcomes included volumetric changes, best-corrected visual acuity, and central subfield thickness. Early morphologic responders were defined post-loading by ≥20% central subfield thickness reduction and/or central subfield thickness below 280 µm. Results: At 1 year, hyper-reflective foci and hard exudate volumes significantly decreased in the central subfield (median differences: −0.025 nL, p = 0.00028; −0.119 nL, p = 0.00025) and outer ring (−0.178 nL, p = 0.00041; −0.612 nL, p = 0.014). Hard exudate volume significantly decreased in the inner ring (−0.740 nL, p < 0.0001). Best-corrected visual acuity and central subfield thickness improved significantly (−0.10 logarithm of the minimum angle of resolution (logMAR), p = 0.0018; −48 µm, p < 0.0001). Total hyper-reflective foci volumes were similar between responders and non-responders. In contrast, hard exudate burden remained numerically higher in non-responders. Conclusions: During the year following the switch to faricimab, HRF and HE burden decreased alongside visual and anatomical improvement. HRF volumes were descriptively similar between early CST responders and non-responders, whereas HE burden remained numerically higher in non-responders. Full article