Search Results (17,299)

Superoxide dismutase 2 (SOD2), a key mitochondrial antioxidant enzyme, is essential for maintaining cellular redox homeostasis by scavenging superoxide radicals. While viruses often induce oxidative stress, the specific role of SOD2 in antiviral defense remains unclear. Here, we report that vaccinia virus (VACV) infection triggers mitochondrial and cellular reactive oxygen species (ROS) and selectively upregulates SOD2, but not SOD1. Genetic knockout of SOD2 exacerbated mitochondrial ROS (mtROS) accumulation and significantly enhanced VACV replication and spread, resulting in larger viral plaques. Conversely, SOD2 overexpression constrained plaque formation and suppressed viral dissemination. Mechanistically, the antiviral function of SOD2 does not strictly rely on its enzymatic activity or mitochondrial targeting, as neither the deacetylation-mimicking mutant nor the mutant lacking the mitochondrial localization signal peptide appreciably impaired its antiviral potency. Furthermore, in a rabbit model, local overexpression of human SOD2 attenuated the poxvirus lesion formation. Our findings unveil an important yet easily overlooked role of SOD2 in antiviral defense and posit it as a promising candidate for the development of host-directed therapeutics against poxviruses. Full article

Spinal pathologies, including degenerative disc disease, spinal cord injury, and conditions requiring spinal fusion, pose a substantial global health burden. While contemporary interventions provide symptomatic relief, achieving durable tissue repair in biologically compromised environments remains a critical challenge. This narrative review synthesizes the current literature on three major nanotechnology applications in spine care: nanostructured implant surfaces, nanoparticle-enhanced bone grafts, and nano-drug delivery systems (NDDSs). Preclinical evidence indicates that nanoscale surface modifications and nanoparticle-augmented synthetic grafts significantly enhance osseointegration and bone fusion by mimicking the native extracellular matrix. Furthermore, in animal models of intervertebral disc degeneration, NDDSs utilizing polymeric nanoparticles and exosomes facilitate sustained, stimuli-responsive therapeutic delivery into the avascular disc space. Although early clinical data on nanostructured cages demonstrate reduced subsidence and stable long-term fusion, the direct translation of these robust preclinical outcomes to widespread clinical efficacy faces substantial hurdles. Significant translational barriers include stringent Class III regulatory classifications, sparse long-term safety data regarding nanoparticle biodistribution, and scale-up manufacturing challenges such as batch variability. Future progress relies on artificial intelligence-guided design, three-dimensional (3D) bioprinting, and multifunctional “smart” nanomaterials. Ultimately, close collaboration among materials scientists, clinicians, and regulatory bodies is essential to safely bridge the gap between preclinical innovation and predictable clinical therapeutic success. Full article

Phytochemicals with antifungal activity against Fusarium graminearum (F. graminearum) are considered potential in-feed anti-mycotoxigenic agents that may complement conventional post-harvest control strategies. Therefore, we screened fourteen phytochemicals, including seven quinolizidine alkaloids (QAs), for anti-F. graminearum activity, evaluated their individual and combined efficacy in inhibiting mycelial growth, spore germination, and deoxynivalenol (DON) production, and explored the underlying mechanisms via transcriptomic analysis. Matrine (MT), sophoridine (SR), and sophocarpine (SC) exhibited antifungal activity against F. graminearum, with minimum inhibitory concentrations (MICs) of 5, 4, and 4 mg/mL, respectively. The three QAs at their MICs completely inhibited mycelial growth and DON production in liquid cultures, but were less effective on potato dextrose agar plates and in pig feed. Particularly pronounced antifungal activity and inhibitory effects on DON production were observed when the three QAs were applied in combination with berberine hydrochloride (BBR). The observed inhibition appears to be attributed to dysregulated expression of the TRI cluster genes and ERG biosynthesis genes, coupled with significant modulation of steroid biosynthesis (ko00100) and central carbon/lipid metabolism pathways. These findings provide preliminary experimental evidence supporting the further exploration of QA–BBR combinations to control fungal proliferation and DON accumulation in pig feed. Full article

Persistent racial and ethnic disparities in type 2 diabetes mellitus (T2DM) are incompletely explained by genetic susceptibility, obesity, lifestyle, and socioeconomic factors, suggesting that additional biological mechanisms may link environmental exposures to metabolic disease risk. Increasing evidence indicates that the exposome, encompassing environmental exposures across the life course, may influence long-term metabolic health through molecular mechanisms that integrate environmental signals with host biology. This Review synthesizes epidemiological, experimental, and mechanistic evidence on the gut microbiota–host epigenetic axis and its potential role in linking environmental exposures to population differences in T2DM susceptibility. Gut microbial dysbiosis alters the production and metabolism of short-chain fatty acids, bile acids, and tryptophan-derived metabolites. These microbial metabolites can modulate host signaling and epigenetic processes, including DNA methylation, histone modifications, and non-coding RNA activity, which may influence the expression of genes involved in glucose homeostasis, inflammation, and insulin sensitivity. Conversely, host epigenetic programs may influence intestinal barrier integrity and immune responses, thereby potentially affecting the gut microbial ecosystem, highlighting the reciprocal nature of host–microbiota interactions. We further examine how diet, psychosocial stress, environmental pollutants, and socioeconomic conditions may shape the microbiota–epigenetic axis across diverse populations, providing a framework for understanding differences in metabolic susceptibility without attributing disparities to intrinsic biological variation. However, direct human evidence linking the gut microbiota–host epigenetic axis to racial and ethnic disparities in T2DM risk remains limited, and much of the current framework is based on mechanistic studies, animal models, and associative human data rather than direct causal evidence. Further research in diverse human populations is needed to validate these pathways and establish their contribution to T2DM disparities. This framework may inform biomarker discovery, stratification, precision nutrition, and microbiome-targeted interventions and generate hypotheses for equitable prevention and personalized management of T2DM across diverse populations. Full article

The classification systems currently in use for Streptococcus suis are primarily based on capsular polysaccharide (CPS) serotyping or multi-locus sequence typing (MLST). A genetic typing system based on the conserved Mac-1 domain of the Ide_Ssuis gene, which encodes an IgM-cleaving protease, could complement these approaches. Specifically, in this study, a genotyping system based on Mac-1 sequence homology was established, qualitative SYBR Green real-time PCR (qPCR) assays for standardized genotype classification were developed, and the global and European distribution of genotypes were analyzed. The Mac-1 classification system identified “two genotypes”, one of which has “two subgenotypes”, based on 427 unique sequences obtained from 4161 global sequences. GT1.1 was the most prevalent, having an amino acid similarity of 97.1%, followed by GT1.2 98.1%, and GT2 91.4%. The qPCR approach enabled reproducible, cross-laboratory-accessible typing. Among 5479 Streptococcus suis European isolates, 64% were GT1.1, 4.5% were GT1.2, and 29.6% were GT2, with a trend toward increasing GT1.1 detection rates between 2018 and 2023. Genotyping classification could complement current Streptococcus suis classification approaches to better support vaccine design and disease control strategies. Full article

Insulin resistance (IR) represents one of the most pressing problems in contemporary public health. Its estimated global prevalence ranges from approximately 15.5% to over 61%, depending on the population studied, the diagnostic criteria applied, and the method used for its assessment. Despite the scale of the problem, IR remains underrecognized and lacks formal definition as a distinct disease entity, even as a growing number of clinicians and researchers worldwide describe it as such. Its asymptomatic or mildly symptomatic course allows it to remain undetected for years, during which it makes a significant contribution to the development of type 2 diabetes, cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD), and has been increasingly linked to cellular senescence, certain cancers, neuropsychiatric disorders, and other metabolic conditions. The aim of this review was to summarize current knowledge on the pathophysiology, diagnosis, and clinical implications of insulin resistance, to discuss current challenges in its diagnosis, and to evaluate whether available scientific evidence supports its recognition as a distinct disease entity. This narrative review is based on clinical, epidemiological, and mechanistic data retrieved from PubMed and Google Scholar. Meta-analyses, systematic reviews, clinical and observational studies, clinical guidelines, and expert position statements were analyzed. Animal studies were excluded to maintain a focus on human public health implications. The diagnostic gold standard—the hyperinsulinemic-euglycemic clamp—was discussed, along with surrogate methods used in clinical practice (HOMA-IR, OGTT with insulin measurements, the TyG index, and the TG/HDL-C ratio). Factors potentially contributing to the pathogenesis of IR were examined, including hyperinsulinemia (HI), high-carbohydrate diets, inflammation, stress, and sleep disturbances, as well as conditions in which IR occurs physiologically. The findings indicate that current evidence supports the need for a clearer clinical and diagnostic framework for insulin resistance and suggest that its recognition as a distinct disease entity could facilitate earlier diagnosis, improve the standardization of clinical management, and enable earlier metabolic intervention. Given the steadily rising prevalence of metabolic disease, systemic efforts directed at the early identification and treatment of IR may be a key component of strategies aimed at reducing the population-level burden of metabolic disease and its negative consequences. Full article

Cow milk and dairy products may reflect environmental elemental inputs transferred through the feed–animal–milk chain. This study investigated the elemental traceability, regional differentiation, dairy processing effects, and dietary exposure associated with milk and dairy products from two contrasting Romanian dairy production systems: the traditional Vaideeni region and the industrial Ibănești region. A total of 88 samples (water, feed, raw milk, and dairy products) were seasonally collected during 2024–2025 and analysed for trace elements, geochemical fingerprint elements, and macroelements using ICP-OES and atomic absorption spectrometry. The strongest regional elemental contrasts were observed in groundwater for V (Δlog₁₀ = +1.30), U (+0.82), Sr (+0.61), and Mn (+0.60), but these differences were substantially attenuated during biological transfer. Nevertheless, Li, U, Sr, Mn, and Cu retained measurable regional differences in milk. Regional elemental contrasts within the feed indicated an important inverse relationship (Pearson r = −0.60, p = 0.018), whereas no significant correlation was found between water and milk (Pearson r = −0.19, p = 0.493), suggesting that the milk elemental patterns may be influenced by biological regulatory processes in addition to the environmental signatures. Dairy processing further modified the elemental distribution, with the trace elements showing increased redistribution compared to the macroelements, while the geochemical fingerprint elements preserved regional information. The dietary exposure estimates for Cd and Ni remained below the corresponding toxicological reference values, whereas the highest estimated Pb exposure from hard cheese reached 0.977 μg/kg body weight/day for children and 0.558 μg/kg body weight/day for adults, exceeding the EFSA BMDL₀₁ reference point. The results indicate that multielement fingerprinting may provide promising information for investigating elemental traceability and supporting dairy product authenticity assessment within the investigated production systems, although extensive geographical validation will be required before application as a general authentication tool. Full article

Ruminal acidosis, particularly subacute ruminal acidosis, remains a major metabolic disorder that compromises animal health, production efficiency, and the sustainability of intensive ruminant systems. Although traditionally defined by reduced ruminal pH, it is increasingly recognized as a multidimensional disorder involving microbial ecological destabilization, disrupted metabolic cross-feeding, impaired epithelial barrier function, and dysregulated host inflammatory responses. This review synthesizes current knowledge of the microbial and metabolic mechanisms underlying acute and subacute ruminal acidosis and highlights processes that extend beyond pH depression alone. High-concentrate feeding shifts the balance among amylolytic and lactate-producing microorganisms, lactate-utilizing populations, and fibrolytic guilds, thereby promoting organic acid accumulation, reducing functional redundancy, and weakening microbial resilience. Concurrent increases in volatile fatty acids, lactate, lipopolysaccharide, histamine, and other microbially derived bioactive compounds increase epithelial acid load, disrupt tight-junction integrity, and facilitate inflammatory signaling. The principal novelty of this review is the integration of microbial functional guilds, metabolic cross-feeding, ecological resilience, epithelial barrier dysfunction, and host inflammation into a unified microbiota–metabolism–barrier–inflammation framework linking dietary perturbation with microbial dysfunction and host pathology. We further critically evaluate nutritional regulation, buffering agents, probiotics, yeast-derived products, postbiotics, and plant bioactive compounds according to their capacity to restore microbial function rather than merely correct ruminal pH. Additionally, this review may support multidimensional risk assessment, guide targeted intervention, and facilitate the integration of continuous ruminal monitoring with precision nutrition for earlier prediction and individualized prevention of ruminal acidosis. Full article

Background: Noise-induced hearing loss (NIHL) is a pervasive occupational health challenge, yet the individual susceptibility mechanisms remain unclear. Ferroptosis, an iron-dependent form of programmed cell death, has been implicated in cochlear hair cell damage. This study aims to elucidate the regulatory role of the transcription factor FOXA2 and the deacetylase SIRT1 in ferroptosis and to investigate the association between SIRT1 genetic polymorphisms and NIHL susceptibility in occupational populations. Methods: We employed a multi-level study design combining epidemiological investigation, animal models, and cellular experiments. First, a case–control study was conducted involving 1314 noise-exposed workers (639 cases vs. 675 controls) from a chemical fiber enterprise in Jiangsu Province to analyze the association between SIRT1 single nucleotide polymorphisms (SNPs) and NIHL risk. Second, a C57BL/6J mouse model exposed to 120 dB white noise was established to assess cochlear morphology and protein expression. Third, in HEI-OC1 cochlear hair cells, we performed siRNA-mediated knockdown of Foxa2 and dual-luciferase reporter assays to verify the transcriptional regulation of SIRT1 and its downstream effects on the ferroptosis pathway. Results: Population analysis revealed that the SIRT1 rs12778366 C allele was significantly associated with increased NIHL risk (OR = 1.386, 95% CI: 1.084–1.772, p = 0.009), and this association remained significant after adjustment (p = 0.041). Stratified analysis further revealed a significant gene–environment interaction in workers with >15 years of noise exposure (OR = 2.126, 95% CI: 1.401–3.226, p < 0.001). In vivo, noise exposure led to significant downregulation of Sirt1 and Foxa2 in cochlear tissues, accompanied by elevated ferroptosis markers (Fe²⁺, MDA) and depleted antioxidant defenses (GSH, xCT, and GPX4). Mechanistically, we demonstrate that FOXA2 transcriptionally activates SIRT1 by binding to its promoter. Knockdown of FOXA2 in vitro suppressed SIRT1 expression, suppressed xCT, a key component of the System Xc⁻/GPX4 antioxidant axis, and promoted ferroptosis-related cellular changes. Conclusions: This study identifies a novel protective axis where FOXA2 prevents noise-induced ferroptosis in cochlear hair cells by transcriptionally upregulating SIRT1 and maintaining xCT-mediated antioxidant defense. Furthermore, the SIRT1 rs12778366 polymorphism is identified as a candidate variant warranting further investigation in independent cohorts before clinical translation. Full article

Fenjiu distillers’ grains are a major by-product of Fenjiu production and contain various bioactive components derived from cereal raw materials and microbial fermentation. Colorectal cancer (CRC) remains a global health challenge, and the development of safe and effective therapeutic agents is urgently needed. In this study, we successfully obtained DGAE-1 (distillers’ grains ethanol extract fraction 1), an ethanol-extracted bioactive fraction derived from Fenjiu distillers’ grains, with anti-colorectal cancer activity. LC-MS analysis tentatively annotated the chemical constituents of DGAE-1 fraction based on MS/MS fragmentation patterns and database similarity matching, with the major annotated compounds belonging to carboxylic acids and derivatives, organic nitrogen compounds, organic phosphoric acid derivatives, and other chemical classes. These annotated compounds may contribute to the biological activity of DGAE-1 fraction, although the specific active constituents remain to be further clarified. DGAE-1 fraction inhibited colorectal cancer cell proliferation and induced autophagy. Further studies indicated that the PI3K/AKT pathway is involved in DGAE-1 fraction-induced autophagy. The results of this study demonstrate that DGAE-1 fraction exerts anti-colorectal cancer activity in both cellular and animal models. These findings provide new insights into the development and utilization of Fenjiu distillers’ grains and highlight their potential as a source of bioactive compounds for health-related applications. Full article

Lactic acid bacteria (LAB) are regarded as promising probiotics with multiple beneficial properties for humans’ and animals’ health. In this study, ten LAB isolates were screened and Lactiplantibacillus plantarum (L. plantarum) CLPX21 was selected as a candidate strain with its probiotic potential based on in vitro screening of antimicrobial activity and environmental stress tolerance, including its resistance to acidic environments and bile salts. This strain displayed adhesion capacity with an auto-aggregation rate of 47.15% at 24 h, co-aggregation rates above 67% with pathogenic bacteria, and an ability to adhere to IPEC-J2 cells (6.37%). CLPX21 showed broad-spectrum antimicrobial activity against common foodborne pathogens including Escherichia coli (E. coli), Salmonella, and Staphylococcus aureus. In addition, CLPX21 inhibited E. coli biofilm formation. Furthermore, CLPX21 significantly suppressed E. coli-induced inflammatory cytokine production in mouse peritoneal macrophages. Importantly, CLPX21 did not exhibit hemolytic activity. Genomic analysis further revealed that the CLPX21 genome encoded multiple functional genes and gene clusters, including biosynthesis of bacteriocins and secondary metabolites associated with antimicrobial and antioxidant functions, which provide a genetic basis for its beneficial phenotypic characteristics. In conclusion, L. plantarum CLPX21 displays probiotic properties with potent antimicrobial and anti-inflammatory activities, representing a promising candidate strain for applications in the food and health industries. Full article

Ticks are hematophagous ectoparasites of major veterinary and public health importance, acting as vectors of numerous pathogens affecting wildlife, domestic animals, and humans. Data on tick species infesting lagomorphs in Croatia remain scarce. This study investigated the species composition and genetic diversity of ticks collected from European brown hares (Lepus europaeus) in Croatia during 2024–2025 using morphological and molecular methods. A total of 158 hares from 18 localities were examined, and ticks were detected on 145 individuals, resulting in an infestation prevalence of 91.8%. Morphological identification and molecular analyses revealed nine tick species. The tick community was dominated by Ixodes ricinus (59.1%; n = 821), followed by Ixodes festai (26.8%; n = 372) and Rhipicephalus bursa (9.6%; n = 133), together accounting for more than 95% of all collected ticks. Molecular analyses confirmed species identification and revealed 10 haplotypes of I. ricinus, eight of I. festai, two of I. ventalloi, and one in I. inopinatus. The results demonstrate that European brown hares are important hosts for diverse tick species in Croatia and provide baseline data for future studies on tick ecology, tick-borne pathogens, and wildlife health management. Full article

The completion of this Special Issue, “Coronaviruses and Influenza Viruses: Evolution, Cross-Species Transmission, and Recombination”, offers a valuable opportunity to reflect on the remarkable scientific progress in understanding two of the most critical groups of emerging and re-emerging viral pathogens that affect both human and animal health [...] Full article

Micro- and nanoplastics (MNPs) are reported in blood, urine, and tissues, including the kidney, raising concern that the urinary system may be both a target and a route of elimination. This narrative review integrates analytical, toxicokinetic, experimental, epidemiological, and dialysis-related evidence on MNPs and renal health. Human studies report polymer-confirmed particles or polymer-associated signals in blood, urine, and kidney-related specimens, supporting systemic presence and compatibility with renal exposure; however, estimates are strongly method-dependent and do not establish anatomical localization, tissue dose, clearance, or a disease threshold. Cell, kidney-organoid, and animal studies consistently identify oxidative and mitochondrial stress, endoplasmic-reticulum dysfunction, inflammation, altered autophagy, regulated cell death, senescence, and fibrotic remodelling. Effects vary with polymer, size, shape, surface ageing, route, dose, and chemical co-exposures, and many experiments remain difficult to map to typical human exposure. Direct human outcome evidence is limited to cross-sectional or exploratory studies; plasticizer epidemiology is informative for chemical co-exposure but cannot establish particle-specific toxicity. Patients with chronic kidney disease may be more susceptible, while kidney dysfunction may also alter measured blood or urinary concentrations. Dialysis introduces an additional, incompletely quantified exposure system. MNP-related renal injury is biologically plausible, but causal contribution to human kidney disease and clinical actionability remain unproven. Standardized methods, paired-matrix kinetics, prospective cohorts, and complete dialysis mass-balance studies are priorities. Full article

Background/Objectives: Bovine heat-stress RNA-seq studies differ in tissue, age, physiological state, and exposure design. We asked which responses recur across these contexts and which depend on the evidence base. Methods: We reprocessed 107 libraries from five in vivo Bos taurus studies and synthesized within-study heat-minus-control log₂ fold changes using restricted maximum-likelihood random-effects models with modified Knapp–Hartung inference. Eight tissue- and age-aware scenarios tested the cross-context estimate. A six-component heat-stress transcriptomic stability index (HSTSI) was benchmarked against five simpler rankings, and an independent mammary single-nucleus dataset provided cell-resolved comparison. Results: Of 266 FDR-significant pathways, 259 retained direction across all five study deletions and 21 remained significant in every deletion. Translation, ribosome, protein folding, endoplasmic-reticulum processing, proteasome, and heat-response programs formed the most recurrent axis. Four principal sensitivity scenarios retained 0.920–0.932 gene-direction agreement and 0.957–0.981 effect-rank correlation with the five-study analysis. In the single-nucleus dataset, leading-edge genes from the principal proteostasis programs showed 89.4–100% pooled-nucleus direction agreement and 94.7–100% agreement among published cluster-level differentially expressed genes. HSTSI had the highest mean top-200 held-out direction agreement (0.583 versus 0.516–0.562), with variation among folds. None of 16,756 genes met a modified Knapp–Hartung FDR below 0.10. IL1R2 and SDCBP2 were externally concordant, whereas GZMK and CD8A were context-dependent. Conclusions: A coordinated proteostasis program was the most transferable heat-stress signal. Energy remodeling, immune-associated bulk signals, and individual genes showed greater context dependence and define priorities for tissue-matched follow-up. Full article