Search Results (275)

Background/Objectives: Although plant-derived dietary fiber and protein are favorable factors for improving host metabolic disorders, it remains unclear whether these two macronutrients exhibit synergistic health benefits. Methods: To address this gap, utilizing oat dietary fiber (GLU) and soybean protein (SBP) as representative bioactive models, we investigated the effects of 5% GLU, 20% SBP, and their combined supplementation on high-fat diet (HFD)-induced metabolic dysregulation in C57BL/6J mice. Results: Our results demonstrated that the combined GLU + SBP intervention provided comprehensive protection against HFD-induced obesity, significantly attenuating body weight gain (12.29 ± 2.02 g vs. 21.90 ± 2.86 g, p < 0.05) and adiposity (3.34 ± 1.19% vs. 10.77 ± 1.16%, p < 0.05) compared with HFD mice, without altering caloric intake. Crucially, the compound formulation exhibited synergistic superiority over individual components, as evidenced by greater reductions in serum aspartate aminotransferase (AST) activity (113.13 ± 28.50 U/L vs. 158.00 ± 30.25 U/L, p < 0.05) and improved glucose tolerance, with lower OGTT AUC values (999.09 ± 95.83 vs. 1434.66 ± 80.56 mmol/L·min, p < 0.05). Mechanistically, 16S rRNA sequencing revealed a distinct remodeling of the gut microbial community, highlighted by a substantial enrichment of Akkermansia. Functional prediction analysis specifically linked this microbial shift to the modulation of Akkermansia-associated metabolic pathways, which subsequently facilitated the activation of host metabolic networks to combat lipid deposition and systemic metabolic stress. Conclusions: Collectively, the GLU + SBP combination offers synergistic metabolic benefits driven by a distinct gut microbiota signature, supporting a feasible “soluble fiber + plant protein” strategy for developing functional foods targeting metabolic health. Full article

Alphaherpesviruses, including Herpes Simplex Virus 1 (HSV-1) and Pseudorabies Virus (PrV), establish lifelong latency in the nervous system and can cause recurrent disease. While latency has classically been attributed to peripheral sensory ganglia, accumulating evidence indicates that the central nervous system (CNS) may also serve as a site of long-term viral persistence and reactivation. Here, we investigated the CNS as a viral reservoir using the attenuated mutant PrV-∆UL21/US3∆kin, which preferentially targets mesiotemporal brain regions. Following intranasal inoculation, mice were analyzed at 11–14, 21, 28, 42, 105, and 190 days post-infection (dpi). To assess the reactivation potential, a subset of animals received cyclophosphamide/dexamethasone at 170 dpi. Viral transcripts were detected by RNAscope™ in situ hybridization and RT-qPCR targeting the lytic gene UL19 encoding the major capsid protein and the latency-associated transcript (LAT). Histopathology included hematoxylin and eosin staining and immunohistochemistry for CD3, Iba1, GFAP, cleaved caspase-3 and viral glycoprotein gB. UL19 RNA signals displayed marked regional and temporal heterogeneity, with prominent detection in mesiotemporal structures. In contrast, LAT RNA levels remained low overall, with a transient peak during the acute phase. RT-qPCR confirmed high UL19 and LAT transcript levels during early infection, while LAT transcription returned to baseline levels thereafter. Histopathology showed a transition from acute necrotizing meningoencephalitis to prolonged low-grade inflammation with glial activation and focal apoptosis. Notably, UL19 RNA signals strongly correlated with T-cell infiltration, particularly at 42 dpi. Together, these findings define regional and temporal patterns of long-term PrV transcriptional activity and associated neuropathology in the murine CNS. Full article

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, currently represent one of the major challenges in contemporary medicine and geriatrics. Progressive degeneration of the nervous system affects not only patients’ physical functioning but also their psychosocial well-being, often leading to social isolation and disruption of interpersonal relationships. These processes are most strongly associated with individuals over 65 years of age, in whom metabolic syndrome is frequently diagnosed and constitutes a significant factor predisposing them to the exacerbation of neuropathological changes. This review analyzes the role of selected vitamins in modulating the course of neurodegenerative disorders, with particular emphasis on their neuroprotective potential. Specific attention is given to their involvement in antioxidant defense mechanisms, regulation of inflammatory pathways, prevention of abnormal protein aggregation, participation in neurotransmitter synthesis, and support of mitochondrial function and cellular energy metabolism. The review also considers key interactions between vitamins and coenzyme Q10, which synergistically enhance neuroprotective mechanisms. Deficiencies in certain vitamins may exacerbate oxidative stress, impair synaptic transmission, and intensify neuroinflammatory responses, thereby contributing to disease progression. The study analyzes the available data on therapeutic doses of vitamins and compares them with the recommended dietary intake and the upper tolerable intake levels (UL). The available evidence suggests that personalized vitamin supplementation, when integrated with a well-balanced and nutrient-dense diet, may constitute a valuable adjunctive therapeutic strategy. Such an approach may help attenuate disease progression, support neuronal integrity, and improve functional outcomes. Ultimately, targeted nutritional interventions may enhance overall well-being and quality of life in patients affected by neurodegenerative diseases. Full article

Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) positive dermatomyositis is a distinct subset of idiopathic inflammatory myopathies (IIMs), often associated with unique cutaneous features and interstitial lung disease (ILD). While East Asian cohorts frequently report high mortality due to rapidly progressive ILD (RP-ILD), data regarding Central and Eastern European populations remain scarce. Methods: We conducted a retrospective multicenter study of anti-MDA5 positive Caucasian patients managed at four Hungarian rheumatology centers between 2020 and 2025. Demographic, clinical, serological, and radiological data were analyzed. Antibody profiling was performed using a standardized 16-antigen immunoblot assay. Results: Anti-MDA5 positivity was confirmed in 24 out of 742 patients (3.23%) treated in the four centers. The median age at diagnosis was 49.5 years (range: 24–81). Classic dermatomyositis was the predominant clinical phenotype (75%), followed by clinically amyopathic dermatomyositis (CADM) (12.5%) and polymyositis (12.5%). ILD was identified in 58.3% of patients, presenting with organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP), and usual interstitial pneumonia (UIP) patterns. At diagnosis, median creatine kinase (CK) (193.5 U/L) and C-reactive protein (CRP) (4.24 mg/L) levels remained low even in the ILD group, whereas lactate dehydrogenase (LDH) was elevated in 91.7% of the cohort. Anti-Ro52 positivity (45.8% overall) emerged as a notable predictor of ILD (odds ratio [OR]: 22.5, 95% confidence interval [CI]: 2.10–240.48; p = 0.0045), being present in 71.4% of affected patients. RP-ILD occurred in two patients (8.3%). Therapeutic management followed an early, aggressive strategy, frequently utilizing cyclophosphamide (45.8%) and methotrexate (37.5%), with Janus kinase (JAK) inhibitors or rituximab employed in refractory cases. Overall disease-specific survival was 100% during the study period (median follow-up: 72.0 months); no mortality was directly attributable to IIM-related complications. Conclusions: Our study demonstrates that anti-MDA5 positive dermatomyositis in a Hungarian cohort is characterized by heterogeneous manifestations and a significant association between anti-Ro52 and ILD. The observed dissociation between low CK/CRP and elevated LDH underscores the necessity for a high index of suspicion, with LDH serving as a superior marker for disease activity. While ILD presents a significant risk, early and intensive multi-modal intervention may yield superior survival outcomes in European patients compared to the historical mortality rates reported in Asian cohorts. Full article

Lactate dehydrogenase (LDH) is widely used as a nonspecific marker of tissue damage and cellular turnover and has been associated with metabolic and inflammatory processes, but its relationship with automated monitoring data and blood biochemical indicators in early-lactation dairy cows is still not well described. The aim of this study was to evaluate associations between LDH activity, blood biochemical parameters, and automated monitoring indicators in early-lactation Holstein cows. A total of 91 clinically healthy cows were classified into two groups according to LDH activity: Group 1 (LDH < 1364 U/L; n = 53) and Group 2 (LDH ≥ 1364 U/L; n = 38). Blood samples were collected once per cow during early lactation, whereas automated monitoring parameters were continuously recorded and daily averages corresponding to the sampling day were used for analysis. Cows with higher LDH activity had significantly higher aspartate aminotransferase (AST) activity and moderate increases in albumin (ALB), creatinine (CREA), gamma-glutamyl transferase (GGT), calcium (Ca), phosphorus (PHOS), and iron (Fe). Correlation analysis showed a strong positive association between LDH and AST (r = 0.799, p < 0.001), while moderate positive correlations were observed with ALB, alanine aminotransferase (ALT), CREA, Ca, GGT, Fe, and PHOS. Receiver operating characteristic (ROC) analysis showed the best discrimination ability for AST, while CREA, ALB, Fe, PHOS, Ca, and GGT showed moderate classification performance. Automated monitoring parameters did not differ significantly between groups; however, cows with higher LDH activity tended to show lower rumination time together with higher milk electrical conductivity, higher milk yield, higher fat-to-protein ratio (FPR), and higher somatic cell count (SCC). Overall, the results indicate that LDH is more closely related to systemic biochemical variation than to immediate changes in production or behavioral indicators, and support the use of biochemical markers together with automated monitoring data when evaluating physiological adaptation during early lactation. Full article

Background/Objectives: Mango is a tropical fruit rich in polyphenols and carotenoids that may support recovery-related physiological responses during athletic training. This study examined the effects of mango puree supplementation on inflammatory biomarkers, muscle damage, and selected T-cell subsets in Thai men’s national beach volleyball players during regular training. Methods: Fifteen male athletes completed a pilot randomized, single-blind, crossover trial. Participants consumed the mango puree or placebo (600 g/day) for 4 weeks, separated by a 2-week washout period. Blood samples and physiological measurements were collected at baseline and at the end of each intervention period. Outcomes were analyzed using linear mixed-effects models. Results: Mango puree supplementation was associated with lower concentrations of C-reactive protein (mean difference: −1.6 mg/L; 95% CI: −2.1 to −1.1; p < 0.001), interleukin-6 (−0.7 pg/mL; 95% CI: −1.2 to −0.3; p = 0.003), and creatine kinase (−290.1 U/L; 95% CI: −356.1 to −224.1; p < 0.001) compared with the placebo. The percentage of CD4+ T cells (9.82 percentage points; 95% CI: 5.0 to 14.6; p < 0.001) and the CD4/CD8 ratio (0.37; 95% CI: 0.11 to 0.63; p = 0.007) were higher during mango puree supplementation, while CD8+ T-cell percentage did not differ between conditions. No significant treatment effects were observed for body composition parameters or blood pressure (all p > 0.05). Total energy intake remained unchanged across intervention periods (p > 0.05). Conclusions: Mango puree supplementation during regular training was associated with lower inflammatory and muscle damage biomarkers and alterations in selected T-cell subsets compared with the placebo. Full article

This study explored the patterns and mechanisms influencing changes in silage quality, mycotoxin accumulation, and microbial community structure in oat silage after lodging. Upright oat forage (control, CK), lodging oat forage (upper layer (UL), lower layer (LL), and mixed layers (MLs) were harvested at 0, 7, 25, and 45 days after lodging and ensiled for 60 days. The results showed that the dry matter (DM) and water-soluble carbohydrate (WSC) content decreased significantly (p < 0.05), whereas crude protein (CP) and fiber content increased significantly compared to upright oats (p < 0.05). The WSC and CP content in silage decreased with increasing lodging duration. The fiber content increased in late harvest after lodging. The risk of mycotoxin infection increased after lodging, with aflatoxin levels exceeding EU limits. The mycotoxins in UL silage were the lowest when lodging lasted for seven days. Lodging oat silage was dominated by Lactobacillus, and the Pseudomonas in the lodging group was less than 4%. The fungi in lodging oat silage was lower, and the UL (upper layer) treatment was the lowest when lodging for 7 days. Overall, the transfer of microorganisms, especially Plectosphaerella, Fusarium, Alternaria, Cladosporium, and Botryotrichum, from soil to silage following oat collapse is of interest. The results suggest the soil–plant microbial interactions and their effects on silage fermentation and mycotoxins in lodging oats. Full article

Human cytomegalovirus (HCMV) infection is a significant complication in transplant recipients. Following HCMV reactivation, the recovery of T-cell responses serves as a key indicator of protection from HCMV disease. This study aimed to assess the HCMV-specific CD4⁺ and CD8⁺ T-cell responses and their cytokine production (IFNγ, TNFα, IL2) against various HCMV proteins (IE-1, pp65, gB, gH/gL/pUL128L) in solid organ transplant recipients (SOTRs) and hematopoietic stem cell transplant recipients (HSCTRs) with active HCMV infection. The cohort consisted of 16 SOTR and 16 HSCTR categorized into two groups: (i) Controllers, who spontaneously controlled the infection, and (ii) Non-Controllers, who required antiviral treatment. T-cell responses were analyzed following stimulation with peptide pools and intracellular cytokine staining. Prior to transplantation, all patients exhibited a significantly higher frequency of CD4⁺ T cells specific to pp65 compared to gH and gL/pUL128L. During the peak of infection, T-cell frequencies across all peptides were similar, but at infection resolution, the frequency of pp65 and gB-specific CD4⁺IFNγ⁺ T cells was significantly higher than gL/pUL128L. Additionally, pp65 and IE-1-specific CD8⁺IFNγ⁺ T-cell responses were significantly greater than those against gH and gL/pUL128L at the resolution of infection. Notably, Controllers exhibited significantly higher frequencies of monofunctional pp65-specific T cells, particularly in CD8⁺ T cells producing IFNγ and TNFα. The response to pp65, especially IFNγ production, may serve as a key marker for identifying patients capable of controlling HCMV infection. Full article

Background and Objectives: Pancreatoduodenectomy (PD) is the primary treatment for patients with resectable, non-metastatic pancreatic adenocarcinoma and periampullary tumors. Although surgical methods and perioperative management have improved, the procedure still carries a high risk of complications, with postoperative pancreatic fistula (POPF) being the most significant. This study focuses on identifying current risk factors for POPF after PD in a single HPB center. Materials and Methods: We retrospectively analyzed prospectively collected data from patients undergoing PD in our department between October 2018 and April 2024. Data included demographics, comorbidities, lifestyle factors, preoperative tests (bilirubin, CA19-9, HbA1c), intraoperative variables (pancreatic texture, duct diameter), and postoperative outcomes. POPF was classified using the International Study Group of Pancreatic Surgery (ISGPS) criteria. Univariate and multivariate logistic regression analyses were performed. Results: A total of 118 patients underwent PD (82 males, 36 females; mean age 67 (45–85) years; mean body mass index (BMI) 26.6 kg/m²). POPF occurred in 37 patients (31%), with 27 Grade B (23%) and 10 Grade C (9%). The 30- and 90-day mortality rates were 5% and 12.7%, respectively. Univariate analysis showed associations between POPF and soft pancreas (p = 0.018), c-reactive protein (CRP) on postoperative day (POD) 5 (p = 0.004), and serum amylase on POD 0 (p = 0.008). Diabetes mellitus was associated with a lower incidence of POPF (p = 0.014). Multivariate analysis confirmed CRP on POD 5 (OR 1.007, p = 0.025) and DM (OR 0.254, p = 0.015), as independent factors. ROC analysis identified POD 0 amylase >113.5 U/L (AUC 0.717) and POD 5 CRP >125.3 mg/dL (AUC 0.669) as predictive values. Conclusions: POPF remains an important complication after PD. CRP > 126 mg/dL on POD 5 was associated with POPF and may serve as an adjunctive signal to guide further assessment, including imaging. The observed inverse association with diabetes mellitus is hypothesis-generating and should be interpreted cautiously, considering potential confounding and the influence of center volume, surgeon heterogeneity, and institutional protocols. Full article

During their natural growth, plants encounter adverse environmental conditions, such as chilling injury, freezing injury, drought, and salt damage, collectively known as abiotic stresses. Several studies have shown that WRKY proteins regulate various abiotic stress responses and plant developmental processes. However, researchers have rarely investigated WRKY genes associated with the stress response in apples. Within this research, Malus baccata (L.) Borkh as the experimental material. We isolated and cloned MbWRKY63 and investigated its function in low-temperature stress tolerance. Subcellular localization analysis shows that MbWRKY63 localizes to the cell nucleus. Tissue-specific expression analysis revealed that MbWRKY63 is relatively highly expressed in the young leaves and root tissues of apples. Under low-temperature treatment at 4 °C, Arabidopsis thaliana plants that overexpressed MbWRKY63 showed greater cold stress resistance than the wild type (WT) and the empty vector (UL) control. In transgenic plants, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were significantly enhanced; meanwhile, the contents of proline, malondialdehyde (MDA), and chlorophyll also changed significantly. In addition, by regulating the expression levels of AtKIN1, AtCBF1, AtCBF2, AtCBF3, AtCOR47, and AtCOR15a, MbWRKY63 enhanced the low-temperature stress tolerance in transgenic Arabidopsis. The results suggest that MbWRKY63 in apples may be involved in the response to low-temperature stress, laying a foundation for understanding the role of WRKY transcription factors (TFs) in abiotic stress responses. Full article

Oxydifficidin is a natural polyketide antibiotic that has long been recognized as a ribosome-targeting agent that inhibits protein synthesis. In this paper, we describe Bacillus velezensis strain EV17 and compare its complete genome sequence with that of the previously characterized B. velezensis strain K-3618 and the difficidin biosynthetic gene cluster (BGC) combined with mass spectrometry to elucidate the production of oxydifficidin by these strains. Toeprinting and small fluorescent peptide assays showed that isolated oxydifficidin induces a generalized inhibition of translation at every step of elongation in protein biosynthesis. In previous studies, it has been demonstrated that oxydifficidin targets bL12 protein. Although spontaneous mutations conferring resistance to oxydifficidin in ribosomal protein bL12 located relatively close to the thiostrepton binding site on uL11, our data show that oxydifficidin binding does not interfere with thiostrepton, thereby refining previous findings about its putative ribosomal target. We are the first to show that this compound does not affect eukaryotic translation and has two orders of magnitude lower effect on eukaryotic cells compared to bacteria. These facts are important to further investigate its potential as a bioprotectant against phytopathogens or even as a therapeutic agent. Full article

Background/Objectives: Preeclampsia is associated with long-term cardiovascular and metabolic risks. This study aimed to evaluate metabolic and cardiovascular biochemical profiles in women with a history of preeclampsia and angiogenic imbalance during pregnancy. Methods: We conducted a cross-sectional study at Hospital de la Santa Creu i Sant Pau between August 2023 and July 2025. Participants had been prospectively enrolled during pregnancy (2018–2022) and were re-evaluated 3 to 6 years later. Blood and urine samples were collected after a 12-h fast to assess hematological, metabolic, and cardiovascular markers. Angiogenic profiles were determined using sFlt-1/PlGF ratios obtained during pregnancy. Multivariable linear regression models were used to assess associations with a history of PE and angiogenic imbalance, adjusting for relevant confounders. Results: 363 participants were included. 113 (31.1%) had a history of preeclampsia. Women with previous preeclampsia showed slightly higher high-sensitivity troponin T concentrations [4.0 (3.0–6.0) ng/L vs. 3.2 (3.0–5.0) ng/L, p = 0.03]. Women with sFlt-1/PlGF ≥38 exhibited significantly higher urinary protein [0.09 (0.07–0.18) g/L vs. 0.08 (0.07–0.13) g/L, p = 0.01], potassium [4.25 (4.07–4.40) mmol/L vs. 4.19 (4.02–4.37) mmol/L, p = 0.048], and LDH concentrations [168 (150–189) U/L vs. 163 (149–177) U/L, p = 0.046], and lower leukocyte counts [6150 (5348–7055) vs. 6250 (5430–7450) U/mL, p = 0.03]. Conclusions: Women with angiogenic imbalance during pregnancy display subtle alterations in renal and endothelial function markers years after delivery, whereas those with preeclampsia show slightly higher troponin concentrations. These findings, though clinically irrelevant, suggest that pregnancy-related vascular dysfunction may have different long-term manifestations depending on whether the maternal cardiovascular system was sufficiently compromised to develop overt preeclampsia. Full article

Duck enteritis virus (DEV), an epornitic pathogen, causes substantial economic losses in the commercial duck industry and poses persistent risks to wild and migratory waterfowl populations. However, due to the large genomic capacity of the DEV, the understanding of the virulence-associated genes of DEV is still limited. In previous studies, we developed an attenuated strain E74 by serial passage of a virulent strain E1 on primary chicken embryo fibroblasts (CEFs). The bird experiment showed that the mortality rate of E1 on ducks reached 100%, and high-titered viruses were detected in all tested tissue samples. In contrast, the E74 virus has lost its pathogenicity in ducks and can only be detected at a relatively low viral load in the spleen. Furthermore, the E74 stimulated a significant increase in antibodies in the ducks at 7 days post-inoculation. To further investigate the molecular basis of the attenuation of DEV in ducks, the complete genomes of E74 and E1 were sequenced and analyzed. Compared with E1, E74 had a 5152 bp deletion in the UL region, which resulted in the lack of the hypothetical protein, LORF5, UL55 and LORF4 genes. To test the influence of the deletion on the viral pathogenicity, a rescued virus rE1-Δ5152 with the 5152 bp deletion in the UL region was generated on the E1 backbone. Animal experiments showed that the lethality of rE1-Δ5152 in ducks had disappeared. Those findings suggest that the hypothetical protein, LORF5, UL55, and LORF4 genes of DEV are associated with virus virulence, and the flexibility of this region provided excellent insertion sites for exogenous genes when DEV is used as a recombinant vaccine vector. Full article

The genome of the herpesvirus is a linear double-stranded DNA. The viral genome replicates in the host cell to form a concatemeric DNA, which is then cleaved to produce a unit-length genome. This unit-length genome is packaged into procapsid to produce mature virus particles. The terminase large subunit, pUL15, mediates the cleavage and packaging of viral concatemeric genomes. Duck plague virus (DPV) is a member of the α herpesvirus subfamily. Previous studies have demonstrated that the C-terminal region of DPV pUL15 exhibits non-sequence-specific DNA cleavage activity in vitro, but the characteristics of DPV full-length pUL15 remain unclear. In this study, it was determined that the full-length pUL15 exerted non-sequence-specific nuclease activity. Additionally, full-length pUL15 was capable of binding to DNA and hydrolyzing ATP. To analyze the functional domain of DPV pUL15, pUL15 mutants were constructed, expressed, and purified. The results revealed that DNA-binding and ATPase functions of pUL15 were primarily mediated by its N-terminal region, and the nuclease activity was conducted by its C-terminus. The loss of the nuclease activity did not effect on the DNA-binding and ATPase activity. Taken together, this study’s findings demonstrated that DPV pUL15 is a multifunctional enzyme with ATPase, nuclease, and DNA-binding activities. These results will provide important clues for subsequent studies on the function of terminase and the process of viral genome packaging, and provide a foundational basis for the development of broad-spectrum anti-herpesviral drugs targeting the conserved terminase complex, with direct relevance to veterinary medicine. Full article