Search Results (3,814)

Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric mucosa, with a global prevalence in humans of approximately 40%. It is likely the cause of 90% of gastric cancer (GC) cases and thus considered the most prominent driver of GC development. However, during gastric mucosal atrophy, other bacteria such as nitrate-reducing bacteria (NRB) also proliferate. In this study, we isolated NRB from patients with gastritis and GC to examine their effects on the epithelial cell cycle and production of various cytokines in monocytic cell lines. Bacterial counts (excluding H. pylori and NRB) increased with the progression of gastric mucosal atrophy and were significantly higher in patients with GC. Gastric epithelial cell lines were stimulated with isolated NRB, and the proportion of cells in each cell cycle was measured. Strains from patients with open-type gastritis progressed more rapidly through cell cycles than those from patients with GC. NRB isolated from gastric cancer had high nitrate-reducing activity. Thus, NRB may contribute to GC progression during H. pylori-induced carcinogenesis. Therefore, evaluating gastric atrophy and microbiota may be important for managing the risk of GC. Full article

Background: Severe jaw atrophy limits traditional endosseous implantation, often necessitating complex regenerative procedures. Advances in digital planning and 3D printing have reintroduced custom-made subperiosteal (juxta-osseous) implants as a viable alternative. This study evaluates the clinical reliability and advantages of next-generation juxta-osseous implants. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines across the PubMed, Scopus, and Web of Science databases. The search focused on English-language studies reporting on custom-made titanium juxta-osseous implants in patients with severe maxillary or mandibular atrophy. Methodological quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Additionally, a representative clinical case of a 60-year-old female treated via a fully digital workflow is presented to illustrate the protocol. Results: Twenty-six articles were included, accounting for 147 clinical cases. Most patients exhibited Cawood and Howell Class V–VI atrophy. All identified treatments utilized integrated digital workflows, including CBCT imaging, CAD/CAM design, and additive manufacturing (SLM/DMLS) of medical-grade titanium alloy. Reported success rates exceeded 90%, with high primary stability enabling immediate or early loading protocols and high patient satisfaction. Complications were primarily limited to manageable soft-tissue dehiscence. Conclusions: Modern juxta-osseous implants represent a promising, minimally invasive alternative to bone grafting for severe atrophy, enabling rapid functional restoration in the short-to-medium-term. However, because current evidence is limited to clinical studies, these findings should be interpreted with caution. Long-term prospective trials are essential to establish definitive clinical predictability and standardized protocols. Full article

Malathion (MLT) is an organophosphate pesticide widely used worldwide. Due to its environmental persistence and accumulation in living organisms, concerns have been raised regarding its potential health effects beyond the classical mechanism of cholinergic inhibition, particularly its impact on immune function. In this study, we aimed to systematically evaluate the immunotoxicity of MLT in mice and identify the lowest-observed-adverse-effect level (LOAEL) for immunotoxic effects. Key parameters assessed included body and organ weights, hematological and clinical chemistry profiles, histopathological changes, and immune function indicators. The results showed that exposure to MLT, particularly at low and intermediate doses, led to a significant increase in thymus weight, along with marked reductions in interleukin-10 (IL-10) levels, neutrophils, polychromatic erythroblasts, and monocyte lineage cells. Histological examination revealed atrophy of splenic white pulp, indicating immunopathological alterations predominantly at these dose levels. In contrast, immunoglobulin G (IgG) levels increased in a dose-dependent manner, possibly reflecting a compensatory humoral response to the observed suppression of cellular immune components. Meanwhile, the plaque-forming cell (PFC) response exhibited a dose-dependent trend but was significantly inhibited only at the highest dose, suggesting a complex, non-linear effect on humoral immunity. Based on significant alterations in thymus weight, cellular immune parameters, and splenic histopathology observed at the lowest dose tested (16 mg/kg bw), this value was preliminarily identified as the LOAEL for MLT-induced immunotoxicity in mice. Full article

Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, dehydration and death in piglets, resulting in significant economic losses in the pig industry. It is crucial to identify the pathogenesis and mechanism between host–PEDV interactions. In our study, we performed transcriptomic and metabolomic analyses in PEDV-infected Large White (LW) pigs. PEDV infection caused blunted and fused intestinal villi, necrosis of the intestinal mucosal epithelial cells and atrophy of intestinal glands. Transcriptomic and metabolomic analyses revealed 692 differentially expressed genes and 1485 differential metabolites, respectively. Among them, differentially expressed genes were enriched in virion assembly, lipoprotein metabolic process and PPAR signaling pathway. Differential metabolites were enriched in primary bile acid biosynthesis and lipoic acid metabolism. An integrated analysis of the transcriptome and metabolome revealed that differentially expressed genes and metabolites were co-enriched in steroid hormone biosynthesis and bile secretion. In addition, key metabolites Dehydroepiandrosterone (DHEA) and Estriol in steroid hormone biosynthesis both inhibited PEDV infection and alleviated the excessive inflammatory response in vitro. Collectively, our study constructed a multi-omics landscape of PEDV infection in LW pigs, providing potential targets for developing metabolic-targeted antiviral interventions. Full article

Background: Chicken infectious anemia virus (CIAV) is a globally significant immunosuppressive pathogen that causes substantial economic losses to the poultry industry, with particularly severe outbreaks in China in recent years. Given the limitations of existing vaccines, especially the residual virulence associated with live attenuated vaccines, there is an urgent need to develop novel, safer, and more effective vaccine strategies. Methods: In this study, the VP1 and VP2 genes of CIAV were cloned and expressed in Escherichia coli to develop a cost-effective subunit vaccine. Since VP1 primarily formed inclusion bodies, a “VP2-assisted co-refolding” strategy was employed. This involved denaturing VP1 and refolding it via gradient dialysis in the presence of soluble VP2, thereby leveraging VP2’s natural chaperone-like function to restore conformational epitopes. The refolded VP1/VP2 protein complexes, emulsified at different ratios, were used to immunize 3-day-old specific pathogen-free (SPF) chickens, followed by challenge with a virulent CIAV strain. Results: The vaccine formulation with a VP1:VP2 ratio of 1:1 provided the best protection, achieving 71.4% (5/7) protective efficacy, as evidenced by significantly reduced thymic atrophy and a higher thymus index. Conclusions: These findings validate the feasibility of using an economical prokaryotic expression system combined with a rational protein refolding strategy to produce a protective subunit vaccine candidate against CIAV, offering a promising alternative for disease control. Full article

Background/Objectives: Pancreatic cancer-associated cachexia (CAC) is a complex, multifactorial and multi-organ metabolic syndrome affecting approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC). Recent epidemiological data show that cachexia is a primary cause of mortality in PDAC, directly accounting for approximately 30% of cancer-related deaths and significantly limiting the tolerability of cancer therapy and is associated with adverse effects of treatment. It is defined by systemic weight loss, skeletal muscle atrophy (sarcopenia), and adipose tissue depletion, often driven by systemic inflammation and metabolic dysregulation. Methods: The literature was searched in PubMed and Scopus using combinations of keywords. The search covers the literature between 2016 and 2026, but papers before this period were also included because of their historical importance. Studies with higher evidential value, such as prospective studies, randomized controlled trials, and meta-analyses, were prioritized and emphasized in our analysis. Results: CAC in PC arises from a systemic inflammatory response driven by tumor–host interactions and the release of pro-inflammatory mediators, such as growth differentiation factor 15 (GDF-15) and parathyroid hormone-related protein (PTHrP), which promotes anorexia and weight loss. The most commonly used diagnostic criteria include unintentional weight loss of more than 5% of body mass within 6 months, a body mass index (BMI) below 20 kg/m², or weight loss greater than 2% in the presence of sarcopenia. Emerging evidence supports the use of AI-based body composition analysis and novel biomarkers, including GDF-15 levels, to improve the detection and monitoring of cachexia. This review highlights that, despite the absence of pharmacological agents specifically approved for CAC in the United States and Europe, current guidelines recommend multimodal supportive care, including low-dose olanzapine, nutritional support, and exercise-based interventions. Furthermore, we identify recent phase 2 trials targeting the GDF-15 pathway, such as the GDF-15 inhibitor ponsegromab, which have demonstrated significant improvements in body weight and physical activity, suggesting a potential breakthrough in targeted therapies for CAC. Conclusions: CAC in PDAC represents a critical unmet medical need in oncology. It manifests as a lethal systemic pathology that demands early identification and targeted personalized pharmacological and nutritional interventions. Early diagnosis and targeted intervention represent promising strategies for improving survival and quality of life in this high-risk patient population. Full article

High myopia is increasingly prevalent and complicates glaucoma diagnosis. Axial elongation remodels the optic nerve head (ONH) and parapapillary tissues, producing structural and functional changes that mimic glaucoma—termed myopic optic neuropathy (MON). We reviewed current concepts on the MON–glaucomatous optic neuropathy (GON) spectrum and practical implications for diagnosis, monitoring, and management. A focused PubMed search targeted high/pathologic myopia, glaucoma, ONH and parapapillary anatomy, optical coherence tomography (OCT)/OCT angiography, visual fields, and progression. Major reviews, population-based studies, and longitudinal investigations were prioritized and integrated into a clinician-oriented framework. Greater myopia severity is associated with higher glaucoma risk and, in some cohorts, greater treatment burden, including surgery. Disc tilt, torsion, parapapillary atrophy, and staphyloma-related curvature complicate structural assessment and reduce reliability of single-visit OCT due to magnification and segmentation artifacts. Visual fields may be atypical, and central defects are under-sampled by standard 24-2 testing. Progression-centered strategies—combining event- and trend-based analyses and confirmation rules—distinguish MON-predominant changes from true GON or overlap and guide follow-up. In highly myopic eyes, multimodal structure–function assessment anchored on reproducible progression enhances diagnostic confidence and guides individualized intraocular pressure–lowering therapy. Standardized reporting of myopia definitions and progression criteria is recommended. Full article

Background and Aims: Autoimmune gastritis (AIG) is a chronic immune-mediated condition characterized by corpus-predominant atrophy, which can lead to vitamin B12 deficiency, achlorhydria, and an increased risk of gastric adenocarcinoma (GC) and neuroendocrine tumours. Diagnosis is often challenging due to a long asymptomatic phase and variable clinical presentation. This study aimed to assess the prevalence of gastric cancer and advanced premalignant lesions and to identify risk factors associated with a worse endoscopic outcome. Methods: This retrospective observational study involving AIG patients undergoing endoscopic surveillance (2006–2024) at the Hospital Clínic de Barcelona. Patients with AIG were identified based on the presence of anti-parietal cell antibodies and/or intrinsic factor antibodies and underwent endoscopic surveillance with histological assessment. Clinical, serological, endoscopic, and histological data were evaluated to estimate the prevalence of gastric lesions. Potential risk factors were evaluated using logistic regression. Results: A total of 70 patients met the inclusion criteria (median age 60 years; 60% female). Advanced premalignant findings (high- and low-grade dysplasia) were identified in 15.7% of the patients, while GC was found in 5.7%. Atrophy and intestinal metaplasia were present in 98.6% and 74.3% of patients, respectively. Female sex was independently associated with a lower risk of advanced neoplastic findings (OR = 0.24; 95% CI: 0.06–0.95; p = 0.044), whereas older age at diagnosis was associated with an increased risk (OR = 1.06; 95% CI: 1.00–1.11; p = 0.031). Conclusions: Given the high prevalence of premalignant lesions in AIG, endoscopic surveillance appears essential for early detection. The observed associations with female sex and older age, toward lower and higher probabilities of advanced neoplastic findings, respectively, may contribute to future risk stratification models. However, the limited identification of significant predictors underlines the complexity of AIG progression and supports the development of individualized follow-up protocols. Full article

Background: Main risk factors associated with the development of sarcopenia (coexistence of muscle mass loss and dysfunction) are a sedentary lifestyle coupled with obesity. Associated mitochondrial dysfunction leads to energy deficits and perturbations in the balance between protein synthesis and degradation, thereby triggering muscle dysfunction or atrophy. Aside from exercise, which is challenging to implement and maintain, particularly in women, treatments for diminishing sarcopenia are scarce. The objective of the present study was to evaluate the effect of the flavanol (−)-epicatechin (EC) in a hypercaloric diet-induced obese female rat model. Muscle strength and endurance, as well as relative mitochondrial DNA content in skeletal muscle, were assessed. Methods: Female rats were fed a hypercaloric diet to induce obesity, as evidenced by increases in body weight, Lee index, and lipid profile alterations, and by abdominal fat accumulation, and to promote a sarcopenic phenotype. Functional tests of grip strength and mobility (treadmill) were performed. Mitochondrial relative content was evaluated by measuring the ratio of mtDNA/nuclear DNA, and the expression of genes related to mitochondrial biogenesis (Pgc1-α, Tfam), fusion (Mfn1 and Opa1), fission (Drp1 and Fis1), and mitophagy (Pink1 and Pkn), and function; citrate synthase and Ucp3 were also evaluated. Results: A significant decrease in mobility and strength was observed in obese female rats, accompanied by reduced mitochondrial numbers, activity, and dynamics, but not by changes in muscle size or weight. Treatment with EC induced mitochondrial biogenesis and positive changes in mitochondrial dynamics (fission and fusion) and activity, as measured indirectly by changes in citrate synthase and Ucp3 expression. Discussion: Results reinforce the potential of EC as a modulator of mitochondrial function in dysfunctional conditions associated with obesity, thereby attenuating the mechanisms underlying sarcopenia. Full article

Background: X-linked immunodeficiency with magnesium defect, Epstein–Barr virus (EBV) infection, and neoplasia (XMEN) disease is a rare inborn error of immunity caused by loss-of-function mutations in MAGT1, leading to impaired N-linked glycosylation. Although chronic EBV viremia is a hallmark of XMEN disease, the mechanisms underlying its marked clinical heterogeneity remain poorly understood. Methods: We performed an in-depth clinical, immunological, and genetic characterization of two siblings carrying a pathogenic MAGT1 variant (c.369_370insCC; p.Gly124fs), validated and deposited in ClinVar (SCV007293792). Assessments included whole-exome sequencing, multiparametric flow cytometry focusing on NKG2D expression, and longitudinal clinical follow-up. Results: Despite shared absence of NKG2D expression, the siblings exhibited strikingly divergent phenotypes. One sibling developed progressive neurodegeneration with central nervous system atrophy. The other presented with a complex immuno-hematologic phenotype, including EBV-positive Hodgkin lymphoma, recurrent autoimmune cytopenias, and lymphoma-associated thrombotic microangiopathy, representing a novel clinical association in XMEN disease. Comparative immunophenotyping revealed shared defects in B-cell maturation but distinct T-cell differentiation patterns. To contextualize neurological variability, we propose a descriptive, hypothesis-generating three-category conceptual classification comprising early-onset neurodevelopmental forms, adult-onset neurodegenerative manifestations, and secondary immune-mediated or vascular involvement of the nervous system. Conclusions: These findings demonstrate profound intrafamilial heterogeneity in XMEN disease and suggest a model in which modifier-sensitive factors influence organ-specific disease expression. The observation of lymphoma-associated thrombotic microangiopathy and the proposed descriptive neurological classification provide a conceptual framework that may help guide tailored, multidisciplinary surveillance beyond the primary genetic defect. Full article

Background/Objectives: Translating brain volumetric biomarkers to individual-level Alzheimer’s disease (AD) diagnosis remains challenging due to difficulty interpreting raw volumes without longitudinal monitoring or matched controls. We tested a classification model using population-referenced volumetric percentiles to distinguish AD from cognitively normal (CN) subjects and evaluated its generalization across independent cohorts. Methods: Brain volumes from 95 regions were extracted using an automated segmentation pipeline and converted to age and sex adjusted percentiles using a reference population (N = 1833). A logistic regression classifier was trained on ADNI subjects (N = 873; AD = 183, CN = 690) split into training (60%), validation (20%), and test (20%) sets. The model was evaluated on two independent validation datasets: the held-out ADNI validation set and an external Korean cohort (N = 72; AD = 36, CN = 36) acquired with different scanner protocols and demographic characteristics. Results: The model achieved excellent discrimination across all evaluation sets: ADNI validation (AUC = 0.963, accuracy = 90.3%), ADNI test (AUC = 0.960, accuracy = 89.7%), and Korean external validation (AUC = 0.981, accuracy = 87.5%). The minimal validation gap (0.018) demonstrated robust generalization. Positive coefficients for ventricular regions reflected AD-associated atrophy patterns, while negative coefficients for medial temporal structures indicated their contribution within multivariate patterns distinguishing AD from normal aging. Conclusions: Population-referenced brain volumetric percentiles enable accurate AD classification with robust generalization across populations and scanner protocols. By contextualizing individual brain structure relative to normative populations while accounting for age and sex, this approach demonstrates potential for clinical translation as an accessible neuroimaging-based diagnostic tool. Full article

(−)-Epigallocatechin 3-gallate (EGCG) is a potent natural antioxidant, but its strong bitterness and poor palatability limit its application in animal production. This study aimed to evaluate the protective effects and underlying mechanisms of chemically synthesized EGCG derivatives against oxidative stress using a diquat-induced mouse model. A total of 36 male ICR mice were randomly assigned into six groups (n = 6): Control (T0), Diquat (T1), EGCG + Diquat (T2), Epigallocatechin octanoate (EGCO) + Diquat (T3), Epigallocatechin p-chloromethylbenzoate (EGCP) + Diquat (T4), and Epigallocatechin ibuprofen ester (EGCI) + Diquat (T5). Oxidative stress was induced by intraperitoneal injection of diquat at day 27 of the experiment, while EGCG or its derivatives were administered via dietary supplementation. At day 28, the mice were weighed, killed, and the tissues were sampled. Diquat challenge significantly impaired growth, increased serum injury markers (ALT, AST, DAO, and D-LA) (p < 0.05), suppressed hepatic and jejunal antioxidant enzymes (GPx, SOD, and TAOC) while elevating MDA (p < 0.05), damaged jejunal morphology (villus atrophy) (p < 0.05), and downregulated tight junction proteins (ZO-1 and Occludin) (p < 0.05). Chemically synthesized EGCG derivatives, especially EGCI, effectively alleviated diquat-induced growth impairment and hepatic and intestinal oxidative damage by improving intestinal barrier function and enhancing systemic antioxidant capacity, possibly in part through activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Compared with EGCG, EGCI exhibited reduced bitterness and improved palatability, which favored normal feed intake. These findings provide strong theoretical support for the future application of EGCG derivatives, especially EGCI, as functional antioxidant additives in broiler production. Full article

Background/Objectives: The OPA1 gene encodes a dynamin-related GTPase essential for mitochondrial fusion. Variants in OPA1 are a major cause of autosomal dominant optic atrophy (DOA). A subset of DOA patients exhibits hearing loss, often manifesting as auditory neuropathy spectrum disorder (ANSD). In this study, we aimed to describe the frequency of OPA1-related hearing loss in a large cohort of patients with hearing loss and to explore the genotype–phenotype correlations and appropriate interventions. Methods: A total of 18,475 Japanese patients with hearing loss were recruited. Targeted massively parallel sequencing of 158 deafness-related genes was performed, and individuals with OPA1 variants were identified. Clinical data, including age of onset, audiological findings, and systemic features, were retrospectively reviewed. Results: Ten individuals from eight independent families carrying OPA1 variants were identified. Three variants were classified as pathogenic or likely pathogenic, while five were variants of uncertain significance. Hearing loss was typically post-lingual in onset and progressive, with predominantly mild-to-moderate severity. Missense variants tended to be associated with DOA-plus phenotypes and ANSD. Five patients obtained only limited benefit from hearing aids, whereas one patient who received a cochlear implant achieved good speech perception. Conclusions: OPA1 is a rare causative gene for hearing loss and is frequently associated with the ANSD phenotype. Affected individuals exhibited phenotypic heterogeneity, which may reflect incomplete penetrance or the influence of mitochondrial DNA-related factors. Full article

Background: Zearalenone (ZEA) is a potent estrogenic mycotoxin that adversely affects the female reproductive system, causing hormonal imbalance, uterine enlargement, structural changes in the reproductive tract, and reduced fertility. This study evaluated the protective effects of melittin-loaded chitosan nanoparticles (MEL-NPs) against ZEA-induced ovarian toxicity in female rats. Methods: Forty-eight adult female Wistar rats (180–200 g) were divided into four groups: Control, ZEA, ZEA + MEL, and ZEA + MEL-NPs. ZEA (2.7 mg/kg b.w.) was administered orally twice weekly for two weeks. MEL and MEL-NPs (40 μg/kg b.w.) were given orally three times weekly for one month. Serum biochemical parameters were measured, and ovarian tissues were examined grossly and histopathologically. qRT-PCR was performed to assess mRNA expression of inflammatory markers (TNF-α, IL-6, IL-1β), apoptotic marker (Caspase-3), and steroidogenic enzyme (CYP19A1). Results: ZEA exposure induced significant ovarian toxicity, evidenced by increased TNF-α, IL-6, IL-1β, LH, FSH, CA-125, and Caspase-3, along with decreased progesterone, antioxidant capacity, and CYP19A1 expression. Histopathology revealed ovarian atrophy, follicular degeneration, and fibrosis. Treatment with MEL-NPs markedly reversed these alterations, normalizing cytokine and hormonal profiles, restoring CYP19A1 expression, and improving ovarian morphology. MEL-NPs demonstrated superior protective effects compared to free MEL. Conclusions: MEL-NPs effectively ameliorate ZEA-induced ovarian toxicity by restoring hormonal balance, enhancing antioxidant defense, and reducing inflammation and apoptosis. These findings suggest that MEL-NPs could be a promising therapeutic strategy for preventing mycotoxin-induced ovarian dysfunction. Full article

Background/Objectives: Children with cerebral palsy (CP) often develop altered muscle architecture and calf muscle contractures. Orthotic immobilization aims to provide prolonged stretch to lengthen the muscle belly and muscle–tendon unit (MTU), but immobilization may also cause atrophy. This study investigated whether immobilization combined with periods of daily muscle activation has a different effect on calf muscle properties than continuous immobilization alone. Methods: Fourteen children with CP and equinus deformity (mean age: 9.9 ± 3.0 years; GMFCS Level I: 10, II: 4) were enrolled in a 12-week randomized controlled trial. Participants were allocated to one of two groups: continuous immobilization (23 h per day) with a dynamic ankle–foot orthosis (AFO), or a combined regimen consisting of immobilization (14 h) and a daily activity phase (10 h). Gastrocnemius medialis (GM) MTU properties, including muscle belly and Achilles tendon (AT) length, fascicle length, and muscle volume, among others, were assessed four times using three-dimensional (3D) freehand ultrasound. Results: Significant within-group increases in MTU and AT lengths were observed over time at both a 90° ankle position (p < 0.01) and a more dorsiflexed ankle position (4 Nm applied torque, p < 0.01). However, no significant group × time interactions were observed for any parameter. Conclusions: Contrary to our hypothesis, combining activity and immobilization did not confer additional benefits. Nevertheless, shorter orthosis-wearing time had the same effect on the MTU and could lead to improved compliance with orthosis treatment in CP. Larger trials are needed to support our findings. Full article