Search Results (5,981)

Morbid obesity is a complex, multifactorial disorder characterized by metabolic and inflammatory dysregulation. The aim of this study was to observe changes in obese patients adhering to a personalized nutrition plan based on multi-omic data. This study included 14 adult patients with a body mass index (BMI) > 40 kg/m² who were consecutively recruited from those presenting to our outpatient clinic and who met the inclusion criteria. Clinical, biochemical, hormonal, and glycomic parameters were assessed, along with whole-genome sequencing (WGS) that included a focused analysis of obesity-associated genes and an extended analysis encompassing genes related to cardiometabolic disorders, hereditary cancer risk, and nutrigenetic profiles. Patients were stratified into nutrigenetic clusters using a patented unsupervised machine learning platform (German Patent Office, No. DE 20 2025 101 197 U1), which was employed to generate personalized nutrigenetic dietary recommendations for patients with morbid obesity to follow over a six-month period. At baseline, participants exhibited elevated glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, and C-reactive protein (CRP) levels, consistent with insulin resistance and chronic low-grade inflammation. The majority of participants harbored risk alleles within the fat mass and obesity-associated gene (FTO) and the interleukin-6 gene (IL-6), together with multiple additional significant variants identified across more than 40 genes implicated in metabolic regulation and nutritional status. Using an AI-driven clustering model, these genetic polymorphisms delineated a uniform cluster of patients with morbid obesity. The mean GlycanAge index (56 ± 12.45 years) substantially exceeded chronological age (32 ± 9.62 years), indicating accelerated biological aging. Following a six-month personalized nutrigenetic dietary intervention, significant reductions were observed in both BMI (from 52.09 ± 7.41 to 34.6 ± 9.06 kg/m², p < 0.01) and GlycanAge index (from 56 ± 12.45 to 48 ± 14.83 years, p < 0.01). Morbid obesity is characterized by a pro-inflammatory and metabolically adverse molecular signature reflected in accelerated glycomic aging. Personalized nutrigenetic dietary interventions, derived from AI-driven analysis of whole-genome sequencing (WGS) data, effectively reduced both BMI and biological age markers, supporting integrative multi-omics and machine learning approaches as promising tools in precision-based obesity management. Full article

Mastitis is a prevalent disease in the dairy cattle industry and has adverse effects on dairy cows’ health and milk quality. Importantly, mastitis is associated with the inflammatory response and mitophagy. As a complement-regulatory factor, C4b-binding protein alpha (C4BPA) has been shown to modulate inflammatory factors. This study further investigates its role and mechanisms in regulating mitophagy and inflammatory responses. Following C4BPA knockout, bovine mammary epithelial cells (BMECs) exhibited reduced expression of TLR4 and key pro-inflammatory cytokines, namely the tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Electron microscopy revealed a marked increase in mitochondrial membrane rupture, as well as cristae disorder and damage and increased reactive oxygen species (ROS) levels. Moreover, Pink1 and Parkin protein levels were increased, as was LC3B lipidation (LC3B-II), whereas p62 protein expression was significantly downregulated. Immunofluorescence indicated substantially increased LC3 colocalization with mitochondria, suggesting that C4BPA gene knockout activated Pink1/Parkin-mediated mitophagy. The fact that C4BPA knockout decreased the levels of p-IκB and p-p65 while increasing those of IκBα and p65 therefore indicates its regulatory role in the NF-κB-mediated inflammatory response. Together, these findings reveal that C4BPA deficiency in BMECs not only activates Pink1/Parkin-mediated mitophagy but also suppresses the NF-κB-mediated inflammatory response. This study provides novel potential molecular targets for predicting mastitis in dairy cattle. Full article

Background/Objectives: The micronutrient iron is closely connected to inflammation and is among the complex factors contributing to beta-cell failure in diabetes. High levels of dietary iron increase the risk of developing type 2 diabetes, and excessive iron uptake by beta-cells can cause oxidative stress and inhibit function. Elevated levels of proinflammatory cytokines in obese individuals, such as interleukin (IL)-1beta and IL-6, increase the risk of developing type 2 diabetes, and there is evidence that these low levels of circulating cytokines can lead to islet dysfunction. Methods: In this study, gene microarray and other data were analyzed for expression differences in islets treated for 48 h with 10 pg/mL IL-1beta + 20 pg/mL IL-6 as a model of low-grade inflammation versus untreated. Results: Three iron-associated genes were among the most cytokine-sensitive in the mouse genome: Hamp, Steap4, and Lcn2. These proteins are all involved with increasing/retaining cellular iron. We hypothesized that increased cellular iron would lead to increased susceptibility to ferroptosis. Surprisingly, 24 h pre-exposure to low-grade inflammation, which upregulates this iron-gene network, prevented subsequent erastin-induced ferroptosis. We also found that Steap4 overexpression reduced islet dysfunction caused by high-dose proinflammatory cytokines (10× low-dose), suggesting an overall protective effect. Steap4 overexpression also upregulated Hamp and Lcn2, suggesting Steap4 regulates these cytokine-sensitive iron genes.; in contrast, ferritin and ferroportin gene expression, which are not sensitive to cytokines, were unchanged. Conclusions: These data suggest an inflammation-induced network of genes involved in cellular iron uptake and retention plays a protective role in islets against oxidative stress and ferroptosis. Full article

Bacillus anthracis displays susceptibility to penicillin despite harboring a β-lactamase gene, a phenotype governed by the anti-sigma factor RsiP. While RsiP represses σ^P-dependent β-lactamase expression, its broader roles in physiology and virulence remain unclear. This study aimed to define the global regulatory functions of RsiP beyond antibiotic resistance. Deletion of rsiP significantly upregulated the nprR gene, which is an important quorum-sensing (QS) system regulator and enhanced protease secretion. The ΔrsiP mutant caused higher mortality in cellular and Galleria mellonella models and triggered elevated inflammatory cytokines (IL-6, IL-1β, TNF-α, MIP-2) in macrophages models. Surprisingly, in DBA/2 mice models, ΔrsiP was attenuated, with increased host survival and reduced bacterial loads. Competitive indices (CI) confirmed fitness defects in mice (spleen CI = 0.39; liver CI = 0.42). These defects were not due to altered oxidative stress tolerance but were attributed to impaired macrophage internalization of ΔrsiP spores, reducing early colonization. Our findings indicate that RsiP not only modulates β-lactam resistance but also influences extracellular protease activity and host adaptation. Full article

The role of extracellular vesicle non-coding RNAs in host–parasite interactions remains poorly understood, particularly for human liver flukes. Although tRNA-derived small RNAs (tsRNAs) are emerging as new regulatory molecules in parasite exosomes, they have not yet been characterized for the liver flukes. We performed small RNA sequencing to profile tsRNAs in the exosome-like vesicles derived from the liver fluke Opisthorchis felineus. Transcriptomic data from human cholangiocytes were analyzed to assess the enrichment of the predicted target genes among differentially expressed genes. We identified 247 functional tRNA genes in the O. felineus genome. Exosome-like vesicles were highly enriched for particular tsRNAs: derived from tRNA-Asp-GTC, tRNA-Ile-AAT, tRNA-Lys, tRNA-His, and tRNA-Tyr. This enrichment was independent of both genomic tRNA copy number and the amino acid composition of the trematode proteome. In silico prediction revealed that these tsRNAs target human genes involved in cell cycle, migration, and proliferation. Notably, these predicted target genes were significantly enriched among the differentially expressed genes in treated cholangiocytes. Our study provides the first evidence that O. felineus exosomes carry a specific repertoire of tsRNAs with the potential to regulate host gene networks. We propose that tsRNAs may contribute to host cell manipulation during O. felineus infection. Full article

The toxicity of micro- and nanoplastics in aquatic life is well documented, yet limited information is available on their effects in humans; moreover, most in vitro nanotoxicology studies rely on cancer cells. This study examined the effects of pristine and aged polystyrene micro- and nanoparticles on human dental pulp stem cells. While both particle sizes were internalized by the cells, primarily through endocytosis, they did not affect cell viability. In contrast, leachates from particles, aged for one month in culture medium, significantly reduced viability, indicating that toxicity arises from degradation byproducts rather than the particles themselves. Atomic force microscopy confirmed surface changes in aged plastics. Both particle sizes disorganized the cytoskeleton, leading to reduced actomyosin cortex integrity. Gene expression analysis revealed that leachates and aged particles activated inflammatory pathways, markedly increasing IL-8 and TGF-β1 expression, while also decreasing SOD levels associated with oxidative stress. No notable effects were observed on genes related to stemness or senescence. These results suggest that, while pristine micro- and nanoplastics may be relatively inert, their degradation products pose greater toxicological risks to human health. The findings highlight the importance of considering leachate toxicity in plastic pollution studies and demonstrate the value of stem cell-based models for evaluating the cellular and molecular impacts of environmental contaminants on human health. Full article

The trematode Clinostomum marginatum, secretes excretory-secretory products (ESPs) which have the potential to increase the viability and antioxidant activity of probiotic strains. The aim of this study was to identify the ESP profile of C. marginatum and to evaluate its anti-inflammatory activity in RAW 264.7 macrophages, as well as its effect on the viability and antioxidant activity of a consortium of bacteria comprising Lactobacillus and/or Bifidobacterium. C. marginatum was maintained in RPMI-1640 medium for ESP collection. Anti-inflammatory activity was assessed in LPS-stimulated RAW264.7 cells treated with 800 µg/mL of ESPs, measuring cell viability, nitric oxide production, and the relative expression of pro-inflammatory cytokines (IL-6, TNF-α, INF-γ) and the COX-2 gene by qPCR. The influence of ESPs (800–1600 µg/mL) on probiotic viability and antioxidant activity was determined using MTT, DPPH, hydroxyl, and superoxide radical scavenging assays. C. marginatum showed 74% survival in vitro, and SDS-PAGE analysis revealed three major protein bands in the ESPs (47, 54, and 58 kDa). ESP treatment significantly reduced nitric oxide and the mRNA expression of pro-inflammatory markers in LPS-activated macrophages. ESPs supplemented at 1200 µg/mL optimized the growth kinetics of Lactobacillus (specific growth rate μ_L = 1.12 h⁻¹, doubling time t_d = 0.62 h) and Bifidobacterium (μ_B = 1.09 h⁻¹, t_d = 0.63 h) compared to control conditions. In conclusion, ESPs from C. marginatum exhibited significant anti-inflammatory and antioxidant effects while enhancing bacterial viability, which positions them as promising candidates for biotherapeutics agents in the management of inflammatory control and gut microbiota modulation. Full article

Fucoidans are natural compounds that exhibit bioactivity against age-related macular degeneration (AMD), the leading cause of central vision loss in industrialized nations. Pathological factors like oxidative stress and lipid peroxidation play vital roles in AMD pathogenesis. Lipid-induced alterations in the retinal pigment epithelium (RPE) contribute to AMD development. In this study, a commercial fucoidan from Fucus vesiculosus (FVs) was tested for its activity regarding lipid-peroxidation-related effects. The human RPE cell line ARPE-19, primary porcine RPE, and RPE/choroid explants were stimulated with erastin, acting as an inducer of lipid peroxidation, and treated with fucoidan. Effects on cell viability (tetrazolium bromide (MTT) or calcein staining), vascular endothelial growth factor (VEGF) and interleukin 8 (IL8) secretion (ELISA), reactive oxygen species (ROS), protein expression (glutathione peroxidase 4 (GPX4), CD59, and retinoid isomerohydrolase (RPE65), analyzed via Western blot), and gene expression (RT-qPCR) were investigated. FVs showed protective effects against erastin-induced reduction in viability (with a 12.7% increase in viability compared to erastin), RPE65 expression (with a 4.2-fold increase compared to erastin), and GPX4 expression (with a 2.3-fold increase compared to erastin) in primary RPE. Erastin-induced VEGF secretion was attenuated by FVs in ARPE-19 and primary RPE (with an up to 1.7-fold reduction compared to erastin). Elevated IL8 levels were reduced by FV treatment in primary RPE (with a 9.1-fold reduction compared to erastin). Induced VEGF in RPE/choroid explants was reduced by FVs (with an up to 2.9-fold reduction compared to erastin), and this reduction was correlated with slight improvements in viability. In conclusion, FVs exerted protective effects against lipid-induced stress. This study reveals further effects of fucoidans against AMD-related pathologies. Full article

Background: This study aimed to assess the presence of thermotolerant Campylobacter resistant to ciprofloxacin and erythromycin in poultry slaughterhouses and retail markets, as well as to characterize their multidrug resistance profiles, genetic determinants, and clonal relationships. Methods: Samples were collected at slaughterhouses from cecal content (n = 270), neck skin (n = 270), and wastewater (n = 9), and at retail markets from breast skin (n = 241). Isolates were obtained from mCCDA agar supplemented with ciprofloxacin (2 μg/mL) and identified as C. jejuni or C. coli by PCR. The agar microdilution test was used to determine the minimum inhibitory concentration for ciprofloxacin and erythromycin, and other critical antibiotics. Point mutations in gyrA (Thr86Ile) and 23S rRNA (A2075G), virulence genes (flaA, flhA, cadF, and cdt), and clonal relationships were assessed by PCR and PFGE. Results: At the slaughterhouses, thermotolerant Campylobacter spp. resistant to erythromycin and ciprofloxacin were detected in 48.55% (107/549) of the samples, whereas 4.56% (11/241) of retail samples were positive. The Thr86Ile substitution in gyrA and the A2075G mutation in the 23S rRNA gene were detected in 92.97% and 89.84% of the isolates, respectively. Most isolates (>80%) were multidrug resistant and harbored key virulence genes (flaA, flhA, and cadF). C. jejuni exhibited the highest prevalence of cdt genes (76.19%). There was substantial genotypic diversity among isolates, with broad distribution across the sampled matrices and sites. Conclusions: These findings highlight the circulation of multidrug-resistant and potentially virulent thermotolerant Campylobacter spp. in the later stages of the poultry meat supply chain. Full article

The recent recognition of the Neotropical otter (Lontra annectens) as a distinct species highlights the need to evaluate its genetic status and connectivity across fragmented tropical habitats. We analyzed genetic diversity, population structure, and recent demographic patterns of L. annectens from two contrasting regions in northern Costa Rica—Tortuguero National Park (TNP) and the Sarapiquí River Basin (SRB). Non-invasive fecal and anal-gland secretion samples collected during 2021–2022 were genotyped at ten nuclear DNA microsatellite loci. Genetic diversity was moderate across regions (mean allelic richness [AR] = 3.98–4.03, observed heterozygosity [Ho] = 0.52–0.58), expected heterozygosity [He] = 0.62–0.65) with no significant inter-regional differences. Bayesian clustering, principal component analysis, and pairwise F_ST (0.002) supported a near-panmictic population. Kinship analyses detected localized clusters of related individuals, suggesting weak but non-random structuring, while contemporary migration estimates indicated low-frequency, asymmetric gene flow from SRB to TNP. Bottleneck tests revealed signatures of recent demographic contraction in both regions, particularly in TNP. These findings demonstrate limited yet ongoing connectivity among riverine subpopulations and emphasize that increasing habitat fragmentation could erode this exchange. Maintaining hydrological corridors and monitoring genetically vulnerable subpopulations should be conservation priorities to preserve gene flow and long-term viability of L. annectens in northern Costa Rica. Full article

The microevolutionary pathways and molecular mechanisms by which the important pathogen Vibrio parahaemolyticus acquires resistance in the aquatic environment under continuous selective pressure from quinolone antibiotic residues are still unknown. Here, the study successfully simulated the long-term pressure of antibiotic residues in aquaculture by susceptible V. parahaemolyticus (VPD14) which was isolated from seafood, to a 30-day in vitro induction with sublethal concentrations of levofloxacin, which yielded the mutants (VPD14M). A phenotypic analysis revealed that VPD14M exhibited resistance to ampicillin, levofloxacin and ciprofloxacin, compared to VPD14. These changes were accompanied by adaptations, including a decreased growth rate and an enhanced biofilm formation capacity. Whole-Genome Sequencing identified that the acquired resistance was primarily attributable to key point mutations in three Quinolone Resistance-Determining Regions (QRDRs). Specifically, a G → T substitution at nucleotide position 248 in the gyrA gene, leading to a serine-to-isoleucine substitution at the 83rd amino acid position (Ser83Ile) of the DNA gyrase subunit A; a C → T substitution at position 254 in the parC gene, resulting in a serine-to-phenylalanine substitution at position 85 (Ser85Phe) of the topoisomerase IV subunit A; and a C → T substitution at position 2242 in the gyrB gene, causing a proline-to-serine substitution at position 748 (Pro748Ser) of the DNA gyrase subunit B. Collectively, the study demonstrated that sublethal antibiotic levels rapidly drive quinolone resistance in V. parahaemolyticus, and the specific mutations identified offer critical support for resistance monitoring and seafood safety alerts. Full article

Background: Obesity-associated inflammation arises from adipose dysfunction and intestinal disturbances, including altered microbiota and short-chain fatty acid (SCFA) metabolism. Beans (Phaseolus vulgaris) are rich in non-digestible carbohydrates and polyphenols, but whether kidney bean varieties differing in seed coat colour exert distinct effects on inflammation in obesity remains unclear. Objective: To determine whether supplementation of an obesogenic high-fat (HF) diet with white or dark red kidney beans modulates gut microbiota, SCFAs, and intestinal, systemic, and neuroinflammatory outcomes. Methods: Male C57Bl/6N mice (n = 12/group) were fed a basal diet (BD; modified AIN-93G), an HF diet (60% kcal from fat), or an HF diet supplemented with 15% cooked white (HF + WK) or dark red kidney beans (HF + DK) for nine weeks. Outcomes included cecal microbiota composition, predicted KEGG pathways with taxon contributors mapped with BURRITO (a tool for linking predicted microbial functions to contributing taxa), and SCFA-related pathways; cecal and fecal SCFA concentrations; colon histomorphometry and expression of gut barrier junction and inflammatory genes; serum cytokines and adipose hormones; and hippocampal inflammatory and barrier genes. Results: Mice consuming bean-supplemented HF diets had higher microbial diversity, enrichment of SCFA-producing taxa (Prevotella, Lactobacillus, Muribaculaceae), and lower obesity-associated genera versus HF alone (Mucispirillum, rc4-4). Bean diets elevated cecal acetate and butyrate concentrations, which aligned with increases in predicted acetate kinase in both bean groups versus HF and BD, and butyrate kinase in HF + DK versus BD. Bean supplementation attenuated HF-induced reduction of goblet cells and systemic interleukin (IL)-10. The HF + DK group had lower colonic tumour necrosis factor (TNF)-α and partially attenuated hippocampal IL-6. SCFAs were inversely associated with systemic and neuroinflammatory markers in HF + DK mice. Conclusions: Kidney bean supplementation mitigated HF diet-induced intestinal, systemic, and neuroinflammatory disturbances in male mice, with microbiota and SCFA modulation. Further, dark red beans exerted stronger anti-inflammatory effects, highlighting the role of seed coat colour in bean-mediated obesity outcomes. Full article

Silicosis, an irreversible occupational lung disease resulting from prolonged exposure to respirable crystalline silica, faces challenges due to limitations in existing mammalian models. This study evaluated whether laboratory-prepared respirable α-quartz silica could induce immune cell–inflammatory–fibrotic initiation related to silicosis in zebrafish embryos as a tool for early toxicity assessment. Zebrafish embryos at 48 h post-fertilization (hpf) were microinjected into hindbrain ventricle with respirable α-quartz silica (test material 3.056 μm vs. standard material 3.217 μm) derived from natural α-quartz ore. The results indicated a significant decrease in zebrafish survival rates and an increase in malformation rates following exposure respirable α-quartz silica materials. Additionally, alterations in midbrain and hindbrain lengths were observed, while body length remained unaffected. Behavioral assessments revealed reduced touch response rates, decreased average speed, and less time spent in the central zone during open field tests in the treatment groups. In vivo imaging demonstrated sequential recruitment of neutrophils (peak at 18 h post-injection) and macrophages (peak at 24 h post-injection). qPCR analysis revealed upregulation of inflammation-related genes (tnf-α, il-6, il-1β) and fibrosis-related genes (tgf-β, acta-2, collagen). Moreover, the hydroxyproline content, a marker for fibrosis, was significantly elevated, although no mature fibrosis was observed histologically. These findings demonstrate that respirable α-quartz silica elicits pathophysiological changes associated with silicosis early initiation in zebrafish embryos. This supports the utility of the zebrafish embryo as a practical tool for early toxicity assessment and mechanistic studies of silica-induced immune–inflammatory–fibrotic initiation, with potential implications for silica exposure early risk warning. Full article

Background/Objectives: Pregnancy is characterized by complex immunological adaptations that may increase susceptibility to infections, including SARS-CoV-2. Interleukin-6 (IL-6), a key pro-inflammatory cytokine, plays a crucial role in the immune response and has been strongly implicated in the pathogenesis of COVID-19. Genetic variations in the IL6 gene, particularly single-nucleotide polymorphisms (SNPs) in the promoter region, can modulate IL-6 expression and potentially influence individual susceptibility to viral infections. This study aimed to evaluate the relationship between promoter region IL6 gene polymorphisms and COVID-19 susceptibility, as well as the inflammatory response, in pregnant women. Methods: We enrolled in this study 204 pregnant women with evidence of SARS-CoV-2 infection in pregnancy and 134 pregnant women with no evidence of SARS-CoV-2 infection in the past. Genotyping was conducted for the two functional SNPs in the IL6 promoter region, rs1800796 and rs1800797, via Sanger sequencing, and for associations with COVID-19 susceptibility and IL-6 levels were analyzed. Results: No significant association was found between IL6 polymorphisms and COVID-19, IL-6 levels, age, or immunization status. IL-6 levels > 5 pg/mL were more frequent in SARS-CoV-2-negative pregnant women than in SARS-CoV-2-positive pregnant women (p = 0.032). Among vaccinated participants, IL-6 levels were significantly higher in SARS-CoV-2-negative pregnant women (p = 0.044), while no difference was observed in the unvaccinated group. Conclusions:IL6 polymorphisms rs1800797 and rs1800796 were not associated with infection susceptibility or IL-6 levels. These results highlight the complex immunological interplay between pregnancy, infection, and genetic background and support the need for further research in larger cohorts. Full article

Metabolic reprogramming is a hallmark of psoriasis, yet the contribution of lactate metabolism to keratinocyte-mediated immune dysregulation remains undefined. Through integrated bulk and single-cell RNA sequencing, validated by immunofluorescence and metabolic assays, we identified the mitochondrial protein SCO2 as a key pathogenic hub gene upregulated in psoriatic lesions. Functionally, SCO2 overexpression promoted keratinocyte migration and triggered a metabolic shift characterized by mitochondrial pyruvate accumulation and intracellular lactate retention. Single-cell analysis further revealed that SCO2-high keratinocytes establish pathogenic crosstalk with CCR7⁺ dendritic cells via MIF-(CD74 + CD44) interactions, wherein these CCR7⁺ dendritic cells serve as the primary source of IL-23 and co-stimulatory signals (CD80/CD86) to drive robust T cell priming. Our findings highlight SCO2 as a pivotal immunometabolic switch linking keratinocyte metabolism to adaptive immunity. Targeting SCO2 offers a novel strategy to disrupt the keratinocyte-driven recruitment of CCR7⁺ DCs, thereby attenuating the IL-23-mediated inflammatory cascade. Furthermore, SCO2 may serve as a potential biomarker for metabolic dysregulation in psoriatic lesions. Full article