Search Results (26,311)

Capsaicin, a naturally occurring polyphenol, is known to affect energy expenditure and muscle fatigue and modulate contractions in skeletal muscle. The L-type Ca²⁺ channels are known to be an important ion channel involved in the various muscle functions and the effect of capsaicin on the skeletal L-type Ca²⁺ channels is currently unknown. In this study, the effects of capsaicin and capsaicin analogs on depolarization-induced Ca²⁺ effluxes through L-type Ca²⁺ channels in transverse tubule membranes from rabbit skeletal muscle and L-type Ca²⁺ currents recorded using the whole-cell patch clamp technique in rat myotubes were examined. Capsaicin, in the concentration range of 3–100 µM, inhibited depolarization-induced Ca²⁺ effluxes. The effect of capsaicin was not reversed by TRPV1 antagonist SB-366791 (10 µM). While vanilloids (30 µM) including vanillin, vanillyl alcohol, and vanillylamine were ineffective, other capsaicinoids (30 µM) including dihydrocapsaicin, nonivamide, and nordihydrocapsaicin significantly inhibited Ca²⁺ effluxes, suggesting that hydrocarbon chains are required for inhibition. In rat myotubes, capsaicin inhibited L-type Ca²⁺ currents with an IC₅₀ value of 27.2 μM in the presence of SB-366791. Furthermore, in docking studies and molecular dynamic simulations, capsaicinoids with an aliphatic tail showed stronger binding and stable bent conformations in CaV1.1, forming hydrogen bonds with Ser1011 and Thr935 and hydrophobic/π–alkyl contacts with Phe1008, Ile1052, Met1366, and Ala1369, resembling the binding mode of amlodipine. In conclusion, the results indicate that the function of L-type Ca²⁺ channels in mammalian skeletal muscle was inhibited by capsaicin and capsaicin analogs in a TRPV1-independent manner. Full article

Background and Objectives: Many “food–medicine homologous traditional Chinese medicines (TCMs)” have been shown to delay vascular aging. In this study, we will select “food–medicine homologous TCMs” with the most potential to delay human-origin vascular aging and predict their core targets and mechanisms. Methods: Human-origin vascular-aging-related genes were screened from the NCBI and Aging Atlas databases. Candidate “food–medicine homologous TCMs” were initially filtered by constructing a protein–protein interaction network, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Key targets were validated in the Gene Expression Omnibus database and further screened by least absolute shrinkage and a selection operator. Finally, molecular docking and molecular dynamics simulations identified core targets. Results: Ten core “food–medicine homologous TCMs” with potential to delay human-derived vascular aging were identified: Crocus Sativus L., Glycyrrhiza uralensis Fisch., Chrysanthemum morifolium Ramat., Astragalus membranaceus (Fisch.) Bunge, Sophora japonica L., Hippophae rhamnoides L., Portulaca oleracea L., Lonicera japonica Thunb., Citrus aurantium L. var. amara Engl., and Morus alba L. Further analysis indicated that β-Carotene within these core “food–medicine homologous TCMs” may represent a potential active component targeting matrix metalloproteinase-1, with its action potentially linked to the interleukin-17 signaling pathway. The present study highlights the new hypothesis that immunosenescence (Th17/IL-17) is involved in vascular aging, suggesting that the top ten core “food–medicine homologous TCMs” may delay vascular aging by regulating immune cell function. Conclusions: The top ten “food–medicine homologous TCMs” provide potential candidates for functional products that delay vascular aging and provide computationally predicted mechanistic insights and a scientific basis for novel therapies. Full article

Background/Objectives: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects—particularly those involving Orexin-A, a peptide implicated in energy regulation—remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. Methods: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m²) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. Results: All participants completed the intervention. The ketogenic diet produced the largest sustained reductions in BMI, fat mass, fasting glucose, and total cholesterol over 12 months. TRF16:8 elicited more rapid early metabolic improvements and showed the most consistent longitudinal increase in Orexin-A levels. The ADF5:2 protocol resulted in moderate improvements across outcomes. In all groups, increases in Orexin-A were associated with markers of improved metabolic flexibility and reduced inflammation; however, mediation analyses were exploratory and non-causal. Between-group differences remained significant for fat mass, glucose, and Orexin-A trajectories after correction for multiple comparisons. Conclusions: The ketogenic diet was associated with the most pronounced long-term metabolic improvements, whereas 16:8 time-restricted eating yielded faster early responses and the most stable enhancement in Orexin-A levels. These findings indicate distinct metabolic and neuroendocrine adaptation profiles across dietary strategies. Given the small sample size, results should be interpreted cautiously, and larger trials are warranted to clarify the role of Orexin-A as a potential biomarker of dietary response in obesity. Full article

Background/Objectives: We investigated whether palmitic acid (PA) induced the expression of inflammatory cytokines and was involved in pyroptosis in a human dental pulp cell line. Methods: Human dental pulp cells cultured in Minimum Essential Medium Alpha (αMEM) were treated with 1 µg/mL LPS and/or PA (100, 300 and 500 µM). As a control, αMEM was added in the culture medium. The WST-1 assay was performed to assess cell proliferation, and morphological changes in cells were examined. RNA expression of IL-1β, IL-6, TNF-α, caspase-4 and gasdermin d were detected by quantitative RT-PCR (qPCR). Results: The WST-1 assay showed that cell viability decreased by 36% at 300 µM and 47% at 500 µM PA compared to the control (p < 0.05). Cell morphology revealed slight shrinkage in 100, 300 and 500 µM PA groups. RNA expression of IL-1β and IL-6 in the PA groups was significantly higher than that in the control groups (p < 0.05), while RNA expression of TNF-α in the PA group was the same as that of control group. The mRNA expression of caspase-4 and gasdermin d in PA groups was significantly higher than that in control group (p < 0.05). Likewise, the concentration of IL-1β and IL-6 was significantly higher in both LPS and PA groups than that in the LPS or PA groups (p < 0.05). Conclusions: The results of this study suggest that PA induces the expression of inflammatory cytokines and is involved in pyroptosis in a human dental pulp cell line. Full article

To address three core deficiencies of the existing research on ZnO varistors (incomplete full-lifecycle datasets, insufficient characterization robustness due to the lack of multi-parameter complementarity, and disconnected remaining life prediction and failure threshold determination), this study proposes a comprehensive technical solution for ZnO varistor remaining life prediction. An 8/20 μs impulse current accelerated deterioration experiment was designed to construct a full-lifecycle dataset (441 sets of data) covering nine same-batch ZnO varistors from their initial state to complete failure. Five core electrical parameters (varistor voltage U_1mA, nonlinear coefficient α, leakage current I_L, parallel resistance R_p, parallel capacitance C_p) were fused, and principal component analysis (PCA) was adopted for dimensionality reduction to form a high-robustness characterization feature (correlation coefficient with deterioration degree = 0.96). A combined model of Particle Swarm Optimization-Support Vector Regression (PSO-SVR) and Isolation Forest (iForest) was established to realize “quantitative prediction–qualitative threshold” collaboration. Experimental results show that the PSO-SVR model achieves high-precision remaining life prediction (test set R² = 0.9726, MSE = 0.00142) and the iForest model accurately identifies the failure threshold (AUC = 0.984, accuracy = 95.9%). The combined model reaches an overall accuracy of 99.89%, effectively solving the core deficiencies of the existing research and providing key technical support for SPD-condition monitoring and operation and maintenance decisions in energy systems. Full article

The development of RNA-based drugs for MAFLD-related fibrosis is severely hampered by the poor oral bioavailability of nucleic acids. This study employed a novel, patent-protected LNP formulation to orally deliver plant-derived miR-55 and investigate its therapeutic potential, focusing on its novel mechanism of action via the CK2α/SMO interaction. In a rat model established with a methionine-choline-deficient diet, orally administered miR-55 markedly improved liver injury, lipid dysregulation, oxidative stress, and pathological collagen deposition. The anti-fibrotic efficacy was quantitatively confirmed by a significant reduction in hepatic hydroxyproline content and downregulation of key fibrogenic genes (Col1a1, Col3a1, TIMP-1, TGF-β1, CTGF) and pro-inflammatory cytokines (TNF-α, IL-6), achieving effects comparable to the full Ge Xia Zhu Yu Decoction. Mechanistically, both bioinformatic prediction and in vivo validation indicated that miR-55 is predicted to target CK2α. This targeting suppressed CK2α expression and disrupted the endogenous CK2α-SMO complex, thereby promoting the ubiquitin-mediated degradation of SMO—a previously unreported mechanism. This cascade inhibited the downstream Gli1 pathway and downregulated pro-fibrotic and pro-angiogenic factors (VEGF, PDGF), thereby providing a comprehensive mechanistic basis for the therapeutic effects. This study is the first to provide evidence that orally delivered, plant-derived miR-55 may act as a natural modulator that potentially through disrupting the CK2α/SMO interaction via a unique complex disruption-promoted degradation mechanism, attenuating Hedgehog signaling and alleviating liver fibrosis. These findings offer important insights into cross-kingdom regulation and highlight miR-55 as a potential targeted therapeutic candidate. Full article

Background: Diabetic peripheral neuropathy (DPN) is a major complication of type 2 diabetes mellitus (T2D) that reduces quality of life and increases the risk of foot ulcers and amputations. Early detection is essential, and blood-based biomarkers may support improved screening and timely intervention. This study aimed to identify novel circulating biomarkers for the identification of DPN in patients with T2D. Methods: In the screening phase, plasma samples from 43 participants (10 healthy volunteers [HV], 20 T2D without complications, and 13 T2D with DPN) were analyzed using an antibody array targeting 310 proteins. Thirteen differentially expressed proteins were identified, and six hub proteins were selected through bioinformatic analysis. In the validation phase, plasma concentrations of the six proteins were measured by ELISA in 252 subjects (100 HV, 97 T2D without complications, and 55 T2D with DPN). Mucin-1 expression in sciatic nerves was further evaluated in db/db mice. Results: Of the six hub proteins (TGFB1, MUC1, PF4, IL2RA, SELL, B2M), only mucin-1 showed a significant increase in the DPN group. Plasma mucin-1 positively correlated with MNSI scores and negatively with motor and sensory nerve conduction velocities. In db/db mice, sciatic nerve mucin-1 expression was elevated, while CD31 expression was reduced. Conclusions: Plasma mucin-1 is strongly associated with DPN in both humans and animals and may serve as a promising biomarker for the screening and early identification of DPN. Full article

Oxidative stress represents a critical threat to aquatic animal health and aquaculture productivity. Allicin, a natural plant extract, has not been systematically investigated for its antioxidant mechanisms in aquatic crustaceans. This study established in vitro and in vivo models of tert-butyl hydroperoxide (T-BHP)-induced oxidative stress in Chinese mitten crabs (Eriocheir sinensis) to evaluate the hepatoprotective effects of allicin. Integrating biochemical, transcriptomic, and ultrastructural analyses, we found that allicin significantly alleviated T-BHP-induced cytotoxicity and oxidative damage in vitro. Mechanistically, allicin up-regulated antioxidant genes including glutathione peroxidase (gpx) and thioredoxin reductase 1 (trxr1), and down-regulated pro-inflammatory cytokines such as interleukin-1 beta (il-1β), suggesting the concomitant activation of the Nrf2 signaling pathway and inhibition of the p38-MAPK/NF-κB pathway. Transcriptomics further indicated its role in restoring proteostasis and mitochondrial function. A 35-day feeding trial validated these findings in vivo; dietary supplementation with 300 mg·kg⁻¹ allicin effectively reversed T-BHP-induced disturbances in antioxidant enzyme activities and immune-related gene expression. These consistent findings demonstrate that allicin alleviates hepatopancreatic oxidative damage through multi-pathway synergism, supporting its potential as a green and effective antioxidant feed additive in aquaculture. Full article

Neonatal neuroinflammation, driven by microglial activation and cytokine signaling, contributes to brain injury and adverse neurodevelopment outcomes. Perinatal inflammatory mediators, including interleukin-6, cyclooxygenase-2, and interleukin-17, prime microglia and influence circuit vulnerability. This study investigated whether oxytocin pretreatment attenuates lipopolysaccharide-induced inflammatory priming in BV-2 microglial cells. BV-2 microglia were preincubated with oxytocin (33 ng/mL) for 2 h, followed by lipopolysaccharide (0.5 µg/mL) for 2 h. Expression of ionized calcium-binding adapter molecule 1, a microglia marker, in BV-2 cells was assessed by immunofluorescence. After lipopolysaccharide treatment, the gene expression of BV-2 cells was assayed at 1, 2, and 6 h post stimulation by RT-qPCR and RNA-seq. Functional characterization of gene expression profile was performed. Analyses of gene expression profile of BV-2 cells by RT-qPCR and RNA-seq revealed that oxytocin pretreatment attenuated lipopolysaccharide-induced transcriptional activation, including interleukin-6 and cyclooxygenase-2 upregulation. Pathway enrichment analyses suggested that oxytocin-responsive genes were linked to the interleukin-17 signaling pathway. Gene Ontology enrichment analysis showed enrichment for genes related to cytokine production, membrane raft, and chemokine activity. Oxytocin pretreatment mitigates lipopolysaccharide-induced microglial activation by modulating the interleukin-17–interleukin-6/cyclooxygenase-2 axis, suggesting its potential role for oxytocin as an endogenous modulator of neuroinflammation during early brain development. Full article

Chronic rhinitis is induced by endotype-diverse inflammatory processes, which complicates effective therapeutic management. According to the current principles of personalized medicine, which also apply to the management of rhinological disorders, the best therapeutic results can be achieved after targeted treatment preceded by analysis of the patient’s endotype. Analysis of immune and cellular mechanisms allows for the use of biological treatment, and its effects provide new information on inflammatory processes in the nasal mucosa. The effects of biological treatment may be particularly interesting in the case of mixed endotypes, which pose a difficult therapeutic challenge. In eosinophilic asthma co-occurring with allergic rhinitis, as well as in eosinophilic asthma associated with non-allergic rhinitis, eosinophils represent a key effector cell population driving the underlying type 2-mediated inflammatory response. The aim of this study is to analyze the efficacy of anti-IL5 or anti-ILR5 therapy in patients with severe eosinophilic asthma and persistent allergic or non-allergic rhinitis. Methods: In this single-center real-life study, the authors analyzed the effects of biological treatment on rhinological symptoms in patients over the age of 18 with severe uncontrolled eosinophilic bronchial asthma with coexisting persistent allergic or non-allergic rhinitis treated with mepolizumab or benralizumab. In all patients, the otolaryngologist performed anterior rhinoscopy. Evaluation of rhinological symptoms and quality of life in patients treated with anti-IL5 or anti-IL5 therapy before and six months after biological treatment was performed using the TNSS and SNOT-22 scales. Results: In total, 67 patients with eosinophilic severe bronchial asthma were included in the study; among them 39 (58.2%) suffered from persistent allergic rhinitis and 28 (41.8%) suffered from chronic non-allergic rhinitis. After six months of treatment, higher absolute differences for SNOT and TNSS were observed in the persistent allergic rhinitis group. Conclusions: Biological treatment with mepolizumab and benralizumab may reduce the severity of rhinological symptoms in both endotypes of inflammation. However, higher therapeutic benefits were observed in patients with co-existing persistent allergic rhinitis. It was demonstrated that, in addition to IgE-mediated responses, the eosinophil represented an important component of the inflammatory reaction in allergic rhinitis. Full article

(1) Background: Neonatal sepsis continues to be one of the leading causes of mortality and morbidity, particularly in underdeveloped countries. We aimed to compare laboratory parameters between clinical early-onset sepsis (clinEOS) and NNNon-clinEOS groups and to evaluate the association between TLR2-Arg753Gln, TLR4-Asp299Gly, IL6-174G/C, and IL10-1082G/A gene single-nucleotide polymorphisms and clinical EOS susceptibility in preterm newborns. (2) Materials and Methods: Genotyping of the TLR2, TLR4, IL6, and IL10 polymorphisms was performed in 36 preterm neonates with polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP). Logistic regression analysis was used to test the associations between the studied gene polymorphisms and EOS susceptibility. (3) Results: Statistically significant differences in gestational age and birth weight were observed between the two groups, with preterm neonates with clinical EOS having a lower mean gestational age (mean (SD): 29.4 (2.8) weeks vs. 32.6 (1.1); p = 0.00002) and a lower mean birth weight (1342.1 (446.5) gr. Vs. 1984 (376.9)) than preterm neonates without clinical EOS. C-reactive protein (CRP) values measured on the first day significantly increased in the clinEOS group compared with the non-clinEOS group (median, 95% CI: 0.80 [0.40, 1.15] vs. 0.30 [0.02, 0.50]). The mean number of neutrophils significantly decreased in the preterm neonates with clinical EOS (mean difference: 17.3%; 95% CI: [4.0%, 30.5%]; p = 0.0126) and non-clinEOS group (mean difference: 20.8%; 95% CI: [1.8%, 39.9%]; p = 0.0354) between the first and seventh hospitalization days. In the dominant model, the A/G + A/A variant genotype of the IL10-1082G/A polymorphism significantly increased the odds of clinical EOS compared with the GG genotype (OR = 5.25; p = 0.0322), but the gestational-age-group adjusted model yielded p = 0.0752. (4) Conclusions: The results of the current study suggest that IL10-1082G/A gene polymorphism is a significant risk factor for clinical early-onset sepsis development in preterm neonates, but there was no evidence of a gestational age-group independent direct effect of IL10-1082G/A gene polymorphism on clinical EOS susceptibility. The results should be considered as exploratory. Full article

The sensory quality of pork constitutes a complex phenotype that arises from the interplay between genetic factors and environmental conditions. As a local pig breed in China, Tibetan pigs (TPs) are known for their high-quality meat. However, their slow growth rate and low production efficiency limit their large-scale breeding. We have used Duroc as a hybrid sire to improve TP. Our study found that TPs have higher intramuscular fat content and higher levels of monounsaturated fatty acids. Duroc × Tibetan crossbred pigs (DZs) not only retain the paternal high productivity but also inherit the superior meat quality of the maternal parent. Transcriptome analysis identified IL6, GPX1, GPX3, AOX1, ALDH7A1, PTGS2, NFKBIA, ADIPOQ and PPARG as being involved in affecting meat quality. Metabolomic analysis found that betaine, carnosine, L-carnitine, and lysophosphatidylcholine were important components that affect meat quality. Joint analysis further reveals that the expression of ATF4, DGKB, GNMT, and ADSL genes is closely related to arachidonic acid, lysophosphatidylcholine, betaines, and hypoxanthine, ultimately affecting the quality of the meat. By comprehensively analyzing the carcass and meat qual Full article

Acute Appendicitis (AA) is the commonest abdominal digestive surgical emergency, but its etiology is not clarified. Based on histologic observations, an allergic cause has been proposed. In a type I hypersensitivity allergic reaction, there is a Th2 immune response characterized by Th2 cells, eosinophils, basophils, IgE, IL-4, IL-5, and IL-13 serum elevation. Recent studies showed a local appendicular endoluminal and parietal Th2 immune response in acute phlegmonous appendicitis. We performed a prospective single-center study where we evaluated the Th2 blood immune response in 38 patients with acute phlegmonous appendicitis, 27 patients with acute gangrenous appendicitis, and 18 patients with the clinical picture of AA, who underwent appendectomy but had negative histology for AA (negative appendectomy group). Higher levels of basophils were found in phlegmonous appendicitis (p = 0.03), and higher levels of eosinophils were found in the control group (p = 0.003). Effector memory CD4 T cells re-expressing CD45RA were higher in gangrenous (p = 0.020) and central memory CD4 T cells in phlegmonous appendicitis (p = 0.004). The number of Th2 circulating cells was higher in gangrenous appendicitis (p = 0.037), while Th1 circulating cells were higher in phlegmonous appendicitis (p = 0.028). IL-4 blood concentrations were elevated in acute gangrenous appendicitis (p = 0.029). No significant differences were found in the levels of IgE, IL-5, or IL-13 in any of the groups. Thus, a Th2 response was not detected in patients’ serum with phlegmonous appendicitis. Serum levels of IgE, IL-5, and IL-13 were not different among patients with acute phlegmonous appendicitis, acute gangrenous appendicitis, and the negative appendectomy group. These findings are in contrast to our previous work in which we evaluated the Th2 response at the local level, at the appendicular luminal aspect and appendicular wall, in phlegmonous appendicitis and control groups, and we unequivocally showed a Th2 response in phlegmonous appendicitis. Thus, in patients with phlegmonous appendicitis, the local Th2 response is not reflected in the serum levels of immune cells and cytokines. Full article

Ultraviolet (UV) radiation is a primary environmental factor responsible for skin photodamage, and exposure to UV rays is strongly linked to a variety of skin diseases. This study examined the prophylactic and therapeutic effects of Seed Oil of Lycium barbarum L. from the Qaidam basin (QLBSO) in a UV-induced skin photodamage model in BALB/c mice, exploring potential mechanisms by analyzing the skin microbiota and metabolites using 16S rDNA sequencing and metabolomics. The results showed that QLBSO effectively alleviated UV-induced histopathological changes in mouse skin. It also significantly increased the activity of superoxide dismutase (SOD) and catalase (CAT) in UV-damaged skin tissue, while reducing levels of inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as matrix metalloproteinases-1 (MMP-1) and MMP-3. Omics analysis revealed that QLBSO successfully restored the balance of the skin microbiota and corrected disruptions in amino acid metabolism caused by UV exposure. Notably, Firmicutes_A and Kineothrix, along with cysteine, cystine, glycine, arginine, proline, and choline, were identified as key microbial species and metabolites responsive to QLBSO’s prophylactic and therapeutic effects. In conclusion, QLBSO likely protects against UV-induced skin photodamage by modulating the skin microbiota and amino acid metabolism, providing a scientific foundation for its potential use in skin health protection. Full article

Vasculitides are a heterogeneous group of disorders characterized by inflammation of blood vessel walls, leading to tissue ischemia and organ injury. Traditional inflammatory markers such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely used but lack diagnostic specificity. This has driven the search for more informative biomarkers across vasculitis subtypes. This review summarizes current evidence for validated and emerging biomarkers in large-, medium-, small-, and variable-vessel vasculitis, as well as single-organ vasculitis. Key analytes reflect systemic inflammation, such as serum amyloid A (SAA) and interleukin-6 (IL-6), as well as endothelial activation, complement pathways, neutrophil and macrophage activation, and organ-specific damage. Promising candidates include pentraxin-3 (PTX3) and matrix metalloproteinase-9 (MMP-9) in large-vessel vasculitis; N-terminal pro-B-type natriuretic peptide (NT-proBNP) and S100 proteins in Kawasaki disease; galactose-deficient immunoglobulin A1 (Gd-IgA1) and urinary angiotensinogen (AGT) in IgA vasculitis; and tissue inhibitor of metalloproteinases-1 (TIMP-1), S100 proteins, complement C3, and PTX3 in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Although these biomarkers provide mechanistic insight, most lack disease-specificity, external validation, or standardized assays. Future progress will require multicenter studies, harmonized testing, and integrated biomarker panels combined with imaging modalities to improve diagnosis, activity assessment, and monitoring. Full article