Search Results (69,777)

Catestatin is a chromogranin A–derived peptide involved in sympathetic, cardiovascular, inflammatory, and metabolic regulation, but its longitudinal profile during pregnancy remains insufficiently defined. This prospective cohort study aimed to evaluate changes in serum catestatin concentrations from the first to the third trimester and to explore their associations with blood pressure and metabolic parameters in initially low-risk singleton pregnancies. Fifty pregnant women were followed longitudinally from 11–13 + 6/7 to 30–41 + 5/7weeks of gestation. Clinical and biochemical parameters were assessed at both visits, and serum catestatin concentrations were measured using a commercial enzyme immunoassay. Serum catestatin concentrations were significantly lower in the third trimester than in the first trimester (median [IQR]: 9.4 [4.9–15.5] vs. 13.4 [9.9–24.6] ng/mL; p < 0.001). Longitudinal changes in catestatin were positively associated with third-trimester insulin concentrations after adjustment for selected covariates. Third-trimester catestatin concentrations were positively correlated with systolic blood pressure (r = 0.356, p = 0.011) and remained associated with systolic blood pressure in a limited multivariable model. These findings suggest that catestatin concentrations decline from early to late pregnancy and may reflect selected metabolic and hemodynamic changes. Larger longitudinal studies including pathological pregnancy cohorts are needed to clarify its clinical relevance. Full article

Background: Hashimoto’s thyroiditis (HT) is a chronic autoimmune disorder characterized not only by thyroid dysfunction but also by metabolic disturbances, micronutrient inadequacies, and low-grade inflammation. Composite indices derived from routine laboratory parameters may therefore help capture the broader systemic profile of the disease. This study explored within-cohort associations of immunonutritional indices including the Prognostic Nutritional Index (PNI), Nutritional Risk Index (NRI), and Controlling Nutritional Status (CONUT), and hemogram-derived inflammatory markers including the Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), Platelet-to-Lymphocyte Ratio (PLR), and Systemic Immune-Inflammation Index (SII), with thyroid function, thyroid autoimmunity, metabolic characteristics, disease duration, and vitamin D status in adults with Hashimoto’s thyroiditis. Methods: This cross-sectional study included 229 adults diagnosed with HT. PNI, NRI, CONUT, and complete blood count-derived inflammatory markers were evaluated in relation to thyroid function, thyroid autoimmunity, disease duration, metabolic characteristics, and vitamin D status. Because most variables were not normally distributed, the main analyses were conducted using non-parametric tests. Correlations were evaluated using Spearman’s rank correlation coefficients. Exploratory regression models were estimated using HC3 heteroscedasticity-consistent robust standard errors, and CRP-based sensitivity analyses were performed by excluding participants with CRP > 10 mg/L. Results: Vitamin D deficiency was highly prevalent and affected 70.3% of the participants. Among the immunonutritional indices, NRI differed significantly according to BMI category and HOMA-defined insulin resistance (both p < 0.001), indicating a closer relationship with metabolic burden. PNI was associated with disease duration (p = 0.009), whereas the inflammatory indices were largely similar across the clinical groupings examined. In exploratory robust regression models, the explanatory power remained modest (R² = 0.066–0.171). PLR showed the most consistent index-related association with TSH, whereas the CONUT–FT3 association observed in the full-sample robust model was not retained after CRP-based sensitivity analysis. Conclusions: Adults with HT in this study showed frequent vitamin D deficiency together with a substantial burden of excess weight and insulin resistance. Routine immunonutritional and inflammatory indices may provide supportive information on within-cohort biochemical and metabolic heterogeneity, but they should not be interpreted as stand-alone diagnostic or prognostic markers. In particular, NRI appeared to reflect metabolic and adiposity-related burden more than nutritional risk alone, while PLR showed the most internally consistent index-related association with TSH. Full article

Recently, an anti-inflammatory effect of no-ozone cold plasma (NCP) has been reported, but the direct use of NCP for treating muscle inflammation is very difficult since NCP is a form of gas. In this study, we tested whether the anti-inflammatory effect of the NCP could be delivered through conductive metal needles to reduce muscle inflammation. C2C12 mouse muscle cells were treated with TNFα to induce muscle inflammation and then treated with NCP and a conductive metal needle separately or in combination. The effects of NCP and a needle were monitored by performing RT‒PCR and Western blot analysis. As a result, NCP effectively suppressed the TNFα-mediated expression of the TNFα, IL1β, and FasL genes, but this effect weakened as the distance between the cells and the NCP increased. On the other hand, treatment of cells with a plasma-needle (PN) had an anti-inflammatory effect regardless of distance, and the anti-inflammatory effect of the PN was maintained under conditions where the gas flow of NCP was not delivered to the cells. It is believed that the PN-mediated activation of media plays a pivotal role in the anti-inflammatory effect of the PN. Finally, this study also showed that electroacupuncture can inhibit TNFα-induced inflammatory gene expression in a manner like a PN. Taken together, the results of this study demonstrate that the anti-inflammatory effect of NCP can be delivered through metal needles, suggesting that PN may be useful for treating inflammatory muscle pain. Full article

Metabolic disorders such as obesity, type 2 diabetes, and lipid disorders are major health challenges worldwide. There is increasing interest in the role of food-derived antioxidants in the context of metabolic disorders due to their documented antioxidant activity. Antioxidants such as flavonoids and polyphenols neutralize reactive oxygen species and reduce oxidative stress, which can affect cell function and metabolic processes. Anthocyanins, curcumin, and resveratrol exhibit physiological and pharmacological properties such as antioxidant, anti-inflammatory, anti-cancer, anti-obesity, and anti-diabetic effects. The main aim of this systematic review is to comprehensively evaluate and synthesize the current scientific evidence on the role of anthocyanins, curcumin, and resveratrol in the prevention and management of metabolic disorders, with a focus on obesity, type 2 diabetes, and dyslipidemia. Databases such as PubMed and Embase were searched, and the final selection included 105 studies that met the inclusion criteria. The analyzed studies demonstrated that anthocyanin supplementation (up to 320 mg/day) was associated with reductions in inflammatory markers such as IL-6 and TNF-α, improvements in HDL cholesterol, and modest reductions in HbA1c (~0.3–0.5%). Curcumin supplementation was associated with decreases in body weight (up to 0.82 kg), BMI (up to 0.30 kg/m²), triglycerides, total cholesterol, and fasting glucose levels. Resveratrol showed mixed but potentially beneficial effects on insulin sensitivity, oxidative stress markers, and lipid metabolism, although the clinical outcomes remained inconsistent across studies. These findings suggest that the antioxidant effects of anthocyanins, curcumin, and resveratrol may be related to their ability to suppress oxidative stress and inflammatory processes, thereby contributing to improvements in glucose and lipid metabolism. The conclusions from this analysis may contribute to a better understanding of the role of antioxidants in the management of metabolic health and indicate directions for future research in this area. Full article

Fermentation is widely used to enhance the bioactivity of herbal phytochemicals through microbial bioconversion. Rehmannia glutinosa contains catalpol, an iridoid glycoside with metabolic and immunomodulatory potential; however, its efficacy in the unfermented form is limited. This study investigated whether fermentation enhances catalpol production and improves metabolic and immune-regulating functions via glucagon-like peptide-1 receptor (GLP-1R) signaling. Rehmannia glutinosa extract was fermented under optimized conditions, and catalpol and iridoid precursor levels were quantified to assess bioconversion efficiency. Biological effects were evaluated in intestinal epithelial cells, macrophages, and an Artemia model, focusing on glucose transport, GLP-1 secretion, dipeptidyl peptidase-4 (DPP-4) expression, mucosal defense, and GLP-1R/protein kinase A/cAMP response element-binding protein (PKA/CREB) signaling. Fermentation significantly increased catalpol content while reducing iridoid precursors. The fermented extract suppressed intestinal glucose absorption by downregulating sodium–glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2). It also enhanced GLP-1 secretion and reduced DPP-4 expression, leading to activation of GLP-1R/PKA/CREB signaling. This activation increased mucin 2 (MUC2) expression and promoted anti-inflammatory. Full article

Diabetic peripheral neuropathy (DPN) remains a leading cause of disability in diabetes, yet current care is largely symptomatic and does not directly address early neurovascular-immune pathology. This narrative review synthesizes clinical, redox, vascular, and immunological evidence into a peripheral nerve neurovascular unit (PNVU)/blood–nerve barrier (BNB)-centered framework for DPN. First, the review outlines the diagnostic and translational endpoint landscape of DPN, emphasizing that commonly used clinical, neurophysiological, small-fiber, and imaging-based tools capture important disease domains but do not directly assess early BNB dysfunction. It then reviews the anatomical and functional basis of the PNVU and BNB, including endoneurial microvascular endothelial cells, pericytes, basement membrane components, immune cells, and tight-junction proteins. Next, it discusses how chronic hyperglycemia and dyslipidemia drive metabolic-to-vascular coupling, redox imbalance, antioxidant defense failure, advanced glycation end products (AGEs), receptor for AGEs (RAGE), and nuclear factor-κB (NF-κB) signaling, endothelial activation, leukocyte recruitment, macrophage polarization, and junctional disassembly, culminating in increased BNB permeability and exposure of peripheral nerves to pro-inflammatory and neurotoxic mediators. Finally, it evaluates incretin-based therapies—including glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors, DPP-4is), and emerging multi-agonists—as potential modulators of oxidative and inflammatory stress within this framework. Although semaglutide and related agents show mechanistic plausibility and preclinical promise, direct evidence for incretin-mediated BNB stabilization in human DPN remains limited. By reframing DPN as a redox-driven neurovascular-immune disorder, this review highlights barrier-focused biomarkers, translational endpoints, and hypothesis-generating therapeutic opportunities that require clinical validation. Full article

Leukemia inhibitory factor (LIF), a member of the interleukin-6 (IL-6) cytokine family, is a well-characterized myokine with pleiotropic regulatory effects on skeletal muscle. LIF modulates several fundamental cellular processes, including myoblast proliferation, apoptosis, angiogenesis, and energy metabolism. Exercise upregulates LIF expression in skeletal muscle, thereby promoting satellite cell activation, proliferation, myoblast differentiation, and angiogenesis, facilitating physiological muscle hypertrophy, and suppressing myocyte apoptosis and muscle atrophy. In addition, LIF plays a critical role in modulating the inflammatory and extracellular matrix remodeling following exercise-induced muscle damage, thereby supporting efficient muscle repair and regeneration. This review elaborates on the biological mechanisms by which LIF regulates skeletal muscle atrophy and contributes to the enhancement of skeletal muscle function. It also highlights the biological characteristics of myogenic LIF and discusses future directions for basic and applied research on exercise interventions targeting LIF signaling pathways. Full article

The number of individuals affected by dementia and cognitive decline is progressively increasing, becoming a serious global health challenge. Several investigations underline the role of nutrition and dietary habits as a preventive strategy. Recent studies suggest that dietary supplementation with polyphenols may constitute an efficient preventive strategy. Indeed, it is emerging that polyphenols exhibit a neuroprotective effect because of their pronounced antioxidant and anti-inflammatory activity. Notably, several studies underline the role of the gut microbiota in the metabolism of the polyphenols, producing bioactive molecules that are absorbed through the gastrointestinal tract. They may exhibit beneficial effects on the central nervous system. Moreover, dietary polyphenols modulate gut microbiota composition, demonstrating a reciprocal regulation between gut microbiota and polyphenol-induced effects on brain functions. Thus, polyphenols are proposed to have an important role on the gut–microbiota–brain axis regulation. The literature search for this narrative review was conducted across three electronic databases PubMed, Scopus, and Web of Science as well as the NIH ClinicalTrials.gov registry, covering the period from January 2000 to 10 February 2026. The following search terms were used: “polyphenols”, “microbiota”, “gut–brain axis”, “dementia”, “cognitive function”, “polyphenols and cognitive dysfunction”, and “polyphenols and microbiota”. The study selection process was performed in two sequential stages: (i) screening of titles and abstracts, followed by (ii) full-text assessment for eligibility. Articles were included if they were peer-reviewed studies (in vitro, in vivo, or clinical trials), published in English, and addressed the effects of polyphenols on cognitive outcomes, gut microbiota composition, or the gut–microbiota–brain axis. Exclusion criteria included non-peer-reviewed sources, studies lacking relevant cognitive or microbiota-related endpoints, and publications not available in full. Full article

Introduction: Live attenuated vaccines (LAVs) are generally avoided in patients with inflammatory bowel disease (IBD) receiving immunomodulatory therapy due to concerns about infection risk. However, real-world data evaluating their safety in this population remain limited. We aimed to assess adverse outcomes following LAV administration in IBD patients treated with biologic agents. Methods: We conducted a retrospective cohort study using the TriNetX multi-institutional database. Adults with IBD receiving immunomodulatory therapy were categorized into two cohorts: those who received an LAV and those who did not. Biologic therapies included tumor necrosis factor inhibitors (infliximab, and adalimumab), integrin antagonists (vedolizumab), interleukin (IL)-12/23 inhibitors (ustekinumab), IL-23 inhibitors (risankizumab, and guselkumab), and Janus kinase inhibitors (tofacitinib, and upadacitinib). LAVs included measles–mumps–rubella (MMR), varicella (Varivax), and yellow fever vaccines. Propensity score matching was performed based on age, sex, IBD subtype (Crohn’s disease vs. ulcerative colitis), and biologic class. Patients with outcomes prior to the risk window were excluded. Adverse outcomes within six months included hospitalization, emergency department (ED) visits, fever, rash, and encephalitis. Results: A total of 672 patients were included in each propensity-score-matched cohort. Live attenuated vaccine (LAV) administration was not associated with significantly increased adverse outcomes compared with no LAV exposure during the six-month follow-up period. Hospitalization occurred in 14.9% versus 15.3% of patients, respectively (risk ratio [RR] 0.97; 95% confidence interval [CI] 0.75–1.25; p = 0.819), while emergency department visits occurred in 12.6% vs 11.3% (RR 1.12; 95% CI 0.84–1.50; p = 0.450). There were no significant differences in fever (3.6% vs. 3.3%; RR 1.09; 95% CI 0.62–1.93; p = 0.764) or rash (4.0% vs. 2.7%; RR 1.50; 95% CI 0.83–2.70; p = 0.172). No cases of measles, mumps, rubella, varicella, yellow fever, or encephalitis were identified in either cohort during follow-up. Conclusions: LAVs were not associated with an increased risk of adverse outcomes within one day to six months among IBD patients receiving immunomodulatory therapy. These real-world findings suggest comparable short-term outcomes between the cohorts of patients with IBD receiving biologic or targeted synthetic therapy who met the predefined eligibility criteria including age ≥ 18 years, and vaccination occurring between two weeks and six months after biologic initiation regarding LAV use in patients with IBD receiving biologic agents. Full article

Neuroinflammation is increasingly implicated in depression pathogenesis, yet the underlying mechanisms are still unclear. This study explores whether PSMB4/MHC-I signaling in the cerebrospinal fluid (CSF)-contacting nucleus mediates neuroinflammatory depression. A persistent neuroinflammation-associated depression model was established in mice by repeated intracerebroventricular lipopolysaccharide (LPS) administration. Depressive-like behaviors were evaluated using established assays. Neuroinflammatory responses and target protein expression were assessed by immunofluorescence, Western blotting, RT-qPCR, and laser capture microdissection. Neuronal activity was mapped by c-Fos staining and manipulated using chemogenetics, alongside pharmacological and genetic interventions. Repeated LPS administration induced significant depressive-like behaviors and obvious neuroinflammation in the CSF-contacting nucleus. Under these conditions, neuronal activity in this nucleus was selectively enhanced. Crucially, chemogenetic activation of these neurons alleviated depressive phenotypes, whereas their inhibition induced depression. Molecularly, LPS significantly upregulated PSMB4 and MHC-I expression. Pharmacological suppression of upstream neuroinflammation reversed this PSMB4 upregulation, and targeted PSMB4 knockdown reduced MHC-I expression, ultimately ameliorating depressive-like behaviors. These findings identify the CSF-contacting nucleus as a critical node in neuroinflammation-induced depression and reveal a novel PSMB4/MHC-I signaling axis linking central inflammatory responses to behavioral deficits. Full article

Post-stroke depression (PSD) is the most prevalent neuropsychological disorder among stroke survivors, affecting over 30% of patients. It significantly impairs patients’ quality of life and imposes a substantial burden on individuals, families, and society. Currently, the primary treatment for PSD focuses on conventional antidepressant therapies, with a lack of innovative approaches. Therefore, there is an urgent need to develop novel targeted therapies for PSD. This review synthesizes PSD pathogenesis as a multi-system network disorder involving monoamine deficits, neuroinflammation, HPA axis dysfunction, and neurotrophic imbalance. Within this framework, mesenchymal stem cells (MSCs) transplantation, as an emerging therapeutic strategy, may exert beneficial effects through anti-inflammatory, neuroprotective mechanisms, and the provision of neurotrophic factors. This review provides a preclinical framework that highlights the potential of MSC-based strategies, while emphasizing the need for further validation in PSD-specific models before clinical translation. Full article

Multisystem inflammatory syndrome in children (MIS-C) is a severe systemic inflammatory complication triggered by prior SARS-CoV-2 infection. It predominantly affects the cardiovascular system, and coronary artery injury, myocardial dysfunction, and myocardial ischemia are closely associated with disease severity and clinical outcomes. This article reviews the immunopathological characteristics and clinical manifestations of MIS-C-related coronary artery lesions, including coronary artery dilation and aneurysm formation, as well as the key pathophysiological mechanisms leading to myocardial ischemia. Based on recent clinical and translational research, we summarize current approaches to diagnosis, risk stratification, acute medical management, and long-term follow-up strategies. By synthesizing updated evidence, this review aims to provide theoretical support and practical clinical guidance for the early identification, timely intervention, and optimized management of affected children, ultimately improving their long-term cardiovascular prognosis. Full article

Background/Objectives: Post-traumatic joint contracture (PTJC) is a common complication in orthopedic surgery characterized by fibrosis and restricted joint mobility. Previous work by our multi-arm study demonstrated that nintedanib monotherapy could effectively mitigate PTJC by targeting fibroblast activation pathways. Since PTJC involves multiple simultaneously activated signaling pathways, we hypothesized that combination therapy targeting both inflammation and fibrosis might be advantageous for improving outcomes. As a candidate for combination treatment with nintedanib, bosentan, an endothelin receptor antagonist that modulates inflammatory responses, was chosen to assess whether this approach could improve the prevention of PTJC. Methods: Thirty-nine Sprague Dawley rats were randomized evenly into three groups after undergoing a standardized hyperextension trauma of the knee and K-wire arthrodesis over a period of two weeks. The experimental groups (n = 13 each) received a combination (COMB) of nintedanib (5 mg/kg/d, twice daily) and bosentan (50 mg/kg/d, twice daily), or nintedanib (5 mg/kg/d, twice daily) alone throughout the immobilization period. The control group (n = 13), meanwhile, was given a placebo. Joint mobility was evaluated quantitatively by measuring the contracture angle (CA) and resistance to extension. Additionally, tissue from the posterior joint capsule was collected for histological analysis. Quantitative PCR was used to analyze tissue and assess the expression levels of genes involved in the pro-fibrotic process, including, Il-6, Tgf-β, Nf-κb, Ctgf, and α-Sma. Statistical analysis involved Kruskal–Wallis and ANOVA tests with post hoc methods, with significance defined at p < 0.05. Results: Both combination therapy and nintedanib monotherapy significantly reduced the contracture angle compared to placebo (p ≤ 0.05 and p ≤ 0.01, respectively), with no significant difference between treatments. Histological analysis showed significantly fewer myofibroblasts in the COMB and nintedanib groups versus placebo (p < 0.05). α-SMA expression was significantly decreased by 8-fold (COMB) and 11-fold (nintedanib) compared to placebo (p < 0.05), with no differences between treatments. No significant differences were detected in upstream pro-fibrotic gene expression among groups. Conclusions: Based on results comparable to those achieved with nintedanib monotherapy, the additional administration of bosentan does not appear to offer any further benefit at the given experimental setup. Full article

Alveolar echinococcosis is a life-threatening zoonotic parasitic disease caused by infection of Echinococcus multilocularis larvae. To survive within the host’s immune milieu, E. multilocularis has evolved sophisticated immune evasion strategies, including the expression of immunomodulatory proteins that regulate the host immune response. Our previous studies have demonstrated that E. multilocularis calreticulin (EmCRT) possessed strong binding ability to human complement component C1q to inhibit C1q-initiated complement activation and biological functions. To further elucidate the mechanism by which EmCRT mediates C1q inactivation and immune evasion, the precise C1q-binding site on EmCRT was identified and analyzed in this study through expression of overlapping fragments and synthesis of overlapping peptides covering the identified functional fragment. The fragment expression and functional assay narrowed down the C1q-binding site to the EmCRT-S1 fragment located between amino acids 140 and 204 of EmCRT. The precise binding site was further pinpointed to the P5 peptide (EmCRT160–174 aa) by testing the synthetic peptides covering this region. The binding of peptide P5 to C1q markedly suppressed the activation of the C1q-mediated classical complement pathway and C1q-induced neutrophil chemotaxis, production of reactive oxygen species, cathepsin G, and myeloperoxidase. These findings suggest that the C1q-binding P5 peptide of EmCRT may serve as a potential target for the development of vaccines against echinococcosis or therapeutic drugs for complement-associated inflammatory or autoimmune diseases. Full article

Autoimmune diseases are characterized by chronic inflammation, immune dysregulation, and excessive oxidative stress, which collectively contribute to a progressive tissue damage and organ dysfunction. Although conventional immunosuppressive and anti-inflammatory therapies remain the main therapeutic approach, their clinical efficacy is often limited by poor pharmacokinetic properties, low tissue selectivity, systemic toxicity, and adverse effects following long-term administration. In this context, antioxidant-based nanoformulations have emerged as promising multi-target therapeutic strategies for the modulation of oxidative and inflammatory pathways involved in autoimmune disorders. This review focuses on polymeric and non-polymeric nanoformulations designed to improve the solubility, stability, bioavailability, controlled release, and targeted delivery of antioxidant and anti-inflammatory agents for autoimmune disease treatment. Recent advances in nanocarrier systems applications, including nanogels, poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), polymethacrylate, chitosan, hyaluronic acid, hydroxyapatite (HAP), lipid-based and ROS-responsive nanosystems, are discussed. The therapeutic potential of nanoencapsulated steroidal and non-steroidal anti-inflammatory drugs, antioxidant compounds, enzymes, inorganic elements, and nucleic acid-binding systems is evaluated through preclinical and limited clinical evidence. Many of these reported nanoformulations exhibit enhanced therapeutic efficacy, improved tissue targeting, reduced systemic toxicity, and the ability to simultaneously modulate oxidative stress and inflammatory signaling pathways. Despite the encouraging findings, important challenges remain regarding clinical translation, long-term safety, reproducibility, and large-scale production. In overall, antioxidant nanoformulations represent a promising and evolving platform for the development of more effective and targeted therapies against autoimmune diseases. Full article