Search Results (27,493)

Psoriasis is classically defined as an immune-mediated disease. However, many patients do not achieve durable remission after immune-targeted therapies, suggesting that further pathogenic mechanisms may contribute to the persistence of psoriasis. Here, we propose ferroptosis, an iron-dependent regulated cell death driven by lipid peroxidation and failure of lipid repair, as a potential link between metabolic stress and immune-mediated inflammation in psoriasis. We summarize experimental evidence showing that membrane lipids remodeling, antioxidant suppression, lipid peroxidation, and dysregulated iron handling together define ferroptosis-permissive niches within psoriatic lesions. We also discuss functional studies demonstrating that ferroptosis modulation can reshape psoriasiform inflammation and explore how ferroptotic stress may amplify inflammatory signaling at the immune-epidermal interface, reinforcing IL-17/TNF/IFN-γ pathways. Finally, we discuss ferroptosis-related transcriptomic signatures as a potential approach to stratify psoriasis, capturing metabolic features that are not reflected by cytokine profiling. The translational opportunities and constraints for ferroptosis-targeted interventions are outlined, highlighting epidermal redox homeostasis as a new therapeutic frontier in psoriasis. Full article

Calcific aortic valve disease (CAVD) is an active pathological process driven by complex cellular and molecular mechanisms rather than passive aging. The disease is characterized by endothelial dysfunction, lipid infiltration, inflammation, extracellular matrix remodeling, and osteogenic differentiation of valvular interstitial cells, ultimately leading to hydroxyapatite deposition and progressive valve calcification. Key signaling pathways, including Notch, Wnt/β-catenin, BMP2, and TGF-β, play critical roles in osteogenic reprogramming, while inflammatory cytokines such as IL-6, IL-1β, and TNF-α contribute to a pro-calcific microenvironment. To summarize current knowledge on CAVD pathophysiology and emerging therapeutic strategies, relevant preclinical studies were identified through searches of PubMed, and clinical trials were identified through ClinicalTrials.gov. Evidence indicates that extracellular matrix remodeling, fibrosis, and dysregulated phosphate metabolism, particularly involving TNAP and DPP-4, further accelerate disease progression. Despite advances in understanding disease mechanisms, effective pharmacological therapies remain limited, with the current treatment largely restricted to valve replacement. Emerging therapeutic approaches targeting molecular pathways, including enzyme inhibition, RNA-based therapeutics, and advanced drug delivery systems, may offer promising strategies for disease modification. A deeper understanding of CAVD pathophysiology may facilitate the development of targeted therapies to delay or prevent disease progression. Full article

Encephalitozoon cuniculi is an atypical, opportunistic, obligate intracellular fungal pathogen that infects vertebrates. It survives within the host by modulating the host immune response. Crotoxin (CTX), a bioactive compound isolated from the venom of Crotalus durissus terrificus, has been reported to modulate immune responses. This study evaluated the effects of CTX on the immune response of mice infected with E. cuniculi. Mice were immunosuppressed with cyclophosphamide (Cy), infected with E. cuniculi spores, and treated with a single dose of CTX on the day of experimental. The animals were euthanized on day 14 post-infection. Levels of T helper (Th1, Th2, and Th17) cytokines were measured in plasma, and macrophage and lymphocyte populations were analyzed in peritoneal lavage fluid and spleen. In addition, histopathological alterations, hepatic fungal burden, and mRNA expression levels of NLRP3 inflammasome–related genes were assessed. CTX upregulated NLRP3 inflammasome expression and increased IL-18 production, while reducing fungal burden in E. cuniculi-infected mice. Moreover, CTX increased the proportions of macrophages and B cells and enhanced IFN-γ expression in CD4⁺ and CD8⁺ T lymphocytes. Collectively, these findings indicate that CTX reduces fungal load in Cy-immunosuppressed mice infected with E. cuniculi by priming the NLRP3 inflammasome complex and upregulating IL-18 production. Full article

Cystic fibrosis (CF) is an autosomal recessive disorder caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and primarily affects the respiratory, digestive, and reproductive systems. Globally, CF is most prevalent among European ancestry, with an incidence rate of approximately 1/2500 to 1/3500. In China, the incidence is about 1/128,000. However, CF is not extremely rare in the Chinese population; rather, its prevalence is significantly underestimated. The CFTR mutation spectrum in China is highly unique, characterized by an extremely low frequency of p.Phe508del. Instead, region-specific mutations such as p.Gly970Asp, p.Ile1023Arg, and p.Arg553Ter predominate, alongside a high proportion of splicing variants and complex rearrangements. A significant proportion of Chinese CF patients primarily present with CF-like phenotypes within the CF-related disease spectrum (such as congenital bilateral absence of the vas deferens and pseudo-Bartter syndrome), exhibiting overlapping features with classic CF but lacking typical respiratory-dominant symptoms. This review examines how these atypical symptoms deviate from the diagnostic pathways established in Western countries. Establishing localised data and functional platforms is a prerequisite for achieving precision medicine. Achieving a transition from symptom-focused care to defect-correcting therapy will require coordinated multicenter collaboration and sustained infrastructure development. Full article

Background: Chenopodium formosanum Koidz. (djulis) is an indigenous cereal crop native to Taiwan, and its effects on patients with inflammatory bowel disease (IBD) warrant exploration. The present study investigated whether the consumption of djulis can alleviate chronic colitis induced by dextran sulfate sodium (DSS) in mice. Methods: Forty mice were randomly divided into five groups: blank group (B), control group (C), low-dose group (L), medium-dose group (M), and high-dose group (H). Body weight and disease activity index (DAI) were recorded throughout this study. Groups C, L, M, and H were administered 2% DSS water on days 1–5 and 10–15 to induce chronic colitis. Groups L, M, and H were administered 5%, 10%, and 15% djulis, respectively. Serum and colon samples were collected for further analysis. Results: The DAI scores of groups L, M, and H were significantly lower than those of group C (p < 0.05), and the DAI scores of group H on day 18 were significantly lower than those of group L (p < 0.05). Colon length analysis revealed that DSS intervention significantly shortened colon length in group C (p < 0.05), whereas mice consuming djulis (groups L, M, and H) exhibited a restoration of colon length, with the effect being most pronounced in group H. DSS significantly increased the secretion of certain pro-inflammatory cytokines in the serum, such as interleukin (IL)-1β (p < 0.05), and the expression of some pro-inflammatory proteins in the colon, such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p < 0.05); however, djulis reversed these effects (especially in group H). In addition, mice in group H exhibited beneficial gut microbiota. Conclusions: Djulis alleviated chronic colitis in mice by reducing inflammation and modulating the gut microbiota. Further research is required to confirm these potential benefits in humans and elucidate the mechanisms involved. Full article

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder characterized by hyperphosphatemia and ectopic calcifications. Mutations in GALNT3, which encodes a key enzyme responsible for O-glycosylation of FGF23, represent a major genetic cause of HFTC. This modification is essential for the stability and secretion of FGF23. We investigated a 4-year and 6-month-old Chinese girl with HFTC to characterize the clinical features, identify the causative variants, and explore the underlying pathogenic mechanism. Whole-exome sequencing followed by Sanger validation identified novel compound heterozygous variants in GALNT3 (c.659T>A, p.Ile220Asn and c.1850C>A, p.Ser617*). The patient exhibited hyperphosphatemia with a biochemical profile consistent with FGF23 deficiency, including extremely low intact FGF23 and elevated C-terminal fragments. Functional studies using Western blotting and wheat germ agglutinin affinity chromatography demonstrated that the mutant GALNT3 caused a severe defect in FGF23 O-glycosylation, leading to impaired secretion of intact FGF23. Glycosylated FGF23 was detected only in the medium of cells expressing wild-type GALNT3. These findings indicate that defective O-glycosylation results in failure of FGF23 secretion and functional inactivation. This study expands the mutational spectrum of GALNT3 and provides mechanistic insight into the role of GALNT3 in phosphate homeostasis. Full article

Newborn sheep rely on passive transfer of immunity via colostrum as well as innate immunity for survival and adaptation to the extrauterine environment. This study examined associations between immunomodulatory constituents of colostrum, namely, immunoglobulin G (IgG), acute-phase proteins (APPs; serum amyloid A (SAA), and haptoglobin) and interleukin-6 (IL-6), and their corresponding concentrations in serum of 2–3-day-old offspring in a cohort of 296 Dorper lambs across three consecutive years. It also assessed the effects of these immunological markers on average daily weight gain (ADWG) during the first four months of life. IgG, APP, and IL-6 concentrations were measured, and mixed linear regression models were used for all analyses. Colostrum and serum concentrations of IgG and IL-6 were positively associated, whereas SAA levels in colostrum were negatively associated with IgG concentrations in serum. Serum IL-6 concentration was negatively associated with colostrum concentrations of IgG and SAA. Serum IgG concentration was positively associated with ADWG, while SAA and IL-6 concentrations were negatively associated with ADWG. These results show the importance of immunomodulating factors in colostrum other than IgG and emphasize the long-term effect of the serum concentrations of these factors on growth performance. Full article

This study aims to develop high-performance hybrid nanocomposites for solid-state energy conversion. We achieved this by improving charge transport and thermoelectric efficiency through the interaction of polymers, nanoparticles, and ionic liquids. Nickel oxide nanoparticles (NiO NPs) were synthesized via a sonochemical route using a novel ionic liquid, 1,2-(propan). In our recent work, this approach enabled the formation of a hybrid [NiO NPs + IL] system, which was subsequently incorporated at different loadings (8, 15, and 30 wt.%) and coated with polyethylene glycol (PEG). The resulting nanocomposites were investigated to elucidate charge-transport mechanisms and assess the influence of the polymer coating on their optical, electrical, and thermal transport properties. Optical measurements showed a shift in the band gap due to π–π* electronic transitions. This effect indicates strong interface interactions. The PEG-coated [NiO NPs + IL] nanocomposites exhibited significantly enhanced charge-carrier mobility, resulting in improved electrical conductivity. Remarkably, a high Seebeck coefficient of 720 μV/K and an electrical conductivity of 0.35 S/cm were achieved, resulting in a maximum power factor of 24.74 μW/m·K², surpassing many recently reported polymer-based nanocomposites. PEG-coated [NiO NPs + IL] systems offer tunable optical properties and superior thermoelectric performance. Consequently, they are a promising alternative to conventional nanocomposites for sustainable energy conversion. Full article

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASLD) represents a prevalent liver disease worldwide. It is crucial to maintain the stability of the gut–liver axis in order to inhibit the advancement of MASLD. Broccoli-derived exosome-like nanoparticles (BDENs) can alleviate constipation and improve colitis. This study investigated whether BDENs possess therapeutic potential for improving induced MASLD by the gut–liver axis. Methods: BDENs were fractionated from fresh broccoli using differential centrifugation, and the microRNAs were identified and analyzed. 24 male C57BL/6J mice (6 weeks old) were randomized into the control group, HFD group, and BDENs group, with 8 mice per group. After 8 weeks of high-fat diet modeling, the BDENs group accepted BDENs daily oral gavage of 100 mg/kg (B.W.), while the control and HFD groups accepted 1 × PBS. Four weeks after BDENs intervention, analysis was conducted on liver injury markers, liver tissue pathology, intestinal barrier, cecal content metabolomics and fecal 16S rRNA, serum inflammatory factors, and hepatic inflammation. Results: BDENs identified 1659 miRNAs associated with physiological processes such as immunity, antioxidant defense, and fatty acid biosynthesis. BDENs significantly reduced weight and ALT/AST ratio (p < 0.05). Furthermore, BDENs attenuated hepatic histopathological damage and lipid accumulation. For the gut–liver axis, BDENs maintained intestinal barrier, regulated intestinal bile acid metabolism and restored the gut microbiota. Additionally, BDENs reduced serum LPS level (p < 0.01) and suppressed hepatic inflammation, including F4/80 and IL-6, IL-1β (p < 0.0001). Conclusions: Oral BDENs therapy demonstrates potential for ameliorating MASLD. Full article

Background/Objectives: To assess the impact of weight loss on the atherogenic profile of patients with obesity, we proposed the Atherogenic Central Load Index (ACLI). The aim of the study was to validate ACLI as a novel lipid biomarker reflecting the balance between atherogenic and antiatherogenic lipoproteins, the overall atherogenic burden, and its association with inflammatory markers. Methods: A prospective study was conducted from January 2024 to July 2024. A total of 73 adults with overweight or obesity completed a six-month dietary-based weight loss intervention. A 15% caloric deficit target was set, excluding the potential influence of pharmacotherapy, and limiting physical activity to daily walking. Statistical analysis focused on anthropometric measures, lipid panel parameters and derived atherosclerosis indices. Results: The intervention returned a median weight loss of 11.8 (IQR: 8–19) kg. Before–after analysis showed a statistically significant improvement in anthropometric indices and most lipid profile components. To assess the effect of weight loss on the atherogenic profile of patients, we proposed an atherogenic load index (Atherogenic Central Load Index (ACLI)). ACLI decreased significantly following the hypocaloric diet and showed a significant correlation with the inflammatory markers hs-CRP and IL-6. ACLI showed a strong, inversely significant correlation (p < 0.05) with AIP, hs-CRP and IL-6, at the time of intervention initiation and after 6 months. The evaluation of the obtained AUC values allowed to clearly highlight the superior discrimination performance of ACLI regarding the inflammatory markers hs-CRP and IL-6 in patients with overweight and obesity involved in dietary interventions for weight loss. Conclusions. The proposed index (ACLI) showed strong and significant associations with key inflammatory markers, including hs-CRP and IL-6. Moreover, ACLI demonstrated superior discriminatory performance for elevated inflammatory status in overweight and individuals with obesity undergoing dietary weight-loss interventions, outperforming traditional atherogenic indices related to atherosclerosis progression (AIP, CRI–1, and CRI–2). These findings support the potential clinical utility of ACLI as an integrative marker of atherogenic burden and cardiometabolic risk. Full article

The high concentration of the inflammatory cytokine IL-36 in the serum of patients with type 2 diabetes mellitus (T2DM), along with the reduced renal damage observed in IL-36R knockout mice following ischemia–reperfusion-induced acute kidney injury, suggests a significant association between IL-36 activity and diabetic complications such as diabetic nephropathy (DN). It is also known that minor structural alterations in glomerular tissues can lead to changes in blood vessel pressure, potentially contributing to the development of DN, with inflammation acting as a triggering factor. However, further studies are needed to confirm this relationship. In this study, we observed that mesangial (MES-SV40) cells cultured under high-glucose conditions produced IL-36α in a dose-dependent manner. This cytokine production was also detected in mesangial cells from the glomerular tissues of mice with a high-calorie diet-induced T2DM, whereas healthy mice did not show such expression. In addition, we observed that mouse endothelial cells (SVECs) showed increased tubule formation in co-culture with MES-SV40 cells that had been previously exposed to 30 mmol/L glucose, as well as with the supernatant from these cells. IL-36R expression was confirmed in endothelial cells, as well as the angiogenic effect of IL-36α. Given that elevated VEGF levels have been reported in patients with DN by other authors, our results suggest that IL-36 produced by mesangial cells under high-glucose conditions may promote angiogenesis in glomerular tissues, potentially initiating the development of diabetic nephropathy. Full article

Pulmonary embolism (PE) is biologically heterogeneous. Despite guideline-directed anticoagulation, a subset of patients develops recurrent venous thromboembolism, persistent exertional limitation, residual perfusion defects, and progression to chronic thromboembolic pulmonary disease (CTEPD) or chronic thromboembolic pulmonary hypertension (CTEPH). Conventional risk factors explain much of the index event but incompletely account for thrombus non-resolution and chronic sequelae. Clonal hematopoiesis of indeterminate potential (CHIP)—the age-associated expansion of hematopoietic clones carrying somatic mutations—defines a measurable thrombo-inflammatory endophenotype that is strongly genotype- and clone-size (variant allele frequency; VAF)-dependent. Across human studies, JAK2-CHIP and TET2-CHIP show the most consistent associations with VTE/PE, whereas isolated DNMT3A-CHIP is frequently neutral, and larger clones tend to confer stronger effects. Mechanistically, CHIP can bias myeloid cells toward inflammasome/IL-1β signaling and endothelial activation, increase monocyte tissue factor activity, and promote immunothrombosis with neutrophil extracellular trap (NET) formation. NET-rich thrombi may adopt a dense fibrin–DNA–histone architecture that resists endogenous fibrinolysis, favoring organization and persistence. CTEPH offers a translational window to interrogate this model because thrombotic material and deep phenotyping are accessible. We synthesize genotype- and VAF-resolved clinical and mechanistic evidence using a structured strength-of-evidence framework and propose a pragmatic phenotyping roadmap with testable predictions for prospective post-PE validation. CHIP testing in PE/CTEPH remains investigational and should not currently change standard care. Full article

Whole-grain rice (Oryza sativa L.) is a rich source of polyphenols. The in vivo mechanisms linking its phytochemical profile to antioxidant and anti-inflammatory effects remain incompletely defined. This study investigated the antioxidant and anti-inflammatory activity of a whole-grain rice flour 70% ethanol extract (OSEE) and correlated these effects with its phenolic composition. OSEE showed high total phenolic content 0.121 ± 0.002 mg GAE/g d.w.), a lower total flavonoid content (61.83 ± 4.03 µg QE/g d.w.), and a phenolic profile dominated by phenolic acids (~87%), with ferulic and protocatechuic acids among the most abundant constituents. OSEE displayed significant in vitro antioxidant activity in DPPH, FRAP, hydrogen peroxide, and nitric oxide scavenging assays. In vivo activity was evaluated in male Wistar rats with turpentine oil-induced acute inflammation using both therapeutic (post-induction) and prophylactic (pre-induction) protocols, testing three oral doses of lyophilized extract (1.0, 0.50, and 0.25 g/kg/day). In vivo, OSEE attenuated systemic oxidative stress (TOS, TAC, OSI, AOPP, MDA, NOx, 3-nitrotyrosine, total thiols) and the expression of pro-inflammatory markers (NF-κB p65, IL-1β, IL-18, caspase-1) in a dose-dependent manner with both protocols, with the highest dose producing the most consistent reductions, while the expression level of the anti-inflammatory factor IL-10 remained unchanged. PCA supported a shift in biomarker networks toward a non-inflamed profile. These findings indicate that OSEE exerts coordinated antioxidant and anti-inflammatory effects in vivo that are strongly associated with its phenolic composition. Full article

Myocardial ischemia/reperfusion (MI/R) injury affects heart attack outcomes. Endothelial cells dysfunction immediately after MI/R, but the key molecules and how to block them remain unclear. We combined single-cell atlas analysis, AI simulation, and experimental single-cell RNA sequencing data from mouse MI/R; we did quality control, cell annotation, hdWGCNA, and differential gene screening to identify endothelial genes. We constructed a protein network with STRING, predicted structure with AlphaFold3, and used AutoDock for molecular docking to find potential drugs. Virtual knockout simulations were used to check gene deletion effects. The compound andrographolide (AG) was tested in in vitro and in vivo MI/R models by measuring cell viability, inflammation, pathway activity, infarct size, and cardiac function. Single-cell analysis showed that S100 calcium binding protein A8 (S100A8) is an important element in vascular inflammation. It promotes inflammation by interacting indirectly with Cluster of differentiation 14 (CD14). Molecular docking showed that AG binds stably to S100A8. In vitro, AG reduced endothelial injury and blocked the IL-17 pathway. In vivo, AG reduced infarct size, improved cardiac function, and lowered S100A8 and IL-17 pathway proteins. Using single-cell analysis, AI, and experiments, we showed that S100A8 is related to MI/R injury. Andrographolide protects microvasculature via the S100A8 pathway, offering a promising treatment approach and new insights into heart injury mechanisms. Full article

Honey, as a natural and nutritious sweetener, is one of the most widely consumed foods worldwide. However, the presence of phytotoxins in honey and the influence of honey’s intrinsic sugar matrix on the toxicity of these phytotoxins remain insufficiently explored. An optimized liquid chromatography–quadrupole trap tandem mass spectrometry method was developed to quantify 17 toxic alkaloids in 150 raw honey samples. Camptothecin was identified for the first time in the tested samples and was the most prevalent contaminant (36% detection, max 3.09 μg/kg), which induced cardiac hypertrophy and impaired cardiac function in zebrafish assays. The honey sugar matrix further potentiated these adverse cardiac effects through exacerbating oxidative stress and upregulating pro-inflammatory and pro-apoptotic gene expression, while natural honey partially mitigated such damage by upregulating the key antioxidant gene nrf2, thereby downregulating il-1β and regulating the bcl2/bax expression ratio. This study offers novel insights into honey phytotoxins’ matrix-modulated toxicity, laying a scientific foundation for optimizing safety protocols and matrix-specific risk standards. Full article