Search Results (27,557)

Inflammatory-oxidative stress generated by immune cells plays an important role in aging and in age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Triple-transgenic mice for AD (3xTg-AD) are a suitable model for mimicking this disease in an age-dependent manner. We previously showed that peritoneal leukocyte functions and their redox-inflammatory state are altered early in female 3xTg-AD mice, which exhibit premature aging compared to non-transgenic (NTg) animals. However, their characteristics at 9 months of age, when they present an early neuropathological state, and the sex differences are not known. Here, we analyzed several spleen and thymus leukocyte functions (chemotaxis, natural killer activity, and lymphoproliferation in response to mitogens), pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) released cytokine concentrations, and redox parameters (glutathione concentrations and glutathione peroxidase, glutathione reductase, and xanthine oxidase activities) in male and female 3xTg-AD mice compared to age-matched controls. We also analyzed the effects of voluntary physical exercise on immune functions. Our results show that 9-month-old male and female 3xTg-AD mice have worse immune functions, redox state, and inflammation than NTg counterparts. Physical exercise improves immune function. Thus, accelerated aging reflected by peripheral immunosenescence and oxidation-inflammation in 3xTg-AD mice precedes hallmark neuropathology, and exercise can slow down AD progression. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune rheumatic disease of unknown etiolgy, characterized by erosive polyarthritis that leads to joint destruction and systemic inflammatory lesions in internal organs. Pain is a primary symptom of RA and a major contributor to psychological disturbances, which influence patients’ subjective evaluation of their condition. These psychological issues may stem from disruptions in central pain regulation mechanisms, such as central sensitization (CS), which can also affect central metabolic processes. The objective was to investigate how the severity of central sensitization, measured by the Central Sensitization Inventory (CSI) questionnaire (Part 1), impacts clinical and neuropsychiatric parameters, as well as the expression of genes related to inflammation, tissue destruction, carbohydrate metabolism, and fatty acid metabolism in peripheral blood mononuclear cells (PBMCs) in patients with RA. Methods involved collecting blood samples from 59 RA patients (mean age 52.0 years). Clinical status was assessed using the DAS28 index and serum levels of CRP, ASPA, and RF. Neuropsychiatric parameters were evaluated through questionnaires measuring CS severity score (CSI), pain intensity (VAS, BPI), neuropathic pain (PainDETECT), anxiety and depression (HADS), fatigue (FSS, FACIT-F), fibromyalgia symptoms (FIRST), and pain catastrophizing. Protein expression in PBMCs was measured by ELISA, while gene expression was analyzed using quantitative real-time RT-PCR. All patients exhibited moderate to high disease activity. Participants were divided into four subgroups according to their CSI scores: subclinical (0–29 points), mild (30–39 points), moderate (40–49 points), and severe/extreme (50–100 points). Higher CSI scores correlated with significant increases in neuropsychiatric symptoms and a notable decrease in vitality. However, clinical parameters showed no significant differences among the subgroups. Gene expression analysis revealed upregulation of genes involved in the pentose phosphate pathway (G6PD), antioxidant defense (SOD1), fatty acid metabolism (FASN, CPT1B), apoptosis (CASP3), and tissue destruction and hypernociception (MMP-9) compared to healthy controls. The pro-inflammatory cytokine IL-1β expression was comparable to controls, while TNFα expression was elevated only in patients with severe/extreme CS scores. These findings suggest that CS-related disturbances may contribute to increased disease severity in RA, even in patients receiving active antirheumatic treatment. At the cellular level, disease severity appears linked to dysregulated expression of genes governing central metabolic processes, despite low expression of pro-inflammatory cytokine genes. Full article

People living with HIV (PLWH) receiving effective antiretroviral therapy (ART) continue to exhibit chronic immune activation and systemic inflammation despite virological suppression. The viral envelope glycoprotein gp120, which binds the CD4 receptor and mediates viral entry, has been implicated in pro-inflammatory and pro-apoptotic effects in neuronal and endothelial cells. Although gp120 is expressed on the viral surface, its oligomeric structure and its ability to form immune complexes with circulating antibodies may reduce the sensitivity of standard detection assays in serum. Soluble gp120 has been associated with increased levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as chemokines. These mediators may contribute to blood–brain barrier dysfunction, endothelial injury, vascular smooth muscle alterations, and subsequent neurodegenerative and cardiovascular complications. Importantly, gp120 shedding may persist due to viral reservoirs and intermittent reactivation, even during ART. Fostemsavir inhibits the interaction between gp120 and CD4, preventing viral entry and potentially limiting gp120-mediated pathogenic effects. Beyond antiviral activity, this mechanism suggests a potential role in attenuating gp120-mediated inflammation. This review discusses the biological effects of gp120 and the rationale for targeting it therapeutically in PLWH. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease driven by immune dysregulation and epidermal barrier dysfunction. Current therapeutic options are often limited by safety concerns or suboptimal tolerability. In this study, we isolated and structurally characterized GRB-H—a λ-carrageenan-enriched sulfated hybrid galactan from the marine red alga Gigartina radula—as a complex polysaccharide containing κ-, ι-, μ-, ν-, and λ-carrageenan structural units, and systematically evaluated its anti-AD potential using both in vitro and in vivo models. In vitro, GRB-H significantly suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in RAW 264.7 macrophages, and reduced 2,4-dinitrochlorobenzene (DNCB)-evoked TNF-α and IL-1β expression in HaCaT keratinocytes. In a DNCB-induced murine model of AD, topical application of GRB-H markedly ameliorated skin inflammation, epidermal hyperplasia, and dermal immune cell infiltration. GRB-H treatment lowered total serum immunoglobulin E (IgE) levels, restored the imbalanced Th1/Th2 cell ratio in the spleen, and downregulated the mRNA expression of key inflammatory cytokines—including TNF-α, IL-4, IL-5, IL-31, and interferon-γ (IFN-γ)—in lesional skin. Collectively, these findings demonstrate that GRB-H alleviates AD symptoms through coordinated local anti-inflammatory and systemic immunomodulatory actions, highlighting its promise as a marine-derived candidate for the topical management of AD. Full article

Background: Systemic inflammation is a key driver of heart failure (HF) progression across all ejection fraction (EF) phenotypes, with diet emerging as a modifiable factor influencing cardiac metabolism and inflammatory signaling. This narrative review integrates current evidence on the inflammatory mechanisms underlying HF, their links with common comorbidities and emerging anti-inflammatory therapeutic strategies, with a particular focus on the role of nutrition in supporting healthy cardiac metabolism. Methods: We searched MEDLINE/PubMed, EMBASE, Web of Science, the Cochrane Library, Scopus and reference lists of relevant publications using terms related to systemic inflammation, dietary patterns and HF prioritizing high-impact studies on nutrition–inflammation–HF interactions published from 2000 onward. Results: Major HF comorbidities sustain chronic, low-grade inflammation through elevated cytokine activity. Dietary patterns—especially those with high Dietary Inflammatory Index (DII)—substantially shape inflammatory milieu. The Mediterranean diet appears to have a favorable inflammatory profile with reduction in circulating pro-inflammatory biomarkers, especially C-reactive protein (CRP) and interleukin-6 (IL-6). Established therapies for HF with reduced ejection fraction and vagus nerve stimulation elicit anti-inflammatory efficacy through cytokine suppression. Sodium glucose cotransporter-2 (SGLT2) inhibitors demonstrate positive metabolic effects and anti-inflammatory actions through decrease in IL-6 and tumor necrosis factor-α (TNF-α). Interleukin-1 blockade has produced heterogeneous clinical outcomes, while definitive findings examining the role of IL-6 inhibitors in inflammation suppression and possible benefit on cardiac outcomes are anticipated. Preliminary data show the potential synergistic effects of dietary patterns/nutrients and pharmacological agents combination on improvement of endothelial function and attenuation of the fibrotic process, although there is a need for further research in large-scale trials. Conclusions: Systemic inflammation demonstrates a key role in HF initiation and progression, and the effect of diet on inflammatory pathways is central. Dietary patterns targeting inflammation-related mechanisms (inflammasome, gut dysbiosis) can lead to attenuation of systemic inflammatory response and restoration of cardiac metabolic flexibility. A deeper mechanistic discernment of cardiac inflammatory cascades, together with identification of HF subpopulations with excessive inflammatory activity, may facilitate the design of targeted randomized controlled trials (RCTs) aiming for novel personalized, inflammation-targeted HF therapies with potential clinical benefit. Full article

Liver fibrosis is driven by persistent oxidative stress and inflammatory signaling, with transforming growth factor-β (TGF-β) acting as a key profibrotic mediator. Rutin (Ru) is a plant-derived flavonoid with antioxidant and anti-inflammatory effects, but its low bioavailability limits therapeutic efficacy. This study investigated whether rutin-phytoreduced gold nanoparticles (RuAuNPs) enhanced rutin delivery leading to antifibrotic and anti-inflammatory effects in a rat model of liver fibrosis. Liver fibrosis was induced by oral administration of thioacetamide (TAA, 150 mg/kg body weight, p.o.) for six weeks. Following fibrosis induction, the animals were treated with free rutin (30 mg/kg body weight), RuAuNPs (0.3 mg/kg body weight), or AuNPs (0.3 mg/kg body weight), both expressed as nanoparticle mass, all administered orally for four weeks. RuAuNPs were synthesized by green rutin-mediated reduction and further characterized by TEM, DLS, and FTIR spectroscopy; they were spherical, showing an average hydrodynamic size of 104.1 nm (PDI 0.345). FTIR confirmed rutin capping. Biological effects were evaluated by liver morphology (H&E histology, TEM), biochemical assessment of liver aminotransferases and glico-lipidic status, ELISA and spectrophotometry measurement of redox biomarkers (lipid peroxidation, glutathione status, antioxidant enzymes), cytokines (TNF-α, IL-1β, IL-6), and TGF-β. TAA-induced hepatic injury and remodeling with increased profibrotic signaling, oxidative stress, and inflammation. Free rutin slightly ameliorated the liver damage, whereas RuAuNP improved histological features, reduced TGF-β and pro-inflammatory cytokines, decreased lipid peroxidation, and supported antioxidant defenses. Overall, RuAuNP may enhance rutin efficacy in TAA-induced liver fibrosis, with novelty stemming from the integrated in vivo evaluation of tissue changes and key profibrotic/oxidative/inflammatory pathway. Full article

Background/Objectives: The gut–brain axis is increasingly recognized as a critical modulator of cognitive function. This study investigated the neurotoxic effects of combined exposure to bacterial lipopolysaccharide (LPS) and the antiretroviral drug zidovudine (ZDV) in a mouse model, and evaluated the protective potential of two probiotic interventions: Bacillus subtilis and a mixture of lactobacilli. Methods: Cognitive function was assessed using the Morris water maze (MWM). Gut microbiota composition was analyzed by 16S rRNA sequencing, and intestinal morphology was examined histologically. Gene expression of neuroinflammatory markers and mitophagy-related genes in brain tissue was quantified by RT-PCR. Plasma levels of cell-free mitochondrial DNA (cf-mtDNA) were measured as a marker of mitochondrial damage. Results: Combined LPS + ZDV exposure induced systemic inflammation, impaired spatial memory, damaged the intestinal mucosa, and caused dysbiosis characterized by an increase in pro-inflammatory Muribaculaceae. In the brain, LPS + ZDV significantly upregulated Tnfa expression, confirming neuroinflammation. Bacillus subtilis administration prevented cognitive deficits, maintained Tnfa at control levels, and significantly reduced Il1b and Il6 expression compared to the LPS + ZDV group. This was accompanied by activation of the PINK1/PTEN-dependent mitophagy pathway, prevention of cf-mtDNA release, and restoration of gut microbial diversity. In contrast, the Lactobacilli mixture not only failed to improve outcomes but was associated with exacerbated intestinal damage, more pronounced cognitive dysfunction, and no reduction in neuroinflammatory markers. Conclusions: Combined exposure to LPS and ZDV induces gut–brain axis dysfunction characterized by neuroinflammation, cognitive impairment, intestinal damage, and dysbiosis. Bacillus subtilis effectively preserves cognitive function through activation of PINK1/PTEN-dependent mitophagy and suppression of neuroinflammation, highlighting its potential as a therapeutic candidate for cognitive impairments associated with gut–brain axis dysfunction. The contrasting effects of the lactobacilli mixture underscore the critical importance of strain-specificity in probiotic interventions. Full article

Background/Objectives: Multiple Sclerosis (MS) is a chronic immune-mediated disorder characterized by neuroinflammation and neurodegeneration. Increasing evidence implies the kynurenine pathway (KP) in the MS pathophysiology; however, data from Mexican populations are lacking. This exploratory study aimed to characterize central and circulating KP metabolites in Mexican patients with MS and to investigate potential genetic variants in KP-related genes. Methods: Serum concentrations of kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK), as well as cerebrospinal fluid (CSF) levels of KYNA, quinolinic acid (QUIN), interleukin-4 (IL-4), and interleukin-6 (IL-6), were determined in treatment-naïve relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and treated PMS patients. Serum levels were compared with those of healthy controls, and CSF findings contrasted with those of non-MS neurological patients and individuals with neurocysticercosis (NCC). Public whole-exome datasets were analyzed for variants in KP-related genes, and target exome sequencing was performed in three Mexican patients with MS. Results: Serum concentrations of KYNA and 3-HK were decreased in MS patients compared with healthy controls. CSF KYNA and QUIN levels did not differ significantly among MS subtypes or the non-MS neurological group, but they were lower than those observed in NCC. IL-4 and IL-6 were detectable in MS CSF samples, supporting the presence of intrathecal inflammation. Genetic and bioinformatic analyses identified variants in genes encoding KP enzymes in both public MS datasets and in Mexican patients with MS. Conclusions: These findings indicate an altered KP metabolism in Mexican MS patients, particularly during the relapse phase, and suggest a possible contribution of genetic variability. Further large-scale studies are needed to confirm these observations and to determine the functional implications of KP-related genetic variants in MS. Full article

Background: Congested tournament schedules impose substantial physiological stress in team sports; however, the integrated endocrine and inflammatory responses to real competitive match load in female handball players remain insufficiently characterized. Objective: This study aimed to characterize the acute biochemical responses, including hormonal, inflammatory, muscle damage, and bone metabolism markers, elicited by competitive tournament load in female handball players and to provide practical insights for optimizing recovery strategies and load management during short-term competitive periods. Methods: In a pre–post study design, venous blood samples were collected from competitive female athletes (n = 8; age 20.83 ± 2.93 years) before the first match and after the fourth consecutive match of an official university qualification tournament. Biochemical analyses included cortisol, insulin, IL-6, creatine kinase (CK), IGF-1, irisin, lactate dehydrogenase (LDH), osteocalcin, and testosterone. Pre-to-post changes were assessed using paired t-tests and effect sizes. Results: Tournament load induced substantial multisystem physiological perturbations. Significant increases were observed in cortisol (p < 0.001), insulin (p = 0.044), IL-6 (p < 0.001), CK (p < 0.001), and osteocalcin (p = 0.005), indicating activation of the hypothalamic–pituitary–adrenal axis, systemic inflammation, muscle membrane disruption, and enhanced bone turnover. Conversely, IGF-1 (p < 0.001) and testosterone (p = 0.004) significantly decreased, reflecting suppression of anabolic signaling and a shift toward a catabolic hormonal environment under cumulative match stress. LDH significantly decreased (p = 0.002), while irisin showed no significant change (p > 0.05). Conclusions: These findings demonstrate that congested tournament schedules provoke an integrated endocrine–inflammatory stress response in female handball players. Importantly, the observed anabolic–catabolic imbalance highlights the need for individualized recovery strategies, optimized load management, and adequate recovery periods to mitigate maladaptation and reduce injury risk during short-term competitive tournaments. Full article

Background/Objectives: Higher iron doses are used in the anemia treatment of hemodialysis patients, which allows for lower doses of erythropoiesis-stimulating agents; however, there are concerns regarding the risk of iron toxicity. This study aimed to evaluate the potential toxicity of iron deposition in prevalent hemodialysis patients on iron therapy and its relationship with parameters used to assess iron status, plasma protein oxidation, and cellular iron toxicity. Methods: Magnetic resonance imaging was performed in 56 patients to assess hepatic iron deposition, which was related to clinical and analytical parameters. In patients included in the first and fourth quartiles, according to hepatic iron deposition, plasma protein oxidative stress was quantified, as were iron and cytokine levels in peripheral blood mononuclear cells (PBMCs). Results: Patients with higher hepatic iron deposition had a longer time on hemodialysis (42.0 ± 43.0 vs. 4.9 ± 3.4 months, p < 0.001) and higher ferritin levels (1200 ± 516 vs. 429 ± 278 ng/mL, p < 0.001) than those with lower hepatic iron deposition, without differences in transferrin saturation or hepatic enzyme serum concentration. No differences were found in plasma protein oxidation, iron content, or cytokine mRNA content in PBMCs, except for a decrease in IL-6 levels in patients with higher hepatic iron deposition. Conclusions: Patients with longer hemodialysis times had higher iron stores, suggesting that iron treatment over time increases hepatic iron deposition. No parameters supporting increased toxicity in patients with higher hepatic iron deposition were observed. Full article

Cytokine storm is a central pathogenic mechanism underlying sepsis-induced acute lung injury (SALI) and severe coronavirus disease 2019 (COVID-19), yet effective therapeutic strategies remain limited. Eupatorium lindleyanum DC. (EL), a traditional Chinese medicinal herb, has been reported to possess anti-inflammatory, antioxidant, and antiviral-related activities; however, its protective mechanisms in SALI and virus-associated inflammatory lung injury remain incompletely understood. In this study, an integrated strategy combining computational prediction and experimental validation was employed to investigate the therapeutic potential and underlying mechanisms of EL. The chemical constituents of EL were characterized by UPLC–Q–TOF/MS, followed by network pharmacology, molecular docking, and molecular dynamics analyses to predict key targets and signaling pathways. A cecal ligation and puncture (CLP)-induced SALI rat model was used to evaluate lung histopathology, pulmonary edema, cytokine production, and inflammatory signaling activation. In parallel, LPS-stimulated RAW264.7 macrophages were used to assess cytokine secretion and pathway regulation in vitro. In addition, a SARS-CoV-2 pseudovirus-induced mouse model was employed to further evaluate the in vivo relevance of the representative bioactive compound hyperoside in pseudovirus-associated lung injury. A total of 32 active compounds and 697 putative targets were identified, among which 116 were associated with sepsis and COVID-19. In vivo, EL markedly alleviated lung injury, reduced the lung coefficient and wet/dry ratio, and suppressed excessive production of proinflammatory cytokines and activation of key signaling proteins. In vitro, EL dose-dependently inhibited TNF-α and IL-6 secretion and regulated the PI3K–Akt and NF-κB signaling pathways. Notably, hyperoside showed favorable predicted interactions with PI3K–Akt pathway-related targets (EGFR, PI3K, and Akt), while molecular dynamics simulations supported stable interactions with several COVID-19-related targets, including ACE2, Mpro, and RdRp. Furthermore, hyperoside significantly alleviated SARS-CoV-2 pseudovirus-associated lung injury, reduced ACE2 protein expression, and downregulated EGFR, PI3K, and Akt mRNA levels in vivo. Collectively, these findings indicate that EL exerts protective effects through multi-component, multi-target, and multi-pathway mechanisms, and support its potential value for further investigation in SALI and virus-associated inflammatory lung injury. Full article

Background: Circulating cytokines and their soluble receptors in body fluids have been implicated in the pathogenesis of multiple sclerosis (MS). Alterations in serum levels of pro- and anti-inflammatory cytokines and/or their soluble receptors can dysregulate central nervous system (CNS) signaling pathways and, therefore, may serve as potential biomarkers for the diagnosis of MS. Therefore, the primary end-point of this study is to investigate the utility of various cytokines and their soluble receptors as diagnostic biomarkers in MS. The secondary outcome is also to assess whether these cytokines are useful in differentiating the severity of MS. Methods: In this case–control study, we compared a panel of pro-inflammatory interleukins (ILs), including IL18 and tumor necrosis factor-alpha (TNFα), soluble IL receptors (sIL7Rα and sIL2Rα), and insulin-like growth factor-1 (IGF-1) in 45 MS patients and in 45 healthy control individuals matched for sex and age. Associations of these biomarkers with age, disease severity (Expanded Disability Status Scale [EDSS]), disease duration, and age at first MS symptom onset were also assessed. Results: Serum levels of cytokines and soluble IL receptors were elevated in MS patients compared to healthy controls. IGF-1 was lower (p < 0.001) in the MS patients than in the healthy individuals. The serum level of IGF-1 was higher (p < 0.01) in the remitting-relapsing phase compared to the primary progression and secondary progression stages. Similarly, only IGF-1 was more elevated (p < 0.01) in the mild stage compared to the moderate stage based on the EDSS score. Receiver operating characteristic (ROC) curve analysis demonstrated that IL18 had excellent discriminatory power for the diagnosis of MS (p < 0.001), with an area under the curve (AUC) of 0.96 ± 0.017, followed by IGF-1 (p < 0.001), which showed strong diagnostic performance (AUC = 0.873 ± 0.037). Soluble (s) IL2Rα exhibited fair diagnostic accuracy (p < 0.001; AUC = 0.717 ± 0.054). In contrast, sIL7Rα and TNFα showed poor discriminatory power despite statistical significance (p < 0.01), with AUC values of 0.675 ± 0.057 and 0.687 ± 0.056, respectively. Results of regression analysis revealed that EDSS, duration of disease, and use of any treatment had no impact on the cytokines. Similarly, no significant correlations were noted between these confounders and cytokines, except a moderate negative correlation (−0.418) between IGF-1 and EDSS. Conclusions: IL18 and IGF-1 have the potential to be used as biomarkers in distinguishing MS from healthy individuals. However, both biomarkers failed to demonstrate the discrimination between various phenotypic patterns of disease, limiting their utility for disease stratification. Future studies with larger, longitudinal cohorts and multi-marker panels are warranted to validate these results and to explore whether combining cytokines with imaging or genetic markers can improve prognostic precision. Full article

This study investigated the effects of Lycium barbarum polysaccharides (LBP) supplementation on various indicators in coral trout (Plectropomus leopardus), including growth performance, digestive enzyme activity, muscle and skin morphology, inflammatory immune gene expression, as well as immune and antioxidant responses. In the experiment, fish were fed diets supplemented with different concentrations of LBP (0%, 0.05%, 0.1%, 0.2%, 0.5%, and 1%) over a designated experimental period. The results showed that moderate supplementation of LBP significantly improved growth performance, with the optimal concentration being around 0.243%, achieving the highest specific growth rate. LBP supplementation also enhanced intestinal digestive enzyme activity, such as trypsin in the 0.1% and 1% groups, and α-amylase in the 0.5% group. Additionally, LBP improved the nutritional composition of muscle, with the 1% group showing higher crude protein content and the 0.2–1% groups having lower crude fat content. Moderate LBP supplementation improved skin color and pigmentation, increasing the brightness, redness, and yellowness of the dorsal skin, as well as boosting carotenoid and astaxanthin concentrations. It also enhanced the immune and antioxidant functions of the skin (e.g., SOD, CAT, GSH-Px, AKP, and LZ) and improved the immune functions of the mucus (e.g., C3, C4, IgM, IgT, AKP, and LZ). Furthermore, the expression of key pro-inflammatory genes, such as TNF-α and IL-1β, was reduced. These findings suggest that LBP can serve as a natural feed additive to enhance the overall quality and health of coral trout, contributing to sustainable aquaculture practices. Full article

NLRP3-associated autoinflammatory diseases (NLRP3-AIDs) are rare autoinflammatory disorders caused by uncontrolled inflammasome activation. While IL-1β blockade is first-line therapy, many patients respond inadequately, highlighting a need for alternative strategies. Transcriptomic analysis was performed on immune cells from a patient with an NLRP3 L573W mutation. Functional validation of CD177 as a downstream effector of NLRP3 activation was conducted. A novel NLRP3 L573W knock-in mouse model was established. Correlation between CD177 expression, disease severity, neutrophilia, and tissue damage was assessed. Therapeutic efficacy of siRNA-mediated CD177 silencing was evaluated and compared with IL-1β blockade. CD177, a neutrophil-specific protein, was significantly upregulated in NLRP3-mutant cells and confirmed as a direct downstream effector of NLRP3 activation. The NLRP3 L573W knock-in mouse recapitulated human disease heterogeneity, from mild self-limited inflammation to severe multi-organ pathology. CD177 expression correlated with disease severity, neutrophilia, and tissue damage. siRNA-mediated CD177 silencing attenuated systemic inflammation, reduced neutrophil infiltration and cytokine levels (IL-1β, IL-6, TNFα), and ameliorated multi-organ damage, with effects comparable to or exceeding those of IL-1β blockade. CD177 is a non-canonical amplifier of NLRP3-driven inflammation. Targeting CD177 represents a superior therapeutic strategy for NLRP3-AIDs, including IL-1β-refractory cases. Full article

Background/Objectives: The aim of the current study was to investigate the mechanistic hepatoprotective efficacy of selenium (SE) and chitosan-coated selenium nanoparticles (CS-SENPs) using a rat model induced by lipopolysaccharide (LPS). Methods: CS-SENP was prepared and characterized for particle size, polydispersity index (PDI), zeta potential, transmission electron microscope (TEM), and Fourier transform infrared spectroscopy (FTIR). Male albino rats (n = 40) were divided into four groups: control, LPS, SE, and CS-SENP. SE and CS-SENPs (5 mg/kg orally for 14 days) were given before LPS injection. Tissue architecture was assessed using histopathological analysis. HSP-47 and STEAP-3 protein expression levels were measured using ELISA, and oxidative stress markers were quantitatively evaluated. The expression of HO-1, TLR-4, STAT-3, TRAF-6, and IL-17A was measured using immunohistochemical analysis. Furthermore, HSP-90 expression was evaluated by immunofluorescence labeling. Results: CS-SENP characterization revealed uniform (PDI = 0.125 ± 0.04) nanoparticle size (108.54 ± 2.24 nm), with high zeta potential (+63.92 ± 6.287 mV), attributed to the CS layer, which was confirmed by FTIR and TEM as an electron-lucent halo enveloping the individual SENP cores. CS-SENPs significantly reduced lipid peroxidation (MDA) and restored glutathione (GSH) more effectively than SE. CS-SENPs improved redox (upregulated HO-1) and iron balance (downregulated STEAP-3), and also increased the anti-inflammatory effect (suppressed TLR-4, IL-17A, TRAF-6, and STAT-3). CS-SENPs showed superior antifibrotic efficacy (suppresses stress proteins, HSP-47 and HSP-90). Rats treated with CS-SENPs had nearly normal liver structure. Conclusions: The results concluded that CS-SENPs had superior and multi-targeted hepatoprotection against LPS-induced liver damage. Full article