Search Results (1,417)

Background: Localized scleroderma (LoS) is a chronic autoimmune condition marked by cutaneous fibrosis and persistent inflammation. Modulating the activation of inflammatory cells and fibroblasts remains a central strategy in LoS treatment. We investigate the anti-fibrotic effects of Annexin A5 (AnxA5), identified as a key inflammatory component in fat extract, and assess its therapeutic efficacy. Methods: In vitro experiments were performed using TGF-β-stimulated primary human dermal fibroblasts treated with recombinant AnxA5. The anti-fibrotic effects and underlying mechanisms were assessed using CCK-8 assays, quantitative real-time PCR, Western blotting, and immunocytochemistry. In vivo, AnxA5 was administered via both preventative and therapeutic protocols in bleomycin-induced LoS mouse models. Treatment outcomes were evaluated by histological staining, collagen quantification, immunostaining, and measurement of pro-inflammatory cytokines. Results: TGF-β stimulation induced myofibroblast differentiation and extracellular matrix (ECM) production in dermal fibroblasts, both of which were significantly attenuated by AnxA5 treatment through the inhibition of phosphorylation of Smad2. In vivo, both preventative and therapeutic administration of AnxA5 effectively reduced dermal thickness, collagen deposition, ECM accumulation, M1 macrophage infiltration, and levels of pro-inflammatory cytokines. Conclusions: Through both preventative and therapeutic administration, AnxA5 ameliorates LoS by exerting dual anti-fibrotic and anti-inflammatory effects, underscoring its potential for treating fibrotic diseases. Full article

In this study, using 70% anhydrous ethanol as the extraction solvent, Moringa oleifera Lam. seed powder was extracted with the microwave-assisted extraction method, followed by purification using macroporous adsorbent resin NKA-9. The purified glucosinolate was subsequently hydrolyzed with myrosinase. The glucosinolate and its enzymatic product were identified as 4-(α-L-rhamnopyranosyloxy) benzyl glucosinolate (4-RBMG) and benzyl isothiocyanate (BITC) by UV–Vis, FT-IR, NMR, and MS. The bioactivities, including anti-oxidation, anti-inflammation, and anti-tumor activities of 4-RBMG and BITC, were systematically evaluated and compared. The results show that at 5–20 mg/mL, the anti-oxidation effects of 4-RBMG on DPPH and ABTS free radicals are superior to those of BITC. However, at the same concentrations, BITC has stronger anti-inflammatory and anti-tumor activities compared to 4-RBMG. Notably, at a concentration of 6.25 μmol/L, BITC significantly inhibited NO production with an inhibitory rate of 96.67% without cytotoxicity. Additionally, at a concentration of 40 μmol/L, BITC exhibited excellent inhibitory effects on five tumor cell lines, with the cell inhibitory rates of leukemia HL-60, lung cancer A549, and hepatocellular carcinoma HepG2 exceeding 90%. This study provides some evidence that the enzymatic product, BITC, shows promise as a therapeutic agent for tumor suppression and inflammation reduction. Full article

Cold-water immersion (CWI), as a common recovery method, has been widely used in the field of post-exercise fatigue recovery. However, there is still a lack of comprehensive and systematic scientific evaluation of the combined effects of cold-water immersion combined with other therapies (CWI + Other). The aim of this study was to compare the effects of CWI and CWI + Other in post-exercise fatigue recovery and to explore the potential benefits of CWI + Other. We systematically searched PubMed, Embase, Web of Science, Cochrane Library and EBSCO databases to include 24 studies (475 subjects in total) and performed a meta-analysis using standardized mean difference (SMD) and 95% confidence intervals (CIs). The results showed that both CWI + Other (SMD = −0.68, 95% CI: −1.03 to −0.33) and CWI (SMD = −0.37, 95% CI: −0.65 to −0.10) were effective in reducing delayed-onset muscle soreness (DOMS). In subgroup analyses of athletes, both CWI + Other (SMD = −1.13, 95% CI: −1.76 to −0.49) and CWI (SMD = −0.47, 95% CI: −0.87 to −0.08) also demonstrated significant effects. In addition, CWI + Other significantly reduced post-exercise C-reactive protein (CRP) levels (SMD = −0.62, 95% CI: −1.12 to −0.13), and CWI with water temperatures higher than 10 °C also showed a CRP-lowering effect (MD = −0.18, 95% CI: −0.30 to −0.07), suggesting a potential benefit in anti-inflammation. There were no significant differences between the two interventions in the metrics of creatine kinase (CK; CWI: SMD = −0.01, 95% CI: −0.27 to 0.24; CWI + Other: SMD = 0.26, 95% CI: −0.51 to 1.03) or countermovement jump (CMJ; CWI: SMD = 0.22, 95% CI: −0.13 to 0.57; CWI + Other: SMD = 0.07, 95% CI: −0.70 to 0.85). Full article

Plant-derived extracellular vesicles (PDEVs) are nanoscale, phospholipid bilayer-enclosed vesicles secreted by living cells through cytokinesis under physiological and pathological conditions. Owing to their high biocompatibility and stability, PDEVs have attracted considerable interest in regenerative medicine applications. They can exhibit the capacity to enhance cellular proliferation, migration, and multi-lineage differentiation through immunomodulation, anti-inflammation effects, antioxidative protection, and tissue regeneration mechanisms. Given their abundant availability, favorable safety profile, and low immunogenicity risks, PDEVs have been successfully employed in therapeutic interventions for skeletal muscle disorders, cardiovascular diseases, neurodegenerative conditions, and tissue regeneration applications. This review mainly provides a comprehensive overview of PDEVs, systematically examining their biological properties, standardized isolation and characterization methodologies, preservation techniques, and current applications in regenerative medicine. Furthermore, we critically discuss future research directions and clinical translation potential, aiming to facilitate the advancement of PDEV-based therapeutic strategies. Full article

Ultraviolet B (UVB) irradiation drives skin photodamage, prompting exploration of natural therapeutics. This study investigated the reparative effects and mechanisms of crude Gastrodia elata polysaccharides (GP) on UVB-induced acute skin damage. GP was extracted from fresh G. elata via water extraction and alcohol precipitation. It is a homogeneous polysaccharide with a weight-average molecular weight of 808.863 kDa, comprising Ara, Glc, Fru, and GalA. Histopathological analysis revealed that topical application of GP on the dorsal skin of mice effectively restored normal physiological structure, suppressing epidermal hyperplasia and collagen degradation. Biochemical assays showed that GP significantly reduced the activities of MPO and MDA following UVB exposure while restoring the enzymatic activities of SOD and GSH, thereby mitigating oxidative stress. Moreover, GP treatment markedly upregulated the anti-inflammatory cytokines TGF-β and IL-10 and downregulated the pro-inflammatory mediators IL-6, IL-1β, and TNF-α, suggesting robust anti-inflammatory effects. Transcriptomics revealed dual-phase mechanisms: Early repair (day 5) involved GP-mediated suppression of hyper inflammation and accelerated necrotic tissue clearance via pathway network modulation. Late phase (day 18) featured enhanced anti-inflammatory, antioxidant, and tissue regeneration processes through energy-sufficient, low-inflammatory pathway networks. Through a synergistic response involving antioxidation, anti-inflammation, promotion of collagen synthesis, and acceleration of skin barrier repair, GP achieves comprehensive repair of UVB-induced acute skin damage. Our findings not only establish GP as a potent natural alternative to synthetic photoprotective agents but also reveal novel pathway network interactions governing polysaccharide-mediated skin regeneration. Full article

Lactate, once regarded as a metabolic byproduct, is now recognized as a critical immunometabolic regulator that shapes immune responses in both physiological and pathological contexts. This review examines how lactate accumulation occurs across diverse disease settings, including cancer, sepsis, and diabetes, through mechanisms such as hypoxia, mitochondrial dysfunction, and pharmacologic intervention. We then explore how lactate modulates immunity via four integrated mechanisms: transporter-mediated flux, receptor signaling (e.g., GPR81), context-dependent metabolic rewiring, and histone/protein lactylation. Particular emphasis is placed on the dichotomous effects of endogenous versus exogenous lactate, with the former supporting glycolytic effector functions and the latter reprogramming immune cells toward regulatory phenotypes via redox shifts and epigenetic remodeling. The review also highlights how the directionality of lactate transport, and the metabolic readiness of the cell determine, whether lactate sustains inflammation or promotes resolution. After analyzing emerging data across immune cell subsets and disease contexts, we propose that lactate serves as a dynamic rheostat that integrates environmental cues with intracellular metabolic and epigenetic programming. Understanding these context-dependent mechanisms is essential for the rational design of lactate-targeted immunotherapies that aim to modulate immune responses without disrupting systemic homeostasis. Full article

Lacticaseibacillus rhamnosus J3205 was isolated from traditional fermented sauces and demonstrated potential probiotic properties. The strain exhibited high tolerance to simulated saliva (93.24% survival) and gastrointestinal conditions (69.95% gastric and 50.44% intestinal survival), along with strong adhesion capacity (58.25%) to intestinal epithelial cells. Safety assessments confirmed the absence of virulence and antibiotic resistance genes. Genomic analysis revealed stress-response genes and 34 insertion sequence (IS) elements, while proteomic profiling identified Pgk as a key enzyme in lactic acid production and SecY in oxidative stress resistance. Functionally, J3205 significantly reduces pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and enhances antioxidant markers (SOD, GSH) in vitro. These results position L. rhamnosus J3205 as a promising candidate for gut-health foods, anti-inflammatory nutraceuticals, and oxidative-stress therapeutics, warranting further in vivo validation. Full article

This article reviews the multifaceted roles of itaconate in immune regulation and inflammatory metabolism. Itaconic acid is a dicarboxylic acid with anti-inflammatory, antioxidant, and anti-tumor properties. It is initially produced by the heating decomposition of citric acid and is closely related to the tricarboxylic acid cycle. In immune regulation, itaconate regulates macrophage function through a variety of mechanisms, including metabolic reprogramming, polarization regulation, inhibition of cytokine production, and regulation of oxidative stress. It can also affect the function of T cells and B cells. In terms of inflammatory metabolism, itaconate can regulate the production of inflammatory factors, inhibit the activity of succinate dehydrogenase, and affect cellular energy metabolism and lipid metabolism. Its mechanism of action involves the inhibition of succinate dehydrogenase, covalent modification of proteins, influence on epigenetic modification, and playing a role through the G protein-coupled receptor OXGR1 (Oxoglutarate Receptor 1). Itaconic acid derivatives have shown good effects in anti-inflammation and anti-oxidation and have broad application prospects in clinical treatment, including the treatment of inflammatory diseases, anti-tumor and anti-microbial infection. However, the long-term safety and side effects of itaconic acid as a therapeutic agent still need to be further studied. Future studies will further explore the synthesis and function of itaconic acid in different cell types, its physiological effects in non-inflammatory conditions, and its potential application in clinical treatment in order to develop new therapeutic strategies and improve the treatment effect of chronic inflammatory and metabolism-related diseases. Full article

Glehnia littoralis Fr. Schmidt ex Miq. has been cultivated in China for a long time and used as a medicinal plant called “Beishashen” in traditional Chinese medicine and has been traditionally known to have antibacterial and anti-inflammatory effects, but its direct role in periodontitis has not been known. Currently used periodontal treatments require long-term administration, which causes many side effects. Therefore, in this study, we evaluated the effects of G. littoralis extract (GLE) on periodontitis in an experimental periodontitis-induced in vitro and vivo model and understood its potential molecular mechanism. The effect of GLE on periodontitis in vitro was investigated using human periodontal ligament (HPDL) cells mediated by PG-LPS. Additionally, a ligature-induced periodontitis model and a PG-LPS-induced periodontal inflammation model were used to investigate the effect of GLE in vivo. In vitro study results showed that GLE down-regulated the increased inflammatory cytokines and mediators in HPDL cells stimulated with PG-LPS, and simultaneously down-regulated the levels of 11β-HSD1 and glucocorticoid receptor (GR), thereby alleviating periodontal inflammation. At the same time, it restored the lost osteoblast differentiation potential of HPDL cells. In addition, in an in vivo model representatively used for periodontitis research, the periodontal inflammation-alleviating effect and the effect of restoring or protecting damaged periodontal tissue were confirmed. GLE can be considered as a new periodontitis treatment agent through regulating 11β-HSD1. Full article

Central nervous system diseases are highly complex in terms of etiology and pathogenesis, making their treatment and interventions for them a major focus and challenge in neuroscience research. Anthocyanins, natural water-soluble pigments widely present in plants, belong to the class of flavonoid compounds. As natural antioxidants, anthocyanins have attracted extensive attention due to their significant functions in scavenging free radicals, antioxidation, anti-inflammation, and anti-apoptosis. The application of anthocyanins in the field of central nervous system injury, particularly in neurodegenerative diseases, neurotoxicity induced by chemical drugs, stress-related nerve damage, and cerebrovascular diseases, has achieved remarkable research outcomes. However, anthocyanins often exhibit low chemical stability, a short half-life, and relatively low bioavailability, which limit their clinical application. Recent studies have found that the stability and bioavailability of anthocyanins can be significantly improved through nanoencapsulation, acylation, and copigmentation, as well as the preparation of nanogels, nanoemulsions, and liposomes. These advancements offer the potential for the development of anthocyanins as a new type of neuroprotective agent. Future research will focus on the innovative design of nano-delivery systems and structural modification based on artificial intelligence. Such research is expected to break through the bottleneck of anthocyanin application and enable it to become a core component of next-generation intelligent neuroprotective agents. Full article

Due to the roles of oxidative stress, inflammation, and neurotransmitter imbalances in cognitive and mental dysfunction, we aimed to develop a functional drink with antioxidant and anti-inflammatory properties as well as the potential to support neurotransmitter balance for improved cognition and mental health. The Teng Mo, Fen Hong Mee, and Hong Chon Su guava varieties were screened for their polyphenol and flavonoid contents, antioxidant and anti-inflammatory effects, and suppressive effects on acetylcholinesterase (AChE), monoamine oxidase (MAO), GABA transaminase (GABA-T), and glutamate decarboxylase (GAD). Juice from the cultivar with the highest potential was selected and mixed with mint and honey syrups, pomelo-derived dietary fiber, ascorbic acid, agar, water, and fruit puree (pear/apple/orange) to create three guava jelly drink formulations. The formulation with pear puree showed the highest biological potential and was selected as the final product. It is rich in vitamin C, gallic acid, and dietary fiber, and provides approximately 37 Kcal/100 g. It also promotes the growth of lactic acid-producing bacteria in the culture. Thus, our drink shows the potential to reduce oxidative stress and inflammation, improve neurotransmitter regulation, and stimulate the gut–brain axis, thereby promoting cognition and mental wellness. However, clinical research is essential to confirm these potential benefits. Full article

Chronic neuroinflammation and oxidative stress play an important role in the onset and progression of neurodegenerative disorders, including Alzheimer’s disease, which can ultimately lead to neuronal damage and loss. The mechanisms of sustained neuroinflammation and the coordinated chain of events that initiate, modulate, and then lead to the resolution of inflammation are increasingly being elucidated, offering alternative approaches for treating pathologies with underlying chronic neuroinflammation. Here, we propose a new multitarget approach to address chronic neuroinflammation and oxidative stress in neurodegenerative disorders by activating the formyl peptide receptor 2 (FPR2) combined with the potentiation of hydrogen sulfide (H₂S) release. FPR2 is a key player in the resolution of inflammation because it mediates the effects of several endogenous pro-resolving mediators. At the same time, H₂S is an endogenous gaseous transmitter with anti-inflammatory and pro-resolving properties, and it can protect against oxidative stress. Starting from potent FPR2 agonists identified in our laboratories, we prepared hybrid compounds by embedding an H₂S-donating moiety within the molecular scaffold of these FPR2 agonists. Following this approach, we identified several compounds that combined potent FPR2 agonism with the ability to release H₂S. The release of H₂S was assessed in buffer and intracellularly. Compounds 7b and 8b combined potent FPR2 agonist activity, selectivity over FPR1, and the ability to release H₂S. Compounds 7b and 8b were next studied in murine primary microglial cells stimulated with lipopolysaccharide (LPS), a widely accepted in vitro model of neuroinflammation. Both compounds were able to counterbalance LPS-induced cytotoxicity and the release of pro-inflammatory (IL-18, IL-6) and anti-inflammatory (IL-10) cytokines induced by LPS stimulation. Full article

Postbiotics, as the metabolic products and cellular components of probiotics, possess the characteristics of being non-living yet retaining biological activity. Postbiotics have unique advantages such as high stability, good security, and a clear target of action. In recent years, they have attracted extensive attention due to their potential roles in immune regulation, anti-inflammation, antioxidation, antibacterial activity, and improving intestinal health. This article systematically reviews the composition of postbiotics and their diversity in fermented foods, with a focus on the impact of different inactivation methods (thermal and non-thermal inactivation) on their biological activities. Many studies have shown that the choice of inactivation method directly affects the immune regulation, anti-inflammatory, and antioxidative functions of postbiotics. Additionally, this review summarizes the application potential of postbiotics in the food industry, the field of medicine and food homology, pet food, and animal breeding, and points out the challenges existing in current research. Future studies need to focus on optimizing inactivation methods to maximize the biological efficacy of postbiotics, thereby promoting the precise application of postbiotics in various fields. Full article

Sepsis acts as the leading cause of mortality in intensive care units, characterized by life-threatening organ dysfunction due to a dysregulated host response to infection. Vitamin D (VD) pleiotropic functions were demonstrated in different biological processes, including inflammation and immunity. VD receptor (VDR) is a member of the nuclear receptor superfamily, involved in immunoregulation and resistance to infections. Previous studies have demonstrated that VD deficiency is a potential risk factor for sepsis development, which may be regulated by VDR-related physiological processes. In this review, we present a comprehensive overview of the roles of VD and VDR in sepsis, focusing on immune modulation, anti-inflammatory and anti-infective responses, oxidative stress regulation, gut microbiome enhancement, vascular endothelial cell modulation, and antiplatelet activity. We also discuss recent advances in clinical research on VD/VDR in sepsis, considering the clinical implications and potential interventions of VD analogs and VDR ligands in treatment. Despite its challenges, VD holds potential for personalized sepsis interventions. Additionally, VD/VDR may serve as a promising bidirectional immunomodulator, capable of addressing both hyperinflammatory and immunosuppressive phases of sepsis, yet require systematic investigations into its dynamic states and functions across different sepsis phases. Ongoing study and evidence-based guidelines are crucial to maximize its therapeutic benefits and improve clinical outcomes. Full article

Porcine epidemic diarrhea (PED), a highly contagious enteric disease caused by the porcine epidemic diarrhea virus (PEDV), is characterized by vomiting, diarrhea, and dehydration, leading to high mortality in newborn piglets and significant economic losses in the swine industry. The shortage of effective PED vaccines emphasizes the need to explore potent natural compounds for therapeutic intervention. It has been shown that glycerol monolaurate (GML) effectively inhibits PEDV replication in vivo and in vitro. Further investigation is needed to assess whether complex medium-chain triglycerides (CMCTs), composed of glyceryl tricaprylate/caprate (GTCC) and GML, offer an efficient anti-PEDV activity. In this study, piglets were orally infected with PEDV and exhibited typical clinical signs, including diarrhea and vomiting, accompanied by intestinal inflammation, oxidative stress, and tissue damage. CMCTs were administered orally twice daily for one week. In vivo findings indicate that CMCT treatment alleviated clinical signs and prevented weight loss. It significantly increased serum immunoglobulins (IgG, IgM, and IgA) and intestinal mucosal sIgA and MUC-2 levels, while reducing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-17) and increasing antiviral interferons (IFN-α and IFN-γ), anti-inflammatory cytokines (IL-4 and IL-10), and IL-22. Antioxidant enzyme activities (T-AOC, SOD, GSH-Px, and CAT) were elevated, whereas oxidative stress markers (iNOS, NO, and MDA) were decreased. Expression of intestinal tight junction proteins claudin-1 and ZO-1 was restored. Moreover, CD4⁺ and CD8⁺ T cell populations increased, and the functions of regulatory T cells (Tregs) were restored. Gut microbiota analysis showed increased beneficial genera (Streptococcus and Ligilactobacillus) and decreased pathogenic Escherichia-Shigella. These results demonstrate that CMCTs mitigate PEDV infection by enhancing anti-inflammation, antioxidation, and intestinal barrier function, as well as modulating gut microbiota composition. This study improves the understanding of the pathogenesis of PEDV and highlights CMCTs as a promising therapeutic candidate for PED. Full article