Search Results (4,062)

This study investigated whether ginsenoside Rg₁ (G-Rg₁) alleviated acute gouty arthritis (AGA) in rats by modulating the TLR4/NLRP3 pathway and neutrophil extracellular trap (NET) formation. Rats were orally administered G-Rg₁ or colchicine (Col) for 7 days, and monosodium urate (MSU) was injected into the ankle joints on day 5 to induce AGA. Joint swelling, histopathology (HE staining), and serum markers (MPO, NE, MPO-DNA, IL-6, IL-1β; ELISA) were assessed at the baseline and 6–36 h post-modeling. Western blot and immunofluorescence analyzed the NET-related and TLR4/NLRP3 pathway proteins in synovial tissue. G-Rg₁ significantly reduced ankle swelling and synovial inflammation compared with the AGA group, lowered the serum IL-6, IL-1β, MPO, NE, and MPO-DNA levels, and suppressed NET-associated protein expression. Mechanistically, G-Rg₁ downregulated TLR4/NLRP3 pathway activation in synovial tissue. These findings suggest that G-Rg₁ mitigates AGA by inhibiting TLR4/NLRP3 signaling, thereby reducing inflammatory cytokine release and NET formation. Full article

Imidacloprid (IMI) is a widely used insecticide known for its high selectivity toward insects. Ellagic acid (EA) is a plant-derived polyphenolic compound recognized for its therapeutic potential and favorable safety profile in the treatment of various diseases. This study aimed to evaluate the therapeutic effects of EA, formulated as novasomes (NOV), against IMI-induced thyroid dysfunction and to investigate the underlying mechanisms. Rats were divided into four equal groups: control, EA-NOV, IMI, and IMI + EA-NOV. Thyroid function was assessed by measuring free triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) levels. Thyroid tissues were examined to evaluate histopathological alterations, as well as to assess the oxidative/antioxidant pathway (Nrf2, SOD, TAC, MDA), inflammatory pathway (IL-1β, TNF-α, NF-κB), apoptotic pathway (Bcl, BAX), and autophagy pathway (PI3K/Akt/mTOR, P53, Beclin-1). Exposure to IMI resulted in impaired thyroid function, the upregulated gene expression of the PI3K/Akt/mTOR pathway, and downregulated P53 expression. Additionally, immunohistochemical staining revealed Beclin-1-mediated autophagy, alongside increased apoptosis, oxidative stress, and elevated levels of inflammatory cytokines. Conversely, EA improved thyroid function and ameliorated histopathological alterations by enhancing autophagy-inducing pathways. Additionally, the alleviation of oxidative stress was evidenced by the increased immunohistochemical staining of Nrf2, which promoted the synthesis and activity of antioxidant enzymes and reduced apoptotic and inflammatory markers. This study proposes the use of EA as a potential protective, naturally occurring phytoceutical against IMI-induced thyroid dysfunction, primarily through the modulation of PI3K/Akt/mTOR-mediated autophagy. Full article

D-glucuronolactone (DGL), a hepatoprotective compound widely used in clinical and energy products, was evaluated for its effects on Chinese soft-shelled turtles (Pelodiscus sinensis) through an 8-week feeding trial with dietary supplementation (0, 200, and 400 mg kg⁻¹). DGL did not alter survival or feed intake, but induced dose-dependent growth improvements, including increased final body weight, weight gain rate, specific growth rate, and muscle/liver glycogen, alongside reduced feed conversion ratio and muscle and liver fat. Serum analysis showed decreased activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and reduced low-density lipoprotein cholesterol, total cholesterol, and triacylglycerols. Antioxidant indices revealed elevated catalase and superoxide dismutase (SOD) activities in serum and intestine, coupled with reduced malondialdehyde, though hepatic SOD activity declined. Histologically, 400 mg kg⁻¹ DGL alleviated liver lesions without impacting intestinal morphology. Molecular analyses demonstrated upregulated muscle mTOR signaling genes (mTOR, IGF1, S6K1) but downregulated hepatic/intestinal mTOR and IGF1 expression. DGL also suppressed inflammatory cytokines (TNF-α, IL-1β, IL-10) in liver and intestine. Challenge tests with Aeromonas hydrophila confirmed the enhanced disease resistance in DGL-supplemented turtles. These findings highlight DGL’s potential as a nutritional strategy to enhance growth, antioxidant capacity, and health in intensive turtle farming. Full article

Diabetic foot ulcers (DFUs) are among the most common and debilitating complications of diabetes mellitus (DM), affecting approximately 15–25% of patients and contributing to over 85% of non-traumatic amputations. DFUs impose a substantial clinical and economic burden due to high recurrence rates, prolonged wound care, and frequent hospitalizations, accounting for billions in healthcare costs worldwide. The multifactorial pathophysiology of DFUs involves peripheral neuropathy, peripheral arterial disease, chronic inflammation, and impaired tissue regeneration. Recent studies underscore the importance of immune dysregulation—specifically macrophage polarization imbalance, regulatory T cell dysfunction, and neutrophil impairment—as central mechanisms in wound chronicity. These immune disruptions sustain a pro-inflammatory environment dominated by cytokines, such as TNF-α, IL-1β, and IL-6, which impair angiogenesis and delay repair. This review provides an updated synthesis of DFU pathogenesis, emphasizing immune dysfunction and its therapeutic implications. We examine emerging strategies in immunomodulation, regenerative medicine, and AI-based wound technologies, including SGLT2 inhibitors, biologics, stem cell therapies, and smart dressing systems. These approaches hold promise for accelerating healing, reducing amputation risk, and personalizing future DFU care. Full article

Cell-based therapy using mesenchymal stem cells (MSCs) shows promise for treating several diseases due to their anti-inflammatory and immunomodulatory properties. To enhance the therapeutic potential of MSCs, in vitro priming strategies have been explored. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, may influence MSC proliferation, differentiation, and immunomodulatory properties. This study evaluates the immunomodulatory potential of equine adipose tissue-derived MSCs (EqAT-MSCs) primed with a CBD-rich cannabis extract. EqAT-MSCs (P3) were primed with CBD concentrations of 5 µM and 7 µM for 24 h. Morphological analysis, MTT assay, β-galactosidase activity, apoptosis assays, and gene expression of interleukins IL-1β, IL-6, IL-10, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) were conducted. Additionally, cannabinoid receptor 1 (CB1) and 2 (CB2) expression were evaluated in naïve EqAT-MSCs (P2–P5). The naïve EqAT-MSCs expressed CB1 and CB2 receptors. Priming with 5 µM significantly increased the expression of IL-10, TNF-α, and IFN-γ, while 7 µM decreased IL-1β and IL-6 expression. No significant changes were observed in other cytokines, MTT, β-galactosidase activity, or apoptosis. These findings demonstrate that naïve EqAT-MSCs express CB1 and CB2 receptors and priming with the extract modulates the expression of pro- and anti-inflammatory cytokines, highlighting its potential immunomodulatory role in EqAT-MSC-based therapies. Full article

Pemphigus-associated interstitial lung disease (P-ILD) is a severe complication observed in pemphigus patients that is characterized by pulmonary interstitial inflammation and fibrosis. This study investigated the role of anti-desmoglein (Dsg) 1/3 antibodies in P-ILD pathogenesis and evaluated the therapeutic potential of molecular hydrogen (H₂). Using a BALB/cJGpt mouse model, we demonstrated that anti-Dsg 1 antibodies, but not anti-Dsg 3 antibodies, induced interstitial inflammation and fibrosis. Immunofluorescence staining confirmed IgG deposition in the alveolar epithelium, suggesting immune complex formation and epithelial damage. Gene expression analysis revealed elevated pro-inflammatory cytokines (IL-1β, IL-13) and upregulated pro-fibrotic markers (α-SMA, S100A4, TGF-β, and collagen genes) in P-ILD progression. Elevated oxidative stress and impaired ROS metabolism further implied the role of oxidative damage in disease pathogenesis. To assess H₂’s therapeutic potential, hydrogen-rich water was administered to P-ILD mice. H₂ treatment significantly reduced oxidative stress, attenuated interstitial inflammation, and prevented pulmonary fibrosis. These protective effects were attributed to H₂’s antioxidant properties, which restored the pro-oxidant–antioxidant balance. Our findings underscore the critical role of anti-Dsg 1 antibodies and oxidative stress in P-ILD and highlight H₂ as a promising therapeutic agent for mitigating anti-Dsg 1 antibody-induced lung injury. Full article

Background: The implantation process is complex and involves numerous factors that can affect its success. In artificial reproductive treatments (ARTs), chronic inflammation seems to be associated with implantation failure, largely contributing to reproductive dysfunction. Pentraxin 3 (PTX3) is overexpressed in several pathological conditions by exerting a pivotal role both as a regulator and indicator of inflammatory response. Some literature data have shown that PTX3 could have an impact on follicle growth and development, influencing women’s fertility. This study aimed to detect PTX3 in follicular fluids collected during an ART protocol in relation to implantation outcomes. Methods: The PTX3/NF-kB/TLR4 pathway and other cytokines were assessed in the follicular fluid of 169 subjects, under the age of 40 years, undergoing IVF cycles, including females without achieved implantation (n = 98) and those with implantation (n = 71). Furthermore, subgroup analyses were performed to evaluate PTX3 values according to age difference. Results: From our data, PTX3 emerged as a strong predictor, more than TNFα and IL-1β, of implantation failure and related inflammatory follicular state. Overall, the results point to PTX3 as a potential biomarker for ART success, and their testing may be helpful in women whose successful implantation remains unexplained. Conclusions: Therefore, PTX3 could constitute a reliable biomarker and a valuable target to improve ART outcomes. Full article

Background: Sapindus mukorossi Gaertn is a deciduous tree with saponins as the main active ingredients and has been utilized in medicine and cosmetic industries. Currently, the investigations of S. mukorossi mainly focus on the pericarp and seed kernel parts, while other parts are yet to be studied and developed. This study aimed to investigate the anti-acne potential of S. mukorossi flower water extract (SMFW) by in vitro experiments. Methods and Results: The DPPH, ABTS, superoxide anion radical scavenging assay, and FRAP assay revealed the strong antioxidant activities of SMFW. The antibacterial activity of SMFW against Cutibacterium acnes has been evaluated with an inhibition diameter of 14.08 ± 0.63 mm. Furthermore, SMFW significantly inhibited the secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-β) in lipopolysaccharide (LPS)-stimulated THP-1 macrophages. Transcriptome analysis showed that SMFW treatment reversed 448 LPS-upregulated DEGs and 349 LPS-downregulated DEGs, and KEGG enrichment analysis indicated that SMFW might exert its anti-inflammatory effect via NOD-like receptor and JAK-STAT signaling pathways. Conclusions: SMFW exhibited antioxidant, antibacterial, and anti-inflammatory properties in in vitro experiments. RNA-seq analysis indicated that SMFW may alleviate inflammation by regulating the NOD-like receptor and JAK-STAT signaling pathways. In summary, SMFW has shown potential for anti-acne efficacy and can be used as a natural raw material in cosmetics. Full article

Background/Objectives: Periodontitis and diabetes mellitus share a well-established bidirectional relationship, where hyperglycemia exacerbates periodontal inflammation, and periodontal disease further impairs glycemic control. Within the diabetic periodontal microenvironment, an imbalance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages promotes chronic inflammation, oxidative stress, delayed healing, and alveolar bone resorption. Resveratrol (RSV), a polyphenol with antioxidant, anti-inflammatory, and pro-osteogenic properties, holds potential to restore macrophage balance. However, its clinical application is limited by poor bioavailability and instability. This study aimed to develop and evaluate a novel RSV delivery system to overcome these limitations and promote periodontal tissue regeneration under diabetic conditions. Methods: A drug delivery system comprising RSV-loaded solid lipid nanoparticles embedded within a cross-linked hyaluronic acid hydrogel (RSV@CLgel) was formulated. The system was tested under hyperglycemic and inflammatory conditions for its effects on macrophage polarization, cytokine expression, oxidative stress, mitochondrial function, and osteoblast differentiation. Results: RSV@CLgel effectively suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while upregulating anti-inflammatory markers (IL-10, TGF-β). It significantly reduced oxidative stress by decreasing ROS and lipid peroxidation levels and improved mitochondrial function and antioxidant enzyme activity. Furthermore, RSV@CLgel enhanced osteoblast differentiation, as evidenced by increased ALP activity, calcium nodule formation, and upregulation of osteogenic genes (COL-I, RUNX2, OCN, OPN). It also inhibited RANKL-induced osteoclastogenesis, contributing to alveolar bone preservation. Conclusions: The RSV@CLgel delivery system presents a promising multifunctional strategy for the management of diabetic periodontitis. By modulating immune responses, reducing oxidative stress, and promoting periodontal tissue regeneration, RSV@CLgel addresses key pathological aspects of diabetes-associated periodontal disease. Full article

Undaria pinnatifida fucoidan (UPF), a bioactive sulphated polysaccharide, is widely recognised for its anti-inflammatory, antioxidant, antitumor, anticoagulant, antiviral, and immunomodulatory properties. However, the precise mechanisms by which UPF regulates inflammation and neuronal health remain unclear. This study aimed to investigate the effects of UPF supplementation on pro-inflammatory cytokines in skeletal muscle, small intestine, and the hypothalamus, as well as plasma cytokine levels. Additionally, a brain proteomic investigation in the nucleus accumbens (NAc) was performed to assess UPF’s impact on neuronal protein expression in mice. A total of 64 C57BL/6J mice were administered either a standard chow or high-fat diet (HFD) with or without UPF (400 mg/kg/day) for 10 weeks. In HFD-fed mice, UPF significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in skeletal muscle, small intestine, and hypothalamus, while also lowering circulating IL-1α and IL-6 levels. Proteomic analysis of the NAc revealed that UPF modulated proteins involved in oxidative stress, neuroinflammation, neurotransmitter regulation, and endoplasmic reticulum stress. In contrast, in chow-fed mice, UPF had no effect on the neuroinflammatory–oxidative stress markers but influenced the abundance of proteins associated with immune response and innate immunity. These findings suggest that UPF modulates stress-response pathways in a diet-dependent manner, supporting its potential neuroprotective role in inflammation-related disorders and brain health. Full article

Bovine viral diarrhea (BVD) is a common viral disease in cattle that causes huge economic losses in naïve herds that are introduced to bovine viral diarrhea virus (BVDV). Currently, there are no available anti-BVDV drugs due to the variety and mutability of strains; therefore, developing new anti-BVDV drugs is of great significance. The aim of this study was to investigate the anti-BVDV effects and immunomodulatory activities of Codonopsis pilosula polysaccharides (CPPs) in BVDV-infected bovine macrophage (BoMac) cells. CPPs directly inactivated BVDV particles and intervened in BVDV absorption process. The immunity suppression resulting from BVDV in BoMac cells was restored by CPPs, as was verified by phagocytosis increase, the expression up-regulation of cell surface co-stimulatory molecules (CD40, CD80, and CD86), and antigen-presenting function recovery. Furthermore, the expressions of cytokines including TNF-α, IFN-γ, IL-6, IL-18, IL-1β, Caspase-3, Bim, and Bcl-xL at the mRNA and proteins levels were modulated, and a reduction in the apoptosis rate was observed, which demonstrates that CPPs attenuated inflammation and apoptosis induced by BVDV. Collectively, our findings reveal new pharmacological properties of CPPs, which exert anti-BVDV efficacy and regulate immune injury induced by BVDV in BoMac cells, indicating that CPPs are a potential option for BVDV prevention in clinical application. Full article

The large yellow croaker (Larimichthys crocea) is a cornerstone species in Chinese marine aquaculture, yet bacterial infections—particularly visceral white nodules disease (VWND) caused by Pseudomonas plecoglossicida—severely compromise its production. This study aimed to elucidate the immunoregulatory mechanisms of tripartite motif-containing protein 38 in the large yellow croaker (Lctrim38) during bacterial infections, with an emphasis on host–pathogen interactions involving P. plecoglossicida, to evaluate its potential for disease-resistant breeding applications. The full-length cDNA of Lctrim38 was cloned and characterized, with structural analysis revealing a conserved domain architecture comprising RING, B-box, coiled-coil, and PRY-SPRY motifs. Functional characterization through Lctrim38 overexpression in large yellow croaker kidney cells (PCK cells) demonstrated significant modulation of key immune-related pathways, including TGF-β, PI3K-Akt, IL-17, and PPAR. Notably, Lctrim38-mediated inhibition of NF-κB signaling was shown to downregulate pro-inflammatory cytokines (TNF-α, IL-6, IFN-γ), establishing its role as a negative regulator of inflammatory responses. These findings provide insights into the immune mechanisms of Trim38 in large yellow croakers and highlight its potential as a molecular target for disease resistance breeding. Future research should explore its broader functions, including its antiviral potential. Full article

Background: The link between periodontal pathogens, inflammation, and neurodegenerative processes, including Alzheimer’s disease (AD), is evident. Porphyromonas gingivalis and Treponema denticola release lipopolysaccharide (LPS), constituting a virulence factor that takes part in the brain inflammatory process. Human gingival fibroblasts (HGF-1) are a source of pro-inflammatory cytokines released during periodontal diseases. Propolis is a rich source of quercetin and apigenin, which exhibit anti-inflammatory and immunomodulatory activities, influencing the concentration of pro-inflammatory cytokines. Considering this aspect, models with stimulated HGF-1, followed by LPS and/or interferon-α (IFN-α), were used. Aim: This study was designed to evaluate the concentrations of selected cytokines produced by HGF-1, which may influence brain inflammation. The immunomodulatory effects of apigenin and quercetin were investigated by measuring the concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-15 (IL-15), and tumour necrosis factor (TNF-α). This study’s novelty is based on insights into the immunomodulatory effects of selected flavonoids by correlating the secretion of pro-inflammatory cytokines by gingival fibroblasts during periodontal disease with inflammatory processes in the brain. The cytotoxicity of apigenin and quercetin was estimated using the MTT assay. Fibroblasts were stimulated with LPS at 200 ng/mL and/or IFN-α at 100 U/mL concentration, followed by incubation with apigenin (25–50 µg/mL) and quercetin (25–50 µg/mL). Cytokine concentrations were measured using the xMAP technology. Results: The most pronounced and statistically significant reduction in cytokine levels, particularly IL-6 and IL-15, was observed for quercetin in both concentrations (25 µg/mL and 50 µg/mL), especially following LPS stimulation. Apigenin in both analysed concentrations also significantly decreased the level of IL-6. These results suggest that quercetin and apigenin may indirectly act as potential immunomodulators in preventing brain inflammation by inhibiting the inflammatory process in periodontitis; however, this should be confirmed in further studies. Full article

Cisplatin (CDDP) is an anticancer drug that is frequently used to treat head and neck cancers; however, it may cause oral mucositis. The discontinuation of CDDP may be required for some patients with a severe status, and the control of oral mucositis is extremely important. β-Cryptoxanthin (β-cry), a carotenoid, exerts anti-inflammatory effects. Its inhibition of 5-FU-induced inflammatory responses was recently demonstrated. However, the effects of β-cry on CDDP-induced oral mucositis remain unclear. In the present study, we stimulated human oral mucosa-derived keratinocytes (hOMK) and fibroblasts (hOMF) with CDDP, added β-cry, and examined its effects, with a focus on the production of inflammatory cytokines, matrix metalloproteinase (MMPs), and reactive oxygen species (ROS). CDDP increased the mRNA expression and production of inflammatory cytokines and MMPs both in hOMK and hOMF. However, increases in IL-6 and MMP-9 mRNA expression levels and IL-6 production in CDDP-treated hOMK and hOMF were inhibited by β-cry. Furthermore, the production of ROS and the rate of SA-β-gal-positive cells were increased by CDDP, but were not affected by β-cry. CDDP may induce oral mucositis by increasing the levels of inflammatory cytokines, MMPs, and ROS. β-cry partially inhibited CDDP-induced increases in inflammatory cytokines and MMPs, suggesting its potential to attenuate the symptoms of chemotherapy-related oral mucositis. Full article

Muscle satellite (stem) cells (MSCs) reside in skeletal muscle and are essential for myogenesis. Thus, MSCs are widely used in cultured meat research. This study aimed to identify substances that promote MSC proliferation and differentiation while maintaining their intrinsic properties, with the long-term goal of replacing fetal bovine serum (FBS) for bovine MSC cultivation. Therefore, this study evaluated the effects of six growth factors (TGF-β, HGF, PDGF, insulin, IGF-1, and EGF) and the cytokine IL-2 on bovine MSCs. Each factor was applied during the proliferation and differentiation of MSCs, and the proliferation rate, differentiation rate, and expression of relevant mRNA and proteins were analyzed. Insulin most effectively promoted MSC proliferation and differentiation. Specifically, insulin increased cell proliferation rates, proliferation markers Ki67 and PCNA expressions, and markers of differentiation, such as myotube formation and creatine kinase activity, alongside the expressions of MYOD, MYOG, and MYH. Furthermore, insulin suppressed low FBS-induced reductions in proliferation and differentiation markers. This study suggests insulin can promote MSC proliferation and differentiation and reduce FBS usage. Thus, this study provides a potential means of cultivating MSCs on a large scale for cultured meat production. Full article