JOURNAL OF FISH DISEASES
·
2025
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IF 2.2
Bo Li,Penghui Yu,Lei Su,Jianguo Su,Yu Gao,Gailing Yuan
Aeromonas hydrophila- induced bacterial sepsis is a major threat to aquaculture, characterised by excessive inflammation, ferroptosis (an iron-dependent lipid peroxidation-driven cell death) and oxidative damage, which collectively lead to high mortality. Taurine (TAU) and glutathione (GSH) have been demonstrated to have potential therapeutic efficacy against ferroptosis-associated pathologies through redox modulation. However, their combined effects and underlying mechanisms in alleviating A. hydrophila infection remain unclear. In this study, we investigated the protective roles of TAU, GSH and their combination in vitro using yellow catfish ( Pelteobagrus fulvidraco ) macrophages and grass carp ( Ctenopharyngodon idella ) kidney (CIK) cells and in vivo using yellow catfish challenged with A. hydrophila . The results showed that TAU and GSH, either alone or in combination, alleviated oxidative stress by significantly reducing reactive oxygen species (ROS) accumulation and inhibited nuclear factor-κB (NF-κB) pathway activation. This led to downregulated expression of pro-inflammatory cytokines ( IL- 1β and TNF -α) and upregulated anti-inflammatory cytokines ( IL- 10 and TGF -β), accompanied by alleviated ferroptosis. In vivo, dietary supplementation with TAU (10 g/kg) or GSH (350 mg/kg) alone improved survival rates (51.7% and 38.3%, respectively), reduced tissue bacterial loads and protected intestinal and hepatic tissues by preserving mucosal barrier function. However, the TAU + GSH combination unexpectedly decreased survival (28.3%) due to excessive immunosuppression (overproduction of IL- 10 and TGF -β) and impaired mucosal barrier, which exacerbated pathogen colonisation. Together, our findings demonstrate that TAU and GSH alleviate A. hydrophila -induced oxidative stress by reducing mitochondrial ROS overproduction and disrupting the ROS/NF-κB signalling pathway, thereby attenuating inflammatory cytokine storms and ferroptosis. These results provide novel insights into the pathological mechanisms of bacterial sepsis in fish and develop sustainable strategies to improve disease resistance in aquaculture.
研究领域:
水产养殖
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鱼类免疫学
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分子病理学
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氧化应激与细胞死亡
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兽医微生物学
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PubMed
高影响因子
AQUACULTURE
·
2025
·
IF 3.9
Feiran Li,Guangyao Hu,Mengsha Zhou,Liqun Lu
Spring viremia of carp virus (SVCV) inflicts substantial economic damage on global cyprinid farming operations, primarily affecting common carp and koi carp. Currently, no effective control measures exist. Baicalein, a flavonoid derived from Scutellaria baicalensis , exhibits broad-spectrum antiviral activity. This study investigated baicalein's inhibitory effects against SVCV in vitro and in vivo. Cytotoxicity assays demonstrated no observable toxicity in EPC cells at concentrations of 1–25 μg/mL. Transcriptome analysis and biochemical assays revealed that baicalein enhances innate immunity via the NF-κB pathway while concurrently suppressing SVCV-induced apoptosis. In SVCV-infected koi, baicalein treatment significantly reduced viral replication, attenuated pathogenicity, and improved survival rates. Pharmacokinetic studies in koi carp indicated favorable properties: rapid absorption (Tmax = 4 h), sustained plasma presence (t 1/2 z/h > 7 h), and dose-proportional exposure (AUC 0-t ). These findings establish baicalein as a novel therapeutic candidate against SVCV in aquaculture.
研究领域:
水产养殖
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病毒学
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药理学
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鱼类健康
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抗病毒研究
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
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IF 5.714
Liping Wang,Tiantian Ji,Ye Yuan,Haoyu Fu,Yang Wang,Shaobo Tian,Jia Hu,Lin Wang,Zheng Wang
The dramatically increasing incidence and prevalence of inflammatory bowel disease (IBD) are reportedly related to a Western diet, which is characterized by high sugar consumption. Dietary simple sugars aggravate IBD in animal models. However, the mechanisms underlying this effect remain unclear. Given that high-fructose corn syrup (HFCS) is a major added sugar in food and beverages, we focus on HFCS and investigated the effects of HFCS on a dextran sulfate sodium (DSS)-induced murine colitis model and in RAW264.7 macrophages. Our data demonstrate that short-term consumption of HFCS aggravates colitis and upregulates the proportion of macrophages in IBD mice but not in healthy mice. We find that HFCS promotes proinflammatory cytokine production through reactive oxygen species (ROS)-mediated nuclear factor-κB (NF-κB) signaling in RAW264.7 macrophages. Furthermore, N-acetylcysteine (NAC), an ROS scavenger, alleviates HFCS-aggravated colitis in mice and inhibits the ROS-mediated NF-κB signaling pathway in RAW264.7 macrophages. Our work unveils the important role of macrophages in HFCS-induced exacerbation of colitis and reveals the mechanism of how HFCS immunologically aggravates IBD.
研究领域:
免疫学
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胃肠病学
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营养学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Xin-Yu Shen,Jing-Mei Lu,Yu-Nan Lu,Guang-Nan Jin,Jing-Wen Ma,Jing-He Wang,Yu Wang,Xiang Xu,Lian-Xun Piao
Toxoplasma gondii ( T. gondii ) is an obligate intracellular protozoan parasite that causes pulmonary toxoplasmosis, although its pathogenesis is incompletely understood. There is no cure for toxoplasmosis. Coixol, a plant polyphenol extracted from coix seeds, has a variety of biological activities. However, the effects of coixol on T. gondii infection have not been clarified. In this study, we infected a mouse macrophage cell line (RAW 264.7) and BALB/c mice with the T. gondii RH strain to establish infection models in vitro and in vivo , respectively, to explore protective effects and potential mechanisms of coixol on lung injury caused by T. gondii infection. Anti- T. gondii effects and underlying anti-inflammatory mechanisms of coixol were investigated by real-time quantitative PCR, molecular docking, localized surface plasmon resonance, co-immunoprecipitation, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence microscopy. The results show that coixol inhibits T. gondii loads and T. gondii -derived heat shock protein 70 ( T.g. HSP70) expression. Moreover, coixol reduced inflammatory cell recruitment and infiltration, and ameliorated pathological lung injury induced by T. gondii infection. Coixol can directly bind T.g. HSP70 or Toll-like receptor 4 (TLR4) to disrupt their interaction. Coixol prevented overexpression of inducible nitric oxide synthase, tumor necrosis factor-α, and high mobility group box 1 by inhibiting activation of the TLR4/nuclear factor (NF)-κB signaling pathway, consistent with effects of the TLR4 inhibitor CLI-095. These results indicate that coixol improves T. gondii infection-induced lung injury by interfering with T.g. HSP70-mediated TLR4/NF-κB signaling. Altogether, these findings suggest that coixol is a promising effective lead compound for the treatment of toxoplasmosis.
研究领域:
寄生虫学
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免疫学
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Yana Ma,Wen Luo,Weijia Zhu,Zhichao Deng,Shijun Xu,Hang Yuan,Wei-jun Fan,Quanjun Yao,Wei Yao,Ho-Young Song,Mingzhen Zhang,Jizhao Wang,Hongtao Hu
Oxidative stress, resulting from excessive reactive oxygen species (ROS), is critically involved in the development and progression of inflammatory diseases such as inflammatory bowel disease. Therefore, targeting ROS for the treatment of inflammation holds great potential, and the underlying mechanism is of great significance for clinical medication. In this work, carbon dots (C-dots) based on chrysanthemum as carbon source were obtained through a hydrothermal method. The as-prepared C-dots exhibited favorable ROS scavenging capacity and biocompatibility. The ROS level and the oxidative damage were reversed, the expression of proinflammatory factors was reduced, and the disrupted barrier was recovered by chrysanthemum-derived C-dots in the cellular inflammatory model. The anti-inflammatory effects were also validated in mice colitis model. Mechanistically, the chrysanthemum-derived C-dots regulated the Keap1/Nrf2 antioxidant signaling and inhibited the NF-κB/NLRP3 inflammasome-mediated inflammatory signaling, thereby restoring redox homeostasis and modulating the inflammatory microenvironment. Collectively, the C-dots from chrysanthemum with preferable biocompatibility hold a bright prospect in inflammation resolution through remodeling redox and inflammatory microenvironment.
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高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Xia Wu,Chun-Feng Liu
Septic cardiomyopathy (SCM) is a prevalent complication among septic patients, accompanied by high mortality. Estrogen‐related receptor alpha (ERRα), a transcription factor, is implicated in various cardiovascular diseases. Nonetheless, its role in SCM remains unclear. Here, the cecum ligation and puncture (CLP) procedure was used to construct a mouse sepsis model. We found that the ERRα expression was downregulated in septic hearts. Adeno-associated virus-9 (AAV-9)-mediated cardiomyocyte-specific ERRα overexpression improved the survival rate of septic mice. Additionally, ERRα overexpression ameliorated CLP-induced cardiac dysfunction and myocardial pathological damage. In vitro , HL-1 mouse cardiomyocytes were transduced with an ERRα overexpression adenovirus before LPS stimulation. The results demonstrated that ERRα overexpression mitigated LPS-induced inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-18) and apoptosis (Bax, cleaved caspase-3/9) in HL-1 cells. Mechanistically, ERRα inhibited the NF-κB/NLRP3 inflammasome activation in septic hearts and LPS-stimulated HL-1 cells. Furthermore, we overlapped the differentially expressed genes of septic hearts (GSE125042) and ERRα KO hearts (GSE7196) to identify the downstream target genes. Meteorin like, glial cell differentiation regulator (METRNL) was identified as the target gene of ERRα. Notably, ERRα bound to the METRNL promoter and upregulated its activity, which was confirmed via dual-luciferase reporter assay, ChIP-qPCR, and oligonucleotide pull-down assay. Knockdown of METRNL prevented the effects of ERRα overexpression on the apoptosis and inflammatory response of cardiomyocytes induced by LPS. Our findings underscore the role of ERRα in mitigating myocardial injury in SCM, indicating its potential as a new therapeutic approach.
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高影响因子
International Journal of Nanomedicine
·
2026
·
IF 8.7
Pongsigeraxi Borjigin,Caixia Deng,Rilaga Su,Juan Li,Ying Ying,Yingsong Chen,Tegexibaiyin Wang
Purpose This study aimed to enzymatically synthesize pearl powder fluorescent carbon dots (PFCDs) and investigate their neuroprotective potential against cerebral ischemia/reperfusion injury (CIRI) by modulating the Anxa2/NF-κB signaling pathway.Methods PFCDs were synthesized through enzymatic digestion and characterized. Neuroprotective effects were assessed using an in vitro oxygen–glucose deprivation/reoxygenation (OGD/R) model in PC12 cells and a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model. Cell viability, neurological function, cerebral infarct volume, and neuronal injury were evaluated. Expression of Anxa2/NF-κB signaling pathway proteins and inflammatory cytokines (TNF-α, IL-6, IL-1β) was analyzed by Western blot, immunofluorescence, and ELISA.Results The synthesized PFCDs exhibited an organic–inorganic hybrid structure, uniform particle size below 10 nm, and distinctive optical properties. In vitro, PFCDs enhanced cell viability under OGD/R conditions, inhibited phosphorylation of Anxa2 and NF-κB p65, and reduced secretion of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). In vivo, treatment with PFCDs in MCAO/R rats improved neurological function, reduced cerebral infarct volume, and alleviated neuronal injury. These protective effects were linked to downregulation of the Anxa2/NF-κB signaling pathway and reduced serum levels of inflammatory cytokines.Conclusion We successfully achieved the enzymatic synthesis of carbon dots from pearl powder, characterized by a unique organic–inorganic hybrid structure. PFCDs effectively alleviated CIRI-induced neuroinflammation by suppressing the Anxa2/NF-κB signaling pathway, highlighting their therapeutic potential as a nanomedicine derived from natural products.
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高影响因子
MOLECULES
·
2026
·Vol. 31
·期 11
·1933
·
IF 5.1
Yanlong Li,Anning Zhan,Xiaobing Zhang,Yu Duan,Jiawen Tang,Hua Bai,Qi Wang
Objective: The present study investigates the effect of 1,8-cineole on improving lipid metabolism disorder by regulating oxidative stress and inflammation via the TLR4/MyD88/NF-κB pathway. 1,8-Cineole is a monoterpene compound widely found in the essential oils of many plants and has been reported to possess anti-inflammatory and antioxidant activities. However, its role in regulating lipid metabolism disorders remains unclear. This study aimed to investigate the effects of 1,8-cineole on lipid metabolism and explore the potential mechanisms related to oxidative stress and inflammation. Methods: Cell viability was assessed by MTT assay to determine the optimal PA concentration for inducing lipid accumulation and the non-cytotoxic range of 1,8-cineole in HepG2 and AML-12 cells. Lipid droplets were visualized by Oil Red O staining, while triglyceride (TG) and total cholesterol (TC) levels were quantified using enzymatic kits. Oxidative stress markers (ROS by DCFH-DA fluorescence; MDA by TBA method; CAT activity by ammonium molybdate method) and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-18 by ELISA) were measured. Western blotting analyzed key proteins in the TLR4/MyD88/NF-κB pathway (TLR4, MyD88, p-P65, p-IκBα). Pathway-specific inhibitors were employed for mechanistic validation. Results: 1,8-Cineole (up to 1000 μg/mL) showed no cytotoxicity. It significantly attenuated PA-induced lipid droplet accumulation, reduced TG and TC levels (p< 0.05), and ameliorated oxidative stress by decreasing ROS and MDA while enhancing CAT activity in AML-12 cells (p< 0.01). Furthermore, 1,8-cineole suppressed pro-inflammatory cytokine release (TNF-α, IL-6, and IL-1β;p< 0.01), whereas no significant effect was observed on IL-18 levels. Downregulated TLR4/MyD88/NF-κB pathway activation. Inhibition of TLR4 or NF-κB mirrored these protective effects. Conclusions: 1,8-Cineole alleviates PA-induced lipid metabolism disorders, oxidative stress, and inflammation in hepatocytes, likely through suppression of the TLR4/MyD88/NF-κB signaling pathway.
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PubMed
高影响因子
Scientific Reports
·
2026
·
IF 4.9
Niu Jiale,Liu Guangxia,He Guangyao,Zhang Xiaomeng,Bai Huihui,Lu Yamin
To investigate the role of IL-17 in macrophage M1 polarization within a type 2 diabetic (T2DM) milieu and to evaluate the therapeutic potential of its neutralizing antibody. PMA-differentiated THP-1 macrophages were polarized to M1 state. Under high glucose, cells were treated with IL-17 and an IL-17 neutralizing antibody. Inflammatory cytokines (IL-1β, IL-6, TNF-α) were measured; mRNA levels of TNF-α, HIF-1α, and NLRP3 were assessed by qPCR; and protein expression related to the NF-κB, mTOR/HIF-1α axis and pyroptosis (NLRP3, Caspase-1, GSDMD) was analyzed by Western Blot. High glucose and IL-17 synergistically promoted M1 polarization, enhancing proinflammatory cytokine secretion. This was associated with activation of the NF-κB, mTOR/HIF-1α signaling axis and induction of pyroptosis, evidenced by NLRP3 inflammasome assembly, Caspase-1 activation, and GSDMD cleavage. The IL-17 neutralizing antibody effectively suppressed these pathological processes. IL-17 acts as a key immunological amplifier in diabetes, driving M1 polarization, oxidative stress, and pyroptosis via the NF-κB, mTOR/HIF-1α axis and NLRP3 inflammasome. Treatment with an αIL-17 effectively reversed the aberrant activation of the aforementioned cellular phenotypes and signaling pathways, partially restoring macrophage functional balance. This finding provides preliminary experimental support for further exploration of IL-17-targeted immunomodulatory strategies to ameliorate diabetes-associated metabolic inflammation.
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INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2022
·Vol. 50
·期 5
·1-14
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IF 5.314
Weichao Sun,Wei Xie,Dixi Huang,Yinxing Cui,Jiaji Yue,Qifei He,Luoyong Jiang,Jianyi Xiong,Wei Sun,Qian Yi
Osteoarthritis (OA) is the most common degenerative disease affecting the joints, and inflammation appears to play a critical role in the initiation and progression of OA. Caffeic acid phenethyl ester (CAPE), a natural flavonoid compound, has anti‑inflammatory and antioxidant functions. However, its anti‑inflammatory effects on OA and the underlying mechanisms of action of CAPE in the treatment of OA remain elusive. Therefore, the present study investigated the anti‑inflammatory effects of CAPE on IL‑1β‑stimulated chondrocytes in vitro and surgically induced rat models of OA in vivo. In vitro, CAPE reduced the expression of inducible nitric oxide synthase and cyclooxygenase‑2 in IL‑1β‑stimulated chondrocytes, as well as the extracellular secretion of nitric oxide and prostaglandin E2 in the cell culture supernatants. In addition, CAPE attenuated the degradation of extracellular matrix by increasing the expression of aggrecan and collagen II, and decreasing the expression of MMP3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motif‑5. Furthermore, CAPE attenuated NF‑κB signaling and activated the nuclear factor erythroid 2‑related factor 2/heme oxygenase‑1 signaling pathway in IL‑1β‑stimulated chondrocytes. In vivo, CAPE protected cartilage from destruction and delayed the progression of OA in rats. Taken together, the findings of the present study indicated that CAPE may be a potential therapeutic agent for the prevention or treatment of OA.
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高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2023
·Vol. 396
·期 6
·1247-1255
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IF 3.6
Su Jie,Yin Wei,Huo Mengmeng,Yao Qing,Ding Liqiong
Glioma is an extremely aggressive primary brain tumor, which is highly resistant to chemotherapy, presenting a therapeutic challenge. Here, we explored the anti-glioma effects and the underlying mechanism of lycorine, an isoquinoline alkaloid isolated from lycoris on glioma cells. We found that lycorine could dose dependently inhibit C6 glioma cell growth and induce cell apoptosis and intracellular reactive oxygen species (ROS) production. The half-maximal inhibitory concentration (IC 50 ) values of lycorine on C6 glioma cells at 48 h was 2.85 μM. Meanwhile, lycorine treatment caused dysfunction of the NF-κB signal, as demonstrated by the up-regulation of NF-κB inhibitor protein IκB and the downregulation of the NF-κB phosphorylation protein p-p65. The addition of NF-κB inhibitor SC75741 further confirmed the importance of the NF-κB pathway in lycorine-induced cell-growth inhibition. Moreover, lycorine might act synergically with temozolomide (TMZ) to reduce drug resistance by blocking the NF-κB pathway. Our study suggested that lycorine exerts an anti-glioma effect by inducing ROS production and inhibiting NF-κB, which validated that lycorine may be a potential candidate for glioma treatment alone or in combination with TMZ.
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Advanced Healthcare Materials
·
2023
·Vol. 12
·期 10
·2203195
·
IF 10
Zhongyin Zhang,Lichan Yuan,Yufeng Liu,Ruobing Wang,Yihong Zhang,Yan Yang,Hui Wei,Junqing Ma
Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease with no complete cure at present. Notably, the inflammatory microenvironment in TMJ OA is modulated by oxidative stress, which impacts cartilage metabolism, chondrocyte apoptosis, inflammatory cytokine release, and extracellular matrix (ECM) synthesis. Thus, it is reasoned that reducing excess reactive oxygen species (ROS) in the chondrocyte microenvironment may be an effective therapeutic strategy for TMJ OA. Recently, cascade nanozymes, including Pt@PCN222-Mn, have been exploited to treat ROS-associated diseases. Nevertheless, cascade nanozymes are not employed for TMJ OA therapy. To fill this gap, it is explored whether the Pt@PCN222-Mn cascade nanozyme could be applied to the treatment of TMJ OA. The in vitro results demonstrate that the Pt@PCN222-Mn nanozyme can inhibit the production of inflammatory factors, the degradation of ECM, and the apoptosis of chondrocytes by inhibiting the ROS-nuclear factor kappa-B (NF- κ B_ and mitogen-activated protein kinase signaling pathways. The in vivo results further demonstrate that the Pt@PCN222-Mn nanozyme can delay the progression of TMJ OA in the rat unilateral anterior crossbite model. It is believed that insightful perspectives on the application of nanozymes in TMJ OA will be provided here.
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高影响因子
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