Journal of Immunology Research
·
2023
·
IF 4.1
Hui Du,Shiwen Tong,Ge Kuang,Xia Gong,Ningman Jiang,Xian Yang,Hao Liu,Nana Li,Yao Xie,Yang Xiang,Jiashi Guo,Zhenhan Li,Yinglin Yuan,Shengwang Wu,Jingyuan Wan
Acetaminophen (APAP) overdose would lead to liver toxicity and even acute liver failure in severe cases by triggering an inflammatory response and oxidative stress. Sesamin has been reported to possess anti-inflammatory and antioxidant actions in several animal disease models. In the present study, the effects and mechanisms of sesamin on APAP-induced acute liver injury (ALI) were explored. The results showed that pretreatment with sesamin significantly alleviated APAP-induced ALI, as indicated by decreased serum aminotransferase activities, hepatic pathological damages, and hepatic cellular apoptosis. But sesamin has no significant effects on the expression of cytochrome P450 2E1 (CYP2E1), APAP-cysteine adducts (APAP-CYS) production, and glutathione content in the liver of APAP-administered mice. Moreover, APAP-induced liver oxidative stress and inflammatory response also were remarkedly attenuated by sesamin, including reducing hepatic reactive oxygen species levels, promoting antioxidant generation, and inhibiting the expression of TNF-α and IL-1β, as well as decreasing inflammatory cell recruitment. Notably, sesamin inhibited serum high-mobility group box 1 (HMGB1) releases and blocked hepatic activation of Toll-like receptor 4 (TLR4)-interleukin 1 receptor-associated kinase 3-nuclear factor kappa B (NF-κB) signaling pathway in APAP-administered mice. These findings indicated that sesamin could mitigate APAP-induced ALI through suppression of oxidative stress and inflammatory response, which might be mediated by the deactivation of HMGB1/TLR4/NF-κB signaling in mice.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Wenqian Wang,Qingfu Zhang,Tong Zhang,Fuping Lu,Fufeng Liu
Current therapeutic options for Parkinson's disease (PD) are limited in efficacy and burdened with severe side-effects. Inflammation, intertwined with oxidative stress and influenced by gut microbiota-related changes making the gut-brain axis the main target of innovative therapies. This study reveals the multiple protective effects of polysaccharides extracted from Ulva lactuca (UPE) on PD models. In vitro, UPE was shown to have direct cytoprotective effects, including mitigating 1-methyl-4-phenylpyridinium-induced cell apoptosis, reducing reactive oxygen species levels, and maintaining mitochondrial membrane potential. In vivo, oral UPE significantly restored motor deficits and dopaminergic neuron loss caused by MPTP. These in vivo benefits were associated with the inhibition of oxidative stress and inflammation. Moreover, oral UPE inhibits the excessive activation of glial cells and the excessive production of pro-inflammatory factors and oxidative stress markers in serum. Furthermore, 16S rRNA analysis of gut microbiota revealed that UPE reshaped the gut microbiota of PD mice by increasing the abundance of norank_f_Murbaculaceae and decreasing the abundance of Desulfovibrio . Mechanically, the Nrf2/HO-1 and TLR4/NF-κB signaling pathways are involved in the anti-PD effect of UPE. In general, UPE offers new perspectives on PD treatment and demonstrates the potential of natural polysaccharides in treating neurodegenerative diseases.
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Advanced Healthcare Materials
·
2024
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IF 10
Jiahao Wang,Liang Zhang,Lingjun Wang,Jincheng Tang,Wei Wang,Yichang Xu,Ziang Li,Zhouye Ding,Xinzhao Jiang,Kun Xi,Liang Chen,Yong Gu
Targeting macrophages can facilitate the site-specific repair of critical bone defects. Herein, a composite hydrogel, gelatin- Bletilla striata polysaccharide-mesoporous bioactive glass hydrogel (GBM gel ), is constructed via the self-assembly of mesoporous bioactive glass on polysaccharide structures, through the Schiff base reaction. GBM gel can efficiently capture macrophages and drive the recruitment of seed stem cells and vascular budding required for regeneration in the early stages of bone injury, and the observed sustained release of inorganic silicon ions further enhances bone matrix deposition, mineralization, and vascular maturation. Moreover, the use of macrophage-depleted rat calvarial defect models further confirms that GBM gel , with ligand-selective macrophage targeting, increases the bone regeneration area and the proportion of mature bone. Mechanistic studies reveal that GBM gel upregulates the TLR4/NF-κB and MAPK macrophage pathways in the early stages and the JAK/STAT3 pathway in the later stages; thus initiating macrophage polarization at different time points. In conclusion, this study is based on the endogenous self-healing properties of bone macrophages, which enhances stem cell homing, and provides a research and theoretical basis upon which bone tissue can be reshaped and regenerated using the body's immune power, providing a new strategy for the treatment of critical bone defects.
研究领域:
生物医学工程
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组织工程
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免疫学
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再生医学
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材料科学
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POULTRY SCIENCE
·
2026
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IF 4.5
Dan Shao,Longqing Hu,Wei Guo,Jinglong Chen,Xuming Guo,Hong Yao
This study aimed to investigate the protective effect and mechanism of dietary dimethylglycine (DMG) on jejunal injury in yellow-feathered broilers subjected to cyclic heat stress (HS). A total of 180 35-day-old male yellow-feathered broilers were randomly allocated into 3 groups: the thermoneutral condition with basal diet group (CON), the cycle heat stress with basal diet group (HS, 32-35°C), and the cycle heat stress with 0.1% DMG in basal diet group (HS_DMG, 32-35°C). The experiment included a 7-day heating period followed by a 14-day cyclic heat stress period. Growth performance, rectal temperature, jejunal morphology and ultrastructure, inflammatory cytokine levels, and protein expression related to the TLR4/NF-κB pathway and MUC2 were evaluated. Additionally, primary chicken jejunal epithelial cells were isolated and exposed to heat stress with or without DMG pretreatment to validate in vivo findings. Results showed that heat stress significantly increased rectal temperature ( P < 0.05), had a tendency to reduce body weight (BW, P = 0.058) and average daily gain (ADG, P = 0.050), and increase the feed-to-gain ratio (F/G, P = 0.053). Histologically, HS caused epithelial shedding, reduced villus height and villus height/crypt depth, and induced microvilli damage and mitochondrial swelling, all of which were attenuated by DMG supplementation. Heat stress also elevated jejunal mucosa levels of IL-6, IL-8, IL-1 β , and TNF- α ( P < 0.05), while DMG reduced IL-6, IL-8, and TNF- α ( P < 0.05). Immunohistochemistry and western blotting revealed that HS decreased MUC2 expression and increased TLR4 and p-NF-κB-p65 protein levels ( P < 0.05), whereas DMG reversed these changes ( P < 0.05). In vitro, DMG pretreatment alleviated HS-induced reduction in inflammatory cytokine release, and alterations in TLR4, NF-κB, and MUC2 protein expression. In conclusion, dietary DMG supplementation alleviates cyclic heat stress-induced jejunal injury in yellow-feathered broilers by suppressing the TLR4/NF-κB signaling pathway and restoring MUC2 expression.
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Cancer Cell International
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2021
·Vol. 21
·期 1
·1-14
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IF 5.722
Li Chunyang,Yang Shuangqing,Ma Huaqing,Ruan Mengjia,Fang Luyan,Cheng Jing
Background Cervical cancer is a type of the most common gynecology tumor in women of the whole world. Accumulating data have shown that icariin (ICA), a natural compound, has anti-cancer activity in different cancers, including cervical cancer. The study aimed to reveal the antitumor effects and the possible underlying mechanism of ICA in U14 tumor-bearing mice and SiHa cells.Methods The antitumor effects of ICA were investigated in vivo and in vitro. The expression of TLR4/MyD88/NF-κB and Wnt/β-catenin signaling pathways were evaluated.Results We found that ICA significantly suppressed tumor tissue growth and SiHa cells viability in a dose-dependent manner. Also, ICA enhanced the anti-tumor humoral immunity in vivo. Moreover, ICA significantly improved the composition of the microbiota in mice models. Additionally, the results clarified that ICA significantly inhibited the migration, invasion capacity, and expression levels of TGF-β1, TNF-α, IL-6, IL-17A, IL-10 in SiHa cells. Meanwhile, ICA was revealed to promote the apoptosis of cervical cancer cells by down-regulating Ki67, survivin, Bcl-2, c-Myc, and up-regulating P16, P53, Bax levels in vivo and in vitro. For the part of mechanism exploration, we showed that ICA inhibits the inflammation, proliferation, migration, and invasion, as well as promotes apoptosis and immunity in cervical cancer through impairment of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways.Conclusion sTaken together, ICA could be a potential supplementary agent for cervical cancer treatment.
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PHARMACEUTICAL BIOLOGY
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2020
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IF 2.971
Zhaohui Wang,Zhi Chen,Bingsheng Li,Bo Zhang,Yongchao Du,Yuhang Liu,Yao He,Xiang Chen
Context Renal interstitial fibrosis (RIF) is characterized by the accumulation of inflammatory cytokines and epithelial-mesenchymal transition (EMT). Curcumin exerts antifibrogenic, anti-inflammatory and antiproliferative effects.Objective To explore the mechanisms underlying the effects of curcumin on RIF.Materials and methods Eight-week-old male C57BL/6 mice were intragastrically administered curcumin (50 mg/kg/day) for 14 days after undergoing unilateral ureteral obstruction (UUO) operations. Renal function (blood urea nitrogen [BUN] and serum creatinine [Scr]) and inflammatory cytokine levels were tested using colorimetric assays and ELISA, respectively. EMT markers were evaluated through immunohistochemistry, western blotting and qPCR. Transforming growth factor beta 1 (TGF-β1; 10 ng/mL) and lipopolysaccharides (LPS; 100 ng/mL) were used to stimulate EMT and an inflammatory response in human renal proximal tubular epithelial (HK-2) cells, respectively, for further investigation.Results In vivo, curcumin significantly improved the levels of BUN and Scr by 28.7% and 21.3%, respectively. Moreover, curcumin reduced the levels of IL-6, IL-1β and TNF-α by 22.5%, 30.3% and 26.7%, respectively, and suppressed vimentin expression in UUO mice. In vitro, curcumin reduced the expression of vimentin and α-smooth muscle actin in TGF-β1-induced HK-2 cells. In LPS-induced HK-2 cells, curcumin decreased the release of IL-6, IL-1β and TNF-α by 43.4%, 38.1% and 28.3%, respectively. In addition, curcumin reduced the expression of TLR4, p-PI3K, p-AKT, p-NF- κB and p-IκBα in both LPS- and TGF-β1-induced HK-2 cells.Discussion and conclusions Curcumin repressed EMT and the inflammatory response by inhibiting the TLR4/NF-κB and PI3K/AKT pathways, demonstrating its potential utility in RIF treatment.
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International Journal of Nanomedicine
·
2024
·
IF 6.6
Kang Dong,Xin Wang,Ze-jia Zhou,Xin-ru Zheng,Zhuang-peng Chang,Rui Zhao,Jun-jin Liu,Rui-gang Hou,Xiao Zhang,Yun-yun Shao
Introduction Ulcerative colitis (UC) is a chronic intestinal disease characterized by spleen-lung qi deficiency and dampness-pathogenic obstruction. Although there are various treatment options available, patients frequently encounter significant drug-related side effects. Previous studies have shown the potential of Codonopsis Radix polysaccharides A (CPA) in treating UC, but their limited bioavailability has restricted their clinical use. Therefore, the objective of this study was to develop a novel formulation that can address the aforementioned limitations and assess its potential advantages.Methods and Results We synthesized a negatively charged amphipathic prodrug called CPA-SA-DHA (CSD), which consists of CPA as the hydrophilic component, and succinic anhydride and docosahexaenoic acid as the hydrophobic segments. The CSD nanoparticles obtained had a particle size of 180.0 ± 3.2 nm, a negative zeta potential of −29.8 ± 5.3 mV, and a uniform shape with a PDI index of 0.230 ± 0.003. The interaction between positive and negative charges significantly increased the retention time of CSD nanoparticles in the colonic microenvironment. Furthermore, CSD nanoparticles demonstrated enhanced bioavailability in UC mice compared to CPA. Additionally, we observed that CSD nanoparticles exhibited therapeutic effects on DSS-induced UC mice by regulating the diversity and abundance of gut microbiota. This effect may be mediated by the inhibition of pro-inflammatory signaling pathways TLR4/NF-κB.Conclusion These findings confirm the potential of CSD nanoparticles as a promising treatment option for UC.
研究领域:
药学
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胃肠病学
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纳米技术
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免疫学
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Honglei Zhang,Yun Lu,Yuanlei Zhang,Jiayu Dong,Su Jiang,Yunping Tang
Objective This study explores the therapeutic effects and mechanisms of DHA-enriched phosphatidylserine (DHA-PS) on liver injury induced by cyclophosphamide (CTX) in mice, focusing on the gut-liver axis. Methods A mouse model was established by administering CTX (80 mg/kg) intraperitoneally for 5 days. DHA-PS (50 or 100 mg/kg) was administered for the next 7 days to assess its reparative impact on liver damage. Results The findings revealed significant improvements in liver biochemical indices, inflammatory markers, and oxidative stress levels in the mice treated with DHA-PS. Through non-targeted metabolomics analysis, DHA-PS mitigated CTX-induced metabolic disruptions by modulating lipid, amino acid, and pyrimidine metabolism. Immunofluorescence analysis further confirmed that DHA-PS reduced the expression of liver-associated inflammatory proteins by inhibiting the TLR4/NF-κB pathway. Additionally, DHA-PS restored the intestinal barrier, evidenced by adjustments in the levels of intestinal lipopolysaccharide (LPS), secretory immunoglobulin A (sIgA), and tight junction proteins (Claudin-1, Occludin, and ZO-1). It also improved gut microbiota balance by enhancing microbial diversity, increasing beneficial bacteria, and altering community structures. Conclusion These results suggest that DHA-PS could be a potential therapeutic agent or functional food for CTX-induced liver injury through its regulation of the gut-liver axis.
研究领域:
药理学
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肝病学
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胃肠病学
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免疫学
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代谢组学
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Food & Function
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2024
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IF 5.1
Bufan Xu,Luyao Zhang,Di Wu,Zihe Qi,Juanjuan Cao,Wenrui Li,Lihua Fan,Yiheng Shi,Yongning Wu,Guoliang Li
Copper II oxide nanoparticles (CuO NPs), a kind of widely used nanomaterial, have been detected in food and the environment, which has aroused widespread public concern. Recently, increasing data have suggested that intestinal microecology is closely related to immune homeostasis. However, the intestinal immunotoxicity induced by CuO NPs through intestinal microbiota is still unknown. Therefore, in this study, zebrafish were exposed to CuO NPs to explore intestinal immunotoxicity by evaluating physiological indicators, intestinal tissue injury, antioxidant enzyme activities, gene expression of immune factors, and changes in intestinal microbiota and its metabolites (short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS)). The results revealed that the intestinal immunotoxicity of CuO NPs was mediated by the impact on intestinal microbiota and its metabolite levels. Specifically, changes were observed in the abundance of microbes that participated in the metabolism of SCFAs and LPS. The reduction in acetic acid, propionic acid and valeric acid upregulated GPR84 expression, and the decline in LPS levels further resulted in the suppression of the key immune regulatory pathways TLR4/MyD88/NF-κB, ultimately leading to intestinal immunotoxicity. This study would provide a scientific basis for the risk assessment of CuO NPs and a new perspective for research on the immunotoxicity of nanoparticles.
研究领域:
环境科学
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毒理学
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微生物学
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免疫学
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水生生物学
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Cell Stem Cell
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2025
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IF 20.4
Lei Fan,Qi Tang,Yutong Wang,Hang Sun,Ge Li,Yi Yang,Huiying Zhu,Zhaoyuan Liu,He Wang,Hongyan Wang,Qing Jing,Christopher L. Antos,Hui Xiao,Renchu Guan,Gang Pei,Florent Ginhoux,Zhigang Zhou,An Zeng
Adult hearts scar after injury, while neonatal hearts regenerate. The mechanisms underlying this dichotomy remain unclear. Through comparative spatiotemporal single-cell analyses and dual recombinase-mediated lineage tracing, we uncovered an injury-induced Clusterin + cardiomyocyte ( Clu + CM) population that coordinates reparative, anti-inflammatory macrophage activity. Following injury, Clu + CMs emerge in the border zone of regenerative hearts but are scarce in non-regenerative contexts. These CMs secrete CLU, which binds to macrophage Toll-like receptor 4 (TLR4), attenuating inflammation and promoting reparative polarization through Cpt1a -dependent fatty acid oxidation. These macrophages secrete bone morphogenetic protein 2 (BMP2), activating bone morphogenetic protein receptor, type 1A (BMPR1A) signaling in CMs to drive proliferation. Reduced CLU levels in myocardial infarction patients correlate with impaired cardiac function, whereas Clu overexpression or transplantation of engineered CLU + human cardiac organoids recapitulates this regenerative modulation, enhancing myocardial repair in adult mice. Our findings reveal a critical cardio-immune mechanism whereby Clu + CMs reprogram macrophages to resolve inflammation and stimulate CM proliferation, providing potential strategies for cardiac regeneration.
研究领域:
心脏病学
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免疫学
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再生医学
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分子生物学
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细胞信号传导
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RESEARCH IN VETERINARY SCIENCE
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2022
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IF 2.554
Mohammad Reza Tabandeh,Sadegh Jozaie,Zohre Ghotbedin,Saad Gorani
The stimulation of pro-inflammatory pathways by lipopolysaccharide (LPS) endotoxins is a key player in the pathological mechanisms involved in the development of ovarian dysfunctions in dairy cows. Dimethyl itaconate acid (DMIA) is a novel immunometabolite that has recently emerged as a regulator of inflammatory responses in mammals. The present study was undertaken to determine the anti-inflammatory effects of DMIA on bovine granulosa cells (GCs) and to explore its possible molecular mechanisms. The ovarian GCs were obtained from small follicles of dairy cows. The GCs were stimulated with 1 μg/mL LPS for 4 h and then treated with 250 μM DMIA for 12 h. The viability, production of pro-inflammatory cytokines, activation of inflammatory signaling pathways and synthesis of steroid hormones were evaluated in treated GCs. Our results showed that DMIA reduced the inflammatory responses in LPS stimulated GCs by down-regulating the expression of nod-like receptor family pyrin domain containing 3 inflammasome , and toll-like receptor 4 and by suppressing the phosphorylation of nuclear factor kappa B and c-Jun N-terminal kinase proteins . DMIA also attenuated the increased production of pro inflammatory cytokines (interleukin 6, tumor necrosis factor α and interleukin 1 beta ( p < 0.01) in LPS stimulated GCs. Exposure of LPS stimulated GCs to DMIA improved the impaired steroidogenesis by up-regulation of steroid synthesis genes including 3-beta-hydroxysteroid dehydrogenase, follicle stimulating hormone receptor and cytochrome P450 aromatase . The results of the present study highlight the potential role of itaconic acid for the improvement of GCs inflammation in dairy cows with ovarian dysfunctions.
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Cell Death Discovery
·
2025
·Vol. 11
·期 1
·1-15
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IF 7
Zheng Xiao-Bo,Wang Xue,Gao Sheng-Qing,Gao Chao-Chao,Li Tao,Han Yan-Ling,Zhao Ran,Sun Yan,Miao Shu-Hao,Qiu Jia-Yin,Jin Wang-Xuan,Zhou Meng-Liang
Brain endothelial cell (bEC) dysfunction is the main factor of blood-brain barrier (BBB) breakdown, which triggers a vicious cycle of aggravating traumatic brain injury (TBI) pathogenesis. Previous studies have revealed that neutrophil extracellular traps (NETs) released by neutrophils can lead to BBB disruption, but there is a lack of research on the underlying mechanisms after TBI. Here, excessive NETs were found in both contused brain tissue and circulation following TBI. We found that NETs could activate the TLR4/NF-κB pathway to induce bEC pyroptosis, which led to BBB disruption after TBI. During this process, ninjurin-1 (NINJ1) was activated in pyroptotic bECs, and it mediated the release of high mobility group box 1 protein (HMGB1) via plasma membrane rupture (PMR) to promote NET formation. NINJ1-mediated release of HMGB1 aggravated NET accumulation by forming a vicious circle following TBI. Knockdown of NINJ1 rescued NET formation, attenuated BBB leakage, and improved neurological outcomes after TBI. NINJ1 may represent a promising target for alleviating NET-induced BBB destruction and other related injuries after TBI.
研究领域:
神经科学
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免疫学
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分子生物学
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病理学
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