RESPIRATORY RESEARCH
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2026
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IF 5.7
Hui Zhang,Wei Dai,Xuanyu Chen,Xinru Xi,Yeqing Chen,Jingjing Song,Xiangting Ge,Qiangwei Xiang,Bing Zhang,Chengguang Zhao,Weixi Zhang,Yali Zhang
Background: Allergic asthma stands as the predominant asthma phenotype propelled by aberrant type 2 immune response. Type-2 innate lymphoid cells (ILC2s) are significant for generating IL-5 and IL-13 cytokines, highlighting their vital role in triggering and escalating the progression of asthma. Myeloid differentiation primary response protein 88 (MyD88) controls innate and adaptive immune responses by orchestrating inflammatory signals. Objective: This work focused on investigating the influence of MyD88 in governing ILC2s-driven allergic airway disease alongside its underlying molecular mechanisms. Methods: We evaluated the effects of MyD88 in IL-33-induced or allergen-induced airway hyperreactivity (AHR) and airway inflammation. The role and mechanism of MyD88 in regulating ILC2s function were examined in vivo and in vitro by using transcriptome sequencing analysis, flow cytometry, clinical samples, ILC2-specific MyD88 knockout mice, and anti-Thy1.2 antibody against ILC2s in mice. Results: The results showed heightened MyD88 expression in ILC2s sourced from allergic asthmatic patients and asthmatic mice. MyD88 knockout in ILC2s was able to mitigate IL-33-induced airway inflammation, while the MyD88 inhibitor LM8 proves efficacious in attenuating allergen-induced airway inflammation and AHR. After elimination of ILC2s via anti-Thy1.2 antibody, the pharmacological activity of LM8 diminished. Mechanistic studies revealed that MyD88 mediates the activation and proliferation of ILC2s through facilitation of P38-GATA3 complex formation. Conclusions: The research highlights MyD88 as a critical regulator of ILC2s activation, suggesting its potential utility as a therapeutic target for interventions in allergic asthma.
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Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
·
IF 3.9
Yu Ling,Luo Qianwen,Rao Xiaohui,Xiao Xiao,Wang Pinghan
Kawasaki disease (KD) is a severe pediatric vasculitis leading to coronary artery complications. Hydrogen sulfide (H 2 S), a recognized endogenous gasotransmitter with anti-inflammatory properties, offers potential as a novel treatment for KD through its cardiovascular benefits. However, the specific effects and underlying mechanisms remain unclear. The objective of present study is to investigate the anti-inflammatory and therapeutic effects of exogenous H 2 S in KD using network pharmacology and experimental validation. By online database searches, a total of 405 pharmacological targets for H 2 S, 826 KD-related targets, and 107 potential therapeutic targets of H 2 S for KD were identified. Through PPI analysis and Cytoscape screening, 9 hub genes were filtered, namely TNF, IL6, JUN, AKT1, IL1B, TP53, NFKB1, MAPK1, and RELA. KEGG pathway enrichment indicated that the TLR4/MyD88/NF-κB signaling pathway may play a crucial role in the therapeutic effects of H 2 S on KD. Additionally, in vivo experiments confirmed that the treatment of sodium hydrosulfide (NaHS), an H 2 S donor, markedly improved body weight, reduced inflammatory pathology in the coronary arteries, and downregulated levels of inflammatory cytokines TNF-α, IL-1β, and IL-6. Furthermore, WB analysis confirmed that NaHS inhibited the expression of TLR4, MyD88, NF-κB, and p-NF-κB. In brief, it is the first to reveal that exogenous H 2 S attenuates the inflammatory response in KD via the TLR4/MyD88/NF-κB pathway, highlighting its potential as a novel therapeutic approach for KD. These findings lay a foundation for further development of H 2 S-based therapies for KD management.
研究领域:
儿科
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药理学
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免疫学
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心血管科学
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ENVIRONMENTAL POLLUTION
·
2021
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IF 8.071
Jiaqi Xu,Qiuhui Qian,Min Xia,Xuedong Wang,Huili Wang
Trichlorocarban (TCC) is ubiquitously detected in environmental matrices, while there is a paucity of information regarding its systemic toxicity. In the present study, we observed that TCC exposure led to high embryo mortality, delayed hatching and yolk absorption, as well as increased malformations, such as closure of swim sac and yolk sac edema. Meanwhile, TCC affected the formation and branch of subintestinal veins (SIVs), intersegmental vessels and posterior cardinal veins. Especially, the SIVs were shrunk, and their branches were reduced or even broken along with reduced coverage area. TCC-induced oxidative stress and excessive apoptosis resulted from abnormal expression of the anti/pro-apoptotic genes. Significant reduction in the number and aggregation function of immune cells proved that TCC had prominent immunotoxicity to zebrafish. TCC-targeted TLR4 signaling pathway was demonstrated by abnormal expression of the marker genes ( tlr4 , MyD88 and nf-κb ) and release of the downstream inflammatory factors (TNF-α, IL-6, etc.). Inhibition of TLR4/MyD88/NF-κB pathway by an inhibitor (CA-4948) rescued the decreasing trend of the immune cells induced by TCC. Molecular docking results demonstrated that TCC could stably bind to TLR4 receptor to form hydrogen bonds and hydrophobic interactions with amino acids. Overall, these findings reveal the underlying molecular mechanisms on TCC-induced developmental and immune toxicity to zebrafish.
研究领域:
毒理学
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环境科学
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分子生物学
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免疫学
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发育生物学
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高影响因子
INFLAMMATION
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2026
·Vol. 49
·期 1
·41
·
IF 5
Zheng-qing Hu,Ruijie Ma,Hang Zhang,Jiahao Miao,Jia-qing Sun,Jinlong Yuan,Jiaqiang Liu,Zihuan Zhang,Dayong Xia
This study aims to elucidate the mechanism by which Heat Shock Protein 60 (HSP60) mediates microglial pyroptosis in the context of early brain injury (EBI) following subarachnoid hemorrhage (SAH), and to investigate the effects of HSP60 inhibition on EBI after SAH. A mouse subarachnoid hemorrhage (SAH) model was established using prechiasmatic cistern blood injection. In vitro, microglia were stimulated with 25 µmol/L oxyhemoglobin (OxyHB) to simulate the SAH pathological environment. In vivo, mice received 100 mg/kg Mizoribine, while in vitro, 80 µmol/L Mizoribine was used to suppress SAH-induced HSP60 upregulation. Techniques including Western blotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, ELISA, modified Garcia neurological scoring, beam walking, brain water content measurement, Morris water maze, TUNEL staining, and Nissl staining were employed to systematically investigate the role of HSP60 inhibition in neuroinflammation and microglial pyroptosis after SAH. Compared to the sham group, both in vivo and in vitro studies with blinded, random sampling of six groups demonstrated a significant increase in HSP60 expression post-SAH. In vivo, 100 mg/kg Mizoribine alleviated blood-brain barrier disruption, cerebral edema, neuronal apoptosis/necrosis, and improved neurological deficits and cognitive impairment. In vitro, 80 µmol/L Mizoribine markedly attenuated microglial activation and pyroptosis, downregulated pro-inflammatory cytokines, and mitigated neuroinflammation. The upregulation of HSP60 after SAH promotes NLRP3 inflammasome assembly by activating the TLR4/MyD88/NF-κB signaling pathway, thereby inducing microglial pyroptosis and exacerbating the progression of early brain injury. Inhibition of HSP60 represents a potential therapeutic strategy for ameliorating EBI after SAH.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Airu Huang,Ling Ji,Yilong Huang,Qian Yu,Yufeng Li
MicroRNAs (miRNAs) are important modulators in the evolvement and progression of neuropathic pain (NP). According to reports, miR-185-5p contributes to various diseases and inflammatory responses. However, it is not clear whether miR-185-5p mediates neuroinflammation and NP following chronic constrictive injury (CCI). The CCI model was constructed in rats to induce NP. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were employed to evaluate pain threshold in CCI rats. The expression of miR-185-5p, GFAP, Iba1, Caspase-3-positive cells, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-labeled apoptotic neurons, inflammatory mediators, including interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) in lumbar portion (L4-L6) of CCI rats were determined. Furthermore, the targets of miR-185-5p were predicted by the Starbase, and the binding association between miR-185-5p and MyD88, miR-185-5p and CXCR4 was verified by the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. As shown by the data, miR-185-5p was distinctly reduced in L4-L6 spinal cord tissues of rats after CCI. Up-regulating miR-185-5p alleviated mechanical and thermal hyperalgesia, inactivated microglia and astrocytes accumulation, and abated the contents of IL-1β, IL-6 and TNF-α in L4-L6 spinal cord tissues of CCI rats. Bioinformatics analysis suggested that MyD88 and CXCR4 were potential target genes of miR-185-5p. Increasing miR-185-5p expression notably impeded the expression of MyD88, CXCR4 and NLRP3 inflammasome in BV2 microglia, while attenuating miR-185-5p expression exerted the opposite effects. Notably, down-regulating MyD88 and CXCR4 significantly enhanced the miR-185-5p-mediated anti-inflammatory effects, and reversed miR-185-5p inhibitor-mediated proinflammatory effects. Additionally, up-regulating miR-185-5p repressed BV2-induced neuronal apoptosis and increased neuronal viability. In conclusion, this study suggested that miR-185-5p chokes CCI-induced NP and neuroinflammation by targeting MyD88 and CXCR4, indicating that miR-186-5p is an underlying therapeutic target for NP.
研究领域:
神经科学
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分子生物学
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药理学
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疼痛研究
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高影响因子
Frontiers in Pharmacology
·
2020
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IF 4.225
Wei Aiwu,Xiao Huidongzi,Xu Guangli,Yu Xile,Guo Jingjing,Jing Zhuqing,Shi Shaoqi,Song Yanli
Anticardiolipin antibody (aCL), an important characterization of antiphospholipid syndrome, shows an intense association with vascular endothelial injury. Hyperoside is a flavonoid extracted from medicinal plants traditionally used in Chinese medicines, displaying anti-inflammatory, anti-cancer, and anti-oxidative properties in various diseases. Recent studies have shifted the focus on the protective effects of hyperoside on vascular endothelial injury. However, little is known about the mechanisms involved. In the present study, we investigated the effect of hyperoside on aCL-induced injury of human umbilical vein endothelial cells (HUVECs) in vitro. Our data illustrated that aCL induced HUVEC injury via inhibiting autophagy. Hyperoside reduced aCL-induced secretion of proinflammatory cytokines IL-1β and IL-8 and endothelial adhesion cytokines TF, ICAM1, and VCAM1 in HUVECs. Additionally, hyperoside activated autophagy and suppressed the mTOR/S6K and TLR4/Myd88/NF-κB signaling transduction pathways in aCL-induced HUVECs. To the best of our knowledge, this is the first study to investigate the effect of hyperoside on aCL-induced injury, as well as offer insights into the involved mechanisms, which is of great significance for the treatment of antiphospholipid syndrome.
研究领域:
免疫学
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药理学
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细胞生物学
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血管生物学
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高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1385
·
IF 7.5
Gong Jiaxin,Wei Feng,Wu Tianyu,Zhang Ningzhi,Zhang Yongqiao,Cui Zhaoqiang,Ge Junbo
Background Obesity-related cardiac injury is a serious global condition associated with excessive fat intake, which is strongly linked to chronic low-degrade inflammation. Pyroptosis, a pro-inflammatory form of cell death, has been implicated in obesity recently. L-Fucose (Fuc), a sulfated polysaccharide with anti-inflammatory and antioxidant properties, remains unexplored in the area of pyroptosis and obesity-related cardiac injury. Methods Six-week-old wide type C57BL/6 mice were subjected to high-fat diet (HFD) feeding for 20 weeks to induce obesity with or without Fuc gavaging, followed by assessment of metabolic related indicators. Echocardiography, histopathological analysis and enzymatic assays were used to assess cardiac function. The level of pro-inflammatory cytokines was detected by ELISA, qRT-PCR and CD68 staining. Pyroptosis-related protein including NLRP3, GSDMD, pro-caspase-1, cleaved-caspase-1, IL-1β, and ASC were evaluated by western blot. Oxidative stress was detected by ROS level. Cardiac mitochondrial structure was assessed by electron microscopy and mitotracker staining. Mitochondrial function was measured by mitochondrial membrane potential (MMP) and oxygen consumption rate (OCR) assay. Molecular docking and molecular dynamics (MD) simulations were conducted to look for the potential target of Fuc. Cellular thermal shift assay (CETSA) and western blot were used to investigate the interaction between Fuc and its target. Palmitic acid (PA) induced lipotoxicity model in AC16 cells was used to further confirm the protective effects of Fuc and its downstream signaling pathway against inflammation, pyroptosis and mitochondrial injury in vitro. Results In vivo, Fuc treatment alleviated obesity-related weight gain, hyperlipidemia, elevated systolic blood pressure and cardiac diastolic dysfunction. It also reduced the expression of pro-inflammatory cytokines and pyroptosis-related proteins, the level of oxidative stress, and mitochondrial abnormalities in the myocardium. Moreover, the vitro lipotoxicity model further confirmed the protective effect of Fuc. The molecular docking analysis identified TLR4 as the key target of Fuc. Fuc reduced the level of TLR4 and its downstream proteins MyD88 and p-NF-κB, while activating TLR4/MyD88/NF-κB pathway by TLR4 agonist Neoseptin3 reversed the protective function of Fuc in vitro. Conclusions These findings demonstrated that Fuc mitigated cardiac inflammation, pyroptosis and mitochondrial injury by inhibiting the TLR4/MyD88/NF-κB pathway, highlighting its potential as a therapeutic agent for obesity-associated cardiac injury.
研究领域:
心脏病学
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分子生物学
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免疫学
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代谢性疾病
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药理学
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Materials Today Bio
·
2026
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IF 11
Zhen-Zhen Wang,Lihua Cao,Zhenzhu Zhao,Mengke Zhao,Yanyan Lu,Yanhui Zhu,Weijie Xie,Ping Li,Siqi Liu,Xuejiao Li,Kang Yang,Xiaobo Sun
TLR4 activation and the cascade of neutrophil extracellular trap (NET) formation exacerbate excessive inflammation and organ damage in the pathogenesis of acute lung injury (ALI), yet effective pharmacological interventions remain unavailable. Nanoaggregates derived from natural products offer promising avenue by leveraging synergistic anti-inflammatory effects. In this study, we surprisingly discovered that leonurine and ursolic acid spontaneously self-assemble into nanoparticles (LUNP) through non-covalent interactions, achieving a drug loading capacity of 100%. The LUNP platform exhibits superior biophysical properties, including enhanced mucus penetration, pH-responsive drug release, improved cellular uptake, and prolonged retention within inflamed lung tissue. Mechanistically, LUNP ameliorates ALI by dampening TLR4/MyD88/NF-κB-driven inflammatory activation, thereby remodeling the microenvironment to limit NOX4-PAD4-mediated NET formation. Notably, inhalational LUNP exhibits outstanding biosafety with minimal off-target distribution. Overall, this work introduces a synergistic self-assembled nanoplatform for precise pulmonary intervention in ALI, showcasing its ability to safely and effectively orchestrate the coordinated modulation of multiple pathological pathways. In summary, by inhibiting both TLR4 activation and NET formation, the synergistic LUNP platform offers an efficient, safe, and easily accessible therapeutic strategy for ALI, providing a promising solution for clinical translation.
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高影响因子
NEUROSCIENCE LETTERS
·
2026
·
IF 2.2
Wuwei Xu,Yanxin Xu,Chunyan Yao,Xianmei Fu,Xiaoling Liu,Jinping Fan,Kexue Wang,Yumeng Zhou,Yuefei Li,Ting Hu,Yan Sai,Peng Luo,Tongjian Cai
T-2 toxin is a widely distributed environmental mycotoxin that poses severe neurotoxic risks to humans and animals. Neuroinflammatory responses constitute a key mechanism underlying the neurotoxicity of T-2 toxin. However, its molecular mechanisms for inducing inflammatory responses in the nervous system remain incompletely understood. This study investigated the role of B-cell translocation gene 2 (BTG2) in T-2 toxin-induced microglial activation and evaluated the neuroprotective potential of resveratrol (Res). In vivo experiments demonstrated that exposure to T-2 toxin resulted in spatial learning, memory impairments and locomotor deficits in mice. These behavioral phenotypes were accompanied by neuroinflammation in the hippocampus and cerebral cortex, characterized by microglial activation and the upregulation of BTG2. Res pre-treatment effectively reversed these neurobehavioral deficits and suppressed the neuroinflammatory response. Mechanistic analyses revealed that Res considerably alleviated T-2 toxin-induced TLR4/MyD88/NF-κB pathway activation. In vitro studies using BV-2 microglial cells confirmed these findings. Notably, siRNA-mediated knockdown of BTG2 also abolished TLR4 pathway activation and subsequent cytokine expression induced by T-2 toxin, establishing BTG2 as a critical upstream regulator. Furthermore, RNA sequencing systematically verified that BTG2 regulates the immune response network, specifically targeting the TLR4 cascades. Collectively, these findings provide novel evidence that Res may target the BTG2-regulated TLR4/MyD88/NF-κB signal pathway to exert neuroprotection, providing a promising intervention option for reducing the environmental and health hazards associated with exposure to T-2 toxin
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 20
·10073
·
IF 4.9
Mei Feng,Xinxiang Chen,Fan Huang,Lin Chen,Can Liu,Wei Li,Yinyan Li,Shaobin Chen,Zhen Deng,Zhengyi Wei,Yuan Luo,Xiyong Yu,Aiping Qin
Alpinetin, a distinctive plant-derived dihydroflavonoid from cardamom seeds, represents an under-explored chemical scaffold compared to common flavonoids like quercetin or kaempferol. While many flavonoids have shown general cardioprotective potential, the structural specificity of alpinetin may confer unique pharmacological advantages. Inspired by its historical use in traditional Chinese medicine for cardiac discomfort, this study systematically investigated its efficacy against acute myocardial infarction (AMI). In a rat AMI model, alpinetin demonstrated superior infarct size reduction and functional recovery relative to other tested flavonoids. It significantly attenuated key AMI pathologies—including inflammatory infiltration, CD68+ macrophage activation, IL-6/TNF-α release, collagen deposition, and cardiomyocyte apoptosis—more effectively than common flavonoid benchmarks. Mechanistically, alpinetin selectively targeted the TLR4/MyD88/NF-κB signaling axis with notable potency, a pathway not robustly modulated by other flavonoids in the screening. These findings not only validate the traditional wisdom of cardamom but also establish alpinetin as a structurally and mechanistically distinct flavonoid with high translational promise, offering a new candidate for the targeted treatment of ischemic heart disease.
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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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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Donglin Sui,Mingxin Li,Chunqing Ai,Shugang Li,Hong Chang,Yixuan Li,Shouhao Zhao,Huan Li,Xiaomeng Ren
This study aimed to investigate the therapeutic efficacy of Larimichthys Crocea Isinglass polysaccharide (CIP) in ameliorating DSS-induced colitis. CIP, a complex polysaccharide composed of six monosaccharides with a molecular weight of 3.97 kDa. Specifically, CIP treatment mitigated weight loss and histopathological damage in the colon, increased colon length, and by inhibiting the TLR4/MyD88/NF-κB pathway significantly downregulated the secretion levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, while simultaneously upregulating the anti-inflammatory cytokine IL-10 and inhibition of the oxidative stress-related enzyme inducible nitric oxide synthase (iNOS). Additionally, CIP treatment enhanced intestinal barrier function by increasing the expression of intestinal tight junction proteins (TJs) and MUC2, and it promoted the production of short-chain fatty acids (SCFAs). Concurrently, CIP modulated the composition of the intestinal microbiota, inhibiting the proliferation of potentially harmful bacteria such as Bacteroidota and Campylobacter . Taken together, these findings suggest that CIP exhibits promising attributes as a functional food constituent, with a particular efficacy in modulating and maintaining intestinal health.
研究领域:
免疫学
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营养学
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肠道健康研究
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