Immunity Inflammation and Disease
·
2024
·Vol. 12
·期 5
·e1229
·
IF 3.1
Meng Zhang,Deyuan Zhi,Pei Liu,Yajun Wang,Meili Duan
Background Dioscin has many pharmacological effects; however, its role in sepsis-induced cardiomyopathy (SIC) is unknown. Accordingly, we concentrate on elucidating the mechanism of Dioscin in SIC rat model. Methods The SIC rat and H9c2 cell models were established by lipopolysaccharide (LPS) induction. The heart rate (HR), left ventricle ejection fraction (LVEF), mean arterial blood pressure (MAP), and heart weight index (HWI) of rats were evaluated. The myocardial tissue was observed by hematoxylin and eosin staining. 4-Hydroxy-2-nonenal (4-HNE) level in myocardial tissue was detected by immunohistochemistry. Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities in serum samples of rats and H9c2 cells were determined by colorimetric assay. Bax, B-cell lymphoma-2 (Bcl-2), toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated-p65 (p-p65), and p65 levels in myocardial tissues of rats and treated H9c2 cells were measured by quantitative real-time PCR and Western blot. Viability and reactive oxygen species (ROS) accumulation of treated H9c2 cells were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and dihydroethidium staining assays. Results Dioscin decreased HR and HWI, increased LVEF and MAP, alleviated the myocardial tissue damage, and reduced 4-HNE level in SIC rats. Dioscin reversed LPS-induced reduction on SOD, CAT, GSH, and Bcl-2 levels, and increment on Bax and TLR4 levels in rats and H9c2 cells. Overexpressed TLR4 attenuated the effects of Dioscin on promoting viability, as well as dwindling TLR4, ROS and MyD88 levels, and p-p65/p65 value in LPS-induced H9c2 cells. Conclusion Protective effects of Dioscin against LPS-induced SIC are achieved via regulation of TLR4/MyD88/p65 signal pathway.
研究领域:
药理学
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心脏病学
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免疫学
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细胞生物学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yiyang Du,Tingxu Yan,Bo Wu,Bosai He,Ying Jia
Ethnopharmacological relevance Increased inflammatory response and disruption of neuroplasticity are important mechanisms in the hypothesis of the pathogenesis of depression. Thus, these two aspects are conducive to the development of treatments for depression. Suanzaoren Decoction (SZRD) is a classic traditional Chinese medicine compound for the treatment of insomnia, which can clinically relieve depression symptoms, but its antidepressant pharmacological mechanism remains to be elucidated. Aim of this study Based on the hypothesis of inflammation and neuroplasticity in depression, this study aimed to investigate the antidepressant effect of SZRD and its specific molecular mechanism through chronic unpredictable mild stress (CUMS) induced SD rat model and lipopolysaccharide (LPS) induced BV2 cell neuroinflammation model. Materials and methods The body weight and behavioral indexes of CUMS model rats treated with orally or without oral SZRD for 4 weeks were detected. Hematoxylin and eosin staining was used to observe brain pathological damage. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining was used to observe neuronal apoptosis. Immunofluorescence, ELISA kit and Western blotting were used to detect the inflammatory index Iba-1 and inflammatory factors, as well as the important inflammatory pathway TLR4/MyD88/NF-κB. Enzyme linked immunosorbent assay (ELISA) and western blotting were used to detect neuroplasticity indexes proteins-brain-derived neurotrophic factor (BDNF), presynaptic membrane protein-synaptophysin (SYP), and postsynaptic protein- 95(PSD95), and the key pathway Wnt/β-catenin. The possible mechanism of SZRD antidepressant was further explored in LPS-induced BV2 cells. Results In vivo and in vitro experiments showed that SZRD treatment significantly reversed the depression-like behaviors in rats, decreased the levels of inflammatory factors and increased the expression levels of BDNF, SYP, PSD95 in depression model rats. Furthermore, SZRD treatment inhibited the activation of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways and reduced the massive nuclear translocation of NF-κB and β-catenin. The addition of NF-κB pathway agonists could partially offset the inhibitory effect of SZRD on the Wnt pathway, and the addition of Wnt pathway agonists could also partially offset the inhibitory effect of SZRD on the TLR4 pathway. Conclusion This study suggestted that SZRD may exert its antidepressant effect by regulating TLR4/MyD88/NF-κB pathway and Wnt/β-catenin pathway in combination.
研究领域:
药理学
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神经科学
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中医
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分子生物学
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yamei Gao,Chao Chen,Chunyu Cao,Xueting Shen,Silin Shi,Shiyu Du,Donghong Sun,Jiliang Lu,Xiaozheng Jiang,Xin Han,Zhiqiang Yin
Psoriasis is a chronic inflammatory dermatosis with excessive activation of toll-like receptors (TLRs). Small interfering RNA (siRNA) has been considered a promising therapeutic approach by significantly suppressing mRNA expression. However, the low skin barrier penetration and the poor stability of siRNA pose a key challenge. Herein, we developed a novel and near-infrared (NIR) activated nanosystem (termed as GD-siMYD88@SPN/DA) that utilizes the gold nanorod (GNR) with highly photothermal conversion efficiency to realize localized thermal effects and photothermal-controlled release of siMYD88. Meanwhile, the shell grafted desmosome core-glycoprotein3 (Dsg3) antibody endowed it with the ability to target keratinocytes. The endocytosis of GD-siMYD88@SPN/DA by HaCaTs was significantly higher than that of the non-targeted nanosystem (GD-siMYD88@SPN), and the GD-siMYD88@SPN/DA exhibited enhanced stability in the skin. The double strand formed by the GNR-linked DNA fragment and siMYD88 serves as controlled element in response to photothermal stimulation, achieving controlled release of siMYD88. Knockdown of the MYD88 gene could effectively inhibit the TLR/MYD88/NF-κB signaling pathway, thereby reducing the production of psoriasis-related inflammatory factors. Notably, the synergistic therapeutic effects of mild-photothermal therapy combined with GD-siMYD88@SPN/DA were observed both in vitro and in vivo . Overall, this spatiotemporally controllable approach provides a versatile strategy for controllable gene therapy and mild-photothermal therapy for psoriasis.
研究领域:
皮肤病学
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分子生物学
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纳米医学
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DOI
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2026
·
IF 4.2
Hongying Zhang,Ru Guo,Youjuan Wu,Jiajun Huang,Zijia Yin,Kaiwen Zhao,Xuefeng Liu,Meifeng Li,Zeyin Jiang,Shanghong Wang,Lihua Fan,Chengyu Hu,Xiaowen Xu
Diniconazole-induced neurodevelopmental disorders are associated with immune inflammatory responses triggered through the TLR4/MyD88 signaling pathway. • Diniconazole-induced immune-inflammatory responses activated oxidative stress, ultimately triggering apoptosis in brain tissues. • The antioxidant astaxanthin effectively mitigated diniconazole-induced neurotoxicity by suppressing immune-inflammatory-indcued oxidative stress and apoptosis. Diniconazole, a widely used triazole fungicide in agriculture and aquaculture, poses potential threats to aquatic organisms and human health, yet its toxic effects and underlying mechanisms remain poorly understood. This study employed zebrafish as a model to systematically investigate the developmental neurotoxicity of diniconazole through both in vitro and in vivo assays. Phenotypic observations revealed that diniconazole exposure caused severe developmental abnormalities in early-life zebrafish, including reduced body length, decreased heart rate, lowered hatching success, and yolk sac edema. Transcriptome analysis revealed that diniconazole exposure significantly downregulated the extracellular matrix receptor interaction pathway and upregulated the retinol metabolism pathway, leading to neurodegenerative-like conditions in zebrafish embryos. Using transgenic zebrafish Tg ( Eno2:GFP ) and histological examination, we confirmed that diniconazole significantly impaired neurodevelopment and induced brain cell injury accompanied with compromised locomotor activity and activated immune-inflammatory responses. Mechanistic investigations demonstrated that neurodevelopmental disruption caused by diniconazole was linked to immune-inflammatory responses triggered through the TLR4/MyD88 signaling pathway. Subsequently, diniconazole-induced immune-inflammatory responses activated oxidative stress, ultimately triggering apoptosis in brain tissues. Notably, the antioxidant astaxanthin effectively mitigated diniconazole-induced neurotoxicity by suppressing immune-inflammatory-induced oxidative stress and apoptosis. This study provides the comprehensive evidence that diniconazole induces severe neurotoxicity in zebrafish through triggering TLR4/MyD88-induced immune-inflammatory responses, offering insights into risk assessment and potential therapeutic strategies for diniconazole exposure.
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Jian Yu,Jiangtao Wang,Ning Feng,Cancan Wang,Bohua Ma,Yuanming Zhang
Background Among the adverse effects of immunotherapy in cancer patients, immune checkpoint inhibitors (ICIs)-induced myocarditis is the most severe. Pyroptosis is involved in the pathogenesis of various cardiovascular diseases; however, its relationship with ICIs-related myocarditis remains unclear. Objective The purpose of this research is to characterize the critical genes mediating pyroptosis in myocarditis related to ICIs, with the goal of informing clinical practice. Materials and methods Based on single-cell RNA sequencing and bulk RNA sequencing, this study identified pyroptosis key genes in ICIs-related myocarditis and validated their expression levels and diagnostic value. Single-cell level validation of key genes, trajectory analysis and cellular interactions were also performed. Finally, ICIs-related myocarditis mouse model was established to verify the expression levels of key genes and pyroptosis-related markers. Results Integration of multiple bioinformatic analyses identified two pyroptosis key genes in ICIs-related myocarditis: Myd88 and Sqstm1. The expression levels of pyroptosis key genes were significantly higher in the ICIs-related myocarditis group compared to the normal group ( P < 0.05 or P < 0.01), and both demonstrated high diagnostic value. Trajectory analysis and cell interaction analysis revealed the interaction strength and relative expression patterns between these two pyroptosis key genes. In the ICIs-related myocarditis mouse model, cardiac injury markers were significantly elevated ( P < 0.001 or P < 0.0001), while cardiac function indices were significantly decreased ( P < 0.01) compared to the normal group. Quantitative real time polymerase chain reaction and western blot analyses revealed that the expression levels of Myd88 and Sqstm1 were significantly upregulated in the myocarditis group compared to the normal group, at both the mRNA and protein expression levels ( P < 0.05 or P < 0.01 or P < 0.0001). Compared with the normal group, the expression levels of pyroptosis-related markers Caspase-1, IL-1β, and GSDMD-N were significantly elevated in the myocarditis group ( P < 0.05 or P < 0.01). Conclusion Pyroptosis is involved in the pathogenesis of ICIs-related myocarditis, and Myd88 and Sqstm1 may serve as potential biomarkers for future clinical application.
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Yi Zhao,Zi-Yan Hu,Ming Lou,Fu-Wei Jiang,Yi-Feng Huang,Ming-Shan Chen,Jia-Xin Wang,Shuo Liu,Yu-Sheng Shi,Hong-Mei Zhu,Jin-Long Li
Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.
研究领域:
毒理学
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胃肠病学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICAL VIROLOGY
·
2025
·Vol. 97
·期 6
·e70432
·
IF 4.6
Qing Miao,Rui Yu,Fanyu Shi,Kaixin Li,Xinqian Du,Yinuo Gao,Yan Li,Ye Cui,Yan Chen,Jie Liu,Zhe Lv,Jing Yuan,Chris J. Corrigan,Sun Ying,Wei Wang
Respiratory syncytial virus (RSV) infection has been associated with disruption of the airway epithelial barrier, potentially increasing the risk of asthma development. However, whether and how RSV and RSV-induced IL-33 contribute to this process are still unclear. In vivo, 7-day-old C57BL/6 mice were infected perinasally with RSV, then viral replication, lung inflammation and barrier integrity were evaluated at various time points postinfection. In vitro, human epithelial cells were infected with RSV in the presence or absence of IL-33, and the expression and localization of apical junction complex proteins (AJC) were assessed by western blot analysis and immunofluorescence staining. The involvement of components of the IL-33/ST2/MyD88 axis was further verified through blockade of endogenous IL-33 signaling and pharmacological inhibition of MyD88. Exposure to RSV infection resulted in impairment of the airway epithelial barrier, as indicated by reduced expression of tight junction proteins (ZO-1, Occludin) and adherents junction protein (E-cadherin) in the lung tissues. These effects on epithelial barrier disruption were significantly attenuated in St2 -/- mice compared with wild-type controls. In vitro, the RSV-induced epithelial barrier disruption was exacerbated by topical application of exogenous IL-33, partially through activation of MyD88-mediated NF-κB signaling. Notably, knockdown of St2 by siRNA transfection or pharmacological inhibition of MyD88 partially restored the expression of E-cadherin, ZO-1 and Occludin in RSV-infected epithelial cells. RSV infection triggers robust IL-33 release from airway epithelial cells, leading to disrupted expression of AJC protein via activation of the MyD88-dependent NF-κB signaling pathway. These findings highlight the IL-33/ST2/MyD88 axis as a critical mediator of epithelial barrier dysfunction, which may represent a potential target for therapeutic intervention in RSV-mediated lung diseases.
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高影响因子
Nano Today
·
2026
·
IF 10.9
Tianwei Lan,Xiaoping Guo,Chang Liu,Pai Wang,Shichen Zhang,Lei Guo,Siyuan Wang,Lu Wang,Rui Zhou,Xinran Yan,Baiqiao Chen,Mujie Kan,Fang Wang,Caina Xu
Allergic asthma (AAS) is a chronic inflammatory airway disease. While zileuton (ZIL) has the efficient ability to relieve AAS symptoms, its systemic, untargeted administration could lead to adverse neurological effects. Thus, we constructed a drug combination nanomicelle (NMs) platform, H(BZP)-NMs, to reach synergistic effect therapy. It was comprised of a hydrophilic end formed from methoxy poly(ethylene glycol) (mPEG) and poly( L -glutamic acid) (PGlu), and a ROS/pH dual-sensitive hydrophobic core. The core was created by coupling 4-(hydroxymethyl)phenylboronic acid (HPBA) to betamethasone (BMZ). Zileuton (ZIL) was strategically loaded in the core. Hyaluronic acid (HA) functionalization further enabled CD44-targeting ability. In pathological microenvironments, the boronate ester bonds undergo responsive cleavage, causing the parallel delivery of the drugs. The slow-release profile addressed the need for rapid early-stage control and prolonged late-stage relief. In vivo, H(BZP)-NMs significantly decreased Penh values, lowered the IL-4, IL-5, IL-13, and LTB4 levels, and ameliorated airway pathological injuries. Given the molecular docking and verification of network pharmacology, these effects were associated with the dual-drug synergistic inhibition of the TLR4-MyD88-NF-κB p65 signals. Collectively, this study shows that H(BZP)-NMs are an inventive nanomedicine approach that unifies targeted delivery and extended co-release, offering promise for accurate and synergistic treatment of AAS.
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高影响因子
CARBOHYDRATE POLYMERS
·
2015
·
IF 4.074
Wuxia Zhang,Feifei Sun,Hong Niu,Qingjie Wang,Jinyou Duan
As a major component in extracellular matrix of the tissue, chondroitin sulfate A (CS-A) has been shown to exhibit either pro- or anti-inflammatory immune response which was largely dependent on its molecular size and cell types. In this study, we determined the signaling pathway involved in immune response of CS and its N -deacetylated derivative (dCS). Our data indicated that both CS and dCS could activate the NF-κB transcription factor in antigen presenting cells and induce TNF-α production through the TLR/MyD88 pathway. Further studies demonstrated that both CS and dCS had a potential in promoting the proliferation of spleen lymphocytes, and promoting the cytokines secretion by OVA-sensitized splenocytes. Thus, our finding provided a mechanistic insight into the understanding of cellular immunity of CS and dCS, which might be helpful to develop CS-based immune modulators against chronic inflammatory conditions, autoimmunity, infectious diseases, allergies and asthmatic conditions.
研究领域:
免疫学
·
分子生物学
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DOI
PubMed
高影响因子
BASIC RESEARCH IN CARDIOLOGY
·
2016
·Vol. 112
·期 1
·1-15
·
IF 6.038
Han Jibo,Zou Chunpeng,Mei Liqin,Zhang Yali,Qian Yuanyuan,You Shengban,Pan Yong,Xu Zheng,Bai Bin,Huang Weijian,Liang Guang
Angiotensin II (Ang II) induces cardiac inflammation and remodeling. Emerging evidence indicates that Ang II may utilize the Toll-like receptor 4 (TLR4) signaling pathway in mediating pro-inflammatory and pro-fibrotic activities. However, the precise mechanism is poorly understood. Myeloid differentiation 2 (MD2), a molecule that physically binds to TLR4, confers lipopolysaccharide responsiveness and may also be involved in mediating the actions of Ang II. We hypothesize that MD2 plays an essential role in cardiac inflammation and remodeling induced by local Ang II, and inhibition of MD2 can attenuate Ang II-induced cardiac dysfunction. Using a specific small molecule MD2 blocker L6H21 and the MD2 knockout mice, we show that MD2 deficiency significantly reduces cardiac inflammation and subsequent fibrosis, hypertrophy, and dysfunction in mice challenged with subcutaneous injection of Ang II. In rat cardiomyocyte-like H9c2 cells as well as rat primary cardiomyocytes, inhibition of MD2 by L6H21 or siRNA knockdown suppressed the Ang II-induced TLR4 signaling pathway activation including MyD88 recruitment, and reduced cardiomyocyte hypertrophy and matrix protein expression. These pro-inflammatory activities of Ang II were independent of the AT1 receptor. Finally, we demonstrated the direct interaction between Ang II and MD2 protein via hydrogen bonds on Arg-90, Glu-92, and Asp-100. Ang II produces an inflammatory response and cardiac remodeling by directly binding to MD2, activating MD2/TLR4 complex, and recruiting MyD88. MD2 may be a new therapeutic target for Ang II-mediated cardiac inflammation and remodeling.
研究领域:
心脏病学
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免疫学
·
分子生物学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Guanghui Jiang,Bulei Wang,Yuwen Wang,Haoyue Kong,Yufei Wang,Peng Gao,Minghao Guo,Wenna Li,Jian Zhang,Zhezhi Wang,Junfeng Niu
Liver fibrosis has proven to be the main predisposing factor for liver cirrhosis and liver cancer; however, an effective treatment remains elusive. Polysaccharides , with low toxicity and a wide range of bioactivities, are strong potential candidates for anti-hepatic fibrosis applications. For this study, a new low molecular weight neutral polysaccharide ( B. striata glucomannan (BSP)) was extracted and purified from Bletilla striata . The structure of BSP was characterized and its activities for alleviating liver fibrosis in vivo were further evaluated. The results revealed that the structural unit of BSP was likely →4)-β-D-Glc p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-2ace-Man p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-Glc p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-Man p -(1 → 4)-β-D-3ace-Man p -(1→, with a molecular weight of only 58.5 kDa. Additionally, BSP was observed to attenuate the passive impacts of liver fibrosis in a manner closely related to TLR2/TLR4-MyD88-NF-κB signaling pathway conduction. In summary, the results of this study provide theoretical foundations for the potential applications of BSP as an anti-liver fibrosis platform.
研究领域:
药理学
·
生物化学
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分子生物学
·
肝病学
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PubMed
高影响因子
NEUROTOXICITY RESEARCH
·
2022
·Vol. 40
·期 6
·1664-1672
·
IF 3.978
Zhou Changlong,Wang Jinping,Shao Gaohai,Xia Xiaohui,Wu Lirong,Yu Anyong,Yang Zhao
Background Mild hypothermia has been identified to reduce brain injury following intracerebral hemorrhage (ICH) by protecting neuron cells through several pathways. However, the role of hypothermia in brain function following ICH and the related mechanisms have not been well identified. Ubiquitination-mediated inflammation plays important roles in the pathogenesis of immune diseases. The experiment analyzed anti-inflammatory effects of mild hypothermia following ICH. Methods The model of ICH was induced by injecting autologous blood. Neuregulin receptor degradation protein-1 (Nrdp1) and downstream molecule were analyzed. In addition, brain inflammatory response, brain edema, and neurological functions of ICH mice were also assessed. Results We found that mild hypothermia attenuated proinflammatory factors production after ICH. Mild hypothermia significantly inhibited BBB injury, water content, and neurological damage following ICH in vivo. Moreover, mild hypothermia also increased Nrdp1/MyD88 levels and thus affect neuronal apoptosis and inflammation. Conclusions Taken together, these results suggest that mild hypothermia can attenuate the neuroinflammatory response and neuronal apoptosis after ICH through the regulation of the Nrdp1 levels.
研究领域:
神经科学
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炎症
·
神经保护
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DOI
PubMed
高影响因子
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