BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2022
·
IF 3.322
Yelin Tang,Wenxin Zhang,Liqin Wu,Bin Bai,Bin Zheng,Mengying Li,Yue Tang,Xiaona Zhu,Yali Zhang,Yi Wang,Bing Zhang
Purpose Acute lung injury (ALI) is a fatal acute inflammatory illness with restricted therapeutic choices clinically. Piperlongumine (PL) is recognized as an alkaloid separated from Piper longum L, which was suggested to exhibit multiple pharmacological activities (e.g., anti-inflammatory activity). However, the effects of PL on LPS-triggered ALI and its anti-inflammatory target remain unclear. This paper intended to assess the roles of PL in LPS-triggered ALI, as well as its underlying mechanism and target. Methods In vivo, ALI was induced by intratracheal injection of LPS to evaluate protective effects of PL and assessed by the changes of histopathological. In vitro, the anti-inflammatory activity and mechanism of PL were investigated by ELISA, RT-qPCR, transcription factor enrichment analysis, Western blotting and Immunofluorescence assay. The binding affinity of PL to MD2 was analyzed using computer docking, surface plasmon resonance , ELISA and immunoprecipitation assay. Results It was reported here that PL treatment alleviated LPS-induced pulmonary damage, inflammatory cells infiltration and inflammatory response in mice. In culture cells, PCR array showed that PL significantly inhibited LPS-induced inflammatory cytokines, chemokines , and type I IFNs genetic expression, along with the inhibition of TAK1 and TBK1 pathway. It is noteworthy that PL is capable of straightly binding to MD2 and inhibiting MD2/TLR4 complex formation and TLR4 dimerization . Conclusions As revealed from this study, PL directly binding to MD2 to block cytokines expression by inhibiting the activation of TAK1 and TBK1 pathway, which then exerted its pulmonary protective activity. Accordingly, PL may act as an underlying candidate for treating LPS-triggered ALI.
研究领域:
药理学
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免疫学
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肺医学
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DOI
PubMed
高影响因子
Advanced Science
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2025
·
IF 14.1
Feng Gao,Zhongkun Zhang,Minzi Ju,Liang Bian,Huijuan Wang,Sibo Zhao,Ningbo Cai,Yu Wang,Yanpeng Jia,Ling Shen,Yuan Zhang,Honghong Yao
RNA therapeutics have recently shown significant promise in treating a variety of diseases, including cancers, infectious diseases, and genetic disorders. However, their potential in addressing neuropsychiatric disorders has been limited by the lack of an efficient delivery system to the central nervous system (CNS). Here, a novel nanoemulsion platform, perillyl alcohol nanoemulsions (PANEs) is introduced, designed for the therapeutic delivery of circDYM to brain and alleviated depressive-like behaviors. PANEs successfully encapsulated circDYM using cationic lipid compositions, enhancing its delivery efficiency to the mouse brain via its perillyl alcohol phase. The optimized formulation, PANE2-4, significantly improved the brain delivery efficiency of circDYM compared to both free circDYM and standard lipid nanoparticle formulations. Intranasal administration of PANE2-4-circDYM effectively alleviated depressive-like behaviors in the LPS-induced mouse model of depression. This effect is achieved by reducing the CD11b + CD45 dim microglia population and iNOS expression, restoring the expression of protein-95 (PSD-95) and synaptophysin. These findings indicated that PANE represents an efficient platform for delivering circRNAs to the brain, and intranasal administration of PANE2-4-circDYM is a promising strategy for ameliorating LPS-induced depressive-like behaviors.
研究领域:
神经科学
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药剂学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
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2025
·Vol. 32
·期 1
·1-15
·
IF 3.5
Zhenfei Mo,Chengcheng Su,Jinxia Liu,Jiabo Ren,Lu Liu,Yueming Wang,Yanqin Li,Chunsun Li,Zhen Yang,Xiuqing Ma,Liangan Chen
The oncogene lung cancer metastasis‑related protein 1 (LCMR1) is associated with neoplastic diseases and LCMR1 conditional knockout affects cell homeostasis. In the present study, the role of LCMR1 in lipopolysaccharide (LPS)‑induced acute lung injury (ALI) was investigated. Firstly, wild‑type C57BL/6 mice were used to establish an LPS‑induced ALI model via intratracheal injection of LPS, and the expression of LCMR1 was examined at 24, 48, 72 and 96 h after injury. The LPS‑induced lung injury model was subsequently constructed in mice with conditional knockout of LCMR1 in type II alveolar epithelial cells (AEC‑II). Subsequently, histopathological analysis, lung wet/dry weight ratio comparisons and lung function tests were performed; survival rates after LPS challenge of the conditional knockout mice were measured; bronchoalveolar lavage fluid (BALF) was collected, and the concentrations of protein and inflammatory cytokines in BALF were measured; and transmission electron microscopy of lung tissue was conducted to evaluate the degree of lung injury. To further investigate the mechanism, a lung‑on‑a‑chip model with overexpression or knockdown of LCMR1 was constructed to simulate the alveolar environment under LPS treatment. The expression levels of E‑cadherin and pro‑pulmonary surfactant C precursor (proSP‑C) in the chips were determined by immunofluorescence, and the integrity of the air‑blood barrier was analyzed using a permeability assay. In the mouse model, LCMR1 expression was downregulated in wild‑type mice with LPS‑induced lung injury. LCMR1 conditional knockout in AEC‑II caused increased mortality, impaired lung function, aggravated pathological damage and increased the inflammatory response in mice with LPS‑induced ALI. Furthermore, in the lung‑on‑a‑chip model, LCMR1 knockdown reduced the expression of E‑cadherin and proSP‑C, and impaired the air‑blood barrier function, whereas LCMR1 overexpression attenuated these effects, which may be related to cell differentiation dysfunction and enhanced apoptosis. In conclusion, the present study revealed that LCMR1 deficiency may exacerbate LPS‑induced ALI and could be considered a novel target for intervention in ALI.
研究领域:
医学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 9
·1662
·
IF 7.675
Yibin Xu,Xiaoqing Ding,Yuanyuan Wang,Danlei Li,Lingyu Xie,Shuang Liang,Yunfeng Zhang,Weifen Li,Aikun Fu,Xiuan Zhan
Reuterin is well-known for its broad-spectrum antimicrobial ability, while the other potential bioactivity is not yet clear. The present study aims to investigate the immunomodulatory activity of reuterin on chicken macrophage HD11 cells for the first time and evaluate whether reuterin is able to regulate the lipopolysaccharide-stimulated inflammatory response. The results showed that the safe medication range of reuterin was less than 250 μM. Reuterin treatment for 6 h decreased the transcriptional ofCD86,IL-1βandiNOSand increased the expression ofCD206in a dose-dependent way, but reuterin treatment for 12 h contrary increased the expression ofIL-1β,IL-6andIL-10. However, it was noticed that reuterin treatment for 12 h significantly decreased the production of reactive oxygen species (ROS) and suppressed the phagocytosis activity of HD11 macrophages against bacteria. Further, the results showed that preincubation or coincubation with reuterin significantly attenuated the promotive effects of lipopolysaccharide (LPS) on transcription of proinflammatory cytokines (includingIL-1β,IL-6andTNF-α) and obviously inhibited nitric oxide (NO) production as well as the protein expression of inducible nitric oxide synthase (iNOS). Meanwhile, Mechanism studies implied that reuterin might exert an anti-inflammatory effect on LPS-stimulated cells by downregulating the expression ofTLR4/MyD88/TRAF6and blocking the activation of NF-κB as well as MAPKs signaling pathways. Additionally, it was found that both pretreatment and cotreatment with reuterin remarkably inhibited the oxidative stress induced by LPS stimulation by activating the Nrf2/HO-1 signaling pathway and enhancing the activities of antioxidative enzymes. These findings suggested the immunoregulatory function of reuterin and indicated this bacterial metabolite was able to inhibit the inflammation and oxidative stress of HD11 macrophages once exposed to LPS stimulation.Keywords:reuterin;HD11 cell line;lipopolysaccharide (LPS);inflammation response;oxidative stress
研究领域:
免疫学
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细胞生物学
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微生物学
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
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2015
·Vol. 86
·期 4
·753-763
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IF 2.485
Jianpeng Feng,Bing Xiao,Wenbo Chen,Ting Ding,Lingfeng Chen,Pengtian Yu,Fengli Xu,Huajie Zhang,Zhiguo Liu,Guang Liang
We previously reported a symmetric monocarbonyl analog of curcumin (MACs), C66, which demonstrated potential anti-inflammatory activity and low toxicity. In continuation of our ongoing research, we designed and synthesized 34 asymmetric MACs based on C66 as a lead molecule. A majority of the C66 analogs effectively inhibited LPS induction of TNF- α and IL-6 expression. Additionally, a preliminary SAR was conducted. Furthermore, active compounds 4a11 and 4a16 were found to effectively reduce the W/D ratio in the lungs and the protein concentration in the bronchoalveolar lavage fluid (BALF). Meanwhile, a histopathological examination indicated that these two analogs significantly attenuate tissue injury in the lungs with LPS-induced ALI rats. 4a11 and 4a16 also inhibited mRNA expression of several inflammatory cytokines, including TNF- α , IL-6, IL-1 β , COX-2, ICAM-1 and VCAM-1, in the Beas-2B cells after LPS challenge. Altogether, the data exhibit a series of new C66 analogs as promising anti-inflammatory agents for the treatment of LPS-induced ALI.
研究领域:
药理学
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合成化学
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免疫学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
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2017
·Vol. 175
·期 5
·840-854
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IF 5.491
Yali Zhang,Tingting Xu,Zheer Pan,Xiangting Ge,Chuchu Sun,Chun Lu,Hongjin Chen,Zhongxiang Xiao,Bing Zhang,Yuanrong Dai,Guang Liang
Background and Purpose Acute lung injury (ALI) is a challenging clinical syndrome, which manifests as an acute inflammatory response. Myeloid differentiation protein 2 (MD2) has an important role in mediating LPS-induced inflammation. Currently, there are no effective molecular-based therapies for ALI or viable biomarkers for predicting the severity of disease. Recent preclinical studies have shown that shikonin, a natural naphthoquinone, prevents LPS-induced inflammation. However, little is known about the underlying mechanisms. Experimental Approach The binding affinity of shikonin to MD2 was analysed using computer docking, surface plasmon resonance analysis and elisa . In vitro , the anti-inflammatory effect and mechanism of shikonin were investigated through elisa , real-time quantitative reverse transcription PCR, Western blotting and immunoprecipitation assay. In vivo , lung injury was induced by intratracheal administration of LPS and assessed by changes in the histopathological and inflammatory markers. The underlying mechanisms were investigated by immunoprecipitation in lung tissue. Key Results Shikonin directly bound to MD2 and interfered with the activation of toll-like receptor 4 (TLR4) induced by LPS. In cultured macrophages, shikonin inhibited TLR4 signalling and pro-inflammatory cytokine production. These effects were produced through suppression of key signalling proteins including the NF-κB and the MAPK pathway. We also showed that shikonin inhibits MD2–TLR4 complex formation and reduces LPS-induced inflammatory responses in a mouse model of ALI. Conclusions and Implications Our studies have uncovered the mechanism underlying the biological activity of shikonin in ALI and suggest that the targeting of MD2 may prove to be beneficial as a treatment option for this condition.
研究领域:
药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2022
·
IF 5.714
Shanshan Wei,Zijun Xiao,Jie Huang,Zhenyu Peng,Bikui Zhang,Wenqun Li
Sepsis-induced cardiac injury leads to the high rate of mortality, the therapeutics for this disorder are limited. Disulfiram (DSF) is an FDA-approved treatment for chronic alcohol addiction, and its cardio-protection is gradually discovered in recent years. In present study, mice were injected with lipopolysaccharide (LPS, 15 mg/kg) to induce a septic cardiac injury model, and aimed to investigate the protective effect of DSF on sepsis-induced cardiac injury and the underlying mechanisms. Results showed that DSF treatment alleviated the lowered left heart function and myocardial cell apoptosis induced by LPS. Moreover, we found that LPS increased myocardium lipid peroxidation, DNA damage and the activation of NLRP3 inflammasome, which were significantly reduced by DSF. These results suggested the protective role of DSF in LPS-induced cardiac injury, and the mechanism involved the inhibition on the oxidative stress and NLRP3 inflammasome activation. Given the potent cardiac protection effect of DSF, repurposing DSF in the clinic would represent a new strategy to protect and treat sepsis-induced cardiac injury.
研究领域:
药理学
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心脏病学
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传染病学
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产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
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2024
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IF 2.5
Jinyun Long,Xiukuan Li,Chunyan Yao,Xiaoling Liu,Na Li,Yumeng Zhou,Dawei Li,Shengquan Su,Liangmei Wang,Hao Liu,Ying Xiang,Long Yi,Yao Tan,Peng Luo,Tongjian Cai
Lipopolysaccharide (LPS) is an important neurotoxin that can cause inflammatory activation of microglia. ZC3H12D is a novel immunomodulator, which plays a remarkable role in neurological pathologies. It has not been characterized whether ZC3H12D is involved in the regulation of microglial activation. The aim of this study was to investigate the role of ZC3H12D in LPS-induced pro-inflammatory microglial activation and its potential mechanism. To elucidate this, we established animal models of inflammatory injury by intraperitoneal injection of LPS (10 mg/kg). The results of the open-field test showed that LPS caused impaired motor function in mice. Meanwhile, LPS caused pro-inflammatory activation of microglia in the mice cerebral cortex and inhibited the expression of ZC3H12D. We also constructed in vitro inflammatory injury models by treating BV-2 microglia with LPS (0.5 μg/mL). The results showed that down-regulated ZC3H12D expression was associated with LPS-induced pro-inflammatory microglial activation, and further intervention of ZC3H12D expression could inhibited LPS-induced pro-inflammatory activation of microglia. In addition, LPS activated the TLR4-NF-κB signaling pathway, and this process can also be reversed by promoting ZC3H12D expression. At the same time, the addition of resveratrol, a nutrient previously proven to inhibit pro-inflammatory microglial activation, can also reverse this process by increasing the expression of ZC3H12D. Summarized, our data elucidated that ZC3H12D in LPS-induced pro-inflammatory activation of brain microglia via restraining the TLR4-NF-κB pathway. This study may provide a valuable clue for potential therapeutic targets for neuroinflammation-related injuries.
研究领域:
神经科学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2021
·
IF 2.73
Shengyu Sun,Yourui Zou,Shaocai Hao,Zhanfeng Niu,Liang Wu
Objective Polydatin has been used in the treatment of various inflammatory diseases. However, its role in the regulation of neuroinflammation has not been reported. In this study, we designed to investigate the anti-inflammatory effects of polydatin in LPS-stimulated BV2 microglia cells.Methods Inflammatory mediators TNF-α, IL-1β, NO, and PGE2 production were measured by ELISA. The protein of signaling pathways were detected by western blot analysis.Results The results showed that polydatin significantly ameliorated the production of TNF-α, IL-1β, NO, and PGE2 up-regulated by LPS. Polydatin also blocked LPS-induced NF-κB activation. In addition, PI3K and AKT, the up-stream molecules of NF-κB signaling pathway, were inhibited by the treatment of polydatin. Also, we found the formation of lipid rafts was inhibited by polydatin through attenuating the cholesterol content. Finally, polydatin was found to increase the expression of ABCA1 and ABCG1.Conclusion In conclusion, the results of the present study suggested that polydatin exhibited its anti-inflammatory effects in BV2 cells through disrupting lipid rafts, which subsequently inhibiting PI3K/AKT signaling pathway.
研究领域:
药理学
·
神经科学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
·
IF 2.559
Xin-Chun Zhang,Hong-Feng Liang,Xiao-Dong Luo,Hua-Jun Wang,Ai-Ping Gu,Chun-Ye Zheng,Qiao-Zhen Su,Jun Cai
Neuroinflammation plays a critical role in the process of neurodegenerative disorders, during which microglia , the principal resident immune cells in the central nervous system, are activated and produce proinflammatory mediators. Yin-Yang 1 (YY1), a multi-functional transcription factor, is widely expressed in cells of the immune system and participate in various cellular processes. However, whether YY1 is involved in the process of neuroinflammation is still unknown. In the present study, we found that YY1 was progressively up-regulated in BV2 microglial cells stimulated with lipopolysaccharide (LPS), which was dependent on the transactivation function of nuclear factor kappa B (NF-κB). Furthermore, YY1 knockdown notably inhibited LPS-induced the activation of NF-κB signaling and interleukin-6 (IL-6) expression in BV-2 cells, but not mitogen-activated protein kinase (MAPK) signaling. Moreover, YY1 strengthened p65 binding to IL-6 promoter by interacting with p65 but decreased H3K27ac modification on IL-6 promoter, eventually increasing IL-6 transcription. Taken together, these results for the first time uncover the regulatory mechanism of YY1 on IL-6 expression during neuroinflammation responses and provide new lights into neuroinflammation.
研究领域:
神经科学
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免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Meng Chen,Yonglu Li,Xin Yu,Yaxuan Wang,Wen Chen,Xiang Ye,Yangyang Liu,Yong Jiang,Xiaodong Zheng
Tetrastigma hemsleyanum Diels et Gilg, a rare herbal plant native to China, possesses high medicinal value. More researches have focused on the flavones in the tubers of Tetrastigma hemsleyanum whereas polysaccharides attract few attentions. In this study, a purified polysaccharide (TTP-1) with the average molecular weights of 478.33 kDa was extracted from Tetrastigma hemsleyanum and conducted multiple analysis to identify its structural information. In vitro , TTP-1 could suppress the inflammation, cytotoxicity, genotoxicity, mitochondrial dysfunction and oxidative damage induced by LPS in RAW264.7 cells. Meanwhile, TTP-1 could attenuate inflammation via COX-2, iNOS, MAPKs pathways and ameliorate oxidative damage through Nrf2-Keap1, Sirt1-FoxO1 pathways in RAW264.7 cells. In vivo , the inflammation induced by LPS triggered the suppression of survival ratio and growing development, as well as the restrain of athletic ability in Caenorhabditis elegans . The treatment of TTP-1 reversed the situation induced by LPS. In a word, TTP-1 could ameliorate LPS-induced inflammation both in vitro and in vivo .
研究领域:
药理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Di Nie,Yishan Lv,Duo Gao,Anqi Xu,Qinyu Li,Jiaxin Li,Xiang Lu,Bingqi Wang,Jie Wang,Chang Liu,Zhuan Zhang,Xiang Li,Ning Wang,Shiyan Guo,Chunliu Zhu,Miaorong Yu,Yong Gan
Achieving efficient and secure cytosolic delivery is crucial for RNA therapeutics. Presently, delivery systems predominantly attain cytosolic release through membrane rupture or destabilization of late endosomes and lysosomes. However, these approaches lead to restricted RNA release and undesirable cytotoxicity, ultimately diminishing therapeutic efficacy. Herein, we proposed an efficient strategy based on early endosome fusion-mediated release, employing probiotic-derived lipopolysaccharide (LPS)-incorporated vesicles to enhance RNA delivery. The LPS is derived from Escherichia coli Nissle 1917 (EcN) and has a high safety confirmed by the authoritative pyrogen test. The LPS-rich outer membrane vesicles (OMVs) and synthetic chimeric liposomes (LPS-Lips) are found capable of efficient cytosolic RNA delivery by using LPS to fuse with early endosomes, as evidenced by super-resolution and real-time imaging. The OMVs and LPS-Lips (containing 10 % and 30 % EcN-derived LPS) exhibit enhanced ability to deliver functional BCL-xL siRNA, leading to more significant gene silencing and cell apoptosis in comparison to the commercial Lipofectamine 2000 and RNAiMAX groups. The in vivo results demonstrate their superior efficacy on inhibiting tumor growth and prolonged survival time with enhanced safety. These findings highlight the early endosome fusion strategy with facilitated release efficiency and safety, offering guidelines for the rational design of enhanced RNA delivery systems.
研究领域:
药学
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分子生物学
·
癌症研究
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生物技术
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）