Current Computer-Aided Drug Design
·
2024
·Vol. 21
·期 4
·503-516
·
IF 1.5
Xiaoyan Meng,Xinming Yan,Peng Xue,Zhaoqing Xi
ObjectiveThis study utilized transcriptomic sequencing combined with cellular and animal models to explore the potential mechanisms of Xuebijing in treating sepsis-induced myocardial dysfunction, also known as sepsis-induced myocardial injury.MethodsWe investigated potential targets and regulatory mechanisms of XBJ injection using network pharmacology and RNA sequencing. The effects of XBJ on oxidative stress and apoptosis levels in human cardiac myocytes (AC16) and C57BL/6 mice exposed to lipopolysaccharide (LPS) were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA), fluorescent probe, Fluorescent Quantitative Polymerase Chain Reaction (qPCR), Western Blot, Transmission Electron Microscopy, oxidative stress-related indicators detection kit, flow cytometry, and Immunohistochemistry (IHC).ResultsFirst, it was verified that XBJ can reduce the deformation of AC16 cardiomyocytes induced by LPS and the production and secretion of ROS (P <0.01). The transcriptome sequencing results showed that the TRIM16 gene was significantly increased after XBJ treatment, and the data of KEGG and GO analyses demonstrated that XBJ could inhibit the pathway expression of oxidative stress damage in AC16 cells, and PCR verified that XBJ could indeed increase the expression level of TRIM16 gene in AC16 cells (P <0.01). Basic animal and cell experiments showed that LPS could inhibit the expression of TRIM16 and NRF2 in cardiomyocytes (P <0.05) and promote the expression of Keap1 (P <0.01), while XBJ could significantly up-regulate the expression levels of TRIM16 and NRF2 (P <0.01) and inhibit the expression of Keap1 (P <0.01), thereby affecting the expression levels of downstream proinflammatory cytokines and alleviating LPS-induced oxidative stress damage. In addition, XBJ also inhibited the expression of the pro-apoptotic proteins Bax and c-caspase3 (P <0.01), promoted the expression of the anti-apoptotic protein Bcl2 (P <0.01), and reduced LPS-induced apoptosis by upregulating TRIM16.ConclusionOur comprehensive data demonstrated that TRIM16 is a key gene in the therapeutic action of Xuebijing in sepsis-induced myocardial dysfunction, protecting myocardial cells from injury through antioxidative stress and anti-apoptotic mechanisms.
研究领域:
医学
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分子生物学
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药理学
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DOI
高影响因子
MOLECULAR BIOLOGY
·
2022
·Vol. 57
·期 1
·105-112
·
IF 1.54
Zeng H. B.,Zhang L. H.,Yuan D. P.,Wang W.,Su X. M.,Weng W. X.,Miao R.,Xu J. Y.,Long J.,Song Y. H.
Abstract As a byproduct of mitochondrial respiration or metabolism, reactive oxygen species (ROS) can act as a signaling molecule to activate NLR family pyrin domain containing 3 (NLRP3) inflammasome, thereby triggering immune response. NLRP3 inflammasome acts as a sensor of various danger signals and is central to the control of pyroptosis occurrence. Macrophage pyroptosis is closely related to atherosclerosis, arthritis, pulmonary fibrosis and other inflammatory diseases. Methylophiopogonanone A (MO-A) is a main homoisoflavonoid in Chinese herb Ophiopogonis Radix, which has antioxidant effect. However, it is not clear whether MO-A can alleviate macrophage pyroptosis by inhibiting oxidative stress. Here we have shown that MO-A increases the activities of superoxide dismutase (SOD) and catalase (CAT), inhibits the production of ROS, reduces the activation of NLRP3 inflammasome and the release of lactate dehydrogenase (LDH), and inhibits pyroptosis in macrophages induced by lipopolysaccharides (LPS) and adenosine triphosphate (ATP). These effects can be reversed by the ROS promoter H 2 O 2 . Therefore, MO-A can inhibit macrophage pyroptosis through the ROS/NLRP3 pathway and may be considered as a candidate drug for the treatment of inflammatory diseases.
研究领域:
免疫学
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药理学
·
炎症
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DOI
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2025
·
IF 3.9
Hai-Chuan Yu,Meng-Yao Chen,Shuang-Ling Zhang,Fang-Chao Tong,Fan-Ping Wang,Lin Wang,Jia-Long Zhang,Jiao-Jie Guo,Bing-Yang Zhang,Jia-Qi Tian,Jiao Wu
Maintaining the hematopoietic balance between erythroid and myeloid lineages is crucial for immune function and oxygen transport. However, the mechanisms underlying the disruption of this balance during acute inflammation remain unclear. In this study, we investigated the effects of Lipopolysaccharide (LPS)-induced acute inflammation on erythroid-myeloid hematopoiesis in zebrafish (Danio rerio) and elucidated the key signaling pathways involved. LPS treatment significantly suppressed erythropoiesis, as evidenced by reduced expression of gata1a and hbae3 and decreased red blood cell production in the caudal hematopoietic tissue (CHT). Conversely, myelopoiesis was enhanced, with increased neutrophil and macrophage accumulation at inflammatory sites. Bioinformatics analysis revealed that LPS modulates hematopoietic differentiation via the Jak2/Stat3-Hif1a signaling axis. Experimental validation demonstrated that LPS activates Jak2/Stat3 signaling, leading to increased expression of hif1a in zebrafish and HIF1α in human hematopoietic cell lines (K562 and THP-1). Inhibition of Jak2 with Ruxolitinib or knockdown of hif1a reversed the LPS-induced suppression of erythropoiesis and expansion of myelopoiesis. Strikingly, acute hypoxia similarly disrupted the hematopoietic balance via the Jak2/Stat3-Hif1a pathway, suggesting a conserved, stress-responsive mechanism. Our findings highlight the critical role of Jak2/Stat3-Hif1a signaling in acute inflammation-induced hematopoietic lineage bias and propose potential therapeutic strategies for hematological disorders associated with acute infection or hypoxia.
研究领域:
发育生物学
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免疫学
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血液学
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信号转导
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2017
·
IF 3.144
Xiang Hou,Tian Wang,Hussain Ahmad,Ziwei Xu
Ampelopsin (APS) is the main bioactive component from Ampelopsis grossedentata and has anti-inflammatory properties. We hypothesize that it could reduce the acute phase response (APR) and help to maintain balance between inflammation-mediated oxidative damage and APS-induced protective mechanisms in liver. In the present study, APS possessed strong DPPH, ABTS, H 2 O 2 and O 2 radical scavenging activities in different in vitro antioxidant assays. Further study demonstrated that APS alleviated APR as reflected in the changes in the whole body metabolic rate, physical conditions, and production of cytokines in LPS-treated piglets. Moreover, APS has the potential to prevent Akt-mediated activation of NF-κB and decreased the levels of STAT3 in inflammation. The administration of APS ameliorated mitochondrial dysfunction and moderated the involvement of Ref-1 and Nrf2 in the attenuation in LPS-induced APR. The present results suggest that the APS attenuate LPS induced inflammation and oxidative stress in liver of piglets.
研究领域:
药理学
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免疫学
·
兽医学
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分子生物学
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DOI
高影响因子
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 9
·5203-5213
·
IF 5.882
Shanshan Dai,Bozhi Ye,Longwang Chen,Guangliang Hong,Guangju Zhao,Zhongqiu Lu
Myocardial injury and cardiovascular dysfunction are serious consequences of sepsis and contribute to high mortality. Currently, the pathogenesis of myocardial injury in sepsis is still unclear, and therapeutic approaches are limited. In this study, we investigated the protective effect of emodin on septic myocardial injury and the underlying mechanism. Lipopolysaccharide (LPS)-induced C57BL/6 mice and cardiomyocytes were used as models of sepsis in vivo and in vitro, respectively. The results showed that emodin alleviated cardiac dysfunction, myocardial injury and improved survival rate in LPS-induced septic mice. Emodin attenuated the levels of inflammatory cytokines and cardiac inflammation induced by LPS. Emodin reduced NOD-like receptor protein 3 (NLRP3) and Gasdermin D (GSDMD) expression in the heart tissue of LPS-induced septic mice. In vitro, emodin alleviated LPS-induced cell injury and inflammation in cardiomyocytes by inhibiting NLRP3 inflammasome activation. In addition, an NLRP3 inhibitor was used to further confirm the function of the NLRP3 inflammasome in LPS-induced myocardial injury. Taken together, our findings suggest that emodin improves LPS-induced myocardial injury and cardiac dysfunction by alleviating the inflammatory response and cardiomyocyte pyroptosis by inhibiting NLRP3 inflammasome activation, which provides a feasible strategy for preventing and treating myocardial injury in sepsis.
研究领域:
药理学
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免疫学
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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
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 23
·16756
·
IF 5.6
Mengyuan Wang,Xingfang Zhang,Juan Guo,Shangze Yang,Fang Yang,Xingjuan Chen
Acute lung injury (ALI) is characterized by endothelial barrier disruption and associated inflammatory responses, and transient receptor potential cation channel 6 (TRPC6)—mediated Ca2+influx is critical for endothelial hyperpermeability. In this study, we investigated the role of TRPC6 in LPS—induced ALI, analyzed gene expression inWTandTRPC6-/-lungs using RNA sequencing, and explored the effects of TRPC6 in the LPS—induced hyperpermeability in human umbilical vein endothelial cells (HUVECs) to elucidate the underlying mechanisms. Intratracheal instillation of LPS caused edema in the mouse lungs. Deletion of TRPC6 reduced LPS—induced lung edema and decreased cell infiltration. RNA sequencing analysis suggested that downregulated cell adhesion molecules inTRPC6-/-lungs may be responsible for their resistance to LPS—induced injury. In addition, downregulation of TRPC6 significantly alleviated the LPS—induced decrease in eNOS expression in lung tissue as well as in HUVECs. Moreover, inhibition of TRPC6 with the channel antagonist larixyl led to a decrease in LPS—induced hyperpermeability and ROS production in HUVECs, which could be reversed by blocking eNOS. Our findings suggest that inhibition of TRPC6 ameliorates LPS—induced ALI, which may be achieved by acting on the cell adhesion molecule signaling pathway and participating in the regulation of eNOS levels in endothelial cells.Keywords:acute lung injury;TRPC6;eNOS;endothelial cells
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DOI
PubMed
高影响因子
Applied Biological Chemistry
·
2025
·Vol. 68
·期 1
·1-11
·
IF 2.7
Dou Yufeng,Yang Jiao,Huang Na,Lu Xiaoxiao,Yan Liping
Background Pneumonia is a serious respiratory disease that significantly impacts human health. Quercetin (QUE), a plant extract, has been shown to exert protective effects against lung injury, but its precise mechanisms remain unclear. Methods Lipopolysaccharide (LPS) was used to induce injury in embryonic lung fibroblasts. Cell viability, proliferation, and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, 5-ethynyl-2’-deoxyuridine (EdU) staining, and flow cytometry assay, respectively. Reactive oxygen species (ROS), malondialdehyde (MDA), and Fe 2+ levels were evaluated using corresponding assay kits. The levels of inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR (qRT-PCR) and western blot were employed to analyze the expression and correlation of related genes. Methylated RNA immunoprecipitation (MeRIP) was employed to verify the regulatory mechanism between genes. Results QUE inhibited embryonic lung fibroblast injury. Both transducin β-like 1 X-linked receptor 1 (TBL1XR1) and methyltransferase 3 (METTL3) were highly expressed in lung injury tissues and cells, which were decreased by QUE treatment. TBL1XR1 deficiency weakened LPS-induced embryonic lung fibroblast injury. Mechanistically, METTL3 mediated the N 6 -methyladenosine (m6A) methylation and stabilized the TBL1XR1 mRNA. TBL1XR1 up-regulation alleviated the retardation of METTL3 absence on embryonic lung fibroblast injury. Furthermore, METTL3 overexpression reversed the inhibition of QUE on embryonic lung fibroblast injury. Conclusion QUE inhibited embryonic lung fibroblast injury by regulating the METTL3-mediated m6A methylation of TBL1XR1 mRNA.
研究领域:
分子生物学
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药理学
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呼吸医学
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表观遗传学
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细胞生物学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yajie Wang,Han Zhou,Yaodong Liu,Xinqiuyue Wang,Lei Zhang,Jiayang Cai,Yi Chen,Chang Liu,Zimei Wu,Jianping Liu,Wenli Zhang
With prevalence of bacterial resistance and decline in antibiotic development, immunotherapy is emerging as a promising strategy for bacterial infections. Macrophages play a crucial role in bacterial eradication and lipopolysaccharide (LPS) detoxification. However, overactivated macrophages triggered by excess LPS can also induce inflammatory injury and impaired antimicrobial response. Therefore, nanotherapies that synergize with and/or steer macrophages to simultaneously eliminate bacteria and LPS, provide an optimal strategy for immunomodulation to achieve a balance between antimicrobial and inflammatory responses. Inspired by antibody-drug conjugates (ADCs), we report a peptide-nanoparticle conjugate (PNC) composed of opsonized peptides (B-mBPI) and engineered nanoparticle (PEGylated liposomes loaded with antibiotic). This PNC could effectively neutralized LPS with high affinity and specifically tag bacteria, then guiding macrophages towards the elimination of bacteria and LPS. With this steering-elimination function, a synergistic interaction was observed by evaluating the combination index (CI) of PNC and macrophages towards the antibacterial effect (CI = 0.103 < 1). Besides, we found that the dual-route administration regimen combining intraperitoneal (i.p) and intravenous (i.v) delivery of PNC demonstrated superior therapeutic efficacy compared to single-route therapy in intraperitoneal infection, highlighting the importance of tailoring nanocarrier delivery to infection dynamics. Consequently, this PNC significantly reduced the bacterial burden by more than 3 orders of magnitude and effectively reduce inflammatory factors (TNF-α, IL-6) and LPS levels to baseline, leading to a substantial improvement in the survival rate of mice infected with drug-resistant Escherichia coli ( E. coli ) (0 % improved to 71.4 %). This PNC presents a paradigm for antimicrobial immunotherapy by steering elimination of bacteria and LPS as well as modulating immune response.
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高影响因子
Polymers
·
2024
·Vol. 16
·期 24
·3451
·
IF 4.7
Caixia Wu,Xiaoqun Ning,Qunfeng Liu,Xiaoyan Zhou,Huilong Guo
Biological tissue defects are typically characterized by various shaped defects, and they are prone to inflammation and the excessive accumulation of reactive oxygen species. Therefore, it is still urgent to develop functional materials which can fully occupy and adhere to irregularly shaped defects by injection and promote the tissue repair process using antioxidant and anti-inflammatory mechanisms. Herein, in this work, phenylboronic acid modified oxidized hyaluronic acid (OHAPBA) was synthesized and dynamically crosslinked with catechol group modified glycol chitosan (GCHCA) and guar gum (GG) into a hydrogel loaded with curcumin liposomes (Cur-LPs) which were relatively uniformly distributed around 180 nm. The hydrogel possessed rapid gelation within 30 s, outstanding injectability and tissue-adaptive properties with self-healing properties, and the ability to adhere to biological tissues and adapt to tissue movement. Moreover, good biocompatibility and higher DPPH scavenging efficiency were illustrated in the hydrogel. And a more sustainable release of curcumin from Cur-LPs-loaded hydrogels, which could last for 10 days, was achieved to improve the bioavailability of curcumin. Finally, they might be injected to fully occupy and adhere to irregularly shaped defects and promote the tissue repair process by antioxidant mechanisms and the sustained release of curcumin for anti-inflammation. And the hydrogel would have potential application as candidates in tissue defect repair.
研究领域:
生物材料学
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组织工程
·
药剂学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2026
·Vol. 57
·期 3
·142
·
IF 2.6
Ye Chunhua,Liu Hua,Ming Zhu,Yi Qinjun,Xiang Rong,Chen Yifu
This study investigated the role of TNF receptor associated factor 6 (TRAF6) in glomerular podocyte pyroptosis. An in vitro LN cell model was established by treating mouse glomerular podocyte MPC5 cells with 100 ng/ml LPS for 12 h. Concurrently, LN cells were treated with TRAF6 knockdown and TXNIP overexpression or NLRP3 activation (Nigericin). MRL/lpr mice were treated with adenovirus vector expressing sh-TRAF6 for in vivo validation. LPS treatment decreased cell viability, increased cell death, elevated Desmin mRNA, malondialdehyde, TRAF6, TXNIP, interleukin (IL)-1β, and IL-18, reduced Nephrin and Podocin mRNA (podocyte markers), superoxide dismutase, and glutathione levels, enhanced cell pyroptosis and lactate dehydrogenase concentration, and activated the NLRP3 inflammasome pathway. TRAF6 knockdown suppressed LPS-stimulated podocyte damage, oxidative stress, and pyroptosis. TRAF6 interacted with TXNIP at the protein level, and TRAF6 increased TXNIP protein expression. The protective functions of TRAF6 silencing on MPC5 cells were counteracted upon TXNIP overexpression or NLRP3 activation. In vivo, TRAF6 knockdown regulated the TXNIP/NLRP3 inflammasome pathway to alleviate renal tissue pathological changes and fibrosis in LN mice. In conclusion, TRAF6 activates the NLRP3 inflammasome pathway through regulating TXNIP, thereby accelerating LPS-induced oxidative stress, pyroptosis, and damage to glomerular podocytes. Hence, TRAF6 may be a promising therapeutic target for LN. Graphical abstract The alternative text for this image may have been generated using AI.
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DOI
PubMed
高影响因子
IONICS
·
2019
·Vol. 26
·期 5
·2335-2342
·
IF 2.289
Jiang Huize,Han Yu,Wang Hui,Guo Qingpeng,Zhu Yuhao,Xie Wei,Zheng Chunman,Xie Kai
Li 3 PS 4 (LPS) was in situ formed at the active material Li 2 S through the reaction of Li 2 S and P 2 S 5 by mechanical ball milling, which can be used to composite cathode for Li/S battery. The fine active materials-electrolyte interface will be generated via in situ reaction. Compared with the direct mixing Li 2 S + LPS, the interface impedance between Li 2 S and LPS of Li 2 S-LPS had a significant decrease from 833.3 Ω to 203.7 Ω at room temperature. The effect of heat treatment temperature on the ionic conductivities of Li 2 S-LPS has been studied, and the Li 2 S-LPS-300 showed the highest ionic conductivity of 2.67 × 10 −4 S cm −1 at room temperature. The all-solid-state cell (Li/LPS/Li 2 S-LPS) possessed a larger capacity and better rate performance than that of the cell using Li 2 S + LPS as cathode material, showing a discharge capacity of 624.5 mAh g −1 (g of Li 2 S) for the 20th cycle. We also find that high carbon content of composite cathode will reduce the utilization of Li 2 S. The composite cathode 90Li 2 S-LPS + 10C (wt%) shows the highest capacity of 763.8 mAh g −1 at the current density of 0.1 mA cm −2 .
研究领域:
材料科学
·
电化学
·
储能
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
·
IF 3.118
Lina Zhang,Jinghua Gao,Peng Tang,Li Chong,Yue Liu,Peng Liu,Xin Zhang,Li Chen,Chen Hou
Nuciferine, a bioactive component extracted from the lotus leaf , has been reported to have various anti-inflammatory effects. In the present study, we aimed to investigate the anti-inflammatory effects and mechanism of nuciferine on lipopolysaccharide (LPS)-stimulated BV2 microglia cells . The anti-inflammatory activity of nuciferine was measured by ELISA to detect the inflammatory mrdiators secretion in LPS-simulated BV2 microglia cells. The results demonstrated that nuciferine significantly inhibited LPS-induced TNF-α, IL-1β, PGE 2 and NO secretion. LPS-induced NF-κB activation was also suppressed by nuciferine. Further studies showed that nuciferine increased the expression of PPAR-γ. Functional aspects were analyzed using PPAR-γ specific inhibitor GW9662 , which attenuated the LPS-induced secretion of proinflammatory mediators, such as TNF-α, IL-1β, PGE 2 , and NO. In conclusion, these results suggested that nuciferine activated PPAR-γ, which subsequently inhibited LPS-induced inflammation in BV2 cells.
研究领域:
药理学
·
免疫学
·
神经科学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）