International Journal of Environmental Research and Public Health
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2019
·Vol. 17
·期 1
·138
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IF 2.468
Chang Liu,Yaohui Zhu,Zhenxiang Lu,Weina Guo,Bayaer Tumen,Yalan He,Chao Chen,Shanshan Hu,Kangzhi Xu,Yan Wang,Lei Li,Shenghe Li
Acute Cadmium (Cd) exposure usually induces hepatotoxicity. It is well known that oxidative stress and inflammation causes Cd-induced liver injury. However, the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in Cd-induced liver injury is not completely understood. In this study, we observed Cd-induced liver damage and the potential contribution of Nrf2, nuclear factor-κB (NF-κB), Nod-like receptor 3 (NLRP3), and mitogen-activated protein kinases (MAPKs) signaling pathways. Changes in serum transaminases and proinflammatory cytokines expression showed that Cd could induce acute hepatotoxicity. Moreover, Nrf2 and its downstream heme oxygenase 1 (HO-1) were inhibited by Cd exposure, and Kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2, was increased. Furthermore, NF-κB, NLRP3, and MAPKs signaling pathways were all activated by Cd intoxication. In conclusion, the inhibition of Nrf2, HO-1, and the activation of NF-κB, NLRP3, and MAPKs all contribute to Cd-induced liver injury.Keywords:Cadmium;acute liver injury;Nrf2;NLRP3;NF-κB;MAPKs
研究领域:
毒理学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
Bioengineered
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2020
·
IF 2.205
Aimin Liu,Buxin Zhang,Wei Zhao,Yuanhui Tu,Qingxing Wang,Jing Li
Psoriasis is a chronic inflammatory skin disease that affects approximately 2% of worldwide population, and causing long-term troubles to the patients. Therefore, it is urgent to develop safe and effective therapeutic drugs. Catalpol is a natural iridoid glucoside, that has several remarkable pharmacological effects, however, whether catalpol can alleviated psoriasis has not been explored. The goal of the present work is to study the role of catalpol in psoriasis in vivo and in vitro. Imiquimod-induced psoriasis-like mice were applied with different concentrations of catalpol for 8 consecutive days. The severity degree of psoriasis was estimated and the skin pathological changes were detected by H&E staining. Also, TNF-α-stimulated keratinocytes were treated with different concentrations of catalpol, then the oxidative stress and inflammation factors, as well as the expression of SIRT1 and activation of NF-kB and MAPK pathways were measured. The results showed that catalpol reduced the erythema, scaling, ear thickness, and changed pathological phenotypes in the lesioned skin region in mice. Treatment with catalpol significantly suppressed the oxidative stress and inflammatory reactions in vivo and in vitro, as reflected by the decreased secretion or expression of oxidative stress indicators and proinflammatory factors. Furthermore, the SIRT1 was up-regulated and the NF-κB and MAPKs signaling pathways were suppressed by the treatment of catalpol in vivo and in vitro. In summary, our data suggested that catalpol may have a therapeutic property of psoriasis by ameliorating oxidative stress and inflammation partly through SIRT1 mediated suppression of NF-κB and MAPKs pathways.Abbreviation: CAT: catalase; ELISA: enzyme-linked immunosorbent assay; GSH: glutathione; HRP: horseradish peroxidase; IMQ: imiquimod; JNK: c-Jun NH 2-terminal kinases; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; NC: negative control group; NF-kB: nuclear factor kappa B; PASI: psoriasis area and severity index; PVDF: polyvinylidene difluoride membranes; qRT-PCR: quantitative real time polymerase chain reaction; ROS: reactive oxygen species; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel; SIRT1: silent information regulator 1; SOD: Cu/Zn superoxide dismutase
研究领域:
药理学
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皮肤科
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF BONE AND MINERAL RESEARCH
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2025
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IF 5.9
Liu Qian,Gan Ying,Hu Xingli,Liu Wei,Liao Xiaoxia,Zhang Jingyun,Li Xiaoxia,Zhou Jie,Wang Baoli
Lysine demethylase 6B (KDM6B) plays a role in regulating osteoblast differentiation and fetal bone ossification. Nevertheless, its involvement in regulating postnatal bone homeostasis and bone mass accrual remains unclear. In this study, we generated mice lacking Kdm6b gene specifically in mesenchyme and osteoprogenitor cells using a conditional strategy. The adult mice of both mutant strains had decreased cancellous bone mass. The absence of Kdm6b in mesenchyme led to decreased numbers of osteoblasts and osteoclasts, increased marrow adipocytes, as well as repressed bone formation and resorption. Additionally, Kdm6b-deficient bone marrow stromal cells (BMSCs) displayed impaired osteogenic differentiation and exerted an inhibitory effect on osteoclastogenesis. RNA-seq combined with gene expression analysis uncovered downregulation of collagen triple helix repeat containing 1 (CTHRC1) and a lower receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) ratio in BMSCs of the mutant mice. Further mechanistic explorations demonstrated that KDM6B epigenetically upregulated CTHRC1 expression by removing the repressive H3K27me3 mark from its promoter, thereby triggering PKCδ/MAPKs signaling to facilitate osteoblast differentiation. CTHRC1 was able to mitigate the dysregulated osteogenic and adipogenic differentiation induced by Kdm6b deficiency. This study provides evidence that KDM6B regulates postnatal bone homeostasis through balancing osteoblast and osteoclast differentiation. Given its predominant promotion of osteoblastic bone formation over osteoclastic bone resorption, KDM6B tends to promote postnatal bone mass accrual.
研究领域:
分子生物学
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骨骼发育
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表观遗传学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Liangrong Wu,Chenchen Qian,Weiqi Zhang,Mengyun Shi,Xiuxiu Chen,Yi Wang,Feng Lin
Background Ginkgo biloba L., a kind of traditional Chinese medicine, is always used to treat various diseases. Ginkgetin is an active biflavonoid isolated from leaves of Ginkgo biloba L., which exhibits diverse biological activities, including anti-tumor, anti-microbial, anti-cardiovascular and cerebrovascular diseases, and anti-inflammatory effects. However, there are few reports on the effects of ginkgetin on ovarian cancer (OC). Hypothesis/Purpose OC is one of the most common cancers with high mortality in women. The purpose of this study was to find out how ginkgetin inhibited OC and which signal transduction pathways was involved to suppress OC. Methods The OC cell lines, A2780, SK-OV-3 and CP70, were used for in vitro experiments. MTT assay, colony formation, apoptosis assay, scratch wound assay and cell invasion assay were used to determine the inhibitory effect of ginkgetin. BALB/c nude female mice were injected with A2780 cells subcutaneously, then treated with ginkgetin by intragastric administration. Western blot experiment was used to verify the inhibitory mechanism of OC in vitro and in vivo . Results We found that ginkgetin inhibited the proliferation and induced apoptosis in OC cells. In addition, ginkgetin reduced migration and invasion of OC cells. In vivo study showed that ginkgetin significantly reduced tumor volume in the xenograft mouse model. Furthermore, the anti-tumor effects of ginkgetin were associated with a down regulation of p-STAT3, p-ERK and SIRT1 both in vitro and in vivo . Conclusion Our results suggest that ginkgetin exhibits anti-tumor activity in OC cells via inhibiting the JAK2/STAT3 and MAPK pathways and SIRT1 protein. Ginkgetin could be a potential candidate for the treatment of OC.
研究领域:
肿瘤学
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药理学
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分子生物学
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中药学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
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2015
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IF 2.709
Yang Bian,Luqing Ren,Lei Wang,Shanmei Xu,Jianjian Tao,Xiuhua Zhang,Yi Huang,Yuanyuan Qian,Xin Zhang,Zongming Song,Wencan Wu,Yi Wang,Guang Liang
Inflammation is a pathological hallmark of ischemia reperfusion (I/R) injury. The present study was conducted to explore the ability of a new anti-inflammatory compound, X22, to attenuate retinal I/R injury via cytokine-inhibitory mechanism. For the in vitro experiment, ARPE-19 cells were pretreated with X22 (5 or 10 μM) or saline for 2 h, followed by stimulation with tert-butyl hydroperoxide (TBHP, 1000 μM) for an indicated amount of time. The expression of inflammatory mediators , cell viability , and cell apoptosis were evaluated. For the in vivo experiment, the rats were randomized to receive treatment with saline or X22 (0.1 μM/kg, 3 μL) before the induction of I/R injury. Histological evaluation, apoptosis of retinal cells, macrophage infiltration, and retina functional changes were further determined. Our data showed that pretreatment with X22 significantly inhibited TBHP-induced inflammatory cytokine expression in ARPE-19 cells. The anti-inflammatory activity of X22 may be associated with its inhibition on MAPKs, rather than NF-κB. Subsequently, our data proved that TBHP induced apoptosis in ARPE-19 cells, while pretreatment of X22 significantly suppressed TBHP-caused ARPE-19 apoptosis. Finally, the in vivo data revealed that X22 administration maintained better inner retinal layer structures, reduced apoptosis of retinal ganglion cell, and improved retinal function in retinal I/R rat models, which were accompanied with a remarkable decrease in retinal macrophage infiltration. These results suggest that the novel compound X22 is a potential agent for the treatment of retinal I/R-related diseases via the MAPKs-targeting anti-inflammatory mechanism and deserves the further development.
研究领域:
眼科学
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药理学
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炎症研究
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神经保护
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2018
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IF 3.118
Zheng Li,Haihua Feng,Yue Wang,Bingyu Shen,Ye Tian,Lin Wu,Qiaoling Zhang,Meiyu Jin,Guowen Liu
Rosmarinic acid (RA) has antioxidation, anticancer, antibacterial, anti-inflammatory and various biological functions. In our study, we aim to evaluate effects of RA on acute liver injury caused by LPS and d -galactosamine ( d -GalN) and its underlying molecular mechanism in mice. Our findings showed that RA could protect C57BL/6 mice from LPS/ d -GalN-induced acute liver injury, which not only reflected on declining aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the serum, but also restrained the phosphorylation of nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinase (ERK1/2) and p38 protein expression and the content of tissue myeloperoxidase (MPO) elevation. Moreover, RA could enhance the level of glutathione-dependent peroxidase (GSH-PX). Furthermore, RA promoted that nuclear factor erythroid-2-related factor 2 (Nrf2) transported into nucleus, and then up-regulated heme oxygenase 1 (HO-1), glutamate-cysteine ligase catalytic (GCLC), glutamate cysteine ligase modifier (GCLM) and quinone oxidoreductase (NQO1). These results indicated that RA could protect the mice from acute liver injury induced by LPS/ d -GalN.
研究领域:
药理学
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肝病学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2022
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IF 4.319
Jiabin Zhou,Fengqi Zhang,Jun Chen,Shilin Zhang,Haijun Wang
Introduction Chlorogenic acid (CGA) is a type of polyphenolic substance that is widely extracted from many traditional Chinese medicines (eg, Lonicera japonica Thunb, Eucommia ulmoides Oliver) and exhibits a wide range of anti-tumor effects. However, the potential molecular mechanisms of CGA in glioma U373 cells remain unclear.Methods Network pharmacology analysis was used to explore the potential therapeutic targets of CGA in glioma. Human glioma U373 cells were treated with different concentrations of CGA for 24 h. CCK-8 assays were used to detect the inhibitory rate of cell growth. Annexin V-FITC/PI staining and Hoechst 33342 staining were used to detect apoptosis. PI staining was used to investigate cell-cycle progression. Wound healing assays and transwell assays were used to detect the cell migration and invasion, respectively. Western blotting and immunohistochemistry were used to measure protein levels in vitro and in vivo.Results The proliferation of U373 cells was significantly inhibited by CGA in a dose- and time-dependent manner. CGA significantly arrested the cell cycle of U373 cells in the G2/M phase and induced apoptosis. Moreover, CGA significantly suppressed the migration and invasion of U373 cells. Additionally, we found that CGA inhibited the growth of U373 cells in vivo. Furthermore, network pharmacology analysis suggested that the anti-tumor effects of CGA on U373 cells were associated with the down-regulation of the SRC/MAPKs signaling pathway.Discussion The present study indicated that CGA had anti-glioma effects on U373 cells by down-regulating SRC/MAPKs signal pathway.
研究领域:
药理学
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肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
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2020
·Vol. 20
·期 1
·1-9
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IF 0
Li Jiashun,Jie Xiang,Liang Xiaoli,Chen Ziyu,Xie Peifang,Pan Xiping,Zhou Beixian,Li Jing
Background Human respiratory system infected with influenza A virus (IAV) elicited a robust pro-inflammatory response that resulted in severe illness and even death. Currently, limited immunomodulator is available to counteract IAV-associated pneumonia in the clinic. Sinensetin, a polymethoxylated flavone with five methoxy groups, has been found to possess anti-agiogenesis, anti-inflammatory and anti-diabetic activities. However, the effects of sinensetin on IAV-triggered pro-inflammatory response remain unclear. In the present study, the anti-inflammatory effects and corresponding possible mechanism of sinensetin in IAV-infected A549 cells were subjected to investigations. Methods The cytotoxic effects of sinensetin towards A549 cells was detected by MTT and LDH assays. The antiviral activity of sinensetin against influenza A virus was assayed in A549 cells with an engineered replication-competent influenza A virus carrying Gaussia luciferase reporter gene infection. The effect of sinensetin on influenza A virus-triggered inflammatory reaction was determined by qRT-PCR, Luminex assays, ELISA and Western blot. Results Our results showed that sinensetin did not exhibit antiviral activity against A/PR/8/34 (H1N1). Meanwhile, sinensetin treatment significantly decreased IAV-induced expression of pro-inflammatory mediators at mRNA and protein levels, including IL-6, TNF-α, IP-10, IL-8 and MCP-1. Additionally, levels of cyclooxygenase (COX)-2 and the downstream product prostaglandin E 2 (PGE 2 ) up-regulated by IAV infection were dramatically suppressed by sinensetin. The mechanistic investigation revealed that sinensetin treatment suppressed the NF-κB transcriptional activity using the NF-κB reporter stable HEK293 cell line stimulated with TNF-α (20 ng/mL) or influenza H1N1 virus. Furthermore, sinensetin abrogated influenza H1N1 virus-induced activation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings. Conclusion Collectively, our results indicated that sinensetin has potential capacity to attenuate IAV-triggered pro-inflammatory response via inactivation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings, which implied that sinensetin may be a promising candidate drug for influenza H1N1 virus infection therapeutics.
研究领域:
药理学
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免疫学
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病毒学
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细胞生物学
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产品关联
DOI
PubMed
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 5
·2118
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IF 4.9
Xiyue Wang,Miaoyunhuan Wang,Yuqing Dong,Shuqing Yu,Shanshan Zhang,Pinghua Sun,Lu Wang,Jibin Liu,Houwen Lin,Xinhui Pan,Xiaobin Li
Chenopodium albumL., as a folkloric herb, is traditionally used to treat poisonous insect bites, vitiligo, and other ailments. However, its impact on thrombosis remains unknown. In this study, we discovered that the ethanol extract ofC. albumexhibited a remarkable antithrombotic effect using a zebrafish thrombosis model for the first time. Activity evaluation showed that fraction CA-C could improve thrombus aggregation in the caudal vein, increase blood return in the heart, and alleviate the slowing of blood flow compared with those in the model group. Then, analysis by ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass (UPLC-Q-TOF-MS) identified 58 constituents of CA-C, with most of them belonging to flavonoids, alkaloids, and steroidal saponin components. Moreover, using a comprehensive strategy of network pharmacological analysis, transcriptomic assay, and RT-qPCR validation, we found that CA-C could mediate the TLR’s signaling pathway and its downstream MAPKs and PI3K/AKT signaling pathways to exert an antithrombotic effect. This study broadens the clinical application of plantC. albumand provides new insight into the chemical profile, pharmacodynamics, and potential mechanisms of CA-C as candidate agents for treating thrombosis.
研究领域:
药理学
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植物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2018
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IF 3.616
Qiaozhu Tan,Ming Zhang,Lujing Geng,Zhenghua Xia,Cen Li,Muhammad Usman,Yuzhi Du,Lixin Wei,Hongtao Bi
Methylmercury (MeHg + ) is an extremely toxic organomercury cation that can induce severe neurological damage. Once it enters the body, methylmercury binds to amino acids or proteins containing free sulfhydryl groups. In particular, methylmercury is known to bind with human serum albumin (HSA) in human plasma; however, the effects of methylmercury-HSA conjugate (MeHg-HSA) on the central nervous system (CNS) are not fully understood. In the present study, we used the microglial cell line N9 as the target cells to evaluate the effect of MeHg-HSA on physiological function of the CNS preliminarily. The various factors in the cell culture were monitored by MTT assay, total lactate dehydrogenase assay, ELISA , qPCR, Western blot and flow cytometry techniques. The results showed that low-dose treatment with MeHg-HSA activated N9 cells, promoting cell proliferation and total cell number, enhancing NO and intracellular Ca 2+ levels, and suppressing the release of TNFα and IL1β without cytotoxic effects; while high-dose MeHg-HSA exhibited cytotoxic effects on N9 cells, including promoting cell death and increasing the secretion of TNFα and IL1β. These results indicate that MeHg-HSA causes hormesis in microglia N9 cells. Furthermore, ERK/MAPKs and STAT3 signaling pathways related to the hormesis of MeHg-HSA on N9 cells. In addition, low dose of MeHg-HSA might be viewed as something very close to a lowest observed adverse effect level (LOAEL) for N9 cells. These findings will be useful for investigating the hormesis mechanism of MeHg + and exploring the specific functions of MeHg-sulfhydryl conjugates on the central nervous system.
研究领域:
神经毒理学
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细胞生物学
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药理学
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毒理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
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2024
·Vol. 68
·期 8
·2300643
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IF 4.5
Xiaobo Wei,Ni Ma,Wen Yang,Jinhu Tian,Huiyan Liu,Haitian Fang
Scope Polyphenols are the major active substances in red jujube fruit, and their anti-inflammatory and antioxidant activities suggest their potential utility in the prevention of ulcerative colitis (UC). Methods and results In this study, the effect of polyphenol extracts from red jujube ( Ziziphus jujuba Mill. “Junzao”) (PERJ) on the dextron sulfate sodium (DSS)-induced UC mice is investigated. The result shows that PERJ effectively improves clinical symptoms, including food and water intake, the disease activity insex (DAI) and spleen index, and routine blood levels, and alleviates the shortening of the colon, in mice with DSS-induced UC. Meanwhile, PERJ remarkably decreases the expression of proinflammatory factors. Moreover, PERJ repairs intestinal barrier damage by increasing the expression level of mucin 2 and mucin 3, and the result is also confirmed in the histological assessment. Besides, the expression levels of Nod-like receptor family pyrin domain-containing 3 (NLRP3) and mitogen-activated protein kinase cascade (MAPKs) signaling pathway-related proteins are inhibited by the PERJ administration. Finally, 16S rRNA sequencing analyses reveal that PERJ reverses intestinal microbiota dysbiosis by enhancing the abundance of Firmicutes and decreasing that of Proteobacteria and Bacteroidetes . Conclusion PERJ probably inhibits the development of UC by suppressing the NLRP3 and MAPKs signaling pathways and regulating gut microbiota homeostasis, and can be considered as a potential resource for preventing UC.
研究领域:
药理学
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免疫学
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微生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2019
·
IF 3.585
Wu Luo,Yiyi Jin,Gaojun Wu,Weiwei Zhu,Yuanyuan Qian,Yali Zhang,Jieli Li,Aisong Zhu,Guang Liang
Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes. A multitude of factors are involved in the pathogenesis of DCM including chronic inflammation and oxidative stress . We have recently shown that compound LF10 prevents inflammatory responses in an animal model of lung injury. In the present study, we explored the protective effects and mechanism of LF10 against DCM using a mouse model of streptozotocin-induced diabetes and high glucose (HG)-challenged cultured cardiomyocytes. We show that LF10 suppressed diabetes-induced cardiomyocyte hypertrophy and fibrosis , which was accompanied by preservation of cardiac function in mice. Mechanistically, LF10 prevented increases in the levels of pro-inflammatory molecules and oxidative stress under in vitro and in vivo diabetic conditions. Moreover, LF10 restored HG-downregulated sirtuin 1 (SIRT1) in cardiomyocytes and prevented HG-induced activation of MAPKs. Using specific small-molecule regulators, we found that SIRT1 was an upstream signal of MAPKs. In conclusion, LF10 inhibited ROS and MAPKs-mediated inflammation by restoring SIRT1, and prevented development of DCM. LF10 targeted both oxidative stress and inflammation, two tightly interconnected pathogenic pathways, which makes LF10 a highly advantageous therapeutic drug potential.
研究领域:
心脏病学
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药理学
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糖尿病
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炎症
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氧化应激
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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）