scholarly journals Rutin mitigates hepatic fibrogenesis and inflammation through targeting TLR4 and P2X7 receptor signaling pathway in vitro and in vivo

2020 ◽  
Vol 64 ◽  
pp. 103700 ◽  
Author(s):  
Li-Shuang Hou ◽  
Zhen-Yu Cui ◽  
Peng Sun ◽  
Hui-Qing Piao ◽  
Xin Han ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P2x7 Receptor ◽  
Receptor Signaling ◽  
Hepatic Fibrogenesis ◽  
Receptor Signaling Pathway

The role of aryl hydrocarbon receptor signaling pathway in cardiotoxicity of acute lead intoxication in vivo and in vitro rat model

Toxicology ◽  
2013 ◽  
Vol 306 ◽  
pp. 40-49 ◽  
Author(s):  
Mushtaq A. Ansari ◽  
Zaid H. Maayah ◽  
Saleh A. Bakheet ◽  
Ayman O. El-Kadi ◽  
Hesham M. Korashy
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Rat Model ◽  
Lead Intoxication ◽  
Receptor Signaling ◽  
Aryl Hydrocarbon ◽  
Receptor Signaling Pathway

scholarly journals Systematic elucidation of the molecular mechanism of scutellarin against osteoarthritis based on network pharmacology

2020 ◽  
Author(s):  
Shijia Guo ◽  
Xinan Zhang ◽  
mingli Sun
Keyword(s):  
Molecular Docking ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Network Pharmacology ◽  
Signaling Proteins ◽  
Receptor Signaling ◽  
In Vivo Experiments ◽  
Receptor Signaling Pathway

Abstract Background Scutellarin was reported to exerted inhibitive effects on osteoarthritis, However, the detailed mechanisms remain unclear. In this study, we investigated underlying multi-target mechanisms of scutellarin against osteoarthritis by using network pharmacology analysis and molecular docking. Results Scutellarin exerted inhibitive effects on osteoarthritis by regulating the function of several new signaling pathways, such as TNF signaling pathway, NOD-like receptor signaling pathway and HIF-1 signaling pathway. Molecular docking analysis showed there was better interaction between scutellarin and several NF-kB signaling proteins, including NFKBIA, RELA and NFKB1. In addition, the results showed Pi-cation, Pi-donor-hydrogen and Pi-alkyl were the main forms of interaction between scutellarin and NFKB1 and NFKBIA, Pi-Pi T-shaped, Pi-alkyl and hydrogen bonding were the main forms of interaction between scutellarin and RELA. Conclusion Taken together, TNF signaling pathway, NOD-like receptor signaling pathway and HIF-1 signaling pathway were possible signaling pathways, NFKBIA, RELA and NFKB1were possible targets associated with the activities of scutellarin against osteoarthritis. However, it is imperative that these targets should be thoroughly verified by in vitro and in vivo experiments.

scholarly journals Heatstroke-induced hepatocyte exosomes promote liver injury by activating the NOD-like receptor signaling pathway in mice

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8216 ◽  
Author(s):  
Yue Li ◽  
Xintao Zhu ◽  
Ming Zhang ◽  
Huasheng Tong ◽  
Lei Su
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
Kegg Pathway ◽  
Target Cells ◽  
Receptor Signaling ◽  
Kegg Pathway Analysis ◽  
Receptor Signaling Pathway

Background Liver injury is a common and important clinical issue of severe heat stress (HS), which has toxic effects and promotes subsequent multiple organ failure. The pathogenesis of HS-induced liver injury has not been fully elucidated. Passively injured hepatocytes also drive liver injury. Exosomes, extracellular vesicles secreted by hepatocytes as “danger signals,” mediate the intercellular transportation of diverse functional protein cargoes and modulate the biological processes of target cells. However, whether hepatocyte exosomes are involved in HS-induced liver injury has not been reported. The purpose of the current study was to clarify the release of hepatocyte exosomes under HS conditions and to explore their role in mediating HS-induced liver injury. Methods HS was induced in hepatocytes or mice by hyperthermic treatment at 43.0 °C for 1 h. Exosomes from control and HS-exposed hepatocytes were isolated by standard differential ultracentrifugation. The hepatocyte exosomes were characterized, and the differentially expressed proteins of the control and HS exosomes were identified by isobaric tags for relative and absolute quantitation (iTRAQ) mass spectrometry and subjected to Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Recipient hepatocytes were treated with control or HS exosomes, whereas in vivo, the exosomes were infused into mice. The internalization of HS hepatocyte exosomes by hepatocytes or the liver was tracked. The effect of HS exosomes on the activation of the NOD-like receptor signaling pathway and liver injury was demonstrated in vitro and in vivo. Results HS induced an increase in the release of exosomes from hepatocytes, which were internalized by recipient liver cells in vitro and taken up by the liver in vivo. HS significantly changed the proteomic profiles of hepatocyte exosomes based on the iTRAQ analysis. The KEGG pathway analysis revealed the enrichment of proteins associated with injury and inflammatory signaling pathways, especially the NOD-like receptor signaling pathway, the activity of which was upregulated. Subsequently, the capacity of HS hepatocyte exosomes to activate the NOD-like receptor signaling pathway was verified and found to aggrevate liver damage and inflammation in vitro and in vivo. Conclusions This study is the first preliminary study to demonstrate the induction of acute liver injury by hepatic exosomes in the setting of severe HS and reveals potentially related pathways. These results provide a basis for future research and the identification of new targets for clinical intervention.

scholarly journals Long Noncoding RNA Expression Profile in BV2 Microglial Cells Exposed to Lipopolysaccharide

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yajuan Li ◽  
Qingmin Li ◽  
Cunjuan Wang ◽  
Shengde Li ◽  
Lingzhi Yu
Keyword(s):  
Neuropathic Pain ◽  
Signaling Pathway ◽  
Noncoding Rna ◽  
Cell Activation ◽  
Differentially Expressed ◽  
Microglial Cells ◽  
Receptor Signaling ◽  
Microglia Cell ◽  
Receptor Signaling Pathway

Neuropathic pain, which is one of the most common forms of chronic pain, seriously increases healthcare costs and impairs patients’ quality of life with an incidence of 7–10% worldwide. Microglia cell activation plays a key role in the progression of neuropathic pain. Better understanding of novel molecules modulating microglia cell activation and these underlying functions will extremely benefit the exploration of new treatment. Recent studies suggested long noncoding RNAs may be involved in neuropathic pain. However, its underlying functions and mechanisms in microglia cell activation remain unclear. To identify the differentially expressed lncRNAs and predict their functions in the progression of microglia cell activation, GSE103156 was analyzed using integrated bioinformatics methods. The expression levels of selected lncRNAs and mRNAs were determined by real-time PCR. In the present study, a total of 56 lncRNAs and 298 mRNAs were significantly differentially expressed. The differentially expressed mRNAs were mainly enriched in NF-kappa B signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, and NOD-like receptor signaling pathway. The top 10 hub genes were Tnf, Il6, Stat1, Cxcl10, Il1b, Tlr2, Irf1, Ccl2, Irf7, and Ccl5 in the PPI network. Our results showed that Gm8989, Gm8979, and AV051173 may be involved in the progression of microglia cell activation. Taken together, our findings suggest that lots of lncRNAs may be involved in BV2 microglia cell activation in vitro. The findings may provide relevant information for the development of promising targets for the microglial cells activation of neuropathic pain in vivo in the future.

scholarly journals The role of the P2X7 receptor signaling pathway for the release of autolysosomes in microglial cells

Autophagy ◽  
2009 ◽  
Vol 5 (5) ◽  
pp. 723-724 ◽  
Author(s):  
Takato Takenouchi ◽  
Masayo Fujita ◽  
Shuei Sugama ◽  
Hiroshi Kitani ◽  
Makoto Hashimoto
Keyword(s):  
Signaling Pathway ◽  
P2x7 Receptor ◽  
Microglial Cells ◽  
Receptor Signaling ◽  
Receptor Signaling Pathway

scholarly journals The Chinese Herbal Prescription JieZe-1 Inhibits Membrane Fusion and the Toll-like Receptor Signaling Pathway in a Genital Herpes Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Qianni Duan ◽  
Tong Liu ◽  
Cong Huang ◽  
Qingqing Shao ◽  
Yonggui Ma ◽  
...  
Keyword(s):  
Mouse Model ◽  
Membrane Fusion ◽  
Signaling Pathway ◽  
Genital Herpes ◽  
Receptor Signaling ◽  
Toll Like Receptor ◽  
Receptor Signaling Pathway ◽  
Membrane Fusion Proteins ◽  
Herbal Prescription

Chinese herbal prescription JieZe-1 is effective for genital herpes with no visible adverse effects clinically. It showed an excellent anti-HSV-2 effect in vitro. However, its mechanism of anti-HSV-2 effect in vivo remains unclear. This study was designed to evaluate the anti-HSV-2 effect of JieZe-1 and berberine in a genital herpes mouse model and explore the underlying mechanism. The fingerprint of JieZe-1 was determined by high-performance liquid chromatography. First, we optimized a mouse model of genital herpes. Next, the weight, symptom score, morphological changes, viral load, membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells of vaginal tissue in mice at different time points were measured. Finally, we treated the genital herpes mouse model with JieZe-1 gel (2.5, 1.5, and 0.5 g/ml) and tested the above experimental indexes at 12 h and on the 9th day after modeling. JieZe-1 improved the symptoms, weight, and histopathological damage of genital herpes mice, promoted the keratin repair of tissues, and protected organelles to maintain the typical morphology of cells. It downregulated the expression of membrane fusion proteins, critical proteins of the Toll-like receptor signaling pathway, cytokines, and immune cells. The vaginal, vulvar, and spinal cord viral load and vaginal virus shedding were also significantly reduced. In summary, JieZe-1 shows significant anti-HSV-2 efficacy in vivo. The mechanism is related to the inhibition of membrane fusion, the Toll-like receptor signaling pathway, inflammatory cytokines, and cellular immunity. However, berberine, the main component of JieZe-1 monarch medicine, showed no efficacy at a concentration of 891.8 μM (0.3 mg/ml).

Inhibiting α1-adrenergic Receptor Signaling Pathway Ameliorates Alzheimer’s Disease Type Pathologies and Behavioral Deficits in an AD Mouse Model

2021 ◽  
Author(s):  
Zhong-Yuan Yu ◽  
Xu Yi ◽  
Ye-Ran Wang ◽  
Gui-Hua Zeng ◽  
Cheng-Rong Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Neuronal Loss ◽  
Behavioral Deficits ◽  
Bace1 Expression ◽  
Receptor Signaling Pathway ◽  
Gsk 3Β

Abstract Background The role of α1 adrenergic receptors (α1-ARs) signaling pathway in the pathogenesis of Alzheimer’s disease (AD) has rarely been investigated. Clarifying pathophysiological functions of α1-ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic target of AD. Methods This study included 2 arms of in vivo investigations: 1) 6-month-old female APPswe/PS1 mice were intravenously treated with AAV-PHP.eB-shRNA (ARs)-GFP or AAV-PHP.eB-GFP for 3 months. 2) 3-month-old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or equal saline for 6 months. SH-SY5Y cell lines bearing human Amyloid precurssor protein were treated with terazosin or saline for investigating possible mechanisms. Results α1-ARs knockdown mice exhibited improved behavioral performances than control mice. α1-ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aβ species, compact and total plaques, than control mice. The α1-ARs inhibitor terazosin substantially reduced Aβ deposition, attenuated downstream pathologies including Tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction, and rescued behavioral deficits of APPswe/PS1 mice. In vitro investigation demonstrated that α1-ARs inhibition down-regulated BACE1 expression, and promoted ser9 phosphorylation of GSK-3β, thus reduced Aβ production. Conclusions This study indicates that inhibition of α1-ARs signaling pathway might represent a promising therapeutic strategy for AD.

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