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Scorpiones,Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1αsignaling pathway

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Chinese Journal of Integrative Medicine 2024年第9期30卷 799-808页

作者： MAO Qi-yuan WANG Xue-qian LIN Fei YU Ming-wei FAN Hui-ting ZHENG Qi LIU Lan-chun ZHANG Chu-chu LI Dao-rui LIN Hong-sheng Department of Oncology Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing100053China Department of Oncology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing100010China Department of Cardiology Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing100053China Institute of Traditional Chinese Medicine Information China Academy of Chinese Medical SciencesBeijing100700China

Objective:To investigate whether Buthus martensii karsch(Scorpiones),Scolopendra subspinipes mutilans ***(Scolopendra)and Gekko gecko Linnaeus(Gekko)could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α(PI3K/AKT/mTOR/HIF-1α)signaling ***:Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models,with rapamycin and cyclophosphamide as positive *** methyl cellulose solutions of Scorpiones,Scolopendra and Gekko were administered intragastrically as 0.33,0.33,and 0.83 g/kg,respectively once daily for 21 *** expression were detected every 7 days after inoculation,and tumor growth curves were *** was performed to determine CD31 and HIF-1αexpressions in tumor tissue and microvessel density(MVD)was *** blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1αsignaling pathway-related ***-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor(bFGF),transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF)in ***:Scorpiones,Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α(all Psignaling pathway.

关键词： Scorpiones Scolopendra Gekko dredging collaterals and activating blood Chinese medicine of worms lung cancer hypoxic tumor microenvironment phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α signaling pathway

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Non-specific Lipid Transfer Protein StLTP6Promotes Virus Infection by Inhibiting Jasmonic Acid signaling pathway in Response to PVS TGB1

Non-specific Lipid Transfer Protein StLTP6Promotes Virus Inf...

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中国植物病理学会2024年学术年会

作者： SHANG Kaijie WANG Chenchen WANG Xipan XU Kaihao WANG Yubo ZHOU Shumei LIU Hongmei ZHU Xiaoping ZHU Changxiang College of Life Sciences Shandong Agricultural University College of Plant Protection Shandong Agricultural University

Plant viruses use host factors for successful ***-specificlipid transfer proteins(nsLTPs) are important in plant-pathogen interactionshowever,their roles and underlying molecular mechanisms in viral infections remain largely *** virus S(PVS) is one of the most serious viruses on *** present,there is no report on the mechanism of interaction between PVS-encoded protein and host factors,and little is known about which host factors are involved in regulating the virus *** acid(JA),as a plant hormone,is an important regulatory factor in the process of plant resistance to virus ***,we screened and verified that our previously reported pro-viral factor,StLTP6,could interact with the PVS-silencing suppressor triple gene block 1(TGB1) *** PVS TGB1 protein can induce the expression of StLTP6 and alter its original localization through ***,StLTP6 interacts with allene oxide cyclase and inhibits its accumulation,suppressing jasmonic acid ***,the inhibition of JA synthesis reduces its induction of host RNA silencing antiviral defense response,there by allowing virus *** summary,the molecular mechanism by which PVS TGB1 interacts with StLTP6 to promote PVS infection was *** findings broaden our understanding of the biological function of nsLTP and provides a new antiviral target for potato research.

关键词： non-specific lipid transfer protein potato virus S triple gene block 1 protein signaling pathway jasmonic acid

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signaling pathway/molecular targets and new targeted agents under development in hepatocellular carcinoma

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World Journal of Gastroenterology 2012年第42期18卷 6005-6017页

作者： Masatoshi Kudo Department of Gastroenterology and Hepatology Kinki University School of MedicineOsaka-SayamaOsaka 589-8511Japan

Advances in molecular cell biology over the last de- cade have clarified the mechanisms involved in can- cer growth, invasion, and metastasis, and enabled the development of molecular-targeted agents. To date, sorafenib is the only molecular-targeted agent whose survival benefit has been demonstrated in two global phase 111 randomized controlled trials, and has been approved worldwide. Phase 111 clinical trials of other molecular targeted agents comparing them with sorafenib as first-line treatment agents are ongoing. Those agents target the vascular endothelial growth factor, platelet-derived growth factor receptors, as well as target the epidermal growth factor receptor, insulin- like growth factor receptor and mammalian target of rapamycin, in addition to other molecules targeting other components of the signal transduction pathways. In addition, the combination of sorafenib with standard treatment, such as resection, ablation, transarterial em- bolization, and hepatic arterial infusion chemotherapy are ongoing. This review outlines the main pathways involved in the development and progression of hepato- cellular carcinoma and the new agents that target these pathways. Finally, the current statuses of clinical trials of new agents or combination therapy with sorafenib and standard treatment will also be discussed.

关键词： Hepatocellular carcinoma Molecular tar-geted agent Sorafenib signaling pathway Moleculartarget

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Oxymatrine reduces neuroinflammation in rat brain A signaling pathway

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Neural Regeneration Research 2012年第30期7卷 2333-2339页

作者： Jiahui Mao Yae Hu Ailing Zhou Bing Zheng Yi Liu Yueming Du Jia Li Jinyang Lu Pengcheng Zhou Department of Pathophysiology Medical School of Nantong University Nantong 226001 Jiangsu Province China Department of Urology the First People's Hospital of Nantong Nantong 226001 Jiangsu Province China Undergraduate of Medical School of Nantong University Nantong 226001 Jiangsu Province China

Cerebral neuroinflammation models were established by injecting 10μg lipopolysaccharide into the hippocampus of male Sprague-Dawley rats. The rats were treated with an intraperitoneal injection of 120, 90, or 60 mg/kg oxymatrine daily for three days prior to the lipopolysaccharide injection. Twenty-four hours after model induction, the hippocampus was analyzed by real-time quantitative PCR, and the cerebral cortex was analyzed by enzyme-linked immunosorbent assay and western blot assay. The results of the enzyme-linked immunosorbent assay and the real-time quantitative PCR showed that the secretion and mRNA expression of the pro-inflammatory cytokines interleukin-113 and tumor necrosis factor-a were significantly decreased in the hippocampus and cerebral cortex of model rats treated with oxymatrine. Western blot assay and real-time quantitative PCR analysis indicated that toll-like receptor 4 mRNA and protein expression were significantly decreased in the groups receiving different doses of oxymatrine. Additionally, 120 and 90 mg/kg oxymatrine were shown to reduce protein levels of nuclear factor-KB p65 in the nucleus and of phosphorylated IKBa in the cytoplasm of brain cells, as detected by western blot assay. Experimental findings indicate that oxymatrine may inhibit neuroinflammation in rat brain via downregulating the expression of molecules in the toll-like receptor 4/nuclear factor-KB signaling Dathwav.

关键词： oxymatrine neuroinflammation toll-like receptor 4 nuclear factor-KB signaling pathway inflammatory factors lipopolysaccharide hippocampus cerebral cortex neural regeneration

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The role of phosphatidylinositol signaling pathway in regulating serotonin-induced oocyte maturation in Mercenaria mercenaria

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Chinese Journal of Oceanology and Limnology 2011年第3期29卷 568-575页

作者：王清张涛 Institute of Oceanology Chinese Academy of Sciences Graduate University of Chinese Academy of Sciences

Serotonin (5-HT) has been found to stimulate meiotic maturation of oocytes in many molluscs. During maturation, several signaling pathways are involved, especially the phosphatidylinositol and cAMP pathways. In order to examine the possible role of the phosphatidylinositol signaling pathway in regulating oocyte maturation in Mercenaria mercenaria, the effects of the activator/inhibitor of phospholipase (PLC) and protein kinase C (PKC) on serotonin-induced maturation were studied. Results show that high-concentrations of neomycin (inhibitor of PLC) blocked oocyte maturation, while 9, 10-dimethyl-1, 2-benzanthracene (DMBA, activator of PLC) promoted oocyte maturation in the presence of serotonin. It was also found that in the presence of serotonin, phorbol 12-myristate 13-acetate (PMA, activator of PKC) inhibited oocyte maturation, while sphingosine (inhibitor of PKC) stimulated oocyte maturation. These results indicate that serotonin-induced oocyte maturation requires the activation of the phosphatidylinositol pathway. Decrease of PLC inhibited serotonin-induced oocyte maturation, whereas a decrease of PKC stimulated the maturation. Thus, our study indicates that serotonin promotes maturation of M. mercenaria oocytes through PLC stimulated increase in calcium ion concentration via inositol-1, 4, 5-trisphosphate (IP3) but not PKC.

关键词： GVBD Mercenaria mercenaria oocyte maturation phosphatidylinositol signaling pathway

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Curcumin Inhibits Viability of Clear Cell Renal Cell Carcinoma by Down-Regulating ADAMTS18 Gene Methylation through NF-κB and AKT signaling pathway

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Chinese Journal of Integrative Medicine 2022年第5期28卷 419-424页

作者： XU Ben PENG Yi-ji ZHU Wei-jie Department of Urology Peking University First Hospital and Institute of UrologyPeking UniversityNational Urological Cancer CenterBeijing(100034)China

Objective:To investigate the effect of curcumin on viability of clear cell renal cell carcinoma(cc RCC)and analyze its possible ***:In cell lines of A498 and 786-O,the effects of curcumin(1.25,2.5,5 and 10μmol/L)on the viability of cc RCC were analyzed at 24,48 and 72 h by MTT *** protein expression levels of ADAMTS18 gene,p65,phosphorylation p65(pp65),AKT,phosphorylation AKT(p AKT)and matrix metallopeptidase 2(MMP-2)before and after curcumin(10μmol/L)treatment were examined by Western ***-time PCR and methylation specific PCR(MSP)were applied to analyze the expression and methylation level of ADAMTS18 gene before and after curcumin treatment(10μmol/L).Results:Curcumin significantly inhibited the viability of A498 and 786-O cell lines in a dose-and time-dependent manner(Psignaling pathway.

关键词： curcumin clear cell renal cell carcinoma ADAMTS18 gene methylation signaling pathway

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Cytotoxic effects of docetaxel as a candidate drug of drug-eluting stent on human umbilical vein endothelial cells and the signaling pathway of cell migration inhibition,adhesion delay and shape change

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Regenerative Biomaterials 2017年第3期4卷 167-178页

作者： Tingzhang Hu Chun Yang Meiling Fu Jiali Yang Rolin Du Xiaolin Ran Tieying Yin Guixue Wang Key Laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing 400030China

Docetaxel(DTX),a paclitaxel analogue,can efficiently inhibit proliferation of vascular smooth muscle cells and has broadly been used as an antiangiogenesis ***,as a candidate drug of drug-eluting stent,the effects of DTX on human umbilical vein endothelial cells(HUVECs)are still not well ***,we investigated the effects of DTX on proliferation,apoptosis,adhesion,migration and morphology of HUVECs in *** found that DTX had the cytostatic and cytotoxic effects at low and high concentrations,*** could inhibit the proliferation and migration of HUVECs,induce HUVECs apoptosis,delay HUVECs adhesion and decrease spreading area and aspect ratio of individual *** signaling pathway that DTX led to the migration inhibition,adhesion delay and shape change of HUVECs is the VE-cadherin mediated integrin b1/FAK/ROCK signaling *** study will provide a theoretical basis for the clinical application of DTX.

关键词： cytotoxic effects docetaxel endothelial cells signaling pathway

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The crosstalk between the caspase family and the cGAS-STING signaling pathway

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Journal of Molecular Cell Biology 2021年第10期13卷 739-747页

作者： Yongai Xiong Yan-Dong Tang Chunfu Zheng Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of EducationZunyi Medical UniversityZunyiChina Department of Immunology School of Basic Medical SciencesFujian Medical UniversityFuzhouChina State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute of Chinese Academy of Agricultural SciencesHarbinChina Department of Microbiology Immunology and Infectious DiseasesUniversity of CalgaryCalgaryAlbertaCanada

Cytosolic nucleic acid sensors are critical for sensing nucleic acids and initiating innate immunity during microbial infections and/or cell *** the last decade,several key studies have characterized the conserved mechanism of cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)and the downstream signaling adaptor stimulator of interferon genes(STING)initiating the innate immune signaling *** from its primary involvement in microbial infections and inflammatory diseases,there is growing interest in the alternate roles of cGAS-STING-mediated *** family members are powerful functional proteins that respond to cellular stress,including cell death signals,inflammation,and innate *** studies have uncovered how the caspase family cooperates with the cGAS-STING signaling *** caspase family members negatively regulate the cGAS-STING signaling *** turn,some caspase family members can also be modulated by *** review gives a detailed account of the interplay between the caspase family and the cGAS-STING signaling pathway,which will shed light on developing novel therapeutics targeting the caspase family and cGAS-STING signaling in antiviral innate immunity,cancer,inflammatory,and autoimmunity.

关键词： cGAS-STING caspases innate immunity signaling pathway

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Effects of Total Saponins from Dioscorea Nipponica Makino on Monosodium Urate-Induced M1-Polarized Macrophages through Arachidonic Acid signaling pathway:An in vitro Study

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Chinese Journal of Integrative Medicine 2023年第1期29卷 44-51页

作者： ZHOU qi SUN Hui-juan LIU Shu-min Research Institute of Chinese Medicine Heilongjiang University of Chinese MedicineHarbin150040China Graduate School Heilongjiang University of Chinese MedicineHarbin150040China Technological Innovation Team of Basic Theory Study Research of Institution of Higher Education in Heilongjiang Province Heilongjiang University of Chinese MedicineHarbin150040China

Objective To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino(TSDN)on the arachidonic acid pathway in monosodium urate(MSU)crystal-induced M1-polarized *** M1 polarization of RAW264.7 cells were induced by 1µg/mL lipopolysaccharide(LPS).The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of ***(500µg/mL)was used to induce the gouty arthritis ***,10µg/L TSDN and 8µmol/L celecoxib,which was used as a positive control,were added to the above LPS and MSU-induced cells for 24 *** mRNA and protein expressions of cyclooxygenase(COX)2,5-lipoxygenase(5-LOX),microsomal prostaglandin E synthase derived eicosanoids(mPGES)-1,leukotriene B(LTB)4,cytochrome P450(CYP)4A,and prostaglandin E_(2)(PGE_(2))were tested by real-time polymerase chain reaction and Western blotting,*** enzyme-linked immunosorbent assay was used to test the contents of M1 markers,including inducible nitric oxid synthase(NOS)2,CD80,and *** TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2,5-LOX,CYP4A,LTB4,and PGE_(2)(Psignaling pathway.

关键词： gouty arthritis Dioscorea nipponica Makino arachidonic acid signaling pathway M1/M2 polarization

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Hedgehog signaling pathway regulated the target genes for adipogenesis in silkworm Bombyx moil

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Insect Science 2015年第5期22卷 587-596页

作者： Shuang Liang Rui-Ting Chen Deng-Pan Zhang Hu-Hu Xin Yan Lu Mei-Xian Wang Yun-Gen Miao Key Laboratory of Animal Virology of Ministry of Agriculture College of Animal Sciences Zhejiang University Hangzhou 310058 China

Hedgehog （Hh） signals regulate invertebrate and vertebrate development, yet the role of the pathway in adipose development remains poorly understood. In this report, we found that Hh pathway components are expressed in the fat body of silkworm larvae. Functional analysis of these components in a BmN cell line model revealed that activa- tion of the Hh gene stimulated transcription of Hh pathway components, but inhibited the expression of the adipose marker gene AP2. Conversely, specific RNA interference- mediated knockdown of Hh resulted in increased AP2 expression. This further showed the regulation of Hh signal on the adipose marker gene. In silkworm larval models, enhanced adipocyte differentiation and an increase in adipocyte cell size were observed in silkworms that had been treated with a specific Hh signaling pathway antagonist, cyclopamine. The fat-body-specific Hh blockade tests were consistent with Hh signaling inhibiting silkworm adipogenesis. Our results indicate that the role of Hh signaling in inhibiting fat formation is conserved in vertebrates and invertebrates.

关键词： adipocyte differentiation adipogenesis Bombyx mori Hedgehog (Hh) signaling pathway silkworm

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