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Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF β1/Smad3 and NF-κB signaling pathways

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World Journal of Gastroenterology 2023年第18期29卷 2798-2817页

作者： Liu Shi Li Zhou Ming Han Yu Zhang Yang Zhang Xiao-Xue Yuan Hong-Ping Lu Yun Wang Xue-Liang Yang Chen Liu Jun Wang Pu Liang Shun-Ai Liu Xiao-Jing Liu Jun Cheng Shu-Mei Lin Department of Infectious Disease Medicine The First Hospital Affiliated to Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina China-Japan Friendship Hospital Department of Infectious Disease China-Japan Friendship HospitalBeijing 100029China Institute of Infectious Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China The Division of Liver Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Institute of Liver Diseases Beijing Pan-Asia Tongze Institute of Biomedicine Co.LtdBeijing 100015China Department of Rehabilitation Medicine The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Beijing Key Laboratory of Emerging Infectious Diseases Peking University Ditan Teaching HospitalBeijing 100015China

BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of ***,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still *** group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains ***,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for *** To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on *** Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were ***-β1 was administered to boost the in vitro cultivation of LX-2 ***3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain *** activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was *** statistical analysis of the data was performed using the Student’s t *** NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 *** proliferation of HSCs was lowered after NS3TP1 interference and elevated after

关键词： Nonstructural protein 3-transactivated protein 1 Calcitriol Liver fibrosis Hepatic stellate cells Mouse model TGFβ1/Smad3 NF-κB signaling pathway

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The molecular mechanism underlying angiogenesis in hepatocellular carcinoma: the imbalance activation of signaling pathways

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Hepatobiliary & Pancreatic Diseases International 2003年第4期2卷 529-536页

作者： Zhi-Cheng Zhao Shu-Sen Zheng Yun-Le Wan Chang-Ku Jia Hai-Yang Xie the Department of Hepatobiliary Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China Department of Hepatobiliary Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China. zyh037@***

OBJECTIVE: To explore the effect of two dominating signaling pathways, VEGF/KDR and angiopoietins/Tie2, on the formation of new blood vessel in hepatocellular carcinoma (HCC) growth and metastasis. METHODS: RT-PCR and Western blot were employed to evaluate the VEGF/KDR and angiopoietins/Tie2 expression in samples from 23 patients with HCC. Meanwhile, microvessel density (MVD) was determined as a marker of angiogenesis by counting CD34 positive cells with the method of immunohistochemistry. RESULTS: The two pathways were activated in all HCC samples. The expressions of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2) were significantly higher (Psignaling pathways, VEGF/KDR and angiopoietins/Tie2 are activated in the process of angiogenesis in HCC and modulate the formation of new blood vessels. The imparity of the two signaling pathways' activation is to benefit HCC metastasis. In the two pathways, VEGF and Ang2 may play an important role in the process of angiogenesis, and are necessary indicators for the prognosis and metastasis of HCC. This study provides another clue for the exploration of anti-angiogenic agents.

关键词： hepatocellular carcinoma signaling pathway angiogenesis VEGF/KDR angiopoietins/Tie2

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Regulatory effect of traditional Chinese medicines on signaling pathways of process from chronic atrophic gastritis to gastric cancer

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Chinese Herbal Medicines 2022年第1期14卷 5-19页

作者： Xinnan Liu Shuping Wang Jingyang Li Jingze Zhang Dailin Liu Tianjin Modern Innovation Chinese Medicine Technology Co. Ltd.Tianjin 300380China Tianjin University of Traditional Chinese Medicine Tianjin 301617China Department of Pharmacy Tianjin Provincial Corps HospitalChinese People’s Armed Police ForcesTianjin 300162China Logistics College of Chinese People’s Armed Police Forces Tianjin 300309China

Chronic atrophic gastritis(CAG),a common disease of digestive system,is an extremely important cause of gastric cancer(GC).The occurrence and development of CAG involves the abnormality of multiple signaling *** Chinese medicines(TCMs)has the advantages of mild action,multi-target and small adverse reaction,etc.,which broadens the way for the treatment of the disease,and TCMs can play a therapeutic role by regulating multiple signaling *** this review,based on the related experiments of TCMs and Chinese herbal compounds in recent years,the related literatures were searched and 10 kinds of signaling pathways involved were summarized,in order to provide a reference for further research on reversing or delaying the progress of CAG and preventing gastric cancer.

关键词： chronic atrophic gastritis gastric cancer signaling pathway traditional Chinese medicines

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Initial effects of inflammation-related cytokines and signaling pathways on the pathogenesis of post-traumatic osteoarthritis

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Frontiers of Nursing 2018年第2期5卷 91-96页

作者： Peng-Fei Han Zhi-Liang Zhang Tao-Yu Chen Rui-Peng Zhao Rong Zhang Xiao-Dong Li Peng-Cui Li Lei Wei Zhi Lv Xiao-Chun Wei Second People's Hospital of Changzhi City ChangzhiShanxi 046010China Second Affiliated Hospital of Shanxi Medical University TaiyuanShanxi 030001China Affiliated Peace Hospital of Changzhi Medical College ChangzhiShanxi 046010China

The main pathological change in post-traumatic osteoarthritis （PTOA） is cartilage degeneration, which is closely related to inflammation and oxidative stress. Inflammation can cause degeneration of articular cartilage. Cartilage degeneration can also stimulate the progression of inflammation. It has been found that inflammatory cytokines can participate in the pathological process of cartilage degeneration through multiple signaling pathways, mainly mitogen-activated protein kinase, nuclear transcription factor kappa B, and Wnt-p-catenin signal transduction pathways. This review aimed at exploring the relationship between PTOA and inflammation-related cytokines by introducing the role of proinflammatory cytokines in chondrocyte destruction and extracellular matrix degradation.

关键词： post-traumatic osteoarthritis cartilage degeneration pminflammatory cytokine signaling pathway

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Effect and signaling pathways of Nelumbinis Folium in the Treatment of Hyperlipidemia Assessed by Network Pharmacology

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World Journal of Traditional Chinese Medicine 2021年第4期7卷 445-455页

作者： Qiu Pan Zhi-Qing Zhang Cong-Yang Tian Tong Yu Ran Yang Xin-Lou Chai Cardiovascular Department Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijingChina Department of Pharmacology School of Traditional Chinese MedicineBeijing University of Chinese MedicineBeijingChina Cardiovascular Department Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijingChina

Objective:In this study,the effects and signaling pathways of Nelumbinis folium in the treatment of hyperlipidemia were analyzed based on network pharmacology and molecular *** and Methods:The main components and targets of Nelumbinis folium were searched through traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),and the active components were selected according to their oral availability and drug-like *** main targets of hyperlipidemia were identified using the Dis Ge NET *** 2.1.0 was used to take the intersection of both targets,which were submitted to the STRING database to construct the protein-protein interaction network *** Database for Annotation,Visualization and Integrated Discovery 6.7 was used to conduct gene ontology and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses of the *** 3.7.1 was used to construct the component-target-pathway *** Dock Vina molecular docking software was used to study the binding effect and mechanism of the core components and targets of ***:Fifteen active components of *** and 195 potential targets were selected through TCMSP,whereas 4216 targets for hyperlipidemia were selected from Dis Ge ***,138 potential cross-targets of hyperlipidemia were identified.A network of component-target-pathway was ***,kaempferol,and isorhamnetin were the core components,which played an important role in anti-hyperlipidemia,mainly through the non-alcoholic fatty liver disease and insulin resistance(IR)signaling *** docking results showed that quercetin had the lowest docking energies with peroxisome proliferator activated receptorα,peroxisome proliferator-activated receptorγ,INSR-6.20,-10.00,and-8.40(kcal/mol,respectively).The binding mode was mainly hydrogen bonds and van der Waals ***:The active components of *** may regulate lipid metabolism by par

关键词： Active components hyperlipidemia molecular docking Nelumbinis folium network pharmacology signaling pathway

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signaling pathways and Molecular Mechanisms of Oxidative Stress in Skeletal Muscle

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Agricultural Science & Technology 2015年第5期16卷 936-939页

作者： Haibing HU Wenjing LI Zhi FANG Bo XUE Longzhou LIU Ye YANG College of Animal Science Yangtze University Yueyang Chia Tai Co. Ltd. Animal Husbandry and Veterinary Bureau of Zhijiang City

Oxidative stress is a major factor affecting animal health and production performance. This paper briefly introduced the signaling pathways(i.e. NF-κB signaling pathway, MAPK, AP-1 and PGC-1α) of oxidative stress and the main genes regulating the signals of oxidative stress in skeletal muscle, providing a theoretical basis for reducing oxidative stress damage.

关键词： Skeletal muscle Oxidative stress signaling pathway Molecular mecha-nism

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Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways

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Chinese Medical Journal 2007年第9期120卷 743-748页

作者： ZHANG Yu-hua WEI Wei XU Hao WANG Yan-yan WU Wen-xi Department of Genaral Surgery First Affiliated Hospital of Nanjing Medical University. Nanjing 210029 China Immunology Research division Department of pathology Brigham Women＇s Hospital Boston MA 02115 USA

Background Vascular endothelial growth factor plays a key role in human colorectal carcinoma invasion and metastasis. However, the regulation mechanism remains unknown. Recent studies have shown that several cytokines can regulate the expression of vascular endothelial growth factor in tumor cells. In this study, we investigated whether hepatocyte growth factor can regulate the expression of vascular endothelial growth factor in colorectal carcinoma cells. Methods Hepatocyte growth factor and vascular endothelial growth factor in human serum were measured by ELISA. The mRNA level of vascular endothelial growth factor was analyzed by reverse transcription-PCR. Western blot assay was performed to evaluate levels of c-Met and several other proteins involved in the MAPK and PI3K signaling pathways in colorectal carcinoma cells. Results Serum hepatocyte growth factor and vascular endothelial growth factor were significantly increased in colorectal carcinoma subjects. In vitro extraneous hepatocyte growth factor markedly increased protein and mRNA levels of vascular endothelial growth factor in colorectal carcinoma cells. Hepatocyte growth factor induced phosphorylation of c-Met, ERK1/2 and AKT in a dose-dependent manner. Specific inhibitors on MEK and PI3K inhibited the hepatocyte growth factor-induced expression of vascular endothelial growth factor in colorectal carcinoma cells.Conclusion This present study indicates that hepatocyte growth factor upregulates the expression of vascular endothelial arowth factor in colorectal carcinoma cells via the MEK/ERK and PI3K/AKT sianalina pathways.

关键词： hepatocyte growth factor/scatter factor vascular endothelial growth factor signaling pathway receptor tyrosine kinases colorectal carcinoma

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Core signaling pathways and new therapeutic targets in pancreatic cancer

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Chinese Medical Journal 2010年第9期123卷 1210-1215页

作者： YOU Lei CHEN Ge ZHAO Yu-pei Department of General Surgery Peking Union Medical College HospitalBeijing 100730China

Objective Pancreatic cancer is a highly aggressive malignancy that has been resistant to treatment. Advances in cancer genetics have improved our understanding of this disease, but the genetics of pancreatic cancer remain poorly understood. A better understanding of the pathogenic role of specific gene mutations and core signaling pathways would propel the development of more effective treatments. The objective in this review was to highlight recent research that shows promise for new treatments for pancreatic cancer. Data sources All articles cited in this review were mainly searched from PubMed, which were published in English from 1993 to 2009. Study selection Original articles and critical reviews selected were relevant to the molecular mechanisms of pancreatic cancer. Results Dysregulation of core signaling pathways and processes through frequently genetic alterations can explain the major features of pancreatic tumorigenesis. New therapeutic targets based on recent research are emerging that hold promise for the future management of pancreatic cancer. Conclusion New agents used in conjunction with standard radiotherapy and chemotherapy might help to overcome drug resistance by targeting multiple signaling pathways to induce responsiveness of pancreatic cancer cells to death signals.

关键词： pancreatic cancer signaling pathway therapeutic target

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Research status of E3 ubiquitin ligase Smurf2 and related signaling pathways in glioma

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Journal of Translational Neuroscience 2020年第2期5卷 1-8页

作者： Qianxu Jin Zongmao Zhao The Second Hospital of Hebei Medical University Shijiazhuang 050051China

Glioma is the tumor with the highest incidence in the brain,and it is eager to seek new and efiective *** interaction of ubiquitination and deubiquitination regulates many cell activities in organisms,and participates in tumor occurrence,development,migration,invasion and other *** article summarized the progress of E3 ubiquitination ligase smad ubiquitination regulatory factor 2(Smurf2)and glioma-related signaling pathways to assist clinical diagnosis and treatment of glioma.

关键词： glioma smad ubiquitination regulatory factor 2(Smurf2) ubiquitin ligase signaling pathway

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Genome-Wide Study Identifies the Regulatory Glycosyltransferase Genes Networks and signaling pathways from Keshan Disease

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Journal of Health Science 2014年第4期2卷 165-173页

作者： Pan Wang Wuhong Tan Chengjuan Qu Feng Zhang Shulan He Jingfing Zheng Hu Shan Xiaohui Su Bin Wang Xiong Guo Key Laboratory of Environment and Genes Related to Diseases Xi 'an Jiaotong University Ministry of Education Xi 'an 710061Shaanxi China Clinical Laboratory The First Hospital of Yulin City Yulin 719000 Shaanxi China Institute of Biomedicine University of Eastern Finland Kuopio 70211 Finland Department of Respiratory Medicine The Second Affiliated Hospital Xi 'an diaotong University Health Science Center Xi 'an710004 Shaanxi China

KD （Keshan disease） is an endemic cardiomyopathy occurring only in China. Its pathogenesis is unclear till now. In the study, gene expression profiles of the PBMC （peripheral blood mononuclear cell） derived respectively from KD patients and healthy in KD areas were compared. Total RNA was isolated, amplified, labeled and hybridized to Agilent 4 ~ 44 K Whole Human Genome Oligonucleotide Microarray. Significant canonical pathways were analyzed by IPA （ingenuity pathway analysis） to identify differently expressed genes and pathways involved in the cardiovascular system development and function. Quantitative RT-PCR was applied to further validate our microarray results. Eighty-three up-regulated （ratios 〉 2.0） and nine down-regulated glycosyltransferase genes （ratios 〈 0.5） in PBMC in KD patients were detected by significance analysis of microarrays. Two significant canonical pathways from glycosyltransferase gene expression profiles were screened by IPA. The results of qRT-PCR show that four up-regulated （BMP 1/7/10 and FGF 18） and one down-regulated （BMP2） genes are consistent with those in microarray experiment, confirming the validity of the microarray data. Based on the results of the study, it is suggested that bone morphogenetic proteins and fibroblast growth factors might play an important role in the pathogenesis of KD. This further helps us to understand the pathogenesis of KD, as well as dilated cardiomyopathy.

关键词： Keshan disease glycosyltransferase gene signaling pathway bone morphogenetic protein fibroblast growth factor.

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