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Journal of Chinese Pharmaceutical Sciences 2013年第1期22卷 71-76页

作者：万箫苟宝迪王夔北京大学医学部药学院化学生物学系北京100191

Gadolinium has been widely used as a contrast agent for magnetic resonance imaging in clinical practice. Recently, it was reported that gadolinium is involved in nephrogenic systemic fibrosis, although the exact mechanism by which gadolinium triggers nephrogenic systemic fibrosis remains unclear. In this study, we show that gadolinium chloride （GdC13） induced human umbilical vein endothelial cells （HUVECs） to migrate in Matrigel and tubulogenesis during wound healing. Chick chorioallantoic membrane assay confirmed that GdC13 stimulates angiogenesis. Under the optimal angiogenic concentration of GdC13 （1 0 ~tM）, intracellular calcium concentration and reactive oxygen species generation were elevated. Moreover, western blotting results indicate that in cells treated with GdC13, Ca2＋-dependent PKCa/132 was phosphorylated, and MAPKs pathways were also activated. Taken together, GdC13 has a potential effect on angiogenesis in HUVECs, and the possible mechanisms may involve oxidative stress and calcium-related signalin~ pathways.

关键词： Gadolinium chloride Angiogenesis Reactive oxygen species signaling pathways Human umbilical vein endothelial cells

Identifying patient-specific flow of signal transduction perturbed by multiple single-nucleotide alterations

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Quantitative Biology 2020年第4期8卷 336-346页

作者： Olha Kholod Chi-Ren Shyu Jonathan Mitchem Jussuf Kaifi Dmitriy Shin MU Institute for Data Science and Informatics University of MissouriColumbiaMO 65201USA Department Pathology and Anatomical Sciences School of MedicineUniversity of MissouriColumbiaMO 65212USA Department of Surgery School of MedicineUniversity of MissouriColumbiaMO 65212USA Harry S.Truman Memorial Veterans'Hospital ColumbiaMO 65201USA Department of Electrical Engineering&Computer Science University of MissouriColumbiaMO 65212USA

Background:Identifying patient-specific flow of signal transduction perturbed by multiple single-nucleotide alterations is critical for improving patient outcomes in cancer ***,accurate estimation of mutational effects at the pathway level for such patients remains an open *** probabilistic pathway topology methods are gaining interest among the scientific community,the overwhelming majority do not account for network perturbation effects from multiple single-nucleotide ***:Here we present an improvement of the mutational forks formalism to infer the patient-specific flow of signal transduction based on multiple single-nucleotide alterations,including non-synonymous and synonymous *** lung adenocarcinoma and skin cutaneous melanoma datasets from TCGA Pan-Cancer Atlas have been employed to show the utility of the proposed ***:We have comprehensively characterized six mutational *** number of mutated nodes ranged from one to four depending on the topological characteristics of a *** confidences(TCs)have been computed for every possible combination of single-nucleotide alterations in the *** performed analysis demonstrated the capacity of the mutational forks formalism to follow a biologically explainable logic in the identification of high-likelihood signaling routes in lung adenocarcinoma and skin cutaneous melanoma *** findings have been largely supported by the evidence from the biomedical ***:We conclude that the formalism has a great chance to enable an assessment of patient-specific flow by leveraging information from multiple single-nucleotide alterations to adjust the transitional likelihoods that are solely based on the canonical view of a disease.

关键词： mutational forks signaling pathways cancer single-nucleotide alterations

The progression of epithelial-mesenchymal transformation in gliomas

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Chinese Neurosurgical Journal 2017年第3期3卷 163-169页

作者： Lei Du Jun-Hai Tang Guo-Hao Huang Yan Xiang Sheng-Qing Lv Department of Neurosurgery Xinqiao Hospital Third Military Medical University Chongqing 400037 People's Republic of China

Epithelial-mesenchymal transformation(EMT) is a coordinated process in which polarized epithelial cells are induced to lose adhesion from the basement membrane and obtain the properties of mesenchymal cells, including invasion and metastasis. It has been proved that EMT greatly contributes to the invasion and therapeutic resistance of various solid human cancers. However, the role of EMT in brain glioma has not yet been fully clarified. So in this review, we mainly elaborate the latest progression about the related regulatory transcription factors, key signaling pathways and microRNAs (miRNAs) of EMT in gliomas.

关键词： Brain glioma Epithelial-mesenchymal transformation(EMT) Transcription factors signaling pathways MicroRNAs

The regulators of BCR signaling during B cell activation

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Blood Science 2019年第2期1卷 119-129页

作者： Yue Wen Yukai Jing Lu Yang Danqing Kang Panpan Jiang Na Li Jiali Cheng Jingwen Li Xingbo Li Zican Peng Xizi Sun Heather Miller Zhiwei Sui Quan Gong Boxu Ren Wei Yin Chaohong Liu Department of Pathogen Biology School of Basic MedicineHuazhong University of Science and TechnologyWuhanChina Department of Medical Imaging Technology Clinical and Molecular Immunology Research CenterMedical school of Yangtze UniversityJingzhouHubeiChina Department of Intracellular Pathogens National Institute of Allergy and Infectious DiseasesMT 59840USA Division of Medical and Biological Measurement National Institute of MetrologyBeijingChina Wuhan Children’s Hospital Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanChina

B lymphocytes produce antibodies under the stimulation of specific antigens,thereby exerting an immune effect.B cells identify antigens by their surface B cell receptor(BCR),which upon stimulation,directs the cell to activate and differentiate into antibody generating plasma *** of B cells via their BCRs involves signaling pathways that are tightly controlled by various *** this review,we will discuss three major BCR mediated signaling pathways(the PLC-g2 pathway,PI3K pathway and MAPK pathway)and related regulators,which were roughly divided into positive,negative and mutual-balanced regulators,and the specific regulators of the specific signaling pathway based on regulatory effects.

关键词： BCR MAPK PI3K PLC-g2 Regulator signaling pathways

Cancer stem cells and HER2 positive breast cancer:The story so far

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Genes & Diseases 2016年第2期3卷 114-123页

作者： Deep Shah Clodia Osipo Department of Molecular Pharmacology and Therapeutics Oncology Research InstituteLoyola University ChicagoMaywoodIL 60153USA Department of Microbiology and Immunology Oncology Research InstituteLoyola University ChicagoMaywoodIL 60153USA

Human Epidermal Growth Factor Receptor type 2(HER2)gene amplification and/or protein overexpression is observed in patients suffering from HER2t breast *** subtype of breast cancer has improved prognosis due to availability of anti-HER2 ***,drug resistance and tumor recurrence still remains a major *** Stem Cells(CSCs)are believed to constitute the subset of cell population that is resistant to drug treatment and possesses characteristics of stem *** enable the tumors to thrive despite major *** review provides a comprehensive idea about the concept of CSCs in context of HER2t breast cancer by providing the description of the markers that are used for the identification of CSCs and by elucidating the signaling pathways that are associated with HER2t breast ***,the review also describes the interaction of HER2 with those signaling pathways and the future of targeting CSCs in HER2t breast cancer.

关键词： Breast cancer Cancer stem cells(CSCs) Drug resistance Human epidermal growth factor receptor type 2(HER2) signaling pathways

Curcumin:reclaiming the lost ground against cancer resistance

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Cancer Drug Resistance 2021年第2期4卷 298-320页

作者： Siraj Shaikh Javed Shaikh Yusufi Sadia Naba Kailas Doke Khursheed Ahmed Mujahid Yusufi Post-Graduate Department of Chemistry and Research Center Abeda Inamdar Senior College of ArtsScience and Commerce(Affiliated to SPPU)Pune 411001India Advanced Scientific Research Laboratory Azam CampusPune 411001India.

Curcumin, a polyphenol, has a wide range of biological properties such as anticancer, antibacterial, antitubercular, cardioprotective and neuroprotective. Moreover, the anti-proliferative activities of Curcumin have been widely studied against several types of cancers due to its ability to target multiple pathways in cancer. Although Curcumin exhibited potent anticancer activity, its clinical use is limited due to its poor water solubility and faster metabolism. Hence, there is an immense interest among researchers to develop potent, water-soluble, and metabolically stable Curcumin analogs for cancer treatment. While drug resistance remains a major problem in cancer therapy that renders current chemotherapy ineffective, curcumin has shown promise to overcome the resistance and re-sensitize cancer to chemotherapeutic drugs in many studies. In the present review, we are summarizing the role of curcumin in controlling the proliferation of drug-resistant cancers and development of curcumin-based therapeutic applications from cell culture studies up to clinical trials.

关键词： Curcumin drug-resistant cancer signaling pathways clinical trials

Molecular regulation of myocardial proliferation and regeneration

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Cell Regeneration 2021年第1期10卷 139-155页

作者： Lixia Zheng Jianyong Du Zihao Wang Qinchao Zhou Xiaojun Zhu Jing-Wei Xiong Beijing Key Laboratory of Cardiometabolic Molecular Medicine Institute of Molecular Medicine and State Key Laboratory of Natural and Biomimetic DrugsPeking UniversityBeijing 100871China

Heart regeneration is a fascinating and complex biological process. Decades of intensive studies have revealed asophisticated molecular network regulating cardiac regeneration in the zebrafish and neonatal mouse heart. Here,we review both the classical and recent literature on the molecular and cellular mechanisms underlying heartregeneration, with a particular focus on how injury triggers the cell-cycle re-entry of quiescent cardiomyocytes toreplenish their massive loss after myocardial infarction or ventricular resection. We highlight several importantsignaling pathways for cardiomyocyte proliferation and propose a working model of how these injury-inducedsignals promote cardiomyocyte proliferation. Thus, this concise review provides up-to-date research progresses onheart regeneration for investigators in the field of regeneration biology.

关键词： Cardiac regeneration Cardiomyocyte proliferation signaling pathways Zebrafish Mouse

Research progress of interleukin-11 in tumor

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TMR Cancer 2018年第1期1卷 2-7页

作者： Chen Huang Ya-Hui Liu Li Ren Tianjin Medical University Inspection College Tianjin China Tianjin Medical University Inspection College Tianjin China. 2National Cancer Clinical Research Center Tianjin Key Laboratory of Cancer Prevention and Treatment Tianjin Cancer Center for Clinical Medicine Tianjin Medical University Cancer Hospital Tianjin China

Interleukin-11 （IL-11） is a cytokine of IL-6 family that mediates signal transduction through a common signal transduction molecule glycoprotein 130gp130. JAK/STAT, Ras/Erk and PI3K-mediated pathways are involved in the IL-11 signaling pathway. IL-11 has traditionally been thought to be an anti-inflammatory cytokine that has a complex role in the body＇s immune response. Simultaneously, the activation of STAT3 by IL-11 provides a functional link to support the survival and growth of cancer cells. There is also evidence that IL-11 may play a role in promoting liver cancer through wound healing mechanisms. In recent years, studies have found that IL-11 could stimulate the development of tumors via promoting the proliferation and inhibiting the apoptosis of cancer cells, mediating the tolerance of cancer cells to radiotherapy and chemotherapy, and mediating the growth and survival of early microtransferred colonies. Sustained activation of JAK-STAT and PI3K-AKT signaling pathway, up-regulating the expression of IL-11 receptor and hypoxia microenvironment mediated by HIF-1a and AP-1 transcription factors are involved in the progression of cancer. Therefore, targeted therapies that treat the over expression of IL-11 or IL-11 receptors and IL-11 signaling pathway such as the JAK 1/2 and STAT3 inhibitor in cancer patients has the potential to completely relieve the tumor, which may provide us a new idea for the treatment of cancer.

关键词： IL-11 Cancer progress signaling pathways

Network Pharmacology Investigation in the Mechanism of Radix Pseudostellariae-Rhizoma Anemarrhenae Therapy for Diabetes Mellitus

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World Journal of Integrated Traditional and Western Medicine 2020年第10期6卷 13-21页

作者： ZHANG Jia-wen CHEN Xin-yan ZHOU Meng-qi LIN Yan-zhao YANG Zhi-min Preventive Treatment Center of Guangdong Province Traditional Chinese Medical Hospital Guangzhou 510120China Dongzhimen Hospital Beijing University of Chinese MedicineBeijing 100700China

Objective:To explore the targets and signaling pathways of Radix Pseudostellariae-Rhizoma Anemarrhenae treating diabetes mellitus by network pharmacology and expound its ***:The TCMSP and SymMap databases were used to screen out the active ingredients and targets of Radix Pseudostellariae-Rhizoma *** GenCards database was used to screen the predicted targets of diabetes *** targets were *** Cytoscape 3.7.2 software was used to construct the network diagram of Chinese medicine-active ingredient-target and screen out the core ingredient and *** GO,KEGG pathway enrichment analysis was carried out by OmicShare and ***:According to the screening criteria,23 active ingredients of Radix Pseudostellariae-Rhizoma Anemarrhenae and 146 potential targets were obtained.138 common targets were obtained related with diabetes mellitus,including 5 key components and 37 core *** enrichment of biological process in GO is mainly related to the reaction to organic substances,the response of cells to chemical stimulation,the reaction to chemical substances,etc..The molecular function is mainly related to the enzyme binding,the same protein binding,and the activity of nuclear *** cell composition is mainly associated with the membrane raft,membrane microdomain,membrane region,etc..The KEGG pathway enrichment is mainly concentrated in TNF,Toll-like receptors,NOD-like receptors,insulin resistance and type II ***:Radix Pseudostellariae-Anemarrhena asphodeloides plays the anti-inflammatory,antioxidant,hypoglycemic,and insulin-resistance improving role through multiple targets and pathways,and therefore achieves the effect on diabetes mellitus.

关键词： Radix Pseudostellariae-Anemarrhena Asphodeloides Diabetes mellitus Network pharmacology Targets signaling pathways

Whole transcriptome analysis on blue light-induced eye damage

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International Journal of Ophthalmology(English edition) 2020年第8期13卷 1210-1222页

作者： Xin-Li Ouyang Bo-Yu Chen Yong-Fang Xie Yi-De Wu Shao-Jia Guo Xiao-Yun Dong Guo-Hui Wang Key Laboratory of Biological Medicines in Universities of Shandong Province Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Shijiazhuang Aier Eye Hospital Bethune International Peace Hospital of PLAShijiazhuang 050082Hebei ProvinceChina

AIM:To analyze abnormal gene expressions of mice eyes exposed to blue light using RNA-seq and analyze the related signaling ***:Kunming mice were divided into an experimental group that was exposed to blue light and a control group that was exposed to natural *** 14 d,the mice were euthanized and their eyeballs were *** transcriptome analysis was attempted to analyze the gene expression of the eyeballs using RNA-seq to reconstruct genetic *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were used to reveal the related signaling ***:The 737 differentially expressed genes were identified,including 430 up and 307 down regulated genes,by calculating the gene FPKM in each sample and conducting differential gene *** and KEGG pathway enrichment analysis showed that blue light damage may associated with the visual perception,sensory perception of light stimulus,phototransduction,and JAKSTAT signaling *** lnc RNA,circ RNA and mi RNA analysis showed that blue light exposure affected pathways for retinal cone cell development and phototransduction,among ***:Exposure to blue light can cause a certain degree of abnormal gene expression and modulate signaling pathways in the eye.

关键词： blue light eye whole transcriptome sequencing gene expression signaling pathways mice