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Chinese Medical Journal 2010年第17期123卷 2471-2474页

作者： GAO Ling-gen YAO Xiu-ping ZHANG Lin WEN Dan LUO Fang ZHOU Xian-liang HUI Ru-tai Department of Cardiology Fu Wai Hospital and Cardiovascular Institute Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China Sino-German Laboratory for Molecular Medicine Key Laboratory for Clinical Cardiovascular Genetics Ministry of Education Fu Wai Hospital and Cardiovascular Institute Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China Very Important Person Health Care Department The General Hospital of Chinese People's Armed Police Forces Beijing 100039 China

Heart failure is currently one of the most common and most cost-intensive of the chronic diseases The main cause of chronic heart failure （CHF） is the abnormalities of both cardiac contractile performance and myocardial energy metabolism. Elevated levels of reactive oxygen species （ROS） have been proposed to contribute to both of them. Xanthine oxidoreductase （XO） is a major source of ROS in the cardiovascular system. XO inhibitors （XOIs） have been the cornerstone of the clinical management of gout and conditions associated with hyperuricemia for several decades.

关键词： febuxostat reactive oxygen species xanthine oxidase inhibitors chronic heart failure signaling pathways

Macrophage polarization in diabetic wound healing

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Burns & Trauma 2022年第1期10卷 20-32页

作者： Xingqian Wu Wenjie He Xingrui Mu Ye Liu Junyu Deng Yiqiu Liu Xuqiang Nie College of Pharmacy Zunyi Medical UniversityZunyi 563000China Joint International Research Laboratory of Ethnomedicine of Chinese Ministry of Education Zunyi Medical UniversityZunyi 563000China Key Lab of the Basic Pharmacology of the Ministry of Education Zunyi Medical UniversityZunyi 563000China Cancer and Ageing Research Program School of Biomedical SciencesQueensland University of Technology37 Kent StreetWoolloongabbaBrisbane 4102Australia

Impaired wound healing is one of the severe complications of diabetes.Macrophages have been shown to play a vital role in wound healing.In different wound environments,macrophages are classified into two phenotypes:classically activated macrophages and alternatively activated macrophages.Dysregulation of macrophage phenotypes leads to severely impaired wound healing in diabetes.Particularly,uncontrolled inflammation and abnormal macrophage phenotype are important reasons hindering the closure of diabetic wounds.This article reviews the functions of macrophages at various stages of wound healing,the relationship between macrophage phenotypic dysregulation and diabetic wound healing and the mechanism of macrophage polarization in diabetic wound healing.New therapeutic drugs targeting phagocyte polarization to promote the healing of diabetic wounds might provide a new strategy for treating chronic diabetic wound healing.

关键词： Diabetic wounds Macrophage polarization signaling pathways Wound healing Therapeutics

Emerging roles of long noncoding RNAs in cholangiocarcinoma:Advances and challenges

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Cancer Communications 2020年第12期40卷 655-680页

作者： Yang Yang Xueting Deng Quanpeng Li Fei Wang Lin Miao Qi Jiang Institute of Digestive Endoscopy and Medical Center for Digestive Diseases Second Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210000P.R.China Nanjing Medical University NanjingJiangsu 210000P.R.China Department of Gastroenterology Dongtai People’s HospitalYanchengJiangsu 224000P.R.China

Cholangiocarcinoma(CCA),a cancer with a relatively low incidence rate,is usually associated with poor prognosis.Current modalities for the diagnosis and treatment of CCA patients are still far from satisfactory.In recent years,numerous long noncoding RNAs(lncRNAs)have been identified as crucial players in the development of various cancers,including CCA.Abnormally expressed lncRNAs in CCA,regulated by some upstream molecules,significantly influence the biological behavior of tumor cells and are involved in tumor development through various mechanisms,including interactions with functional proteins,participation in competing for endogenous RNA(ceRNA)regulatory networks,activation of cancer-related signaling pathways and epigenetic modification of gene expression.Furthermore,several lncRNAs are closely associated with the clinicopathological features of CCA patients,and are promising biomarkers for diagnosing and prognostication of CCA.Some of these lncRNAs play an important role in chemotherapy drug resistance.In addition,lncRNAs have also been shown to be involved in the inflammation microenvironment of CCA and malignant outcome of CCA risk factors,such as cholestatic liver diseases.In view of the difficulty of diagnosing CCA,more attention should be paid to detectable lncRNAs in the serum or bile.This review summarizes the recent knowledge on lncRNAs in CCA and provides a new outlook on the molecular mechanisms of CCA development from the perspective of lncRNAs.Moreover,we also discussed the limitations of the current studies and differential expression of lncRNAs in different types of CCA.

关键词： bile biomarkers cancer development cholangiocarcinoma long noncoding RNA molecular mechanisms signaling pathways tumor microenvironment

Network Pharmacology-based Research of Active Components of Albiziae Flos and Mechanisms of Its Antidepressant Effect

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Current Medical Science 2020年第1期40卷 123-129页

作者： Wei-chen XIONG He-zhen WU Yi-yi XIONG Bo LIU Zhou-tao XIE Song-tao WU Yun-feng YAO Yan-fang YANG Faculty of Pharmacy Hubei University of Chinese MedicineWuhan 430065China Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province Wuhan 430061China Collaborative Innovation Center of Traditional Chinese Medicine of New Products for Geriatrics Hubei Province Wuhan 430065China Key Laboratory of Traditional Chinese Medicine Resource and Compound Preparation Ministry of Education Wuhan 430065China

Albiziae Flos(AF)has been experimentally proven to have an antidepressant effect.However,due to the complexity of botanical ingredients,the exact pharmacological mechanism of action of AF in depression has not been completely deciphered.This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF.The methods included collection and screening of chemical components,prediction of depression-associated targets of the active components,gene enrichment,and network construction and analysis.Quercetin and 4 other active components were found to exert an tidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand・wceptor interaction pathways.DRD2,HTR1 A,and SLC6A4 were identified as important targets of the studied bioactive components of AF.This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.

关键词： Albiziae Flos network pharmacology antidepressant active components signaling pathways

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 cells.Activation of B cells via their BCRs involves signaling pathways that are tightly controlled by various regulators.In 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

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

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 cancer.This subtype of breast cancer has improved prognosis due to availability of anti-HER2 therapy.However,drug resistance and tumor recurrence still remains a major concern.Cancer Stem Cells(CSCs)are believed to constitute the subset of cell population that is resistant to drug treatment and possesses characteristics of stem cells.CSCs enable the tumors to thrive despite major insults.This 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 CSCs.Furthermore,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

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

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 cases.However,accurate estimation of mutational effects at the pathway level for such patients remains an open problem.While 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 alterations.Methods: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 mutations.The lung adenocarcinoma and skin cutaneous melanoma datasets from TCGA Pan-Cancer Atlas have been employed to show the utility of the proposed method.Results:We have comprehensively characterized six mutational forks.The number of mutated nodes ranged from one to four depending on the topological characteristics of a fork.Transitional confidences(TCs)have been computed for every possible combination of single-nucleotide alterations in the fork.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 patients.The findings have been largely supported by the evidence from the biomedical literature.Conclusion: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

Dietary isoflavones,the modulator of breast carcinogenesis:Current landscape and future perspectives

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Asian Pacific Journal of Tropical Medicine 2018年第3期11卷 186-193页

作者： Javed Iqbal Banzeer Ahsan Abbasi Ali Talha Khalil Barkat Ali Tariq Mahmood Sobia Kanwal Sayed Afzal Shah Wajid Ali Department of Plant Sciences Quaid-i-Azam University Department of Eastern Medicine and Surgery Qarshi University UNESCO UNISA Africa chair in nanoscience and nanotechnology Nanosciences African Network(NANOAFNET) Department of Zoology University of GujratSub Campus

Breast cancer is a frightful disease and serious concern in women around the world causing significant health care burden in both developed and developing countries. Extensive research work has shown that breast cancer provides strong resistance to chemical agents, U V radiation,and hormonal treatments. It is generally accepted that cell genetics is not the only main reason for breast cancer and genetic risk factors, for example, mutations in RRCAI and BRCA2 genes constitute 5%-10% of all breast cancer rates. Other related factors include age, gender,race, ethnicity, weight, reproductive factors, exo-and endogenous hormonal exposures, oral contraceptives use, ultraviolet radiation, diet, and night work(circadian disruption). Many studies have revealed that dietary isoflavones regulate breast cancer occurrence, recurrence and prognosis. Dietary isoflavones have long been part of Asian population diet and there is a significant increase as compared to dietary isoflavones intake among other populations. Dietary isoflavones are natural phytoestrogens having both estrogenic and anti-estrogenic potentials on breast cancer cells in culture, animal models and in experimental trials. This literature survey provides a comprehensive overview on the tumor preventive and tumor promoting potentials of dietary isoflavones on breast cancer. In addition, this paper provides a literature review of dietary isoflavones and their effects on up-regulation and down-regulation of different signaling pathways, genes and proteins. Finally, future perspectives of dietary isoflavones and breast cancer researchers are also critically discussed, which will provide a deeper insight regarding the inner molecular mechanisms of action.

关键词： Dietary isoflavones Breast cancer signaling pathways Natural phytoestrogens