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Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism

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World Journal of Hepatology 2024年第7期16卷 1051-1066页

作者： Xiao-Li Mei Shu-Yi Wu Si-Lan Wu Xiao-Lin Luo Si-Xing Huang Rui Liu Zhe Qiang Department of pharmacology and toxicology Sichuan-Chongqing Joint Key Laboratory of New Chinese Medicine Creation LaboratoryChongqing Academy of Chinese Materia MedicaChongqing 400061China College of Chinese Medicine Chongqing College of Traditional Chinses MedicineChongqing 402760China Department of Oncology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China College of Pharmacy Chongqing Medical UniversityChongqing 400010China

BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient ***,the molecular mechanisms underlying that remain *** To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and *** A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary *** tissues were collected for western blotting and immunohisto chemistry(IHC)*** accumulation and hepatic fibrosis were detected using oil red staining and Sirius red *** serum samples were collected for biochemical assays and NMR-based metabonomics *** inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against *** MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic *** western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of *** metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic ***,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male *** MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male *** male hormone related metabolic pathways may be the potential therapeutic app

关键词： Hepatic steatosis Inflammation Sex hormone metabolism Male hormone Phosphatase and tensin homolog deleted on chromosome ten

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The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center research Institute Tokyo 104-0045Japan Department of laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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Cellular interplay to 3D in vitro microphysiological disease model:cell patterning microbiota-gut-brain axis

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Bio-Design and Manufacturing 2024年第3期7卷 320-357页

作者： Kamare Alam Lakshmi Nair Souvik Mukherjee Kulwinder Kaur Manjari Singh Santanu Kaity Velayutham Ravichandiran Sugato Banerjee Subhadeep Roy Department of pharmacology and toxicology National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of Pharmaceutical Sciences Assam UniversitySilchar 788011India Department of Pharmaceutical Sciences Guru Ghasidas UniversityKoniBilaspur 495009C.G.India School of Pharmacy and Biomolecular Sciences RCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Tissue Engineering research Group Department of Anatomy and Regenerative MedicineRCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Department of Pharmaceutics National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of Natural Products National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India

The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the *** between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological *** most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune ***,each pathway is intertwined with a complex *** the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative *** paper briefly retraces the possible communication pathways between the gut microbiome and the *** further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the *** diseases also decrease patients’quality of ***,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the *** of MGBA in the laboratory uses many molecular technologies and biomaterial *** and organoids provide a more realistic picture of the cell and tissue structure than *** them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between ***-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

关键词： Microbiota-gut-brain axis Neurodegeneration 3D disease model Organoid Transwell system

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Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~*** statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in *** surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has *** 38,000 people died of cancer in *** National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key laboratory for research and Evaluation of Drug Metabolism&Guangdong Provincial Key laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and Medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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Notum protects against myocardial infarction-induced heart dysfunction by alleviating cardiac fibrosis

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Frigid Zone Medicine 2024年第1期4卷 41-50页

作者： Tongzhu Jin Zhen Ye Ruonan Fang Yue Li Wei Su Qianqian Wang Tianyu Li Hongli Shan Yanjie Lu Haihai Liang laboratory of Frigid Zone Cardiovascular Diseases(SKLFZCD) Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Department of Pharmacy Suqian First HospitalSuqian 223800China research Unit of Noninfectious Chronic Diseases in Frigid Zone(2019RU070) Chinese Academy of Medical SciencesHarbin 150081China

Background and Objective:Cardiac fibrosis is a pathological reparative process that follows myocardial infarctionand is associated with compromised cardiac systolic and reduced cardiac *** Wnt signaling pathway is closely implicated in organ fibrosis,and Notum,a highly conserved secreted inhibitor,modulates Wnt *** objective of this study was to explore the role and mechanism of Notum in cardiac ***:A mouse model of cardiac remodeling was established through left coronary artery ligation surgery,with the addition of Notum injection following myocardial infarction *** protective effect of Notum on myocardial infarction was assessed by evaluating cardiac function,including survival rate,echocardiographic assessment,and cardiac contraction *** cell necrosis and infiltration were confirmed through H&E and Masson *** expression of fibrosis-related genes andβ-catenin pathway markers was detected using Western blot quantificational RT-PCR(qRT-PCR).Additionally,EdU,wound healing,and immunofluorescence staining analyses were performed to detect the effect of Notum's in transforming growth factor beta-1(TGF-β1)induced myofibroblast ***:The administration of Notum treatment resulted in enhanced survival rates,improved cardiac function,and decreased necrosis and infiltration of inflammatory cells in mice subjected to left coronary artery ***,Notum effectively impeded the senescence of cardiac fibroblasts and hindered their pathological transformation into cardiac ***,it significantly reduced collagen production and attenuated the activation of the Wnt/β-catenin *** preliminary investigations successfully demonstrated the therapeutic potential of Notum in both fibroblasts in vitro and in a mouse model of myocardial infarction-induced cardiac fibrosis in ***:Notum inhibition of the Wnt/β-catenin signaling pathway and cardiac fibroblast

关键词： cardiac fibrosis Notum Wnt/β-catenin senescence myocardial infarction

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YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway

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Frigid Zone Medicine 2024年第1期4卷 51-64页

作者： Fangfang Bi Miao Cao Yuquan Wang Qingming Pan Zehong Jing Danyang Bing Lifang Lyu Tong Yu Tianyu Li Xuelian Li Haihai Liang Hongli Shan Yuhong Zhou Department of pharmacology(State-Province Key laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Shanghai Frontiers Science research Center for Druggability of Cardiovascular noncoding RNA Institute for Frontier Medical TechnologyShanghai University of Engineering ScienceShanghai 201620China Department of Basic Medicine Xiamen Medical CollegeXiamen 361023China

Background:Myocardial infarction(MI)is associated with higher morbidity and mortality in the world,especially in cold ***1 is an RNA-binding protein that is required for pathological growth of cardiomyocyte by regulating cell growth and protein *** YBX1,as an individual RNA-binding protein,regulates cardiomyocytes through signaling cascades during myocardial infarction remain largely ***:In vivo,the mouse MI model was induced by ligating the left anterior descending coronary artery(LAD),and randomly divided into sham operation group,MI group,MI+YBX1 knockdown/overexpression group and MI+negative control(NC)*** protective effect of YBX1 was verified by echocardiography and triphenyltetrazolium chloride *** vitro,mitochondrial-dependent apoptosis was investigated by using CCK8,TUNEL staining,reactive oxygen species(ROS)staining and JC-1 staining in hypoxic neonatal mouse cardiomyocytes(NMCMs).Results:YBX1 expression of cardiomyocytes was downregulated in a mouse model and a cellular model on the ischemic *** to mice induced by MI,YBX1 overexpression mediated by adeno-associated virus serotype 9(AAV9)vector reduced the infarcted size and improved cardiac *** of endogenous YBX1 by shRNA partially aggravated ischemia-induced cardiac *** hypoxic cardiomyocytes,YBX1 overexpression decreased lactic dehydrogenase(LDH)release,increased cell viability,and inhibited apoptosis by affecting the expression of apoptosis related proteins,while knockdown of endogenous YBX1 by siRNA had the opposite *** of YBX1 restored mitochondrial dysfunction in hypoxic NMCMs by increasing mitochondrial membrane potential and ATP content and decreasing *** hypoxic NMCMs,YBX1 overexpression increased the expression of phosphorylated phosphatidylinositol 3 kinase(PI3K)/AKT,and the anti-apoptosis effect of YBX1 was eliminated t by LY294002,PI3K/AKT ***:YBX1 protected the heart

关键词： YBX1 PI3K/AKT apoptosis mitochondrial function myocardial infarction

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Toxicological Study of the Hydroalcoholic Extract of a Recipe of Three Plants Used in Traditional Togolese Medicine

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Journal of Biosciences and Medicines 2024年第8期12卷 270-280页

作者： Yao Hoinsou Sossawè Poli Fodoh Clefasse Koula Luckman Gbati Ablam Alognon Tibanguebé Doumongue Minyo Ega Sossa Montant Gérard Akouétévi Toudji Efui Holaly Gbekley Bouraïma Djeri Microbiology and Food Quality Control laboratory (LAMICODA) Higher School of Biological and Food Techniques (ESTBA) University of Lom Lom Togo laboratory of Biomedical Sciences Food and Environmental Health-Research Unit in Biomedical Sciences and Bioactive Substances (LaSBASE-UR-2SB) Higher School of Biological and Food Techniques (ESTBA) University of Lom Lom Togo Department of Biochemistry/Nutrition Laboratory of Biochemistry Applied to Nutrition Faculty of Sciences University of Lom Lom Togo laboratory of Biology Phytochemistry Toxicology Pharmacology and Agrifood Institute African Biomedical Agrifood Societal and Environmental Sciences (IASBASE) Lom Togo

This work consisted of assessing the toxicity of a recipe of three plants used in traditional Togolese medicine. Acute and sub-acute toxicity was assessed according to OECD chemical test guidelines n˚423 dated December 17, 2001 and n˚407 dated October 3, 2008 respectively. Cytotoxicity was assessed using the 3-(4,5-dimethylthiazolyl-2-yl-2,5-diphenyltetrazolium bromide (MTT) test. No significant toxicity was observed after 14 and 28 days, although a dose-dependent decrease in creatinemia was observed in male rats (the recipe to be used to moderate creatinine levels). Cytotoxicity was without effect on NCM 365 cells. The results obtained justify the use of the recipe in traditional medicine.

关键词： Carica papaya Cocos nucifera Persea americana Toxicity Togo

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SP-141 targets Trs85 to inhibit rice blast fungus infection and functions as a potential broadspectrum antifungal agent

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Plant Communications 2024年第2期5卷 169-184页

作者： Xi-Yu Wu Bo Dong Xue-Ming Zhu Ying-Ying Cai Lin Li Jian-Ping Lu Bin Yu Jing-Li Cheng Fei Xu Jian-Dong Bao Ying Wang Xiao-Hong Liu Fu-Cheng Lin State Key laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Institute of BiotechnologyZhejiang UniversityHangzhou 310058Zhejiang ProvinceChina State Key laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Institute of Plant Protection and MicrobiologyZhejiang Academy of Agricultural SciencesHangzhou 310058Zhejiang ProvinceChina Department of pharmacology and Nutritional Science College of MedicineThe University of KentuckyLexingtonKY 40506USA Markey Cancer Center College of MedicineThe University of KentuckyLexingtonKY 40506USA College of Life Sciences Zhejiang UniversityHangzhou 310058Zhejiang ProvinceChina Institute of Pesticide and Environmental toxicology Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and InsectsZhejiang UniversityHangzhou 310058Zhejiang ProvinceChina Institute of Edible Fungi Shanghai Academy of Agricultural SciencesShanghai 201106ShanghaiChina

Rice blast is a devastating disease worldwide,threatening rice production and food *** blast fun-gus Magnaporthe oryzae invades the host via the appressorium,a specialized pressure-generating struc-ture that generates enormous turgor pressure to penetrate the host ***,owing to ongoing evolution of fungicide resistance,it is vitally important to identify new targets and ***,we show that Trs85,a subunit of the transport protein particle III complex,is essential for appressorium-mediated infection in *** explain how Trs85 regulates autophagy through Ypt1(a small guano-sine triphosphatase protein)in *** then identify a key conserved amphipathic a helix within Trs85 that is associated with pathogenicity of *** computer-aided screening,we identify a lead compound,SP-141,that affects autophagy and the Trs85–Ypt1 ***-141 demonstrates a substantial capacity to effectively inhibit infection caused by the rice blast fungus while also exhibiting wide-ranging potential as an antifungal agent with broad-spectrum *** together,our data show that Trs85 is a potential new target and that SP-141 has potential for the control of rice *** thus provide a novel strategy that may help in thefight against rice blast.

关键词： Magnaporthe oryzae rice blast TRAPPIII complex trs85 fungicide

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Improvements in SOD mimic AEOL-10150, a potent broad-spectrum antioxidant

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Military Medical research 2019年第1期6卷 78-88页

作者： Xiao-rui Zhang Wen-xia Zhou Yong-xiang Zhang State Key laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology

AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase(SOD) mimic specifically designed to neutralize reactive oxygen and nitrogen species. research has shown that AEOL-10150 is a potent medical countermeasure against national security threats including sulfur mustard(SM), nerve agent exposure and radiation pneumonitis following a radiological/nuclear incident sufficient to cause acute radiation syndrome(ARS). AEOL-10150 performed well in animal safety studies, and two completed phase 1 safety studies in patients demonstrated that the drug was safe and well tolerated, indicating that AEOL-10150 has potential as a new catalytic antioxidant drug. In this article, we review improvements in AEOL-10150 in preclinical pharmacodynamic studies, especially regarding anti-SM,chlorine gas and radiation exposure studies.

关键词： Catalytic antioxidant Metalloporphyrins Chemical warfare agent Radiation damage Pharmacodynamics Pharmacokinetics

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