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Investigating the Potential Mechanism of Huazhi Rougan Granules Against Alcoholic Liver Disease by Network Pharmacology and Experiment

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 191-203页

作者： Ying-Ying Tan Ying-Ying Liu Yi-Yan Zhai Yi-Xuan Wang Zhi-Shan Wu Antony Stalin Guo-Liang Cheng Bing Li Chao Wu Zhi-Hong Huang Shan Lu Xiao-Tian Fan Zheng Zhao Jia-Rui Wu Department of clinical Chinese Pharmacy School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijingChina Department of Bioinformatics Institute of Fundamental and Frontier SciencesUniversity of Electronic Science and Technology of ChinaChengduChina Department of Traditional Chinese Medicine State Key Laboratory of Generic Manufacture Technology of Chinese Traditional MedicineLinyiChina Department of clinical Medicine Beijing Zest Bridge Medical Technology Inc.BeijingChina

Objective: Huazhi Rougan granules(HRGs) are a promising drug to improve alcoholic liver disease(ALD), but its mechanism remains unclear. Materials and Methods: Network pharmacology, molecular docking, and animal experiments were used to reveal the potential mechanism of HRG against ALD. Results: A total of 245 potential targets of HRG against ALD were obtained. Functional enrichment analysis suggests that HRG could synergistically regulate various biological pathways to exert therapeutic effects on ALD. Molecular docking showed that the key targets exhibited the good binding ability with the key compounds. The in vivo experiments showed that HRG can effectively alleviate pathological changes in liver tissue, improve blood lipid levels, antioxidant stress ability, and liver function, and reduce the release of inflammatory cytokines in the liver. Conclusions: This study reflects that HRG is an effective strategy for treating ALD, providing a basis for revealing the prevention and treatment mechanisms of ALD.

关键词： Alcoholic liver disease Huazhi Rougan granules inflammatory response network pharmacology

Versatile strategies for adult neurogenesis:avenues to repair the injured brain

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Neural Regeneration Research 2024年第4期19卷 774-780页

作者： Junyi Zhao Siyu Liu Xianyuan Xiang Xinzhou Zhu The Brain Cognition and Brain Disease Institute(BCBDI) Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences Faculty of Life and Health Sciences Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences Shenzhen-Hong Kong Institute of Brain Science-Shenzhen fundamental Research Institutions

Brain injuries due to trauma or stroke are major causes of adult death and ***,few interventions are effective for post-injury repair of brain *** a long debate on whether endogenous neurogenesis actually happens in the adult human brain,there is now substantial evidence to support its *** neurogenesis is usually significantly stimulated by injury,the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually ***,exogenous stem cell transplantation has shown promising results in animal models,but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical ***,a high focus was placed on glia-to-neuron conversion under single-factor *** some inspiring results,the validity of this strategy is still *** this review,we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain *** also discuss their advantages and drawbacks,as to provide a comprehensive account of their potentials for further studies.

关键词： adult neurogenesis glia-to-neuron conversion ischemic stroke neurogenic niche neuroinflammation stem cell transplantation traumatic brain injury

Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2598-2612页

作者： Jinbo Hu Wen Liu Yi Zou Chenyang Jiao Jiazhen Zhu Qiang Xu Jianjun Zou Yang Sun Wenjie Guo State Key Laboratory of Pharmaceutical Biotechnology Nanjing Drum Tower HospitalSchool of Life SciencesNanjing UniversityNanjing 210093China Department of clinical Pharmacology Nanjing First HospitalNanjing Medical UniversityNanjing 210006China Jiangsu Key Laboratory of New Drug Research and clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China

Src homology 2 domain-containing tyrosine phosphatase 2(SHP2)is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth,differentiation,and *** activation of SHP2 has been shown to have a therapeutic effect in colitis and Parkinson's ***,the identification of SHP2 activators and a complete understanding of their mechanism is *** used a two-step screening assay to determine a novel allosteric activator of SHP2 that stabilizes it in an open *** acid was identified as a suitable *** binding to R362,K364,and K366 in the active center of the PTP domain,oleanolic acid maintained the active open state of SHP2,which facilitated the binding between SHP2 and its *** oleanolic acid-activated SHP2 hindered Th17 differentiation by disturbing the interaction between STAT3 and IL-6Rαand inhibiting the activation of ***,via the activation of SHP2 and subsequent attenuation of the STAT3-Th17 axis,oleanolic acid effectively mitigated colitis in *** protective effect was abrogated by SHP2 knockout or administration of the SHP2 inhibitor *** findings underscore the potential of oleanolic acid as a promising therapeutic agent for treating inflammatory bowel diseases.

关键词： Oleanolic acid SHP2 STAT3 Th17 Colitis Allosteric activator

CMKLR1 senses chemerin/resolvin E1 to control adipose thermogenesis and modulate metabolic homeostasis

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fundamental Research 2024年第3期4卷 575-588页

作者： Zewei Zhao Siqi Liu Bingxiu Qian Lin Zhou Jianglin Shi Junxi Liu Lin Xu Zhonghan Yang Department of biochemistry Molecular Cancer Research CenterSchool of MedicineSun Yat-sen UniversityShenzhenGuangdong 518107China Department of biochemistry Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China School of Public Health Sun Yat-sen UniversityGuangzhouGuangdong 510080China

Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of brown fat in ***,β3-AR has low expression in human adipose tissue,precluding its activation as a standalone clinical *** study aimed at identifying a potential GPCR target to induce beige *** found that chemerin chemokine-like receptor 1(CMKLR1),one of the novel GPCRs,mediated the development of beige fat via its two ligands,chemerin and resolvin E1(RvE1).The RvE1 levels were decreased in the obese mice,and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat ***,despite sharing the same receptor as RvE1,the chemerin levels were increased in obesogenic conditions,and chemerin treatment led to an augmented obese phenotype and a decline of beige fat ***,RvE1 and chemerin induced or restrained the development of beige fat,respectively,via the mechanistic target of rapamycin complex 1(mTORC1)signaling *** further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of *** conclusion,our study showed that RvE1 and chemerin affected metabolic homeostasis differentially,suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.

关键词： Obesity Insulin resistance Thermogenesis CMKLR1 Resolvin E1 Chemerin

Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration

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International Journal of Oral Science 2024年第2期16卷 306-321页

作者： Jiayi Wu Feifei Li Peng Yu Changhao Yu Chuyi Han Yitian Wang Fanyuan Yu Ling Ye State Key Laboratory of Oral Diseases&National Center for Stomatology&National clinical Research Center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National clinical Research Center for Oral Diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National clinical Research Center for Oral Diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal *** extensive studies on mineralized parenchymal tissue rebuilding,regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances *** knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic *** to date,the absence of promising therapeutic biomaterials/scaffolds *** reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of *** address these issues,in this study,we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial *** data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses.A feasible scaffold,polylactic acid electrospinning membrane(PLA),was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center,meanwhile supporting proper osteointegration with defect bony ***,transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were *** study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing,offering clinicians potential choices for regenerating such complicated injuries.

关键词： injuries healing suture

Fe-Zn alloy, a new biodegradable material capable of reducing RoS and inhibiting oxidative stress

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Regenerative Biomaterials 2024年第2期3卷 114-122页

作者： Shuaikang Yang Weiqiang Wang Yanan Xu Yonghui Yuan Shengzhi Hao School of Materials Science and Engineering Dalian University of TechnologyDalian 116024PR China clinical Research Center for Malignant Tumor of Liaoning Province Cancer Hospital of Dalian University of TechnologyShenyang 110042PR China

Fe-based biodegradable materials have attracted significant attention due to their exceptional mechanical properties and favorable ***,research on Fe-based materials mainly focuses on regulating the degradation ***,excessive release of Fe ions during material degrada-tion will induce the generation of reactive oxygen species(ROS),leading to oxidative stress and ***,the con-trol of RoS release and the improvement of biocompatibility for Fe-based materials are very *** this study,new Fe-Zn alloys were prepared by electrodeposition with the intention of using Zn as an antioxidant to reduce oxidative damage during alloy ***,the impact of three potential degra-dation ions(Fe^(2+),Fe^(3+),Zn^(2+))from the Fe-Zn alloy on human endothelial cell(EC)activity and migration ability was ***,cell adhesion,cell activity,ROs production and DNA damage were assessed at various locations surrounding the ***,the influence of different concentrations of Zn^(2+) in the medium on cell viability and ROS production was *** levels of ROS exhibited evident toxic effects on ECs and promoted DNA *** an antioxidant,Zn?+effectively reduced ROS production around Fe and improved the cell viability on its surface at a concentration of 0.04 mmol/*** findings demonstrate that Fe-Zn alloy can attenuate the ROS generated from Fe degradation therebyenhancingcytocompatibility.

关键词： biodegradable iron Fe-Zn alloys reactive oxygen species oxidative stress cytocompatibility

UniBind:a novel artificial intelligence-based prediction model for SARS-CoV-2 infectivity and variant evolution

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Signal Transduction and Targeted Therapy 2024年第1期9卷 14-15页

作者： Qihong Yan Jincun Zhao State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

In a recent study published in Nature Medicine,Wang et *** an excellent framework called UniBind based on artificial intelligence(AI),which enables accurately predicting infectivity of SARS-CoV-2 variants and evolutionary trends of future viral variants.1 This computational method holds the possibility to not only serve as a valuable early-warning tool for monitoring potential pathogenic SARS-CoV-2 variants but also facilitate fundamental research on protein-protein interactions(PPIs).

关键词： artificial Bind prediction

Prognostic significance of SOX2 for chemotherapeutic patients with oral squamous cell carcinoma

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Journal of Pharmaceutical Analysis 2024年第4期14卷 619-621页

作者： Xuefeng Zhang Hao Xu Tong Zhou Xiaodong Feng Qianming Chen State Key Laboratory of Oral Diseases National Center of StomatologyNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041China

Oral squamous cell carcinoma(OSCC)is the most common oral cancers worldwide,accounting for over 90%of all oral malignancies[1].Despite encouraging improvements in therapeutic approaches,including surgical resection,chemotherapy,and radiotherapy,the five-year overall survival rate of OSCC has not been improved significantly over the past decades,mainly due to the high ratio of tumor recurrence and metastasis.

关键词： SOX2 therapeutic squamous

Emerging clinical relevance of microbiome in cancer:promising biomarkers and therapeutic targets

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Protein & Cell 2024年第4期15卷 239-260页

作者： Jia-Hao Dai Xi-Rong Tan Han Qiao Na Liu State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510050China

The profound influence of microbiota in cancer initiation and progression has been under the spotlight for years,leading to numerous researches on cancer microbiome entering clinical *** promising biomarkers and therapeutic targets,the critical involvement of microbiota in cancer clinical practice has been increasingly ***,recent progress in this field is *** describe the potential of tumor-associated microbiota as effective diagnostic and prognostic biomarkers,*** addition,we highlight the relationship between microbiota and the therapeutic efficacy,toxicity,or side effects of commonly utilized treatments for cancer,including chemotherapy,radiotherapy,and *** that microbial factors influence the cancer treatment outcome,we further summarize some dominating microbial interventions and discuss the hidden risks of these *** review aims to provide an overview of the applications and advancements of microbes in cancer clinical relevance.

关键词： microbiome cancer diagnosis prognosis therapy