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Small-molecule agents for cancer immunotherapy

Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu Kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer therapy.They induce long-term tumor regression and overall survival benefit in many types of cancer.With the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for immunotherapy.Small molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively investigated.Monotherapy of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance.Here,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

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Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy

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Neural Regeneration research 2024年第3期19卷 680-686页

作者： Jie Wu Yulei Huang Hanrui Yu Kaixiu Li Shifeng Zhang Guoqing Qiao Xiao Liu Hongmei Duan Yifei Huang Kwok-Fai So Zhaoyang Yang Xiaoguang Li Liqiang Wang Department of Ophthalmology the Third Medical CenterChinese PLA General HospitalBeijingChina The PLA Medical College Department of NephrologyChinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijingChina Department of Ophthalmology Hainan Hospital of Chinese PLA General HospitalSanyaHainan ProvinceChina Medical School of chinese PLA BeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative medicine and Health guangdong Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administrative RegionChina center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina School of engineering medicine Beijing Key Laboratory for Biomaterials and Neural RegenerationBeihang UniversityBeijingChina Beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Big Data-Based Precision MedicineBeihang UniversityBeijingChina

Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic keratopathy are limited.In this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic keratopathy.In the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation model.CTH-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in vivo.Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy.Patients received topical CTH-mNGF twice daily for 8 weeks.Fluorescein sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were evaluated.In total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were enrolled.After 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by fluorescence.Overall,six out of seven eyes had fluorescence staining scores<5.Moreover,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement.An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes.This study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release properties.Its effectiveness in healing corneal epithelial defects in

关键词： chitosan corneal reinnervation murine nerve growth factor neurotrophic keratopathy thermosensitive hydrogel

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A comprehensive review on the potential therapeutic benefits of prospective probiotic Christensenella minuta

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Food Science and Human Wellness 2024年

作者： Yueyao Fan Yuhang Xiao Yingying Zhang Shiqing Zhang Weibin Bai Jiali Chen Department of Food Science and engineering Institute of Food Safety and Nutrition guangdong engineering Technology center of Food Safety Molecular Rapid Detection jinan university State Key Laboratory of Bioactive Molecules and Druggability Assessment jinan university Centre for Cancer and Inflammation research School of chinese medicine Hong Kong Baptist university

Bacterial family Christensenellaceae performed high heritability and associated with human health status. Numerous studies observed that the abundance of Christensenellaceae could be significantly reduced in patients with intestinal diseases or metabolic disorders， inferred that it may be treated as an effective biomarker. Christensenella minuta (C. minuta) was the first member of Christensenellaceae family isolated from human fecal samples. Accumulating evidences suggested that C. minuta may demonstrate a positive bio-therapeutic effects toward unhealthy status. Hence， this review aimed to systematically summarize the characterization of Christensenellaceae under specific health or diseases， and discover its promising application. Besides， the latest studies on the pharmacological research of C. minuta also summarized. Current important literatures grasped the potential health benefits of C. minuta in managing metabolic disorders， gut ecosystem， and inflammation. Whereas， several critical knowledge gaps about the safe and clinical application remain should be addressed in future verification. C. minuta is worthy to be elevated as the next prospective probiotic star in nutraceutical or medical field and should not be overlooked.

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The evolution and significance of medicine and food homology

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Acupuncture and Herbal medicine 2024年第1期4卷 19-35页

作者： Huan Zhong Zhi-Qing Tang Yi-Fang Li Mei Wang Wan-Yang Sun Rong-Rong He guangdong engineering research center of Traditional chinese medicine&disease susceptibility/International Cooperative Laboratory of TCM Modernization and Innovative Drug Development of chinese Ministry of Education(MOE)/guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs research/State Key Laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhouChina Naturalis Biodiversity center Darwinweg RA Leidenthe Netherlands SU Biomedicine BD Leidenthe Netherlands School of Pharmacy Shenyang Pharmaceutical UniversityShenyangChina State Key Laboratory of Quality research in chinese medicine Macao University of Science and TechnologyMacaoChina School of chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization Yunnan University of Chinese MedicineKunmingChina

Historical insights into medicine and food homology(MFH)Evolution of the MFH theory MFH,a basic concept in traditional chinese medicine(TCM),suggests that many materials function as both food and medicine,providing nourishment and simultaneously treating ailments.This concept has evolved significantly throughout TCM history^([1]).Integral to this evolution was the discovery of certain materials with dual purposes during early searches for food.These materials not only offer sustenance and nutrition but are also capable of treating simple illnesses^([2]).

关键词： evolution insight medicine

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RSPSSL:A novel high-fidelity Raman spectral preprocessing scheme to enhance biomedical applications and chemical resolution visualization

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Light(Science & Applications) 2024年第2期13卷 366-386页

作者： Jiaqi Hu Gina Jinna Chen Chenlong Xue Pei Liang Yanqun Xiang Chuanlun Zhang Xiaokeng Chi Guoying Liu Yanfang Ye Dongyu Cui De Zhang Xiaojun yu Hong Dang Wen Zhang Junfan Chen Quan Tang Penglai Guo Ho-Pui Ho Yuchao Li Longqing Cong Perry Ping Shum State Key Laboratory of Optical Fiber and Cable Manufacture Technology Guangdong Key Laboratory of Integrated Optoelectronics IntellisenseDepartment of EEESouthern University of Science and TechnologyShenzhen 518055China College of Optical and Electronic Technology China Jiliang UniversityHangzhou 310018China Department of Nasopharyngeal Carcinoma Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhou 510060China Department of Ocean Science and engineering Southern University of Science and TechnologyShenzhen 518055China Department of Nephrology Chaozhou People’s HospitalChaozhou 521011China Clinical research Design Division Sun Yatsen Memorial HospitalGuangzhouGuangdong 510120China School of Automation Northwestern Polytechnical UniversityXi’anShaanxi 710072China Department of Biomedical engineering The Chinese University of Hong KongHong KongChina guangdong Provincial Key Laboratory of Nanophotonic Manipulation Institute of NanophotonicsJinan UniversityGuangzhou 511443China

Raman spectroscopy has tremendous potential for material analysis with its molecular fingerprinting capability in many branches of science and technology.It is also an emerging omics technique for metabolic profiling to shape precision medicine.However,precisely attributing vibration peaks coupled with specific environmental,instrumental,and specimen noise is problematic.Intelligent Raman spectral preprocessing to remove statistical bias noise and sample-related errors should provide a powerful tool for valuable information extraction.Here,we propose a novel Raman spectral preprocessing scheme based on self-supervised learning(RSPSSL)with high capacity and spectral fidelity.It can preprocess arbitrary Raman spectra without further training at a speed of~1900 spectra per second without human interference.The experimental data preprocessing trial demonstrated its excellent capacity and signal fidelity with an 88%reduction in root mean square error and a 60%reduction in infinite norm(L__(∞))compared to established techniques.With this advantage,it remarkably enhanced various biomedical applications with a 400%accuracy elevation(ΔAUC)in cancer diagnosis,an average 38%(few-shot)and 242%accuracy improvement in paraquat concentration prediction,and unsealed the chemical resolution of biomedical hyperspectral images,especially in the spectral fingerprint region.It precisely preprocessed various Raman spectra from different spectroscopy devices,laboratories,and diverse applications.This scheme will enable biomedical mechanism screening with the label-free volumetric molecular imaging tool on organism and disease metabolomics profiling with a scenario of high throughput,cross-device,various analyte complexity,and diverse applications.

关键词： spectral scheme resolution

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GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

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Acta Pharmaceutica Sinica B 2024年第2期14卷 698-711页

作者： Qiwei Jiang Yong Li Songwang Cai Xingyuan Shi Yang Yang Zihao Xing Zhenjie He Shengte Wang Yubin Su Meiwan Chen Zhesheng Chen Zhi Shi Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineState Key Laboratory of Bioactive Molecules and Druggability AssessmentMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Department of Gastrointestinal Surgery&General Surgery the Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Thoracic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou 510632China Department of Radiation Oncology The Fifth Hospital of Guangzhou Medical UniversityGuangzhou 510150China State Key Laboratory of Quality research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 519000China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA

Glutamate-ammonia ligase(GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

关键词： Gastric cancer GLUL N-Cadherin β-Catenin Enzyme

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Consensus statement on research and application of chinese herbal medicine derived extracellular vesicles-like particles(2023 edition)

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chinese Herbal medicines 2024年第1期16卷 3-12页

作者： Qing Zhao Tong Wang Hongbin Wang Peng Cao Chengyu Jiang Hongzhi Qiao Lihua Peng Xingdong Lin Yunyao Jiang Honglei Jin Huantian Zhang Shengpeng Wang Yang Wang Ying Wang Xi Chen Junbing Fan Bo Li Geng Li Bifeng Liu Zhiyang Li Suhua Qi Mingzhen Zhang Jianjian Zheng Jiuyao Zhou Lei Zheng Kewei Zhao guangdong engineering research center of chinese Herbal Vesicles The Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510378China Guangzhou Key Laboratory of chinese medicine research on Prevention and Treatment of Osteoporosis The Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510378China Institute of Life and Health engineering the First Affiliated HospitalJinan UniversityGuangzhou 510630China School of Pharmaceutical Sciences Guangzhou University of Chinese MedicineGuangzhou 510006China College of Pharmacy Nanjing University of Chinese MedicineNanjing 210046China Institute of Basic medicine Chinese Academy of Medical SciencesBeijing 100005China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310030China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China Department of Bone and Joint Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou 510630China State Key Laboratory of Quality research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoAomen 999078China Shanghai Jiao Tong university Affiliated Sixth People’s Hospital Shanghai 200233China School of Basic Medical Sciences Southern Medical UniversityGuangzhou 510515China School of Life Sciences Nanjing UniversityNanjing 210008China Nanfang Hospital Southern Medical UniversityGuangzhou 510515China Laboratory Animal center Guangzhou University of Chinese MedicineGuangzhou 510405China College of Life Science and Technology Huazhong University of Science and TechnologyWuhan 430074China Nanjing university Medical School Affiliated Nanjing Drum Tower Hospital Nanjing 210008China School of Medical and Technology Xuzhou Medical UniversityXuzhou 221004China School of Basic Medical Sciences Xi’an Jiaotong UniversityXi’an 710065China The First Affiliated Hospital of Wenzhou Medical university WenZhou 325035China

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization,led by the National Expert Committee on research and Application of chinese Herbal Vesicles,research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on research and Application of chinese Herbal Vesicles,Professional Committee on Extracellular Vesicle research and Application,chinese Society of research Hospitals and the guangdong engineering research center of chinese Herbal Vesicles.Based on the collation of relevant literature,we have adopted the Delphi method,the consensus meeting method combined with the nominal group method to form a discussion draft of“Consensus statement on research and application of chinese herbal medicine derived extracellular vesicles-like particles(2023)”.The first draft was discussed in online and offline meetings on October 12,14,November 2,2022 and April and May 2023 on the current status of research,nomenclature,isolation methods,quality standards and research applications of extracellular vesicles of chinese herbal medicines,and 13 consensus opinions were finally formed.At the Third Academic Conference on research and Application of chinese Herbal Vesicles,held on May 26,2023,Kewei Zhao,convenor of the consensus,presented and read the consensus to the experts of the Expert Committee on research and Application of chinese Herbal Vesicles.The consensus highlights the characteristics and advantages of chinese medicine,inherits the essence,and keeps the righteousness and innovation,aiming to provide a reference for colleagues engaged in research and application of chinese herbal vesicles at home and abroad,decode the mystery behind chinese herbal vesicles together,establish a safe,effective and controllable accurate chinese herbal vesicle prevention and treatment system,and build a bridge for chinese medicine to the world.

关键词： chinese herbal medicine extracellular vesicles research application consensus

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Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

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Neural Regeneration research 2024年第2期19卷 409-415页

作者： Hongmei Duan Shulun Li Peng Hao Fei Hao Wen Zhao Yudan Gao Hui Qiao Yiming Gu Yang Lv Xinjie Bao Kin Chiu Kwok-Fai So Zhaoyang Yang Xiaoguang Li Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Engineering MedicineBeihang UniversityBeijingChina Department of Epidemiology and Statistics School of Public Health and ManagementNingxia Medical UniversityYinchuanNingxia Hui Autonomous RegionChina Department of Physical Education Capital University of Economics and BusinessmBeijingChina Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Psychology State Key Lab of Brain and Cognitive SciencesThe University of Hong KongHong Kong Special Administration RegionChina guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative medicine and Health guangdong Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Biomedical engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

关键词： adult endogenous neurogenesis angiogenesis basic fibroblast growth factor-chitosan gel chitosan functional recovery ischemic stroke neural stem cell newborn neuron

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Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba

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Acta Pharmaceutica Sinica B 2024年第1期14卷 1-19页

作者： Weile Ye Jiaojiao Wang Peter JLittle Jiami Zou Zhihua Zheng Jing Lu Yanjun Yin Hao Liu Dongmei Zhang Peiqing Liu Suowen Xu Wencai Ye Zhiping Liu International Cooperative Laboratory of Traditional chinese medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China Jinan UniversityGuangzhou 510632China guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional chinese medicine and New Drugs research College of PharmacyJinan UniversityGuangzhou 510632China State Key Laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhou 510632China Pharmacy Australia Centre of Excellence School of PharmacyUniversity of QueenslandWoolloongabba QLD 4102Australia Sunshine Coast Health Institute and School of Health and Behavioural Sciences University of the Sunshine CoastBirtinya QLD 4575Australia National-Local Joint engineering Lab of Druggability and New Drugs Evaluation Guangdong Provincial Key Laboratory of New Drug Design and EvaluationSun Yat-sen UniversityGuangzhou 510006China School of Pharmacy Bengbu Medical CollegeBengbu 233030China Institute of Endocrine and Metabolic diseases the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a well-known traditional chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries.Preclinical studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease models.Of clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia stroke.Here,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy.We highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and others.Finally,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

关键词： Cardiovascular disease Atherosclerosis Ginkgo biloba Ginkgolide B Endothelial dysfunction LOX-1 PCSK9 PAF-R antagonist

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The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages

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Acta Pharmaceutica Sinica B 2022年第1期12卷 197-209页

作者： Yanping Wu Xiang Luo Qingqing Zhou Haibiao Gong Huaying Gao Tongzheng Liu Jiaxu Chen Lei Liang Hiroshi Kurihara Yi-Fang Li Rong-Rong He guangdong engineering research center of chinese medicine&disease susceptibility Jinan UniversityGuangzhou 510632China International Cooperative Laboratory of Traditional chinese medicine Modernization and Innovative Drug Development of chinese Ministry of Education College of PharmacyJinan UniversityGuangzhou 510632China guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional chinese medicine and New Drugs research College of PharmacyJinan UniversityGuangzhou 510632China Formula-pattern research center School of Traditional Chinese MedicineJinan UniversityGuangzhou 510632China Integrated chinese and Western medicine Postdoctoral research Station Jinan UniversityGuangzhou 510632China Institute of Tumor Pharmacology College of PharmacyJinan UniversityGuangzhou 510632China

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies;however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stressevoked tumor susceptibility, and the stress hormone glucocorticoid(GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor(low-density lipoprotein receptor-related protein-1, LRP1) and the "don’t eat me" signal receptor(signal regulatory protein alpha, SIRPa). Further analysis revealed that GC led to a direct, glucocorticoid receptor(GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevatedgene level of SIRPa by down-regulating mi RNA-4695-3 p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPa axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPa axis may serve as a potential therapeutic strategy for tumor treatment.

关键词： Psychological stress Tumorigenesis Macrophages Phagocytosis LRP1 SIRPa Therapeutic target

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