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Investigating the molecular mechanism of Chelidonii Herba against liver cancer using network pharmacology and molecular docking validation

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Integrative Medicine Discovery 2024年第22期8卷 1-12页

作者： Ming-Zhi Yang Zi-Xuan Yang Zhang Yu Ju-Min Xie Hubei Key Laboratory of Renal Disease Occurrence and intervention Medical SchoolHubei Polytechnic UniversityHuangshi 435003China

Background:The molecular mechanism of Chelidonii Herba in treating hepatocellular carcinoma was investigated using network pharmacology and molecular docking ***:The main active components of Chelidonii Herba were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database,and the targets of these active ingredients were identified using the SwissTargetPrediction *** related to liver cancer were sourced from GeneCards,therapeutic Targets Database,and Online Mendelian Inheritance in Man *** targets between the active components of Chelidonii Herba and liver cancer were determined using the jvenn online *** protein interaction network was analyzed via STRING database and visualized using Cytoscape *** targets were identified and further analyzed within the protein interaction *** Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted for the intersection targets using the DAVID database to correlate gene *** bubble diagrams for Gene Ontology enrichment analysis and circular diagrams for Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were generated using CNSknowall and SangerBox online *** docking and visualization were performed using AutoDockTools 1.5.7 and PyMOL 2.5.7 software,*** survival and pan-cancer analysis of core targets were conducted using the GEPIA2 online ***:Twelve active components of Chelidonii Herba were identified through screening.A total of 103 intersection targets and 12 core targets were found between these active constituents of Chelidonii Herba and liver *** Herba may exert its effects on liver cancer through these 12 core *** signaling pathways are implicated,including chemical carcinogen-receptor activation,endocrine resistance,HIF-1 signaling pathway,and proteoglycans in ***

关键词： Chelidonii Herba liver cancer network pharmacology molecular docking

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

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Neuroscience Bulletin 2024年第5期40卷 621-634页

作者： Xiuxiu Liu Ying Zhang Yanming Zhao Qian Zhang Feng Han Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases Ministry of EducationNanjing211166China International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical UniversityNanjing211166China Institute of brain Science The Affiliated Brain Hospital of Nanjing Medical UniversityNanjing211166China Gusu School Nanjing Medical UniversitySuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou210019China

Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous *** pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,and endothelium,leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous *** current research on epilepsy treatments primarily centers around anti-seizure drugs,it is imperative to seek effective interventions capable of disrupting *** this end,a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic *** early diagnosis and timely intervention is paramount,as it stands to significantly improve patient prognosis and alleviate the socioeconomic *** this review,we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.

关键词： Epileptogenesis Neurovascular unit Molecular mechanisms Drug targets

Tumor microenvironment-responsive arsenic-loaded layered double hydroxides film with synergistic anticancer and bactericidal activity

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Rare Metals 2024年第3期43卷 1207-1221页

作者： Shun Xing Dong-Hui Wang Hai-Feng Zhang Li-Dan Liu Cheng-Ce Li Chao Wei Jun-Yu Liu Nai-Jian Ge Xuan-Yong Liu State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai200050China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing100049China intervention Center Eastern Hepatobiliary Surgery HospitalThe Third Affiliated Hospital of Naval Medical UniversityShanghai200438China School of Health Sciences and Biomedical Engineering Hebei University of TechnologyTianjin300130China

Malignant obstruction makes gallbladder cancer have a high mortality ***-titanium alloy(nitinol)stents are commonly used as a local intervention to maximize patient survival time,but the stents lack antitumor and antibacterial capacity and are vulnerable to secondary ***-based drugs show good therapeutic promise against gallbladder *** meet clinical *** layered double hydroxides(LDHs)film is constructed on the nitinol,whose arsenite loading amounts rose by 60%after simple heat treatment compared with the conventional anion-exchange *** addition,calcination promotes the dissolution of nickel ions from the LDHs lattice,resulting in a powerful synergistic killing effect on tumor cells together with the released *** importantly,the calcined arsenic-loaded LDHs are sensitive to the acidic microenvironment of tumor tissues,which presents a much lower arsenic and nickel release amount in the normal tissues,guaranteeing its ***,the vertically sharp LDHs nanosheets can synergize with arsenic to achieve effective physical cleavage and chemical killing of adherent and planktonic *** short,we attempt to use arsenic drugs for local interventions and reasonably avoid their toxic side effects,which provides a new design idea for nitinol stents applied in the treatment of gallbladder cancer.

关键词： Nitinol Layered double hydroxides Arsenic Gallbladder cancer

Tumor microenvironment of cancer stem cells:Perspectives on cancer stem cell targeting

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Genes & Diseases 2024年第3期11卷 275-302页

作者： Qianqian Guo Yi Zhou Tianyuan Xie Yin Yuan Huilong Li Wanjin Shi Lufeng Zheng Xiaoman Li Wenzhou Zhang Department of Pharmacy The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450003China Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of PharmacyNanjing University of Chinese MedicineNanjingJiangsu 210023China School of Life Science and Technology Jiangsu Key Laboratory of Carcinogenesis and InterventionChina Pharmaceutical UniversityNanjingJiangsu 211198China

There are few tumor cell subpopulations with stem cell characteristics in tumor tis-sue,defined as cancer stem cells(CSCs)or cancer stem-like cells(CSLCs),which can recon-struct neoplasms with malignant biological behaviors such as invasiveness via self-renewal and unlimited *** microenvironment that CsCs depend on consists of various cellular components and corresponding medium *** these factors existing at a variety of levels and forms,cytokine networks and numerous signal pathways play an important role in signaling *** factors promote or maintain cancer cell stem-ness,and participate in cancer recurrence,metastasis,and *** review aims to summarize the recent molecular data concerning the multilayered relationship between CsCs and CsC-favorable *** also discuss the therapeutic implications of target-ing this synergistic interplay,hoping to give an insight into targeting cancer cell stemness for tumortherapyandprognosis.

关键词： Cancer stem cells Cancerstem-like cells Cellular factors Non-cellularfactors Tumor microenvironment

Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia:A Promising Supportive Therapy

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Chinese Medical Sciences Journal 2024年第2期39卷 102-110页

作者： Rong-Rong Li Wei Chen Xin-Hua Xiao Miao Yu Fan Ping Lian Duan Department of Clinical Nutrition Beijing Key Laboratory of the Innovative Development of Functional Staple and the Nutritional Intervention for Chronic DiseaseChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Endocrinology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Objective To investigate the efficacy of raw corn starch(RCS)in clinical management of insulinoma-induced *** We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively,and analyzed the therapeutic effects of the RCS intervention on blood glucose control,weight change,and its adverse *** The study population consisted of 24 cases of insulinoma patients,7 males and 17 females,aged 46.08±14.15 *** RCS-supplemented diet,all patients had frequent hypoglycemic episodes(2.51±3.88 times/week),concurrent with neuroglycopenia(in 83.3% of patients)and autonomic manifestations(in 75.0% of patients),with the median fasting blood glucose(FBG)of 2.70(interquartile range[IQR]:2.50-2.90)mmol/*** patients'weight increased by 0.38(IQR:0.05-0.65)kg per month,with 8(33.3%)cases developing overweight and 7(29.2%)cases developing *** patients maintained the RCS-supplemented diet until they underwent tumor resection(23 cases)and transarterial chemoembolization for liver metastases(1 case).For 19 patients receiving RCS throughout the day,the median FBG within one week of nutritional management was 4.30(IQR:3.30-5.70)mmol/L,which was a significant increase compared to pre-nutritional level[2.25(IQR:1.60-2.90)mmol/L;P<0.001].Of them,10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment[3.20(IQR:2.60-3.95)mmol/L vs.2.15(IQR:1.83-2.33)mmol/L;P<0.001].Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management[3.50(IQR:2.50-3.65)mmol/L vs.2.20(IQR:1.80-2.60)mmol/L;P<0.001],but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in *** improvement in weight gain was observed upon RCS *** diarrhea(2 cases)and flatulence(1 case)occurred,and were relieved by reduction of RCS ***

关键词： corn starch hypoglycemia insulinoma nutrition therapy

Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1690-1705页

作者： Yan Fu Keyu Shen Hao Wang Shun Wang Xufeng Wang Le Zhu Yan Zheng Tiantian Zou Hongfei Ci Qiongzhu Dong Lun-Xiu Qin Hepatobiliary Surgery Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan University200040 ShanghaiChina Center of interventional Radiology and Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast University87 Dingjiaqiao Road210009 NanjingChina institutes of Biomedical Sciences Fudan University200032 ShanghaiChina Key Laboratory of Whole-period Monitoring and Precise intervention of Digestive Cancer Shanghai Municipal Health CommissionMinhang HospitalFudan UniversityShanghaiChina

Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor *** cells could exhibit a"neural addiction"property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated *** the dysregulated nervous systems might represent a novel strategy for cancer ***,whether intrahepatic cholangiocarcinoma(ICC)could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely *** staining and Enzyme-linked immunosorbent assay suggested that IcC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes IcC metastasis by inducing epithelial-mesenchymal transition(EMT).Acetylcholine promoted iCC metastasis through interacting with its receptor,alpha 5 nicotine acetylcholine receptor subunits(CHRNA5).Furthermore,acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca^(2+)-mediated activation of Ca/calmodulin-dependent protein kinases(CAMKll).In addition,acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of brain-Derived Neurotrophic Factor(BDNF),which formed a feedforward acetylcholine-BDNF axis to promote ICC ***93,a small-molecule inhibitor of CAMKIll,significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC *** all,Acetylcholine/CHRNA5 axis increased the expression ofβ-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKIl/GSK3βsignaling,and the CAMKIl inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

关键词： GSK3β metastasis Alpha

Reduced efficacy of single-dose albendazole against Ascaris lumbricoides, and Trichuris trichiura, and high reinfection rate after cure among school children in southern Ethiopia: a prospective cohort study

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Infectious Diseases of Poverty 2024年第1期13卷 95-96页

作者： Tigist Dires Gebreyesus Eyasu Makonnen Tafesse Tadele Kalkidan Mekete Habtamu Gashaw Heran Gerba Eleni Aklillu Department of Global Public Health Karolinska Institutet Karolinska University Hospital Stockholm Sweden Ethiopian Food and Drug Authority Addis Ababa Ethiopia Center for Innovative Drug Development and therapeutic Trials for Africa College of Health Sciences Addis Ababa University Addis Ababa Ethiopia Departments of Pharmacology and Clinical Pharmacy College of Health Sciences Addis Ababa University Addis Ababa Ethiopia College of Medicine and Health Sciences Hawassa University Hawassa Ethiopia Ethiopian Public Health Institute Addis Ababa Ethiopia

Background Mass drug administration(MDA)program of albendazole to at-risk populations as preventive chemo-therapy is the core public health intervention to control soil-transmitted helminths(STHs).Achieving this goal relies on drug effectiveness in reducing the parasite reservoirs in the community and preventing *** assessed the effcacy of albendazole against STH parasite infection and reinfection status after *** A total of 984 schoolchildren infected with at least one type of STH parasite(hookworm,Ascaris lumbri-coides,Trichuris trichiura)in southern Ethiopia were enrolled and received albendazole and praziquantel in MDA campaign conducted from January to March *** exams at week-4 and at week-8 of post-MDA were done using Kato Katz *** primary outcome was effcacy assessed by cure rate(CR)and fecal egg reduction rates(ERRs)at four weeks of *** secondary outcome was reinfection status defined as parasite egg positivity at eight weeks among those who were cured at 4 weeks of *** comparisons in CR and related factors were assessed with chi-square or Fisher's exact *** of CR were examined through univariate and multi-variate regression *** The overall CR and ERR for hookworm infection were 97.2%(95%CI:94.6-99.4)and 97.02%,*** overall CR and ERR for *** were 71.5%(95%CI:68.3-74.6)and 84.5% *** overall CR and ERR and for *** were 49.5%(95%CI:44.8-54.2)and 68.3%,*** CR among moderate *** infec-tion intensity was 28.6%.Among children cured of hookworm,*** and *** at week 4 post-MDA,4.6%,18.3% and 52.4% became reinfected at week-8 post-MDA,*** lower CR(36.6%)and higher reinfection after cure(60.6%)among *** and *** coinfected children than *** only(CR=69.6%,reinfection rate=15.1%)or *** only infected children(CR=55.6%,reinfection rate=47.1%)was obse

关键词： Soil transmitted helminths Neglected tropical diseases Preventive chemotherapy Albendazole School age children Ethiopia

Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

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Journal of Pharmaceutical Analysis 2024年第3期14卷 348-370页

作者： Binbin Zhao Dongfeng Wei Qinghua Long Qingjie Chen Fushun Wang Linlin Chen Zefei Li Tong Li Tao Ma Wei Liu Linshuang Wang Caishui Yang Xiaxia Zhang Ping Wang Zhanjun Zhang State Key Laboratory of Cognitive Neuroscience and Learning&IDG/McGovern Institute for brain Research Beijing Normal UniversityBeijing100875China Institute of Gerontology Hubei University of Chinese MedicineWuhan430065China Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing100700China Medical School Hubei Minzu UniversityEnshiHubei445000China HuBei University of Science and Technology XianningHubei437100China Institute of brain and Psychological Science Sichuan Normal UniversityChengdu610066China Key Laboratory of Traditional Chinese Medicine Resource and Compound Prescription Ministry of EducationHubei University of Chinese MedicineWuhan430065China Dongfang Hospital Beijing University of Chinese MedicineBeijing100078China Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijing100700China School of Systems Science Beijing Normal UniversityBeijing100875China BABRI centre Beijing Normal UniversityBeijing100875China

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with alterations in synaptic currents and mitochondrial ***,the specific associations between these pathological changes remain *** this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro *** investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,transmission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assessment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular *** results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD ***,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic *** cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular *** intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and ***,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial *** conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

关键词： Alzheimer's disease Synaptic currents Mitophagy Mitochondrial fusion and fission Dengzhan Shengmai capsules

Targeting the organelle for radiosensitization in cancer radiotherapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 52-71页

作者： Xiaoyan Sun Linjie Wu Lina Du Wenhong Xu Min Han Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Department of Radiation Oncology Key Laboratory of Cancer Prevention and InterventionThe Second Afliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang UniversityHangzhou 310058China

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

关键词： Cancer radiotherapy Organelle-target Radiosensitization Boron neutron capture therapy Nanomedicines