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Nuance of inward rectifying potassium(Kir) channel dysfunctions in neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1195-1196页

作者： Benjamin Garland Linlin Ma Griffith institute for drug discovery & School of Environment and Science Griffith University

Neurodegenerative disorders are highly prevalent and diverse in nature. Their manifestation largely depends on the cell types involved, with aberrant inflammatory episodes progressively inducing a constellation of phenotypes that are classified into specific diseases based on their neuropathological traits. The two most prevalent neurodegenerative diseases worldwide,

关键词： K-ATP CHANNELS PARKINSONS-DISEASE MODEL

A novel strategy for treating oncogene-mutated tumors by targeting tumor microenvironment and synergistically enhancing anti-PD-1 immunotherapy

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Cancer Communications 2024年第3期44卷 438-442页

作者： Yingqiang Liu Linjiang Tong Mengge Zhang Qi Zhang Qiupei Liu Fang Feng Yan Li Mengzhen Lai Haotian Tang Yi Chen Meiyu Geng Wenhu Duan Jian Ding Hua Xie Division of Antitumor Pharmacology&State Key Laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiP.R.China University of Chinese Academy of Sciences BeijingP.R.China Department of Chemical and Environmental Engineering University of Nottingham Ningbo ChinaNingboZhejiangP.R.China zhongshan institute for drug discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshanGuangdongP.R.China Shandong Laboratory of Yantai drug discovery Bohai Rim Advanced Research Institute for Drug DiscoveryYantaiShandongP.R.China Small-Molecule drug Research Center Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiP.R.China

Oncogenes are critical factors in tumorigenesis of diverse cancer types and play essential roles in tumor immune escape.Mutations in Kirsten rat sarcoma viral oncogene homolog(KRAS)and epidermal growth factor receptor(EGFR)are among the most frequent gain-of-function alterations[1].After many years of in-depth research,inhibitors targeting EGFR or KRAS mutations have been successfully developed,however,their clinical benefit is relatively limited,and they will inevitably encounter the challenge of drug resistance.The emergence of resistance is attributed to secondary mutations in driver genes and other complicated factors.

关键词： alterations KRAS sarcoma

Anti-inflammatory germacrane-type sesquiterpene lactones from Vernonia sylvatica

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Chinese Journal of Natural Medicines 2024年第6期22卷 568-576页

作者： WANG Min LI Han HU Bintao TANG Chunping XU Hui KE Changqiang XIE Zuoquan YE Yang YAO Sheng State Key Laboratory of drug Research&Natural Products Research Center Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China School of Life Science and Technology Shanghai Tech UniversityShanghai 201210China State Key Laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China zhongshan institute for drug discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshan 528400China

Nine new germacranolides,sylvaticalides A−H(1-9),and three known analogues(10-12)were isolated from the aeri-al part of Vernonia sylvatica.Their structures were established using comprehensive spectroscopic analysis,including high-resolution electrospray ionization mass spectroscopy(HR-ESI-MS)and 1D and 2D nuclear magnetic resonance(NMR)spectra.Their absolute configurations were determined by X-ray diffraction experiments.The anti-inflammatory activities of all isolated compounds were as-sessed by evaluating their inhibitory effects on the nuclear factor kappa B(NF-κB)pathway,which was activated by lipopolysacchar-ide(LPS)-stimulated human THP1-Dual cells,and the interferon-stimulated gene(ISG)pathway,activated by STING agonist MSA-2 in the same cell model.Compounds 1,2 and 6 showed inhibitory effects on the NF-κB and ISG signaling pathways,with IC_(50)values ranging from 4.12 to 10.57μmol·L^(−1).

关键词： Vernonia sylvatica Germacrane-type sesquiterpene lactone Sylvaticalides A−H Anti-inflammatory NF-κB path-way ISG pathway

AI enhances drug discovery and development

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National Science Review 2024年第3期11卷 52-54页

作者： Fang Bai Shiliang Li Honglin Li Shanghai institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech University Lingang Laboratory Innovation Center for AI and drug discovery East China Normal University

The advent of the third wave of artificial intelligence(AI) heralds a new era in drug discovery. AI-powered techniques can be characteristic of identifying features that are difficult for humans to interpret from big ...

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Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications

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World Journal of Diabetes 2024年第3期15卷 572-574页

作者： Asis Bala Pharmacology and drug discovery Research Laboratory Division of Life SciencesInstitute of Advanced Study in Science and TechnologyGuwahati 781035AssamIndia

The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

关键词： Diabetes Cardiovascular complication Advanced glycation end products Reactive oxygen species Reactive nitrogen species Peroxynitrite

Composition analysis of Compound Shenhua Tablet,a seven-herb Chinese medicine for IgA nephropathy:evaluation of analyte-capacity of the assays

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Chinese Journal of Natural Medicines 2024年第2期22卷 178-192页

作者： ZHANG Haiyan WANG Qiuyue WANG Jianan ZHANG Sichao JIA Weiwei HE Ning XIA Xiaoyan WANG Ting LAI Liyu LI Jiaying DU Jing OLALEYE Olajide E CHEN Xiangmei YANG Junling LI Chuan Graduate School Tianjin University of Traditional Chinese MedicineTianjin 301617China State Key Laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Pharmacy University of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100049China Department of Nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People’s Liberation ArmyNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing 100853China zhongshan institute for drug discovery Zhongshan 528400China Haihe Laboratory of Modern Chinese Medicine Tianjin 301617China

Compound Shenhua Tablet,a medicine comprising seven herbs,is employed in treating IgA nephropathy.This study aimed to meticulously analyze its chemical composition.Based on a list of candidate compounds,identified through extensive literature review pertinent to the tablet’s herbal components,the composition analysis entailed the systematic identification,characterization,and quantification of the constituents.The analyte-capacity of LC/ESI-MS-based and GC/EI-MS-based assays was evaluated.The identified and characterized constituents were quantified to determine their content levels and were ranked based on the constituents’daily doses.A total of 283 constituents,classified into 12 distinct categories,were identified and characterized in the Compound Shenhua Tablet.These constituents exhibited content levels of 1−10982μg·g^(−1),with daily doses of 0.01−395μmol·d^(−1).The predominant constituents,with daily doses of≥10μmol·d^(−1),include nine organic acids(citric acid,quinic acid,chlorogenic acid,cryptochlorogenic acid,gallic acid,neochlorogenic acid,isochlorogenic acid C,isochlorogenic acid B,and linoleic acid),five iridoids(specnuezhenide,nuezhenoside G13,nuezhenidic acid,secoxyloganin,and secologanoside),two monoterpene glycosides(paeoniflorin and albiflorin),a sesquiterpenoid(curzerenone),a triterpenoid(oleanolic acid),and a phenylethanoid(salidroside).Additionally,there were 83,126,and 55 constituents detected in the medicine with daily doses of 1–10,0.1–1,and 0.01–0.1μmol·d^(−1),respectively.The combination of the LC/ESI-MS-based and GC/EI-MS-based assays demonstrated a complementary relationship in their analyte-capacity for detecting the constituents present in the medicine.This comprehensive composition analysis establishes a solid foundation for further pharmacological research on Compound Shenhua Tablet and facilitates the quality evaluation of this complex herbal medicine.

关键词： Compound Shenhua Tablet Composition analysis Analyte-capacity

Virtual reality-based cognitive-behavioural therapy for the treatment of anxiety in patients with acute myocardial infarction:a randomised clinical trial

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General Psychiatry 2024年第2期37卷 189-196页

作者： Yuanyuan Li Juan Peng Pingyuan Yang Jiajun Weng Yan'e Lu Jiajia Liu Shikun Xu Lihua Guan Dong Huang Qibing Wang Juying Qian Zexin Zhao Yabin Wei Junbo Ge Xiao Huang Department of Psychological Medicine Zhongshan Hospital Fudan UniversityShanghaiChina Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesNational Clinical Research Center for Interventional MedicineShanghaiChina Department of Psychological Medicine Shanghai Geriatric Medical CenterShanghaiChina School of Nursing Peking UniversityBeijingChina Beijing Key Laboratory of drug Dependence Research National Institute on Drug DependencePeking UniversityBeijingChina

Background The presence of mental health conditions is pervasive in patients who experienced acute myocardial infarction(AMI),significantly disrupting their recovery.Providing timely and easily accessible psychological interventions using virtual reality-based cognitive-behavioural therapy(VR-CBT)could potentially improve both acute and long-term symptoms affecting their mental health.Aims We aim to examine the effectiveness of VR-CBT on anxiety symptoms in patients with AMI who were admitted to the intensive care unit(ICU)during the acute stage of their illness.Methods In this single-blind randomised clinical trial,participants with anxiety symptoms who were admitted to the ICU due to AMI were continuously recruited from December 2022 to February 2023.Patients who were Han Chinese aged 18-75 years were randomly assigned(1:1)via block randomisation to either the VR-CBT group to receive VR-CBT in addition to standard mental health support,or the control group to receive standard mental health support only.VR-CBT consisted of four modules and was delivered at the bedside over a 1-week period.Assessments were done at baseline,immediately after treatment and at 3-month follow-up.The intention-to-treat analysis began in June 2023.The primary outcome measure was the changes in anxiety symptoms as assessed by the Hamilton Anxiety Rating Scale(HAM-A).Results Among 148 randomised participants,70 were assigned to the VR-CBT group and 78 to the control group.The 1-week VR-CBT intervention plus standard mental health support significantly reduced the anxiety symptoms compared with standard mental health support alone in terms of HAM-A scores at both post intervention(Cohen’s d=−1.27(95%confidence interval(CI):−1.64 to−0.90,p<0.001)and 3-month follow-up(Cohen’s d=−0.37(95%CI:−0.72 to−0.01,p=0.024).Of the 70 participants who received VR-CBT,62(88.6%)completed the entire intervention.Cybersickness was the main reported adverse event(n=5).Conclusions Our results indicate that VR-CBT can significantly reduce post-AMI anxiety at t

关键词： admitted behaviour treatment

Total synthesis of a putative yuzurimine-type Daphniphyllum alkaloid C_(14)–epi-deoxycalyciphylline H

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Chinese Chemical Letters 2024年第4期35卷 336-339页

作者： Jingping Hu Jing Xu Shenzhen Grubbs institute and Department of Chemistry and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule drug discovery and Synthesis Southern University of Science and TechnologyShenzhen 518055China

One of the largest subfamilies within the famous Daphniphyllum alkaloid family is made up of the yuzurimine-type(or macrodaphniphyllamine-type) alkaloids. Their complex aza-polycyclic caged structures, several contiguous stereogenic centers, and vicinal all-carbon quaternary centers make these alkaloids formidable challenge for synthetic chemists. Recently, synthesis of these alkaloids has received extensive attention from our community. Herein, we wish to report the total synthesis of C_(14)–epideoxycalyciphylline H, a putative member of yuzurimine-type alkaloid subfamily. Key transformations employed in our approach include an intramolecular Prins reaction and a Pd-catalyzed enyne cycloisomerization. In addition, synthesis of a daphnezomine L-type alkaloid, paxdaphnidine A, was also studied.

关键词： Total synthesis Daphniphyllum alkaloids Yuzurimine-type alkaloids Prins reaction Enyne cycloisomerization

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Transient receptor potential channels and calcium dysregulation: a pathogenic duo in Parkinson's disease

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Neural Regeneration Research 2025年第3期20卷 808-810页

作者： Iqira Saeed Linlin Ma Griffith institute for drug discovery Griffith UniversityNathanBrisbaneQLDAustralia School of Environment and Science Griffith University NathanBrisbaneQLDAustralia

Parkinson's disease(PD) has a complex and multifactorial pathophysiology. Various studies, conducted both in pre-clinical models and PD patients, have reported a link between the disruption of calcium(Ca^(2+)) homeostasis and the subsequent development of PD. Ca^(2+) regulation is crucial for neuronal survival, differentiation,exocytosis at synapses,gene transcription,and proliferation.

关键词： homeostasis clinical subsequent

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