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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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Research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network Research Center Sungkyunkwan University School of MedicineSuwonKorea Research institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information Research institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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Platelet-derived microparticles and their cargos: The past, present and future

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 72-88页

作者： Jingwen Guo Bufeng Cui Jie Zheng Chang Yu Xuran Zheng Lixin Yi Simeng Zhang Keke Wang Department of pharmacy The First Hospital of China Medical UniversityShenyang 110001 China School of pharmacy China Medical UniversityShenyang 110122China Key Laboratory of Medical Cell Biology of Ministry of Education Key Laboratory of Major Chronic Diseases of Nervous System of Liaoning ProvinceHealth Sciences Institute of China Medical UniversityShenyang 110122China Department of pharmacy The Fourth Affiliated Hospital of China Medical UniversityShenyang 110032China Department of Medical Oncology the First Hospital of China Medical UniversityShenyang 110001China

All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.

关键词： Platelet-derived particles Application Heter ogeneity Potential and limitations

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Mapping COVID-19 in India:Southern states at the forefront of new JN.1 variant

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Asian Pacific Journal of Tropical Medicine 2024年第1期17卷 1-3页

作者： Rabin Debnath Arshdeep Singh Kushal Seni Anjali Sharma Viney Chawla Pooja A Chawla Department of Pharmaceutical Chemistry ISF College of PharmacyG.T RoadGhal KalanMogaPunjab142001India Department of Pharmaceutical Analysis ISF College of PharmacyG.T RoadGhal KalanMogaPunjab142001India University institute of Pharmaceutical Sciences and Research Baba Farid University of Health SciencesFaridkotPunjabIndia

A new variant,JN.1,stemming from the omicron subvariant BA.2.86,garnered the attention of the World Health Organization(WHO)as a"variant of interest."Despite its rapid global spread,especially in the US,Canada,France,Singapore,Sweden[1],and the UK,JN.1 is considered to pose minimal *** vaccinations are believed to remain effective against *** WHO underscores the importance of maintaining immunization records amid co-occurring respiratory illnesses,and epidemiologists recommend monitoring hospitalizations,particularly in areas with low vaccination rates.

关键词： Canada Mapping spite

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Isoimperatorin alleviates acetic acid-induced colitis in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第4期14卷 147-153页

作者： Saied Goodarzi Amir Hossein Abdolghaffari Behnaz Najafi Mostafa Pirali Hamedani Saeed Tavakoli Mahshad Marvi Maryam Baeeri Narguess Yassa Abbas Hadjiakhoondi Mohammad Abdollahi Zahra Tofighi Medicinal Plants Research Center Faculty of PharmacyTehran University of Medical SciencesTehranIran Department of Toxicology and Pharmacology Faculty of PharmacyTehran Medical SciencesIslamic Azad UniversityTehranIran Department of Pharmacognosy Faculty of PharmacyTehran University of Medical SciencesTehranIran Medicinal Plants Research Center Institute of Medicinal PlantsACECRKarajIran International Campus School of pharmacy Tehran University of Medical SciencesTehranIran Toxicology and Diseases group The Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran Department of Toxicology and Pharmacology Faculty of PharmacyTehran University of Medical SciencesTehranIran

Objective:To investigate the effect of isoimperatorin on histopathological and biochemical changes in acetic acid-induced colitis ***:Colitis was induced by intracolonic administration of acetic acid solution(4%v/v)in *** were divided into six groups including the sham group,the negative control group,the dexamethasone-treated group,and the groups treated with isoimperatorin(0.1,1,and 10 mg/kg/d by gavage).The treatments were administered for three days and then colonic status was assessed by macroscopic,histopathological,and biochemical ***:Isoimperatorin significantly alleviated colonic damage in a dose-dependent manner and improved histological changes in rats with acetic acid-induced *** also significantly reduced myeloperoxidase,TNF-α,IL-1β,and malodialdehyde ***:Isoimperatorin alleviates acetic acid-induced colitis in rats and may be a potential therapeutic agent for the treatment of colitis.

关键词： Isoimperatorin Inflammatory bowel disease Acetic acid Colitis TNF-α IL-1β

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Beyond boundaries:Neuroprotective effects of steroids and ecdysteroids in SH-SY5Y cells-A systematic review

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Neuroprotection 2024年第2期2卷 151-166页

作者： Bizhar Ahmed Tayeb PhD Isaac Kinyua Njangiru PhD Renata Minorics PhD institute of Pharmacodynamics and Biopharmacy Faculty of PharmacyUniversity of SzegedSzegedHungary

Steroids and ecdysteroids have been shown to exhibit a range of biological effects,including anti-inflammatory,anticancer,and *** systematic review aims to highlight the evidence-based neuroprotective and antioxidant effects of steroids and ecdysteroids in SH-SY5Y neuroblastoma cells.A comprehensive literature search was conducted on May 11,2023,without publication source restrictions,using various electronic databases,including PubMed,Web of Science(WoS),Scopus,and Cumulative Index toNursing and Allied Health *** 103articles,only20 studies were included for investigating the neuroprotective effects of steroids and ecdysteroids in SH-SY5Y cells exposed to oxidative stress or neurotoxic *** risk of bias and quality assessment of the included studies were evaluated in accordance with the Nature Publication Quality Improvement Project specific *** selected studies reported the antioxidant effects of the tested compounds on SH-SY5Y cells and demonstrated their ability to scavenge free radicals and prevent lipid *** findings suggest that neurosteroids have potential therapeutic applications for the prevention and treatment of neurodegenerative diseases characterized by oxidative stress and neuronal *** studies have investigated the molecular mechanisms underlying the neuroprotective and antioxidant effects of steroids and ecdysteroids in SH-SY5Y *** mechanisms include the activation of antioxidant enzymes,such as superoxide dismutase and glutathione peroxidase,and the modulation of various signaling pathways,including the phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase/extracellular signal-regulated kinase *** review provides evidence that the tested compounds have remarkable neuroprotective and antioxidant effects in human neuroblastoma SH-SY5Y cells.

关键词： antiapoptotic cytoprotective neuroblastoma neurosteroids oxidative stress SH-Y5Ycells

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C-phycocyanin shows neuroprotective effect against rotenone-induced Parkinson’s disease in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 279-287页

作者： Hritik Rathod Ritu M.Soni Jigna S.Shah Department of Pharmacology Institute of Pharmacy Nirma UniversityAhmedabadGujaratIndia

Objective:To investigate the neuroprotective effect of C-phycocyanin in a mouse model of rotenone-induced Parkinson’s ***:C-phycocyanin(50 mg/kg,i.p.,daily)was administered to rotenone(30 mg/kg,p.o.,daily)treated mice for 28 *** studies(Y-maze,rotarod,round beam walk,and wire-hang tests)were carried out to assess neurobehavioral *** and malondialdehyde were determined in both serum and striatal *** proteins(AKT,AMPK,NF-κB,BDNF,and alpha-synuclein)in the striatum were estimated using *** analyses(hematoxylin and eosin stainning as well as Nissl staining)were carried out to assess structural abnormalities in the ***:C-phycocyanin significantly increased BDNF levels and decreased alpha-synuclein *** also slightly upregulated AMPK and AKT levels without significant difference compared with the rotenone ***,rotenone-induced elevated oxidative stress and structural abnormalities in the striatum were markedly mitigated by ***:C-phycocyanin might have potential neuroprotective effects against Parkinson’s *** studies are warranted to verify its efficacy and to understand the molecular mechanisms behind the neuroprotective effects of C-phycocyanin in Parkinson’s disease.

关键词： Parkinson’s disease C-phycocyanin Alphasynuclein BDNF Oxidative stress Rotenone

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Mitigating gut immune adverse effects in CTLA-4 blockade for antitumor efficacy

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Science China(Life Sciences) 2024年第7期67卷 1539-1541页

作者： Shijun He Jianping Zuo Zemin Lin Laboratory of Immunopharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Innovation Research institute of Traditional Chinese Medicine Shanghai University of Traditional Chinese MedicineShanghai 201203China School of pharmacy University of Chinese Academy of SciencesBeijing 100049China

By creating an immune checkpoint blockade-induced colitis model,Lo et al.(2024)have suggested a strategy for alleviating gastrointestinal immune-related adverse events while preserving the antitumor stimulatory effect... 详细信息

关键词： immune gastrointestinal

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Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent

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Acta Pharmaceutica Sinica B 2024年第2期14卷 729-750页

作者： Xin Chen Xianggang Mu Lele Ding Xi Wang Fei Mao Jinlian Wei Qian Liu Yixiang Xu Shuaishuai Ni Lijun Jia Jian Li State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell MetabolismFrontiers Science Center for Materiobiology and Dynamic ChemistryShanghai Key Laboratory of New Drug DesignSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China Cancer institute Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China College of pharmacy Jinan UniversityGuangzhou 510632China

Chemotherapy-induced complications,particularly lethal cardiovascular diseases,pose significant challenges for cancer *** intertwined adverse effects,brought by cancer and its complication,further complicate anticancer therapy and lead to diminished clinical *** supplementation of cardioprotective agents falls short in addressing these *** bifunctional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events *** repurposing was naturally endowed with co-therapeutic potential of two indications,implying a unique chance in the development of bi-functional ***,we further proposed a novel“trilogy of drug repurposing”strategy that comprises function-based,targetfocused,and scaffold-driven repurposing approaches,aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional *** function-based repurposing,a cardioprotective agent,carvedilol(CAR),was identified as a potential neddylation inhibitor to suppress lung cancer *** target-focused SAR studies and scaffold-driven drug design,we synthesized 44 CAR derivatives to achieve a balance between anticancer and ***,optimal derivative 43 displayed promising bi-functional effects,especially in various self-established heart failure mice models with and without ***,the present study validated the practicability of the“trilogy of drug repurposing”strategy in the development of bi-functional cotherapy agents.

关键词： Anticancer Heartfailure Complication Drug repurposing Bi-functional drug

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Chemical construction and anti-HCoV-OC43 evaluation of novel 10,12-disubstituted aloperine derivatives as dual cofactor inhibitors of TMPRSS2 and SR-B1

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Chinese Chemical Letters 2024年第5期35卷 201-206页

作者： Yulong Shi Fenbei Chen Mengyuan Wu Xin Zhang Runze Meng Kun Wang Yan Wang Yuheng Mei Qionglu Duan Yinghong Li Rongmei Gao Yuhuan Li Hongbin Deng Jiandong Jiang Yanxiang Wang Danqing Song Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of pharmacy Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJining 272000China

Thirty-one new 10,12-disubstituted aloperine derivatives were subtly constructed through a selective oxidation on the 10-α-C-H induced by sulfonyl and a nucleophilic substitution with the stereoselectivity and *** them,compound 6b displayed a moderate anti-human coronavirus OC43(HCoV-OC43)potency and blocked the viral entry stage through a host mechanism of *** chemoproteomic techniques,both transmembrane serine protease 2(TMPRSS2)and scavenger receptor class B type 1(SR-B1)proteins,which act as host cofactors of viral entry,were identified to be the direct targets of 6b against ***,6b may deactivate the TMPRSS2 by inducing a change in protein conformation,rather than binding to its catalytic center,thus suppressing the viral membrane ***,our study provided key scientific data for the development of aloperine derivatives into a new class of antiviral candidates against humanβ-coronavirus,including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).

关键词： Aloperine SARS-CoV-2 TMPRSS2 SR-B1 Synthesis

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A naturally derived small molecule compound suppresses tumor growth and metastasis in mice by relieving p53-dependent repression of CDK2/Rb signaling and the Snail-driven EMT

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Chinese Journal of Natural Medicines 2024年第2期22卷 112-126页

作者： REN Boxue LI Yang DI Lei CHENG Ranran LIU Lijuan LI Hongmei LI Yi TANG Zhangrui YAN Yongming LU Tao FU Rong CHENG Yongxian WU Zhaoqiu State Key Laboratory of Natural Medicines Department of PharmacologySchool of PharmacyChina Pharmaceutical UniversityNanjing 211198China institute for Inheritance-Based Innovation of Chinese Medicine School of Pharmaceutical SciencesShenzhen University Health Science CenterShenzhen 518060China

The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in *** study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant ***22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 *** interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal ***22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling ***,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal ***,LZ22 administration in tumor-bearing mice did not manifest notable side *** findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.

关键词： LZ22 Wild-type p53 p53 Reactivator Snail-driven EMT Tumor growth and metastasis

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