检索结果-南通市图书馆

Genome editing of PAR2 through targeted delivery of CRISPR-Cas9 system for alleviating acute lung inflammation via ERK/NLRP3/IL-1β and NO/iNOS signalling

引用

Acta Pharmaceutica Sinica B 2024年第3期14卷 1441-1456页

作者： Xin Zhuo Yue Wu Xiujuan Fu Jianbin Li Yuxin Xiang Xiaoyu Liang Canquan Mao Yuhong Jiang Sichuan engineering research center for Biomimetic Synthesis of natural drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases,immune cell infiltration and protease-driven tissue *** is an urgent need to explore potential drug strategies for mitigating lung ***-activated receptor 2(PAR2)as a vital molecular target principally participates in various inflammatory diseases via intracellular signal ***,it has been rarely reported about the role of PAR2 in lung *** study applied CRISPR-Cas9 system encoding Cas9 and sg RNA(p Cas9-PAR2)for PAR2 knockout and fabricated an anionic human serum albuminbased nanoparticles to deliver p Cas9-PAR2 with superior inflammation-targeting efficiency and stability(TAP/p Cas9-PAR2).TAP/p Cas9-PAR2 robustly facilitated p Cas9-PAR2 to enter and transfect inflammatory cells,eliciting precise gene editing of PAR2 in vitro and in ***,PAR2 deficiency by TAP/p Cas9-PAR2 effectively and safely promoted macrophage polarization,suppressed proinflammatory cytokine releases and alleviated acute lung inflammation,uncovering a novel value of *** also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/p Cas9-PAR2was mainly dependent on ERK-mediated NLRP3/IL-1β and NO/i NOS ***,this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases.

关键词： Protease-activated receptor 2(PAR2) CRISPR-Cas9 Gene editing Inflammation Acute lung inflammation NLRP3 Nanoparticles Drug delivery

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Mannogalactoglucan from mushrooms protects pancreatic islets via restoring UPR and promotes insulin secretion in TIDM mice

引用

Food Science and Human Wellness 2024年第3期13卷 1390-1401页

作者： Ting Liu Si Chen Yunhe Qu Lujuan Zheng Xiaoxuan Yang Shuhan Men Yuanning Wang Hanrui Ma Yifa Zhou Yuying Fan engineering research center of Glycoconjugates Ministry of EducationJilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural DrugsSchool of Life SciencesNortheast Normal UniversityChangchun 130024China

Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-*** pancreatic islets and enhancing insulin secretion has been therapeutic *** is the main type of polysaccharide from natural mushroom,which has potential medicinal ***,the antidiabetic property of mannogalactoglucan in T1DM has not been fully *** this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of *** and investigated the potential therapeutic value of AAMP-N in *** demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM ***-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in *** that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.

关键词： Mannogalactoglucan Mushroom Pancreatic islets Insulin secretion Insulin synthesis Unfolded protein response(UPR) Type 1 diabetes mellitus(T1DM)

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Cognitive impairment in cerebral small vessel disease induced by hypertension

引用

Neural Regeneration research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of Pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical research center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular *** r,the causal relationship between hypertension and cerebral small vessel disease remains *** has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular *** hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and *** is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of *** review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive *** also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Therapeutic strategies of targeting nonapoptotic regulated cell death (RCD) with smallmolecule compounds in cancer

引用

Acta Pharmaceutica Sinica B 2024年第7期14卷 2815-2853页

作者： Xin Jin Wenke Jin Linlin Tong Jia Zhao Lan Zhang Na Lin Department of Ultrasound Department of Medical Oncology and Department of Hematologythe First Hospital of China Medical UniversityChina Medical UniversityShenyang 110001China Sichuan engineering research center for Biomimetic Synthesis of natural drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Regulated cell death(RCD)is a controlled form of cell death orchestrated by one or more cascading signaling pathways,making it amenable to pharmacological *** subroutines can be categorized as apoptotic or non-apoptotic and play essential roles in maintaining homeostasis,facilitating development,and modulating *** evidence has recently revealed that RCD evasion is frequently the primary cause of tumor *** non-apoptotic RCD subroutines have garnered attention as promising cancer therapies due to their ability to induce tumor regression and prevent relapse,comparable to ***,they offer potential solutions for overcoming the acquired resistance of tumors toward apoptotic *** an increasing understanding of the underlying mechanisms governing these non-apoptotic RCD subroutines,a growing number of small-molecule compounds targeting single or multiple pathways have been discovered,providing novel strategies for current cancer *** this review,we comprehensively summarized the current regulatory mechanisms of the emerging non-apoptotic RCD subroutines,mainly including autophagy-dependent cell death,ferroptosis,cuproptosis,disulfidptosis,necroptosis,pyroptosis,alkaliptosis,oxeiptosis,parthanatos,mitochondrial permeability transition(MPT)-driven necrosis,entotic cell death,NETotic cell death,lysosome-dependent cell death,and immunogenic cell death(ICD).Furthermore,we focused on discussing the pharmacological regulatory mechanisms of related small-molecule *** brief,these insightful findings may provide valuable guidance for investigating individual or collaborative targeting approaches towards different RCD subroutines,ultimately driving the discovery of novel small-molecule compounds that target RCD and significantly enhance future cancer therapeutics.

关键词： Regulated cell death(RCD) Non-apoptotic RCD subroutine Autophagy Ferroptosis Necroptosis Regulatory mechanism Small-molecule compound Cancer therapy

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Mechanism of action of the bile acid receptor TGR5 in obesity

引用

Acta Pharmaceutica Sinica B 2024年第2期14卷 468-491页

作者： Weijun Lun Qihao Yan Xinghua Guo Minchuan Zhou Yan Bai Jincan He Hua Cao Qishi Che Jiao Guo Zhengquan Su Guangdong engineering research center of natural Products and New drugs Guangdong Provincial University Engineering Technology Research Center of Natural Products and DrugsGuangdong Pharmaceutical UniversityGuangzhou 510006China Guangdong Metabolic Disease research center of Integrated Chinese and Western Medicine Key Laboratory of Glucolipid Metabolic DisorderMinistry of Education of ChinaGuangdong TCM Key Laboratory for Metabolic DiseasesGuangdong Pharmaceutical UniversityGuangzhou 510006China School of Public Health Guangdong Pharmaceutical UniversityGuangzhou 510310China School of Chemistry and Chemical engineering Guangdong Pharmaceutical UniversityZhongshan 528458China Guangzhou Rainhome Pharm&Tech Co. Ltd.Science CityGuangzhou 510663China

G protein-coupled receptors(GPCRs)are a large family of membrane protein receptors,and Takeda G protein-coupled receptor 5(TGR5)is a member of this *** a membrane receptor,TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism,including the processes of energy consumption,weight loss and blood glucose *** studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver,obesity and *** the global obesity situation becoming more and more serious,a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently *** this review,we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target,and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands,which can effectively provide new ideas for ligand research and promote drug research.

关键词： Obesity TGR5 Bile acids Ligand Appetite Metabolism GLP-1 Inflammation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Facile synthesis of nanoparticles-stacked Co_(3)O_(4)nanoflakes with catalase-like activity for accelerating wound healing

引用

Regenerative Biomaterials 2024年第3期3卷 82-91页

作者： Yanan Huang Wanyi Liao Wenxuan Wang Tingting Zhang Yan Zhang Lei Lu school and Hospital of Stomatology Wenzhou Medical UniversityWenzhou 325027China sichuan engineering research center for Biomimetic Synthesis of natural drugs School of Life Science and EngineeringSouthwest jiaotong UniversityChengdu 610031China Key Lab of Advanced Technology of Materials of Education Ministry School of Materials Science and EngineeringSouthwest jiaotong UniversityChengdu 610031China school of Chemistry Southwest Jiaotong UniversityChengduSichuan 610031China

Delayed wound healing caused by excessive reactive oxygen species(Ros)remains a considerable *** recent years,metal oxide nanozymes have gained significant attention in biomedical ***,a comprehensive investigation of Co_(3)O_(4)-based nanozymes for enhancing wound healing and tissue regeneration is *** study focuses on developing a facile synthesis method to produce high-stability and costeffective Co_(3)O_(4)nanoflakes(NFs)with promising catalase(CAT)-like activity to regulate the oxidative microenvironment and accelerate wound *** closely arranged Co_(3)O_(4)nanoparticles(NPs)within the NFs structure result in a significantly larger surface area,thereby amplifying the enzymatic activity compared to commercially available Co_(3)O_(4)*** physiological conditions,itwas observed that CogO,NFs efficientlybreak down hydrogen peroxide(H_(2)O_(2))without generating harmful radicals(OH).Moreover,they exhibit excellent compatibility with various cells involved in wound healing,promoting fibroblast growth and protecting cells from oxidatives *** a ratmodel,Co_(3)O_(4) NFs facilitate both the hemostatic and proliferative phases of wound healing,consequently accelerating the ***,thepromising results of Co_(3)O_(4)NFs highlight their potential in promoting wound healing and tissue regeneration.

关键词： Co_(3)O_(4) nanoflake nanozyxygen species wound healing

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Lewis Base Catalyzed Selenofunctionalization of Alkynes with Acid-Controlled Divergent Chemoselectivity

引用

Chinese Journal of Chemistry 2024年第14期42卷 1623-1629页

作者： Ling-Ling Chen Ren-Fei Cao Hua Ke Zhi-Min Chen School of Chemistry and Chemical engineering Shanghai Key Laboratory for Molecular Engineering of Chiral DrugsShanghai Jiao Tong UniversityShanghai200240 China engineering Technology research center for Environmental Protection Materials Pingxiang UniversityPingxiangJiangxi337055 China

Lewis base catalyzed and Brønsted acid controlled chemodivergent electrophilic selenofunctionalizations of alkynes were developed for the first *** selenium-containing tetrasubstituted alkenes were readily obtained in moderate to excellent yields with complete E/Z *** the substrates were 1-ethynyl naphthol derivatives,linear selenium-containing tetrasubstituted alkenes were produced via intermolecular oxygen nucleophilic attack in the absence of acid additive;in contrast,cyclic selenium-containing tetrasubstituted alkenes were generated through intramolecular carbon nucleophilic capture with the addition of Brønsted acid.

关键词： Alkynes Electrophilic addition Chemoselectivity Lewis base catalysis Selenofunctionalization

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Encouraging Solution to the Problem of Synthesizing Protein α-Thioester

引用

Chinese Journal of Chemistry 2024年第10期42卷 1114-1120页

作者： Xinliang Liu Zijun Gao Jie Zhao Farong Ye Ping Huang Ping Wang center for Chemical Glycobiology Shanghai Key Laboratory for Molecular Engineering of Chiral DrugsFrontiers Science Center for Transformative MoleculesSchool of Chemistry and Chemical EngineeringZhangjiang Institute for Advanced StudyShanghai JiaoTongUniversityShanghai 200240China Shenzhen research Institute of Shanghai Jiao Tong University ShenzhenGuangdong 518057China

Expressed protein ligation(EPL)provides a powerful tool to access large-size proteins with precise *** methods for constructing the critical protein thioester for EPL have predominantly relied on the recombinant intein fusion expressed in Escherichia coli(***).Despite its powerful applications,the expression of thioester derived from eukaryotic protein in *** inherently suffers from its limited solubility,the inactivity of intein,premature hydrolysis and low *** overcome these obstacles,we present herein the facile one-flask synthesis of inaccessible proteinα-thioester via a SUMO-protein-intein(SPI)sandwich *** utility of SUMO enhances the protein fusion yield and solubility,prevents premature hydrolysis and simplifies the purification *** inaccessible protein thioester with internal Cys residues can be readily produced and is compatible with the EPL-desulfurization protocol used to prepare complex proteins,which is otherwise difficult to obtain using traditional *** utility has been highlighted through the synthesis of human granulocyte colony-stimulating factor(G-CSF).

关键词： Desulfurization Glycoproteins Glycopeptides Protein expression Peptide thioester

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Josephin domain containing 2(JOSD2)promotes lung cancer by inhibiting LKB1(Liver kinase B1)activity

引用

Signal Transduction and Targeted Therapy 2024年第2期9卷 693-708页

作者： Tao Yuan Chenming Zeng Jiawei Liu Chenxi Zhao Fujing Ge Yuekang Li Meijia Qian Jiamin Du Weihua Wang Yonghao Li Yue Liu Xiaoyang Dai Jianya Zhou Xueqin Chen Shenglin Ma Hong Zhu Qiaojun He Bo Yang Institute of Pharmacology&Toxicology Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 311199China Ministry of Education Key Laboratory of Chinese Medicinal Plants Resource from Lingnan Research Center of Medicinal Plants Resource Science and EngineeringGuangzhou University of Chinese MedicineGuangzhou 510006China center for Drug Safety Evaluation and research of Zhejiang University Hangzhou 310058China Department of Respiratory Disease Thoracic Disease CenterThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310006China Department of Oncology Hangzhou Cancer HospitalHangzhou 310002China Cancer center of Zhejiang University HangzhouChina engineering research center of Innovative anticancer drugs Ministry of EducationHangzhouChina

Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths *** the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC ***,the need for novel strategies addressing NSCLC remains ***(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic ***,the mechanisms by which DUBs promote NSCLC remain poorly *** a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of *** of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in ***,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 ***,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in *** findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.

关键词： LKB1 inhibiting removing

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Palladium-catalyzed stereoselective decarboxylative[4+2]cyclization of 2-methylidenetrimethylene carbonates with pyrrolidone-derived enones:Straightforward access to chiral tetrahydropyran-fused spiro-pyrrolidine-2,3-diones

引用

Chinese Chemical Letters 2024年第6期35卷 279-282页

作者： Ke Zhang Sheng Zuo Pengyuan You Tong Ru Fen-Er Chen Key Laboratory of natural Medicines of the Changbai Mountain Ministry of EducationCollege of PharmacyYanbian UniversityYanji 133002China College of Chemistry and Chemical engineering Jiangxi Normal UniversityNanchang 330022China engineering center of Catalysis and Synthesis for Chiral Molecules Fudan UniversityShanghai 200433China Shanghai engineering center of Industrial Catalysis for Chiral drugs Shanghai 200433China

A novel asymmetric[4+2]cycloaddition of 2-methylidenetrimethylene carbonate with pyrrolidonederived enones has been achieved to produce the functionalized tetrahydropyran-fused spirocyclic scaffolds via *** array of enantioenriched spiro-pyrrolidine-2,3-diones bearing adjacent quaternary and tertiary stereocenters are obtained in high yields with excellent enantioselectivities(up to 96% yield and 99% ee).The further transformation of the product has been accomplished for the construction of medical interesting β^(2,2)-amino acids and β-*** mechanistic research was well conducted.

关键词： Pyrrolidine-2,3-diones 2-Methylidenetrimethylene carbonate Asymmetric annulation Spiroheterocycles Allylic 1,3-strain

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：