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Genes & Diseases 2024年第1期11卷 87-90页

作者： Hongxia Zhang Yueya Zhong Yuanming He Yujia Xu Ying Ren Haixia Zhuang Tong Sun Zhigang Zhu Xinliang Mao Institute of Clinical pharmacology Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouGuangdong 510403China Guangdong Provincial Key Laboratory of Protein Modification and Degradation School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouGuangdong 511436China department of pharmacology College of Pharmaceutical SciencesSoochow UniversitySuzhouJiangsu 215123China Division of Hematology&Oncology Department of GeriatricsGuangzhou First People's HospitalCollege of MedicineSouth China University of TechnologyGuangzhouGuangdong 510180China

Chronic myelogenous leukemia(CML)is a malignancy from bone marrow myeloid stem cells mainly driven by the fusion gene *** addition to BCR-ABL,other genes including RNF6 are also dysregulated in CML cells.1 RNF6,a ubiquitin ligase of the RING family,promotes various cancer cell proliferation,chemoresistance,and tumor growth in vivo by targeting various proteins for ubiquitination and degradation,including SHP1,TLE3,FOXA1,and MAD1.^(2) However,its specific mechanism in CML is not known.

关键词： ubiquitin myelogenous leukemia

Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2429-2438页

作者： Peng-Fei Jing Jin Chen En-Da Yu Chao-Yu Miao department of Colorectal Surgery Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China department of Endocrinology and Metabolism Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China department of pharmacology Second Military Medical University/Naval Medical UniversityShanghai 200433China

BACKGROUND In recent years,the incidence of colorectal cancer(CRC)has been *** the popularization of endoscopic technology,a number of early CRC has been ***,despite current treatment methods,some patients with early CRC still experience postoperative recurrence and *** To search for indicators associated with early CRC recurrence and metastasis to identify high-risk *** A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this *** of blood routine test,liver and kidney function tests and tumor markers were collected before *** were followed up through disease-specific database and telephone *** recurrence,metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and *** We comprehensively compared the predictive value of preoperative blood routine,blood biochemistry and tumor markers for disease-free survival(DFS)and overall survival(OS)of *** multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS[hazard ratio(HR)=0.995,95% confidence interval(CI):0.991-0.999,P=0.015],while serum carcinoembryonic antigen(CEA)level(HR=1.008,95%CI:1.001-1.016,P=0.027)and serum total cholesterol level(HR=1.538,95%CI:1.026-2.305,P=0.037)were independent risk factors for *** cutoff value of serum CEA level for predicting OS was 2.74 ng/*** the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level,the difference between the two groups was not statistically significant(P=0.075).CONCLUSION For patients with T2N0M0 or T3N0M0 CRC,preoperative platelet count was a protective factor for DFS,while serum CEA level was an independent risk factor for *** that these measures are easier to detect and more acceptable to patients,they may have broader applications.

关键词： Colorectal cancer Platelet count Serum carcinoembryonic antigen Total cholesterol level Overall survival Disease-free survival

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

Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina department of Physiology and pharmacology Karolinska InstitutetStockholmSweden department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

Emerging tropane alkaloids:Global development and potential health threats

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Food Quality and Safety 2024年第1期8卷 12-26页

作者： Zile Wang Shiqi Chen Pimiao Zheng Zhenhui Ren Huixia Zhang Jing Zhang Bing Shao Congming Wu Haiyang Jiang department of Veterinary pharmacology and toxicology Beijing Key Laboratory of Detection Technology for Animal-Derived Food SafetyBeijing Laboratory for Food Quality and SafetyNational Key Laboratory of Veterinary Public Health and SafetyCollege of Veterinary MedicineChina Agricultural UniversityBeijingChina. College of Veterinary Medicine Shandong Agricultural UniversityTaianChina. Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry College of Animal Science and Veterinary MedicineTianjin Agricultural UniversityTianjinChina Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning Beijing Center for Disease Prevention and ControlBeijingChina.

Tropane alkaloids(TAs)are a kind of plant secondary metabolite that mainly originate from *** have potent anticholinergic activity,and are well-known anticholinergic drugs,but have also been reported as plant *** studies have been conducted on TAs,but no scientometric research has been *** study aimed to expound the knowledge network and development of the feld of TAs and predict the emerging development topics based on *** particular,this research combined VOSviewer and CiteSpace for visualization and covered 1,298 related scientifc publications(1953–2022).The research on TAs is rapidly developing,with the participation of 86 countries,1,129 research institutions,and 4,087 ***,the University of Geneva,and *** are the most productive country,institution,and researcher,***,the main research topics on TAs include biosynthesis,in vitro synthesis,chemical synthesis,and determination *** 2018,the monitoring of TAs in food related to human health has shown citation burst characteristics,which is considered an emerging development trend in the *** fndings of this study will enable researchers to quickly tap into the knowledge background/structure of TAs from massive data to provide a reference for further research.

关键词： Tropane alkaloids bibliometrics biosynthesis in vitro synthesis chemical synthesis determination contamination food safety

Cellular Chemical Field and Cellular Homeostasis

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Engineering 2024年第8期39卷 18-24页

作者： Bin Cong Lu Li Qian Wang Tao He Junwei Li Hongliang Xie Aolin Zhang Xiaohui Fan Hebei Key Laboratory of Forensic Medicine College of Forensic MedicineHebei Medical UniversityShijiazhuang 050017China College of Integrated Traditional Chinese and Western Medicine Hebei Medical UniversityShijiazhuang 050017China Research Unit of Digestive Tract Microecosystem pharmacology and toxicology Chinese Academy of Medical SciencesShijiazhuang 050017China Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314100China department of Obstetrics and Gynecology Sir Run Run Shaw HospitalMedical College of Zhejiang UniversityHangzhou 310058China department Obstetrics and Gynaecology Prince of Wales HospitalThe Chinese University of Hong KongHong Kong 999077China

*** Cell structure and function are controlled by a complex regulatory networking process,in which molecular adaptation and interaction are essential to maintain cellular homeostasis following dynamic multi-omics rules and multi-systematic *** complex chemical process is an important mechanism for stabilizing the cell microenvironment.

关键词： maintain stabilizing Cellular

Site-specific incorporation of reduction-controlled guest amino acids into proteins for cucurbituril recognition

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Chinese Chemical Letters 2024年第5期35卷 193-196页

作者： Zhen Dai Linzhi Tan Yeyu Su Kerui Zhao Yushun Tian Yu Liu Tao Liu College of Chemistry State Key Laboratory of Elemento-Organic ChemistryNankai UniversityTianjin 300071China State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Protein recognition using host-guest recognition approach is of great interest but has been limited mainly to the protein N-terminal ***,we site-specific incorporated two novel non-canonical amino acids containing supramolecular guest motifs into protein via an expanded genetic *** Staudinger reduction reactions,the encoded unnatural residues on protein becoming activated and can be specifically recognized by cucurbit[7]uril(CB[7])and cucurbit[8]uril(CB[8]).We demonstrated that enzyme containing guest amino acid incorporated near the active site can be reversibly regulated by CB[7]recognition,and CB[8]recognition induces protein *** amino acids will make useful addition to the supramolecular toolbox for protein targeting using molecular recognition approaches.

关键词： Protein recognition Host-guest recognition Non-canonical amino acids Staudinger reduction Expanded genetic code

Context-dependent role of sirtuin 2 in inflammation

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Neural Regeneration Research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta department of Pharmaceutical Sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for Health Research(IdiSNA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2

Astrocytes dynamically regulate the blood-brain barrier in the healthy brain

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Neural Regeneration Research 2024年第4期19卷 709-710页

作者： AgnėPociūtė Augustas Pivoriūnas Alexei Verkhratsky department of Stem Cell Biology State Research Institute Centre for Innovative MedicineVilniusLithuania Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK Achucarro Centre for Neuroscience IKERBASQUEBasque Foundation for ScienceBilbaoSpain department of Forensic Analytical toxicology School of Forensic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina

The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to *** primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.

关键词： Ehrlich barrier blood

Investigating causal links between gastroesophageal reflux disease and essential hypertension

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World Journal of Clinical Cases 2024年第14期12卷 2304-2307页

作者： Gowthami Sai Kogilathota Jagirdhar Yatinder Bains Salim Surani department of Medicine Saint Francis Health Science CenterNewarkNJ 07107United States department of Gastroenterology Saint Michaels Medical CenterNewarkNJ 07102United States department of Medicine and pharmacology Texas A&M UniversityCollege StationTX 77843United States

Gastroesophageal reflux disease(GERD)is a prevalent global health concern with a rising *** risk factors,including obesity,hiatal hernia,and smo-king,contribute to its *** research suggests associations bet-ween GERD and metabolic syndrome,cardiac diseases,and hypertension(HTN).Mechanisms linking GERD to HTN involve autonomic dysfunction,inflammatory states,and endothelial ***,GERD medications such as pro-ton-pump inhibitors may impact blood pressure ***,antihy-pertensive medications like beta-blockers and calcium channel blockers can exacerbate GERD *** bidirectional causality exists between GERD and HTN,longitudinal studies are warranted to elucidate the precise *** of GERD,including anti-reflux surgery,may positively influence HTN ***,the interplay of lifestyle factors,comorbidities,and medications necessitates further investigation to comprehensively understand this *** this editorial,we comment on the article published by Wei et al in the recent issue of the World Journal of Clinical *** evaluate their claims on the causal association between GERD and HTN.

关键词： Gastroesophageal reflux disease Hypertension Metabolic syndrome Gastro-esophageal reflux disease Hiatal hernia