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Pharmacokinetic enhancement of oncolytic virus M1 by inhibiting JAK-STAT pathway

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Acta Pharmaceutica Sinica b 2024年第6期14卷 2554-2566页

作者： Jingyi Tan Jiayu Zhang Cheng Hu Gongwei Wang Qianyao Ren Chaoqun Wang Jia dan Zexin Zeng Jun Hu Wenbo Zhu Jiankai Liang Jing Cai Ying Liu Guangmei Yan Yuan Lin Department of Pharmacology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China The Sixth Affiliated Hospital Sun Yat-sen UniversityGuangzhou 510655China Department of Urology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Advanced Medical Technology Center the First Affiliated Hospital-Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Key Laboratory of Human Microb.ome and Elderly Chronic Diseases Ministry of EducationGuangzhou 510655China Department of Infectious Diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

oncolytic viruses(oVs),a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact,are emerging as promising living anticancer *** traditional drugs composed of non-replicating compounds or b.omolecules,the replicative nature of viruses confer unique pharmacokinetic properties that require further *** some pharmacokinetics studies of oVs,mechanistic insights into the connection between oV pharmacokinetics and antitumor efficacy remain ***,we characterized the pharmacokinetic profile of oncolytic virus M1(oVM)in immunocompetent mouse tumor models and identified the JAK-STAT pathway as a key modulator of oVM *** suppressing the JAK-STAT pathway,early oVM pharmacokinetics are ameliorated,leading to enhanced tumor-specific viral accumulation,increased AUC and Cmax,and improved antitumor *** than compromising antitumor immunity after JAK-STAT inhibition,the improved pharmacokinetics of oVM promotes T cell recruitment and activation in the tumor microenvironment,providing an optimal opportunity for the therapeutic outcome of immune checkpoint b.ockade,such as *** together,this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in oV therapy.

关键词： Pharmacokinetics oncolytic virus JAK-STAT Anticancer

Effects of β-Glucan Supplementation on Repairing of Phenol-Induced Vaginal Mucosal Epithelium Damage in Rats

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open Journal of obstetrics and Gynecology 2024年第4期14卷 535-546页

作者： Song fei Weidong Wu Ying Wang dan Li bo Jin Department of Thoracic and Cardiovascular Surgery Guangzhou Red Cross Hospital of Jinan University Guangzhou China Guangzhou Xiaomanyao Medical Equipment Co. Ltd. Guangzhou China

objective: To investigate the effects of different concentrations of β-glucan on the repair of damaged vaginal mucosa, the expression of vascular endothelial growth factor (VEGf), and the inflammatory factor-6 (IL-6) in vaginal tissues. Methods: Thirty-six adult female specific pathogen free (SPf)-grade Wistar rats were randomly divided into 3 phase groups with 12 rats each. Vaginal inflammation rat models were established by injecting phenol gel into the vagina of each rat at a dose of 0.1 ml/100g body weight. After modeling, rats were divided into 4 groups based on different concentrations of the test agent. The control group was injected with 0.5 ml of saline, experimental group A was injected with 0.375 ml saline 0.125 ml β-glucan, experimental group b was injected with 0.25 ml saline 0.25 ml β-glucan, and experimental group C was injected with 0.50 ml β-glucan. The injection sites were selected at the 3 o’clock and 9 o’clock positions of the vagina. Rats were sacrificed at 7-, 14-, and 28-days post-injection, and tissue samples were collected from the injection sites and prepared for histological analysis. New b.ood vessels and fib.oblast numbers in the tissues were observed after Hematoxylin-eosin (HE) staining. The expression levels of VEGf and IL-6 in the tissues were measured using quantificational reverse transcription polymerase chain reaction (qRT-PCR). Results: Histological examination of vaginal tissue specimens at 7-, 14-, and 28-days post-injection showed that on day 7, there were no significant changes in the experimental groups compared to the control group. However, on days 14 and 28, the experimental groups showed more new b.ood vessels, macrophages, and fib.oblasts with increased activity compared to the control group. The expression levels of VEGf in vaginal tissues were elevated on days 14 and 28 in the experimental groups. The comparison of IL-6 levels in vaginal tissues on day 28 showed that serum IL-6 levels returned to normal, and there wa

关键词： β-Glucan Vaginal Mucosa Damage Repair

baicalein suppresses Coxsackievirus b3 replication by inhibiting caspase-1 and viral protease 2A

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Virologica Sinica 2024年第4期39卷 685-693页

作者： Yanyan Dong Enze Shao Siwei Li Ruiqi Wang dan Wang Lixin Wang Hong Yang Yingxia He Tian Luan Yang Chen Yao Wang Lexun Lin Yan Wang Zhaohua Zhong Wenran Zhao Department of Cell b.ology Harbin Medical UniversityHarbin 150081China Department of Microb.ology Harbin Medical UniversityHarbin 150081China

Myocarditis is an inflammatory disease of the cardiac muscle and one of the primary causes of dilated *** b coxsackievirus(CVb)is one of the leading causative pathogens of viral myocarditis,which primarily affects children and young *** to the lack of vaccines,the development of antiviral medicines is crucial to controlling CVb infection and the progression of *** this study,we investigated the antiviral effect of baicalein,a flavonoid extracted from Scutellaria *** results demonstrated that baicalein treatment significantly reduced cytopathic effect and increased cell viability in CVb3-infected *** addition,significant reductions in viral protein 3D,viral RNA,and viral particles were observed in CVb3-infected cells treated with *** found that baicalein exerted its inhibitory effect in the early stages of CVb3 *** also suppressed viral replication in the myocardium and effectively alleviated myocarditis induced by CVb3 *** study revealed that baicalein exerts its antiviral effect by inhibiting the activity of caspase-1 and viral protease *** together,our findings demonstrate that baicalein has antiviral activity against CVb3 infection and may serve as a potential therapeutic option for the myocarditis caused by enterovirus infection.

关键词： baicalein Coxsackievirus b(CVb) Myocarditis 2A protease Caspase-1

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系统性红斑狼疮的b细胞靶向治疗现状

中国新药杂志 2024年第8期33卷 785-791页

作者：强丹孙铀哈尔滨医科大学附属第二医院哈尔滨150000

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种高度异质性自身免疫性疾病,其发病机制复杂、临床表现多样化,目前仍然难以实现达标治疗及长期改善预后。近些年随着对SLE发病机制的不断探索,针对T细胞、b细胞、Ⅰ型干扰素和细... 详细信息

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种高度异质性自身免疫性疾病,其发病机制复杂、临床表现多样化,目前仍然难以实现达标治疗及长期改善预后。近些年随着对SLE发病机制的不断探索,针对T细胞、b细胞、Ⅰ型干扰素和细胞内信号分子等不同靶点的新药物层出不穷,其中b细胞及其相关分子作为SLE治疗的重要靶点一直备受关注。本文重点阐述b细胞靶向治疗在SLE中的最新研究结果和应用现状,以期为临床治疗提供参考。

关键词：系统性红斑狼疮 b细胞靶向治疗临床研究生物制剂

Role of hsa_circ_0007482 in pterygium development: insights into proliferation, apoptosis, and clinical correlations

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International Journal of ophthalmology(English edition) 2024年第8期17卷 1387-1395页

作者： Li-Yun Zhang Xin Liu Shuo Zheng Wen-Qun Xi Xue-Ping Wu dan-Yao Nie Hui-Ling Hu Jian-Tao Wang Xin-Hua Liu Jing Zhang Shenzhen Eye Hospital Jinan UniversityShenzhen Eye InstituteShenzhen 518000Guangdong ProvinceChina

AIM:To investigate the impact of hsa_circ_0007482 on the proliferation and apoptosis of human pterygium fib.oblasts(HPfs)and its correlation with the severity grades of ***:Pterygium and normal conjunctival tissues were collected from the superior area of the same patient’s eye(n=33).The correlation between pterygium severity and hsa_circ_0007482 expression using quantitative reversetranscription polymerase chain reaction(RT-qPCR)were *** distinct siRNA sequences targeting hsa_circ_0007482,along with a negative control sequence,were transfected into *** proliferation was assessed using the cell counting *** levels of Ki67,proliferating cell nuclear antigen(PCNA),Cyclin D1,bax,b-cell lymphoma-2(bcl-2),and Caspase-3 were measured via *** staining was employed to detect Ki67 and vimentin *** was evaluated using flow ***:Hsa_circ_0007482 expression was significantly higher in pterygium tissues compared to normal conjunctival tissues(Positive correlations were observed between hsa_circ_0007482 expression and pterygium severity,thickness,and vascular *** of hsa_circ_0007482 inhibited cell proliferation,reducing the mRNA expression of Ki67,PCNA,and Cyclin D1 in ***_circ_0007482 knockdown induced apoptosis,increasing mRNA expression levels of bax and Caspase-3,while decreasing bcl-2 expression in ***,hsa_circ_0007482 knockdown attenuated vimentin expression in ***:The downregulation of hsa_circ_0007482 effectively hampers cell proliferation and triggers apoptosis in *** are discernible positive correlations detected between the expression of hsa_circ_0007482 and the severity of pterygium.

关键词： hsa_circ_0007482 circular RNA pterygium cell proliferation apoptosis

A Critical Review of Single-Crystal LiNi_(x)Mn_(y)Co_(1-x-y)o_(2) Cathode Materials

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Renewables 2024年第1期2卷 25-51页

作者： Wenbo Liu Dongyang Li Yongqiang Liu dan Luo Rui Xu School of Materials Science and Engineering University of Science and Technology BeijingBeijing 100083 School of Physics and Telecommunications Engineering ZhouKou Normal UniversityHenan 466001 Department of Chemical Engineering Waterloo Institute for NanotechnologyWaterloo Institute for Sustainable EnergyUniversity of WaterlooOntario N2L 3G1

To meet the range requirements of electric vehicles,the lithium nickel-rich manganese cobalt oxides(nickel-rich LiNi_(x)Mn_(y)Co_(1-x-y)o_(2);x≥0.5 or NMC)material is a promising contender due to its superior energy and power *** polycrystalline nickel-rich NMC(PC-NMC)materials typically exhibit layered structures in which primary particles aggregate to form secondary particles to increase the contact area *** increasing the cathode energy ***,PC-NMC materials present a number of challenges in terms of cycle life and thermal stability,many of which stem from their extensive surface area,including severe surface phase transitions,intergranular microcracks,oxygen evolution,and transition metal *** address these challenges,single-crystal NMC(SCNMC)materials were introduced,which exhibited higher capacity retention and thermal robustness owing to their unique structures,characterized by lower active surface area and heightened mechanical ***,SC-NMC materials also had their own problems,including sluggish Li+bulk diffusion kinetics and nonuniform distribution of lattice strain,as well as their complex high-temperature calcination *** review concentrates on discussing the merits and demerits of SC-NMC over PC-NMC materials and introduces the current research efforts aimed at improving the electrochemical performance of SC-NMC.

关键词： Li-ion batteries single-crystal NMC nickel-rich layered oxides synthesis modification strategies

A Study on the Implementation Path of the blended Teaching Model in Geological Hazards Investigation and Evaluation

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Journal of Contemporary Educational Research 2024年第9期8卷 106-111页

作者： Liu Yang Wenjuan Wang Weijian Zhou dan Wang Ping Yin Hunan Vocational College of Engineering Changsha 410151Hunan ProvinceChina

Geological Hazards Investigation and Evaluation is the core course of Environmental Geological Engineering,aiming to cultivate skilled talents with solid theoretical knowledge and excellent practical *** present,the course faces several issues,including a teaching environment disconnected from real-world work scenarios,course content that deviates from job-related tasks,a lack of digital teaching resources,and reliance on a single teaching method,leading to students’poor feedback from *** on the concept of outcome-based education,the course team of Geological Hazards Investigation and Evaluation establishes a“five-step double-rotation”blended teaching model with the help of a Small Private online Course *** program is designed to improve the teaching environment and expand the digitalized teaching resources in order to improve students’learning motivation,enhance learning effectiveness,and cultivate skillful talents who meet employers’satisfaction.

关键词： outcome-based education concept Geological Hazards Investigation and Evaluation Teaching mode blended teaching and learning

基于网络药理学探讨中药逍遥丸治疗失眠的药理机制

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Journal of Chinese Pharmaceutical Sciences 2024年第2期33卷 169-177页

作者：王丹沈阳体育学院运动健康学院辽宁沈阳110102

本文旨在基于网络药理学探讨逍遥丸(XYP)治疗失眠症的作用机制。通过TCMSP数据库对XYP的活性成分和靶点进行预测筛选,GeneCards数据库检索失眠的潜在靶点,分析了活性成分靶点与失眠相关靶点之间的重叠基因。我们利用Cytoscape软件和STR... 详细信息

本文旨在基于网络药理学探讨逍遥丸(XYP)治疗失眠症的作用机制。通过TCMSP数据库对XYP的活性成分和靶点进行预测筛选,GeneCards数据库检索失眠的潜在靶点,分析了活性成分靶点与失眠相关靶点之间的重叠基因。我们利用Cytoscape软件和STRIng构建了XYP的活性组分-靶点、靶点通路网络,在DAVID中进行Go和KEGG富集分析。从XYP中筛选出161个活性成分,并筛选出与活性成分相关的76个潜在的靶点,活性成分与失眠的重叠基因36个。网络药理学分析显示XYP组方中柴胡、当归和甘草可能对失眠有重要作用,机制可能涉及10个核心靶点(TNf、IL1b、CASP3、TP53、HSP90AA1、PPARG、SLC6A4、ESR1、GSK3b、AChE);主要涉及7个Go富集项和6个相关通路,包括神经活性配体受体相互作用通路、肿瘤通路、钙信号通路等。

关键词：逍遥丸失眠网络药理学核心靶点

Whole-genome resequencing of Hu sheep identifies candidate genes associated with agronomic traits

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Journal of Genetics and Genomics 2024年第8期51卷 866-876页

作者： Liming Zhao Lvf.ng Yuan fadi Li Xiaoxue Zhang Huibin Tian Zongwu Ma Deyin Zhang Yukun Zhang Yuan Zhao Kai Huang Xiaolong Li Jiangbo Cheng dan Xu Xiaobin Yang Kunchao Han Xiuxiu Weng Weimin Wang State Key Laboratory of Herbage Improvement and Grassland Agro-Ecosystems Key Laboratory of Grassland Livestock Industry InnovationMinistry of Agriculture and Rural AffairsEngineering Research Center of Grassland IndustryMinistry of EducationCollege of Pastoral Agriculture Science and TechnologyLanzhou UniversityLanzhouGansu 730020China Lanzhou Veterinary Research Institute Chinese Academy of Agricultural SciencesLanzhouGansu 730046China College of Animal Science and Technology Gansu Agricultural UniversityLanzhouGansu 730070China

The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human *** sheep are a local sheep breed unique to China with high reproductive rates and rapid *** selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in ***,we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep(Asiatic mouflon)to investigate the genetic characteristics and selection signatures of Hu *** on six signatures of selection approaches,we detect genomic regions containing genes related to reproduction(bMPR1b,bMP2,PGfS,CYP19,CAMK4,GGT5,and GNAQ),vision(ALDH1A2,SAG,and PDE6b),nervous system(NAV1),and immune response(GPR35,SH2b2,PIK3R3,and HRAS).Association analysis with a population of 1299 Hu sheep reveals that those missense mutations in the GPR35(GPR35 g.952651 A>G;GPR35 g.952496 C>T)and NAV1(NAV1 g.84216190 C>T;NAV1 g.84227412 G>A)genes are significantly associated(Powth traits in Hu sheep,*** research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.

关键词： Hu sheep Whole-genome resequencing Selection signature GPR35 NAV1 Single nucleotide polymorphism