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Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

Genes & Diseases 2024年第1期11卷 189-204页

作者： Ebrahim H.Maleki Ahmad Reza Bahrami Maryam M.Matin Department of Biology Faculty of ScienceFerdowsi University of Mashhad*** MashhadIran Jagiellonian Centre for Experimental therapeutics(JCET) Jagiellonian University31-007 KrakowPoland Doctoral School of Exact and Natural Sciences Jagiellonian University30-348 KrakowPoland Industrial Biotechnology research group Institute of BiotechnologyFerdowsi University of Mashhad*** MashhadIran novel diagnostics and therapeutics research group Institute of BiotechnologyFerdowsi University of Mashhad***MashhadIran Stem Cell and Regenerative Medicine research group Iranian Academic Center for EducationCulture and Research(ACECR)Khorasan Razavi Branch917751376 MashhadIran

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer *** tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the *** on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against *** discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"***,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer *** understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to ***-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in ***,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.

关键词： Cancer stem cells(CSCs) Carcinoma Cell cycle heterogeneity Quiescence Therapy resistance Therapy tolerance Tumor dormancy

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Mucopolysaccharidosis typeⅢB:a current review and exploration of the AAV therapy landscape

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Neural Regeneration research 2024年第2期19卷 355-359页

作者： Courtney J.Rouse Victoria N.Jensen Coy D.Heldermon Lacerta therapeutics AlachuaFLUSA University of Florida College of Medicine GainesvilleFLUSA

Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for *** results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological *** treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢ***-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential *** group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy ***,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.

关键词： adeno-associated virus central nervous system gene therapy heparan sulfate immune response mucopolysaccharidoses type IIIB N-acetyl-alpha-glucosaminidase newborn screening

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ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian Ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong Kin Yip Tam Jochen H.M.Prehn Hongfeng Wang Zheng Ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China MOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering research Center of Precision diagnostics and therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&Medical Physics and FUTURE-NEURO research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of Health Sciences University of MacaoTaipaMacao 999078China Insititutes of Biology and Medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative *** GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)*** there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between BECN1 and BCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy BCL2 BECN1/Beclin 1 Dipeptide repeat Neurodegeneration

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Initial decrease in the lipoprotein(a)level is a novel prognostic biomarker in patients with acute coronary syndrome

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World Journal of Cardiology 2024年第6期16卷 329-338页

作者： Yasuhiko Saeki Jun Sawaguchi Satori Akita Taka-aki Takamura Kosuke Fujibayashi Minoru Wakasa Hironobu Akao Michihiko Kitayama Yasuyuki Kawai Kouji Kajinami Department of Cardiology Kanazawa Medical UniversityUchinada 9200293Japan Trans-catheter Cardiovascular therapeutics Kanazawa Medical UniversityUchinada 9200293Japan

BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains *** To investigate the hypothesis that the Lp(a)levels are altered by various conditions during the acute phase of ACS,resulting in subsequent cardiovascular *** From September 2009 to May 2016,377 patients with ACS who underwent emergent coronary angiography,and 249 who completed≥1000 d of follow-up were ***(a)levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention(PCI)to 48 h after *** primary endpoint was the occurrence of major adverse cardiac events(MACE;cardiac death,other vascular death,ACS,and non-cardiac vascular events).RESULTS The mean circulating Lp(a)level decreased significantly from pre-PCI(0 h)to 12 h after(19.0 mg/dL to 17.8 mg/dL,Pgroup than in the remaining two tertile groups(66.2%vs 53.6%,P=0.034).A multivariate analysis revealed that Lp(a)Δ0-12[hazard ratio(HR):0.96,95%confidence interval(95%CI):0.92-0.99]and basal creatinine(HR:1.13,95%CI:1.05-1.22)were independent determinants of subsequent *** Circulating Lp(a)levels in patients with ACS decreased significantly after emergent PCI,and a greater decrease was independently associated with a worse prognosis.

关键词： Lipoprotein(a) Acute coronary syndrome Percutaneous coronary intervention Major adverse cardiac events Prognosis

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Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

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Military Medical research 2024年第2期11卷 180-205页

作者： Hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor Biological Behaviors Wuhan 430071China Department of Pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Pathology and Molecular diagnostics Wuhan UniversityWuhan 430071China Wuhan research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain ***,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of ***:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan *** advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in *** expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting *** elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in *** Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided Pnovel inhibitor of PCa *** expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,mig

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

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Antigen epitopes of animal coronaviruses:a mini-review

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Animal Diseases 2024年第1期4卷 19-26页

作者： Mingjun Su Guanghui Zheng Xiangwen Xu Houhui Song Key Laboratory of Applied Technology On Green-Eco-Healthy Animal Husbandry of Zhejiang Province Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics&Advanced TechnologyZhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health ManagementChina-Australia Joint Laboratory for Animal Health Big Data AnalyticsCollege of Animal Science and Technology&College of Veterinary Medicine of ZhejiangA&F University666 Wusu StreetLin'an DistrictHangzhou 311300Zhejiang ProvinceChina

Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health ***,prevention and control of emerging and re-emerging animal coronaviruses is a great *** mecha-nisms of virus-mediated immune responses have important implications for research on virus prevention and *** antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lympho-cytes,playing an important role in antiviral immune ***,it can shed light on the development of diagnos-tic methods and novel ***,we have reviewed advances in animal coronavirus antigenic epitope research,aiming to provide a reference for the prevention and control of animal and human coronaviruses.

关键词： Animal coronavirus Antigen epitope B-cell epitope T-cell epitope Immune responses Vaccines

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A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea *** with Experimental Support in Chronic Unpredictable Mild Stress Model Mice

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Chinese Journal of Integrative Medicine 2022年第4期28卷 339-348页

作者： SUN Dan-chen WANG Ran-ran XU Hao ZHU Xue-hui SUN Yan QIAO Shi-qing QIAO Wei Tianjin Key Laboratory on Technologies Enabling Development of Clinical therapeutics and diagnostics School of PharmacyTianjin Medical UniversityTianjin300070China

Objective:To investigate the pharmacodynamic material basis,mechanism of actions and targeted diseases of Salicornia europaea L.(SE)based on the network pharmacology method,and to verify the antidepressant-like effect of the SE extract by pharmacological ***:Retrieval tools including Chinese medicine(CM),PubMed,PharmMapper,MAS 3.0 and Cytoscape were used to search the components of SE,predict its targets and related therapeutic diseases,and construct the"Component-TargetPathway"network of SE for central nervous system(CNS)***,protein-protein interaction(PPI)network,Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of *** unpredictable mild stress(CUMS)model was used to construct a mouse model with depression-like *** the animals were randomly divided into 6 groups(n=10)including the normal group(nonstressed mice administered with distilled water),the CUMS group(CUMS mice administered with distilled water),the venlafaxine group(CUMS mice administered with venlafaxine 9.38 mg/kg),SE high-,medium-,and low-dose groups(CUMS mice administered with SE 1.8,1.35 and 0.9 g/kg,respectively).Then some relevant indicators were determined for experimental verification by the forced swim test(FST),the tail suspension test(TST)and open-field test(OFT).Dopamine(DA)concentration in hippocampus and cerebral cortex,IL-2 and corticosterone(CORT)levels in blood,and nuclear factor E2 related factor 2(Nrf2),kelch-like epichlorohydrin related protein 1(Keap1),NAD(P)H dehydrogenase[quinone]1(NQO1)and heme oxygenase-1(HO-1)levels in mice were measured by enzyme linked immunosorbent assay(ELISA)and Western blot respectively to explore the possible ***:The"target-disease"network diagram predicted by network pharmacology,showed that the potential target of SE involves a variety of CNS diseases,among which depression ac

关键词： Salicornia europaea L. network pharmacology tail suspension test forced swim test depression

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and Medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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Isolation and molecular identification of cellulolytic bacteria from Dig Rostam hot spring and study of their cellulase activity

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BIOCELL 2020年第1期44卷 63-71页

作者： Sareh HAJIABADI Mansour MASHREGHI Ahmad Reza BAHRAMI Kiarash GHAZVINI Maryam M.MATIN Department of Biology Faculty of ScienceFerdowsi University of MashhadMashhadIran novel diagnostics and therapeutics research group Institute of BiotechnologyFerdowsi University of MashhadMashhadIran Microbiology research Center&Department of Microbiology and Virology Ghaem Medical CenterMashhad University of Medical SciencesMashhadIran

Cellulose is the main structural component of lignocellulosic wastes that can be converted to sugars and biofuels by *** to wide applications of this enzyme in various industries around the world,cellulase is considered as the third industrial *** ability of thermophilic bacteria in the production of heat-stable cellulases has made them valuable tools in *** aim of this study was isolation and molecular identification of cellulolytic thermophile bacteria from Dig Rostam hot spring and investigating their cellulase *** were taken from water and sediments of this hot spring,and cellulolytic bacteria were enriched in media containing cellulose as the only carbon *** bacteria were incubated at 60℃,and single colonies were then isolated on solid *** red assay was used as a quick test for the qualitative screening of cellulase *** to these qualitative results,four colonies named CDB1,CDB2,CDB3,and CDB4 were isolated,and their growth curve and some other characteristics were determined by biochemical ***,endoglucanase,exoglucanase,and FPase activities of the isolates were investigated *** indicated that CDB1 exhibited the highest endoglucanase(0.096 U/mL)and exoglucanase(0.156 U/mL)activities among other isolates.16S rDNA partial sequencing indicated that CDB1 had 99%similarity to the genus Anoxybacillus,and the other isolates showed the highest similarity to the genus *** cellulase gene of CDB1 isolate with the highest cellulase activity was also cloned,and its sequence is reported for the first *** studies on this thermophilic enzyme might be useful for industrial applications.

关键词： Anoxybacillus Cellulase Enzyme activity assay Thermophilic bacteria 16S rDNA

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SecA inhibitors:next generation antimicrobials

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Journal of Chinese Pharmaceutical Sciences 2012年第6期21卷 526-530页

作者： Arpana Chaudhary Yinghsin Hsieh Hsiuchin Yang Phang C.Tai 王炳和 Departments of Biology Center for Diagnostics and Therapeuticsand Center for Biotechnology and Drug DesignGeorgia State University Departments of Chemistry Center for Diagnostics and Therapeuticsand Center for Biotechnology and Drug DesignGeorgia State University

Health problems caused by bacterial infection have become a major public health concern in recent years due to the widespread emergence of drug-resistant bacterial ***,the need for the development of new types of antimicrobial agents,especially those with a novel mechanism of action,is ***,one of the key components of the secretion(Sec) pathway,is a new promising target for antimicrobial agent *** recent years,promising leads targeting SecA have been identified and the feasibility of developing antimicrobial agents through the inhibition of SecA has been *** hope this review will help stimulate more research in this area so that new antimicrobials can be obtained by targeting SecA.

关键词： SecA inhibitors Antimicrobials Natural sources Small-molecule inhibitors

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