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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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Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： Toshiaki Tsurui Yuya Hirasawa Yutaro Kubota Kiyoshi Yoshimura Takuya Tsunoda Department of Medical Oncology Showa UniversityTokyo 1428555Japan Department of Clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic ***,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently *** SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe *** tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated *** RAS or BRAF mutations were *** Eastern Cooperative Oncology group(ECOG)performance status(PS)score was *** drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly ***,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse *** Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

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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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Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural Regeneration Research 2025年第2期20卷 475-476页

作者： Jackson Powell Tobias Steinschaden Rose Horowitz Yuanquan Song Raymond G.Perelman Center for Cellular and Molecular therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate group University of PennsylvaniaPhiladelphiaPAUSA Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPAUSA Medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural *** intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following *** the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to *** works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of *** role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

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The potential mechanism of Isodon suzhouensis against COVID-19 via EGFR/TLR4 pathways

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Food Science and Human Wellness 2024年

作者： Hong Duan Wei Wang Shu Li Han Li Ghulam Jilany Khan Fawang Liu Kefeng Zhai Lili Li Zhaojun Wei General Clinical Research Center， Anhui Wanbei Coal-Electricity group General Hospital Department of Pharmacology and therapeutics， Faculty of Pharmacy， University of Central Punjab College of Biological and Food Engineering， Anhui Polytechnic University School of Biological and Food Engineering， Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province， Suzhou University School of Food and Biological Engineering， Hefei University of Technology

Corona Virus Disease 2019 (COVID-19) has brought the new challenges to scientific research. Isodon suzhouensis has good anti-inflammatory and antioxidant stress effects， which is considered as a potential treatment for COVID-19. The possibility for the treatment of COVID-19 with suzhouensis and its potential mechanism of action were explored by employing molecular docking and network pharmacology. Network pharmacology and molecular docking were used to screen drug targets， and Lipopolysaccharide (LPS) induced RAW264.7 and NR8383 cells inflammation model was used for experimental verification. Collectively a total of 209 possible linkages against 18 chemical components from suzhouensis and 1194 COVID-19 related targets were selected. Among these， 164 common targets were obtained from the intersection of suzhouensis and COVID-19. GO and KEGG enriched 582 function targets and 87 target proteins pathways， respectively. The results from molecular docking studies revealed that rutin， vitexin， isoquercitrin and quercetin had significant binding ability with SARS-CoV-23CLpro and ACE2. In vitro studies showed that Isodon suzhouensis extract (ISE) may inhibit the activation of PI3K/Akt pathway and the expression level of downstream pro-inflammatory factors by inhibiting the activation of EGFR in RAW264.7 cells induced by LPS. In addition， ISE was able to inhibit the activation of TLR4/NF-κB signaling pathway in NR8383 cells exposed to LPS. Overall， the network pharmacology and in vitro studies conclude that active components from suzhouensis have strong therapeutic potential against COVID-19 through multi-target， multi-pathway dimensions and can be a promising candidate against COVID-19.

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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Latest updates on structure and recommendations of cardiac rehabilitation programs in chronic heart failure

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World Journal of Clinical Cases 2024年第8期12卷 1382-1387页

作者： Christos Kourek Alexandros Briasoulis Dimitrios E Magouliotis John Skoularigis Andrew Xanthopoulos Medical School of Athens National and Kapodistrian University of AthensAthens 15772Greece Department of Clinical therapeutics Alexandra HospitalFaculty of MedicineNational and Kapodistrian University of AthensAthens 11528Greece Department of Surgery University Hospital of LarissaLarissa 41110Greece of Cardiology University Hospital of LarissaLarissa 41110Greece

Chronic heart failure(HF)is a clinical syndrome with high morbidity and mor-tality *** rehabilitation(CR)is a medically supervised program designed to maintain or improve cardiovascular health of people living with HF,recommended by both American and European guidelines.A CR program con-sists of a multispecialty group including physicians,nurses,physiotherapists,trainers,nutritionists,and psychologists with the common purpose of improving functional capacity and quality of life of chronic HF *** activity,lifestyle,and psychological support are core components of a successful CR *** has been shown to be beneficial in all ejection fraction categories in HF and most patients,who are stable under medication,are capable of *** individualized exercise prescription should be developed on the basis of a baseline evaluation in all *** main modalities of exercise training are aerobic exercise and muscle strength training of different intensity and *** is important to set the appropriate clinical outcomes from the beginning,in order to assess the effectiveness of a CR *** are still significant limitations that prevent patients from participating in these programs and need to be solved.A significant limitation is the generally low quality of research in CR and the presence of negative trials,such as the rehabilitation after myocardial infarction trial,where comprehensive rehabilitation following myocardial infraction had no important effect on mortality,morbidity,risk factors,or health-related quality of life or *** the present editorial,we present all the updated knowledge and recommendations in CR programs.

关键词： Cardiac rehabilitation Heart failure Outcomes Exercise protocols Prescription Future perspectives Limitations

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The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens

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Infectious Microbes & Diseases 2024年第2期6卷 65-73页

作者： Alexandra Stream Ross Corriden Simon Döhrmann Richard L.Gallo Victor Nizet Ericka L.Anderson Division of Host-Microbe Systems and therapeutics Department of PediatricsUniversity of California San Diego School of MedicineLa JollaCaliforniaUSA Department of Dermatology University of California San Diego School of MedicineLa JollaCaliforniaUSA Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San DiegoLa JollaCaliforniaUSA

Vitamin A and its biologically active derivative,retinoic acid(RA),are important for many immune ***,in particular,is essential for the development of immune cells,including neutrophils,which serve as a front-line defense against *** vitamin A deficiency has been linked to higher susceptibility to infections,the precise role of vitamin A/RA in host-pathogen interactions remains poorly ***,we provided evidence that RA boosts neutrophil killing of methicillin-resistant Staphylococcus aureus(MRSA).RA treatment stimulated primary human neutrophils to produce reactive oxygen species,neutrophil extracellular traps and the antimicrobial peptide cathelicidin(LL-37).Because RA treatment was insufficient to reduce MRSA burden in an in vivo murine model of skin infection,we expanded our analysis to other infectious *** did not affect the growth of a number of common bacterial pathogens,including MRSA,Escherichia coli K1 and Pseudomonas aeruginosa;however,RA directly inhibited the growth of group A Streptococcus(GAS).This antimicrobial effect,likely in combination with RA-mediated neutrophil boosting,resulted in substantial GAS killing in neutrophil killing assays conducted in the presence of ***,in a murine model of GAS skin infection,topical RA treatment showed therapeutic potential by reducing both skin lesion size and bacterial *** findings suggest that RA may hold promise as a therapeutic agent against GAS and perhaps other clinically significant human pathogens.

关键词： retinoic acid neutrophil bacterial infection Staphylococcus aureus group A Streptococcus neutrophil extracellular traps antimicrobial peptide cathelicidin

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Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

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