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Cancer and neurodegenerative disorders:pathogenic convergence through microRNA regulation

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分子细胞生物学报:英文版 2011年第3期3卷 176-180页

作者： Liqin Du Alexander Pertsemlidis Harold C.Simmons Comprehensive Cancer center UT Southwestern Medical Center5323 Harry Hines BoulevardDallasTexas 75390USA eugene mcdermott center for human growth and development UT Southwestern Medical Center5323 Harry Hines BoulevardDallasTexas 75390USA Department of Internal Medicine UT Southwestern Medical Center5323 Harry Hines BoulevardDallasTexas 75390USA

Although cancer and neurodegenerative disease are two distinct pathological disorders,emerging evidence indicates that these two types of disease share common mechanisms of genetic and molecular *** studies show that individual microRNAs(miRNAs)could be involved in the pathology of both diseases,indicating that the mechanisms of these two seemingly dichotomous diseases converge in the dysregulation of gene expression at the post-transcriptional *** the increasing evidence showing that miRNA-based therapeutic strategies that modulate the activity of one or more miRNAs are potentially effective for a wide range of pathological conditions,the involvement of miRNAs in the common pathways of leading both diseases suggests a bright future for developing common therapeutic approaches for both ***,the miRNAs that are dysregulated in both diseases may hold promise as uniquely informative diagnostic ***,we review recent studies on the miRNAs that have been implicated in both cancer and neurodegenerative diseases.

关键词： microRNA cancer neurodegenerative disease

The cartilage matrisome in adolescent idiopathic scoliosis

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Bone Research 2020年第1期8卷 1-13页

作者： Carol AWise Diane Sepich Aki Ushiki Anas MKhanshour Yared HKidane Nadja Makki Christina AGurnett Ryan SGray Jonathan JRios Nadav Ahituv Lila Solnica-Krezel center for Pediatric Bone Biology and Translational Research Texas Scottish Rite Hospital for Children2222 Welborn St.DallasTX 75219USA mcdermott center for human growth and development University of Texas Southwestern Medical CenterDallasTX 75235USA Departments of Pediatrics University of Texas Southwestern Medical CenterDallasTX 75235USA Orthopaedic Surgery University of Texas Southwestern Medical CenterDallasTX 75235USA Department of developmental Biology Washington University School of MedicineSt.LouisMO 63110USA Department of Bioengineering and Therapeutic Sciences University of California San FranciscoSan FranciscoCA 94158USA Institute for human Genetics University of California San FranciscoSan FranciscoCA 94158USA Department of Anatomy and Cell Biology University of FloridaCollege of MedicineGainesvilleFL 32610USA Departments of Neurology Washington University School of MedicineSt LouisMO 63110USA Pediatrics Washington University School of MedicineSt LouisMO 63110USA Orthopaedic Surgery Washington University School of MedicineSt LouisMO 63110USA Department of Pediatrics Dell Pediatric Research InstituteUniversity of Texas at Austin Dell Medical SchoolAustinTX 78723USA

The human spinal column is a dynamic,segmented,bony,and cartilaginous structure that protects the neurologic system and simultaneously provides balance and *** with developmental disorders that affect the patterning or shape of the spine can be at risk of neurologic and other physiologic *** most common developmental disorder of the spine is scoliosis,a lateral deformity in the shape of the spinal *** may be part of the clinical spectrum that is observed in many developmental disorders,but typically presents as an isolated symptom in otherwise healthy adolescent *** idiopathic scoliosis(AIS)has defied understanding in part due to its genetic *** have come from recent genome-wide association studies(GWAS)and next generation sequencing(NGS)of human AIS cohorts,as well as investigations of animal *** studies have identified genetic associations with determinants of cartilage biogenesis and development of the intervertebral disc(IVD).Current evidence suggests that a fraction of AIS cases may arise from variation in factors involved in the structural integrity and homeostasis of the cartilaginous extracellular matrix(ECM).Here,we review the development of the spine and spinal cartilages,the composition of the cartilage ECM,the so-called"matrisome"and its functions,and the players involved in the genetic architecture of *** also propose a molecular model by which the cartilage matrisome of the IVD contributes to AIS susceptibility.

关键词： cartilage adolescent scoliosis

Phytogenic feed additives alleviate pathogenic Escherichia coli-induced intestinal damage through improving barrier integrity and inhibiting inflammation in weaned pigs

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Journal of Animal Science and Biotechnology 2023年第1期14卷 295-306页

作者： Se Yeon Chang Min Ho Song Ji Hwan Lee Han Jin Oh Yong Ju Kim Jae Woo An Young Bin Go Dong Cheol Song Hyun AhCho Seung Yeol Cho Dong Jun Kim Mi Suk Kim Hyeun Bum Kim Jin Ho Cho Department of Animal Science Chungbuk National UniversityCheongju 28644South Korea. Division of Animal and Dairy Science Chungnam National UniversityDaejeon 34134South Korea. eugene-Bio Suwon 16675South Korea. Department of Animal Resources Science Dankook UniversityCheonan 31116South Korea.

Background:This study was conducted to investigate the effects of each phytogenic feed additive(PFA;PFA1,bitter citrus extract;PFA2,a microencapsulated blend of thymol and carvacrol;PFA3,a mixture of bitter citrus extract,thymol,and carvacrol;PFA4,a premixture of grape seed,grape marc extract,green tea,and hops;PFA5,fenugreek seed powder)on the growth performance,nutrient digestibility,intestinal morphology,and immune response in weaned pigs infected with Escherichia coli(***).Results:A total of 634-week-old weaned pigs were placed in individual metabolic cages and assigned to seven treatment *** seven treatments were as follows:1)NC;basal diet without *** challenge,2)PC;basal diet with *** challenge,3)T1;PC+0.04%PFA1,4)T2;PC+0.01%PFA2,5)T3;PC+0.10%PFA3,6)T4;PC+0.04%PFA4,7)T5;PC+0.10%*** experiments lasted in 21 d,including 7 d before and 14 d after the first *** *** the *** challenge treatments,all pigs were orally inoculated by dividing a total of 10 mL of *** F18 for 3 consecutive *** PFA-added groups significantly increased(Pgrowth *** them,the mixed additive of bitter citrus extract,thymol,and carvacrol showed the most effective results,improving immune response,intestinal morphology,and expression of tight junction

关键词： Barrier integrity Escherichia coli Immunity Phytogenic feed additive Post-weaning diarrhea Weaned pigs

Targeting cancer stem cell pathways for cancer therapy

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2395-2429页

作者： Liqun Yang Pengfei Shi Gaichao Zhao Jie Xu Wen Peng Jiayi Zhang Guanghui Zhang Xiaowen Wang Zhen Dong Fei Chen Hongjuan Cui State Key Laboratory of Silkworm Genome Biology Southwest University400716 ChongqingChina Cancer center Medical Research InstituteSouthwest University400716 ChongqingChina Department of Pharmaceutical Sciences Eugene Applebaum College of Pharmacy and Health SciencesWayne State UniversityDetroitMI 48201USA

Since cancer stem cells(CSCs)were first identified in leukemia in 1994,they have been considered promising therapeutic targets for cancer *** cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies,such as recurrence,metastasis,heterogeneity,multidrug resistance,and radiation *** biological activities of CSCs are regulated by several pluripotent transcription factors,such as OCT4,Sox2,Nanog,KLF4,and *** addition,many intracellular signaling pathways,such as Wnt,NF-κB(nuclear factor-κB),Notch,Hedgehog,JAK-STAT(Janus kinase/signal transducers and activators of transcription),PI3K/AKT/mTOR(phosphoinositide 3-kinase/AKT/mammalian target of rapamycin),TGF(transforming growth factor)/SMAD,and PPAR(peroxisome proliferator-activated receptor),as well as extracellular factors,such as vascular niches,hypoxia,tumor-associated macrophages,cancer-associated fibroblasts,cancer-associated mesenchymal stem cells,extracellular matrix,and exosomes,have been shown to be very important regulators of ***,vaccines,antibodies,and CAR-T(chimeric antigen receptor T cell)cells have been developed to specifically target CSCs,and some of these factors are already undergoing clinical *** review summarizes the characterization and identification of CSCs,depicts major factors and pathways that regulate CSC development,and discusses potential targeted therapy for CSCs.

关键词： cancer stem pathways

早期成长与发展研究:利用前瞻性的养子女设计研究遗传与环境的互动(英文)

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心理学报 2008年第10期40卷 1106-1115页

作者： Leslie D. Leve Jenae M. Neiderhiser Laura V. Scaramella David Reiss Oregon Social Learning center EugeneOregonUSA The Pennsylvania State University University ParkPA USA University of New Orleans New OrleansLAUSA Yale Child Study center New Haven CTUSA

"早期成长与发展研究"(EGDS)是一个前瞻性的养子女研究计划。此项目包括了360组相连的生身父母、养父母以及刚出生就被收养的子女。此项目从婴儿3个月就开始跟踪这些被试,现在又加上200组被试,从遗传与环境的关联与互动着手,本项目将研... 详细信息

"早期成长与发展研究"(EGDS)是一个前瞻性的养子女研究计划。此项目包括了360组相连的生身父母、养父母以及刚出生就被收养的子女。此项目从婴儿3个月就开始跟踪这些被试,现在又加上200组被试,从遗传与环境的关联与互动着手,本项目将研究家庭环境和养育方式如何影响遗传因素的表达。所有被试均需要是在美国国内收养的婴儿。该研究收集了儿童的心理特征、生身父母与养父母的心理特征、养育方式、父母的生活状况等数据,以及唾液和DNA,初步分析发现,遗传与环境的互动在婴儿期就已经开始。本文也从干预的角度讨论了未来行为遗传学的走向。

关键词：遗传学领养基因环境交互作用干预儿童期

Kruppel-like factors and vascular wall homeostasis

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Journal of Molecular Cell Biology 2017年第5期9卷 352-363页

作者： Yanbo Fan Haocheng Lu Wenying Liang Wenting Hu Jifeng Zhang Y. eugene Chen Cardiovascular center Department of Internal Medicine University of Michigan Medical Center Ann Arbor MI 48109 USA

Cardiovascular diseases (CVDs) are major causes of death worldwide. Identification of promising targets for prevention and treatment of CVDs is paramount in the cardiovascular field. Numerous transcription factors regulate cellular function through modulation of specific genes and thereby are involved in the physiological and pathophysiological processes of CVDs. Although Krüppel-like factors (KLFs) have a similar protein structure with a conserved zinc finger domain, they possess distinct tissue and cell distribution patterns as well as biological functions. In the vascular system, KLF activities are regulated at both transcriptional and posttranscriptional levels. Growing in vitro, in vivo, and genetic epidemiology studies suggest that specific KLFs play important roles in vascular wall biology, which further affect vascular diseases. KLFs regulate various functional aspects such as cell growth, differentiation, activation, and development through controlling a whole cluster of functionally related genes and modulating various signaling pathways in response to pathological conditions. Therapeutic targeting of selective KLF family members may be desirable to achieve distinct treatment effects in the context of various vascular diseases. Further elucidation of the association of KLFs with human CVDs, their underlying molecular mechanisms, and precise protein structure studies will be essential to define KLFs as promising targets for therapeutic interventions in CVDs.

关键词： atherosclerosis drug development endothelial cells inflammation shear stress vascular injury vascular smooth muscle cells

Efficacy of sequential treatment of HCT116 colon cancer monolayers and xenografts with docetaxel,flavopiridol,and 5-fluorouracil

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Acta Pharmacologica Sinica 2006年第10期27卷 1375-1381页

作者： Jun GUO~2 an-wu ZHOU~2 Yu-cai FU~3 Udit N VERMA~2 Debu TRIPATHY~2 eugene P FRENKEL~(2,5) Carlos R BECERRA~4 ~2Harold C.Simmons Cancer center,Division of Hematology-Oncology,Department of Medicine,University of Texas Southwestern Medical Centel.Dallas,Texas 75390,USA ~3Laboratory of Cell Senescence,Shantou University Medical College,Shantou 515041,China ~4Sammons Cancer center,Baylor University Medical center,TOPA-US Oncology,Dallas,Texas 75246,USA Division of Hematology-Oncology Department of Medicine Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas USA Laboratory of Cell Senescence Shantou University Medical College Shantou China Sammons Cancer center Baylor University Medical Center TOPA-US Oncology Dallas USA

Aim:Clinical treatment of solid tumors with docetaxel,flavopiridol,or 5-fluorou-racil(5-FU)often encounters undesirable side effects and drug *** aims to evaluate the potential role of combination therapy with docetaxel,flavopiridol,or 5-FU in modulating chemosensitivity and better understand howthey might be used ***:HCT116 colon cancer cells were treatedwith docetaxel,flavopiridol,and 5-FU in several different administrative sche-dules in vitro,either sequentially or *** survival was measuredby MTT *** activity of caspase-3 was determined by caspase-3 assaysand the soft agar colony assay was used to test the colony formation of HCT116cells in soft *** also established xenograft models to extend in vitro obser-vations to an in vivo ***:The maximum cytotoxicity was found whenhuman colon cancer HCT116 cells were treated with docetaxel for 1 h followed byflavopiridol for 24 h and 5-FU for another 24 *** sequential combinationtherapy not only inhibits tumor cell growth more strongly compared to othercombination therapies but also significantly reduces colony formation in soft agarand augments apoptosis of HCT116 *** of docetaxel followed 1 hlater by flavopiridol,followed 24 h later by 5-FU in xenograft models,also resultedin delayed tumor growth and higher survival ***:These resultshighlight the importance of an administrative schedule when combining docetaxelwith flavopiridol and 5-FU,providing a rationale explanation for its developmentin clinical trials.

关键词： combination drug therapy docetaxel flavopiridol fluorouracil colonic neoplasms

Disease modifying treatment of spinal cord injury with directly reprogrammed neural precursor cells in non-human primates

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World Journal of Stem Cells 2021年第5期13卷 452-469页

作者： Vladimir P Baklaushev Oleg V Durov Vladimir A Kalsin eugene V Gulaev Sergey V Kim Ilya L Gubskiy Veronika A Revkova Ekaterina M Samoilova Pavel A Melnikov Dzhina D Karal-Ogly Sergey V Orlov Alexander V Troitskiy Vladimir P Chekhonin Alexander V Averyanov Jan-Eric Ahlfors Biomedical Research Federal Research and Clinical Center of Specialized Medical Care and Medical TechnologiesFMBA of RussiaMoscow 115682MoskvaRussia Department of Neurosurgery Federal Research and Clinical Center of Specialized Medical Care and Medical TechnologiesFMBAMoscow 115682MoskvaRussia Department of Anesthesiology N.N.Blokhin Russian Cancer Research CentreMoscow 115478MoskvaRussia Radiology and Clinical Physiology Scientific Research center Federal center of brain research and neurotechnologies of the Federal Medical Biological AgencyMoscow 117997Russia Department of Neurobiology Serbsky National Medical Research Center for Psychiatry and NarcologyMoscow 119992MoskvaRussia Department of Primatology Russian Acad Med SciResearch Institute of Medical PrimatologySochi 119992SochiRussia Department of Vascular Surgery Federal Research and Clinical Center of Specialized Medical Care and Medical TechnologiesFMBA of RussiaMoscow 115682MoskvaRussia Department of Basic and Applied Neurobiology V.P.Serbsky Federal Medical Research Center for Psychiatry and NarcologyRussia Department of Medical Nanobiotechnology Pirogov Russian National Research Medical University(RNRMU)Moscow 115682MoskvaRussia New World Laboratories Laval H7V 4A7QuebecCanada

BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical *** reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first *** use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human *** To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of *** Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured *** resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid *** immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth *** Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after *** functional improvement described was not associated with neuronal differentiation of th

关键词： Direct cell reprogramming Neural precursor cells Directly reprogrammed neural precursor cells Spinal cord injury Nonhuman primates Regenerative therapy,Evoked potentials

Ab initio investigation of the cyclodehydrogenation process for polyanthrylene transformation to graphene nanoribbons

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npj Computational Materials 2019年第1期5卷 339-344页

作者： Zhongcan Xiao Chuanxu Ma Wenchang Lu Jingsong Huang Liangbo Liang Kunlun Hong An-Ping Li Bobby G.Sumpter Jerzy Bernholc Department of Physics North Carolina State UniversityRaleighNC 27695USA center for Nanophase Materials Sciences Oak Ridge National LaboratoryOak RidgeTN 37831USA Computational Sciences&Engineering Division Oak Ridge National LaboratoryOak RidgeTN 37831USA

Graphene nanoribbons(GNRs)can be synthesized from molecular precursors with atomic precision.A prominent case is the 7-atom-wide armchair GNR made from 10,10′-dibromo-9,9′-bianthryl(DBBA)precursors on metal substrates through dehalogenation/polymerization followed by *** investigate the key aspects of the cyclodehydrogenation process by evaluating the energy profiles of various reaction pathways using density functional theory and the nudged elastic band *** metal substrate plays a critical catalytic role by providing stronger adsorption for products and facilitating H *** polyanthrylene on an extra layer of GNR on Au,the underlying GNR insulates it from the Au substrate and increases the reaction barriers,rendering the polyanthrylene“quasi-freestanding”.However,positive charge injection can induce localized *** find that this is due to the stabilization of an intermediate state through an arenium ion mechanism and favorable orbital *** results provide mechanistic insight into the effects of the metal substrate and charge injection on cyclodehydrogenation during GNR synthesis and offer guidance for the design and growth of new graphitic structures.

关键词： method rendering stabilization