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Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

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Neural Regeneration Research 2025年第9期20卷 2655-2666页

作者： Yiyang Qin Wenzhen Zhu Tingting Guo Yiran Zhang Tingting Xing Peng Yin Shihua Li Xiao-Jiang Li Su Yang Guangdong Key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong–HongKong–Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto *** mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy *** aggregates alter protein-protein interactions and compromise transcriptional *** this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic *** n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor *** down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor *** findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

关键词： androgen receptor mesencephalic astrocyte-derived neurotrophic factor mouse model neurodegeneration neuronal loss neurotrophic factor polyglutamine disease protein misfolding spinal and bulbar muscular atrophy transcription factor

Gastrointestinal B-cell lymphomas:From understanding B-cell physiology to classification and molecular pathology

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World Journal of Gastrointestinal Oncology 2012年第12期4卷 238-249页

作者： Xavier Sagaert Thomas Tousseyn Rhonda K Yantiss Department of pathology University Hospitals Leuven Department of pathology and laboratory Medicine Weill Cornell Medical College

The gut is the most common extranodal site where lymphomas arise. Although all histological lymphoma types may develop in the gut, small and large B-cell lymphomas predominate. The sometimes unexpected finding of a lymphoid lesion in an endoscopic biopsy of the gut may challenge both the clinician (who is not always familiar with lymphoma pathogenesis) and the pathologist (who will often be hampered in his/her diagnostic skill by the limited amount of available tissue). Moreover, the past 2 decades have spawned an avalanche of new data that encompasses both the function of the reactive B-cell as well as the pathogenic pathways that lead to its neoplastic counterpart, the B-cell lymphoma. Therefore, this review aims to offer clinicians an overview of B-cell lymphomas in the gut, and their pertinent molecular features that have led to new insights regarding lymphomagenesis. It addresses the question as how to incorporate all presently available information on normal and neoplastic B-cell differentiation, and how this knowledge can be applied in daily clinical practice (e.g., diagnostic tools, prognostic biomarkers or therapeutic targets) to optimalise the managment of this heterogeneous group of neoplasms.

关键词： B-cell Non-Hodgkin’s lymphomas Gut Molecular pathology

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

Three-dimensional structure of the Chinese Sacbrood bee virus

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Science China(Life Sciences) 2001年第4期44卷 443-448页

作者：张景强冯建勋梁玉尧谌东华周正洪张勤奋卢炘英 State Key laboratory for bio-control Zhongshan University Guangzhou 510275 China Department of pathology and laboratory Medicine University of Texas-Houston Medicine School Houston TX 77030 USA

The RNA of Chinese Sacbrood Bee Virus (CSBV) was purified and used as template to obtain a 1096 bp cDNA fragment by RT-PCR amplification. This DNA fragment was cloned into pGEM-T Easy Vector for sequencing. Analyses of the sequenced CSBV RNA fragment revealed a nucleotide sequence homology of 87.6% and a deduced amino-acid sequence homology of 94.6% with that of the Sacbrood Virus (SBV), indicating that CSBV is a different but highly homologous virus of SBV. The three-dimensional (3D) structure of CSBV was determined at 2.5 nm resolution by using electron cryo-microscopy (cryoEM) and computer reconstruction methods. The 3-D structure showed that the capsid has a T= 1 (or P= 3) icosahedral capsid shell with a smooth surface. There were 12 pentons at its icosahedral vertices (5-fold axes) and 132 holes penetrating the shell. The 3-D structure also revealed densities corresponding to the CSBV genome, suggesting icosahedrally-ordered RNA organization, a novel feature not previously reported for any picornavi-ruses.

关键词： Chinese Sacbrood virus (CSBV), sequence, three-dimensional structure, electron cryo-microscopy.

Early detection and prevention of pancreatic cancer:Is it really possible today?

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World Journal of Gastroenterology 2014年第34期20卷 12118-12131页

作者： Marco Del Chiaro Ralf Segersvrd Matthias Lohr Caroline Verbeke Division of Surgery Department of Clinical ScienceIntervention and Technology (CLINTEC)Karolinska Institute141 86 StockholmSweden Division of pathology Department of Laboratory MedicineKarolinska Institute141 86 StockholmSweden

Pancreatic cancer is the 4th leading cause of cancer-related death in Western countries. Considering the low incidence of pancreatic cancer, population-based screening is not feasible. However, the existence of a group of individuals with an increased risk to develop pancreatic cancer has been well established. In particular, individuals suffering from a somatic or genetic condition associated with an increased relative risk of more than 5- to 10-fold seem to be suitable for enrollment in a surveillance program for prevention or early detection of pancreatic cancer. The aim of such a program is to reduce pancreatic cancer mortality through early or preemptive surgery. Considering the risk associated with pancreatic surgery, the concept of preemptive surgery cannot consist of a prophylactic removal of the pancreas in high-risk healthy individuals, but must instead aim at treating precancerous lesions such as intraductal papillary mucinous neoplasms or pancreatic intraepithelial neoplasms, or early cancer. Currently, results from clinical trials do not convincingly demonstrate the efficacy of this approach in terms of identification of precancerous lesions, nor do they define the outcome of the surgical treatment of these lesions. For this reason, surveillance programs for individuals at risk of pancreatic cancer are thus far generally limited to the setting of a clinical trial. However, the acquisition of a deeper understanding of this complex area, together with the increasing request for screening and treatment by individuals at risk, will usher pancreatologists into a new era of preemptive pancreatic surgery. Along with the growing demand to treat individuals with precancerous lesions, the need for low-risk investigation, low-morbidity operation and a minimally invasive approach becomes increasingly pressing. All of these considerations are reasons for preemptive pancreatic surgery programs to be undertaken in specialized centers only.

关键词： Preemptive pancreatic surgery Cystic tumors of the pancreas Familial pancreatic cancer Early detection Pancreas cancer screening

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

Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells

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Journal of Zhejiang University-Science B(biomedicine & biotechnology) 2012年第1期13卷 11-19页

作者： Zhong SHI1,Rui BAI1,Zhi-xuan FU1,Yong-liang ZHU2,Rong-fu WANG3,Shu ZHENG1(1Cancer Institute(Key laboratory of Cancer Prevention and intervention,China National Ministry of Education,Key laboratory of Molecular biology in Medical Sciences,Zhejiang Province,China),the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China)(2Department of Gastroenterology,the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,China)(3Center for Cell and Gene Therapy,Department of pathology and Immunology,Baylor College of Medicine,Houston,Texas 77030,USA) Cancer Institute Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Zhejiang Province China.

Objective:We aimed to perform a preliminary study of the association between induced pluripotent stem cell(iPS)-related genes and biological behavior of human colorectal cancer(CRC) cells,and the potential for developing anti-cancer drugs targeting these ***:We used real-time reverse transcriptase polymerase chain reaction(RT-PCR) to evaluate the transcript levels of iPS-related genes NANOG,OCT4,SOX2,C-MYC and KLF4 in CRC cell lines and cancer stem cells(CSCs)-enriched tumor *** was knockdowned in CRC cell line SW620 by lentiviral transduction.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assays,plate colony formation,and a mouse xenograft model were used to evaluate alterations in biological behavior in NANOG-knockdown SW620 ***,mock-knockdown and NANOG-knockdown cells were treated with 5-fluorouracil(5-FU) and survival rate was measured by MTT assay to evaluate drug ***:A significant difference in the transcript levels of iPS-related genes between tumor spheres and their parental bulky cells was *** knockdown suppressed proliferation,colony formation,and in vivo tumorigenicity but increased the sensitivity to 5-FU of SW620 cells.5-FU treatment greatly inhibited the expression of the major stemness-associated genes NANOG,OCT4,and ***:These results collectively suggest an overlap between iPS-related genes and CSCs in *** a certain gene NANOG may truncate the aggressiveness of CRC cells.

关键词： Induced pluripotent stem cell Cancer stem cell Colorectal cancer NANOG 5-Fluorouracil

pathology of Alcoholic Liver Disease

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Journal of Clinical and Translational Hepatology 2014年第2期2卷 103-109页

作者： Romulo Celli Xuchen Zhang Department of pathology Yale University School of Medicine New Haven CT USA pathology and laboratory Service VA Connecticut Health System and Department of Pathology Yale University School of Medicine West Haven CT USA

Alcohol-attributable burden on global health is increasing, and the relationship between population alcohol consumption and liver-related deaths is strong. Longstanding scientific and clinical work has led to a relatively thorough, if not complete, understanding of the effects of alcohol consumption on the liver. Pathologic features of alcoholic liver disease (ALD) are recognized by pathologists and used to assist clinicians in diagnosing and determining severity of disease in patients suspected of ALD. In this review, we discuss the pathologic manifestations of ALD and provide salient points on their pathophysiology. In addition, the benefits and indications of liver biopsy and important differential diagnoses, including features distinguishing these entities, are reviewed.

关键词： Alcoholic liver disease Steatosis Steatohepatitis pathology

The COI1 and DFR Genes are Essential for Regulation of Jasmonate-lnduced Anthocyanin Accumulation in Arabidopsis

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Journal of Integrative Plant biology 2007年第9期49卷 1370-1377页

作者： Qin-Fang Chen Liang-Ying Dai Shi Xiao Yun-Sheng Wang Xiong-Lun Liu Guo-Liang Wang Department of Plant pathology College of Bio-Safety Science & Technology Hunan Agricultural University Changsha 410128 China Rice Functional Genomics laboratory Hunan Agricultural University Changsha 410128 China Department of Plant pathology Ohio State University Columbus OH 43210 USA

Jasmonates （JAs） are a class of plant hormones that play important roles in the regulation of plant development and plant defense. It has been shown that Arabidopsis plants produce much higher levels of anthocyanins when treated exogenously with methyl jasmonate （MeJA）. However, a molecular link between the JA response and anthocyanin production has not been determined. The CORONATINE INSENTITIVE1 （COI1） gene is a key player in the regulation of many JA-related responses. In the present study, we demonstrate that the COI1 gene is also required for the JA-induced accumulation of anthocyanins in Arabidopsis. Furthermore, the MeJA-inducible expression of DIHYDROFLAVONOL REDUCTASE （DFR）, an essential component in the anthocyanin biosynthesis pathway, was completely eliminated in the coil mutant. Jasmonateinduced anthocyanin accumulation was found to be independent of auxin signaling. The present results indicate that the expression of both COI1 and DFR genes is required for the regulation of JA-induced anthocyanin accumulation and that DFR may be a key downstream regulator for this process.

关键词： anthocyanin Arabidopsis, COI1 DFR jasmonates.