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Asian Journal of Urology 2023年第2期10卷 210-212页

作者： Yuki Kohada Hiroki Kusumoto Takashi Kukimoto Jotaro Mikami Jun Ito Katsutoshi Asano Toru Yaegashi Kanichi Nakagawara Jun Teishima Yasuhiro Kaiho Nobuyuki Hinata Yasuhiro Nakamura Makoto Sato Division of Urology Faculty of MedicineTohoku Medical and Pharmaceutical UniversitySendaiJapan Department of Urology Hiroshima University Graduate School of Biomedical SciencesHiroshimaJapan nihon gene research laboratories inc SendaiJapan Division of Pathology Faculty of MedicineTohoku Medical and Pharmaceutical UniversitySendaiJapan

Dear Editor,Prostate cancer is the most common cancer among men[1].Androgen deprivation therapy(ADT)has remained the primary treatment of metastatic-hormone-sensitive prostate cancer(mHSPC),providing a temporary disease control in the majority of *** initial ADT response,castration-resistance prostate cancer(CRPC)still *** study have attempted to determine possible biomarkers for poor prognosis in patients with CRPC[2].

关键词： patients metastatic cancer

Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions

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World Journal of Gastroenterology 2015年第30期21卷 9067-9078页

作者： Yukihito Ishii Yu Motohashi Makoto Muramatsu Yoshiaki Katsuda Katsuhiro Miyajima Tomohiko Sasase Takahisa Yamada Tohru Matsui Shinichi Kume Takeshi Ohta Japan Tobacco inc. Central Pharmaceutical Research Institute Japan Tobacco inc. Central Pharmaceutical Research InstituteToxicology Research Laboratories Niigata University Graduate School of Science and Technology Kyoto University Graduate School of Agriculture

AIM:To investigate the histological features of the liver in spontaneously diabetic Torii(SDT) fatty rats compared with age-matched Sprague-Dawley(SD) ***:Female SDT Leprfa(SDT fatty) rats and age-matched SD rats were fed ad libitum. Body weight and biochemical parameters,such as serum glucose,triglyceride(TG),total cholesterol(TC),alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels as well as fatty acid and TG accumulation in the liver were evaluated at 8 wk of age in the nonfasting state and at 8-wk intervals from 8 to 40 wk of age. Histopathological examinations of the liver were performed using hematoxylin and eosin and Sirius Red staining as well as double staining for ED-1 and toluidine blue. The expression of genes involved in TG synthesis,inflammation,and fibrosis was examined in the ***:SDT fatty rats showed significantly increased body weight compared with SD rats. Serum glucose,TG,and TC levels were significantly higher in SDT fatty rats compared with SD rats. The serum AST and ALT levels in SDT fatty rats were significantly elevated at 8 wk of age compared with the levels in SD rats. Hepatic TG content was marked in SDT fatty rats from 8 to 32 wk of age. Histopathologically,severe hepatosteatosis accompanied by inflammation was observed at 8 wk of age,and fibrosis started to occur at 32 wk of age. Furthermore,Sirius Red and ED-1 staining were increased in the liver at 32 wk of age. Hepatic gene expression related to TG synthesis,inflammation and fibrosis tended to increase in SDT fatty rats compared with SD rats,and the gene expression related to TG secretion was decreased in SDT fatty rats compared with SD rats. CONCLUSION:Female SDT fatty rats have the potential to become an important animal model of nonalcoholic steatohepatitis with type 2 diabetes and obesity.

关键词： Nonalcoholic steatohepatitis Spontaneouslydiabetic Torii fatty rat Fibrosis Fatty liver Metabolicsyndrome

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选择性雄激素受体调节子的开发及其治疗应用

中华男科学杂志 2002年第3期8卷 162-168页

作者： Fang Chen( 陈芳)（Department of Bone Biology & Osteoporosis research Merck Research Laboratories Merck & Co Inc. WP26A-1000 West Point PA 19486 USA）

雄激素控制着广泛的生理学功能.雄激素受体作为调节雄激素多种生物学作用的甾体类受体,是一种配基诱导的转录因子.雄激素信号系统的异常导致了从性别确定和性征发育到精神和情感失常的许多紊乱.雄激素替代治疗能改善许多临床症状,包括... 详细信息

雄激素控制着广泛的生理学功能.雄激素受体作为调节雄激素多种生物学作用的甾体类受体,是一种配基诱导的转录因子.雄激素信号系统的异常导致了从性别确定和性征发育到精神和情感失常的许多紊乱.雄激素替代治疗能改善许多临床症状,包括性腺机能低下与骨质疏松,但由于疗效不高和缺少方便给药的安全制剂而受到限制.最近甾体类受体和选择性受体调节子的基因调控技术,为选择性雄激素受体调节子能否解答现行雄激素治疗中存在的问题,提供了验证的机会.配基化的雄激素受体转录引发复合物的组成决定了基因调控的特异性,设计用于引发组织和启动子特异基因转录的合成配基提供了开发更有效的雄激素治疗的希望.建立能预测合成配基活性的测试方法是选择性雄激素受体调节子开发的关键.化合物筛选的高效率和基因指纹技术的进步,如微阵列技术和蛋白质组学,将加速有效的选择性受体调节子鉴定.

关键词：雄激素雄激素受体选择性雄激素受体调节子核受体调节子

Enhanced genome editing to ameliorate a genetic metabolic liver disease through co-delivery of adeno-associated virus receptor

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Science China(Life Sciences) 2022年第4期65卷 718-730页

作者： Shuming Yin Lie Ma Tingting Shao Mei Zhang Yuting Guan Liren Wang Yaqiang Hu Xi Chen Honghui Han Nan Shen Wenjuan Qiu Hongquan Geng Yongguo Yu Shichang Li Weishi Yu Mingyao Liu Dali Li Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai200241China Bioray laboratories inc. Shanghai200241China Xinhua Hospital Shanghai Jiao Tong University School of MedicineShanghai200092China College of Physical Education and Health East China Normal UniversityShanghai200241China Key Laboratory of Adolescent Health Assessment and Exercise Intervention Ministry of EducationCollege of Physical Education and HealthEast China Normal UniversityShanghai200241China CIPHER gene LLC Beijing100089China

Genome editing through adeno-associated viral(AAV) vectors is a promising gene therapy strategy for various diseases,especially genetic disorders. However, homologous recombination(HR) efficiency is extremely low in adult animal models. We assumed that increasing AAV transduction efficiency could increase genome editing activity, especially HR efficiency, for in vivo gene therapy. Firstly, a mouse phenylketonuria(PKU) model carrying a pathogenic R408W mutation in phenylalanine hydroxylase(Pah) was generated. Through co-delivery of the general AAV receptor(AAVR), we found that AAVR could dramatically increase AAV transduction efficiency in vitro and in vivo. Furthermore, co-delivery of SaCas9/sgRNA/donor templates with AAVR via AAV8 vectors increased indel rate over 2-fold and HR rate over 15-fold for the correction of the single mutation in Pah;mice. Moreover, AAVR co-injection successfully increased the site-specific insertion rate of a 1.4 kb Pah cDNA by 11-fold, bringing the HR rate up to 7.3% without detectable global off-target effects. Insertion of Pah cDNA significantly decreased the Phe level and ameliorated PKU symptoms. This study demonstrates a novel strategy to dramatically increase AAV transduction which substantially enhanced in vivo genome editing efficiency in adult animal models, showing clinical potential for both conventional and genome editing-based gene therapy.

关键词： CRISPR/Cas9 gene therapy adeno-associated virus(AAV) AAVR Pah PKU

Granulysin and its clinical significance as a biomarker of immune response and NK cell related neoplasms

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World Journal of Hematology 2014年第4期3卷 128-137页

作者： Masayuki Nagasawa Kazuyuki Ogawa Kinya Nagata Norio Shimizu Department of Hematology Oncologyand ImmunologyTokyo Bay Urayasu/Ichikawa Medical CenterChiba 279-0001Japan Bio Medical laboratories inc. Research and Development CenterSaitama 602-0841Japan Tokyo Medical and Dental University Post Graduate SchoolDepartment of VirologyTokyo 113-8519Japan

Granulysin is a cytotoxic granular protein that was identified from human T cells by using the gene subtraction method in 1987. Based on its amino acid homology, granulysin belongs to the saposin-like protein family. The bioactive 9-k Da form of granulysin is processed from the 15-k Da pro-product in the cytoplasmic granules. It is expressed in CD8-positive αβT cells 5 d after mitogenic stimulation and constitutively in natural killer(NK) cells and γδT cells, although regulation of its expression has not yet been precisely determined. The 9-k Da granulysin form has anti-microbial activity against microorganisms such as bacteria, fungi, mycobacteria and parasites, as well as tumoricidal activity against some tumors at 1-10 μmol/L concentrations. Granulysin is secreted in both Ca-dependent and-inde-pendent manners. In sera, only the 15-k Da form is detectable and is expected to be a biomarker for immune potency, acute viral infection, anti-tumor immune reaction, acute graft vs host disease, and NK cell associated neoplasm.

关键词： Granulysin Saposin-like protein family Natural killer cell Cytotoxic T lymphocyte

A novel alternative for pyrogen detection based on a transgenic cell line

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1221-1229页

作者： Qing He Chuan-Fei Yu Gang Wu Kai-Qin Wang Yong-Bo Ni Xiao Guo Zhi-Hao Fu Lan Wang De-Jiang Tan Hua Gao Can Wang Gang Chen Xu-Hong Chen Bo Chen Jun-Zhi Wang National Institutes for Food and Drug Control BeijingChina School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyangChina Shanghai Institute for Food and Drug Control ShanghaiChina KeyMed Biosciences inc. ChengduChina

Pyrogen,often as a contaminant,is a key indicator affecting the safety of almost all parenteral drugs(including biologicals,chemicals,traditional Chinese medicines and medical devices).It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted‘reduction,replacement and refinement’principle,which has been highly considered by regulatory agencies from different *** used NF-κB,a central signalling molecule mediating inflammatory responses,as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence ***,we show that this test can quantitatively and sensitively detect endotoxin(lipopolysaccharide from different strains)and nonendotoxin(lipoteichoic acid,zymosan,peptidoglycan,lectin and glucan),has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals(group A&C meningococcal polysaccharide vaccine;basiliximab;rabies vaccine(Vero cells)for human use,freeze-dried;Japanese encephalitis vaccine(Vero cells),inactivated;insulin aspart injection;human albumin;recombinant human erythropoietin injection(CHO Cell)).The within-laboratory reproducibility of the test in three independent laboratories was 85%,80%and 80%and the interlaboratory reproducibility among laboratories was 83.3%,95.6%and 86.7%.The sensitivity(true positive rate)and specificity(true negative rate)of the test were 89.9%and 90.9%,*** summary,the test provides a novel alternative for pyrogen detection.

关键词： pyrogen rabbit replace

Comparison of approaches to quantify SARS-CoV-2 in wastewater using RT-qPCR: Results and implications from a collaborative inter-laboratory study in Canada

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Journal of Environmental Sciences 2021年第9期33卷 218-229页

作者： Alex H.S.Chik Melissa B.Glier Mark Servos Chand S.Mangat Xiao-Li Pang Yuanyuan Qiu Patrick M.D’Aoust Jean-Baptiste Burnet Robert Delatolla Sarah Dorner Qiudi Geng John P.Giesy Jr Robert Mike McKay Michael R.Mulvey Natalie Prystajecky Nivetha Srikanthan Yuwei Xie Bernadette Conant Steve E.Hrudey Canadian SARS-CoV-Inter-Laboratory Consortium Consultant to Canadian Water Network inc. KitchenerCanada Presently at Ontario Clean Water Agency MississaugaCanada Environmental Microbiology BC Centre for Disease ControlVancouverCanada Department of Biology University of WaterlooWaterlooCanada National Microbiology Laboratory Public Health Agency of CanadaWinnipegCanada Public Health Laboratory Alberta Precision LaboratoryEdmontonCanada Department of Laboratory Medicine&Pathology Faculty of Medicine and DentistryUniversity of AlbertaEdmontonAB T6G 2G3Canada Faculty of Engineering University of OttawaOttawaCanada Département des génies civil géologique et des minesPolytechnique MontréalMontréalCanada Veterinary Biomedical Sciences University of SaskatchewanSaskatoonCanada Toxicology Centre University of SaskatchewanSaskatoonCanada Great Lakes Institute for Environmental research University of WindsorWindsorCanada Department of Medical Microbiology University of ManitobaWinnipegCanada Department of Pathology and Laboratory Medicine University of British ColumbiaVancouverCanada Canadian Water Network inc. WaterlooCanada Group author details below

Detection of SARS-CoV-2 RNA in wastewater is a promising tool for informing public health decisions during the COVID-19 ***,approaches for its analysis by use of reverse transcription quantitative polymerase chain reaction(RT-q PCR)are still far from standardized *** characterize inter-and intra-laboratory variability among results when using various methods deployed across Canada,aliquots from a real wastewater sample were spiked with surrogates of SARS-CoV-2(gamma-radiation inactivated SARS-CoV-2 and human coronavirus strain 229E[HCoV-229E])at low and high levels then provided"blind"to eight *** estimates reported by individual laboratories were consistently within a 1.0-log_(10) range for aliquots of the same spiked *** laboratories distinguished between low-and high-spikes for both *** expected,greater variability was observed in the results amongst laboratories than within individual laboratories,but SARS-CoV-2 RNA concentration estimates for each spiked condition remained mostly within 1.0-log_(10) *** no-spike wastewater aliquots provided yielded non-detects or trace levels(gene copies/mL)of SARS-CoV-2 *** appear linked to methods that included or focused on the solids fraction of the wastewater matrix and might represent in-situ SARS-CoV-2 to the wastewater ***-229E RNA was not detected in the no-spike ***,all methods yielded comparable results at the conditions *** behavior of SARS-CoV-2 and spiked surrogates in wastewater should be considered to evaluate method effectiveness.A consistent method and laboratory to explore wastewater SARS-CoV-2 temporal trends for a given system,with appropriate quality control protocols and documented in adequate detail should succeed.

关键词： COVID-19 Wastewater surveillance Public health Quality assurance Quality control

PA基因影响欧亚类禽型H1N1猪流感病毒致病性和传播能力的机制

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中国预防兽医学报 2022年第9期44卷 1023-1023页

作者： MENG FEI YANG HUANG-LIANG QU ZHI-YUAN State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences Harbin 150001 People's Republic of China. Guangdong Laboratory for Lingnan Modern Agriculture Guangzhou 510642 People's Republic of China. Division of Virology Department of Microbiology and Immunology International Research Center for Infectious Diseases Institute of Medical Science University of Tokyo Tokyo 108-8639 Japan. The research Center for Global Viral Diseases National Center for Global Health and Medicine Research Institute Tokyo 162-8655 Japan. Influenza research Institute Department of Pathobiological Sciences School of Veterinary Medicine University of Wisconsin-Madison Madison WI 53711.

不同宿主来源的流感病毒在猪体内经基因重配后可以产生新型病毒,解析新型流感病毒生物学表型变化机制对保护动物健康和预防人类流感大流行具有重要意义。近日,美国科学院院报《PNAS》杂志在线发表了题为“A Eurasian avian-like H1N1 sw... 详细信息

不同宿主来源的流感病毒在猪体内经基因重配后可以产生新型病毒,解析新型流感病毒生物学表型变化机制对保护动物健康和预防人类流感大流行具有重要意义。近日,美国科学院院报《PNAS》杂志在线发表了题为“A Eurasian avian-like H1N1 swine influenza reassortant virus became pathogenic and highly transmissible due to mutations in its PA gene”的研究论文,揭示了猪流感病毒(SIV)致病性和传播能力增强的分子机制。

关键词：动物健康流感病毒美国科学院 H1N1 新型病毒致病性

Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight