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Genes & Diseases 2024年第4期11卷 131-133页

作者： Dechao Feng Xu Shi Dengxiong Li Ruicheng Wu Jie Wang Wuran Wei Ping Han department of urology Institute of UrologyWest China HospitalSichuan UniversityChengduSichuan 610041China

Prostate cancer(PCa)is considered as an age-related disease and accounts for the most prevalence of urinary malignancies in men.1 We previously analyzed the cellular landscape of tumor microenvironment in PCa patients,where we found that cancer-related fibroblasts might play an important role in tumorigenesis and the development of PCa and tumor-associated macrophage(TAM)could function synergistically with them.2 Thus,we further integrated single-cell and bulk RNA sequencing with meta-analysis to specify the prognostic effect of TAM on PCa and construct molecular subgroups and predictive index to guide clinical practice.

关键词： patients macrophage cancer

PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3049-3067页

作者： Jianming Yang Yawen Xiao Ningning Zhao Geng Pei Yan Sun Xinyu Sun Kaiyuan Yu Chunhui Miao Ran Liu Junqiang Lv Hongyu Chu Lu Zhou Bangmao Wang Zhi Yao Quan Wang Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Institute of ImmunologyState Key Laboratory of Experimental Hematologythe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsDepartment of ImmunologySchool of Basic Medical SciencesTianjin Institute of Urologythe Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Cellular and Molecular ImmunologyTianjin Medical UniversityTianjin 300070China department of Pathology Tianjin Medical University Cancer Institute and Hospital/National Clinical Research Center of Cancer/Key Laboratory of Cancer Prevention and TherapyTianjin/Tianjin’s Clinical Research Center of CancerTianjin 30060China department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300070China

The mucosal barrier is crucial for intestinal homeostasis,and goblet cells are essential for maintaining the mucosal barrier *** proviral integration site for Moloney murine leukemia virus-1(PIM1)kinase regulates multiple cellular functions,but its role in intestinal homeostasis during colitis is ***,we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models,in the presence of intestinal *** PIM1 leads to decreased goblet cells,thus impairing resistance to colitis and colitis-associated colorectal cancer(CAC)in ***,PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling ***,PIM1 interacts with histone deacetylase 2(HDAC2)and downregulates its level via phosphorylation,thereby altering the epigenetic profiles of Wnt signaling pathway ***,these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis,which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

关键词： PIM1 HDAC2 Goblet cell Gut microbiota Intestinal homeostasis Epigenetic modification Ulcerative colitis CAC

Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China departments of Orthopaedic Surgery and urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

Semen analysis in 21st century medicine： the need for sperm function testing

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Asian Journal of Andrology 2010年第1期12卷 64-70页

作者： Dolores J. Lamb scott department of urology and the department of molecular and cellular biology Baylor College of MedicineHouston TX 77030 USA

Sperm function testing, once commonly performed for the infertile couple before employing assisted reproductive technology （ART）, has fallen out of favour in many reproductive medicine centers throughout the world. Indeed, the most recent addition of the ＇World Health Organisation （WHO） Laboratory Manual for the Examination and Processing of Hu- man Semen＇ now groups many of these procedures into a section termed Research Procedures. In large part, this reflects the current clinical practice of bypassing the in-depth evaluation of the male partner, while assuming that if a spermatozoon can be found for intracytoplasmic sperm injection （ICSI）, it must be a healthy cell capable of achieving fertilization. Never- theless, sperm function testing can provide valuable clinical insights into defects causing male infertility. Admittedly, in some cases, functional sperm deficiencies can be overcome using an ART. In other cases, couples will be empowered by the knowledge of the cause of their infertility, and for some couples, perhaps even the likelihood of ICSI success （relative to the spermatozoa）. The knowledge allows them to make truly informed reproductive decisions, including （perhaps） the de- cision to seek donor insemination, to adopt or to remain childless. Knowledge of the cause of their infertility may provide closure for couples and a sense of confidence regarding their choice of reproductive treatment.

关键词： semen analysis sperm function tests

Men with a complete absence of normal sperm morphology exhibit high rates of success without assisted reproduction

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Asian Journal of Andrology 2017年第1期19卷 39-42页

作者： Jason R Kovac Ryan P Smith Miguel Cajipe Dolores J Lamb Larry I Lipshultz Center of Reproductive Medicine and the department of molecular and cellular biology Scott Department of Urology Baylor College of Medicine Houston TX USA department of urology University of Virginia Charlottesville VA USA.

In couples with infertility, abnormal strict morphology of 0% normal forms （NF） is a criterion to proceed rapidly to in vitro fertilization （IVF）. Since no data currently exist, we investigated the outcomes for men with 0% NF to determine reproductive success without the use of assisted reproductive technologies （ART）. A cohort of 24 men with 0% NF were identified （2010-2013） with 27 randomly selected men with 〉4% NF as controls. Patient charts were reviewed with men contacted and administered an Institutional Review Board （IRB）-approved telephone questionnaire to ascertain outcomes. After a median follow-up time of 2.5 years, 29.2% of men with 0% NF did not require ART for their first pregnancy （controls = 55.6%, P〈 0.05）. When all pregnancies were analyzed together, men with 0% NF achieved twenty pregnancies of which 75% did not require IVF （controls - thirty pregnancies; 76.7% did not require IVF）. The average age of men and female partners was similar between men with 0% NF and 〉4% NF. All men had normal follicle-stimulating hormone （FSH）, testosterone, prolactin, sex hormone-binding globulin （SHBG）, and estradiol. Although, global semen parameters were worse in men with 0% NF, when a first pregnancy was a natural conception （NC）, 100% of men with 0% NF （n = 7/7） and 37.5% of controls in = 3/8） went on to have a subsequent pregnancy via NC. Men with 0% NF conceived without IVF in 29.2% of cases compared to 55.6% of controls. Strict morphology should not be used to predict fertilization, pregnancy, or live birth potential. In men with 0% NF, alternative modalities should be considered before immediate IVF.

关键词： conception infertility intrauterine insemination in vitro fertilization strict morphology success

In vivo exploration of the functional activity of the non-coding 8q24 prostate cancer risk locus

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Asian Journal of Andrology 2010年第6期12卷 787-789页

作者： Dolores J. Lamb Mounia Tannour-Louet scott department of urology Baylor College of Medicine Houston TX 77030 USA department of molecular and cellular biology Baylor College of Medicine Houston TX 77030 USA

Genome-wide association studies （GWAS） have successfully identified a substantial number of risk variants for prostate cancer [1-10]. In total, more than 20 single nucleotide polymorphisms （SNPs） that predispose to prostate malignancy have been found scattered throughout the genome in coding and non-coding regions. The 8q24 chromosomal region is an intriguing locus as it harbors five independent susceptibility variants （rs10086908; rs16901979; rs620861; rs6983267; rs1447295） that span a 440-kb genomic interval devoid of genes or protein-coding transcripts.

关键词： Genomes Cancer (genus) Neoplasms Variants Prostate Genes Andean region

Triplex-structure based DNA circuits with ultra-low leakage and high signal-to-noise ratio

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Chinese Chemical Letters 2024年第1期35卷 465-470页

作者： Huan Liu Zhihao Ming Yuanpeng Zhang Qidong Xia Hao Hu Ruijie Liu Yuheng Liao Yizhou Liu Xiao Liu Xiaoping Zhang Longjie Li Shaogang Wang Xianjin Xiao Institute of Reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department and Institute of urology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department and Institute of urology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China School of Life Science and Technology Wuhan Polytechnic UniversityWuhan 430030China department of Laboratory Medicine Tongji hospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

DNA circuits are powerful tools in various applications such as logical computation,molecular diagnosis and synthetic *** is a major problem in constructing complex DNA *** directly affects the output signal and harms the circuit’s performance *** the traditional DNA circuits,the gate complex is a duplex *** are insufficient energy barriers to prevent spontaneous detachment of strands,resulting in a leak ***,we have developed triplex-structure based DNA circuit with ultra-low leakage and high signal-to-noise ratio(SNR).The triplex structure improves the stability in the absence of *** the same time,the driving force of the strand displacement cascades reduces the influence of the triplex structure on the desired *** SNR of the DNA circuit was increased to 695,while the desired reaction rate remained 90%of the conventional translator *** triplex-structure mediated leakage prevention strategy was further tested at different temperatures and in DNA translator and seesaw *** also constructed modular basic logic gates with a high efficiency and low *** this basis,we further constructed triplex-structure based tertiary DNA logic circuits,and the SNR reached 295,which,to the best of our knowledge,was among the highest of the *** believe that our scheme provides a novel,valid,and general tool for reducing leakages,and we anticipate that it will be widely adopted in DNA nanotechnology.

关键词： Leakage DNA strand displacement cascades Triplex DNA circuits molecular programming

The varicocele： diagnostic dilemmas, therapeutic challenges and future perspectives

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Asian Journal of Andrology 2016年第2期18卷 276-281,J0007页

作者： Koji Chiba Ranjith Ramasamy Dolores J Lamb Larry I Lipshultz Center for Reproductive Medicine Baylor College of Medicine Houston TX USA scott department of urology Baylor College of Medicine Houston TX USA department of molecular and cellular biology Baylor College of Medicine Houston TX USA.

A varicocele is defined as the abnormal dilation of the internal testicular vein and pampiniform venus plexus within the spermatic cord. If a semen analysis is not obtained from the adolescent male, in the absence of other symptoms, the main clinical indication used by many urologists to recommend repair is testicular atrophy. The varicocele may result in testicular damage in some males causing testicular atrophy with impaired sperm production and decreased Leydig cell function, while in other males the varicocele may seemingly cause no ill effects. In adult men, varicoceles are frequently present and surgically correctable, yet the measurable benefits of surgical repair are slight according to a Cochrane review. While occurring more commonly in infertile men than fertile men, only 20% of men with a documented varicocele will suffer from fertility problems. Most varicoceles found in adolescents are detected during a routine medical examination, and it is difficult to predict which adolescent presenting with a varicocele will ultimately show diminished testicular function in adolescence or adulthood. As in adults, the mainstay of treatment for varicocele in adolescents is surgical correction. However, unlike an adult varicocelectomy （the microsurgical approach is the most common）, treatment for an adolescent varicocele is more often laparoscopic. Nevertheless, the goals of treatment are the same in the adolescent and adult patients. Controversy remains as to which patients to treat, when to initiate the treatment, and what type of treatment is the best. This review will present the current understanding of the etiology, diagnosis and treatment of the adolescent varicocele.

关键词： adolescent adult management varicocele

In vitro production of functional sperm in mice

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Asian Journal of Andrology 2011年第6期13卷 791-792页

作者： Kathleen Hwang Dolores J Lamb scott department of urology Baylor College of Medicine Houston TX 77030 USA scott department of urology and molecular and cellular biology Baylor College of Medicine Houston TX 77030 USA Laboratory for Male Reproductive Research and Testing Baylor College of Medicine Houston TX 77030 USA

Spermatogenesis refers to the process by which the production and development of the spermatozoa （the mature male gamete of most sexually reproducing species） occurs. It is a complex, stepwise process of sperm development, taking more than a month depending upon the species involving three specific functional phases： spermatogonial proliferation, meiosis and metamorphosis.1 Investigators have been successful in recreating this process in some species of fish; however, this whole process has never been reproduced in vitro in mammals.

关键词： Spermatogenesis refers production the spermatozoa

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

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Neural Regeneration Research 2025年第2期20卷 378-393页

作者： Jingxiang Zhang Xia Sheng Quanju Ding Yujun Wang Jiwei Zhao Jingfa Zhang department of Ophthalmology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina department of urology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of MedicineShanghaiChina National Clinical Research Center for Eye Diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghaiChina

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular *** causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular *** pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely ***,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential *** current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/*** review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

关键词： choroidal neovascularization epithelial-mesenchymal transition mesenchymal transition myofibroblast neovascular age-related macular degeneration submacular fibrosis subretinal fibrosis therapeutic targets transforming growth factor-β vascular endothelial growth factor