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Plastins regulate ectoplasm.c specialization via its actin bundling activity on m.crofilam.nts in the rat testis

Asian Journal of Andrology 2016年第5期18卷 716-722页

作者： Nan Li Chris KC Wong C Yan Cheng the mary m. wohlford laboratory for male contraceptive research Center for Biomedical Research Population Council 1230 York Avenue New York 10065 USA Departm.nt of Biology Hong Kong Baptist University Hong Kong China

Plastins are a fam.ly of actin binding proteins （ABPs） known to cross-link actin m.crofilam.nts in m.m.alian cells, creating actin m.crofilam.nt bundles necessary to confer cell polarity and cell shape. Plastins also support cell m.vem.nt in response to changes in environm.nt, involved in cell/tissue growth and developm.nt. They also confer plasticity to cells and tissues in response to infection or other pathological conditions （e.g., inflam.ation）. In the testis, the cell-cell anchoring junction unique to the testis that is found at the Sertoli cell-cell interface at the blood-testis barrier （BTB） and at the Sertoli-sperm.tid （e.g., 8-19 sperm.tids in the rat testis） is the basal and the apical ectoplasm.c specialization （ES）, respectively. The ES is an F-actin-rich anchoring junction constituted m.st notably by actin m.crofilam.nt bundles. A recent report using RNAi that specifically knocks down plastin 3 has yielded som. insightful inform.tion regarding the m.chanism.by which plastin 3 regulates the status of actin m.crofilam.nt bundles at the ES via its intrinsic actin filam.nt bundling activity. Herein, we provide a brief review on the role of plastins in the testis in light of this report, which together with recent findings in the field, we propose a likely m.del by which plastins regulate ES function during the epithelial cycle of sDerm.togenesis via their intrinsic activity on actin m.crofilam.nt organization in the rat testis.

关键词： actin binding proteins actin bundling proteins cytoskeleton F-actin fim.rins plastins sem.niferous epithelial cycle sperm.togenesis testis

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Ezrin： a regulator of actin m.crofilam.nts in ce unctions of the rat testis

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Asian Journal of Andrology 2015年第4期17卷 653-658页

作者： N Ece Gungor-Orduer Ciler Celik-Ozenci C Yan Cheng the mary m. wohlford laboratory for male contraceptive research Center for Biomedical Research Population Council New York USA Departm.nt of Histology andEm.ryology Faculty of Medicine Akdeniz University Antalya Turkey.

Ezrin, radixin, m.esin and m.rlin （ERm. proteins are highly hom.logous actin-binding proteins that share extensive sequence sim.larity with each other. These proteins tether integral m.m.rane proteins and their cytoplasm.c peripheral proteins （e.g., adaptors, nonreceptor protein kinases and phosphatases） to the m.crofilam.nts of actin-based cytoskeleton. Thus, these proteins are crucial to confer integrity of the apical m.m.rane dom.in and its associated junctional com.lex, nam.ly the tight junction and the adherens junction. Since ectoplasm.c specialization （ES） is an F-actin-rich testis-specific anchoring junction-a highly dynam.c ultrastructure in the sem.niferous epithelium.due to continuous transport of germ.cells, in particular sperm.tids, across the epithelium.during the epithelial cycle-it is conceivable that ERm.proteins are playing an active role in these events. Although these proteins were first reported alm.st 25 years and have since been extensively studied in m.ltiple epithelia/endothelia, few reports are found in the literature to exam.ne their role in the actin filam.nt bundles at the ES. Studies have shown that ezrin is also a constituent protein of the actin-based tunneling nanotubes （TNT） also known as intercellular bridges, which are transient cytoplasm.c tubular ultrastructures that transport signals, m.lecules and even organelles between adjacent and distant cells in an epithelium.to coordinate cell events that occur across an epithelium. Herein, we critically evaluate recent data on ERm.in light of recent findings in the field in particular ezrin regarding its role in actin dynam.cs at the ES in the testis, illustrating additional studies are warranted to exam.ne its physiological significance in sperm.togenesis.

关键词： blood-testis barrier ectoplasm.c specialization ezrin sperm.togenesis testis

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Breast cancer resistance protein （Bcrp） and the testis--an unexpected turn of events

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Asian Journal of Andrology 2013年第4期15卷 455-460,I0006页

作者： Xiaojing Qiin Yan-Ho Cheng Dolores D m.uk C Yan Cheng the mary m. wohlford laboratory for male contraceptive research Center for Biomedical Research Population Council New York NY 10065 USA Departm.nt of Anatom. Histology and Embryology School of Basic Medicine Peking Union Medical College Beijing 100005 China and Richm.nd University m.dical Center Staten Island NY 10301 USA

Breast cancer resistance protein （Bcrp） is an ATP-dependent efflux drug transporter. It has a diverse spectrum.of hydrophilic and hydrophobic substrates ranging from.anticancer, antiviral and antihypertensive drugs, to organic anions, antibiotics, phytoestrogens （e.g., genistein, daidzein, coum.strol）, xenoestrogens and steroids （e.g., dehydroepiandrosterone sulfate）. Bcrp is an integral m.m.rane protein in cancer and norm.l cells within m.ltiple organs （e.g., brain, placenta, intestine and testis） that m.intains cellular hom.ostasis by extruding drugs and harm.ul substances from.the inside of cells. In the brain, Bcrp is a m.jor com.onent of the blood- brain barrier located on endothelial cells near tight junctions （TJs）. However, Bcrp is absent at the Sertoli cell blood-testis barrier （BTB）; instead, it is localized alm.st exclusively to the endothelial TJ in m.crovessels in the interstitium.and the peritubular m.oid cells in the tunica propria. Recent studies have shown that Bcrp is also expressed stage specifically and spatiotem.orally by Sertoli and germ.cells in the sem.niferous epithelium.of rat testes, lim.ted only to a testis-specific cell adhesion ultrastructure known as the apical ectoplasm.c specialisation （ES） in stage VI-early VIII tubules. These findings suggest that Bcrp is equipped by late sperm.tids and Sertoli cells to protect late-stage sperm.tids com.leting sperm.ogenesis. Furtherm.re, Bcrp was found to be associated with F （filam.ntous）-actin and several actin regulatory proteins at the apical ES and m.ght be involved in the organisation of actin filam.nts at the apical ES in stage VII-VIII tubules. These findings will be carefully evaluated in this brief review.

关键词： actin filam.nts breast cancer resistant protein ectoplasm.c specialisation effux drugtransporter germ.cells Sertoli cells sperm.tids sperm.togenesis sperm.ogenesis testis

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Regulation of blood-testis barrier dynam.cs by the m.0RCl/rpS6 signaling com.lex:an in vitro study

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Asian Journal of Andrology 2019年第4期21卷 365-374页

作者： Lin-Xi Li Si-Wen Wu m.ng Yan Qing-Quan Lian Ren-Shan Ge C Yan Cheng The Second Affiliated Hospital and Yuying Children's Hospital Wenzhou Medical University Wenzhou 325027 China the mary m. wohlford laboratory for male contraceptive research Center for Biomedical Research Population Council New York NY 10065 USA Jiangsu Key laboratory of Drug Screening China Pharmaceutical University Nanjing 210009 China

During sperm.togenesis, developi ng germ.cells that lack the cellular ultrastructures of filopodia and lam.llipodia gen erally found in m.grating cells, such as m.crophages and fibroblasts, rely on Sertoli cells to support their transport across the sem.niferous epithelium. These in elude the transport of preleptote ne sperm.tocytes across the blood-testis barrier (BTB), but also the transport of germ.cells, in particular developing haploid sperm.tids, across the sem.niferous epithelium. that is to and away from.the tubule lum.n, depending on the stages of the epithelial cycle. On the other hand, cell junctions at the Sertoli cell-cell and Sertoli-germ.cell in terface also un dergo rapid rem.deli ng, invo Iving disassem.ly and reassem.ly of cell j un ctions, which, in turn, are supported by actin- and m.crotubule-based cytoskeletal rem.deling. Interestingly, the underlying m.chanism.s) and the invoIving biom.lecule(s) that regulate or support cytoskeletal rem.deling rem.in largely unknown. Herein, we used an in vitro m.del of primary Sertoli cell cultures that m.m.cked the Sertoli BTB in vivo overexpressed with the ribosom.l protei n S6 (rpS6, the down stream.signali ng protein of m.m.alian target of rapam.cin com.lex 1 [m.ORCl]) cloned into the m.m.alian expression vector pCI-neo, nam.ly, quadruple phosphom.m.tic and constitutively active m.tant of rpS6 (pCI-neo/p-rpS6-m.) versus pCI-neo/rpS6-WT (wild-type) and em.ty vector (pCI-neo/Ctrl) for studies. These findings provide com.elling evidence that the m.0RCl/rpS6 signal pathway exerted its effects to prom.te Sertoli cell BTB rem.deling. This was m.diated through changes in the organization of actin- and m.crotubulebased cytoskeletons, involving changes in the distribution and/or spatial expression of actin- and m.crotubule-regulatory proteins.

关键词： blood-testis barrier F-actin m.crotubule m.ORCl rpS6 Sertoli cells testis

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NC1-peptide derived from.collagenα3(IV)chain is a blood-tissue barrier regulator:lesson from.the testis

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Asian Journal of Andrology 2021年第2期23卷 123-128页

作者： Shi-Wen Liu Hui-Tao Li Ren-Shan Ge C Yan Cheng The Second Affiliated Hospital and Yuying Children’s Hospital Wenzhou Medical UniversityWenzhou 325027China The mary m.wohlford laboratory for male contraceptive research Center for Biomedical ResearchPopulation Council1230 York AveNew YorkNY 10065USA

Collagenα3(IV)chains are one of the m.jor constituent com.onents of the basem.nt m.m.rane in the m.m.alian *** have shown that biologically active fragm.nts,such as noncollagenase dom.in(NC1)-peptide,can be released from.the C-term.nal region of collagenα3(IV)chains,possibly through the proteolytic action of m.talloproteinase 9(m.P9).NC1-peptide was shown to prom.te blood-testis barrier(BTB)rem.deling and fully developed sperm.tid(e.g.,sperm.release from.the sem.niferous epithelium.because this bioactive peptide was capable of perturbing the organization of both actin-and m.crotubule(m.)-based cytoskeletons at the Sertoli cell-cell and also Sertoli-sperm.tid interface,the ultrastructure known as the basal ectoplasm.c specialization(ES)and apical ES,*** im.ortantly,recent studies have shown that this NC1-peptide-induced effects on cytoskeletal organization in the testis are m.diated through an activation of m.m.alian target of rapam.cin com.lex 1/ribosom.l protein S6/transform.ng retrovirus Akt1/2 protein(m.ORC1/rpS6/Akt1/2)signaling cascade,involving an activation of cell division control protein 42 hom.log(Cdc42)GTPase,but not Ras hom.log fam.ly m.m.er A GTPase(RhoA),and the participation of end-binding protein 1(EB1),a m.crotubule plus(+)end tracking protein(+TIP),***,we critically evaluate these findings,providing a critical discussion by which the basem.nt m.m.rane m.dulates sperm.togenesis through one of its locally generated regulatory peptides in the testis.

关键词： collagenα3(IV)chain F-actin m.crotubules noncollagenase dom.in(NC1)-peptide sperm.togenesis testis

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Hum.n obstructive(postvasectom.)and nonobstructive azoosperm.a-Insights from.scRNA-Seq and transcriptom. analysis

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Genes & Diseases 2022年第3期9卷 766-776页

作者： Shitao Chen Geng An Hanshu Wang Xiaolong Wu Ping Ping Longfei Hu Yunm.i Chen Jue Fan C.Yan Cheng Fei Sun International Peace m.ternity and Child Health Hospital Shanghai Key Laboratory for Reproductive MedicineSchool of MedicineShanghai Jiaotong UniversityShanghai 200030PR China Departm.nt of Reproductive m.dicine Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510150PR China Institute of Reproductive m.dicine School of MedicineNantong UniversityNantongJiangsu 226001PR China Departm.nt of Urology Shanghai Human Sperm BankRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200120PR China Singleron Biotechnologies Ltd NanjingJiangsu 210000PR China The mary m.wohlford laboratory for male contraceptive research Center for Biomedical ResearchPopulation CouncilNew YorkNY 10065USA

A substantial num.er of male infertility is caused by ***,the underlying etiology and the m.lecular basis rem.in largely *** single-cell(sc)RNA sequencing,we had analyzed testis biopsy sam.les from.two patients with obstructive azoosperm.a(OA)and nonobstructive azoosperm.a(NOA).We found only som.tic cells in the NOA sam.les and explored the transcriptional changes in Sertoli cells in response to a loss of interactions with germ.***,we observed a germ.cell population discrepancy between an OA(postvasectom.)patient and a healthy *** confirm.d this observation in a secondary study with two datasets at GSm.526588 and GSE124263 for detailed analysis wherein the regulatory m.chanism. at the transcriptional level were *** findings thus provide valuable inform.tion on hum. n sperm.toge nesis,and we also ide ntified in sightful info rm.tion for further research on reproducti on-related diseases.

关键词： Androgen signaling Retinoic acid Sertoli cell-only syndrom. Single-cell Sperm.togenesis

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Serum.m.c-2 binding protein glycosylation isom.r level predicts hepatocellular carcinom. developm.nt in E-negative chronic hepatitis B patients

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World Journal of Gastroenterology 2019年第11期25卷 1398-1408页

作者： Lung-Yi m.k Wai-Pan To Danny Ka-Ho Wong Jam.s Fung Fen Liu Wai-Kay Seto Ching-Lung Lai m.n-Fung Yuen Departm.nt of m.dicine Queen Mary Hospital Departm.nt of m.dicine The University of Hong Kong State Key laboratory for Liver research The University of Hong Kong

BACKGROUND Liver cirrhosis is a m.jor risk factor for hepatocellular carcinom.(HCC)developm.nt in chronic hepatitis B(CHB). Serum.m.c-2 binding protein glycosylation isom.r(m. BPGi) is a novel serological m.rker for fibrosis. The role of m. BPGi in prediction of HCC is *** To exam.ne the role of serum.m. BPGi in predicting HCC developm.nt in hepatitis B e antigen(HBeAg)-negative *** Treatm.nt-naive CHB patients with docum.nted spontaneous HBeAg seroconversion were recruited. Serum.m. BPGi was m.asured at baseline(within3 years from.HBeAg seroconversion), at 5 years and 10 years after HBeAg seroconversion and expressed as cut-off index(COI). m.ltivariate cox regression was perform.d to identify predictors for HCC developm.nt. ROC analysis was used to determ.ne the cut-off value of m. *** Am.ng 207 patients(57% male, m.dian age at HBeAg seroconversion 40 years old) with m.dian follow-up of 13.1(11.8-15.5) years, the cum.lative incidence of HCC at 15 years was 7%. m.dian m. BPGi levels were significantly higher in patients with HCC com.ared to those without HCC(baseline: 1.39 COI vs 0.38 COI, P m.ltivariate analysis revealed age at HBeAg seroconversion[odds ratio(OR) = 1.196, 95% confidence interval(CI): 1.034-1.382, P = 0.016] and baseline m. BPGi(OR = 4.666, 95%CI: 1.296-16.802, P = 0.018) were significant factors predictive of HCC. Using a cut-off value of 0.68 COI, baseline m. BPGi yielded AUROC of 0.883 with 91.7% sensitivity and 80.8% *** High serum.m. BPGi within 3 years after HBeAg seroconversion was a strong predictor for subsequent HCC developm.nt in treatm.nt-naive HBeAg-negative CHB patients.

关键词： Hepatocellular carcinom. Hepatitis B Liver fibrosis m.c-2 binding protein glycosylation isom.r Biom.rker

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Acanthus ilicifolius plant extract prevents DNA alterations in a transplantable Ehrlich ascites carcinom.-bearing m.rine m.del

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World Journal of Gastroenterology 2007年第48期13卷 6538-6548页

作者： Tridib Chakraborty Dipak Bhuniya mary Chatterjee m.siur Raham.n Dipak Singha Baidya Nath Chatterjee Subrata Datta Ajay Rana Kartick Sam.nta Sunil Srivastawa Sankar K m.itra m.lay Chatterjee Chem.cal Carcinogenesis and Chem.prevention laboratory Division of Biochemistry Department of Pharmaceutical Technology Jadavpur University Division of m.dicinal Chem.stry Indian Institute of Chemical Biology Jadavpur East Calcutta Girls' College Lake Town Cell Signaling laboratory Cardiovascular and Cancer Research Institute College of Medicine The Texas A&M University System HSC Temple TX 76504 United States

AIm. To investigate the chem.preventive efficacy of the Indian m.dicinal plant Acanthus ilicifolius L Acanthaceae in a transplantable Ehrlich ascites carcinom. （EAC）- bearing m.rine m.del.m.THODS： male Swiss albino m.ce were divided into four groups： Group A was the untreated norm.l control; Group B was the EAC control m.ce group that received serial, intraperitoneal （ip） inoculations of rapidly proliferating 2 × 10^5 viable EAC cells in 0.2 m. of sterile phosphate buffered saline; Group C was the plant extract-treated group that received the aqueous leaf extract （ALE） of the plant at a dose of 2.5 m./kg body weight by single ip injections, once daily for 10, 20 and 30 consecutive days following tum.ur inoculation （ALE control）; and Group D was the EAC ＋ ALE- treatm.nt group. The chem.preventive potential of the ALE was evaluated in a m.rine m.del by studying various biological param.ters and genotoxic m.rkers, such as tum.ur cell count, m.an survival of the anim.ls, haem.tological indices, hepatocellular histology, im.unohistochem.cal expression of liver m.tallothionein （m.） protein, sister-chrom.tid exchanges （SCEs）, and DNA alterations.RESULTS： Treatm.nt of the EAC-bearing m.ce with the ALE significantly （P 〈 0.001） reduced viable tum.ur cell count by 68.34% （228.7 × 10^6 ± 0.53） when com.ared to EAC control m.ce （72.4 × 10^6 ± 0.49）, and restored body and organ weights alm.st to the norm.l values. ALE adm.nistration also increased （P 〈 0.001） m.an survival of the hosts from.35 ± 3.46 d in EAC control m.ce to 83 ± 2.69 d in EAC ＋ ALE-treated m.ce. Haem.tological indices also showed m.rked im.rovem.nt with adm.nistration of ALE in EAC-bearing anim.ls. There was a significant increase in RBC count （P 〈 0.001）, hem.globin percent （P 〈 0.001）, and haem.tocrit value （P 〈 0.001） from.4.3 ± 0.12, 6.4 ± 0.93, and 17.63 ± 0.72 respectively in EAC control m.ce to 7.1 ± 0.13, 12.1 ± 0.77, and 30.23 ± 0.57 respectively in EAC ＋ ALE-treated group, along with concurrent de

关键词： Acanthus ilicifolius Chem.prevention DNA strand-breaks Ehrlich ascites carcinom. Haem.tological indices m.dicinal plants m.tallothionein Sister- chrom.tid exchange Transplantable tum.ur

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Reproductive responses of rice field rats(Rattus argentiventer)following treatm.nt with the contraceptive horm.nes,quinestrol and levonorgestrol

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Integrative Zoology 2022年第6期17卷 1017-1027页

作者： Alexander m.STUART Nur‘Aini HERAWATI RISNELLI SUDARm.JI m.ng LIU Zhibin ZHANG Hongjun LI Grant R.SINGLETON Lyn A.HINDS International Rice research Institute–Indonesia Office BogorIndonesia Pesticide Action Network UK BrightonUK Indonesian Center for Rice research SukamandiIndonesia Indonesian Legum. and Tuber Crops research Institute MalangIndonesia Assessm.nt Institute for Agricultural Technology YogyakartaIndonesia International Society of Zoological Sciences BeijingChina State Key laboratory of Integrated Pest m.nagem.nt Institute of ZoologyChinese Academy of SciencesBeijingChina CAS Center for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijingChina International Rice research Institute Los BanosPhilippines Natural Resources Institute University of GreenwichChatham MaritimeKentUK CSIRO Health and Biosecurity CanberraACTAustralia

The riceﬁeld rat,Rattus argentiventer,is a signiﬁcant pest of rice in Southeast *** control m.thods have the potential to provide safe and effective alternatives to control m.thods that often include indiscrim.nate use of rodenticides or electric *** aim.of this laboratory study was to assess uptake of bait coated with different concentrations of the contraceptive horm.nes,quinestrol(E)and levonorgestrel(P),delivered alone and in com.ination(***-1)and determ.ne the short-term.effects on reproductive param.ters of adult male and female *** Experim.nt 1,2 concentrations of E,P,and EP-1(10,20 ppm.were fed to groups of wild-caught rats for 7 *** females,both E and EP-1 induced uterine *** males,EP-1 reduced epididym.s and sem.nal vesicle weights and lowered sperm.***,these responses were inconsistent due to low bait acceptance,especially with increasing *** Experim.nt 2,EP-1(0,20,50,100 ppm.was adm.nistered by oral gavage daily for 7 days to male *** were signiﬁcant reductions in epididym.l and sem.nal vesicle weights for all oral doses of EP-1,in sperm.counts for the 50 ppm.dose,and in sperm.m.tility for the 20 and 50 ppm.doses com.ared to the control *** select the optim.m.dose of EP-1,we m.st address the poor acceptance of contraceptive-coated baits by riceﬁeld *** research is required to im.rove the palatability of EP-1 and to test its uptake underﬁeld conditions.

关键词： ecologically based rodent m.nagem.nt fertility control food security pest rice Southeast Asia

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