Background: Community-based test and start (TAS) models have shown the potential to improve clinical outcomes for key populations because early access to treatment will have population level impact by reducing transmi...Background: Community-based test and start (TAS) models have shown the potential to improve clinical outcomes for key populations because early access to treatment will have population level impact by reducing transmission through the promotion and provision of hassle-free quality HIV testing, on the spot ART initiation and unrestricted access to culturally competent health professionals. We assessed the effectiveness of a pioneer community-based test and start (TAS) model for key populations in Lagos along UNAIDS 90/90/90 cascade. Methods: Men who have sex with men (MSM), female sex workers (FSW), and persons who inject drugs (PWID), >14 years of age were recruited through peer-referral for HIV testing services (HTS) at a community-based KP-friendly clinic in Lagos between June 2015 and September 2016. The clinic provides comprehensive HIV services, including HIV treatment. Those who test positive are enrolled and provided with TAS services. Using routine service data, we deployed descriptive cross tabulations at p < 5% to determine the performance along the 90/90/90 cascade. Results: In total, 8812 KPs comprising MSM (51.6%), FSW (32.7%) and PWID (15.7%) were tested during this period. About one-half (46.4%) were young KP (15 - 25 years). The majority (76.1%) were male, single (86.1%), almost all (99%) had at least primary school level education, and about one-quarter (25.1%) were employed. Among MSM, 506 (11.1%) tested positive, 276 (54.5%) were initiated on ART, of whom 155 conducted viral load testing and 88 (56.7%) had achieved viral suppression (<1000 copies per milliliter). Among FSW, 88 (3.1%) tested positive, only 28 (31.8%) were initiated on ART, of whom 15 conducted viral load testing and 9 (60%) achieved viral suppression. Among PWID, of 15 (1.1%) who tested positive, only 2 (13%) were initiated on ART and none had conducted viral load testing. Client satisfaction index was 96.1%. Conclusion: The current community-based model showed excellent capacity to achieve the first 90 goal among target KP communities. However, linkage to care and treatment, adherence, and retention remain major challenges in achieving the second and third nineties at the community level.展开更多
In order to design appropriate HIV prevention programs, it is important to examine the perception and knowledge of HIV/AIDS and methods of preventive. This article explores comprehensive knowledge of HIV/AIDS preventi...In order to design appropriate HIV prevention programs, it is important to examine the perception and knowledge of HIV/AIDS and methods of preventive. This article explores comprehensive knowledge of HIV/AIDS prevention methods among women and men in slum and non-slum areas in the National Capital Territory of Delhi, India. Data were drawn from the National Family Health Survey, 2005-06 (NFHS-3). The sample included 3096 women aged 15 - 49 years and 1321 men aged 15 - 54 years. Pearson Chi-square test and logistic regression analyses were conducted to examine the association between the study variables and the background characteristics of the slum and non-slum populations. Comprehensive knowledge of HIV/AIDS prevention methods was significantly lower among women and men in slum areas as compared with non-slum areas. Compared to men, women had less comprehensive knowledge of HIV/AIDS prevention methods in slum and non-slum areas, even after controlling for various demographic and socio-economic and exposure variables. Findings indicate that comprehensive knowledge of HIV prevention methods is low among women in slum areas. Interventions are needed to build knowledge of HIV transmission and prevention methods in this vulnerable group. Strategies to build awareness of HIV/AIDS could include mass media campaigns HIV/AIDS, and information, education and communication programs (IEC) on HIV/AIDS in slum areas.展开更多
During spermatogenesis, developi ng germ cells that lack the cellular ultrastructures of filopodia and lamellipodia gen erally found in migrating cells, such as macrophages and fibroblasts, rely on Sertoli cells to su...During spermatogenesis, developi ng germ cells that lack the cellular ultrastructures of filopodia and lamellipodia gen erally found in migrating cells, such as macrophages and fibroblasts, rely on Sertoli cells to support their transport across the seminiferous epithelium. These in elude the transport of preleptote ne spermatocytes across the blood-testis barrier (BTB), but also the transport of germ cells, in particular developing haploid spermatids, across the seminiferous epithelium, that is to and away from the tubule lumen, 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 remodeli ng, invo Iving disassembly and reassembly of cell j un ctions, which, in turn, are supported by actin- and microtubule-based cytoskeletal remodeling. Interestingly, the underlying mechanism(s) and the invoIving biomolecule(s) that regulate or support cytoskeletal remodeling remain largely unknown. Herein, we used an in vitro model of primary Sertoli cell cultures that mimicked the Sertoli BTB in vivo overexpressed with the ribosomal protei n S6 (rpS6, the down stream signali ng protein of mammalian target of rapamycin complex 1 [mTORCl]) cloned into the mammalian expression vector pCI-neo, namely, quadruple phosphomimetic and constitutively active mutant of rpS6 (pCI-neo/p-rpS6-MT) versus pCI-neo/rpS6-WT (wild-type) and empty vector (pCI-neo/Ctrl) for studies. These findings provide compelling evidence that the mT0RCl/rpS6 signal pathway exerted its effects to promote Sertoli cell BTB remodeling. This was mediated through changes in the organization of actin- and microtubulebased cytoskeletons, involving changes in the distribution and/or spatial expression of actin- and microtubule-regulatory proteins.展开更多
Plastins are a family of actin binding proteins （ABPs） known to cross-link actin microfilaments in mammalian cells, creating actin microfilament bundles necessary to confer cell polarity and cell shape. Plastins als...Plastins are a family of actin binding proteins （ABPs） known to cross-link actin microfilaments in mammalian cells, creating actin microfilament bundles necessary to confer cell polarity and cell shape. Plastins also support cell movement in response to changes in environment, involved in cell/tissue growth and development. They also confer plasticity to cells and tissues in response to infection or other pathological conditions （e.g., inflammation）. 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-spermatid （e.g., 8-19 spermatids in the rat testis） is the basal and the apical ectoplasmic specialization （ES）, respectively. The ES is an F-actin-rich anchoring junction constituted most notably by actin microfilament bundles. A recent report using RNAi that specifically knocks down plastin 3 has yielded some insightful information regarding the mechanism by which plastin 3 regulates the status of actin microfilament bundles at the ES via its intrinsic actin filament 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 model by which plastins regulate ES function during the epithelial cycle of sDermatogenesis via their intrinsic activity on actin microfilament organization in the rat testis.展开更多
The objective of the present study was to investigate the effects of genistein and equol on 3β-hydroxysteroid de- hydrogenase （3β-HSD） and 17β-hydroxysteroid dehydrogenase 3 （17β-HSD3） in human and rat testis ...The objective of the present study was to investigate the effects of genistein and equol on 3β-hydroxysteroid de- hydrogenase （3β-HSD） and 17β-hydroxysteroid dehydrogenase 3 （17β-HSD3） in human and rat testis microsomes. These enzymes （3β-HSD and 17β-HSD3）, along with two others （cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17α-hydroxylase/17-20 lyase）, catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3β-HSD activity （0.2 μmol L^-1 pregnenolone） with half-maximal inhibition or a half-maximal inhibitory concentration （IC50） of 87 ± 15 （human） and 636 ± 155 nmol L^-1 （rat）. Genistein＇s mode of action on 3β-HSD activity was competitive for the substrate pregnenolonrge and noncompetitive for the cofactor NAD＋. There was no difference in genistein＇s potency of 3β-HSD inhibition between intact rat Leydig cells and testis microsomes. In contrast to its potent inhibition of 3β-HSD, genistein had lesser effects on human and rat 17β-HSD3 （0.1 μmol L^-1 androstenedione）, with an IC50 〉 100μmol L^-1. On the other hand, equol only inhibited human 3β-HSD by 42%, and had no effect on 3β-HSD and 17β-HSD3 in rat tissues. These observations imply that the ability of soy isoflavones to regulate androgen biosynthesis in Leydig cells is due in part to action on Leydig cell 3β- HSD activity. Given the increasing intake of soy-based food products and their potential effect on blood androgen levels, these findings are greatly relevant to public health.展开更多
Progenitor Leydig cells are derived from stem cells. The proliferation and differentiation of progenitor Leydig cells significantly contributes to Leydig cell number during puberty. However, the regulation of these pr...Progenitor Leydig cells are derived from stem cells. The proliferation and differentiation of progenitor Leydig cells significantly contributes to Leydig cell number during puberty. However, the regulation of these processes remains unclear. The objective of the present study was to determine whether luteinizing hormone （LH） or androgen contributes to the proliferation and differentiation of progenitor Leydig cells. Fourteen-day-old male Sprague-Dawley rats were treated for 7 days with NalGlu, which is a gonadotropin- releasing hormone antagonist, to reduce the secretion of LH in the pituitary and thus, androgen in the testis. Rats were co-administered with LH or 7a-methyl-nortestosterone （MENT）, which is an androgen resistant to metabolism by 5a-reductase 1 in progenitor Leydig cells, and the subsequent effects of LH or androgen were measured. 3H-Thymidine was also intravenously injected into rats to study thymidine incorporation in progenitor Leydig cells. Progenitor Leydig cells were examined. NalGlu administration reduced progenitor Leydig cell proliferation by 83%. In addition, LH or MENT treatment restored Leydig cell proliferative capacity to 73% or 50% of control, respectively. The messenger RNA levels of proliferation-related genes were measured using real-time PCR. The expression levels of Igfl, Lifr, Pdgfra, Bcl2, Ccnd3and Pcnawere upregulated by MENT, and those of Pdgfra, Ccnd3and Pcnawere upregulated by LH. Both LH and MENT stimulated the differentiation of progenitor Leydig cells in vitro. We concluded that both LH and MENT were involved in regulating the development of progenitor Leydig cells.展开更多
Ezrin, radixin, moesin and merlin （ERM） proteins are highly homologous actin-binding proteins that share extensive sequence similarity with each other. These proteins tether integral membrane proteins and their cyto...Ezrin, radixin, moesin and merlin （ERM） proteins are highly homologous actin-binding proteins that share extensive sequence similarity with each other. These proteins tether integral membrane proteins and their cytoplasmic peripheral proteins （e.g., adaptors, nonreceptor protein kinases and phosphatases） to the microfilaments of actin-based cytoskeleton. Thus, these proteins are crucial to confer integrity of the apical membrane domain and its associated junctional complex, namely the tight junction and the adherens junction. Since ectoplasmic specialization （ES） is an F-actin-rich testis-specific anchoring junction-a highly dynamic ultrastructure in the seminiferous epithelium due to continuous transport of germ cells, in particular spermatids, 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 almost 25 years and have since been extensively studied in multiple epithelia/endothelia, few reports are found in the literature to examine their role in the actin filament 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 cytoplasmic tubular ultrastructures that transport signals, molecules 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 dynamics at the ES in the testis, illustrating additional studies are warranted to examine its physiological significance in spermatogenesis.展开更多
Antibodies raised against rabbit sperm membrane protein(rSMP-B)interacted with a rattestis cytosolic protein with an estimated molecular weight of 70 kD.The clone expressingrSMP-B was isolated by epitope selection fro...Antibodies raised against rabbit sperm membrane protein(rSMP-B)interacted with a rattestis cytosolic protein with an estimated molecular weight of 70 kD.The clone expressingrSMP-B was isolated by epitope selection from a rat testis,λgt11 vector cDNA library,An Eco Rl-eut 2.0 kb cDNA fragment encoding rSMP-B was identified.The cDNA fragment(RSD-1)was isolated,subcloned and restriction mapped.Dot hybridization analysis of mRNAprepared from human,rabbit and rat testes showed that the gene encoding rSMP-B is ex-pressed in the testes of all three mammals.展开更多
11β-hydroxysteroid dehydrogenase type 1 （11β-HSD1） and type 2 （11β-HSD2） are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and lo...11β-hydroxysteroid dehydrogenase type 1 （11β-HSD1） and type 2 （11β-HSD2） are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and localization of 11β-HSD in rat testis during postnatal development, and the regulation of these genes by luteinizing hormone （LH） and androgens, mRNA and protein levels were analyzed by quantitative real-time-polymerase chain reaction and western blotting, respectively, in testes collected from rats at postnatal day （PND） 7, 14, 21, 35, and 90, and from rats treated with LH, 7α.methyl-19-nortestosterone （MENT） and testosterone at PND 21 and PND 90. Immunohistochemical staining was used to identify the localization of the 11β-HSD in rat testis at PND 7, 14, and 90. We found that 11β-HSD1 expression was restricted to the interstitial areas, and that its levels increased during rat testis development. In contrast, whereas 11β-HSD2 was expressed in both the interstitial areas and seminiferous tubules at PND 7, it was present only in the interstitial areas at PND 90, and its levels declined during testicular development. Moreover, 11β-HSD1 mRNA was induced by LH in both the PND 21 and 90 testes and by MENT at PND 21, whereas 11β-HSD2 mRNA was induced by testosterone and MENT in the PND 21 testis and by LH in the PND 90 testis. In conclusion, our study indicates that the 11β-HSD1 and 11β-HSD2 genes have distinct patterns of spatiotemporal expression and hormonal regulation during postnatal development of the rat testis.展开更多
Background: A systematic review portraying the changing pattern of sexual behaviors, STI and HIV prevalence and key strategies curb HIV and STI among truckers in India is lacking. This paper therefore aims to present ...Background: A systematic review portraying the changing pattern of sexual behaviors, STI and HIV prevalence and key strategies curb HIV and STI among truckers in India is lacking. This paper therefore aims to present a chronological review of literature regarding sexual behaviors, STI/HIV prevalence, and various HIV prevention programs implemented among truckers in India. Methodology: Published and unpublished studies (1990-2011) were identified through electronic databases, and hand searching. Results: Most studies on sexual behaviors and STI/HIV prevalence among truckers focused only on drivers and ignored their helpers. Evidences suggest that consistent condom use by truckers with both paid and non-paid female partners has increased during the past decade. Many recent studies suggest that the HIV prevalence among truckers is about 2% and it has been declining slowly during the past decade. The HIV prevention programs among truckers which started with the aim of raising awareness about HIV during early 1990s, have grown multi-folds to encompass not only the standard strategies like mid-media events, interpersonal counselling and STI care for HIV prevention, but also innovations such as the use of business franchisee models, and integrated research and evidence based planning in the program. The possibilities of using new approaches such as male circumcision and the use of pre-exposure prophylaxes are underway. Conclusion: More studies are needed to explore helpers’ vulnerabilities to HIV. Very few studies have attempted to examine the impact of large-scale prevention programs among truckers. Efforts are required to examine the impact of different components of such programs to guide the HIV prevention efforts among truckers in India.展开更多
Aim: Epididymal proteins are known to play an important role in the maturation of spermatozoa, we ougnt to deter-mine if there are regional differences in androgen-dependent epididymal proteins. Methods: A group of ad...Aim: Epididymal proteins are known to play an important role in the maturation of spermatozoa, we ougnt to deter-mine if there are regional differences in androgen-dependent epididymal proteins. Methods: A group of adult rats wascastrated and epididymides were removed three days following castration. The epididymides were dissected into caput,corpus and cauda segments, homogenized, and proteins were fractionated by anion exchange HPLC. Proteins in select-ed fractions were resolved by SDS-PAGE and visualized by silver staining. Results: It was observed that the levels ofmultiple proteins drastically reduced in the various regions of epididymis of the orchiectomized rats. Conclusion: Theepididymal proteins appear to be useful markers to study androgenic action in the epididymis.展开更多
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,...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, coumestrol）, xenoestrogens and steroids （e.g., dehydroepiandrosterone sulfate）. Bcrp is an integral membrane protein in cancer and normal cells within multiple organs （e.g., brain, placenta, intestine and testis） that maintains cellular homeostasis by extruding drugs and harmful substances from the inside of cells. In the brain, Bcrp is a major component 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 almost exclusively to the endothelial TJ in microvessels in the interstitium and the peritubular myoid cells in the tunica propria. Recent studies have shown that Bcrp is also expressed stage specifically and spatiotemporally by Sertoli and germ cells in the seminiferous epithelium of rat testes, limited only to a testis-specific cell adhesion ultrastructure known as the apical ectoplasmic specialisation （ES） in stage VI-early VIII tubules. These findings suggest that Bcrp is equipped by late spermatids and Sertoli cells to protect late-stage spermatids completing spermiogenesis. Furthermore, Bcrp was found to be associated with F （filamentous）-actin and several actin regulatory proteins at the apical ES and might be involved in the organisation of actin filaments at the apical ES in stage VII-VIII tubules. These findings will be carefully evaluated in this brief review.展开更多
Collagenα3(IV)chains are one of the major constituent components of the basement membrane in the mammalian testis.Studies have shown that biologically active fragments,such as noncollagenase domain(NC1)-peptide,can b...Collagenα3(IV)chains are one of the major constituent components of the basement membrane in the mammalian testis.Studies have shown that biologically active fragments,such as noncollagenase domain(NC1)-peptide,can be released from the C-terminal region of collagenα3(IV)chains,possibly through the proteolytic action of metalloproteinase 9(MMP9).NC1-peptide was shown to promote blood-testis barrier(BTB)remodeling and fully developed spermatid(e.g.,sperm)release from the seminiferous epithelium because this bioactive peptide was capable of perturbing the organization of both actin-and microtubule(MT)-based cytoskeletons at the Sertoli cell-cell and also Sertoli-spermatid interface,the ultrastructure known as the basal ectoplasmic specialization(ES)and apical ES,respectively.More importantly,recent studies have shown that this NC1-peptide-induced effects on cytoskeletal organization in the testis are mediated through an activation of mammalian target of rapamycin complex 1/ribosomal protein S6/transforming retrovirus Akt1/2 protein(mTORC1/rpS6/Akt1/2)signaling cascade,involving an activation of cell division control protein 42 homolog(Cdc42)GTPase,but not Ras homolog family member A GTPase(RhoA),and the participation of end-binding protein 1(EB1),a microtubule plus(+)end tracking protein(+TIP),downstream.Herein,we critically evaluate these findings,providing a critical discussion by which the basement membrane modulates spermatogenesis through one of its locally generated regulatory peptides in the testis.展开更多
Passive immunization of female mice by the intraperitoneal administration of ascitic fluidscontaining monoclonal antisperm antibodies blocked the development of mouse zygotes tomorulae and blastocysts when cultured in...Passive immunization of female mice by the intraperitoneal administration of ascitic fluidscontaining monoclonal antisperm antibodies blocked the development of mouse zygotes tomorulae and blastocysts when cultured in vitro.Radioiodinated YWK-I monoclonal anti-bodies were prepared and administered intraperitoneally to Jemale mice.Significant radioac-tivity was found in washes of the oviductal lumens.The results suggest that antispermantibodies block fertilization and may have a deleterious effect on early developing embryos.展开更多
Background: Mental health has been a largely neglected issue among Men Who Have Sex with Men (MSM) across the world. This study examines the prevalence and correlates of depression among MSM. Data and Methods: Data fo...Background: Mental health has been a largely neglected issue among Men Who Have Sex with Men (MSM) across the world. This study examines the prevalence and correlates of depression among MSM. Data and Methods: Data for this study are used from a cross-sectional Behavioral Tracking Survey—2012 conducted among 1176 MSM from Andhra Pradesh (undivided), a southern state of India. Depression of MSM was assessed using Patient Health Questionnaire-2 scale. Descriptive statistics, bivariate and multivariate logistic regression techniques were used for analysis. Results: More than one-third of MSMs (35%) in the survey reported to have depression. The likelihood of experiencing depression was 5 times higher among MSM who were mobile for sex work outside their place of residence (55% vs 17%, AOR: 5.2, 95% CI: 3.7 - 7.3) and had experienced physical or sexual violence (82% vs 33%, AOR: 6.0, 95% CI: 2.1 - 17.4) than their respective counterparts. Rates of depression were significantly higher among MSM who had experienced Sexually Transmitted Infections symptoms;knowledge of their HIV positivity;who didn’t use condoms during anal sex with any clients/partners;those who consumed alcohol and were in financial debt at the time of survey than others. Those who were associated with any community groups have significantly less chances of reporting depression. Discussion: The study certainly highlighted that the HIV prevention efforts with MSM in India require an integrated approach on addressing the mental health issues. To support this, programs and research-based evidence will be highly needed to ensure that mental health issues are properly addressed among MSM and other high risk groups.展开更多
文摘Background: Community-based test and start (TAS) models have shown the potential to improve clinical outcomes for key populations because early access to treatment will have population level impact by reducing transmission through the promotion and provision of hassle-free quality HIV testing, on the spot ART initiation and unrestricted access to culturally competent health professionals. We assessed the effectiveness of a pioneer community-based test and start (TAS) model for key populations in Lagos along UNAIDS 90/90/90 cascade. Methods: Men who have sex with men (MSM), female sex workers (FSW), and persons who inject drugs (PWID), >14 years of age were recruited through peer-referral for HIV testing services (HTS) at a community-based KP-friendly clinic in Lagos between June 2015 and September 2016. The clinic provides comprehensive HIV services, including HIV treatment. Those who test positive are enrolled and provided with TAS services. Using routine service data, we deployed descriptive cross tabulations at p < 5% to determine the performance along the 90/90/90 cascade. Results: In total, 8812 KPs comprising MSM (51.6%), FSW (32.7%) and PWID (15.7%) were tested during this period. About one-half (46.4%) were young KP (15 - 25 years). The majority (76.1%) were male, single (86.1%), almost all (99%) had at least primary school level education, and about one-quarter (25.1%) were employed. Among MSM, 506 (11.1%) tested positive, 276 (54.5%) were initiated on ART, of whom 155 conducted viral load testing and 88 (56.7%) had achieved viral suppression (<1000 copies per milliliter). Among FSW, 88 (3.1%) tested positive, only 28 (31.8%) were initiated on ART, of whom 15 conducted viral load testing and 9 (60%) achieved viral suppression. Among PWID, of 15 (1.1%) who tested positive, only 2 (13%) were initiated on ART and none had conducted viral load testing. Client satisfaction index was 96.1%. Conclusion: The current community-based model showed excellent capacity to achieve the first 90 goal among target KP communities. However, linkage to care and treatment, adherence, and retention remain major challenges in achieving the second and third nineties at the community level.
文摘In order to design appropriate HIV prevention programs, it is important to examine the perception and knowledge of HIV/AIDS and methods of preventive. This article explores comprehensive knowledge of HIV/AIDS prevention methods among women and men in slum and non-slum areas in the National Capital Territory of Delhi, India. Data were drawn from the National Family Health Survey, 2005-06 (NFHS-3). The sample included 3096 women aged 15 - 49 years and 1321 men aged 15 - 54 years. Pearson Chi-square test and logistic regression analyses were conducted to examine the association between the study variables and the background characteristics of the slum and non-slum populations. Comprehensive knowledge of HIV/AIDS prevention methods was significantly lower among women and men in slum areas as compared with non-slum areas. Compared to men, women had less comprehensive knowledge of HIV/AIDS prevention methods in slum and non-slum areas, even after controlling for various demographic and socio-economic and exposure variables. Findings indicate that comprehensive knowledge of HIV prevention methods is low among women in slum areas. Interventions are needed to build knowledge of HIV transmission and prevention methods in this vulnerable group. Strategies to build awareness of HIV/AIDS could include mass media campaigns HIV/AIDS, and information, education and communication programs (IEC) on HIV/AIDS in slum areas.
基金grants from the National Institutes of Health (R01 HD056034 to CYC)the Natural Science Foundation of China (NSFC)(No. 81601264 to LXLand No. 81730042 to RSG).
文摘During spermatogenesis, developi ng germ cells that lack the cellular ultrastructures of filopodia and lamellipodia gen erally found in migrating cells, such as macrophages and fibroblasts, rely on Sertoli cells to support their transport across the seminiferous epithelium. These in elude the transport of preleptote ne spermatocytes across the blood-testis barrier (BTB), but also the transport of germ cells, in particular developing haploid spermatids, across the seminiferous epithelium, that is to and away from the tubule lumen, 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 remodeli ng, invo Iving disassembly and reassembly of cell j un ctions, which, in turn, are supported by actin- and microtubule-based cytoskeletal remodeling. Interestingly, the underlying mechanism(s) and the invoIving biomolecule(s) that regulate or support cytoskeletal remodeling remain largely unknown. Herein, we used an in vitro model of primary Sertoli cell cultures that mimicked the Sertoli BTB in vivo overexpressed with the ribosomal protei n S6 (rpS6, the down stream signali ng protein of mammalian target of rapamycin complex 1 [mTORCl]) cloned into the mammalian expression vector pCI-neo, namely, quadruple phosphomimetic and constitutively active mutant of rpS6 (pCI-neo/p-rpS6-MT) versus pCI-neo/rpS6-WT (wild-type) and empty vector (pCI-neo/Ctrl) for studies. These findings provide compelling evidence that the mT0RCl/rpS6 signal pathway exerted its effects to promote Sertoli cell BTB remodeling. This was mediated through changes in the organization of actin- and microtubulebased cytoskeletons, involving changes in the distribution and/or spatial expression of actin- and microtubule-regulatory proteins.
文摘Plastins are a family of actin binding proteins （ABPs） known to cross-link actin microfilaments in mammalian cells, creating actin microfilament bundles necessary to confer cell polarity and cell shape. Plastins also support cell movement in response to changes in environment, involved in cell/tissue growth and development. They also confer plasticity to cells and tissues in response to infection or other pathological conditions （e.g., inflammation）. 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-spermatid （e.g., 8-19 spermatids in the rat testis） is the basal and the apical ectoplasmic specialization （ES）, respectively. The ES is an F-actin-rich anchoring junction constituted most notably by actin microfilament bundles. A recent report using RNAi that specifically knocks down plastin 3 has yielded some insightful information regarding the mechanism by which plastin 3 regulates the status of actin microfilament bundles at the ES via its intrinsic actin filament 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 model by which plastins regulate ES function during the epithelial cycle of sDermatogenesis via their intrinsic activity on actin microfilament organization in the rat testis.
文摘The objective of the present study was to investigate the effects of genistein and equol on 3β-hydroxysteroid de- hydrogenase （3β-HSD） and 17β-hydroxysteroid dehydrogenase 3 （17β-HSD3） in human and rat testis microsomes. These enzymes （3β-HSD and 17β-HSD3）, along with two others （cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17α-hydroxylase/17-20 lyase）, catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3β-HSD activity （0.2 μmol L^-1 pregnenolone） with half-maximal inhibition or a half-maximal inhibitory concentration （IC50） of 87 ± 15 （human） and 636 ± 155 nmol L^-1 （rat）. Genistein＇s mode of action on 3β-HSD activity was competitive for the substrate pregnenolonrge and noncompetitive for the cofactor NAD＋. There was no difference in genistein＇s potency of 3β-HSD inhibition between intact rat Leydig cells and testis microsomes. In contrast to its potent inhibition of 3β-HSD, genistein had lesser effects on human and rat 17β-HSD3 （0.1 μmol L^-1 androstenedione）, with an IC50 〉 100μmol L^-1. On the other hand, equol only inhibited human 3β-HSD by 42%, and had no effect on 3β-HSD and 17β-HSD3 in rat tissues. These observations imply that the ability of soy isoflavones to regulate androgen biosynthesis in Leydig cells is due in part to action on Leydig cell 3β- HSD activity. Given the increasing intake of soy-based food products and their potential effect on blood androgen levels, these findings are greatly relevant to public health.
基金We are grateful to Ms Chantal Sottas for technical assistance. This work was in part supported by the National Nature Science Foundation of China （nos. 30871434 and 31171425 to RS Ge, no. 30900846 to CQ Wang and no. 81200430 to YF Zhang）.
文摘Progenitor Leydig cells are derived from stem cells. The proliferation and differentiation of progenitor Leydig cells significantly contributes to Leydig cell number during puberty. However, the regulation of these processes remains unclear. The objective of the present study was to determine whether luteinizing hormone （LH） or androgen contributes to the proliferation and differentiation of progenitor Leydig cells. Fourteen-day-old male Sprague-Dawley rats were treated for 7 days with NalGlu, which is a gonadotropin- releasing hormone antagonist, to reduce the secretion of LH in the pituitary and thus, androgen in the testis. Rats were co-administered with LH or 7a-methyl-nortestosterone （MENT）, which is an androgen resistant to metabolism by 5a-reductase 1 in progenitor Leydig cells, and the subsequent effects of LH or androgen were measured. 3H-Thymidine was also intravenously injected into rats to study thymidine incorporation in progenitor Leydig cells. Progenitor Leydig cells were examined. NalGlu administration reduced progenitor Leydig cell proliferation by 83%. In addition, LH or MENT treatment restored Leydig cell proliferative capacity to 73% or 50% of control, respectively. The messenger RNA levels of proliferation-related genes were measured using real-time PCR. The expression levels of Igfl, Lifr, Pdgfra, Bcl2, Ccnd3and Pcnawere upregulated by MENT, and those of Pdgfra, Ccnd3and Pcnawere upregulated by LH. Both LH and MENT stimulated the differentiation of progenitor Leydig cells in vitro. We concluded that both LH and MENT were involved in regulating the development of progenitor Leydig cells.
文摘Ezrin, radixin, moesin and merlin （ERM） proteins are highly homologous actin-binding proteins that share extensive sequence similarity with each other. These proteins tether integral membrane proteins and their cytoplasmic peripheral proteins （e.g., adaptors, nonreceptor protein kinases and phosphatases） to the microfilaments of actin-based cytoskeleton. Thus, these proteins are crucial to confer integrity of the apical membrane domain and its associated junctional complex, namely the tight junction and the adherens junction. Since ectoplasmic specialization （ES） is an F-actin-rich testis-specific anchoring junction-a highly dynamic ultrastructure in the seminiferous epithelium due to continuous transport of germ cells, in particular spermatids, 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 almost 25 years and have since been extensively studied in multiple epithelia/endothelia, few reports are found in the literature to examine their role in the actin filament 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 cytoplasmic tubular ultrastructures that transport signals, molecules 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 dynamics at the ES in the testis, illustrating additional studies are warranted to examine its physiological significance in spermatogenesis.
基金This work was supported by the Rockefeller Foundation,NIH Grant and the Mellon Foundation,New York
文摘Antibodies raised against rabbit sperm membrane protein(rSMP-B)interacted with a rattestis cytosolic protein with an estimated molecular weight of 70 kD.The clone expressingrSMP-B was isolated by epitope selection from a rat testis,λgt11 vector cDNA library,An Eco Rl-eut 2.0 kb cDNA fragment encoding rSMP-B was identified.The cDNA fragment(RSD-1)was isolated,subcloned and restriction mapped.Dot hybridization analysis of mRNAprepared from human,rabbit and rat testes showed that the gene encoding rSMP-B is ex-pressed in the testes of all three mammals.
文摘11β-hydroxysteroid dehydrogenase type 1 （11β-HSD1） and type 2 （11β-HSD2） are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and localization of 11β-HSD in rat testis during postnatal development, and the regulation of these genes by luteinizing hormone （LH） and androgens, mRNA and protein levels were analyzed by quantitative real-time-polymerase chain reaction and western blotting, respectively, in testes collected from rats at postnatal day （PND） 7, 14, 21, 35, and 90, and from rats treated with LH, 7α.methyl-19-nortestosterone （MENT） and testosterone at PND 21 and PND 90. Immunohistochemical staining was used to identify the localization of the 11β-HSD in rat testis at PND 7, 14, and 90. We found that 11β-HSD1 expression was restricted to the interstitial areas, and that its levels increased during rat testis development. In contrast, whereas 11β-HSD2 was expressed in both the interstitial areas and seminiferous tubules at PND 7, it was present only in the interstitial areas at PND 90, and its levels declined during testicular development. Moreover, 11β-HSD1 mRNA was induced by LH in both the PND 21 and 90 testes and by MENT at PND 21, whereas 11β-HSD2 mRNA was induced by testosterone and MENT in the PND 21 testis and by LH in the PND 90 testis. In conclusion, our study indicates that the 11β-HSD1 and 11β-HSD2 genes have distinct patterns of spatiotemporal expression and hormonal regulation during postnatal development of the rat testis.
文摘Background: A systematic review portraying the changing pattern of sexual behaviors, STI and HIV prevalence and key strategies curb HIV and STI among truckers in India is lacking. This paper therefore aims to present a chronological review of literature regarding sexual behaviors, STI/HIV prevalence, and various HIV prevention programs implemented among truckers in India. Methodology: Published and unpublished studies (1990-2011) were identified through electronic databases, and hand searching. Results: Most studies on sexual behaviors and STI/HIV prevalence among truckers focused only on drivers and ignored their helpers. Evidences suggest that consistent condom use by truckers with both paid and non-paid female partners has increased during the past decade. Many recent studies suggest that the HIV prevalence among truckers is about 2% and it has been declining slowly during the past decade. The HIV prevention programs among truckers which started with the aim of raising awareness about HIV during early 1990s, have grown multi-folds to encompass not only the standard strategies like mid-media events, interpersonal counselling and STI care for HIV prevention, but also innovations such as the use of business franchisee models, and integrated research and evidence based planning in the program. The possibilities of using new approaches such as male circumcision and the use of pre-exposure prophylaxes are underway. Conclusion: More studies are needed to explore helpers’ vulnerabilities to HIV. Very few studies have attempted to examine the impact of large-scale prevention programs among truckers. Efforts are required to examine the impact of different components of such programs to guide the HIV prevention efforts among truckers in India.
文摘Aim: Epididymal proteins are known to play an important role in the maturation of spermatozoa, we ougnt to deter-mine if there are regional differences in androgen-dependent epididymal proteins. Methods: A group of adult rats wascastrated and epididymides were removed three days following castration. The epididymides were dissected into caput,corpus and cauda segments, homogenized, and proteins were fractionated by anion exchange HPLC. Proteins in select-ed fractions were resolved by SDS-PAGE and visualized by silver staining. Results: It was observed that the levels ofmultiple proteins drastically reduced in the various regions of epididymis of the orchiectomized rats. Conclusion: Theepididymal proteins appear to be useful markers to study androgenic action in the epididymis.
文摘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, coumestrol）, xenoestrogens and steroids （e.g., dehydroepiandrosterone sulfate）. Bcrp is an integral membrane protein in cancer and normal cells within multiple organs （e.g., brain, placenta, intestine and testis） that maintains cellular homeostasis by extruding drugs and harmful substances from the inside of cells. In the brain, Bcrp is a major component 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 almost exclusively to the endothelial TJ in microvessels in the interstitium and the peritubular myoid cells in the tunica propria. Recent studies have shown that Bcrp is also expressed stage specifically and spatiotemporally by Sertoli and germ cells in the seminiferous epithelium of rat testes, limited only to a testis-specific cell adhesion ultrastructure known as the apical ectoplasmic specialisation （ES） in stage VI-early VIII tubules. These findings suggest that Bcrp is equipped by late spermatids and Sertoli cells to protect late-stage spermatids completing spermiogenesis. Furthermore, Bcrp was found to be associated with F （filamentous）-actin and several actin regulatory proteins at the apical ES and might be involved in the organisation of actin filaments at the apical ES in stage VII-VIII tubules. These findings will be carefully evaluated in this brief review.
基金This work was supported in part by grants from the National Institutes of Health(NICHD,R01 HD056034 to CYC)the National Natural Science Foundation of China(NSFCNo.81730042 to RSG).
文摘Collagenα3(IV)chains are one of the major constituent components of the basement membrane in the mammalian testis.Studies have shown that biologically active fragments,such as noncollagenase domain(NC1)-peptide,can be released from the C-terminal region of collagenα3(IV)chains,possibly through the proteolytic action of metalloproteinase 9(MMP9).NC1-peptide was shown to promote blood-testis barrier(BTB)remodeling and fully developed spermatid(e.g.,sperm)release from the seminiferous epithelium because this bioactive peptide was capable of perturbing the organization of both actin-and microtubule(MT)-based cytoskeletons at the Sertoli cell-cell and also Sertoli-spermatid interface,the ultrastructure known as the basal ectoplasmic specialization(ES)and apical ES,respectively.More importantly,recent studies have shown that this NC1-peptide-induced effects on cytoskeletal organization in the testis are mediated through an activation of mammalian target of rapamycin complex 1/ribosomal protein S6/transforming retrovirus Akt1/2 protein(mTORC1/rpS6/Akt1/2)signaling cascade,involving an activation of cell division control protein 42 homolog(Cdc42)GTPase,but not Ras homolog family member A GTPase(RhoA),and the participation of end-binding protein 1(EB1),a microtubule plus(+)end tracking protein(+TIP),downstream.Herein,we critically evaluate these findings,providing a critical discussion by which the basement membrane modulates spermatogenesis through one of its locally generated regulatory peptides in the testis.
基金Supported by Rockefeller Foundation Grant and Mellon Foundation Grant
文摘Passive immunization of female mice by the intraperitoneal administration of ascitic fluidscontaining monoclonal antisperm antibodies blocked the development of mouse zygotes tomorulae and blastocysts when cultured in vitro.Radioiodinated YWK-I monoclonal anti-bodies were prepared and administered intraperitoneally to Jemale mice.Significant radioac-tivity was found in washes of the oviductal lumens.The results suggest that antispermantibodies block fertilization and may have a deleterious effect on early developing embryos.
文摘Background: Mental health has been a largely neglected issue among Men Who Have Sex with Men (MSM) across the world. This study examines the prevalence and correlates of depression among MSM. Data and Methods: Data for this study are used from a cross-sectional Behavioral Tracking Survey—2012 conducted among 1176 MSM from Andhra Pradesh (undivided), a southern state of India. Depression of MSM was assessed using Patient Health Questionnaire-2 scale. Descriptive statistics, bivariate and multivariate logistic regression techniques were used for analysis. Results: More than one-third of MSMs (35%) in the survey reported to have depression. The likelihood of experiencing depression was 5 times higher among MSM who were mobile for sex work outside their place of residence (55% vs 17%, AOR: 5.2, 95% CI: 3.7 - 7.3) and had experienced physical or sexual violence (82% vs 33%, AOR: 6.0, 95% CI: 2.1 - 17.4) than their respective counterparts. Rates of depression were significantly higher among MSM who had experienced Sexually Transmitted Infections symptoms;knowledge of their HIV positivity;who didn’t use condoms during anal sex with any clients/partners;those who consumed alcohol and were in financial debt at the time of survey than others. Those who were associated with any community groups have significantly less chances of reporting depression. Discussion: The study certainly highlighted that the HIV prevention efforts with MSM in India require an integrated approach on addressing the mental health issues. To support this, programs and research-based evidence will be highly needed to ensure that mental health issues are properly addressed among MSM and other high risk groups.
