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
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
Aim： To understand the biological functions of the ectoplasmic specializations between Sertoli cells and maturing spermatids in seminiferous epithelia. Methods： In order to disrupt the function of the ectoplasmic sp...Aim： To understand the biological functions of the ectoplasmic specializations between Sertoli cells and maturing spermatids in seminiferous epithelia. Methods： In order to disrupt the function of the ectoplasmic specializations, nectin-2, which is expressed at the specialization, was neutralized with anti-nectin-2 antibody micro-injected into the lumen of the mouse seminiferous tubule. Anti-nectin-3 antibody was also micro-injected into the lumen in order to neutralize nectin-3, which is expressed at the specialization. Results： The actin filaments at the specialization disappeared, and exfoliation of maturing spermatids was observed by electron microscopy. Conclusion： Nectin-2 was neutralized by anti-nectin-2 antibody and nectin-3 was neutralized by anti-nectin-3 antibody, respectively. Inactivated nectin-2 and nectin-3 disrupted the nectin-afadin-actin system, and finally the actin filaments disappeared. As a result, the specialization lost the holding function and detachment of spermatids was observed. One of the functions of the specialization seems to be to hold maturing spermatids until spermiation.展开更多
Background:Oligoasthenospermia is one of the main causes of male infertility.Researchers usually use chemical drugs to directly damage germ cells to prepare oligoasthenospermia models,which disregards the adhesion and...Background:Oligoasthenospermia is one of the main causes of male infertility.Researchers usually use chemical drugs to directly damage germ cells to prepare oligoasthenospermia models,which disregards the adhesion and migration between spermatogenic cells and Sertoli cells.TAp73 is a critical regulator of the adhesin of germ cell;thus,we sought to explore a novel oligoasthenospermia model based on TAp73 gene suppression.Methods:Mice in the Pifithrin-αgroup were injected intraperitoneally with 2.5 mg/kg Pifithrin-α(TAp73 inhibitor)daily for 30 consecutive days.Reproductive hormone levels and epididymal sperm quality,as well as the network morphology of Sertoli cells were tested.Results:Sperm density,motility,and the relative protein and mRNA expression of TAp73 and Nectin 2 were obviously decreased in the Pifithrin-αgroup compared with the normal control group.No significant distinction was observed in the relative mRNA and protein expression of ZO-1.Furthermore,the tight junctions(TJs)and api-cal ectoplasmic specialization(ES)were destroyed in the Pifithrin-αgroup.Conclusion:The above results indicate that we successfully established a new oli-goasthenospermia mouse model.This study provides a foundation for further explo-ration of the roles of TAp73 genes during spermatogenesis and provides new research objects for further oligospermia research and future drug discovery.展开更多
Healing therapies are a set of techniques used with the aim of transfusing healthy “bioenergy” to other people in order to restore physical, mental, and emotional balance. It is necessary that something is donated f...Healing therapies are a set of techniques used with the aim of transfusing healthy “bioenergy” to other people in order to restore physical, mental, and emotional balance. It is necessary that something is donated from the healer, that is, something results from his organic metabolism. Also, based on your physical, mental, and emotional health, the energy resulting from your metabolism is assumed to be healthy for the healing of patients. On the other hand, also in many cases, healing does not occur due to the “vicious” quality of the energy to be transfused and the low receptivity of the patient. However, in most cases, it depends not only on the healer but also on the receiver, but usually on other healers, such as higher order consciousnesses. In fact, in many cases of healing, the effect is almost instantaneous with just the healer’s “magnetic energy”, especially in painful crises. Without a doubt, I believe that biophoton is an anti-inflammatory, analgesic, antibacterial and immunomodulatory bioenergy. The healing effectiveness of these therapies is well established. It is a cell-restoring product that can rebuild tissues and organs in a short time, which in many cases leads to the restoration of the patient’s health and well-being. The aim of this study is to address a brief history of ancestral energies of Asian philosophy (Chinese, Japanese and Indian), highlight the role of consciousness and the healer in healing therapies. In addition, the study emphasizes the similarity of these energies with the one called “ectoplasm”, as well as it establishes connections with the newly elected ultra-weak emission of photons. Finally, bibliographic research was carried out in an English language database and innovative concepts were introduced about the role of consciousness as well as the healer in healing therapies.展开更多
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.
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.
文摘Aim： To understand the biological functions of the ectoplasmic specializations between Sertoli cells and maturing spermatids in seminiferous epithelia. Methods： In order to disrupt the function of the ectoplasmic specializations, nectin-2, which is expressed at the specialization, was neutralized with anti-nectin-2 antibody micro-injected into the lumen of the mouse seminiferous tubule. Anti-nectin-3 antibody was also micro-injected into the lumen in order to neutralize nectin-3, which is expressed at the specialization. Results： The actin filaments at the specialization disappeared, and exfoliation of maturing spermatids was observed by electron microscopy. Conclusion： Nectin-2 was neutralized by anti-nectin-2 antibody and nectin-3 was neutralized by anti-nectin-3 antibody, respectively. Inactivated nectin-2 and nectin-3 disrupted the nectin-afadin-actin system, and finally the actin filaments disappeared. As a result, the specialization lost the holding function and detachment of spermatids was observed. One of the functions of the specialization seems to be to hold maturing spermatids until spermiation.
基金This project was supported by the Natural Science Foundation of Anhui Provincial Department of Education(no.KJ2020A0386)National Natural Science Foundation of China(no.82174162).
文摘Background:Oligoasthenospermia is one of the main causes of male infertility.Researchers usually use chemical drugs to directly damage germ cells to prepare oligoasthenospermia models,which disregards the adhesion and migration between spermatogenic cells and Sertoli cells.TAp73 is a critical regulator of the adhesin of germ cell;thus,we sought to explore a novel oligoasthenospermia model based on TAp73 gene suppression.Methods:Mice in the Pifithrin-αgroup were injected intraperitoneally with 2.5 mg/kg Pifithrin-α(TAp73 inhibitor)daily for 30 consecutive days.Reproductive hormone levels and epididymal sperm quality,as well as the network morphology of Sertoli cells were tested.Results:Sperm density,motility,and the relative protein and mRNA expression of TAp73 and Nectin 2 were obviously decreased in the Pifithrin-αgroup compared with the normal control group.No significant distinction was observed in the relative mRNA and protein expression of ZO-1.Furthermore,the tight junctions(TJs)and api-cal ectoplasmic specialization(ES)were destroyed in the Pifithrin-αgroup.Conclusion:The above results indicate that we successfully established a new oli-goasthenospermia mouse model.This study provides a foundation for further explo-ration of the roles of TAp73 genes during spermatogenesis and provides new research objects for further oligospermia research and future drug discovery.
文摘Healing therapies are a set of techniques used with the aim of transfusing healthy “bioenergy” to other people in order to restore physical, mental, and emotional balance. It is necessary that something is donated from the healer, that is, something results from his organic metabolism. Also, based on your physical, mental, and emotional health, the energy resulting from your metabolism is assumed to be healthy for the healing of patients. On the other hand, also in many cases, healing does not occur due to the “vicious” quality of the energy to be transfused and the low receptivity of the patient. However, in most cases, it depends not only on the healer but also on the receiver, but usually on other healers, such as higher order consciousnesses. In fact, in many cases of healing, the effect is almost instantaneous with just the healer’s “magnetic energy”, especially in painful crises. Without a doubt, I believe that biophoton is an anti-inflammatory, analgesic, antibacterial and immunomodulatory bioenergy. The healing effectiveness of these therapies is well established. It is a cell-restoring product that can rebuild tissues and organs in a short time, which in many cases leads to the restoration of the patient’s health and well-being. The aim of this study is to address a brief history of ancestral energies of Asian philosophy (Chinese, Japanese and Indian), highlight the role of consciousness and the healer in healing therapies. In addition, the study emphasizes the similarity of these energies with the one called “ectoplasm”, as well as it establishes connections with the newly elected ultra-weak emission of photons. Finally, bibliographic research was carried out in an English language database and innovative concepts were introduced about the role of consciousness as well as the healer in healing therapies.
