Although suppressed serum testosterone （T） is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual （e.g., erectile dysfunction）, physical （e.g...Although suppressed serum testosterone （T） is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual （e.g., erectile dysfunction）, physical （e.g. loss of vigor and frailty） and psychological （e.g., depression） symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male （PADAM）. Late-onset hypogonadism （LOH） describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure （low T, high luteinizing hormone （LH）） or secondary to a hypothalamic-pituitary failure （low T, low or inappropriately normal LH）. The latter form is more common and it is usually associated with overweight/obesity or chronic diseases （e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty）. A problem with the diagnosis of LOH is that often the symptoms （in 20%-40% of unselected men） and low circulating T （in 20% of men 〉70 years of age） do not coincide in the same individual. The European Male Ageing Study （EMAS） has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T （total T 〈11 nmol 1-1 and free T 〈220 pmol 1-1） and three sexual symptoms （erectile dysfunction, and reduced frequency of sexual thoughts and morning erections）. By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefits and short- and long-term risks, is not yet available. In this review, we will summarize the current conceets and controversies in the Dathogenesis, diagnosis and treatment of LOH.展开更多
We investigated the ability of fetal mesenchymal stem cells （fMSCs） to differentiate into brown and white adi- pocytes and compared the expression of a number of marker genes and key regulatory factors. We showed th...We investigated the ability of fetal mesenchymal stem cells （fMSCs） to differentiate into brown and white adi- pocytes and compared the expression of a number of marker genes and key regulatory factors. We showed that the expression of key adipocyte regulators and markers during differentiation is similar to that in other human and mu- rine adipocyte models, including induction of PPARy2 and FABP4. Notably, we found that the preadipocyte marker, Pref-1, is induced early in differentiation and then declines markedly as the process continues, suggesting that fMSCs first acquire preadipocyte characteristics as they commit to the adipogenic lineage, prior to their differentiation into mature adipocytes. After adipogenic induction, some stem cell isolates differentiated into cells resembling brown adi- pocytes and others into white adipocytes. Detailed investigation of one isolate showed that the novel brown fat-deter- mining factor PRDM16 is expressed both before and after differentiation. Importantly, these cells exhibited elevated basal UCP-1 expression, which was dependent on the activity of the orphan nuclear receptor ERRa, highlighting a novel role for ERRa in human brown fat. Thus fMSCs represent a useful in vitro model for human adipogenesis, and provide opportunities to study the stages prior to commitment to the adipocyte lineage. They also offer invaluable in- sights into the characteristics of human brown fat.展开更多
Dear Editor, In the central nervous system, cell migration and accumulation occur widely to construct a complex neural network during mammalian development [1]. Previous studies reported that both the gaseous messeng...Dear Editor, In the central nervous system, cell migration and accumulation occur widely to construct a complex neural network during mammalian development [1]. Previous studies reported that both the gaseous messenger molecule nitric oxide （NO） [2-4] and widely studied axon guidance/migration cues such as Netrins [5, 6] regulated the migratory behavior of cells in the nervous system.展开更多
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by maternal pruritus in the third trimester, raised serum bile acids and increased rates of adverse fetal outcomes. The ...Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by maternal pruritus in the third trimester, raised serum bile acids and increased rates of adverse fetal outcomes. The etiology of ICP is complex and not fully understood, but it is likely to result from the cholestatic effects of reproductive hormones and their metabolites in genetically susceptible women. Equally unclear are the mechanisms by which the fetal complications occur. This article reviews the epidemiology, clinical features, diagnosis, etiology and management of ICP.展开更多
Sperm dysfunction is the single most common cause of infertility, yet what is remarkable is that, there is no drug a man can take or add to his spermatozoa in vitroto improve fertility. One reason for the lack of prog...Sperm dysfunction is the single most common cause of infertility, yet what is remarkable is that, there is no drug a man can take or add to his spermatozoa in vitroto improve fertility. One reason for the lack of progress in this area is that our understanding of the cellular and molecular workings of the mature spermatazoon is limited. However, over the last few years there has been considerable progress in our knowledge base and in addressing new methods to diagnose sperm dysfunction. We review the current state of the field and provide insights for further development. We conclude that： （i） there is little to be gained from more studies identifying/categorizing various populations of men using a basic semen assessment, where an effort is required in making sure the analysis is performed in an appropriate high quality way; （ii） technological development is likely to bring the reality of sperm function testing closer to implementation into the clinical pathways. In doing this, these assays must be robust, cheap （or more appropriately termed cost effective）, easy to use and clinically useful; and （iii） clinical necessity, e.g., the need to identify the highest quality spermatozoon for injection is driving basic research forward. This is an exciting time to be an andrologist and, likely, a fruitful one.展开更多
Uterine fibroids are the most common benign tumours in the reproductive system. They are proliferations of smooth muscle cells of the myometrium containing a large quantity of extracellular matrix and they are surroun...Uterine fibroids are the most common benign tumours in the reproductive system. They are proliferations of smooth muscle cells of the myometrium containing a large quantity of extracellular matrix and they are surrounded by a pseudo capsule of compressed areolar tissue and smooth muscle cells. They can cause various symptoms such as menorrhage, pain and infertility and therefore they can be a traumatic experience for several women. The treatment of choice is myomectomy. In the past, myomectomy was performed by relatively atraumatic techniques, which involved stretching the myoma from its pseudocapsule to extract the fibroid directly from the surrounding fibromuscular tissue, breaking up the fibrous bridge. Modern laparoscopic intracapsular myomectomy (LIM), however, leaves the fibrovascular network surrounding the myoma (namely the “fibroid neurovascular bundle”) intact which reduces the bleeding and/or uterine musculature trauma, and spares the neuropeptide fibers of the pseudocapsule. In this observational study, we compare the two techniques-laparoscopic intracapsular myomectomy (LIM) and conventional abdominal myomectomy (CAM) regarding the longterm uterine healing and a significantly faster healing process of the uterine incision was achieved by LIM compared to CAM.展开更多
Aremarkable advance in sperm physiology has recently been published in Nature. Two groups using patch damping techniques on human sperm have solved a mystery about the sperm cell that has puzzled both andrologists and...Aremarkable advance in sperm physiology has recently been published in Nature. Two groups using patch damping techniques on human sperm have solved a mystery about the sperm cell that has puzzled both andrologists and those involved in non-genomic cellular signalling for over 20 years. In these papers, Lishko1 and Strunker2 independently demonstrate that the universal characteristic effect of progesterone on sperm--a rapid influx of calcium--is via a sperm-specific channel CatSper.展开更多
Preterm babies are exposed to multiple stressors and this may have long- term effects. In particular, high levels of endogenous cortisol might have a programming effect on the hypothalamicpituitary- adrenal axis as ma...Preterm babies are exposed to multiple stressors and this may have long- term effects. In particular, high levels of endogenous cortisol might have a programming effect on the hypothalamicpituitary- adrenal axis as may administered glucocorticoids. In this study, we aimed to test the hypothesis that the level of endogenous and exogenous glucocorticoid exposure during the neonatal period predicts the saliva cortisol response to immunization at 4 mo of age. We followed 45 babies born below 32 wk gestation. We showed that their concentration of plasma cortisol during the first 4 wk was 358, 314, 231, and 195 nmol/L cortisol, respectively (geometric mean). This is four to seven times higher than fetal levels at the same gestational age range. We used routine immunization at 4 mo and 12 mo as a stressor and measured the change in saliva cortisol as the stress response. Mean circulating cortisol in the first 4 wk predicted the cortisol response at 4 but not at 12 mo. Path analysis showed that birthweight for gestational age, thera- peutic antenatal steroids, and therapeutic postnatal steroids also contributed to the magnitude of the saliva cortisol response at 4 mo. This provides evidence that the magnitude of glucocorticoid exposure, both endogenous and exogenous, may have an effect on later stress responses.展开更多
Fertilisation in mammals involves many synchronized steps including spermegg adhesion. Prior to sperm-oolemma fusion, spermatozoa need to undergo the acrosome reaction （AR） or exocytosis. The universal belief, for ...Fertilisation in mammals involves many synchronized steps including spermegg adhesion. Prior to sperm-oolemma fusion, spermatozoa need to undergo the acrosome reaction （AR） or exocytosis. The universal belief, for many years, has been that the AR was initiated upon binding to the zona pellucida （ZP）. As such acrosomal proteins were not thought to be involved in the primary contact with the ZP. These proteins were only suggested to be biologically relevant once the sperm were attached to the ZP and during subsequent events. However,展开更多
Tumor cells are characterized by metabolic reprogram-ming,a step that is necessary to support their high demand for energy and nutrients[1,2].Furthermore,once metastatic tumor cells are seeded,tumor microen-vironment ...Tumor cells are characterized by metabolic reprogram-ming,a step that is necessary to support their high demand for energy and nutrients[1,2].Furthermore,once metastatic tumor cells are seeded,tumor microen-vironment remodeling is immediately initiated,leading to the formation of more suitable conditions for growth.Tumor cells secrete several types of growth factors,cytokines,and chemokines to induce angiogenesis and tumor-associated immune cell recruitment,all of which can promote proliferation and metastasis,as well as trig-ger immune tolerance and drug resistance[3].Exploring the synergistic effect between metabolic reprogramming and microenvironment remodeling will likely facili-tate the discovery of novel biomarkers and therapeutic targets.展开更多
Objective:Long noncoding RNAs(lncRNAs)play important roles in embryonic development and in various diseases.Gm48853 is a predicted natural antisense lncRNA gene of unknown function.The present study aimed to investiga...Objective:Long noncoding RNAs(lncRNAs)play important roles in embryonic development and in various diseases.Gm48853 is a predicted natural antisense lncRNA gene of unknown function.The present study aimed to investigate its expression and function.Methods:Quantitative reverse transcription-polymerase chain reaction and sequencing were used to detect the expression of Gm48853 antisense lncRNA.Hematoxylin and eosin staining and pathological analysis were applied to evaluate the effects of Gm48853 mutations on embryonic/placental development.5-Ethynyl-2’-deoxyuridine(EdU)and terminal deoxynucleotidyl transferase deoxy-UTP-nick-end labeling assays were used to analyze the status of cell proliferation and apoptosis in Gm48853-deficient embryos and placentas.Results:PiggyBac(PB)transposon insertion into the intron of Gm48853 resulted in a significant decrease in Gm48853 expression and embryonic lethality at midgestation.Homozygous Gm48853 mutations led to severe growth retardation of embryos and impaired the morphogenesis of the placental labyrinth.In addition,cell proliferation was dramatically decreased in Gm48853^(PB/PB) embryos and placentas,and apoptosis was radically increased in the mutant embryos but not in the mutant placentas.Conclusion:Antisense lncRNA Gm48853 may regulate embryonic/placental development by enhancing cell proliferation and/or inhibiting apoptosis.展开更多
This study reports radiological deformities in the vertebral column of six fishes viz,Scomberomorus commerson,Chanos chanos,Sillago sihama,Pampus chinensis,Rastrelliger kanagurta and Netuma thalassina that were collec...This study reports radiological deformities in the vertebral column of six fishes viz,Scomberomorus commerson,Chanos chanos,Sillago sihama,Pampus chinensis,Rastrelliger kanagurta and Netuma thalassina that were collected from the Coromandel coast,Bay of Bengal.Four main different types of vertebral column deformities were found:(i)whole body kypho-lordo-kyphosis(Sillago sihama,Rastrelliger kanagurta,Netuma thalassina);(ii)tail region kypho-lordosis(Scomberomorus commerson);(iii)tail region lordo-kyphosis(Chanos chanos);(iv)platyspondyly(Pampus chinensis).Seven types of vertebra body deformities,describing the pathology of single vertebrae,were present;reduced intervertebral space,compression,fusion,compresion&fusion,fusion center,dorsal wedge-shaped and compressed&dorsal wed-shaped.The present documentation of deformities in six different species that are also very different with regard to habitat,diet and swimming activity may suggest that fish deformities are widespread in the study area.展开更多
Zika virus（ZIKV）is a mosquito-borne flavivirus,first discovered in the 1940s.ZIKV was originally limited to sporadic cases in Africa and Asia,until the Brazil ZIKV incidences in 2015,when it rapidly spread throughou...Zika virus（ZIKV）is a mosquito-borne flavivirus,first discovered in the 1940s.ZIKV was originally limited to sporadic cases in Africa and Asia,until the Brazil ZIKV incidences in 2015,when it rapidly spread throughout the Americas.Usually ZIKV infections are subclinical or characterized by mild febrile illness,展开更多
文摘Although suppressed serum testosterone （T） is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual （e.g., erectile dysfunction）, physical （e.g. loss of vigor and frailty） and psychological （e.g., depression） symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male （PADAM）. Late-onset hypogonadism （LOH） describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure （low T, high luteinizing hormone （LH）） or secondary to a hypothalamic-pituitary failure （low T, low or inappropriately normal LH）. The latter form is more common and it is usually associated with overweight/obesity or chronic diseases （e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty）. A problem with the diagnosis of LOH is that often the symptoms （in 20%-40% of unselected men） and low circulating T （in 20% of men 〉70 years of age） do not coincide in the same individual. The European Male Ageing Study （EMAS） has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T （total T 〈11 nmol 1-1 and free T 〈220 pmol 1-1） and three sexual symptoms （erectile dysfunction, and reduced frequency of sexual thoughts and morning erections）. By these criteria, only 2% of 40- to 80-year-old men have LOH. In particular obesity, but also impaired general health, are more common causes of low T than chronological age per se. Evidence-based information whether, and how, LOH should be treated is sparse. The most logical approach is lifestyle modification, weight reduction and good treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefits and short- and long-term risks, is not yet available. In this review, we will summarize the current conceets and controversies in the Dathogenesis, diagnosis and treatment of LOH.
文摘We investigated the ability of fetal mesenchymal stem cells （fMSCs） to differentiate into brown and white adi- pocytes and compared the expression of a number of marker genes and key regulatory factors. We showed that the expression of key adipocyte regulators and markers during differentiation is similar to that in other human and mu- rine adipocyte models, including induction of PPARy2 and FABP4. Notably, we found that the preadipocyte marker, Pref-1, is induced early in differentiation and then declines markedly as the process continues, suggesting that fMSCs first acquire preadipocyte characteristics as they commit to the adipogenic lineage, prior to their differentiation into mature adipocytes. After adipogenic induction, some stem cell isolates differentiated into cells resembling brown adi- pocytes and others into white adipocytes. Detailed investigation of one isolate showed that the novel brown fat-deter- mining factor PRDM16 is expressed both before and after differentiation. Importantly, these cells exhibited elevated basal UCP-1 expression, which was dependent on the activity of the orphan nuclear receptor ERRa, highlighting a novel role for ERRa in human brown fat. Thus fMSCs represent a useful in vitro model for human adipogenesis, and provide opportunities to study the stages prior to commitment to the adipocyte lineage. They also offer invaluable in- sights into the characteristics of human brown fat.
文摘Dear Editor, In the central nervous system, cell migration and accumulation occur widely to construct a complex neural network during mammalian development [1]. Previous studies reported that both the gaseous messenger molecule nitric oxide （NO） [2-4] and widely studied axon guidance/migration cues such as Netrins [5, 6] regulated the migratory behavior of cells in the nervous system.
文摘Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by maternal pruritus in the third trimester, raised serum bile acids and increased rates of adverse fetal outcomes. The etiology of ICP is complex and not fully understood, but it is likely to result from the cholestatic effects of reproductive hormones and their metabolites in genetically susceptible women. Equally unclear are the mechanisms by which the fetal complications occur. This article reviews the epidemiology, clinical features, diagnosis, etiology and management of ICP.
文摘Sperm dysfunction is the single most common cause of infertility, yet what is remarkable is that, there is no drug a man can take or add to his spermatozoa in vitroto improve fertility. One reason for the lack of progress in this area is that our understanding of the cellular and molecular workings of the mature spermatazoon is limited. However, over the last few years there has been considerable progress in our knowledge base and in addressing new methods to diagnose sperm dysfunction. We review the current state of the field and provide insights for further development. We conclude that： （i） there is little to be gained from more studies identifying/categorizing various populations of men using a basic semen assessment, where an effort is required in making sure the analysis is performed in an appropriate high quality way; （ii） technological development is likely to bring the reality of sperm function testing closer to implementation into the clinical pathways. In doing this, these assays must be robust, cheap （or more appropriately termed cost effective）, easy to use and clinically useful; and （iii） clinical necessity, e.g., the need to identify the highest quality spermatozoon for injection is driving basic research forward. This is an exciting time to be an andrologist and, likely, a fruitful one.
文摘Uterine fibroids are the most common benign tumours in the reproductive system. They are proliferations of smooth muscle cells of the myometrium containing a large quantity of extracellular matrix and they are surrounded by a pseudo capsule of compressed areolar tissue and smooth muscle cells. They can cause various symptoms such as menorrhage, pain and infertility and therefore they can be a traumatic experience for several women. The treatment of choice is myomectomy. In the past, myomectomy was performed by relatively atraumatic techniques, which involved stretching the myoma from its pseudocapsule to extract the fibroid directly from the surrounding fibromuscular tissue, breaking up the fibrous bridge. Modern laparoscopic intracapsular myomectomy (LIM), however, leaves the fibrovascular network surrounding the myoma (namely the “fibroid neurovascular bundle”) intact which reduces the bleeding and/or uterine musculature trauma, and spares the neuropeptide fibers of the pseudocapsule. In this observational study, we compare the two techniques-laparoscopic intracapsular myomectomy (LIM) and conventional abdominal myomectomy (CAM) regarding the longterm uterine healing and a significantly faster healing process of the uterine incision was achieved by LIM compared to CAM.
文摘Aremarkable advance in sperm physiology has recently been published in Nature. Two groups using patch damping techniques on human sperm have solved a mystery about the sperm cell that has puzzled both andrologists and those involved in non-genomic cellular signalling for over 20 years. In these papers, Lishko1 and Strunker2 independently demonstrate that the universal characteristic effect of progesterone on sperm--a rapid influx of calcium--is via a sperm-specific channel CatSper.
文摘Preterm babies are exposed to multiple stressors and this may have long- term effects. In particular, high levels of endogenous cortisol might have a programming effect on the hypothalamicpituitary- adrenal axis as may administered glucocorticoids. In this study, we aimed to test the hypothesis that the level of endogenous and exogenous glucocorticoid exposure during the neonatal period predicts the saliva cortisol response to immunization at 4 mo of age. We followed 45 babies born below 32 wk gestation. We showed that their concentration of plasma cortisol during the first 4 wk was 358, 314, 231, and 195 nmol/L cortisol, respectively (geometric mean). This is four to seven times higher than fetal levels at the same gestational age range. We used routine immunization at 4 mo and 12 mo as a stressor and measured the change in saliva cortisol as the stress response. Mean circulating cortisol in the first 4 wk predicted the cortisol response at 4 but not at 12 mo. Path analysis showed that birthweight for gestational age, thera- peutic antenatal steroids, and therapeutic postnatal steroids also contributed to the magnitude of the saliva cortisol response at 4 mo. This provides evidence that the magnitude of glucocorticoid exposure, both endogenous and exogenous, may have an effect on later stress responses.
文摘Fertilisation in mammals involves many synchronized steps including spermegg adhesion. Prior to sperm-oolemma fusion, spermatozoa need to undergo the acrosome reaction （AR） or exocytosis. The universal belief, for many years, has been that the AR was initiated upon binding to the zona pellucida （ZP）. As such acrosomal proteins were not thought to be involved in the primary contact with the ZP. These proteins were only suggested to be biologically relevant once the sperm were attached to the ZP and during subsequent events. However,
文摘Tumor cells are characterized by metabolic reprogram-ming,a step that is necessary to support their high demand for energy and nutrients[1,2].Furthermore,once metastatic tumor cells are seeded,tumor microen-vironment remodeling is immediately initiated,leading to the formation of more suitable conditions for growth.Tumor cells secrete several types of growth factors,cytokines,and chemokines to induce angiogenesis and tumor-associated immune cell recruitment,all of which can promote proliferation and metastasis,as well as trig-ger immune tolerance and drug resistance[3].Exploring the synergistic effect between metabolic reprogramming and microenvironment remodeling will likely facili-tate the discovery of novel biomarkers and therapeutic targets.
基金This work was supported by the grants from the National Key Research and Development Program of China(2016YFC1000500)the National Natural Science Foundation of China(81430005,31521003)the Commission for Science and Technology of Shanghai Municipality(13JC1407600)to H_Y Wang.
文摘Objective:Long noncoding RNAs(lncRNAs)play important roles in embryonic development and in various diseases.Gm48853 is a predicted natural antisense lncRNA gene of unknown function.The present study aimed to investigate its expression and function.Methods:Quantitative reverse transcription-polymerase chain reaction and sequencing were used to detect the expression of Gm48853 antisense lncRNA.Hematoxylin and eosin staining and pathological analysis were applied to evaluate the effects of Gm48853 mutations on embryonic/placental development.5-Ethynyl-2’-deoxyuridine(EdU)and terminal deoxynucleotidyl transferase deoxy-UTP-nick-end labeling assays were used to analyze the status of cell proliferation and apoptosis in Gm48853-deficient embryos and placentas.Results:PiggyBac(PB)transposon insertion into the intron of Gm48853 resulted in a significant decrease in Gm48853 expression and embryonic lethality at midgestation.Homozygous Gm48853 mutations led to severe growth retardation of embryos and impaired the morphogenesis of the placental labyrinth.In addition,cell proliferation was dramatically decreased in Gm48853^(PB/PB) embryos and placentas,and apoptosis was radically increased in the mutant embryos but not in the mutant placentas.Conclusion:Antisense lncRNA Gm48853 may regulate embryonic/placental development by enhancing cell proliferation and/or inhibiting apoptosis.
文摘This study reports radiological deformities in the vertebral column of six fishes viz,Scomberomorus commerson,Chanos chanos,Sillago sihama,Pampus chinensis,Rastrelliger kanagurta and Netuma thalassina that were collected from the Coromandel coast,Bay of Bengal.Four main different types of vertebral column deformities were found:(i)whole body kypho-lordo-kyphosis(Sillago sihama,Rastrelliger kanagurta,Netuma thalassina);(ii)tail region kypho-lordosis(Scomberomorus commerson);(iii)tail region lordo-kyphosis(Chanos chanos);(iv)platyspondyly(Pampus chinensis).Seven types of vertebra body deformities,describing the pathology of single vertebrae,were present;reduced intervertebral space,compression,fusion,compresion&fusion,fusion center,dorsal wedge-shaped and compressed&dorsal wed-shaped.The present documentation of deformities in six different species that are also very different with regard to habitat,diet and swimming activity may suggest that fish deformities are widespread in the study area.
文摘Zika virus（ZIKV）is a mosquito-borne flavivirus,first discovered in the 1940s.ZIKV was originally limited to sporadic cases in Africa and Asia,until the Brazil ZIKV incidences in 2015,when it rapidly spread throughout the Americas.Usually ZIKV infections are subclinical or characterized by mild febrile illness,
