Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis.Sex-determining region Y box-containing...Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis.Sex-determining region Y box-containing genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical,and endometrial cancer.In this review, we summarize the contrasting regulatory roles of Sex-determining region Y box-containing genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression levels.Expression levels of Sex-determining region Y box-containing genes were also identified as biomarkers of clinical features, including International Federation of Gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological cancers.An understanding of the mechanisms whereby Sex-determining region Y box-containing genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of Sex-determining region Y box-containing expression levels will help to predict the prognosis of patients with gynecological cancers.展开更多
Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the c...Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence.The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical,imaging,laboratorical and pathological characteristics of 37 SCCOPT cases,in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases(n=37)was 56.00(range,22-80)years.Almost 80%of them had a stageⅢorⅣtumor.All patients underwent an operation and postoperative chemotherapy.Nevertheless,all cases had a poor prognosis,with a median overall survival time of 12 months.Immunohistochemical y,the SCCOPT of all patients showed positive expressions of epithelial markers,such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2(SOX-2),and negative expressions of estrogen receptor,progesterone receptor,vimentin,Leu-7,and somatostatin receptor 2.The tumor of above 80%cases expressed synaptophysin.Only a few cases expressed neuron-specific enolase,chromogranin A,and thyroid transcription factor-1.Conclusions SCCOPT had a poor prognosis.SOX-2 could be a biomarker to be used to diagnose SCCOPT.展开更多
After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflam...After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflammation but hinders axon regeneration.Meanwhile,microglia gradually accumulate at the lesion border to form microglial scar and can polarize to generate a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype.However,the effect of microglia polarization on astrocytes is unclear.Here,we found that both microglia(CX3 CR1^(+))and astrocytes(GFAP^(+))gathered at the lesion border at 14 days post-injury(dpi).The microglia accumulated along the inner border of and in direct contact with the astrocytes.M1-type microglia(i NOS^(+)CX3 CR1^(+))were primarily observed at 3 and 7 dpi,while M2-type microglia(Arg1^(+)CX3 CR1^(+))were present at larger numbers at 7 and 14 dpi.Transforming growth factor-β1(TGFβ1)was highly expressed in M1 microglia in vitro,consistent with strong expression of TGFβ1 by microglia in vivo at 3 and 7 dpi,when they primarily exhibited an M1 phenotype.Furthermore,conditioned media from M1-type microglia induced astrocytes to secrete chondroitin sulfate proteoglycan in vitro.This effect was eliminated by knocking down sex-determining region Y-box 9(SOX9)in astrocytes and could not be reversed by treatment with TGFβ1.Taken together,our results suggest that microglia undergo M1 polarization and express high levels of TGFβ1 at 3 and 7 dpi,and that M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFβ1/SOX9 pathway.The study was approved by the Institutional Animal Care and Use Committee of Anhui Medical University,China(approval No.LLSC20160052)on March 1,2016.展开更多
Sex is prevalent in nature and sex determination is one of the most fundamental biological processes, while the way of initiating female and male development exhibits remarkable diversity and variability across verteb...Sex is prevalent in nature and sex determination is one of the most fundamental biological processes, while the way of initiating female and male development exhibits remarkable diversity and variability across vertebrates. The knowledge on why and how sex determination mechanisms evolve unusual plasticity remains limited. Here, we summarize sex determination systems,master sex-determining genes and gene-regulatory networks among vertebrates. Recent research advancements on sex determination system transition are also introduced and discussed in some non-model animals with multiple sex determination mechanisms. This review will provide insights into the origin, transition and evolutionary adaption of different sex determination strategies in vertebrates, as well as clues for future perspectives in this field.展开更多
Sex-determination mechanisms evolve rapidly and vary between species.Occasionally,polymorphic systems are found,like in the housefly.Studying the dynamics and stability of such systems can provide a better understandi...Sex-determination mechanisms evolve rapidly and vary between species.Occasionally,polymorphic systems are found,like in the housefly.Studying the dynamics and stability of such systems can provide a better understanding of the evolution of sex-determination systems.In the housefly,dominant male-determining loci(M)can lie not only on the Y chromosome(M^(Y)),but also on autosomes(M^(A))or the X chromosome(M^(X)).M enforces male development by inhibiting the female-determining gene transformer(tra).A mutant tra allele,tra^(D),is insensitive to M and is a dominant female determiner.M^(Y) prevails at high latitudes and polymorphic M loci together with tra^(D) at low latitudes.To get more insight into the stability and frequencies of these sex determiners with mutually exclusive dominance,we investigated 5 regional Spanish populations.We found strong variation among populations.Two populations with hemizygous M^(III) were found,2 contained homozygous M^(X) with additional hemizygous MI and M^(II) in 1 population.One population contained homozygous and hemizygous M^(X) with additionally hemizygous M^(II).All females in populations with homozygous M,had tra^(D),whereas no tra^(D) was found in populations without homozygous M.Our results indicate locally stable systems may either harbor a single hemizygous M and no tra^(D),corresponding to a male heterogametic system,or homozygous and/or multiple M and heterozygous tra^(D),reminiscent of a female heterogametic system.They support that M loci can accumulate in the presence of a dominant female determiner.Limited migration between populations may contribute to the stability of these systems.展开更多
Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(S...Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(Sox13)gene is expressed in mouse spermatogonia.In addition,it has been identified as islet cell autoantigen 12(ICA12),which is involved in the pathogenesis of autoimmune diseases,including type 1 diabetes mellitus(DM)and primary biliary cirrhosis.SOX13 expression has never been investigated in patients with KS.In this age-matched,case-control study performed on ten patients with KS and ten controls,we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls.This finding might be consistent with the germ cell loss typical of patients with KS.However,the role of SOX13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.展开更多
Tumor initiating cells(TICs)have been identified as cells that account for tumor heterogeneity.Recent studies demonstrated that genes controlling stem cell biology play key roles in maintaining TICs and promote their ...Tumor initiating cells(TICs)have been identified as cells that account for tumor heterogeneity.Recent studies demonstrated that genes controlling stem cell biology play key roles in maintaining TICs and promote their development into cancer.In this review,we summarize findings from human and animal studies that indicate the presence of TICs during liver cancer development.Markers identified for liver development and regeneration are used to identify liver cancer TICs.Expression of these markers is often upregulated in human hepatocellular carcinoma(HCC)specimen.Using flow cytometry analysis and lineage tracing approaches,the presence of TICs is confirmed.Expression of TIC markers and the presence of TICs are also observed in genetically modified animals that target genes that are frequently altered in human HCC.The presence of these TICs represents a major challenge for therapeutic development.Elucidating signals that can regulate the fate,transformation and growth of liver TICs is an emerging need in liver research.Sex-determining region Y-box 9(SOX9)has recently become an important marker for liver TICs.Here,we summarize the role of SOX9 in TICs and its potential interaction with other signals.This includes the Notch-Numb signal that controls asymmetrical-symmetrical cell division,Wnt-b-catenin signal that maintains cell fate and transforming growth factor(TGF)-b signal that acts as upstream inducers.展开更多
基金supported by grants from the National Natural Science Foundation of China (Grant No.81572568 and 81272863)
文摘Sex-determining region Y box-containing genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis.Sex-determining region Y box-containing genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical,and endometrial cancer.In this review, we summarize the contrasting regulatory roles of Sex-determining region Y box-containing genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression levels.Expression levels of Sex-determining region Y box-containing genes were also identified as biomarkers of clinical features, including International Federation of Gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological cancers.An understanding of the mechanisms whereby Sex-determining region Y box-containing genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of Sex-determining region Y box-containing expression levels will help to predict the prognosis of patients with gynecological cancers.
文摘Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence.The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical,imaging,laboratorical and pathological characteristics of 37 SCCOPT cases,in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases(n=37)was 56.00(range,22-80)years.Almost 80%of them had a stageⅢorⅣtumor.All patients underwent an operation and postoperative chemotherapy.Nevertheless,all cases had a poor prognosis,with a median overall survival time of 12 months.Immunohistochemical y,the SCCOPT of all patients showed positive expressions of epithelial markers,such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2(SOX-2),and negative expressions of estrogen receptor,progesterone receptor,vimentin,Leu-7,and somatostatin receptor 2.The tumor of above 80%cases expressed synaptophysin.Only a few cases expressed neuron-specific enolase,chromogranin A,and thyroid transcription factor-1.Conclusions SCCOPT had a poor prognosis.SOX-2 could be a biomarker to be used to diagnose SCCOPT.
基金supported by the National Natural Science Foundation of China,Nos.81801220(to MGZ),81671204(to JHJ)Key Research and Development Projects of Anhui Province of China,No.202004j07020042(to JHJ)。
文摘After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflammation but hinders axon regeneration.Meanwhile,microglia gradually accumulate at the lesion border to form microglial scar and can polarize to generate a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype.However,the effect of microglia polarization on astrocytes is unclear.Here,we found that both microglia(CX3 CR1^(+))and astrocytes(GFAP^(+))gathered at the lesion border at 14 days post-injury(dpi).The microglia accumulated along the inner border of and in direct contact with the astrocytes.M1-type microglia(i NOS^(+)CX3 CR1^(+))were primarily observed at 3 and 7 dpi,while M2-type microglia(Arg1^(+)CX3 CR1^(+))were present at larger numbers at 7 and 14 dpi.Transforming growth factor-β1(TGFβ1)was highly expressed in M1 microglia in vitro,consistent with strong expression of TGFβ1 by microglia in vivo at 3 and 7 dpi,when they primarily exhibited an M1 phenotype.Furthermore,conditioned media from M1-type microglia induced astrocytes to secrete chondroitin sulfate proteoglycan in vitro.This effect was eliminated by knocking down sex-determining region Y-box 9(SOX9)in astrocytes and could not be reversed by treatment with TGFβ1.Taken together,our results suggest that microglia undergo M1 polarization and express high levels of TGFβ1 at 3 and 7 dpi,and that M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFβ1/SOX9 pathway.The study was approved by the Institutional Animal Care and Use Committee of Anhui Medical University,China(approval No.LLSC20160052)on March 1,2016.
基金supported by the Key Program of Frontier Sciences of the Chinese Academy of Sciences (QYZDY-SSWSMC025)the National Natural Science Foundation of China (31502148 and 31873036)+3 种基金the Earmarked Fund for Modern Agro-industry Technology Research System (NYCYTX-49)the Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology (2016FBZ01)the Autonomous Project of the Institute of Hydrobiology, Chinese Academy of Sciences (Y25A171)the Knowledge Innovation Program of the Chinese Academy of Science
文摘Sex is prevalent in nature and sex determination is one of the most fundamental biological processes, while the way of initiating female and male development exhibits remarkable diversity and variability across vertebrates. The knowledge on why and how sex determination mechanisms evolve unusual plasticity remains limited. Here, we summarize sex determination systems,master sex-determining genes and gene-regulatory networks among vertebrates. Recent research advancements on sex determination system transition are also introduced and discussed in some non-model animals with multiple sex determination mechanisms. This review will provide insights into the origin, transition and evolutionary adaption of different sex determination strategies in vertebrates, as well as clues for future perspectives in this field.
基金supported by China Scholarship Council(CSC)Scholarship no.201706300123supported by CSC Scholarship no.201606330077.
文摘Sex-determination mechanisms evolve rapidly and vary between species.Occasionally,polymorphic systems are found,like in the housefly.Studying the dynamics and stability of such systems can provide a better understanding of the evolution of sex-determination systems.In the housefly,dominant male-determining loci(M)can lie not only on the Y chromosome(M^(Y)),but also on autosomes(M^(A))or the X chromosome(M^(X)).M enforces male development by inhibiting the female-determining gene transformer(tra).A mutant tra allele,tra^(D),is insensitive to M and is a dominant female determiner.M^(Y) prevails at high latitudes and polymorphic M loci together with tra^(D) at low latitudes.To get more insight into the stability and frequencies of these sex determiners with mutually exclusive dominance,we investigated 5 regional Spanish populations.We found strong variation among populations.Two populations with hemizygous M^(III) were found,2 contained homozygous M^(X) with additional hemizygous MI and M^(II) in 1 population.One population contained homozygous and hemizygous M^(X) with additionally hemizygous M^(II).All females in populations with homozygous M,had tra^(D),whereas no tra^(D) was found in populations without homozygous M.Our results indicate locally stable systems may either harbor a single hemizygous M and no tra^(D),corresponding to a male heterogametic system,or homozygous and/or multiple M and heterozygous tra^(D),reminiscent of a female heterogametic system.They support that M loci can accumulate in the presence of a dominant female determiner.Limited migration between populations may contribute to the stability of these systems.
文摘Klinefelter syndrome(KS)is the most common sex chromosome disorder in men.It is characterized by germ cell loss and other variable clinical features,including autoimmunity.The sex-determining region of Y(SRY)-box 13(Sox13)gene is expressed in mouse spermatogonia.In addition,it has been identified as islet cell autoantigen 12(ICA12),which is involved in the pathogenesis of autoimmune diseases,including type 1 diabetes mellitus(DM)and primary biliary cirrhosis.SOX13 expression has never been investigated in patients with KS.In this age-matched,case-control study performed on ten patients with KS and ten controls,we found that SOX13 is significantly downregulated in peripheral blood mononuclear cells of patients with KS compared to controls.This finding might be consistent with the germ cell loss typical of patients with KS.However,the role of SOX13 in the pathogenesis of germ cell loss and humoral autoimmunity in patients with KS deserves to be further explored.
基金Dr.Stiles acknowledges support from National Institute of Health grants R01CA154986-01 and R01DK084241-01We also acknowledge support from University of Southern California center for Liver Disease(P30DK48522)Norris Comprehensive Cancer Center(P30CA014089)。
文摘Tumor initiating cells(TICs)have been identified as cells that account for tumor heterogeneity.Recent studies demonstrated that genes controlling stem cell biology play key roles in maintaining TICs and promote their development into cancer.In this review,we summarize findings from human and animal studies that indicate the presence of TICs during liver cancer development.Markers identified for liver development and regeneration are used to identify liver cancer TICs.Expression of these markers is often upregulated in human hepatocellular carcinoma(HCC)specimen.Using flow cytometry analysis and lineage tracing approaches,the presence of TICs is confirmed.Expression of TIC markers and the presence of TICs are also observed in genetically modified animals that target genes that are frequently altered in human HCC.The presence of these TICs represents a major challenge for therapeutic development.Elucidating signals that can regulate the fate,transformation and growth of liver TICs is an emerging need in liver research.Sex-determining region Y-box 9(SOX9)has recently become an important marker for liver TICs.Here,we summarize the role of SOX9 in TICs and its potential interaction with other signals.This includes the Notch-Numb signal that controls asymmetrical-symmetrical cell division,Wnt-b-catenin signal that maintains cell fate and transforming growth factor(TGF)-b signal that acts as upstream inducers.
