BACKGROUND Endothelial colony-forming cells(ECFCs)have been implicated in the process of vascularization,which includes vasculogenesis and angiogenesis.Vasculogenesis is a de novo formation of blood vessels,and is an ...BACKGROUND Endothelial colony-forming cells(ECFCs)have been implicated in the process of vascularization,which includes vasculogenesis and angiogenesis.Vasculogenesis is a de novo formation of blood vessels,and is an essential physiological process that occurs during embryonic development and tissue regeneration.Angiogenesis is the growth of new capillaries from pre-existing blood vessels,which is observed both prenatally and postnatally.The placenta is an organ composed of a variety of fetal-derived cells,including ECFCs,and therefore has significant potential as a source of fetal ECFCs for tissue engineering.AIM To investigate the possibility of isolating clonal ECFCs from human early gestation chorionic villi(CV-ECFCs)of the placenta,and assess their potential for tissue engineering.METHODS The early gestation chorionic villus tissue was dissociated by enzyme digestion.Cells expressing CD31 were selected using magnetic-activated cell sorting,and plated in endothelial-specific growth medium.After 2-3 wks in culture,colonies displaying cobblestone-like morphology were manually picked using cloning cylinders.We characterized CV-ECFCs by flow cytometry,immunophenotyping,tube formation assay,and Dil-Ac-LDL uptake assay.Viral transduction of CVECFCs was performed using a Luciferase/tdTomato-containing lentiviral vector,and transduction efficiency was tested by fluorescent microscopy and flow cytometry.Compatibility of CV-ECFCs with a delivery vehicle was determined using an FDA approved,small intestinal submucosa extracellular matrix scaffold.RESULTS After four passages in 6-8 wks of culture,we obtained a total number of 1.8×107 CV-ECFCs using 100 mg of early gestational chorionic villus tissue.Immunophenotypic analyses by flow cytometry demonstrated that CV-ECFCs highly expressed the endothelial markers CD31,CD144,CD146,CD105,CD309,only partially expressed CD34,and did not express CD45 and CD90.CV-ECFCs were capable of acetylated low-density lipoprotein uptake and tube formation,similar to cord blood-derived ECFCs(CB-ECFCs).CV-ECFCs can be transduced with a Luciferase/tdTomato-containing lentiviral vector at a transduction efficiency of 85.1%.Seeding CV-ECFCs on a small intestinal submucosa extracellular matrix scaffold confirmed that CV-ECFCs were compatible with the biomaterial scaffold.CONCLUSION In summary,we established a magnetic sorting-assisted clonal isolation approach to derive CV-ECFCs.A substantial number of CV-ECFCs can be obtained within a short time frame,representing a promising novel source of ECFCs for fetal treatments.展开更多
Objective To investigate the role of mifepristone in regulating cytokines of materno-fetal interface and serum of human early gestationMethods Thirty-five women with early pregnancy received mifepristone 50 mg orallyo...Objective To investigate the role of mifepristone in regulating cytokines of materno-fetal interface and serum of human early gestationMethods Thirty-five women with early pregnancy received mifepristone 50 mg orallyon study d 1 and d 2, respectively, followed by undergoing artificial abortion to getdecidua and villi on study d 3. Twenty-five women with early pregnancy withoutmifepristone administration as control also underwent artificial abortion to get de-cidua and villi. The expressions of TGF-β1 and TGF-β1 receptor mRNA in the earlydecidua and villi were assessed by using RT-PCR . The concentrations of serum TNF-α were measured by radioimmunoassay.Results The decidual expressions of TGF- β1 mRNA and TGF-β1 receptor mRNA in thetreated group were significantly lower than those of the control (P<0.05), while thevillus expressions of TGF-β1 and TGF-β1 receptor mRNA in the treated group were notsignificantly different from those of the control (P>0.05). The serum TNF-β1 levelselevated significantly after mifepristone treatment.Conclusion The antigestational effect of mifepristone might act through suppressingthe transcription of TGF-β1 and TGF-β1 receptor in the decidua and increasing theserum TNF-α level, which interfered in the materno-fetal interface Th2 bias.展开更多
Fourteen normal human placental villi at a fetal age of 5-8 weeks were examined withelectron microscope. The results were vide infra.(1)The cytotrophoblasts were characterized by largenucleus with less heterochromatin...Fourteen normal human placental villi at a fetal age of 5-8 weeks were examined withelectron microscope. The results were vide infra.(1)The cytotrophoblasts were characterized by largenucleus with less heterochromatin and prominent nucleolus with a number of free polyribosomes as well asscattered mitochondria in the cytoplasm.(2) There was a layer of dense microvilli on the surface of thesyncytiotrophoblastic cells.The size and shape of microvilli were variable. Usually fine globular expansions were present at the apical pole of microvilli and the cell membrane between the base of microvillihad invaginations into the cytoplasm forming small vesicles and tubules. Rough endoplasmic reticulum,free polyribosomes,mitochondria, lipid droplets and few myelinlike figures were also found in the cytoplasm.Part of cytoplasm penetrated into the interspaces of cytotrophoblastic cells and became in directcontact with the basement membrane.(3) Numerous desmosomes were seen between the cells of cytotrophoblast and syncytiotrophoblast.And (4) in the strom a of villi,mesenchymal cells were abundant inrough endoplasmic reticulum and well developed Golgi complex. Mesenchymat cells were markedlyfunctionally active. Ultrastructural characteristics of placental villin in connexion with their functionwere discussed.展开更多
<strong>Objective</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><strong>:</strong...<strong>Objective</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><strong>:</strong></span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> To investigate the changes of hsMAD2 protein and gene expression levels during chromosome segregation of human embryos. </span><b><span style="font-family:Verdana;">Method</span></b></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">:</span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> The embryos of spontaneous abortion were collected in our hospital from 2009 to 2013, the chromosomal numbers of the embryonic villi were subsequently detected by fluorescence in situ hybridization (FISH). The patients were then divided into the normal and abnormal groups based on the chromosome number. The hsMAD2 protein and gene expression levels in the villi tissues of the two embryo groups were detected by western blotting and qRT-PCR, respectively. The hsMAD2 protein and gene levels in the embryonic villus tissue of the patient were detected. </span><b><span style="font-family:Verdana;">Results</span></b></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">:</span></b></span></span><span><span><b><span style="font-family:""> </span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">From 2009 to 2013, we collected 50 embryos from spontaneous abortion patients. The chromosome abnormality and no abnormality were 36 cases (abnormal number of 28 cases (56.0%) and chimerism in 8 cases (16.0%)) and 14 cases (28.0%), respectively.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The expression of hsmad2 protein and its gene in the villi of spontaneously aborted embryo with chromosomal abnormality in the abnormal group was significantly higher than that in those without chromosomal abnormalities (0.88 ± 0.20 vs 0.61 ± 0.19, P < 0.05), (23.46 ± 0.07 vs 18.35 ± 0.10, P < 0.05).</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Conclusion</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">:</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> Abnormal number of chromosomes is closely related to spontaneous abortion Linked, hsMAD2 factor has a card effect on the cell cycle, can block the mitotic process of cells, and play an important role in maintaining the normal separation and stability of chromosomes</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.</span></span></span>展开更多
Pancreatic cancer(PC)is a highly lethal tumor with controversial high glucose uptake and hypomicrovascularity.And,the hypomicrovasculature,which is considered to have poor perfusion,blocks the delivery of drugs to tum...Pancreatic cancer(PC)is a highly lethal tumor with controversial high glucose uptake and hypomicrovascularity.And,the hypomicrovasculature,which is considered to have poor perfusion,blocks the delivery of drugs to tumors.Previously,we described the preferential existence of a novel endothelial projection with trafficking vesicles in PCs,referring to basal microvilli.However,whether the basal microvilli microvessels have good perfusion or deliver nutrients to the tumor milieu is unknown.Here,we perfused multiple endothelial markers and nutrients to autochthonous PC-bearing mice to study the nutrient trafficking and perfusion status of the basal microvilli microvasculature.展开更多
Objective:This study aims to explore its role in embryo damage and the relationship between them by testing the expression of PCNA,Caspase-3,IL-6 and Survivin protein in the chorionic villi and decidual tissue of pati...Objective:This study aims to explore its role in embryo damage and the relationship between them by testing the expression of PCNA,Caspase-3,IL-6 and Survivin protein in the chorionic villi and decidual tissue of patients with unexplained early embryo damage and normal early pregnancy at the same time voluntarily requested uterine aspiration abortion in order to clarify the pathogenesis of early embryo damage from the cellular and molecular perspectives,and provide theoretical basis for the diagnosis and treatment of embryo damage.Methods:From July 2018 to July 2019,30 patients with unexplained embryo damage were selected as embryo damage group,thirty normal early pregnancy patients with aspiration abortion were selected as the normal early pregnancy group.The decidual tissue and chorionic villi of the two groups were collected to observe the structural and pathological changes.Immunohistochemical method was used to detect the distribution of PCNA,Caspase-3,IL-6 and Survivin in the chorionic villi and decidual tissue,as well as the expression changes of the above four proteins.Results:Compared with the normal early pregnancy group,the chorionic villi in the early embryo damage group were obviously dysplasia,degenerative changes,structural disorders,homogeneous destruction,obvious reduction or even disappearance of trophoblast cells,inflammatory cell infiltration,more neutrophils and lymphocytes,interstitial edema and cell atrophy,accompanied by hemorrhage;The decidual tissue of the intima was not good,most of the cells were spindle-shaped,the structure was disordered,the stroma has edema,inflammatory cells can be seen,and hemorrhage existed.The results of immunohistochemistry showed that the expression of PCNA protein in chorionic villi and decidual tissue of early embryo damage group decreased significantly(P<0.05),while the expression of Caspase-3 protein increased significantly(P<0.05).The expression of IL-6 protein decreased significantly(P<0.05),and the expression of Survivin protein decreased significantly(P<0.05).Conclusion:During early pregnancy,due to the down-regulation of the expression of proliferating cell nuclear antigen PCNA and apoptosis inhibitor protein Survivin in chorionic and decidual tissues,the balance between proliferation and apoptosis is broken,which has an increase in Caspase-3 expression and a decrease in IL-6 expression.It may be that the balance of Th1/Th2 in chorionic and decidual tissues inclines to Th1,which leads to excessive apoptosis of chorionic and decidual tissues and the cessation of early embryo damage.展开更多
The effects of mifepristone with misoprostol on the expression of the integrin β 3 and intercellular adhesion molecule 1 (ICAM 1) in decidua and chorionic villi tissues in early pregnancy in 10 cases were investigate...The effects of mifepristone with misoprostol on the expression of the integrin β 3 and intercellular adhesion molecule 1 (ICAM 1) in decidua and chorionic villi tissues in early pregnancy in 10 cases were investigated by immuno flow cytometry (the experiment group). At the same time, the other 10 cases induced by mechanical vacuum aspiration were collected as the control. The results showed that, the positive rate of integrin β 3 and ICAM 1 in decidua of the experiment group were 19.1±5.01% and 20.61 ±6.51%; while those in chorionic villi were 21.32±4.38% and 20.29± 6.49%, which were significantly lower than those in the control group. These results suggested that integrin β 3 and ICAM 1 may take part in the maintenance of early pregnancy. The mechanism of mifepristone induced abortion may be mediated by the down regulation of the integrin β 3 and ICAM 1 expression in decidua and chorionic villi.展开更多
Most of the reports on human placental villi endocrinology focus on the study of neuropeptides, pituitary-or gonadal-like hormones, growth factors and cytokines, and only a few of them concern the function of biogenic...Most of the reports on human placental villi endocrinology focus on the study of neuropeptides, pituitary-or gonadal-like hormones, growth factors and cytokines, and only a few of them concern the function of biogenic amine. We first discovered that trophoblast of placental villi can produce 5-hydroxytryptamine (5-HT) and that its展开更多
Evidence so far accumulated suggests that the human early placenta can be considered as a complicated neuroendocrine organt. Our previous reports have demonstrated that the human early placenta presents not only a var...Evidence so far accumulated suggests that the human early placenta can be considered as a complicated neuroendocrine organt. Our previous reports have demonstrated that the human early placenta presents not only a variety of neuropeptides but also neurotransmitters such as 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE). It has been shown that these neurotransmitters in human placenta may play an important role in the process of blastocyst implantation and maintenance of normal pregnancy. As far as we are aware, no information concerning the DA and/or NE receptors localized in展开更多
Objective To investigate the difference of the expression of HOXAIO gene in placental villi before and after the onset of labor. Methods Immunohistochemistry was used to detect the location of HOXAIO in placental vill...Objective To investigate the difference of the expression of HOXAIO gene in placental villi before and after the onset of labor. Methods Immunohistochemistry was used to detect the location of HOXAIO in placental villi. The expression of HOXAIO mRNA and protein were measured by RT-PCR and Western blotting. Results lmmunohistochemistry showed that HOXAIO was only weakly expressed in placental villi of the natural labor group. However, it was strongly expressed in placental Villi of the surgical labor group. RT-PCR and Western blotting showed that the expression of HOXAIO mRNA and protein were significantly lower in the natural labor group than in the surgical labor group (P〈0.05). Conclusion The lower expression of HOXAIO during the onset of labor may be one of the major factors in initiating the normal labor. And to some extent, the lower expression of HOXAIO gene in the natural labor group may be related to "functional progesterone withdrawal".展开更多
Gastric acidity-associated disorders such as peptic ulcer and reflux diseases are widespread,and the reported resistance and side effects of currently used medicines suggest an urgent requirement for alternative thera...Gastric acidity-associated disorders such as peptic ulcer and reflux diseases are widespread,and the reported resistance and side effects of currently used medicines suggest an urgent requirement for alternative therapeutic approaches.Here we demonstrate a critical role of ASAP3 in regulating the microvilli structure of parietal cells in vivo,and reveal the feasibility of controlling gastric acidity by targeting ASAP3.Conditional knockout of ASAP3 in mice caused elongation and stacking of microvilli in parietal cells,and substantially decreased gastric acid secretion.These were associated with active assembly of F-actin caused by a higher level of GTP-bound Arf6 GTPase.Consistently,a small molecular compound QS11 inhibited ASAP3 function and significantly reduced gastric acidity in vivo.Of note,the expression of ASAP3 was positively correlated with gastric acid secretion in 90 human cases,and high expression of ASAP3 was associated with reflux disease and peptic ulcer.These results reveal for the first time that ASAP3 regulates the microvilli structures in parietal cells.Our data also suggest ASAP3 as a feasible and drugable therapeutic target for gastric acidity-associated diseases.展开更多
基金the Shriners Hospital for Children Postdoctoral Research Fellowship award,No.84704-NCA-19UC Davis School of Medicine Dean’s Fellowship award and funding from the NIH,No.5R01NS100761-02 and No.R03HD091601-01+2 种基金the California Institute of Regenerative Medicine,No.PC1-08103 and No.CLIN1-11404Shriners Hospitals for Children,No.85120-NCA-16,No.85119-NCA-18,No.85108-NCA-19 and No.87200-NCA-19March of Dimes Foundation,No.5FY1682
文摘BACKGROUND Endothelial colony-forming cells(ECFCs)have been implicated in the process of vascularization,which includes vasculogenesis and angiogenesis.Vasculogenesis is a de novo formation of blood vessels,and is an essential physiological process that occurs during embryonic development and tissue regeneration.Angiogenesis is the growth of new capillaries from pre-existing blood vessels,which is observed both prenatally and postnatally.The placenta is an organ composed of a variety of fetal-derived cells,including ECFCs,and therefore has significant potential as a source of fetal ECFCs for tissue engineering.AIM To investigate the possibility of isolating clonal ECFCs from human early gestation chorionic villi(CV-ECFCs)of the placenta,and assess their potential for tissue engineering.METHODS The early gestation chorionic villus tissue was dissociated by enzyme digestion.Cells expressing CD31 were selected using magnetic-activated cell sorting,and plated in endothelial-specific growth medium.After 2-3 wks in culture,colonies displaying cobblestone-like morphology were manually picked using cloning cylinders.We characterized CV-ECFCs by flow cytometry,immunophenotyping,tube formation assay,and Dil-Ac-LDL uptake assay.Viral transduction of CVECFCs was performed using a Luciferase/tdTomato-containing lentiviral vector,and transduction efficiency was tested by fluorescent microscopy and flow cytometry.Compatibility of CV-ECFCs with a delivery vehicle was determined using an FDA approved,small intestinal submucosa extracellular matrix scaffold.RESULTS After four passages in 6-8 wks of culture,we obtained a total number of 1.8×107 CV-ECFCs using 100 mg of early gestational chorionic villus tissue.Immunophenotypic analyses by flow cytometry demonstrated that CV-ECFCs highly expressed the endothelial markers CD31,CD144,CD146,CD105,CD309,only partially expressed CD34,and did not express CD45 and CD90.CV-ECFCs were capable of acetylated low-density lipoprotein uptake and tube formation,similar to cord blood-derived ECFCs(CB-ECFCs).CV-ECFCs can be transduced with a Luciferase/tdTomato-containing lentiviral vector at a transduction efficiency of 85.1%.Seeding CV-ECFCs on a small intestinal submucosa extracellular matrix scaffold confirmed that CV-ECFCs were compatible with the biomaterial scaffold.CONCLUSION In summary,we established a magnetic sorting-assisted clonal isolation approach to derive CV-ECFCs.A substantial number of CV-ECFCs can be obtained within a short time frame,representing a promising novel source of ECFCs for fetal treatments.
文摘Objective To investigate the role of mifepristone in regulating cytokines of materno-fetal interface and serum of human early gestationMethods Thirty-five women with early pregnancy received mifepristone 50 mg orallyon study d 1 and d 2, respectively, followed by undergoing artificial abortion to getdecidua and villi on study d 3. Twenty-five women with early pregnancy withoutmifepristone administration as control also underwent artificial abortion to get de-cidua and villi. The expressions of TGF-β1 and TGF-β1 receptor mRNA in the earlydecidua and villi were assessed by using RT-PCR . The concentrations of serum TNF-α were measured by radioimmunoassay.Results The decidual expressions of TGF- β1 mRNA and TGF-β1 receptor mRNA in thetreated group were significantly lower than those of the control (P<0.05), while thevillus expressions of TGF-β1 and TGF-β1 receptor mRNA in the treated group were notsignificantly different from those of the control (P>0.05). The serum TNF-β1 levelselevated significantly after mifepristone treatment.Conclusion The antigestational effect of mifepristone might act through suppressingthe transcription of TGF-β1 and TGF-β1 receptor in the decidua and increasing theserum TNF-α level, which interfered in the materno-fetal interface Th2 bias.
文摘Fourteen normal human placental villi at a fetal age of 5-8 weeks were examined withelectron microscope. The results were vide infra.(1)The cytotrophoblasts were characterized by largenucleus with less heterochromatin and prominent nucleolus with a number of free polyribosomes as well asscattered mitochondria in the cytoplasm.(2) There was a layer of dense microvilli on the surface of thesyncytiotrophoblastic cells.The size and shape of microvilli were variable. Usually fine globular expansions were present at the apical pole of microvilli and the cell membrane between the base of microvillihad invaginations into the cytoplasm forming small vesicles and tubules. Rough endoplasmic reticulum,free polyribosomes,mitochondria, lipid droplets and few myelinlike figures were also found in the cytoplasm.Part of cytoplasm penetrated into the interspaces of cytotrophoblastic cells and became in directcontact with the basement membrane.(3) Numerous desmosomes were seen between the cells of cytotrophoblast and syncytiotrophoblast.And (4) in the strom a of villi,mesenchymal cells were abundant inrough endoplasmic reticulum and well developed Golgi complex. Mesenchymat cells were markedlyfunctionally active. Ultrastructural characteristics of placental villin in connexion with their functionwere discussed.
文摘<strong>Objective</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><strong>:</strong></span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> To investigate the changes of hsMAD2 protein and gene expression levels during chromosome segregation of human embryos. </span><b><span style="font-family:Verdana;">Method</span></b></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">:</span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;"> The embryos of spontaneous abortion were collected in our hospital from 2009 to 2013, the chromosomal numbers of the embryonic villi were subsequently detected by fluorescence in situ hybridization (FISH). The patients were then divided into the normal and abnormal groups based on the chromosome number. The hsMAD2 protein and gene expression levels in the villi tissues of the two embryo groups were detected by western blotting and qRT-PCR, respectively. The hsMAD2 protein and gene levels in the embryonic villus tissue of the patient were detected. </span><b><span style="font-family:Verdana;">Results</span></b></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">:</span></b></span></span><span><span><b><span style="font-family:""> </span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">From 2009 to 2013, we collected 50 embryos from spontaneous abortion patients. The chromosome abnormality and no abnormality were 36 cases (abnormal number of 28 cases (56.0%) and chimerism in 8 cases (16.0%)) and 14 cases (28.0%), respectively.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The expression of hsmad2 protein and its gene in the villi of spontaneously aborted embryo with chromosomal abnormality in the abnormal group was significantly higher than that in those without chromosomal abnormalities (0.88 ± 0.20 vs 0.61 ± 0.19, P < 0.05), (23.46 ± 0.07 vs 18.35 ± 0.10, P < 0.05).</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Conclusion</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">:</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> Abnormal number of chromosomes is closely related to spontaneous abortion Linked, hsMAD2 factor has a card effect on the cell cycle, can block the mitotic process of cells, and play an important role in maintaining the normal separation and stability of chromosomes</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.</span></span></span>
文摘Pancreatic cancer(PC)is a highly lethal tumor with controversial high glucose uptake and hypomicrovascularity.And,the hypomicrovasculature,which is considered to have poor perfusion,blocks the delivery of drugs to tumors.Previously,we described the preferential existence of a novel endothelial projection with trafficking vesicles in PCs,referring to basal microvilli.However,whether the basal microvilli microvessels have good perfusion or deliver nutrients to the tumor milieu is unknown.Here,we perfused multiple endothelial markers and nutrients to autochthonous PC-bearing mice to study the nutrient trafficking and perfusion status of the basal microvilli microvasculature.
文摘Objective:This study aims to explore its role in embryo damage and the relationship between them by testing the expression of PCNA,Caspase-3,IL-6 and Survivin protein in the chorionic villi and decidual tissue of patients with unexplained early embryo damage and normal early pregnancy at the same time voluntarily requested uterine aspiration abortion in order to clarify the pathogenesis of early embryo damage from the cellular and molecular perspectives,and provide theoretical basis for the diagnosis and treatment of embryo damage.Methods:From July 2018 to July 2019,30 patients with unexplained embryo damage were selected as embryo damage group,thirty normal early pregnancy patients with aspiration abortion were selected as the normal early pregnancy group.The decidual tissue and chorionic villi of the two groups were collected to observe the structural and pathological changes.Immunohistochemical method was used to detect the distribution of PCNA,Caspase-3,IL-6 and Survivin in the chorionic villi and decidual tissue,as well as the expression changes of the above four proteins.Results:Compared with the normal early pregnancy group,the chorionic villi in the early embryo damage group were obviously dysplasia,degenerative changes,structural disorders,homogeneous destruction,obvious reduction or even disappearance of trophoblast cells,inflammatory cell infiltration,more neutrophils and lymphocytes,interstitial edema and cell atrophy,accompanied by hemorrhage;The decidual tissue of the intima was not good,most of the cells were spindle-shaped,the structure was disordered,the stroma has edema,inflammatory cells can be seen,and hemorrhage existed.The results of immunohistochemistry showed that the expression of PCNA protein in chorionic villi and decidual tissue of early embryo damage group decreased significantly(P<0.05),while the expression of Caspase-3 protein increased significantly(P<0.05).The expression of IL-6 protein decreased significantly(P<0.05),and the expression of Survivin protein decreased significantly(P<0.05).Conclusion:During early pregnancy,due to the down-regulation of the expression of proliferating cell nuclear antigen PCNA and apoptosis inhibitor protein Survivin in chorionic and decidual tissues,the balance between proliferation and apoptosis is broken,which has an increase in Caspase-3 expression and a decrease in IL-6 expression.It may be that the balance of Th1/Th2 in chorionic and decidual tissues inclines to Th1,which leads to excessive apoptosis of chorionic and decidual tissues and the cessation of early embryo damage.
文摘The effects of mifepristone with misoprostol on the expression of the integrin β 3 and intercellular adhesion molecule 1 (ICAM 1) in decidua and chorionic villi tissues in early pregnancy in 10 cases were investigated by immuno flow cytometry (the experiment group). At the same time, the other 10 cases induced by mechanical vacuum aspiration were collected as the control. The results showed that, the positive rate of integrin β 3 and ICAM 1 in decidua of the experiment group were 19.1±5.01% and 20.61 ±6.51%; while those in chorionic villi were 21.32±4.38% and 20.29± 6.49%, which were significantly lower than those in the control group. These results suggested that integrin β 3 and ICAM 1 may take part in the maintenance of early pregnancy. The mechanism of mifepristone induced abortion may be mediated by the down regulation of the integrin β 3 and ICAM 1 expression in decidua and chorionic villi.
文摘Most of the reports on human placental villi endocrinology focus on the study of neuropeptides, pituitary-or gonadal-like hormones, growth factors and cytokines, and only a few of them concern the function of biogenic amine. We first discovered that trophoblast of placental villi can produce 5-hydroxytryptamine (5-HT) and that its
文摘Evidence so far accumulated suggests that the human early placenta can be considered as a complicated neuroendocrine organt. Our previous reports have demonstrated that the human early placenta presents not only a variety of neuropeptides but also neurotransmitters such as 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE). It has been shown that these neurotransmitters in human placenta may play an important role in the process of blastocyst implantation and maintenance of normal pregnancy. As far as we are aware, no information concerning the DA and/or NE receptors localized in
基金supported by grants from the National Natural Science Foundation of China (No. 81000240,No.30973205)the National Science and Technology Major Project of China (No. 2009ZX09103-739)
文摘Objective To investigate the difference of the expression of HOXAIO gene in placental villi before and after the onset of labor. Methods Immunohistochemistry was used to detect the location of HOXAIO in placental villi. The expression of HOXAIO mRNA and protein were measured by RT-PCR and Western blotting. Results lmmunohistochemistry showed that HOXAIO was only weakly expressed in placental villi of the natural labor group. However, it was strongly expressed in placental Villi of the surgical labor group. RT-PCR and Western blotting showed that the expression of HOXAIO mRNA and protein were significantly lower in the natural labor group than in the surgical labor group (P〈0.05). Conclusion The lower expression of HOXAIO during the onset of labor may be one of the major factors in initiating the normal labor. And to some extent, the lower expression of HOXAIO gene in the natural labor group may be related to "functional progesterone withdrawal".
基金This project was supported by grants from the Major Program of National Natural Science Foundation of China(81530072),the Projects of International Cooperation and Exchanges NSFC(81320108024),and the Innovative group projects(81421001)to Jing-Yuan FangNational Natural Science Foundation of China(81572326,81322036,81272383,81602518,81502015 and 81572303)+4 种基金Top-Notch Young Talents Program of China(ZTZ2015-48)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20152514)National Key Research and Development(R&D)Plan(2016YFC0906000 and 2016YFC0906002)National Key Technology Support Program(2015BAI13B07)the Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine to JQ(BXJ201419).
文摘Gastric acidity-associated disorders such as peptic ulcer and reflux diseases are widespread,and the reported resistance and side effects of currently used medicines suggest an urgent requirement for alternative therapeutic approaches.Here we demonstrate a critical role of ASAP3 in regulating the microvilli structure of parietal cells in vivo,and reveal the feasibility of controlling gastric acidity by targeting ASAP3.Conditional knockout of ASAP3 in mice caused elongation and stacking of microvilli in parietal cells,and substantially decreased gastric acid secretion.These were associated with active assembly of F-actin caused by a higher level of GTP-bound Arf6 GTPase.Consistently,a small molecular compound QS11 inhibited ASAP3 function and significantly reduced gastric acidity in vivo.Of note,the expression of ASAP3 was positively correlated with gastric acid secretion in 90 human cases,and high expression of ASAP3 was associated with reflux disease and peptic ulcer.These results reveal for the first time that ASAP3 regulates the microvilli structures in parietal cells.Our data also suggest ASAP3 as a feasible and drugable therapeutic target for gastric acidity-associated diseases.