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1.
J Clin Lab Anal ; 36(4): e24325, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35235705

RESUMO

BACKGROUND: Currently, mass vaccine inoculation against coronavirus disease-2019 (COVID-19) has been being implemented globally. Rapid and the large-scale detection of serum neutralizing antibodies (NAbs) laid a foundation for assessing the immune response against SARS-CoV-2 infection and vaccine. Additional assessments include the duration of antibodies and the optimal time for a heightened immune response. METHODS: The performance of five surrogate NAbs-three chemiluminescent immunoassay (CLIA) and two enzyme-linked immunosorbent assays (ELISAs)-and specific IgM and IgG assays were compared using COVID-19-vaccinated serum (n = 164). Conventional virus neutralization test (cVNT) was used as a criterion and the diagnostic agreement and correlation of the five assays were evaluated. We studied the antibody responses after the two-dose vaccine in volunteers up to 6 months. RESULTS: The sensitivity and specificity of five surrogate NAb assays ranged from 84% to 100%. Our cVNT results indicated great consistency with the surrogate assays. At 28 days after primary vaccination, the seropositivities of the NAbs, IgG, and IgM were 6%, 4%, and 13%, respectively. After the booster dose, seropositivities reached 14%, 65%, and 97%, respectively. Six months after receipt of the second dose, the NAb positive rate was eventually maintained at 66%. In all COVID-19 convalescents, patients were detected with 100% NAb sat three months after discharge. CONCLUSION: COVID-19 vaccine induced a humoral immune response lasting at least six months. Rapid serological detection was used as a proxy for identifying changes in immunity levels and as a guide to whether an individual may require a booster vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Humanos , Imunoglobulina G , Imunoglobulina M , SARS-CoV-2 , Testes Sorológicos , Vacinação
2.
BMC Infect Dis ; 22(1): 157, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35168557

RESUMO

OBJECTIVE: Reliable high-throughput serological assays for SARS-CoV-2 antibodies present an important role in the strength and duration of immunity after vaccination. The study investigated the analytical and clinical performances of neutralizing antibodies (NTAb) assay by chemiluminescent (CLIA), and SARS-CoV-2 neutralizing antibody after vaccination in real world. METHODS: The analytical performances of CLIA for SARS-CoV-2 NTAb were evaluated, followed by the sensitivity and specificity identified with a PRNT test from 50 volunteers. Then, a cohort of vaccine recipients (n = 37) were tracked with SARS-CoV-2 NTAb assay at prior to vaccination, one, three and six months post two doses. In real world, a total of 737 cases were recruited from physical examination center in Shenzhen Luohu People's Hospital (from Jun to August 2021) to analyze vaccination status. RESULTS: Serological assays on the CLIA were found with excellent characteristics including imprecision, repeatability and linearity. Besides, it was robust to icterus, lipemia and hemolysis. The good sensitivity and specificity were obtained at 98% and 100%, respectively. NTAb results showed a high correlation with PRNT50 titers (r 0.61). Until July 2021, the BBIBP-CorV (76.3%) and Sinovac CoronaVac (20.5%) were the predominant vaccines injection in Shenzhen, China. Adolescent less than 18 years was the main unvaccinated group (52.1%). The seropositive rate of inactive SRAR-CoV-2 vaccines exceeded 97% after inoculation. The NTAb generated by Sinovac CoronaVac with the schedule of 0-56 days was found significantly lower than that by BBIBP-CorV (P < 0.001). The follow-up of NTAb changes in a cohort and the dynamic variation of NTAb in real world disclosed steep downward by almost three times for NTAb level occurred at three months post twice vaccinations. The seropositive ratio was at least 50% over 6 months. CONCLUSIONS: SARS-CoV-2 neutralizing antibodies assay show excellent analytical and clinical performances, and a high correlation with neutralizing activity. Anti-epidemic measures and the urgent trial of SARS-CoV-2 vaccine was calling for adolescents.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adolescente , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Luminescência , SARS-CoV-2 , Vacinação
3.
Cell Death Dis ; 12(4): 387, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846304

RESUMO

Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma and is required to establish and support pregnancy. Dysregulated decidualization has been reported to be a critical cause of recurrent implantation failure (RIF). In this study, we found that Activating transcription factor 3 (ATF3) expression was significantly downregulated in the endometrium of RIF patients. Knockdown of ATF3 in human endometrium stromal cells (hESCs) hampers decidualization, while overexpression could trigger the expression of decidual marker genes, and ameliorate the decidualization of hESCs from RIF patients. Mechanistically, ATF3 promotes decidualization by upregulating FOXO1 via suppressing miR-135b expression. In addition, the endometrium of RIF patients was hyperproliferative, while overexpression of ATF3 inhibited the proliferation of hESCs through CDKN1A. These data demonstrate the critical roles of endometrial ATF3 in regulating decidualization and proliferation, and dysregulation of ATF3 in the endometrium may be a novel cause of RIF and therefore represent a potential therapeutic target for RIF.


Assuntos
Fator 3 Ativador da Transcrição/deficiência , Implantação do Embrião/fisiologia , Endométrio/fisiologia , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo , Proliferação de Células/fisiologia , Células Cultivadas , Decídua/metabolismo , Endométrio/metabolismo , Feminino , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Células Estromais/metabolismo , Transfecção
4.
J Clin Lab Anal ; 35(1): e23681, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33340166

RESUMO

BACKGROUND: Seldom performance evaluation and diagnosis comparison studies were reported for different chemiluminescent immunoassay (CLIA) kits approved under an emergency approval program for SARS-CoV-2 infection. METHODS: A total of 100 and 105 serum separately from non-infected populations and COVID-19 patients were detected with SARS-CoV-2 IgM and IgG kits. The characteristics including precision, functional sensitivity, linearity, and accuracy were evaluated for Axceed, iFlash, and Maglumi CLIA kits. RESULTS: Maglumi and iFlash had the best analytical sensitivity for IgM and IgG, respectively. Axceed kits had a linearity response in the detected concentration. The clinical sensitivity of Axceed, iFlash, and Maglumi was 68.0%, 64.9%, and 63.9% with a specificity of 99.0%, 96.0%, and 100% for IgM, 85.6%, 97.9%, and 94.8% with a specificity of 97.0% for IgG. ROC analysis indicated all kits had a diagnostic power greater than 0.9. Notably, either IgM or IgG kits obtained a poor agreement (Kappa value from 0.397 to 0.713) with others. Among 38 recovered patients, 94.7% had an effective immune response, and both seropositive IgM and IgG accounted for the biggest proportion (medium, 42 days onset), then followed by the single seropositive IgG (medium, 50 days onset) in Ab profile. CONCLUSION: The performance of CLIA kits satisfied the diagnosis of SARS-CoV-2 infection. Both positive of IgG and IgM contributes to improve the specificity, and a positive one will enhance the sensitivity.


Assuntos
Teste para COVID-19/métodos , COVID-19/etiologia , Imunoensaio/métodos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Adulto , Idoso , Anticorpos Antivirais/sangue , Automação Laboratorial , COVID-19/diagnóstico , Feminino , Humanos , Luminescência , Gravidez , Complicações Infecciosas na Gravidez/etiologia , Complicações Infecciosas na Gravidez/terapia , Reprodutibilidade dos Testes , SARS-CoV-2/imunologia , Fatores de Tempo
5.
J Mol Endocrinol ; 64(4): 249-258, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32197234

RESUMO

Decidualization is a critical process for embryo implantation and pregnancy maintenance in humans. The homeobox gene HOXA10 has been widely studied in endometrial receptivity establishment and decidualization. MEIS1, a three-amino-acid loop extension (TALE) family homeobox gene, has been proven to be a co-factor for HOXA10 in mouse uterus. However, the interaction between MEIS1 and HOXA10 in the human decidual cells remains to be elucidated. siRNA and CRISPR-Cas9 were employed to knockdown and knockout MEIS1 in the cultured human endometrial stromal cells, and it was found that MEIS1 deficiency leads to impaired decidualization. The physical interaction between the MEIS1 and HOXA10 in human endometrial stromal cell was confirmed by immunoprecipitation. Moreover, KAT2B and ETA were proved to be downregulated in the absence of MEIS1, and luciferase reporter and ChIP assays demonstrated that MEIS1-HOXA10 complex binds to the promoters of KAT2B and ETA and regulates their activity. Overexpression of KAT2B and ETA can partially rescue the decidualization defects in MEIS1-knockout HESCs. Taken together, these data suggest that MEIS1 plays an indispensable role in decidualization in human endometrial stromal cells, and MEIS1 interacts with HOXA10 to regulate the downstream genes, such as KAT2B and ETA. These findings will contribute to our understanding about the regulatory network in the process of decidualization in humans.


Assuntos
Decídua/fisiologia , Endométrio/fisiologia , Proteína Meis1/fisiologia , Sistemas CRISPR-Cas/genética , Células Cultivadas , Decídua/metabolismo , Implantação do Embrião/genética , Endométrio/citologia , Feminino , Técnicas de Inativação de Genes , Redes Reguladoras de Genes/fisiologia , Células HEK293 , Proteínas Homeobox A10/metabolismo , Humanos , Proteína Meis1/antagonistas & inibidores , Proteína Meis1/genética , Proteína Meis1/metabolismo , Ligação Proteica , RNA Interferente Pequeno/farmacologia , Células Estromais/fisiologia
6.
Reprod Toxicol ; 90: 109-117, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31520687

RESUMO

Our understanding of the relationship between stress-derived epinephrine and early pregnancy failure remains incomplete. Here, we explored the effect of epinephrine exposure on early pregnancy and pseudopregnancy in mice. Increased expression of adrenergic receptors Adra1b, Adra2b and Adrb2 was observed during decidualization and post-implantation embryogenesis was delayed or survival impaired. Epinephrine treatment also impaired decidualization in both the gravid and pseudopregnant uterus, suggesting the effect on decidualization was independent of the conceptus. This included a suppression of endometrial stroma cell proliferation and of key decidualization regulators, including COX2, BMP2 and WNT4. Collectively, these data demonstrate that maternal epinephrine exposure during early pregnancy impairs uterine decidualization and embryo development, underlying early pregnancy failure.


Assuntos
Agonistas Adrenérgicos/toxicidade , Epinefrina/toxicidade , Receptores Adrenérgicos/genética , Útero/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Camundongos , Gravidez , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Útero/metabolismo , Útero/patologia , Proteína Wnt4/metabolismo
7.
Sci Rep ; 9(1): 9437, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263155

RESUMO

Accumulation of iron has been associated with the pathobiology of various disorders of the central nervous system. Our previous work has shown that hephaestin (Heph) and ceruloplasmin (Cp) double knockout (KO) mice induced iron accumulation in multiple brain regions and that this was paralleled by increased oxidative damage and deficits in cognition and memory. In this study, we enriched astrocytes and oligodendrocytes from the cerebral cortex of neonatal wild-type (WT), Heph KO and Cp KO mice. We demonstrated that Heph is highly expressed in oligodendrocytes, while Cp is mainly expressed in astrocytes. Iron efflux was impaired in Cp KO astrocytes and Heph KO oligodendrocytes and was associated with increased oxidative stress. The expression of Heph, Cp, and other iron-related genes was examined in astrocytes and oligodendrocytes both with and without iron treatment. Interestingly, we found that the expression of the mRNA encoding ferroportin 1, a transmembrane protein that cooperates with CP and HEPH to export iron from cells, was positively correlated with Cp expression in astrocytes, and with Heph expression in oligodendrocytes. Our findings collectively demonstrate that HEPH and CP are important for the prevention of glial iron accumulation and thus may be protective against oxidative damage.


Assuntos
Ceruloplasmina/genética , Ferro/metabolismo , Proteínas de Membrana/genética , Estresse Oxidativo , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Ceruloplasmina/deficiência , Proteínas de Membrana/deficiência , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Estresse Oxidativo/genética
8.
Mol Reprod Dev ; 86(5): 516-529, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30779242

RESUMO

Female fertility declines dramatically over the age of 35 due to age-related decreases in oocyte quality and quantity. Although mitochondrial transfer promises to be a technology that can improve the quality of such age-impaired oocytes, the ideal mitochondrial donor remains elusive. In the present study, we aimed to identify whether aged adipose-derived stem cells constitute an excellent mitochondrial donor that would improve the quality of aged mouse oocytes. We showed that aging significantly impaired the mitochondrial function in mouse oocytes, but did not significantly affect the mitochondrial function of adipose-derived stem cells. However, the mitochondrial transfer from aged adipose-derived stem cells did not mitigate the poor fertilization and embryonic development rates of aged oocytes.


Assuntos
Adipócitos/citologia , Senescência Celular/fisiologia , Mitocôndrias/fisiologia , Oócitos , Células-Tronco/citologia , Animais , Células do Cúmulo/citologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Oócitos/citologia , Oócitos/fisiologia
9.
J Neurotrauma ; 36(10): 1571-1583, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30484375

RESUMO

Kutcher and Giza suggested incorporating levels of certainty in concussion diagnosis decisions. These guidelines were based on clinical experience rather than objective data. Therefore, we combined data-driven optimization with predictive modeling to identify which athletes are unlikely to have concussion and to classify remaining athletes as having possible, probable, or definite concussion with diagnostic certainty. We developed and validated our framework using data from the Concussion Assessment, Research, and Education (CARE) Consortium. Acute concussions had assessments at <6 h (n = 1085) and 24-48 h post-injury (n = 1413). Normal performances consisted of assessments at baseline (n = 1635) and the time of unrestricted return to play (n = 1345). We evaluated the distribution of acute concussions and normal performances across risk categories and identified inter-class and intra-class differences in demographics, time-of-injury characteristics, the Standard Assessment of Concussion (SAC), Sport Concussion Assessment Tool (SCAT) symptom assessments, and Balance Error Scoring System (BESS). Our algorithm accurately classified concussions as probable or definite (sensitivity = 91.07-97.40%). Definite and probable concussions had higher SCAT symptom scores than unlikely and possible concussions (p < 0.05). Definite concussions had lower SAC and higher BESS scores (p < 0.05). Baseline to post-injury change scores for the SAC, SCAT symptoms, and BESS were significantly different between acute possible and probable concussions and normal performances (p < 0.05). There were no consistent patterns in demographics across risk categories, although a greater proportion of concussions classified as unlikely were reported immediately compared with definite concussions (p < 0.05). Although clinical interpretation is still needed, our data-driven approach to concussion risk stratification provides a promising step toward evidence-based concussion assessment.


Assuntos
Traumatismos em Atletas/classificação , Traumatismos em Atletas/diagnóstico , Concussão Encefálica/classificação , Concussão Encefálica/diagnóstico , Modelos Logísticos , Atletas , Feminino , Humanos , Masculino , Adulto Jovem
10.
Cell Death Discov ; 4: 23, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30109142

RESUMO

Recurrent implantation failure (RIF) caused by various etiological factors remains a challenge for fertility clinicians using assisted reproductive technology (ART) worldwide. Dysregulation of leukemia inhibitory factor (LIF) in the endometria of women with RIF is involved in impaired endometrial receptivity and embryo adhesion. However, the mechanism through which LIF expression is regulated in women with RIF is still poorly understood. Our previous study noted that the abnormally increased endometrial Krüppel-like factor 12 (KLF12) in RIF women led to impaired decidualization and embryo implantation. Here, we further found that KLF12 inhibited embryo adhesion in vivo and in vitro by repressing LIF expression. Mechanistically, KLF12 bound to conserved sites (CAGTGGG, -6771 to -6765 and -7115 to -7109) within the LIF promoter region and repressed LIF transcription directly. Exogenous LIF significantly reversed the KLF12-mediated repression of BeWo spheroid adhesion. KLF12 expression was reduced significantly in Ishikawa cells treated with progestogen, which was due to the activation of Akt signaling. These findings may provide novel potential therapeutic regimens for patients with RIF and disrupted endometrial receptivity.

11.
J Nutr ; 148(4): 643-649, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29659961

RESUMO

Background: The accumulation of iron occurs in the central nervous system (CNS) in several neurodegenerative diseases. Although multi-copper ferroxidases (MCFs) play an important role in cellular iron metabolism and homeostasis, the mechanism of MCFs in the CNS remains unclear. Objective: The aim was to study the role of MCFs in CNS iron metabolism and homeostasis by using hephaestin/ceruloplasmin (Heph/Cp) double knockout (KO) mice. Methods: Heph/Cp double KO male mice were generated by crossing both single KO mice. In Heph/Cp KO and wild-type (WT) control mice at 4 wk and 6 mo of age, iron concentrations of selected brain regions were measured by atomic absorption spectrophotometry, and gene expressions of Heph, Cp, ferroportin 1 (Fpn1) [+ iron responsive element (IRE)], L-ferritin, H-ferritin, transferrin receptor 1 (Tfrc), and divalent metal transporter 1 (Dmt1) (+IRE) were quantitated by quantitative reverse transcriptase-polymerase chain reaction. Brain region L-ferritin protein concentration, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and malondialdehyde (MDA) concentration were also determined. Learning and memory abilities in Heph/Cp KO and WT control mice at 6 mo of age were tested by the IntelliCage system (New Behavior). Results: Iron concentration was significantly higher in Heph/Cp KO mice than in WT control mice at 4 wk of age in the cortex (50%), hippocampus (120%), brainstem (35%), and cerebellum (220%) and at 6 mo of age in the cortex (140%), hippocampus (420%), brainstem (560%), and cerebellum (340%). L-Ferritin and MDA concentrations were significantly higher and SOD and GPx activities were significantly lower in the cortex, hippocampus, brainstem, and cerebellum of KO mice than in those of WT controls at both 4 wk and 6 mo of age. Iron-related gene expressions also differed significantly between groups. Learning and memory deficits occurred in Heph/Cp KO mice at 6 mo of age. Conclusion: Mutation of both MCFs in mice induces iron accumulation in brain regions, oxidative damage, and learning and memory defects.


Assuntos
Encéfalo/metabolismo , Ceruloplasmina/deficiência , Cobre/metabolismo , Ferro/metabolismo , Deficiências da Aprendizagem/etiologia , Transtornos da Memória/etiologia , Estresse Oxidativo , Animais , Comportamento Animal , Proteínas de Transporte de Cátions/metabolismo , Ceruloplasmina/metabolismo , Ferritinas/metabolismo , Glutationa Peroxidase/metabolismo , Aprendizagem , Masculino , Malondialdeído/metabolismo , Memória , Camundongos Knockout , Receptores da Transferrina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxido Dismutase/metabolismo
12.
Sci China Life Sci ; 61(12): 1554-1565, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29546669

RESUMO

Premature ovarian failure (POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study, umbilical cord mesenchymal stem cells on a collagen scaffold (collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.


Assuntos
Infertilidade Feminina/terapia , Transplante de Células-Tronco Mesenquimais , Folículo Ovariano/metabolismo , Insuficiência Ovariana Primária/terapia , Geleia de Wharton/citologia , Adulto , Animais , Colágeno/química , Modelos Animais de Doenças , Estradiol/sangue , Estradiol/metabolismo , Feminino , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O3/metabolismo , Humanos , Camundongos , Folículo Ovariano/crescimento & desenvolvimento , Fosforilação , Gravidez , Tecidos Suporte/química , Resultado do Tratamento
13.
Cell Death Dis ; 9(3): 291, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29459744

RESUMO

Endometriosis (ENDO) is a common gynecological disease that causes infertility in many women. Previous studies noted that the dysregulation of Homeo box A10 (HOXA10) in the endometrium of women with ENDO was involved in the failure of embryo implantation. However, the mechanism by which HOXA10 expression is reduced in women with ENDO is still poorly understood. Here we found that a member of the calcium (Ca2+)-dependent cysteine protease family calpain7 (CAPN7), negatively correlated with HOXA10, was highly expressed in the endometrium of infertile women with ENDO and was significantly downregulated during the window of embryo implantation in mice. Overexpression of CAPN7 in Ishikawa cells or in the uterus of mice inhibited embryo implantation in vitro and in vivo. In the current study, we identified a sequence rich in proline, glutamic acid, serine, and threonine (PEST sequence) that enhanced the Ca2+-dependent degradation of HOXA10 by CAPN7. Furthermore, the interaction between HOXA10 and CAPN7 repressed the transcriptional activity and protein stability of HOXA10. In contrast, the administration of the calpain inhibitor ALLN reversed the CAPN7-induced HOXA10 degradation. Moreover, truncation of the PEST motif in HOXA10 abolished its CAPN7-dependent proteolysis. These studies reveal a novel pattern of HOXA10 regulation via PEST sequence-mediated calpain proteolysis that was demonstrated to be reversed by a calpain inhibitor. Thus, the inhibition of CAPN7-induced HOXA10 degradation may represent a novel potential therapeutic method to improve impaired embryo implantation in women with ENDO.


Assuntos
Calpaína/metabolismo , Endometriose/metabolismo , Proteínas de Homeodomínio/genética , Infertilidade Feminina/terapia , Integrina beta3/genética , Adulto , Animais , Calpaína/genética , Regulação para Baixo , Implantação do Embrião , Endometriose/enzimologia , Endometriose/genética , Endométrio/metabolismo , Feminino , Proteínas Homeobox A10 , Proteínas de Homeodomínio/metabolismo , Humanos , Infertilidade Feminina/enzimologia , Infertilidade Feminina/genética , Infertilidade Feminina/metabolismo , Integrina beta3/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR
14.
Biomed Res Int ; 2018: 2549789, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30687738

RESUMO

Objective: The aim of this study was to investigate the potential role of IL-10 in regulating the receptivity marker HOXA10 in the endometrium of women with adenomyosis. Methods: The expression levels of IL-10, HOXA-10, STAT3, and p-STAT3 in the endometrium of women with adenomyosis and controls were examined by means of western blotting and immunohistochemistry. The expression of the HOXA10 protein in Ishikawa cells treated with rIL-10 was examined by western blotting. The attachment rate of BeWo cell spheroids to Ishikawa cells treated with rIL-10 was expressed as a percentage of the total number of spheroids. Results: The expression levels of HOXA10 and IL-10 in the adenomyosis group were significantly lower than those in the control group, and there was a positive correlation between HOXA10 and IL-10 protein levels in all the women examined. rIL-10 increased HOXA10 expression in a concentration- and time-dependent manner by inducing the phosphorylation of STAT3 in Ishikawa cells. Treatment with rIL-10 promoted the attachment of BeWo spheroids to Ishikawa cells, which was reversed by the inhibition of STAT3 phosphorylation. The expression of p-STAT3 in the adenomyosis group was significantly lower than that in the control group, and there was a positive correlation between IL-10 and p-STAT3 protein levels in all the women examined. Conclusions: Both IL-10 and HOXA10 levels in the endometrium are significantly reduced in women with adenomyosis compared with those in control women. The phosphorylation of STAT3 has been proven to be a critical mediator between IL-10 and HOXA10, which may play critical roles in embryo implantation.


Assuntos
Adenomiose/metabolismo , Regulação para Baixo/fisiologia , Endométrio/metabolismo , Proteínas de Homeodomínio/metabolismo , Interleucina-10/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Proteínas Homeobox A10 , Humanos , Fosforilação/fisiologia , Fator de Transcrição STAT3/metabolismo
15.
Cell Death Dis ; 8(10): e3088, 2017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28981116

RESUMO

Oxidative stress impairs follicular development by inducing granulosa cell (GC) apoptosis, which involves enhancement of the transcriptional activity of the pro-apoptotic factor Forkhead box O1 (FoxO1). However, the mechanism by which oxidative stress promotes FoxO1 activity is still unclear. Here, we found that miR-181a was upregulated in hydrogen peroxide (H2O2)-treated GCs and a 3-nitropropionic acid (NP)-induced in vivo model of ovarian oxidative stress. miR-181a overexpression promoted GC apoptosis, whereas knockdown of endogenous miR-181a blocked H2O2-induced cell apoptosis. Moreover, we identified that Sirtuin 1 (SIRT1), a deacetylase that suppresses FoxO1 acetylation in GCs, was downregulated by miR-181a and reversed the promoting effects of H2O2 and miR-181a on FoxO1 acetylation and GC apoptosis. Importantly, decreased miR-181a expression in the in vivo ovarian oxidative stress model inhibited apoptosis by upregulating SIRT1 expression and FoxO1 deacetylation. Together, our results suggest that miR-181a mediates oxidative stress-induced FoxO1 acetylation and GC apoptosis by targeting SIRT1 both in vitro and in vivo.


Assuntos
Apoptose/efeitos dos fármacos , Proteína Forkhead Box O1/genética , MicroRNAs/genética , Sirtuína 1/genética , Acetilação , Apoptose/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Nitrocompostos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Propionatos/farmacologia , Transdução de Sinais/efeitos dos fármacos
16.
Medicine (Baltimore) ; 96(43): e8409, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29069038

RESUMO

The purpose of this study is to compare the clinicopathological characteristics and outcomes of esophageal foreign body (FB) ingestion in adults between weekdays and holidays. This is a retrospective study including 1058 patients with esophageal FB ingestion from 2012 to 2016. Patient characteristics, the types and locations of FB, and clinical outcomes were compared between patients on weekdays and holidays. Furthermore, independent risk factors of complication on weekdays and holidays respectively were evaluated. The locations of FB, underlying diseases, and complications significantly differed between weekdays and holidays groups, while no difference was found in the types of FB. Patients got higher percentage of erosion complication on holidays than that on weekdays (60.8% vs 47.6%, P < .0001). Multivariate logistic regression analysis revealed that jujube shell was a significant predictor of complication on weekdays (P < .001). However, complication was significantly associated with nonfood bolus FB ingestion on holidays (P < .001). Our data suggest that there were different clinicopathological characteristics of FB ingestion between weekdays and holidays, and more patients got complications on holidays. On holidays, a latex protector hood or an overtube should be applied to patients who swallowed nonfood bolus in order to reduce esophageal mucosal damage.


Assuntos
Esôfago , Corpos Estranhos/epidemiologia , Férias e Feriados/estatística & dados numéricos , Adulto , Ingestão de Alimentos , Feminino , Corpos Estranhos/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
17.
Cell Death Discov ; 3: 17057, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29018572

RESUMO

HOXA10 has emerged as an important molecular marker of endometrial receptivity. Recurrent implantation failure (RIF) after in vitro fertilization-embryo transplantation (IVF-ET) treatment is associated with impaired endometrial receptivity, but the exact underlying mechanism of this phenomenon remains elusive. Here we found that HOXA10 was modified by small ubiquitin like-modifier 1 (SUMO1) at the evolutionarily conserved lysine 164 residue. Sumoylation inhibited HOXA10 protein stability and transcriptional activity without affecting its subcellular localization. SUMO1-modified HOXA10 expression was decreased in estradiol- and progesterone-treated Ishikawa cells. Sumoylation inhibited the accelerant role of HOXA10 in BeWo spheroid and mouse embryo attachment to Ishikawa cells. Importantly, aberrantly high SUMO1-HOXA10 expression was detected in mid-secretory endometria of women with RIF compared with that of the control fertile women. Together, our results suggest that HOXA10 sumoylation impairs the process of embryo implantation in vitro and takes part in the development of RIF.

18.
Stem Cells Int ; 2017: 3175748, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28874910

RESUMO

Human mesenchymal stem cells derived from the umbilical cord (UC) are a favorable source for allogeneic cell therapy. Here, we successfully isolated the stem cells derived from three different compartments of the human UC, including perivascular stem cells derived from umbilical arteries (UCA-PSCs), perivascular stem cells derived from umbilical vein (UCV-PSCs), and mesenchymal stem cells derived from Wharton's jelly (WJ-MSCs). These cells had the similar phenotype and differentiation potential toward adipocytes, osteoblasts, and neuron-like cells. However, UCA-PSCs and UCV-PSCs had more CD146+ cells than WJ-MSCs (P < 0.05). Tube formation assay in vitro showed the largest number of tube-like structures and branch points in UCA-PSCs among the three stem cells. Additionally, the total tube length in UCA-PSCs and UCV-PSCs was significantly longer than in WJ-MSCs (P < 0.01). Microarray, qRT-PCR, and Western blot analysis showed that UCA-PSCs had the highest expression of the Notch ligand Jagged1 (JAG1), which is crucial for blood vessel maturation. Knockdown of Jagged1 significantly impaired the angiogenesis in UCA-PSCs. In summary, UCA-PSCs are promising cell populations for clinical use in ischemic diseases.

19.
Reprod Biol Endocrinol ; 15(1): 42, 2017 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-28577574

RESUMO

BACKGROUND: A receptive endometrium is essential for maternal-embryonic molecular communication during implantation. However, the specific molecular regulatory mechanisms of the endometrial capacity remain poorly understood. Here, we examined activating transcription factor 3 (ATF3) expression in human endometria and the functional effect of ATF3 on embryo attachment in vitro. METHODS: Immunohistochemistry (IHC) was used to assess the ATF3 expression patterns in human endometria. Quantitative real-time PCR (qRT-PCR), western blotting and immunofluorescence (IF) studies were applied to explore ATF3 expression in Ishikawa cells upon estrogen (E2) and medroxyprogesterone acetate (MPA) treatment. qRT-PCR and western blotting were performed to inspect LIF (leukemia inhibitory factor) expression after enhancement or inhibition of ATF3, and a luciferase reporter assay and ChIP-PCR were used to confirm the regulatory mechanism of ATF3 to LIF. Endometrial epithelial capacity was assessed by an in vitro model of attachment of BeWo spheroids to Ishikawa cells. Western blotting was performed to compare the expression of ATF3 in endometrial samples of recurrent implantation failure (RIF) patients with that in samples from fertile women (FER) who had undergone no less than one successful embryo transplantation. RESULTS: ATF3 was located in human endometrial epithelial cells and stromal cells and was significantly induced by E2 and MPA in Ishikawa cells. Adenovirus-mediated overexpression of ATF3 in Ishikawa cells activated LIF promoter activity and enhanced its expression. Accordingly, the stimulation of BeWo spheroid adhesion promoted by ATF3 was inhibited by pretreatment with a specific antibody against LIF via the antibody-blocking assay. Moreover, ATF3 was aberrantly decreased in the endometria of RIF patients. CONCLUSIONS: Our findings suggest that ATF3 plays a significant role in regulating human endometrial receptivity and embryo attachment in vitro via up-regulation of leukemia inhibitory factor. TRIAL REGISTRATION: Construction and management of the Nanjing multi-center biobank. No. 2013-081-01 . Registered 10 Dec. 2013.


Assuntos
Fator 3 Ativador da Transcrição/fisiologia , Implantação do Embrião/genética , Fator Inibidor de Leucemia/genética , Aborto Habitual/genética , Aborto Habitual/metabolismo , Aborto Habitual/patologia , Adulto , Estudos de Casos e Controles , Células Cultivadas , Transferência Embrionária , Endométrio/citologia , Endométrio/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Feminino , Fertilização In Vitro , Humanos , Fator Inibidor de Leucemia/metabolismo , Regulação para Cima/genética , Adulto Jovem
20.
Am J Reprod Immunol ; 78(5)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28543977

RESUMO

PROBLEM: To define a more precise parameter for a better understanding of natural killer (NK) cells and its relation with regulatory T cells (Tregs) in women with recurrent implantation failure (RIF). METHOD OF STUDY: The percentages of CD56+ cells, CD57+ cells and Foxp3+ cells in the endometrium and blood from 23 normal controls and 32 women with RIF were measured by immunocytochemistry and flow cytometry. RESULTS: Women with RIF had significantly increased ratio of CD57+ cells to CD56+ cells in both the endometrium (P<.01) and blood (P<.05), and decreased percentage of Foxp3+ cells in the endometrium (P<.05). There was a significant negative correlation between CD57+ cells to CD56+ cells ratio and the percentage of Foxp3+ cells in the blood of RIF patients (P<.05). CONCLUSION: Our study provides a novel assessment parameter, CD57+ cells to CD56+ cells ratio, to evaluate NK cells and its relation with Tregs in RIF patients.


Assuntos
Aborto Habitual/imunologia , Endométrio/patologia , Células Matadoras Naturais/imunologia , Linfócitos T Reguladores/imunologia , Aborto Habitual/diagnóstico , Adulto , Antígeno CD56/metabolismo , Antígenos CD57/metabolismo , Separação Celular , Implantação do Embrião , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imuno-Histoquímica , Gravidez
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