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1.
Am J Hum Genet ; 108(2): 337-345, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33434492

RESUMO

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/genética , Anormalidades Congênitas/genética , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/crescimento & desenvolvimento , Mutação , Ductos Mesonéfricos/crescimento & desenvolvimento , Adulto , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 7/genética , Códon sem Sentido , Feminino , Estudos de Associação Genética , Pleiotropia Genética , Proteínas Homeobox A10/genética , Proteínas de Homeodomínio/genética , Humanos , Fator de Transcrição PAX8/genética , Herança Paterna , Penetrância , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Proteínas Wnt/genética , Ductos Mesonéfricos/anormalidades
2.
Front Immunol ; 11: 595970, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281824

RESUMO

The pandemic caused by emerging Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents a global public health threat. Illustrating human antibody responding to viral antigen could potentially provide valuable information for basic research and clinical diagnosis. The antibody can be used as a complement to the viral detection for the rapid diagnosis of infected patients. Compared with spike protein (SP), nucleocapsid protein (NP) is normally conserved and highly immunogenic in many coronavirus members. As a major antigen, NP is a potential target for the diagnosis of SARS-CoV-2 infection. Here, we constructed a combinatorial fragment of antigen-binding (Fab)antibody phage library based on peripheral blood-derived from five coronavirus disease 2019 (COVID-19) infected donors. From the library, 159 Fab antibodies were obtained and identified by panning with NP. Among them, 16 antibodies were evaluated for their binding properties and epitopes recognition. Among these 16 antibodies, two well-paired antibodies were finally screened out for SARS-CoV-2 diagnosis by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) method. Our works may provide a potential resource for the clinical diagnosis of SARS-CoV-2 infection.

3.
Cancer Cell Int ; 20: 338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760216

RESUMO

Background: Cell autophagy has been proposed to be involved in drug resistance therapy. However, how the long non-coding RNA (lncRNA) reduces risks of drug resistance in renal cancer (RC) cells needs a thorough inquiry. This study was assigned to probe the effect and mechanism of HOTAIR on sunitinib resistance of RC. Methods: Clinical RC tissues and para-carcinoma tissues were obtained to detect the expressions of miR-17-5p, HOTAIR and Beclin1. Sunitinib-resistant cells (786-O-R and ACHN-R) were constructed using parental RC cells (786-O and ACHN). The resistance of 786-O-R and ACHN-R cells to sunitinib was examined. Western blot and qRT-PCR were assayed to obtain the expressions of miR-17-5p, HOTAIR and Beclin1. The effects of HOTAIR knockdown or miR-17-5p overexpression/knockdown on cell autophagy and sunitinib resistance were measured by MDC staining, immunofluorescence and Western blot. The sensitivity of RC cells to sunitinib and change in cell clone formation after sunitinib treatment were assessed by CCK-8 assay and colony formation assay, respectively. The relationships among HOTAIR, miR-17-5p and Beclin1 were verified by dual-luciferase reporter gene and RIP assay. The role of HOTAIR knockdown in sunitinib resistance was verified in nude mice. Results: HOTAIR expression in sunitinib-resistant cells is higher than that in parental cells. Knockdown of HOTAIR in sunitinib-resistant cells lead to refrained sunitinib resistance and cell autophagy both in vivo and in vitro. Activation of autophagy could raise resistance to sunitinib in RC cells, while inhibition of autophagy could improve the sensitivity of sunitinib-resistant cells to sunitinib. HOTAIR could compete with miR-17-5p to regulate Beclin1 expression. Knockdown of miR-17-5p in parental cells increases cell resistant to sunitinib, and overexpression of miR-17-5p in sunitinib-resistant cells increases cell sensitive to sunitinib. Conclusion: HOTAIR negatively targets miR-17-5p to activate Beclin1-mediated cell autophagy, thereby enhancing sunitinib resistance in RC cells.

4.
Curr Mol Pharmacol ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32368989

RESUMO

BACKGROUND: Cancer is one of the major causes of human death at present. It is the leading cause of death in developed countries. Moreover, Circular RNAs (circRNAs) play important roles in tumor genesis and development and are abnormally expressed in bladder cancer have been discovered at present. OBJECTIVE: The present study aims to investigate the anti-cancer effects of circ 001418 on bladder carcinoma and its possible mechanism. METHODS: Quantitative PCR (qPCR) and gene chip were used to measure the circ 001418 expression. Cell proliferation and transfer, apoptosis and caspase-8 and caspase-3 activity levels were measured using MTT, Transwell assay, Flow cytometry. Caspase-3 and 9 activity levels, EphA2, cytochrome c and FADD protein expression were detected using Western blotting. RESULTS: The expression of circ 001418 was increased in patients with bladder carcinoma. Over-expression of circ 001418 promoted cell proliferation and transfer, and reduced apoptosis in vitro model of bladder carcinoma. Down-regulation of Circ 001418 inhibited cell proliferation and transfer, and induced apoptosis in vitro model of bladder carcinoma. Meanwhile, Overexpression of circ 001418 induced EphA2 and cytochrome c protein expression, suppressed FADD protein expression in vitro model of bladder carcinoma by suppression of miR-1297. MiR-1297 reduced the pro-cancer effect of circ 001418 on apoptosis of bladder carcinoma. CONCLUSION: Results showed thatcircRNA 001418 promoted cell growth and metastasis of bladder carcinoma via EphA2 by miR-1297.

5.
Orphanet J Rare Dis ; 15(1): 121, 2020 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448241

RESUMO

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital disease characterized by uterovaginal agenesis. The diagnosis of MRKH syndrome generally leads to considerable emotional burdens on patients. However, studies focusing on the psychological influence on patients are limited and of unsatisfactory quality. The aim of this study was to investigate the prevalence of depressive symptoms in Chinese patients with MRKH syndrome and to identify the factors associated with depressive symptoms. We recruited 141 patients with MRKH syndrome and 178 age-matched healthy women as control group in this cross-sectional study. Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9). Other parameters such as sociodemographic characteristics, treatment histories, personality traits, and attitudes toward femininity and offspring, were also gathered in the self-administered questionnaire. RESULTS: The PHQ-9 score was significantly higher in MRKH patient group than the age-matched control group (7.0 (4.5-11.0) vs. 6.0 (3.0-9.0)), median and IQRs) (P = 0.015). A total of 75.2% of MRKH patients suffered from depressive symptoms, and 34.0% reached a moderate to severe level, while the proportion in the control group was 61.2 and 24.2% respectively. Compared with other age groups, patients in their 20s scored higher on the PHQ-9. Patients with higher neuroticism levels in personality traits (OR 1.19 95% CI 1.11-1.28), negative self-evaluation of femininity (OR 3.964, 95% CI 1.371-11.464) and sexual dysfunction (OR 4.81 95% CI 1.24-18.72) (compared with those having no sexual activity) were more likely to exhibit depressive symptoms. CONCLUSIONS: Three-quarters of MRKH patients show depressive symptoms, and one-third of these individuals are even at risk for depressive disorders. Therefore, depressive symptom screening and proper psychotherapy in MRKH patients are of great importance.

6.
J Minim Invasive Gynecol ; 27(7): 1465-1466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32259653
7.
Chin Med J (Engl) ; 133(4): 388-394, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31977552

RESUMO

BACKGROUND: As a congenital malformation that results in infertility and an inability to have vaginal intercourse, Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome places a considerable psychological burden on patients, which results in anxiety symptoms. However, only single case studies or a few small to medium-sized cross-sectional studies were identified to focus on anxiety symptoms in MRKH patients. Thus, the aim of this study was to explore the status of anxiety symptoms and the related factors in patients with MRKH syndrome. METHODS: This cross-sectional study involving 141 patients with MRKH syndrome and 178 healthy women was conducted from January 2018 to December 2018. All participants were required to complete a demographic questionnaire and the Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire-9, Eysenck Personality Questionnaire-Revised, Short Scale for Chinese, and Chinese Version of the Female Sexual Function Index. The main outcome was the anxiety symptoms measured by the GAD-7. Main outcome was compared between the MRKH syndrome group and the healthy control group. Then, we explored the related factors by comparing patients with and without anxiety symptoms. RESULTS: Of the respondents, 24.1% experienced moderate to severe anxiety symptoms. Patients with MRKH syndrome manifested more severe anxiety symptoms than healthy women. Negative self-evaluation of femininity (odds ratio [OR] 2.706, 95% confidence interval [CI] 1.010-7.247), neurotic personality traits (OR 1.100, 95% CI 1.029-1.175), and coexisting depressive symptoms (OR 4.422, 95% CI 1.498-13.049) were more prevalent in anxious patients. CONCLUSION: The findings stress the importance of anxiety symptom screening in MRKH patients and identify patients at risk of anxiety symptoms, providing a possible basis for future intervention.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31517310

RESUMO

Objective: The aim of this study was to use whole genome sequencing (WGS) help detect de novo mutations or pathogenic genes of Mayer-Rokitansky-Küster-Hauser syndrome type 1(MRKH syndrome type 1). Study design: This was a case-parent trios study. Nine unrelated probands, with MRKH syndrome type 1 and their parents were enrolled. The enrollment, sequencing process, establishment of the de novo mutations detecting procedure and experiment part were performed over a 2-year period. Results: we detected 632 de novo single nucleotide variants (SNVs), 267 de novo small insertions/deletions (indels), 39 de novo structural variations (SVs) and 28 de novo copy number alterations (CNAs). Three novel damaging coding de novo SNVs with three damaging coding de novo genes (PIK3CD, SLC4A10 and TNK2) were revealed. Two SNVs were annotated of the promoter region of gene NBPF10 and 3'UTR of NOTCH2NL, potentially contributing to the pathogenesis of MRKH. Conclusion: We identified five de novo mutations in BAZ2B, KLHL18, PIK3CD, SLC4A10 and TNK2 by performing WGS, the functional involvement of all deleterious mutations in MRKH candidate genes of the trios warrant further study. WGS may complement conventional array to capture the complete landscape of the genome in MRKH.

9.
Eur J Obstet Gynecol Reprod Biol ; 228: 313-318, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30075412

RESUMO

OBJECTIVE: The aim of this study was to examine if the advanced tool of 3D MRI model provides more precise information on the anatomy of pelvic organs than MRI alone, and compare to clinical and operative finding of patients with vagina in Müllerian duct anomalies. STUDY DESIGN: One hundred and ten patients with clinically and operatively proven Müllerian duct anomalies were included. The consistency of diagnosis of Mullerian tract anomalies by MRI and 3D MRI compared to clinically and surgically proven anomalies defined according to ASRM classification. RESULTS: We successfully reconstructed retrospectively all 110 patients' three-dimensional models from the simple MRI scans. Eighty-six of the patients (78.2%) showed an agenesis of the uterus, four patients presented with uterine didephys (3.6%). Septate uterus was detectable in 8 of 110 cases (7.3%). Arcuate uterus was detectable in 3 of 110 cases (2.7%). The remaining patients presented with either unilateral (n = 4; 3.6%) or bilateral (n = 5; 4.5%) uterine horns. Reviewed by radiologists, comparing the agreement rate between 3D- MRI reconstruction models and simple MRI, there was a trend towards but not significant difference (P = 0.064). Reviewed by trained surgeons, the agreement between three-dimensional MRI reconstruction models and MRI, there was significant difference (P = 0.003). CONCLUSION: 3D MRI model is a non-expensive add-on software tool that enhance the ability of expert surgeon to reach a more precise diagnosis of the pelvic anatomy structures, compared to MRI alone. Getting a more precise description of the pelvic anatomy allows a better planning of the corrective procedure needed and preoperative assessment of the expected prognosis.


Assuntos
Ductos Paramesonéfricos/anormalidades , Anormalidades Urogenitais/diagnóstico por imagem , Útero/anormalidades , Adolescente , Adulto , Criança , Feminino , Humanos , Imageamento Tridimensional , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Retrospectivos , Útero/diagnóstico por imagem , Adulto Jovem
10.
Gene ; 652: 7-15, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29412153

RESUMO

Bladder cancer has shown great challenge for people's life. Traditional therapeutics against bladder cancer including surgery could not bring much benefit for patients, particularly for the late stage patients. So it is necessary to keep in mind why and how bladder cancer cells survive in our body. In this study, we explored the function and the molecular mechanism of GGN gene in bladder cancer. GGN was shown to be expressed at a high level in bladder cancer tissues compared to the control and was associated with the unsatisfactory survival rate of patients. GGN was also expressed abundantly in bladder cancer cell lines such as T24, 5637 and BIU87. Then GGN was knocked down in 5637 cells and T24 cells at both RNA and protein level. In accordance, aberrant growth and proliferation were demonstrated in bladder cancer cells. The ability of migration and invasion of bladder cancer cells was also inhibited. The in vivo data further proved that the xenograft tumor growth was dramatically suppressed by GGN knockdown. Then we demonstrated that the level of IκB, bax and truncated caspase3 was upregulated after GGN was knocked down in 5637 cells. In contrast, expression level of NFκB, IKK, c-Myc, cyclin D1 and Bcl-2 was reduced. Further, the phosphorylation level of IκB was also downregulated. These data suggest that NFκB/caspase3-mediated apoptosis signaling was regulated by GGN. Conclusively, GGN played a tumor-promoting role in bladder cancer through regulation of NFκB/caspase3-mediated apoptosis signaling. This study provides a new clue for the treatment of patients with bladder cancer.


Assuntos
Caspase 3/genética , Regulação Neoplásica da Expressão Gênica , NF-kappa B/genética , RNA Interferente Pequeno/genética , Hormônios Testiculares/genética , Neoplasias da Bexiga Urinária/terapia , Animais , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Feminino , Humanos , Camundongos , Camundongos Nus , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de Sobrevida , Hormônios Testiculares/antagonistas & inibidores , Hormônios Testiculares/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
11.
Minim Invasive Ther Allied Technol ; 26(2): 111-118, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27830594

RESUMO

It was a different study from traditional anatomy to construct three-dimensional (3D) model of the corona mortis (CMOR) through contrasted enhanced computed tomography (CT) scanning. This will provide an aid for the understanding of the fine anatomy of CMOR, as well as surgical produces. A medical image processing system was used to process computed tomography scanning data collected from 330 cases of woman patients. Accurate digital 3D models of the CMOR were used to study the incidence, location, and the morphological patterns. These models have a rotation of 360° and allow displaying from different views. The incidence was 51.1% for the venous CMOR, 14.1% for the arterial CMOR in the 660 sides pelvic wall and vessel models. The mean distance from the symphysis pubis for the venous CMOR was 66.87 mm, and 59.60 mm for the arterial CMOR. The morphological patterns we identified were classified in three types (I-III). The model of CMOR serves as a useful tool for the learning and investigation of the CMOR. In the future, the digital anatomical data can be beneficial to illustrating the operation approach and decreasing the surgical complications.


Assuntos
Imageamento Tridimensional , Modelos Anatômicos , Pelve/anatomia & histologia , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Criança , Meios de Contraste/administração & dosagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade , Pelve/diagnóstico por imagem , Adulto Jovem
12.
Fertil Steril ; 106(5): 1190-1194, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27349924

RESUMO

OBJECTIVE: To analyze the phenotypic and clinical aspects of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): Five hundred and ninety-four patients with MRKH syndrome. INTERVENTION(S): Clinical examination, abdominal or perineal/rectal ultrasound, magnetic resonance imaging, hormonal profile, karyotype, and laparoscopy. MAIN OUTCOME MEASURE(S): Clinicopathologic data, VCUAM (vagina cervix uterus adnex-associated malformation) classification, types with cycle phase, and karyotype. RESULT(S): We identified associated malformations in 43 out of 594 (7.2%) cases of MRKH. The 594 patients could be grouped into hormone phases: 53.7% follicular, 35.2% luteal, and 11.1% ovulatory. The major karyotype of MRKH patients was 46,XX; abnormal karyotypes were found in two cases. CONCLUSION(S): A lower proportion of associated malformations were found when compared with those provided in the current literature. Renal anomalies were the most frequent associated malformations, and most of the patients presented with a normal karyotype. Given the large cohort of this study, the lower malformation rates might be related to geographic or referral patterns, so further investigation is warranted.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/diagnóstico , Anexos Uterinos/anormalidades , Colo do Útero/anormalidades , Anormalidades Congênitas/diagnóstico , Ductos Paramesonéfricos/anormalidades , Vagina/anormalidades , Transtornos 46, XX do Desenvolvimento Sexual/sangue , Transtornos 46, XX do Desenvolvimento Sexual/genética , Transtornos 46, XX do Desenvolvimento Sexual/fisiopatologia , Anexos Uterinos/diagnóstico por imagem , Adolescente , Adulto , Biomarcadores/sangue , Colo do Útero/diagnóstico por imagem , Colo do Útero/fisiopatologia , Criança , China , Cromossomos Humanos X , Anormalidades Congênitas/sangue , Anormalidades Congênitas/genética , Anormalidades Congênitas/fisiopatologia , Estudos Transversais , Feminino , Predisposição Genética para Doença , Hormônios/sangue , Humanos , Cariótipo , Cariotipagem , Laparoscopia , Imagem por Ressonância Magnética , Ciclo Menstrual/sangue , Ductos Paramesonéfricos/fisiopatologia , Fenótipo , Ultrassonografia , Vagina/diagnóstico por imagem , Adulto Jovem
13.
Int J Gynaecol Obstet ; 133(3): 320-4, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27087418

RESUMO

OBJECTIVE: To evaluate the outcomes of laparoscope-assisted peritoneal vaginoplasty for the treatment of congenital vaginal atresia. METHODS: A retrospective study enrolled patients diagnosed with congenital vaginal atresia who were treated with one of two different laparoscope-assisted peritoneal vaginoplasty techniques (named Luohu-one and Luohu-two) between October 31, 2001 and December 31, 2014. Operative time, intraoperative bleeding volume, surgical difficulty, complications, and post-procedure sexual satisfaction were reported. RESULTS: Data were collected for 620 patients. The Luohu-one procedure was used in the treatment of 145 patients, while 475 patients were treated with the Luohu-two procedure. In 5 (0.8%) patients, it was necessary to perform a sigmoid colon vaginoplasty. During surgery, 16 patients experienced a rectal injury, among whom, 9 patients experienced a rectal-vaginal fistula. Follow-up data extending to 7years were available for 285 patients. Of these 285 patients, 231 agreed to report details of their sexual experiences. In total, 222 (96.1%) patients reported being very satisfied with their vaginal conditions and sex life. The Luohu-two procedure demonstrated shorter operative and recovery time, and reduced intraoperative bleeding. However, both procedures demonstrated satisfactory results. CONCLUSION: Laparoscope-assisted peritoneal vaginoplasty demonstrated good safety and effectiveness in the treatment of patients with congenital vaginal atresia.


Assuntos
Anormalidades Congênitas/cirurgia , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Vagina/anormalidades , Adolescente , Adulto , China , Colo Sigmoide/cirurgia , Feminino , Seguimentos , Humanos , Laparoscopia/efeitos adversos , Duração da Cirurgia , Orgasmo , Períneo/cirurgia , Peritônio/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Fístula Retovaginal/cirurgia , Estudos Retrospectivos , Vagina/cirurgia , Adulto Jovem
14.
Pharmacogenet Genomics ; 20(5): 298-306, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20300047

RESUMO

OBJECTIVES: To clarify the effects of the association between combined oral contraceptives (COC) use and ACE/AGT gene on stroke risk, and to undertake a preliminarily study of the molecular mechanism of the association between COC exposure and predisposing genes of hypertension on the increased risk of stroke. METHODS: This study was a multi-center case-control study based on the population of 25 towns in the surveillance regions of Jiangsu province, China. RESULTS: (i) The univariate analysis of the frequency of the DD genotype of ACE insert/delete (I/D) polymorphism between the cases and controls indicated its significant association with the stroke (P<0.01), especially for hemorrhagic stroke (P<0.01). (ii) Women with COC exposure and ACE I/D genotype had an increased risk for all strokes [adjusted odds ratio 5.63; 95% confidence interval (CI), 2.20, 15.68], and an increased risk for hemorrhagic stroke (adjusted odds ratio 31.53; 95% CI, 3.54, 281.14) after adjustment for education and occupation. (iii) Multivariate analyses showed that hypertension was the most important risk factor for hemorrhagic stroke and ischemic stroke. COC use was a significant risk factor for hemorrhagic stroke. The combined effects of COC use, for 15 years and above, and ACE I/D polymorphism increased the risk of all strokes by more than eight times, and the risk of hemorrhagic stroke by more than 15 times. CONCLUSION: Hypertension was a most important risk factor for stroke incidence. The D allele of ACE I/D polymorphism may be a potential risk allele for stroke. COC users carried the ID+DD genotype that may further increase the risk of stroke, especially for hemorrhagic stroke.


Assuntos
Angiotensinogênio/genética , Anticoncepcionais Orais Combinados/efeitos adversos , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Risco , Acidente Vascular Cerebral/genética , Adulto , Idoso , Alelos , Pressão Sanguínea , Estudos de Casos e Controles , China , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Fatores de Risco
15.
Arch Med Res ; 41(8): 599-605, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21199728

RESUMO

BACKGROUND AND AIMS: Estrogen receptor beta (ESR2) plays an important role in cardiovascular physiology and blood pressure regulation, whereas estrogens may influence gene expression, growth, and cellular differentiation in target tissues by activating estrogen receptors. This study aims to investigate the association between common genetic variants of ESR2 gene and the risk of hypertension and to explore the combined effected of ESR2 variants and combined oral contraceptive (COC) use for hypertension risk. METHODS: A population-based case-control study was conducted in 621 female hypertensive patients and 621 female normotensive controls. RESULTS: ESR2 G1082A heterozygote genotype (GA) was in significant relationship with hypertension (crude odds ratio [OR] = 1.38, 95% CI: 1.09-1.76; adjusted odds ratio [OR] = 1.38, 95% CI: 1.09-1.76). No association was observed for ESR2 G1730A polymorphism. Furthermore, the joint effects of the heterozygote of G1082A polymorphism (heterozygote model: GG/AA vs. GA) and cumulative COC use time ≥15 years significantly increased the risk of hypertension [adjusted odds ratio (OR) = 2.19, 95% CI: 1.49-3.24], and the interaction effects between those two risk factors were significant (p = 0.0001). CONCLUSIONS: The heterozygote GA genotype of ESR2 gene G1082A polymorphism may be a risk genotype for hypertension in Chinese women, and the GA genotype (heterozygote model: GG/AA vs. GA) of G1082A locus together with COC use simultaneously contributed to hypertension development.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Anticoncepcionais Orais Combinados/efeitos adversos , Receptor beta de Estrogênio/genética , Hipertensão , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Hipertensão/induzido quimicamente , Hipertensão/genética , Pessoa de Meia-Idade , Fatores de Risco
16.
Clin Chem Lab Med ; 44(10): 1218-25, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17032134

RESUMO

BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65 were investigated by Western blotting or immunochemistry. RESULTS: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IkappaBalpha were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IkappaBalpha and pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.


Assuntos
Aspirina/uso terapêutico , Aterosclerose/prevenção & controle , Inibidores de Proteassoma , Ubiquitina/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Aorta/química , Aorta/efeitos dos fármacos , Aorta/patologia , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Colesterol/sangue , Dieta Aterogênica , Modelos Animais de Doenças , Proteínas I-kappa B/análise , Lipídeos/sangue , Masculino , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Fator de Transcrição RelA/análise
17.
Toxicol Appl Pharmacol ; 210(1-2): 24-31, 2006 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-16045953

RESUMO

The effect of terephthalic acid (TPA) on urinary bladder carcinogenesis was examined. Male Wistar rats were initiated by injection of N-Methyl-N-Nitrosourea (MNU) (20 mg/kg b.w. ip) twice a week for 4 weeks, then given basal diet containing 5% TPA, 5% TPA plus 4% Sodium bicarbonate (NaHCO3) or 1% TPA for the next 22 weeks, and then euthanized. 5% TPA treatment induced a high incidence of urinary bladder calculi and a large amount of precipitate. Though 5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1% TPA treatment did not induce urinary bladder calculi formation, they resulted in a moderate increase in urinary precipitate. Histological examination of urinary bladder revealed that MNU-5% TPA treatment resulted in a higher incidence of simple hyperplasia, papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer than MNU control. MNU-5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1% TPA treatment increased slightly the incidence of simple hyperplasia and PN hyperplasia (not statistically significant). The major elements of the precipitate are phosphorus, potassium, sulfur, chloride, calcium and TPA. The present study indicated that the calculi induced by TPA had a strong promoting activity on urinary bladder carcinogenesis and the precipitate containing calcium terephthalate (CaTPA) may also have weak promoting activity on urinary bladder carcinogenesis.


Assuntos
Cocarcinogênese , Metilnitrosoureia/toxicidade , Ácidos Ftálicos/toxicidade , Neoplasias da Bexiga Urinária/induzido quimicamente , Bexiga Urinária/efeitos dos fármacos , Animais , Testes de Carcinogenicidade , Relação Dose-Resposta a Droga , Hiperplasia , Masculino , Microscopia Eletrônica de Varredura , Ratos , Ratos Wistar , Bicarbonato de Sódio/farmacologia , Urinálise , Bexiga Urinária/ultraestrutura , Cálculos da Bexiga Urinária/induzido quimicamente , Cálculos da Bexiga Urinária/complicações , Cálculos da Bexiga Urinária/prevenção & controle , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/ultraestrutura , Neoplasias da Bexiga Urinária/urina
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