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1.
Zhonghua Gan Zang Bing Za Zhi ; 30(3): 316-322, 2022 Mar 20.
Artigo em Zh | MEDLINE | ID: mdl-35462489

RESUMO

Objective: To dynamically observe the clinical efficacy of entecavir and the changes of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 levels in peripheral blood of HBeAg-positive chronic hepatitis B virus carriers treated with entecavir, and further explore its clinical significance. Methods: There were 31 cases of chronic hepatitis B virus carriers in the treatment group (A), 32 cases of chronic hepatitis B virus carriers in the treatment group (B), and 15 cases of chronic hepatitis B virus carriers in the non-treatment group (C).Three groups peripheral blood samples and clinical data at 0, 24 and 48 weeks were collected and compared. PD-1+CXCR5+CD4+T lymphocytes were detected by flow cytometry, and the level of sPD-1 was detected by enzyme-linked immunosorbent assay. ANOVA and Spearman correlation analysis were performed on the measurement data among the three groups. Results: At week 0, the serum levels of HBsAg, HBeAg and HBV DNA were significantly higher in groups A and C than group B. PD-1+CXCR5+CD4+T lymphocytes in peripheral blood were significantly higher in group B (4.70%±1.58%) than group A (3.25%±1.01%) and group C (2.77%±0.67%) (F=16.65, P<0.05). There was no significant difference between group A and group C (P>0.05). Peripheral blood sPD-1 in group B [(1 866.62±1 472.70) pg/ml] was significantly higher than group A [(824.86±538.66) pg/ml] and group C [(618.19±602.62) pg/ml] (F=10.95, P<0.05). There was no significant difference between group A and group C (P>0.05). At 48 weeks, the serum HBsAg did not decrease significantly in groups A and C than baseline (P>0.05), but were significantly higher than group B (P<0.05). Serum HBeAg levels were decreased significantly in groups A and B than baseline (P<0.05). <0.05), but group A was significantly higher than group B (P<0.05), and there was no significant difference between group A and group C (P>0.05). Serum HBV DNA level was significantly lower in groups A and B than group C (P<0.05), and there was no significant difference between group A and group B (P>0.05). Peripheral blood PD-1+CXCR5+CD4+T lymphocytes were significantly lower in Group A (1.56%±0.73%) and group B (1.32%±0.43%) than group C (2.64%±0.85%) (P<0.05). Peripheral blood sPD-1 were significantly lower in group A [(289.05±215.86) pg/ml] and group B [(236.01±173.92) pg/ml] than group C [(650.34±598.46) pg/ml] (P<0.05). There was no significant difference between group A and group B. Correlation analysis results: In group A at 48 weeks, the decreased level of PD-1+CXCR5+CD4+T lymphocyte ratio had no correlation with the decreased level of HBsAg and HBV DNA, but was positively correlated with the decreased level of HBeAg (r=0.376, P<0.05). The decreased level of sPD-1 had no correlation with the changes of HBsAg, but was positively correlated with the decreased levels of HBeAg and HBV DNA (r=0.598 and 0.384, P<0.05). In group B at 48 weeks, the decreased levels of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 were positively correlated with the decreased levels of HBsAg, HBeAg, and HBV DNA (P<0.05). Conclusion: Hepatitis B virus replication and expressions in HBeAg-positive chronic hepatitis B virus carriers were significantly inhibited after 48 weeks of antiviral treatment, which is related not only to entecavir treatment, but also to the immunological mechanism involved in sPD-1. Moreover, the inhibition of HBeAg expression is associated with a decrease in the number and/or activity of PD-1+CXCR5+CD4+T lymphocytes.


Assuntos
Antígenos E da Hepatite B , Hepatite B Crônica , Antivirais/uso terapêutico , DNA Viral , Guanina/análogos & derivados , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Humanos , Receptor de Morte Celular Programada 1 , Receptores CXCR5/análise , Linfócitos T
2.
Zhonghua Fu Chan Ke Za Zhi ; 55(4): 253-258, 2020 Apr 25.
Artigo em Zh | MEDLINE | ID: mdl-32375432

RESUMO

Objective: To investigate the effect of gonadotropin (Gn) on embryo aneuploidy rate and pregnancy outcome during preimplanptation genetic testing for aneuploidy (PGT-A) cycles. Methods: The clinical data of patients undergoing PGT-A cycle at the First Medical Center of the PLA General Hospital from January 1, 2013 to May 31, 2019 were retrospectively analyzed. Patients were divided into younger patient group (<35 years old) and elder patient group (≥35 years old) by maternal age, then divided into two groups in line with Gn dosage (≤2 250 U, >2 250 U), and into four groups by number of oocytes retrieved (1-5, 6-10, 11-15 and ≥16 oocytes). The embryo aneuploidy rate and pregnancy outcome between the groups were compared. Logistic regression was used to analyze the relationship between the cumulative amount of Gn, embryo aneuploidy rate and live-birth rate. Results: A total of 402 cycles (338 patients) and 1 883 embryos were included in the study. (1) In the younger patients, the aneuploidy rate was 52.5% (304/579) in the group of Gn≤2 250 U and 48.6% (188/387) in the group of Gn>2 250 U, with no significant difference between them (P=0.232). In the elderly patients, the difference in embryo aneuploidy rate between the two Gn group [57.9% (208/359) versus 60.6% (319/526)] was not statistically significant (P=0.420). (2) The embryonic aneuploidy rate in different protocol of ovary stimulation was analyzed,in the younger group, the embryonic aneuploidy rate in patients using antagonist long protocol was 50.3% (158/314), it was 50.0% (121/242) in agonist long protocol, 52.1% (207/397) in agonist short protocol and 6/13 in luteal phase protocol, no statistical difference was found in above groups (P=0.923); in the elder group, embryonic aneuploidy rate was 60.8% (191/314) in antagonist protocol, 58.4% (132/226) in agonist long protocol, 59.2%(199/336) in agonist short protocol, 5/9 in luteal phase protocol, respectively,no significant difference was found (P=0.938). (3) In the younger patients, the aneuploidy rate in 1-5 oocytes group, 6-10 oocytes group, 11-15 oocytes group and ≥16 oocytes group was 37.9% (11/29), 54.0% (94/174), 52.5% (104/198) and 50.1% (283/565) respectively, no significant difference was found between the groups (P=0.652); while in the elder patients, the difference between aneuploidy rate in each retrieved oocytes group [73.6% (89/121), 57.5% (119/207), 56.3% (108/192), 57.8% (211/365)] was statistically significant (P=0.046). (4) Logistic regression analysis of age, cumulative dosage of Gn, number of oocytes obtained, and embryo aneuploidy rate showed that there was no association between the amount of Gn and embryo aneuploidy rate (P>0.05); the increase in maternal age would increase the risk of aneuploidy rate of embryos, which was statistically significant (OR=1.031, 95%CI: 1.010-1.054, P=0.004); the increase in oocytes retrived would significantly decrease the risk of aneuploidy (OR=0.981, 95%CI: 0.971-0.991, P<0.01). (5) There was no significant difference in biochemical pregnancy rate [55.6% (80/144) versus 52.1% (63/121)], clinical pregnancy rate [50.0% (72/144) versus 47.9% (58/121)] and live-birth rate [46.5% (67/144) versus 40.5% (49/121)] between different Gn dosage groups (P=0.613, P=0.738, P=0.324). The logistic regression analysis showed that the maternal age, the cumulative dosage of Gn, the number of oocytes obtained, and the ovarian stimulation protocol had no effect on the live-birth rate (all P>0.05). Conclusions: In PGT-A cycle, the dosage of Gn has no association with the embryo aneuploidy rate and pregnancy outcome. In the patients ≥35 years old, the increase in number of oocytes obtained may decrease the risk of aneuploidy. Age is an important factor affecting the embryo aneuploidy in PGT-A cycle.


Assuntos
Aneuploidia , Fertilização in vitro/métodos , Testes Genéticos/métodos , Gonadotropinas/efeitos adversos , Gonadotropinas/farmacologia , Resultado da Gravidez , Diagnóstico Pré-Implantação/métodos , Adulto , Idoso , Feminino , Gonadotropinas/administração & dosagem , Humanos , Indução da Ovulação , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
5.
Int J Immunogenet ; 43(3): 151-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27122304

RESUMO

Interleukin-21 (IL-21), as a multifunctional cytokine, plays an important role in many diseases, such as cancer, inflammatory and autoimmune diseases. We aimed to investigate the relationship between polymorphisms of IL-21 gene and susceptibility of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in a Chinese population. Studied subjects were divided into three groups: 100 patients with HBV-related HCC, 115 patients with chronic HBV infection and 127 healthy controls. Genomic DNA was isolated from peripheral blood, and the polymerase chain reaction-ligase detection reaction (PCR-LDR) method was used to genotype the SNPs (rs2221903, rs907715 and rs12508721) within IL-21 gene. Our results showed that IL-21 polymorphisms were associated with the risk of HCC and chronic HBV infection when compared with healthy controls. The rs2221903A/G AG genotype was associated with a higher risk of chronic HBV infection when compared with healthy controls [AG versus AA + GG, P = 0.036, OR = 1.898, 95%CI = 1.038-3.471]. The rs12508721C/T TT genotype was related with a lower risk of chronic HBV infection and HBV-related HCC than in healthy controls [TT versus CT + CC, P = 0.026, OR = 0.451, 95%CI = 0.221-0.920; P = 0.049, OR = 0.482, 95%CI = 0.231-1.005]. No significant difference in the genotype and allele distrubutions of rs907715G/A SNP was observed in the HBV-related HCC group, chronic HBV-infected group and the healthy control group when compared to each other. Our findings suggest that the rs12508721T/C and rs2221903A/G polymorphisms of IL-21 gene are associated with the susceptibility of HBV-related HCC and chronic HBV infection. The genetic variant may in fact cause protection against the HBV-related HCC. However, the function in these SNPs of IL-21 gene needs to clarify the mechanisms involved in the pathogenesis of HBV-related HCC further.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite B Crônica/genética , Interleucinas/genética , Neoplasias Hepáticas/genética , Adulto , Idoso , Alelos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
6.
Zhonghua Gan Zang Bing Za Zhi ; 24(6): 465-8, 2016 Jun.
Artigo em Zh | MEDLINE | ID: mdl-27465955

RESUMO

Chronic hepatitis B virus (HBV) carriers are facing the risk of progression to liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. However, due to low risk, slow disease progression, and unsatisfactory short-term effect of antiviral treatment, controversy still exists over whether such patients should be given antiviral treatment. This article reviews the research advances in the necessity and feasibility of antiviral therapy for chronic hepatitis B virus carriers, so as to provide a reference for clinical practice.


Assuntos
Antivirais/uso terapêutico , Portador Sadio/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Carcinoma Hepatocelular/prevenção & controle , Progressão da Doença , Humanos , Cirrose Hepática/prevenção & controle , Neoplasias Hepáticas/prevenção & controle
7.
Zhonghua Gan Zang Bing Za Zhi ; 24(5): 352-7, 2016 May 20.
Artigo em Zh | MEDLINE | ID: mdl-27470888

RESUMO

OBJECTIVE: To investigate the association between the single nucleotide polymorphisms (SNPs) IL-18-137G/C (rs187238) and IL-18-607A/C (rs1946518) in interleukin-18 (IL-18) gene and hepatocellular carcinoma (HCC) caused by the hepatitis B virus (HBV). METHODS: The subjects were divided into HBV-related HCC group (109 patients), chronic HBV infection group (113 patients), and healthy control group (127 patients). The polymerase chain reaction-ligase detection reaction (PCR-LDR) was used to determine the alleles and genotypes of the two SNPs IL-18-137G/C and IL-18-607A/C. The t-test and chi-square test were used for baseline data. The chi-square test was used to investigate the differences in genotype and allele frequencies across the three groups. Non-conditional logistic regression analysis was used to compare the odds ratios (ORs) and 95% confidence intervals (CIs) for different genotypes/alleles in predicting the risk of HBV-related HCC. RESULTS: The HBV-related HCC group showed significantly higher AA genotype and A allele frequencies of the SNP IL-18-607A/C than the healthy control group (AA genotype frequency: 29.4% vs 18.1%, χ (2) = 4.152, P < 0.05; A allele frequency: 54.6% vs 44.1%, 5.169, P < 0.05), which were positively correlated with the risk of HBV-related HCC (AA genotype frequency: OR = 1.879, 95% CI: 1.020-3.464; A allele frequency: OR = 1.524, 95% CI: 1.059-2.193). The chronic HBV infection group had a significantly higher A allele frequency of the SNP IL-18-607A/C than the healthy control group (54.0% vs 44.1%, χ (2) = 4.680, P < 0.05), which was positively correlated with the risk of chronic HBV infection (OR = 1.487, 95% CI: 1.037-2.132). The genotype and allele frequencies of the SNP IL-18-607A/C showed no significant differences between the HBV-related HCC group and the chronic HBV infection group (P > 0.05). The genotype and allele frequencies of the SNP IL-18-137G/C showed no significant differences between any two groups of the three groups (P > 0.05). CONCLUSION: The AA genotype and A allele frequencies of the SNP IL-18-607A/C are positively correlated with the morbidity of HBV-related HCC, and the A allele frequency of the SNP IL-18-607A/C is positively correlated with the morbidity of chronic HBV infection.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Vírus da Hepatite B/patogenicidade , Interleucina-18/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Alelos , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Hepatite B Crônica/genética , Humanos , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único
8.
Zhonghua Wai Ke Za Zhi ; 54(10): 772-775, 2016 Oct 01.
Artigo em Zh | MEDLINE | ID: mdl-27686642

RESUMO

Objective: To evaluate the clinical effect and safety of oxycodone hydrochloride in the anesthesia for percutaneous radiofrequency ablation (PRFA) in hepatocellular carcinoma. Methods: Between March and December 2015, 60 cases of hepatocellular carcinoma patients undergoing percutaneous radiofrequency ablation surgery in Peking University Cancer Hospital were randomly divided into three groups: oxycodone group (group Q), fentanyl group (group F) and dezocine group (group D), 20 cases in each group. Respectively intravenously injection oxycodone 0.1 mg/kg, fentanyl 0.001 mg/kg, dezocine 0.1 mg/kg before surgery. After the surgeon completed puncture administer propofol to maintain anesthesia. Recorded mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2) changes in each group at entrance, beginning of radiofrequency ablation (T1), radiofrequency ablation began after 10 minutes (T2), the end of the surgical and awake. Observe the analgesia effect, respiratory depression, nausea, vomit and other complications. Postoperative pain scores were recorded.Using ANOVA, repeated measure variance analysis, SNK test, χ2 test and other tests to evaluate the anesthetic effect indexes. Results: The observation completed in all patients. Patients of three groups had no significant differences in general information. No significant difference between MAP, HR and SpO2 at each time points among the three groups. At the T1 time point (group Q: (11.7±1.6)/min, group D: (12.1±1.7)/min, group F: (10.3±2.3)/min, F=5.068, P=0.009) and T2 time point (group Q: (11.9±1.3)/min, group D: (12.2±1.4)/min, group F: (10.7±1.3)/min, F=7.024, P=0.002), RR in group F were lower than in group Q and group D. Pain visual analogue scores after waking (group Q: 0.2±0.7, group D: 0.3±0.7, group F: 1.7±1.5, F=12.981, P=0.000) and postoperative pain score of 1 hour (group Q: 2.0±0.9, group D: 1.8±0.8, group F: 4.3±0.9, F=42.362, P=0.000) in the group Q and group D were significantly lower than in group F. The body movements in group Q and group D were significantly less than in group F (3 cases, 3 cases, 9 cases, χ2=6.400, P=0.041 ). Intraoperative respiratory depression in group Q and group D were lower than group F (3 cases, 2 cases, 9 cases, χ2=8.012, P=0.018). Conclusions: Oxycodone hydrochloride can be used safely and effectively for radiofrequency ablation. It has favorable hemodynamic stability, lower incidence of respiratory depression, and advantage in terms of postoperative pain.


Assuntos
Analgésicos Opioides/uso terapêutico , Carcinoma Hepatocelular/terapia , Ablação por Cateter , Oxicodona/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Feminino , Fentanila/uso terapêutico , Humanos , Neoplasias Hepáticas , Masculino , Dor Pós-Operatória/prevenção & controle , Propofol/uso terapêutico , Tetra-Hidronaftalenos/uso terapêutico
9.
Genet Mol Res ; 14(4): 14356-65, 2015 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-26600495

RESUMO

Limited information on oocytes and fertilization prevents the efficient therapy of patients with infertility. The most important reason for this lack of understanding is a deficiency in research dedicated to oocytes and fertilization. Currently, we are concerned with the role of nutrition in the process of oocyte development to better understand the relationship between nutrition and infertility. The aim of this study was to explore the relationship between some exceptional materials and infertility to elucidate the role of these materials in oocyte development. We used proteomic analysis to identify numerous nutrition-related proteins in three developmental stages: the germinal vesicle stage, the metaphase II-arrested stage, and the fertilized oocyte-zygote stage. Specific proteins were abundantly expressed during the three stages. These proteins included astacin-like metalloendopeptidase, selenium-binding proteins, and other proteins involved in metabolic and signaling pathways. Other proteins were involved in the citrate cycle, the electron transport chain, the urea cycle, fatty acid metabolism, and the insulin signaling pathway. Almost all these proteins exhibited different expression levels in the three stages. The results of the present study provide a better understanding of the molecular mechanisms of early embryonic development and suggest new treatment methods for infertility.


Assuntos
Desenvolvimento Embrionário/genética , Oócitos/crescimento & desenvolvimento , Biossíntese de Proteínas/genética , Proteômica , Animais , Feminino , Fertilização in vitro , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Meiose/genética , Camundongos , Oócitos/metabolismo , Oogênese/genética , Gravidez , Reprodução/genética , Transdução de Sinais , Zigoto/crescimento & desenvolvimento
10.
J Obstet Gynaecol ; 35(5): 508-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25549755

RESUMO

The aim of this study is to investigate the accuracy and adequacy of the Pipelle endometrial sampler for endometrial biopsy as compared with those of conventional dilatation and curettage (D&C). A total of 245 patients subject to endometrial biopsy were included in this study. We have shown that the failure rates with D&C and Pipelle were 7.75% and 8.98%, respectively, without statistical difference. Additionally, the obtained specimen quality and accurate diagnosis of various diseases using the two methods had no significant statistical differences. Furthermore, patients experienced less pain when Pipelle sampler was used than D&C. Therefore, Pipelle sampler is effective in obtaining adequate endometrial tissue for histodiagnosis, and is applicable in most of the cases for Chinese endometrial biopsy.


Assuntos
Dilatação e Curetagem/instrumentação , Endométrio/patologia , Adulto , Biópsia/instrumentação , Dilatação e Curetagem/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Dor/etiologia
11.
Eur Rev Med Pharmacol Sci ; 27(20): 9586-9600, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37916325

RESUMO

OBJECTIVE: Vacuolar protein sorting-associated protein 29 (VPS29) plays a certain role in cancer, but its biological significance in hepatocellular carcinoma (HCC) has not been studied. We utilized bioinformatics and Mendelian randomization (MR) analysis to explore the potential function of the VPS29 gene in HCC, as well as the causal relationship between VPS29 protein and HCC. MATERIALS AND METHODS: We downloaded the raw data from TCGA, GEO, and IEU OpenGWAS databases. We used R software for data processing and analysis to explore the relationship between the VPS29 gene and the expression, prognosis, clinical features, methylation, immune microenvironment, tumor mutation burden, and drug sensitivity in HCC patients. Additionally, a two-sample Mendelian randomization analysis was conducted to investigate the causal relationship between the VPS29 protein and HCC. RESULTS: VPS29 was found to be overexpressed in various types of cancer, including HCC, and its elevated expression often predicts poor prognosis in HCC patients. Univariate and multivariate Cox analysis demonstrated that VPS29 was an independent prognostic factor in HCC patients. The ROC curve indicated that VPS29 has a high diagnostic value in HCC. There were differential expressions of VPS29 in various clinical feature subgroups. The expression of VPS29 was negatively correlated with methylation levels, and multiple methylation sites were identified in the promoter region, including cg20877181, cg03867797, cg10025392, cg21605021, which were associated with poorer overall survival (OS) at low methylation levels. VPS29 was associated with immune cell infiltration disorders, including CD8+ T cells, Eosinophils, Neutrophils, Tcm, NK CD56bright cells, TFH, Th2 cells, Th17 cells, etc. Drug sensitivity analysis showed that VPS29 could be indicative of treatment response to 10 common antineoplastic drugs in different expression subgroups. Inverse variance weighted (IVW) analysis revealed a significant increase in HCC risk associated with VPS29 [odds ratio (OR): 1.440; 95% confidence interval (CI): 1.195-1.736], and sensitivity analysis showed no heterogeneity or pleiotropy. CONCLUSIONS: VPS29 is a risk factor for the occurrence and progression of HCC and may serve as a molecular biomarker for the diagnosis and prognosis of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Análise da Randomização Mendeliana , Neoplasias Hepáticas/genética , Fatores de Risco , Biologia Computacional , Prognóstico , Microambiente Tumoral , Proteínas de Transporte Vesicular/genética
12.
Sci Adv ; 6(37)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32917695

RESUMO

Embryonic diapause is a maternally controlled phenomenon. The molecule controlling the onset of the phenomenon is unknown. We demonstrated that overexpression of microRNA let-7a or incubation with let-7g-enriched extracellular vesicles from endometrial epithelial cells prolonged the in vitro survival of mouse blastocysts, which developed into live pups after having been transferred to foster mothers. Similar to in vivo dormant blastocysts, let-7-induced dormant blastocysts exhibited low level of proliferation, apoptosis, and nutrient metabolism. Let-7 suppressed c-myc/mTORC1 and mTORC2 signaling to induce embryonic diapause. It also inhibited ODC1 expression reducing biosynthesis of polyamines, which are known to reactivate dormant embryos. Furthermore, the overexpression of let-7 blocked trophoblast differentiation and implantation potential of human embryo surrogates, and prolonged survival of human blastocysts in vitro, supporting the idea that embryonic diapause was an evolutionary conserved phenomenon. In conclusion, let-7 is the main factor inducing embryonic diapause.


Assuntos
Diapausa , Vesículas Extracelulares , MicroRNAs , Animais , Blastocisto/fisiologia , Implantação do Embrião/genética , Desenvolvimento Embrionário/genética , Endométrio/metabolismo , Vesículas Extracelulares/metabolismo , Feminino , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo
13.
Eur Rev Med Pharmacol Sci ; 24(3): 1481-1491, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32096198

RESUMO

OBJECTIVE: This study aimed to investigate the efficacy and molecular mechanisms of ZSP1603 as a novel anti-fibrotic compound. MATERIALS AND METHODS: The unilateral left pulmonary fibrosis model was established in the Sprague Dawley (SD) rats. The bilateral pulmonary fibrosis model was established in the C57BL/6J mice. The therapeutic treatment regimen began after the induction of pulmonary fibrosis. The preventive treatment regimen began on the first day of bleomycin administration. Animals were randomly divided into the sham, model, Nintedanib, and ZSP1603 treatment groups. Haematoxylin and eosin (H&E) and Masson's trichrome staining were performed to evaluate pulmonary injury, inflammation, and fibrosis. Cell Counting Kit-8 (CCK-8) assay and Western blot were used to investigate the effects and mechanisms of ZSP1603 on the proliferation of primary human pulmonary fibroblasts (pHPFs). The messenger ribonucleic acid (mRNA) expression of transforming growth factor (TGF)-ß1, tissue inhibitor of metalloproteinase 1 (TIMP-1), and collagen 1A1 (COL1A1) in pHPFs was detected by quantitative Real Time-Polymerase Chain Reaction (PCR). RESULTS: ZSP1603 inhibited the proliferation of pHPFs in vitro by blocking the platelet-derived growth factor receptor-ß (PDGF-Rß) and extracellular signal-regulated kinase (ERK) signalling pathway. ZSP1603 also inhibited the differentiation of pHPFs by reducing the expression of TGF-ß1, TIMP-1, and COL1A1. ZSP1603 significantly attenuated pulmonary injury, inflammation, and fibrosis in vivo in four independent animal studies of pulmonary fibrosis. CONCLUSIONS: ZSP1603 is an effective anti-fibrotic compound with clear mechanisms.


Assuntos
Antifibrinolíticos/uso terapêutico , Modelos Animais de Doenças , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Fibrose Pulmonar/tratamento farmacológico , Animais , Antifibrinolíticos/química , Antifibrinolíticos/farmacologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/metabolismo , Fibrose Pulmonar/enzimologia , Fibrose Pulmonar/patologia , Ratos , Ratos Sprague-Dawley
14.
Placenta ; 30(1): 74-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19007982

RESUMO

The regulation of trophoblast cell invasion is a crucial aspect of implantation and placental development. Evidence indicates that the uterine microenvironment exerts important influence over trophoblast cell invasion. However, the precise effect of decidual cells on trophoblast cell invasion remained unidentified. In the present study, a cell line representative of normal human trophoblast (B6Tert) was used to examine the effect of decidual stromal cell conditioned media (DSCM) on trophoblast cell invasion. In vitro assay showed the concentration-dependent effect of DSCM on B6Tert cell invasion. RT-PCR and gelatin zymography demonstrated that DSCM evidently produced an effect on the mRNA expression and proenzyme production of MMP-2 in a dose-dependent manner, but exerted no effect on mRNA expression and proenzyme production of MMP-9. The data indicates that the decidual microenvironment may exert the key control for trophoblast cell invasion mainly through influencing MMP-2 expression.


Assuntos
Decídua/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Trofoblastos/efeitos dos fármacos , Adulto , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Decídua/metabolismo , Relação Dose-Resposta a Droga , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , RNA Mensageiro/metabolismo , Células Estromais/metabolismo , Trofoblastos/citologia , Trofoblastos/fisiologia , Adulto Jovem
15.
Plant Biol (Stuttg) ; 11(1): 57-67, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19121114

RESUMO

Phenotypic and genotypic characteristics of 48 Phytophthora infestans isolates, collected in five provinces in Northern China between 1997 and 2003, were determined and compared with reference isolates. Characterisation included mating type, virulence, mitochondrial DNA (mtDNA) haplotype and DNA fingerprinting patterns based on simple sequence repeats (SSR) and amplified fragment length polymorphisms (AFLP). All isolates had the A1 mating type, mtDNA haplotype IIa and an identical SSR genotype (designated as SG-01-01) that differed from SSR genotypes found in the reference isolates, including those representing the 'old' US-1 lineage that dominated the P. infestans population worldwide prior to 1980. In contrast, the virulence spectra were highly variable and virulence to all resistance genes present in the standard differential set (R1 to R11) was found. AFLP analysis revealed some diversity; eight different AFLP genotypes were found that could be grouped into two major clusters. This study shows that there is very little genotypic diversity in the P. infestans population in Northern China. The occurrence of many different races within this rather uniform population is discussed in the framework of recent insights into the molecular determinants of avirulence in potato-P. infestans'gene-for-gene' interactions.


Assuntos
Variação Genética , Phytophthora infestans/genética , Phytophthora infestans/patogenicidade , Doenças das Plantas/microbiologia , Solanum tuberosum/microbiologia , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados/métodos , China , DNA Mitocondrial/genética , Genótipo , Haplótipos , Repetições Minissatélites , Fenótipo , Dinâmica Populacional , Virulência/genética
16.
Fertil Steril ; 71(2): 232-9, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9988390

RESUMO

OBJECTIVE: To investigate the effect of human oviductal cells on various sperm functions in vitro. DESIGN: Controlled experimental laboratory study. SETTING: University gynecology unit. PATIENT(S): Women undergoing tubal ligation or hysterectomy and men who were visiting our subfertility clinics. INTERVENTION(S): Coculture of oviductal cells with human spermatozoa in vitro; sperm functions were determined after coculture. MAIN OUTCOME MEASURE(S): Capacitation, acrosome reaction, zona binding, and oocyte fusion. RESULT(S): Oviductal cells and conditioned medium induced more spermatozoa to capacitate than did control medium. Although there was no difference in the spontaneous acrosome reaction between any of the groups, the coculture group had a lower percentage of acrosome-reacted spermatozoa after calcium ionophore challenge than did the control and conditioned medium groups. Coculture and conditioned medium treatment reduced the number of spermatozoa bound to the zona pellucida. The penetration rate and penetration index of the control spermatozoa in the zona-free hamster oocyte penetration test were significantly higher than that of the cocultured or conditioned medium-treated spermatozoa. CONCLUSION(S): Human oviductal cells promoted capacitation, stabilized the acrosome, and suppressed binding to the zona pellucida and fusion with the oocyte in vitro.


Assuntos
Tubas Uterinas/citologia , Interações Espermatozoide-Óvulo , Reação Acrossômica , Animais , Fusão Celular , Técnicas de Cocultura , Cricetinae , Meios de Cultivo Condicionados , Feminino , Humanos , Masculino , Oócitos/citologia , Capacitação Espermática , Zona Pelúcida
17.
Trans R Soc Trop Med Hyg ; 87(3): 319-21, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8236407

RESUMO

Fourteen cases of alveolar echinococcosis were examined by computed tomographic (CT) scanning of the liver, including 3 cases before treatment and 11 cases 2.0-7.5 years after long-term continuous albendazole therapy. In 7 cases the hepatic lesions were almost completely calcified and cured, while in 3 cases incomplete calcification of the peripheral margin of the hepatic lesions was observed. CT scanning of the one uncured case and the 3 cases before treatment showed active lesions with heterogeneous hypodense areas in the liver without calcification on the peripheral margin. Long-term continuous albendazole therapy can result in parasitological cure with death of the parasite.


Assuntos
Albendazol/uso terapêutico , Equinococose Hepática/diagnóstico por imagem , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Equinococose Hepática/tratamento farmacológico , Equinococose Hepática/patologia , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
18.
Trans R Soc Trop Med Hyg ; 91(4): 476-8, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9373660

RESUMO

Eleven cases of alveolar echinococcosis (Echinococcus multilocularis infection) with non-resectable lesions but treated with albendazole for 17 to 69 months were followed-up clinically and serologically for 4.5-11.5 years. Based on the clinical outcome and computerized tomography (CT) scanning, they were divided into 4 groups of 2 cured cases, 5 stabilized cases, 3 cases with recurrences, and one treatment failure. Forty-seven sequentially collected sera from the 11 cases were analysed by sequential enzyme-linked immunosorbent assay (ELISA) using Em2plus antigen (Em2plus-ELISA) and Western blotting to detect antibody response against Em18 (Em18-Western blots). The antibody levels in one of the cured and 2 of the stabilized cases fell below the cut-off level in the Em2plus-ELISA 4.5-6 years after effective treatment, whereas all other cases, including 2 of those with recurrences, showed large reductions initially but increased again during the follow-up period. Em18-Western blots of the 2 cured cases and 2 of the stabilized cases became negative. IgG subclasses with responses against Em18 which fell to zero included IgG1 (2), IgG3 (one) and IgG4 (one). All other cases showed no decrease in antibody response against Em18. There were, in general, reasonably reliable correlations between the success or failure of chemotherapy and antibody responses by Em2plus-ELISA and Em18-Western blots. These results suggest that both Em2plus-ELISA and Em18-Western blot are potentially useful in evaluating and predicting the efficacy of chemotherapy.


Assuntos
Albendazol/uso terapêutico , Anticestoides/uso terapêutico , Equinococose Pulmonar/tratamento farmacológico , Adulto , Anticorpos Anti-Helmínticos/sangue , Western Blotting , Equinococose Pulmonar/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/análise , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
19.
Contraception ; 66(6): 453-7, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12499039

RESUMO

Two doses of 750-microg levonorgestrel at 12 h apart is one of the regimens for emergency contraception. The mechanism of action of this regimen is not fully known. We investigated whether levonorgestrel influences sperm functions and thereby, exerts contraceptive activity. The motility, acrosome reaction, zona binding capacity, and oocyte fusion capacity of human spermatozoa treated with 1, 10, and 100 ng/mL levonorgestrel for 3 h were evaluated. Levonorgestrel decreased the curvilinear velocity of the treated spermatozoa in a dose-dependent manner. A significant decrease in straight-line velocity, average path velocity and linearity were also found with 100 ng/mL levonorgestrel treatment. This concentration of levonorgestrel, but not others, also marginally decreased (p = 0.045) the zona binding capacity of the treated spermatozoa. The steroid had no effect on acrosome reaction but had a dose-dependent inhibition on spermatozoa-oocyte fusion. These data show that levonorgestrel affects sperm function only at high concentration and the contribution of these effects to emergency contraception is unlikely to be significant.


Assuntos
Anticoncepcionais Pós-Coito/farmacologia , Levanogestrel/farmacologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Reação Acrossômica/efeitos dos fármacos , Animais , Cricetinae , Relação Dose-Resposta a Droga , Feminino , Humanos , Levanogestrel/administração & dosagem , Masculino , Motilidade dos Espermatozoides/efeitos dos fármacos , Interações Espermatozoide-Óvulo/efeitos dos fármacos , Zona Pelúcida/metabolismo
20.
Chin Med J (Engl) ; 107(10): 750-4, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7835101

RESUMO

To assess the value of intravascular ultrasound in detecting carotid atherosclerosis, we compared the ultrasound images of 48 carotid artery segments from autopsies with their histological findings. The results showed that by intravascular ultrasonography one could distinguish between elastic and muscular tissues of arteries, determine the lesions of fibroelastosis and calcified plaques on arterial wall, and precisely measure the wall thickness, inner and outer diameter, luminal area and cross-sectional area of arteries with a high correlation between the data measured from ultrasonography and histological study (r values were 0.98, 0.97, 0.97, 0.96 and 0.96, respectively). This study suggests that intravascular ultrasound might be effectively used for morphological study and detection of atherosclerotic lesions in vivo.


Assuntos
Arteriosclerose/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Ultrassonografia de Intervenção , Idoso , Arteriosclerose/patologia , Doenças das Artérias Carótidas/patologia , Artéria Carótida Externa/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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