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Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), pegylated-interferon-α(PEG-IFNα) and long-term nucleos(t)ide analogs (NUCs) are mainly drugs used to treat HBV infection, but the effectiveness is unsatisfactory in different populations, the exploration of novel therapeutic approaches is necessary. RAD51C is associated with DNA damage repair and plays an important role in the development and progression of tumors. Early cDNA microarray results showed that RAD51C expression was significantly increased in HBV-infected HCC cells, however, the relationship between HBV infection and abnormal expression of RAD51C has not been reported. Therefore, we conducted RT-PCR, western blot, Co-immunoprecipitation(Co-IP), and immunofluorescence(IF) to detect HBV-RAD51C interaction in RAD51C overexpression or interfering HCC cells. Our results showed that RAD51C and HBV X protein(HBX) produced a direct interaction in the nucleus, the HBV infection of HCC cells promoted RAD51C expression, and the increased expression of RAD51C promoted HBV replication. This indicated that RAD51C is closely related to the occurrence and development of HCC caused by HBV infection, and may bring a breakthrough in the the prevention and treatment study of HCC.
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Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Hepatite B/complicações , Hepatite B/genética , Expressão Gênica , Replicação Viral , Proteínas de Ligação a DNA/genéticaRESUMO
Injury to the anterior talofibular ligament (ATFL) is a common acute injury of the lateral foot ligament. Untimely and improper treatment significantly affects the quality of life and rehabilitation progress of patients. The purpose of this paper is to review the anatomy and the current methods of diagnosis and treatment of acute injury to the ATFL. The clinical manifestations of acute injury to the ATFL include pain, swelling, and dysfunction. At present, non-surgical treatment is the first choice for acute injury of the ATFL. The standard treatment strategy involves the "peace and love" principle. After initial treatment in the acute phase, personalized rehabilitation training programs can be followed. These may involve proprioception training, muscle training, and functional exercise to restore limb coordination and muscle strength. Static stretching and other techniques to loosen joints, acupuncture, moxibustion massage, and other traditional medical treatments can relieve pain, restore range of motion, and prevent joint stiffness. If the non-surgical treatment is not ideal or fails, surgical treatment is feasible. Currently, arthroscopic anatomical repair or anatomical reconstruction surgery is commonly used in clinical practice. Although open Broström surgery provides good results, the modified arthroscopic Broström surgery has many advantages, such as less trauma, rapid pain relief, rapid postoperative recovery, and fewer complications, and is more popular with patients. In general, when treating acute injury to the ATFL, treatment management and methods should be timely and reasonably arranged according to the specific injury scenario and attention should be paid to the timely combination of multiple therapies to achieve the best treatment results.
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Objectives: Subject to ethical constraints, real-world data are an important resource for evaluating treatment effects of medication use during pregnancy and the postpartum period. This study investigated whether motherwort injection, a traditional Chinese medicine preparation, was more effective than intramuscular (IM) oxytocin for preventing postpartum hemorrhage (PPH) in a real-world setting when intravenous (IV) oxytocin is administered. Methods: We conducted an active-controlled, propensity-score matched cohort study using an established pregnancy registry database. Women who underwent cesarean section and received IV oxytocin at the third stage of labor were included. We used an active-comparator design to minimize indication bias, in which we compared IM motherwort injection in the uterus versus IM oxytocin, both on top of IV oxytocin use. We applied 1:1 propensity-score matching (PSM) to balance patient baseline characteristics and used a logistic regression model to estimate treatment effect (i.e., risk difference (RD) and odds ratio (OR)) by using the counterfactual framework. The outcomes of interest were blood loss over 500 ml within 2 h after delivery (PPH, primary) and blood loss over 1,000 ml (severe PPH, secondary). We conducted four sensitivity analyses to examine the robustness of the results. Results: A total of 22,519 pregnant women underwent cesarean sections, among which 4,081 (18.12%) PPH and 480 (2.13%) severe PPH occurred. Among included women, 586 (2.60%) were administrated with IM motherwort injection, and 21,933 (97.40%) used IM oxytocin. After PSM, patient baseline characteristics were well balanced. Compared with IM oxytocin, the use of IM motherwort injection was associated with significantly lower risk of PPH (RD -25.26%, 95% CI -30.04% to -20.47%, p < 0.001; OR 0.25, 95% CI 0.18 to 0.32, p < 0.001) and severe PPH (RD -3.58%, 95% CI -5.87% to -1.30%, p < 0.001; OR 0.39, 95% CI 0.20 to 0.71, p < 0.002). Sensitivity analyses showed that the results were similar. Conclusion: With the use of data from a real-world setting, the findings consistently showed that among women undergoing cesarean section who had received IV oxytocin, the additional use of IM motherwort injection could achieve a lower risk of PPH as compared to the additional use of IM oxytocin. Our study suggested a paradigm for investigating the treatment effect of Chinese herbal medicine in the real-world practice setting.
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BACKGROUND: Downstream of tyrosine kinase 6 (DOK6), which is specifically expressed in the nervous system, was previously recognized as an adapter only in neurite outgrowth. Recent studies also demonstrated the potential role of DOK6 in solid tumors such as gastric cancer and breast cancer. However, previous studies of DOK6 have not dealt with its roles in myeloid malignancies. Herein, we verified the promoter methylation status of DOK6 and further explored its clinical implication in de novo acute myeloid leukemia (AML). METHODS: A total of 100 newly diagnosed adult AML patients were involved in the current study. DOK6 expression and methylation were detected by real-time qPCR and methylation-specific PCR (MSP), respectively. Bisulfite sequencing PCR (BSP) was performed to assess the methylation density of the DOK6 promoter. RESULTS: Downstream of tyrosine kinase 6 promoter methylation was significantly increased in AML patients compared to controls (P = .037), whereas DOK6 expression significantly decreased in AML patients (P < .001). The expression of DOK6 was markedly up-regulated after treated by 5-aza-2'-deoxycytidine (5-aza-dC) in THP-1 cell lines. The methylation status of the DOK6 promoter was associated with French-American-British classifications (P = .037). There was no significant correlation existed between DOK6 expression and its promoter methylation (R = .077, P = .635). Interestingly, of whole-AML and non-APL AML patients, both have a tendency pertaining to the DOK6 methylation group and a significantly longer overall survival (OS) than the DOK6 unmethylation group (P = .042 and .036, respectively). CONCLUSION: Our study suggested that DOK6 promoter hypermethylation was a common molecular event in de novo AML patients. Remarkably, DOK6 promoter methylation could serve as an independent and integrated prognostic biomarker not only in non-APL AML patients but also in AML patients who are less than 60 years old.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Metilação de DNA , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Regiões Promotoras Genéticas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biomarcadores Tumorais , Linhagem Celular Tumoral , Epigênese Genética , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Adulto JovemRESUMO
BACKGROUND: To assess whether the peri-conceptional or pregnancy exposure of human papillomavirus (HPV) vaccination would increase the risk of spontaneous abortion. METHODS: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for clinical trials and observational studies that investigated the association between exposure of HPV vaccines (2vHPV, 4vHPV or 9vHPV) during peri-conceptional period or pregnancy and spontaneous abortion before 28 gestational weeks. We pooled data from 2vHPV, 4vHPV and 9vHPV separately. Subgroup analyses were conducted according to data sources, and raw data or adjusted data. RESULTS: Seven observational studies were eligible and all studies were low risk of bias. Meta-analyses suggested that 2vHPV vaccination did not increase the risk of spontaneous abortion regardless of exposure period during 90 days before last menstrual period (LMP) or pregnancy: risk ratio, 95% confidence intervals (RR, 95% CI), 1.15 (0.95-1.39), and 45 days before LMP or pregnancy: 1.28 (0.96-1.70). However, 2vHPV vaccination during Pre-45 days to LMP seemed to increase the risk of spontaneous abortion: 1.59 (1.04-2.45). The current evidence did not support the association between 4vHPV vaccination and spontaneous abortion regardless of exposure period during 45 days before LMP or pregnancy: 0.88 (0.73-1.06); and 45 days before LMP: 1.00 (0.80-1.24). Additionally, 9vHPV during within 30 days of conception also seemed to increase the risk: 2.04 (1.28-3.24). CONCLUSIONS: The association between peri-conceptional or pregnancy exposure of HPV vaccine and spontaneous abortion is still uncertain, and additional research is warranted to assess the impact of exposure of HPV vaccination on spontaneous abortion.
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Aborto Espontâneo/induzido quimicamente , Exposição Materna/efeitos adversos , Vacinas contra Papillomavirus/efeitos adversos , Cuidado Pré-Concepcional/métodos , Feminino , Humanos , Vacinas contra Papillomavirus/administração & dosagem , Gravidez , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: BCL2 protein inhibitor venetoclax (ABT-199) has been authorized by Food and Drug Administration for relapsed/refractory chronic lymphoid leukemia with 17p deletion. Although venetoclax/ABT-199 also caused cell death in acute myeloid leukemia (AML), whether it could be applied to clinical treatment needs further studies. Here, we revealed clinical implication of BCL2 overexpression in de novo adult AML, and may provide theoretical basis for targeted therapy using venetoclax. METHODS: BCL2 expression was analyzed in adult AML patients from public datasets The Cancer Genome Atlas (TCGA) and confirmed by another independent cohort from our own data. RESULTS: BCL2 expression showed up-regulated in AML patients among TCGA data and confirmed by our own data. BCL2 overexpression was correlated with FAB-M0/M1, whereas BCL2 under-expression was related to FAB-M5. However, BCL2 expression has no effect on overall survival (OS) and leukemia-free survival (LFS) of AML patients (determined in BCL2low and BCL2high groups). Interestingly, in the BCL2low group, patients undergoing autologous or allogeneic hematopoietic stem cell transplantation (auto/allo-HSCT) had significantly better OS and LFS compared with patients only received chemotherapy, whereas, no significant difference was found in OS and LFS between chemotherapy and auto/allo-HSCT patients in the BCL2high group. BCL2 expression was found positively correlated with HOX family gene, and negatively correlated with tumor suppressor microRNA such as miR-195, miR-497, and miR-193b. CONCLUSIONS: BCL2 overexpression identified specific FAB subtypes of AML, but it did not affect prognosis. Patients with BCL2 overexpression did not benefit from auto/allo-HSCT among whole-cohort-AML and cytogenetically normal AML.
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Regulação Neoplásica da Expressão Gênica/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Regulação para Cima , Adulto JovemRESUMO
Placental hypoxia serves a role in the early stages of normal pregnancy and is involved in the pathophysiology of preeclampsia. Previously, it was suggested that p57kinase inhibitory protein (KIP)2 regulates the cell cycle during embryogenesis and apoptosis. Recent evidence has indicated that p57KIP2 is increased in preeclamptic placentas and absence of p57KIP2 induces preeclampsiatype symptoms in rats. However, effects of p57KIP2 on apoptosis under hypoxic conditions remain to be elucidated. In the present study, HTR8/SVneo trophoblasts were cultured under hypoxic conditions (2% O2). Knockdown using small interfering (si)RNA and overexpression of p57KIP2 were utilized to explore the biological function of p57KIP2 in apoptosis and cell function in vitro. Furthermore, expression of p57KIP2 and apoptosis were evaluated by western blotting, flow cytometry and TUNEL assays, and the response of trophoblasts to hypoxia and the role of p57KIP2 in trophoblast migration and invasion was assessed. The role of p57KIP2 in the JNK signaling pathway in HTR8/SVneo trophoblasts was further studies. In vitro, protein expression of p57KIP2 was increased in HTR8/SVneo cells exposed to 2% O2. Exogenous p57KIP2 overexpression significantly decreased the expression of proapoptosis proteins, including p53, Bax and cleaved caspase3, under hypoxic conditions for 24 h. In addition, knockdown of p57KIP2 increased the response to apoptosis following hypoxia for 24 h. The present study revealed that overexpression of p57KIP2 decreased the levels of phosphorylatedJNK. JNK inhibitor treatment combined with the overexpression of p57KIP2 significantly decreased the levels of apoptosis and increased cell invasion and migration. Taken together, p57KIP2 knockdown significantly increased apoptosis in HTR8/SVneo cells exposed to 2% O2, whereas overexpression of p57KIP2 had opposite effects, mediated by the JNK/stress activated protein kinase (SAPK) signaling pathway. The results indicated that hypoxiainduced expression of p57KIP2 promoted trophoblast migration and invasion by mediating the JNK/SAPK signaling pathway, which is crucial during placentation. These results may provide a novel molecular mechanism to understand the involvement of p57KIP2 in the pathogenesis of preeclampsia.
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Apoptose , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Sistema de Sinalização das MAP Quinases , Pré-Eclâmpsia/metabolismo , Trofoblastos/metabolismo , Caspase 3/metabolismo , Hipóxia Celular , Linhagem Celular , Feminino , Humanos , Pré-Eclâmpsia/patologia , Gravidez , Trofoblastos/patologia , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Cancer is the second leading cause of mortality worldwide. More importantly, the mortality rates for cancer are increasing. In China, lung cancer, liver cancer and gastric cancer are the top three leading causes of mortality in males, whereas lung cancer, gastric cancer and liver cancer are ranked the top three causes of mortality in females. Exosomes are extracellular vesicles that are produced and released by many different cells; these vesicles have a size range between 30 and 100 nm in diameter, and contain a lipid bilayer. Exosomes exist in various bodily fluids, contain plentiful amounts of nucleic acids and proteins, and shuttle these materials between cells to mediate the development of cancers. The present review summarizes the composition of exosomes and methods for their isolation and then intensively highlights the latest findings on the contributions of exosomal microRNAs (miRNAs) and proteins to lung cancer, liver cancer and gastric cancer. Taken together, exosomal miRNAs and proteins may be used as noninvasive, novel biomarkers for cancer diagnosis, prognosis or precision treatment owing to their ability to promote tumor progression and metastasis, and their ability to regulate the immune response and tumor cell sensitivity to chemotherapy drugs.
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BACKGROUND: The effect of maternal weights on the risk of iron deficiency anemia (IDA) during pregnancy remains unclear. The study aimed to investigate the association between maternal weight indicators and IDA during pregnancy. METHODS: We conducted a cohort study to examine the association between maternal weight indicators, including prepregnancy body mass index and the rate of gestational weight gain (GWG), and the risk of IDA among Chinese pregnant women. Data about new-onset IDA at different trimesters from a national cross-sectional survey were collected; information regarding baseline variables and rate of GWG from women participating in the survey were retrospectively collected. Tested IDA and reported IDA were documented. Multilevel logistic regression to examine the association between maternal weight indicators and the risk of IDA after adjusting for potential confounders was conducted. RESULTS: This study enrolled 11,782 pregnant women from 24 hospitals from September 19, 2016, to November 20, 2016. Among those, 1515 (12.9%) IDA events were diagnosed through test (test IDA); 3915 (33.3%) were identified through test and patient reporting (composite IDA). After adjusting for confounders and cluster effect of hospitals, underweight pregnant women, compared with normal women, were associated with higher risk of test IDA (adjusted odds ratio [aOR]: 1.35, 95% confidence interval [CI]: 1.17-1.57 and composite IDA (aOR: 1.35, 95% CI: 1.21-1.51); on the contrary, overweight and obese women had lower risk of test IDA (aOR: 0.68, 95% CI: 0.54-0.86 overweight; aOR: 0.30, 95% CI: 0.13-0.69 obese) and composite IDA (aOR: 0.77, 95% CI: 0.67-0.90 overweight; aOR: 0.34, 95% CI: 0.21-0.55 obese). The higher rate of GWG was associated with higher risk of IDA (test aOR: 1.86 95% CI: 1.26-2.76; composite aOR: 1.54, 95% CI: 1.16-2.03). CONCLUSIONS: Pregnant women who are underweight before pregnancy and who have faster GWG are more likely to develop IDA. Enforced weight control during pregnancy and use of iron supplements, particularly among underweight women, may be warranted.
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Anemia Ferropriva/metabolismo , Anemia Ferropriva/patologia , Adulto , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Feminino , Ganho de Peso na Gestação/fisiologia , Humanos , Gravidez , Estudos RetrospectivosRESUMO
Despite implications of persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the development of hepatocellular carcinoma (HCC), little is known about serum cccDNA in HBV-infected diseases. We developed a cccDNA-selective droplet digital PCR (ddPCR) to assess cccDNA content and dynamics across different stages of HCC development. One hundred forty-seven serum samples and 35 formalin-fixed, paraffin-embedded tumor tissues were derived from patients with HCC or HBV hepatitis/cirrhosis. After specific amplification and selective digestion, probe-based ddPCR was used to quantify cccDNA copy numbers in single cells and clinical samples. The cccDNA in single HepG2.2.15 cells ranged from 0 to 10.8 copies/cell. Compared with non-HCC patients, HCC patients showed a higher cccDNA-positive rate (89.9% versus 53.2%; P = 4.22 × 10-6) and increased serum cccDNA contents (P = 0.002 and P = 0.041 for hepatitis and cirrhosis patients, respectively). Serum cccDNA ranged from 84 to 1.07 × 105 copies/mL. Quantification of serum cccDNA and HBV-DNA was an effective way to discriminate HCC patients from non-HCC patients, with areas under the curve of receiver operating characteristic of 0.847 (95% CI, 0.759-0.935; sensitivity, 74.5%; specificity, 93.7%). cccDNA-selective ddPCR is sensitive to detect cccDNA in single cells and different clinical samples. Combined analysis of serum cccDNA and HBV-DNA may be a promising strategy for HBV-induced HCC surveillance and antiviral therapy evaluation.
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DNA Circular/sangue , DNA Viral/sangue , Vírus da Hepatite B/genética , Reação em Cadeia da Polimerase/métodos , Adulto , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Feminino , Dosagem de Genes , Células Hep G2 , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC). Kinesin family member 4A (KIF4A) is a microtubulebased motor protein, which is upregulated in cervical and lung cancer. However, the expression of KIF4A in HBVassociated HCC, and the effect of HBV on the expression of KIF4A remain to be elucidated. In the present study, the expression profiles of KIF4A were examined in cancerous tissues and paracancerous tissues from patients with HCC, who presented with histories of chronic HBV infection, and the role of HBV in the induction of the expression of KIF4A was investigated. HepG2 cells were transfected with the pHBV1.3, HBV infectious clone and a construct, which contained the luciferase gene under the control of the KIF4A gene promoter. The results demonstrated that the expression of KIF4A was significantly higher in the HCC tissues than in the paracancerous tissues. HBV activated the KIF4A gene promoter and upregulated the mRNA and protein expression of KIF4A. Furthermore, activation of the gene expression of KIF4A increased in a pHBV1.3 concentrationdependent manner. These results provide novel insights into the understanding of HCC oncogenesis caused by HBV.
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Carcinoma Hepatocelular/metabolismo , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/metabolismo , Cinesinas/genética , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Hepatite B Crônica/complicações , Hepatite B Crônica/genética , Humanos , Cinesinas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Regulação para CimaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is strongly associated with hepatitis B virus (HBV) infection. False-negative results are common in routine serological tests and quantitative real-time PCR because of HBV surface antigen (HBsAg) variation and low HBV copy number. Droplet digital PCR (ddPCR), a next generation digital PCR, is a novel, sensitive, and specific platform that can be used to improve HBV detection. METHODS: A total of 131 HCC cases with different tumor stages and clinical features were initially classified with a serological test as HBsAg positive (n = 107) or negative (n = 24) for HBV infection. Next, DNA templates were prepared from the corresponding formalin-fixed paraffin-embedded (FFPE) tissues to determine HBV copy number by ddPCR. RESULTS: HBV copy numbers, successfully determined for all clinical FFPE tissues (n = 131), ranged from 1.1 to 175.5 copies/µL according to ddPCR. The copy numbers of HBV were positively correlated with tumor-nodes-metastasis (P = 0.008) and Barcelona-Clinic Liver Cancer (P = 0.045) classification. Moreover, serum cholinesterase correlated with hepatitis B viral load (P = 0.006). CONCLUSIONS: HBV infection is a key factor that influences tumorigenesis in HCC by regulating tumor occurrence and development. ddPCR improves the analytical sensitivity and specificity of measurements in nucleic acids at a single-molecule level and is suitable for HBV detection.
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Carcinoma Hepatocelular/virologia , Dosagem de Genes , Vírus da Hepatite B/isolamento & purificação , Hepatite B/virologia , Neoplasias Hepáticas/virologia , Carcinoma Hepatocelular/patologia , DNA Circular/genética , DNA Viral/genética , Feminino , Hepatite B/patologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inclusão em Parafina , Reação em Cadeia da Polimerase/métodosRESUMO
Novel 2H-benzo[b][1,4]oxazin-3(4H)-ones have been synthesized by condensation, reduction, O-alkylation and Smiles rearrangement using 3-bromo-4-hydroxy benzaldehyde, anilines, and chloroacetyl chloride as starting materials. All the synthesized compounds have been characterized by (1)H NMR, (13)C NMR, and HRMS, and tested for the inhibitory ability on platelet aggregation. The results have shown that the ADP (adenosine 5'-diphosphate)-induced platelet aggregation was inhibited by 7a-g with the IC(50) value at 10.14-18.83 µmol/L. Compound 7a exhibited the most potent inhibitory effect (IC(50)=10.14 µmol/L) among all the compounds, but less potent than the control drug ticlopidine (3.18 µmol/L) and aspirin (6.07 µmol/L). The preliminary structure-activity relationship (SAR) was initially investigated in the study.
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Benzoxazinas/farmacologia , Química Farmacêutica/métodos , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/farmacologia , Antineoplásicos/farmacologia , Aspirina/farmacocinética , Benzoxazinas/síntese química , Desenho de Fármacos , Glicoproteínas/química , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética/métodos , Modelos Químicos , Modelos Moleculares , Agregação Plaquetária/efeitos dos fármacos , Relação Estrutura-Atividade , Ticlopidina/farmacocinéticaAssuntos
Ácidos e Sais Biliares/sangue , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/tratamento farmacológico , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/epidemiologia , Feminino , Monitorização Fetal , Humanos , Testes de Função Hepática , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Prurido/sangue , Prurido/diagnóstico , Prurido/tratamento farmacológico , S-Adenosilmetionina/análogos & derivados , S-Adenosilmetionina/uso terapêutico , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
Sprague-Dawley (SD) rat model of Pneumocystis carinii pneumonia (PCP) was established by groin subcutaneous injection with dexamethasone sodium phosphate 35 mg each twice a week for eight weeks. There were two groups: infected group (eighteen rats) and normal control group (six rats) . Pathological changes in lung tissues were observed in the lung imprint after staining with Gomori methenamine silver (GMS) and in tissue sections after staining with hematoxylin-eosin (HE). The activity of superoxide dismutase (SOD) and the content of lipid peroxide (LPO) in lung tissue homogenate were detected by spectrophotometric method. Results showed that in infected group more PC cysts were found in the lung imprint and typical pathological change observed in the lung section. SOD activity in infected group [(31.49 +/- 7.18) U/mgprot] decreased significantly compared with the control [(54.41 +/- 8.97) U/mgprot] (P < 0.01), but LPO in infected group [(2.26 +/- 0.21) nmol/mgprot] was higher significantly than the control [(1.63 +/- 0.01) nmol/mgprot] (P < 0.01).
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Peróxidos Lipídicos/metabolismo , Pulmão/patologia , Pneumonia por Pneumocystis/metabolismo , Superóxido Dismutase/metabolismo , Animais , Feminino , Pulmão/metabolismo , Masculino , Pneumonia por Pneumocystis/patologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the effect of core protein of hepatitis C virus (HCV) on the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF). METHODS: Huh7.5.1 cells were transfected with plasmid flag2B-core carrying HCV core gene, expression of HIF-1alpha and VEGF were measured by reverse transcription-polymorphism chain reaction (RT-PCR) and western blot. Enzyme link immunoabsorbent assay (ELISA) were used to detect the level of VEGF in the supernatants. RESULTS: The expression of HIF-1alpha and VEGF mRNA and protein were upregulated after flag2B-core was transfected into Huh7.5.1 cells, and VEGF level in the supernatant was significant elevated as compared to controls [(654.5+/-43.7) pg/ml vs (365.9+/-26.8) pg/ml, t = 653.1%, P less than 0.01]. The expression of HIF-1alpha and VEGF mRNA and protein were downregulated after flag2B-core and HIF-1alpha siRNA were co-transfected into Huh7.5.1 cells, and VEGF level in the supernatant was significantly reduced as compared to controls [(389.2+/-29.6) pg/ml vs (768.8+/-47.3)pg/ml, t = 1330.22, P less than 0.01]. CONCLUSIONS: HCV core protein enhances the expression of HIF-1alpha and VEGF. HCV may regulate the expression of HIF-1alpha and VEGF via the core protein.
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Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Transfecção , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas do Core Viral/genética , Linhagem Celular Tumoral , Humanos , RNA Interferente PequenoRESUMO
OBJECTIVE: To study the expression of vasohibin and vascular endothelial growth factor (VEGF) in placentae from normal pregnancies and pregnancies complicated by severe pre-eclampsia. METHODS: Placental tissues were obtained by caesarean section for 30 cases of pregnancy with severe pre-eclampsia and 30 cases of matched normal pregnancies. Protein levels of vasohibin and VEGF in placental tissue were quantified by Western blot analysis. Immunohistochemistry was used to determine the localization of the vasohibin protein in placental tissue. RESULTS: The mean value of vasohibin in normal pregnant women was 0.91 +/- 0.12, and in women with severe pre-eclampsia was 0.58 +/- 0.09. These values were statistically different between the two groups (P < 0.05). Moreover, VEGF expression was also significantly reduced in the patients compared with the controls (0.65 +/- 0.20 vs. 0.24 +/- 0.13, P < 0.05). There was a significant positive correlation between vasohibin and VEGF levels (r = 0.262, P < 0.05). Immunolocalization of vasohibin in normal term villous placenta was specifically expressed in the vascular endothelial cells, and no positive staining of other cell types such as syncytiotrophoblast cells, cytotrophoblast cells, and chorionic villi interstitial cells was found. CONCLUSION: These results suggest that reduced vasohibin and VEGF expression may be responsible, at least in part, for the impaired vascular development which occurs in the pre-eclampsia.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Proteínas de Ciclo Celular/genética , Feminino , Humanos , Gravidez , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
OBJECTIVE: To find out the bacterial species in the vagina of postpartum women and the possible influencing factors on colonization. METHODS: From Jun. 2007 to Oct. 2007, 560 postpartum women from 7 hospitals in China were enrolled. Questionnaire survey, gynecological examination and Nugent score of vaginal smear and microbial spectrum study of the vaginal flora were completed. RESULTS: (1) According to the Nugent score, 48 out of the 560 women were normal (8.6%), 337 at the borderline (60.2%) and 175 (31.2%) were complicated with bacterial vaginosis (BV). Among the 560 women, Bacterium lacticum were identified in 74 cases (13.2%), but not in the rest 486 cases (86.8%). Gardnerella and bacteroids were detected in 322 women (57.5%) and small flectobacillus in 214 women (38.2%) out of the 560 subjects. (2) Influencing factors on vaginal microflora: among the 266 women who had normal vaginal delivery, 25 (9.4%) showed normal vaginal microflora, 148 (55.6%) at borderline and BV was diagnosed in 93 women (35.0%). The corresponding figures among the 294 women who underwent cesarean section were 23 (7.8%), 189 (64.3%) and 82 (27.9%), respectively. However, the incidence of BV had no statistical difference between these two groups (P = 0.204). In the 233 women who received episiotomy, 22 (9.4%) showed normal vaginal microflora, 135 (57.9%) at borderline and 76 presented with BV (32.6%), the corresponding figures among the 327 women without episiotomy were 26 (8.0%), 202 (61.8%) and 99 (30.2%), respectively. The incidence of BV did not show any statistical difference between the above two groups (P = 0.790). (3) Prenatal vaginitis were reported in 46 women, among which 5 (10.9%) with normal vaginal flora, 26 (56.5%) at borderline and 15 (32.6%) with BV, and again in the 514 women without prenatal vaginits, the above figures changed to 43 (8.4%), 311 (60.5%) and 160 (31.1%). No significant difference was found in the incidence of BV between the two groups (P = 0.962). The rate of BV in women without sex, with sex occasionally and with sex frequently during pregnancy was 27.5% (78/284), 35.6% (96/270) and 1/6, respectively (P = 0.185), and the numbers in women who had breast-feeding, bottle feeding and mixed feeding were 31.0% (67/216), 39.3% (35/89) and 28.6% (73/255), respectively (P = 0.573). CONCLUSIONS: The amount of Lactobacillus in vagina of postpartum women is greatly reduced leading to dysbacteria. The incidence of BV is not affected by vaginal delivery, episiotomy, vaginitis, prenatal intercourse and the way of feeding, but is higher in postpartum women.
Assuntos
Lactobacillus/isolamento & purificação , Período Pós-Parto , Vagina/microbiologia , Vaginose Bacteriana/microbiologia , Adulto , Cesárea , Feminino , Gardnerella/isolamento & purificação , Gardnerella/fisiologia , Humanos , Lactobacillus/fisiologia , Parto Normal , Gravidez , Comportamento Sexual , Esfregaço Vaginal , Vaginite/microbiologia , Vaginose Bacteriana/epidemiologia , Wolinella/isolamento & purificação , Wolinella/fisiologia , Adulto JovemRESUMO
OBJECTIVE: To assess the allele and genotype frequencies of the estrogen receptor alpha ( ESR alpha) Pvu II and Xba I polymorphisms in patients with severe preeclampsia and compare them with those of normal pregnant women. METHODS: Blood samples from 131 patients with severe preeclampsia and 223 normal pregnant women from Chinese Han in Chengdu area were analyzed, using PCR-RFLP method. Pregnant patients with blood pressure exceeding 140/90 mmHg (or 18.7/12 kPa) were recruited with a strict definition of preeclampsia. Genotyping was performed using PCR-RFLP for Pvu II and Xba I polymorphisms in the ESR alpha gene. RESULTS: The T and C allele frequencies for Pvu II site were 0.580 and 0.420 in the patient group, and 0.576 and 0.424 in the controls, respectively. The A and G allele frequencies for Xba I site were 0.763 and 0.237 in the patient group, and 0.807 and 0.193 in control group, respectively. No significant difference in the allele frequencies of either site was observed between the two groups. However, the CC homozygotes or CT heterozygotes in the control pregnant women had higher systolic blood pressure levels than TT homozygotes for Pvu II site after the data was adjusted for age and BMI (114.00+/-21.44 mmHg or 114.33+/-1.21 mmHg vs. 108.62+/-1.91 mmHg, P<0.05). No genotype effect on the blood pressures was found for Pvu II site in the case group, nor for Xba I site in either group. CONCLUSION: Our work has excluded the association of the ESRalpha Pvu II and Xb I polymorphism with severe preeclampsia in a Southwest Chinese population, although this polymorphism may be associated with the systolic blood pressure level in the normal pregnant women.
Assuntos
Povo Asiático/genética , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Receptor alfa de Estrogênio/genética , Polimorfismo Genético , Pré-Eclâmpsia/genética , Adulto , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Genótipo , Humanos , Pré-Eclâmpsia/patologia , GravidezRESUMO
OBJECTIVE: To investigate calcium, iron and magnesium intakes of preterm infants' mothers before and during pregnancy and calcium, iron and magnesium levels of preterm infants and their mothers in order to provide basis for studying the effect of nutritional factors on the occurrence of prematurity. METHODS: Two hundred and forty matched cases (preterm infants and their mothers) and controls (term infants and their mothers) were recruited. A nutritional survey of calcium, iron and magnesium intakes was performed in the mothers before and during pregnancy. Calcium, iron and magnesium levels in maternal plasma and in cord blood, placenta, breast milk, meconium, and amniotic fluid were measured with axial view inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS: Iron and magnesium intakes in preterm infants' mothers were significantly less than those in term infants' mothers before pregnancy (P<0.05). Iron and calcium intakes in preterm infants' mothers were also significantly less than those in term infants' mothers during pregnancy (P<0.05). Multivariate analysis of variance showed that iron and calcium levels of preterm infants' mothers were significantly lower than those of term infants' mothers (P<0.05). The preterm infants showed significantly lower iron and magnesium levels than term infants (P<0.05). Plasma levels of calcium, iron and magnesium in infants were positively correlated to maternal plasma levels of calcium, iron and magnesium (r=0.517, 0.622, 0.518, respectively; P<0.05). CONCLUSIONS: The iron and calcium levels of preterm infants' mothers were lower than those of term infants' mothers, and the iron and magnesium levels of preterm infants were lower than those of term infants. The exact relationship between calcium, iron and magnesium levels and intakes before and during pregnancy needs to be explored further.