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1.
Medicine (Baltimore) ; 99(13): e19649, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221090

RESUMO

RATIONALE: Hepatic ectopic pregnancy is an extremely rare ectopic pregnancy. This study aimed to report a case of primary hepatic pregnancy in a patient with polycystic syndrome. PATIENT CONCERNS: A 30-year-old woman presented with vaginal bleeding after 63 days of amenorrhea. DIAGNOSIS: The patient was initially diagnosed with liver ectopic pregnancy using abdominal ultrasound and abdominal computed tomography (CT). INTERVENTIONS: The patient underwent laparoscopic exploration to reconfirm the gestational sac in the liver and abdominal surgery to remove liver gestation. The postoperative review of abdominal CT and the level of serum human chorionic gonadotropin (hCG) was performed. OUTCOMES: The postoperative pathological examination revealed a fluffy tissue in the liver tissue and a blood clot. The patient's vital signs were normal, and she was advised regular follow-up after discharge from the hospital. One month later, the serum hCG level reduced to 0.32 mIU/mL (reference range 0-5 mIU/mL). LESSONS: If the level of beta-human chorionic gonadotropin (ß-HCG) is higher than normal in women of childbearing age and no gestational sac is found in the uterine cavity, the location of pregnancy and gestational sac should be positively confirmed. Also, the possibility of ectopic pregnancy in the abdominal cavity should be considered, and the relevant imaging and biochemical examinations should be improved to avoid delay in diagnosis and treatment.

2.
Clin Rehabil ; 34(3): 287-298, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31793340

RESUMO

OBJECTIVE: To systematically investigate how fatigue, depression, anxiety, sleep quality, and life quality are influenced by the Internet-based self-management program (IBSMP) among cancer patients. DATA SOURCES: Eight databases (Cochrane Library, Ovid, Web of Science, Medline, Embase, Chinese biomedical database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang) were systematically searched from inception to January 2019. METHODS: The aim of this study is to identify randomized controlled trials (RCTs) associated with the IBSMP among cancer-related fatigue (CRF) patients. Two reviewers independently screened 1128 records and selected 13 articles, including 1603 patients for inclusion. The quality of the evidence was assessed at the study level and at the outcome level. RESULTS: The meta-analysis showed that the IBSMP was effective for ameliorating fatigue and related symptoms among cancer survivors (the Brief Fatigue Index, relative risk = 0.74, 95% confidence interval (CI; 0.69, 0.79), P < 0.01; the Cancer Fatigue Scale or the Multidimension Fatigue Scale, weighted mean difference = -10.15, 95% CI (-11.42, -8.89), P < 0.01; the Self-rating Anxiety scale, relative risk = 1.07, 95% CI (0.55, 2.05), P < 0.01; the Self-rating Depression scale, relative risk = 0.70, 95% CI (0.60, 0.81), P < 0.01; the Pittsburgh Sleep Quality Index, relative risk = 0.46, 95% CI (0.33, 0.62), P < 0.01; and the Function Assessment of Cancer Therapy-General scale or the Function Assessment of Cancer Therapy-Breast, weighted mean difference = 13.76, 95% CI (3.38, 24.14), P < 0.01.). CONCLUSION: This meta-analysis demonstrates that the IBSMP, as one of the rehabilitation forms, can reduce the incidence of fatigue, depression, and anxiety and improve sleep quality and life quality among CRF patients.

3.
Medicine (Baltimore) ; 98(37): e17087, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517830

RESUMO

Human papillomavirus (HPV) infection is a crucial health problem and caused substantial malignancy diseases among female worldwide. We aim to investigate the distribution of HPV subtype and the status of cervical cancer and precancerous lesions caused by HPV infection in North China Plain population. A total of 61,870 samples of outpatients and inpatients from January 2015 to May 2017 at the Affiliated Hospital of Jining Medical University were collected. All of the samples were tested by rapid flow-through hybridization HPV genotyping. Approximately 17,280 of the cases tested positive for HPV, indicating an infection rate of 27.9%. Approximately 7009 cases were compared to the results of cytological diagnosis. The top five HPV genotypes were HPV-16 (4.5%), HPV-52 (2.9%), HPV-58 (2.8%), HPV-53 (1.9%), and HPV-81 (1.9%). The youngest age group (age < 20 years) showed the highest infection rate (59.9%), and then decreased with age. As the degree of cervical lesions worsened gradually, the rate of high-risk HPV infection increased, such as 24.3% (322/1324) in the Cervicitis, 31.30% (560/1785) in the CINI, 54.1% (568/1050) in the CINII, 80.1% (693/865) in the CIN III, and 99.5% (428/430) in the cervical cancer group. These findings were significantly different from the 9.7% (155/1555) observed in the normal medical examination group (P < .05). This is the first study to demonstrate the characteristics of HPV and the association with cervical lesions in North China Plain population.


Assuntos
Genótipo , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Idoso , Neoplasia Intraepitelial Cervical/patologia , China/epidemiologia , Feminino , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Distúrbios Menstruais/patologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/classificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/epidemiologia , Descarga Vaginal/patologia
4.
Medicine (Baltimore) ; 98(31): e16620, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374028

RESUMO

Psychological state of patients with ovarian cancer is worthy of attention. We aimed to investigate the levels of anxiety and depression in patients with ovarian cancer. We also investigated the dynamic changes in anxiety and depression levels after chemotherapy.A total of 228 females were included in this study. Among them, a total of 111 participants had ovarian cancer and 117 females who underwent a physical examination were selected as healthy controls. All patients enrolled were asked to fill in the Self-rating Depression Scale and the Self-rating Anxiety Scale. For patients with ovarian cancer, repeat questionnaires were measured after cycle 1 chemotherapy.The depression score of patients with ovarian cancer was 45.90 ± 10.19, significantly higher than in controls (36.08 ± 9.06, P < .001). Similar results were observed in respect of anxiety score. The score of ovarian cancer patients was 39.53 ± 12.92, significantly higher than of controls (32.15 ±â€Š7.44, P < .001). Multivariate analyses were conducted, and the results showed that young age was the independent risk factor associated with depression among patients with ovarian cancer, while young age and singleness were the independent risk factors associated with anxiety. Repeat questionnaires were measured after chemotherapy. Interestingly, we found depression scores decreased from 45.90 ±â€Š10.19 to 36.29 ±â€Š8.98 after chemotherapy (P < .001), while anxiety score increased from 39.53 ±â€Š12.92 to 42.75 ±â€Š9.96 after chemotherapy (P = .009). Multivariate analysis suggested that only higher income and higher baseline depression score were the independent and most relevant risk factors associated with depression remission after chemotherapy. For patients with anxiety remission, only higher baseline anxiety score was the independent risk factor associated with anxiety remission.This study suggests that for patients with ovarian cancer, timely monitoring of the patient's psychological state, especially before and after chemotherapy treatment, is very important. Assessing the changes in the patient's psychological state, screening the population with risk factors, and prompt intervention by mobilizing social support may be effective in preventing depression and anxiety in such population.


Assuntos
Antineoplásicos/uso terapêutico , Ansiedade/epidemiologia , Depressão/epidemiologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/epidemiologia , Adulto , Fatores Etários , Idoso , Antineoplásicos/administração & dosagem , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/psicologia , Fatores de Risco , Fatores Socioeconômicos
5.
Front Pharmacol ; 10: 338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130856

RESUMO

Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon that specifically causes cancer and is widely distributed in the environment. Poly (ADP-ribosylation), as a key post-translational modification in BaP-induced carcinogenesis, is mainly catalyzed by poly (ADP-ribose) glycohydrolase (PARG) in eukaryotic organisms. Previously, it is found that PARG silencing can counteract BaP-induced carcinogenesis in vitro, but the mechanism remained unclear. In this study, we further examined this process in vivo by using heterozygous PARG knockout mice (PARG+/-). Wild-type and PARG+/- mice were individually treated with 0 or 10 µg/m3 BaP for 90 or 180 days by dynamic inhalation exposure. Pathological analysis of lung tissues showed that, with extended exposure time, carcinogenesis and injury in the lungs of WT mice was progressively worse; however, the injury was minimal and carcinogenesis was not detected in the lungs of PARG+/- mice. These results indicate that PARG gene silencing protects mice against lung cancer induced by BaP inhalation exposure. Furthermore, as the exposure time was extended, the protein phosphorylation level was down-regulated in WT mice, but up-regulated in PARG+/- mice. The relative expression of Wnt2b and Wnt5b mRNA in WT mice were significantly higher than those in the control group, but there was no significant difference in PARG+/- mice. Meanwhile, the relative expression of Wnt2b and Wnt5b proteins, as assessed by immunohistochemistry and Western blot analysis, was significantly up-regulated by BaP in WT mice; while in PARG+/- mice it was not statistically affected. Our work provides initial evidence that PARG silencing suppresses BaP induced lung cancer and stabilizes the expression of Wnt ligands, PARG gene and Wnt ligands may provide new options for the diagnosis and treatment of lung cancer.

6.
Oncol Lett ; 17(1): 1211-1216, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30655886

RESUMO

Ovarian cancer is the most aggressive type of gynecological cancer. The cause of the poor survival rate is the development of chemotherapy resistance to platinum-based therapies, including cisplatin. The present study aimed to investigate the mechanism of cancerous inhibitor of protein phosphatase 2A (CIP2A)-induced chemoresistance in ovarian cancer. The present study initially investigated the expression of CIP2A in the ovarian tumor tissue, cisplatin-sensitive SKOV-3 cell line, and cisplatin-resistant ovarian carcinoma SKOV-3CDDP/R cell line. In addition, CIP2A was knocked down using small interference RNA in ovarian cancer cells and the chemosensitivity of these cells was analyzed. The results demonstrated that CIP2A expression was significantly higher in patients with ovarian cancer and in the cisplatin-resistant ovarian carcinoma SKOV-3CDDP/R cell line at the mRNA and protein levels. The proliferation and chemosensitivity were decreased and enhanced, respectively, when CIP2A was knocked down. CIP2A silencing significantly promoted the apoptosis induced by cisplatin in SKOV-3CDDP/R cells, suggesting that CIP2A participated in the cisplatin resistance of ovarian cancer cells and that CIP2A silencing enhanced the apoptosis induced by cisplatin. CIP2A may be considered as a potential candidate for modulating cisplatin therapy in ovarian cancer.

7.
Medicine (Baltimore) ; 97(48): e13418, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30508948

RESUMO

RATIONALE: Primary squamous cell carcinoma of the endometrium (PSCCE) is a rare entity, and only sporadic cases have been reported in the literature since the 1st report in 1892. This report describes a case of a perimenopausal woman with PSCCE. PATIENT CONCERNS: A 47-year-old, human papilloma virus type 16-positive, perimenopausal woman was admitted to our hospital with irregular vaginal bleeding for 6 months and secondary anemia. DIAGNOSES: The patient was diagnosed with stage IIIc primary and moderately differentiated endometrial squamous cell carcinoma. INTERVENTIONS: The patient underwent diagnostic curettage twice and cold knife conization (CKC). Following this total abdominal hysterectomy combined with bilateral adnexectomy and pelvic lymph node, dissection was performed. After the surgery, the patient was treated with radiotherapy and chemotherapy. Tumor markers were followed up regularly after the operation to monitor tumor recurrence and therapeutic effect. OUTCOMES: Ninety-two days after the operation, there was tumor recurrence of the left pelvic cavity and the patient died after 11 months of follow-up. LESSONS: Intrauterine pathology after the 1st diagnostic curettage suggests that high-grade squamous intraepithelial lesion should make the clinician vigilant and investigate the origin of the lesion. Magnetic resonance imaging scans and tumor markers can be used to confirm the diagnosis as soon as possible and avoid unnecessary interventions like CKC.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias do Endométrio/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Conização , Curetagem/métodos , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Evolução Fatal , Feminino , Humanos , Histerectomia/métodos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Perimenopausa , Ultrassonografia , Procedimentos Desnecessários , Útero/diagnóstico por imagem , Útero/patologia
8.
Oncol Rep ; 40(3): 1803-1812, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015946

RESUMO

Downregulation of microRNA­152 (miR­152) has been observed in various types of human malignancies, including Bladder cancer (BC). However, the role of miR­152 in the development and progression of BC is still unclear. In our previous study, we identified a functional crosstalk between miR­152 and DNA methyltransferase 1 (DNMT1) involved in Nis­induced malignant transformation. In the present study, we found that the expression of miR­152 was specifically downregulated in BC cells and tissues via the DNA hypermethylation of the miR­152 promoter. The overexpression of miR­152 in BC cells resulted in a reduction of DNMT1, whereas the inhibition of the expression of miR­152 induced an elevated level of DNMT1. Further studies revealed that miR­152 directly downregulated the expression of DNMT1 by targeting the 3'­UTR of its transcript in BC cells. In addition, ectopic expression of miR­152 in BC cells significantly inhibited cell proliferation, whereas the inhibition of miR­152 expression led to increased cell proliferation. These findings indicated a novel regulatory circuit of miR­152/DNMT1 in BC, and more importantly, the combination of miR­152 and DNMT1 may function as promising therapeutic modalities and early biomarkers for BC.


Assuntos
Biomarcadores Tumorais/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Bexiga Urinária/patologia , Idoso , Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Proliferação de Células , DNA (Citosina-5-)-Metiltransferase 1/genética , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Regiões Promotoras Genéticas , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
9.
Oncotarget ; 9(4): 4915-4923, 2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-29435151

RESUMO

Epidemiologic study has suggested that arsenic exposure is positively related to increased blood pressure. However, the underlying mechanism concerning interaction between genetic polymorphisms and arsenic exposure remains unclear. In present study, within 395 Chinese, the effects of interaction between arsenic exposure and CCM3 gene polymorphisms on elevation of blood pressure were probed by multiple Logistic regression models after adjusting for confounding factors. Firstly, we found that serum arsenic was positively associated with blood pressure, cholesterol, glucose and C-reactive protein. Then, adjusted for confounding factors of age, gender, smoking, alcohol consumption, BMI and degree of education, arsenic exposure incurred the hazard of increased systolic pressure and diastolic pressure, with odds ratios (ORs) being 1.725 and 1.425, respectively. Distinctly, we found that interactions between rs3804610* rs9818496, rs6784267*rs9818496, and rs3804610* rs6784267 variant genotype can increase significantly risks of SBP. Additionally, interactions between rs9818496, rs3804610 and rs6784267 genotypic variantions and arsenic exposure boosted the hazard of increased systolic pressure, with ORs being 1.496, 1.496 and 1.312. In conclusion, our fingdings suggest that As exposure of population can assist CCM3 polymorphism in elevating SBP.

10.
Biomed Pharmacother ; 96: 1403-1410, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29169726

RESUMO

Piperine (PP), an alkaloid from black and long peppers (Piper nigrum Linn &Piper longum Linn), exhibits antitumor activities in vitro and in vivo. We investigated the ability of piperine (PP) to reverse the drug resistance of human cervical cancer cells. In our study, the cervica cancer cells resistant to mitomycin-C (MMC) treatment were used. We found the growth inhibitory effects of piperine on human cervical cancer cell, which were resistant to MMC. Piperine and MMC co-treatment resulted in a dose-dependent suppression of the cell proliferation. Decreasing of phosphorylated-signal transducer and activator of transcription (p-STAT3) was linked to the suppression of p65 by PP and MMC combinational treatment. Additionally, the presence of PP potentiated the effects of MMC on apoptosis induction in cervical cancer cells with drug resistance, which was dependent on Bcl-2 inhibition. The pro-apoptotic proteins of Bax and Bid were up-regulated, accompanied with Caspase cleavage. Moreover, in mice xenograft models, the combined therapy inhibited tumor growth compared to the PP or MMC mono-therapy group. Our data indicated a novel therapeutic strategy of PP to potentiate MMC-induced anti-tumor effect on cervical cancer cells with drug resistance through blocking p-STAT3/p65 and Bcl-2 activation.


Assuntos
Alcaloides/farmacologia , Benzodioxóis/farmacologia , Mitomicina/farmacologia , NF-kappa B/metabolismo , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Neoplasias do Colo do Útero/metabolismo
11.
Mutat Res ; 803-805: 17-21, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28759748

RESUMO

We evaluated DNA damage levels of different categories of workers exposed to hazards inside electronics factories in Southern China. To find out the most dangerous risk factor, a cross-sectional study was conducted on a total of 584 exposed subjects and 138 controls in an electronics factory in Southern China, where the electronics industry is prevalent. The exposed hazards included isopropanol (IPO), lead, noise, video display terminals (VDT), lead in a high-temperature (high-temp) environment, and IPO in a high-temp environment. DNA damage detection was performed by the micro-whole blood comet assay using peripheral blood. DNA damage levels were estimated by percent tail DNA (%T). Linear regression models were used to test DNA damage differences between exposed groups and control group with adjustments for potential confounding factors. The level of DNA damage was more significant in both lead in a high-temp and IPO in a high-temp environment groups than in that of the controls (p<0.05). The differences remained significant after stratifying by smoking status (p<0.05). There were no significant differences between groups exposed to IPO, lead, noise, VDT environment and controls. In conclusion, we identified potential risk factors for DNA damage to electronics workers. Special attention should be paid to workers exposed to IPO and lead in a high-temp environment.


Assuntos
Dano ao DNA/efeitos dos fármacos , Substâncias Perigosas/toxicidade , Indústria Manufatureira , Exposição Ocupacional/efeitos adversos , 2-Propanol/toxicidade , Acetona/toxicidade , Adolescente , Adulto , Benzeno/toxicidade , China , Ensaio Cometa , Estudos Transversais , Feminino , Temperatura Alta , Humanos , Chumbo/toxicidade , Modelos Lineares , Masculino , Inquéritos e Questionários , Tolueno/toxicidade , Xilenos/toxicidade , Adulto Jovem
12.
Toxicol Lett ; 280: 213-221, 2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28757444

RESUMO

Nano-SiO2 materials play a significant role in the engineered nanomaterials (ENMs) field. The ease of their production as well as their relatively low cost has promoted the wide use of these products in many fields. Nano-SiO2 exposure is known to cause severe DNA damage; however, the underlying mechanisms remain poorly understood. In a previous study, we found that nano-SiO2 exposure regulate the expression of the poly(ADP-ribose) polymerases-1 (PARP-1), a pivotal DNA repair gene, in human HaCaT cells. Here, we employed lentivirus-mediated RNA interference (RNAi) to knock down PAPR-1 expression in HaCaT cells and explored the potential role of PARP-1 in nano-SiO2 induced cytotoxicity. We found that nano-SiO2 treatment of HaCaT cells causes decreased cell viability, increased apoptosis and DNA damage. Nano-SiO2-treated HaCaT cells were also found to have slightly changed cell cycle distribution. Lentivirus-mediated PAPR-1 knockdown partially aggravated cytotoxicity and increased apoptosis induced by nano-SiO2 treatment. Nano-SiO2 had significant toxicity to human HaCaT cells and causes DNA damage. PAPR-1 knock-down cell line appears more sensitive to nano-SiO2 than the control cells in DNA damage. The results suggest that PAPR-1 is involved in protecting cells from damage caused by nano-SiO2.


Assuntos
Nanopartículas/toxicidade , Poli(ADP-Ribose) Polimerase-1/metabolismo , Dióxido de Silício/toxicidade , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Aberrações Cromossômicas/induzido quimicamente , Deleção de Genes , Humanos , Nanopartículas/química , Poli(ADP-Ribose) Polimerase-1/genética , Dióxido de Silício/química
13.
IUBMB Life ; 68(7): 516-25, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27192959

RESUMO

Inducible nitric oxide synthase (NOS2) and endothelial nitric oxide synthase (NOS3) gene play important roles in the susceptibility to type 2 diabetes mellitus (T2DM). The present study aims to detect the potential association of NOS2 and NOS3 gene polymorphisms with the susceptibility toT2DM and diabetic nephropathy (DN) in the Chinese Han population. Four hundred and ninety T2DM patients and 485 healthy controls were enrolled in this case-control study. The genotypes of NOS2 and NOS3 gene polymorphisms were analyzed by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method. Our data demonstrated that the NOS2 rs2779248 and NOS2 rs1137933 genetic polymorphisms were significantly associated with the increased susceptibility to T2DM in the heterozygote comparison, dominant model, and allele contrast; and NOS3 rs3918188 genetic polymorphism was significantly associated with the increased susceptibility to T2DM in the homozygote comparison and recessive model. The allele-C and genotype-TC of NOS2 rs2779248, allele-A and genotype-GA of NOS2 rs1137933 and genotype-AA of NOS3 rs3918188 genetic polymorphisms might be the risk factors for increasing the susceptibility to T2DM. And a significant haplotype effect of NOS2 rs10459953/C- rs1137933/G- rs2779248/T was found between T2DM cases and controls. Moreover, NOS3 rs1800783 polymorphism was significantly associated with the increased susceptibility to DN in the heterozygote comparison, recessive model and allele contrast. At last, a positive correlation of family history of diabetes with NOS3 rs11771443 polymorphism was found in DN. These preliminary findings indicate that the NOS2 rs2779248, NOS2 rs1137933, and NOS3 rs3918188 genetic polymorphisms are potentially related to the susceptibility to T2DM, and the rs1800783 polymorphism might be considered as genetic risk factors for diabetic nephropathy, and family history of diabetes was closely associated with rs11771443 polymorphism in DN, and the genetic variants might be used as molecular markers for evaluating the risk of T2DM and diabetic nephropathy. © 2016 IUBMB Life, 68(7):516-525, 2016.


Assuntos
Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo II/genética , Adulto , Idoso , China , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
Int J Toxicol ; 35(3): 336-43, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26960346

RESUMO

Benzo[a]pyrene (B[a]P) exposure has been associated with the alteration in epigenetic marks that are involved in cancer development. Biotinidase (BTD) and holocarboxylase synthetase (HCS) are 2 major enzymes involved in maintaining the homeostasis of biotinylation, and the deregulation of this pathway has been associated with a number of cancers. However, the link between B[a]P exposure and the dysregulation of BTD/HCS in B[a]P-associated tumorigenesis is unknown. Here we showed that the expression of both BTD and HCS was significantly decreased upon B[a]P treatment in human bronchial epithelial (16HBE) cells. Benzo[a]pyrene exposure led to the global loss of DNA methylation by immunofluorescence, which coincided with the reduction in acetylation levels on histones H3 and H4 in 16HBE cells. Consistent with decreased histone acetylation, histone deacetylases (HDACs) HDAC2 and HDAC3 were significantly upregulated in a dosage-dependent manner. When DNA methylation or HDAC activity was inhibited, we found that the reduction in BTD and HCS was separately regulated through distinct epigenetic mechanisms. Together, our results suggested the potential link between B[a]P toxicity and deregulation of biotin homeostasis pathway in B[a]P-associated cancer development.


Assuntos
Benzo(a)pireno/toxicidade , Biotina/metabolismo , Carcinógenos/toxicidade , Células Epiteliais/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Biotinidase/metabolismo , Brônquios/citologia , Carbono-Nitrogênio Ligases/metabolismo , Linhagem Celular , Metilação de DNA , Epigênese Genética , Células Epiteliais/metabolismo , Histona Desacetilase 2/metabolismo , Histona Desacetilases/metabolismo , Histonas/efeitos dos fármacos , Histonas/metabolismo , Humanos
15.
Toxicol Ind Health ; 32(10): 1774-83, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26045551

RESUMO

Trichloroethylene (TCE), a halogenated organic solvent widely used in industries, is known to cause severe hepatotoxicity. However, the mechanisms underlying TCE hepatotoxicity are still not well understood. It is predicted that membrane proteins are responsible for key biological functions, and recent studies have revealed that TCE exposure can induce abnormal levels of membrane proteins in body fluids and cultured cells. The aim of this study is to investigate the TCE-induced alterations of membrane proteins profiles in human hepatic L-02 liver cells. A comparative membrane proteomics analysis was performed in combination with two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. A total of 15 proteins were identified as differentially expressed (4 upregulated and 11 downregulated) between TCE-treated cells and normal controls. Among this, 14 of them are suggested as membrane-associated proteins by their transmembrane domain and/or subcellular location. Furthermore, the differential expression of ß subunit of adenosine triphosphate synthase (ATP5B) and prolyl 4-hydroxylase, ß polypeptide (P4HB) were verified by Western blot analysis in TCE-treated L-02 cells. Our work not only reveals the association between TCE exposure and altered expression of membrane proteins but also provides a novel strategy to discover membrane biomarkers and elucidate the potential mechanisms involving with membrane proteins response to chemical-induced toxic effect.


Assuntos
Proteínas de Membrana/análise , Proteínas de Membrana/metabolismo , Proteoma/efeitos dos fármacos , Proteômica/métodos , Tricloroetileno/toxicidade , Linhagem Celular , Eletroforese em Gel Bidimensional , Humanos , Fígado/citologia , Proteínas de Membrana/classificação , Proteoma/análise , Proteoma/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
16.
Toxicol Lett ; 243: 1-6, 2016 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-26656300

RESUMO

A matched case-control study was conducted to examine the relationship between chromium (Cr) exposure and variation in mitochondrial (mt) DNA methylation. We enrolled 29 pairs of subjects in this study; Cr exposure was confirmed in the cases by detecting blood Cr and other metal ion concentrations. DNA damage caused by Cr exposure was determined in terms of binucleated micronucleus frequency (BNMN) and mtDNA copy number. Finally, a Sequenom MassARRAY platform was applied to inspect the DNA methylation levels of mitochondrially encoded tRNA phenylalanine (MT-TF), mitochondrially encoded 12S RNA (MT-RNR1), and long interspersed nucleotide element-1 (LINE-1) genes. The blood Cr ion concentration and micronucleus frequency of the Cr-exposed group were higher than those of the control group, whereas the mtDNA copy number remained unchanged. The methylation levels of MT-TF and MT-RNR1 but not LINE-1 were significantly lower in Cr-exposed workers. Pearson correlation analysis showed that workers with higher blood Cr ion concentrations exhibited lower MT-TF and MT-RNR1 gene methylation, and multiple linear regression analysis indicated that CpG sites 1 and 2 in MT-TF and CpG site 6 in MT-RNR1 were affected. These results suggested that methylation level of mtDNA has the possibility of acting as an alternative effect biomarker for Cr exposure.


Assuntos
Cromo/toxicidade , Metilação de DNA , DNA Mitocondrial , Exposição Ocupacional/efeitos adversos , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Cromo/sangue , Variações do Número de Cópias de DNA , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Elementos Nucleotídeos Longos e Dispersos , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade
17.
Artigo em Chinês | MEDLINE | ID: mdl-26653644

RESUMO

OBJECTIVE: To study the effect of silicon dioxide nanoparticles on the expression and promoter region CpG islands methylation of (Poly [ADP-ribose] polymerase 1, PARP-1) gene in human HaCaT Cell. METHODS: HaCaT Cells were treated with nm-SiO2at 0, 2.5, 5 and 10 µg/mL and micro-SiO2at 10 µg/ml for 24 h and DAC treatment was given at 10 µg/ml group for 48 h. Real-time PCR and western blot assay was used to detect the expression of PARP-1 mRNA and protein. BSP (Bisulfite Pyrosequence, BSP) assay was used to detect the promoter region CpG islands methylation status of PARP-1 gene. RESULTS: After exposure to nano-SiO2particles, compared to CTRL group, the mRNA and protein expression of PARP-1 in micro-SiO2and 2.5 µg/ml group unchanged, but he mRNA and protein expression of PARP-1 in 5, 10 µg/ml as well as DAC group was down-regulated and there are statistical significance between CTRL group and 5, 10 µg/ml as well as DAC group and the PARP-1 promoter region CpG islands showed methylation. CONCLUSION: nano-SiO2can down-regulate PARP-1 expression in HaCaT Cell and this is associated with the change in the methylation of PARP-1 gene promoter region CpG islands induced by nano-SiO2particles.


Assuntos
Ilhas de CpG , Metilação de DNA , Nanopartículas/efeitos adversos , Poli(ADP-Ribose) Polimerases/metabolismo , Dióxido de Silício/efeitos adversos , Linhagem Celular Tumoral , Humanos , Poli(ADP-Ribose) Polimerase-1 , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo
18.
Inhal Toxicol ; 27(10): 502-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26308105

RESUMO

BACKGROUND: The relationship between lung cancer and smoking has been demonstrated. The Rap2B gene is usually overexpressed in lung cancers. This study was aimed to investigate the Rap2B gene expression and its promoter methylation in human bronchial epithelial cells (16HBE) treated by cigarette smoke condensate (CSC). METHODS: 16HBE cells were treated with CSC (1/8 IC50). Soft ager assay, tumorigenicity test, chromosome aberrations analysis were used to identify the transformed cells. The expression level of mRNA and protein of Rap2B was detected using real time PCR and Western blotting, respectively. The genome DNA methylation level was detected using combined bisulfite restriction analysis (COBRA) and the methylation status of the target fragment in Rap2B gene promoter was determined by bisulfite sequencing PCR (BSP). RESULTS: The 16HBE cells were successfully malignant transformed after the chronic exposure to CSC. The expression of Rap2B gradually increased in the process of malignant transformation. Meanwhile, global DNA was hypomethylated. However, no obvious change was observed in the methylation level of Rap2B gene promoter in transformed 16HBE cells. CONCLUSIONS: Rap2B gene may play an important role in the process of lung cancer and global DNA hypomethylation might be an early event in tumorigenesis.


Assuntos
Metilação de DNA/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Fumaça/efeitos adversos , Tabaco , Proteínas rap de Ligação ao GTP/genética , Brônquios/citologia , Linhagem Celular , Transformação Celular Neoplásica , Células Epiteliais/metabolismo , Humanos , Regiões Promotoras Genéticas , Proteínas rap de Ligação ao GTP/metabolismo
19.
Am J Cancer Res ; 5(1): 155-67, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25628927

RESUMO

Benzo(a)pyrene (BaP) is a ubiquitously distributed environmental pollutant. BaP is a known carcinogen and can induce malignant transformation of rodent and human cells. Many evidences suggest that inhibitor of poly(ADP-ribose) glycohydrolase (PARG) is potent anticancer drug candidate. However, the effect of PARG on BaP carcinogenesis remains unclear. We explored this question in a PARG-deficient human bronchial epithelial cell line (shPARG cells) treated with various concentration of BaP for 15 weeks. Soft agar assay was used to examine BaP-induced cell malignancy of human bronchial epithelial cells and shPARG cells. Mechanistic investigations were used by 2D-DIGE and mass spectrometry. Western blot analysis and Double immunofluorescence detection were used to confirm some of the results obtained from DIGE experiments. We found that PARG silencing could dramatically inhibit BaP-induced cell malignancy of human bronchial epithelial cells in soft agar assay. Altered levels of expression induced by BaP were observed within shPARG cells for numerous proteins, including proteins required for cell mobility, stress response, DNA repair and cell proliferation pathways. Among these proteins, TCTP and Cofilin-1 involved in malignancy, were validated by western blot analysis and immunofluorescence assay. PARG inhibition contributed to down-regulation of TCTP and Cofilin-1. This is the first experimental demonstration of a link between PARG silencing and reduced cell migration after BaP exposure. We propose that PARG silencing might down-regulate TCTP and Cofilin-1 associated with metastasis in BaP carcinogenesis.

20.
J Alzheimers Dis ; 43(4): 1413-27, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25159668

RESUMO

Copper is an essential element for human growth and development; however, excessive intake of copper could contribute to neurotoxicity. Here we show that chronic exposure to copper in drinking water impaired spatial memory with simultaneous selective loss of hippocampal pre-synaptic protein synapsin 1, and post-synaptic density protein (PSD)-93/95 in mice. Copper exposure was shown to elevate the levels of nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampus, two markers of oxidative stress. Concurrently, we also found that copper exposure activated double stranded RNA-dependent protein kinase (PKR) as evidenced by increased ratio of phosphorylated PKR at Thr451 and total PKR and increased the phosphorylation of its downstream signaling molecule eukaryotic initiation factor 2α (eIF2α) at Ser51 in hippocampus. Consistent with activation of PKR/eIF2α signaling pathway which was shown to mediate synaptic deficit and cognitive impairment, the levels of activating transcription factor 4 (ATF-4), a downstream signaling molecule of eIF2α and a repressor of CREB-mediated gene expression, were significantly increased, while the activity of cAMP response elements binding protein (CREB) was inactivated as suggested by decreased phosphorylation of CREB at Ser133 by copper exposure. In addition, the expression of the pro-apoptotic target molecule C/EBP homology protein (CHOP) of ATF-4 was upregulated and hippocampal neuronal apoptosis was induced by copper exposure. Taken together, we propose that chronic copper exposure might cause spatial memory impairment, selective loss of synaptic proteins, and neuronal apoptosis through the mechanisms involving activation of PKR/eIF2α signaling pathway.


Assuntos
Sulfato de Cobre/toxicidade , Proteínas de Ligação a DNA/metabolismo , Hipocampo/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Neurônios/efeitos dos fármacos , Fatores de Transcrição/metabolismo , eIF-2 Quinase/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Doença Crônica , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Proteína 4 Homóloga a Disks-Large , Guanilato Quinases/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Proteínas de Membrana/metabolismo , Transtornos da Memória/patologia , Transtornos da Memória/fisiopatologia , Camundongos Endogâmicos C57BL , Neurônios/patologia , Neurônios/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Sinapsinas/metabolismo , Fator de Transcrição CHOP/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo
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