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1.
Talanta ; 271: 125684, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38262131

RESUMO

This work presented a FRET-ICT based fluorescent probe (named NTC) composed of coumarin-benzothiazole as the acceptor and 4-nitrobenzo[c][1,2,5] oxadiazole (NBD) as the donor for the detection of SO2 derivatives in NIR. Probe NTC possessed superior performance including selectivity, quickly response toward SO32-/HSO3- and high energy transfer efficiency (94 %). The test strips provided a simple and effective tool in detecting the presence of bisulfite. Besides, NTC was applied to test the sulfur dioxide derivatives in food samples and cells.


Assuntos
Colorimetria , Corantes Fluorescentes , Humanos , Dióxido de Enxofre , Sulfitos , Transferência Ressonante de Energia de Fluorescência , Células HeLa
2.
Front Nutr ; 9: 974443, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407550

RESUMO

Background: Erectile dysfunction (ED) mainly affects men over 40 years of age and is a common clinical condition. In addition to hypertension and diabetes, environment, and lifestyle are also significantly associated with erectile dysfunction. The relationship between dietary trace metal intake and ED has not been studied. Materials and methods: Data on participants were obtained from the National Health and Nutrition Examination Survey for this study, and those with incomplete information on clinical variables were excluded. Dose-response curve analysis was used to investigate the relationship between dietary trace metal intake and ED prevalence. Multivariate logistic regression analysis was used to adjust for confounders to further investigate the relationship between dietary trace metal intake and ED prevalence. 1:1 propensity score matching (PSM) was performed to adjust for differences between clinical variables for data reanalysis to confirm the reliability of the results. Results: A total of 3,745 individuals were included in the study, including 1096 ED patients and 2,649 participants without ED. Dietary intake of trace metals (Mg, Zn, Cu, and Se) was significantly higher in participants without ED than in ED patients (all P < 0.001). Dose-response curve analysis showed a significant negative association between these dietary metal intakes and ED prevalence (all P < 0.001). Multivariate logistic regression analysis adjusted for confounders (age, education, BMI, annual household income, hypertension, diabetes, marital status, race, and current health status) revealed that increased dietary metal intake reduced the odds ratio of ED. 1:1 PSM reanalysis further confirmed the validity of the results. Conclusion: Increasing dietary intake of trace metals (magnesium, zinc, copper, and selenium) within the upper limit is beneficial in reducing the prevalence of ED.

3.
Front Surg ; 9: 967525, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157402

RESUMO

Background: The calyceal diverticulum is a rare cystic cavity that communicates with the collecting system via a narrow neck or infundibulum. In clinical practice, part of the calyceal diverticula is difficult to differentiate from simple renal cysts even after contrast-enhanced CT. To date, there have been few kinds of literature works on the diagnosis and treatment of calyceal diverticulum combined with renal pelvis dilatation, especially concerning the treatment of prolonged postoperative urine leakage. Case description: A 53-year-old woman with calyceal diverticulum and renal pelvis dilatation mimicking a simple renal cyst suffered urine leakage after receiving laparoscopic unroofing of the renal cyst. A persistent urine leakage was observed immediately after surgery, with about 200 ml of drainage fluid per day. We first attempted to place a double-J ureteral stent and indwell a catheter. After failing that, conservative treatment was performed. The core idea of the conservative treatment is retaining the drainage tube for more than 1 month, then clamping the drainage tube for 1 week, and finally removing the drainage tube. By 3 weeks of follow-up, the urine leakage disappeared, and the CT scan showed hydronephrosis of the right kidney without perirenal exudation and the lower pole cyst of the right kidney shrank significantly. Conclusion: This case, we reported here, is to attract the attention of clinicians. Renal cysts should exclude the possibility of the calyceal diverticulum. If urine leakage is inevitable after surgical treatment, our conservative treatment strategy is also an alternative method.

4.
Front Chem ; 10: 990734, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118317

RESUMO

A chemical investigation on the kiwi endophytic fungus Bipolaris sp. Resulted in the isolation of eight new terpenoids (1-8) and five known analogues (9-13). Compounds 1-5 are novel sativene sesquiterpenoids containing three additional skeletal carbons, while compounds 4 and 5 are rare dimers. Compounds 6-8 and 13 are sesterterpenoids that have been identified from this species for the first time. Compounds 4 and 5 showed antibacterial activity against kiwifruit canker pathogen Pseudomonas syringae pv. Actinidiae (Psa) with MIC values of 32 and 64 µg/ml, respectively.

5.
Front Oncol ; 12: 852515, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35425712

RESUMO

Background: BAP1 is an important tumor suppressor involved in various biological processes and is commonly lost or inactivated in clear-cell renal cell carcinoma (ccRCC). However, the role of the BAP1-deficient tumor competing endogenous RNA (ceRNA) network involved in ccRCC remains unclear. Thus, this study aims to investigate the prognostic BAP1-related ceRNA in ccRCC. Methods: Raw data was obtained from the TCGA and the differentially expressed genes were screened to establish a BAP1-related ceRNA network. Subsequently, the role of the ceRNA axis was validated using phenotypic experiments. Dual-luciferase reporter assays and fluorescence in situ hybridization (FISH) assays were used to confirm the ceRNA network. Results: Nuclear enriched abundant transcript 1 (NEAT1) expression was significantly increased in kidney cancer cell lines. NEAT1 knockdown significantly inhibited cell proliferation and migration, which could be reversed by miR-10a-5p inhibitor. Dual-luciferase reporter assay confirmed miR-10a-5p as a common target of NEAT1 and Serine protease inhibitor family E member 1 (SERPINE1). FISH assays revealed the co-localization of NEAT1 and miR-10a-5p in the cytoplasm. Additionally, the methylation level of SERPINE1 in ccRCC was significantly lower than that in normal tissues. Furthermore, SERPINE1 expression was positively correlated with multiple immune cell infiltration levels. Conclusions: In BAP1-deficient ccRCC, NEAT1 competitively binds to miR-10a-5p, indirectly upregulating SERPINE1 expression to promote kidney cancer cell proliferation. Furthermore, NEAT1/miR-10a-5p/SERPINE1 were found to be independent prognostic factors of ccRCC.

7.
Phytochemistry ; 195: 113050, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34906836

RESUMO

Development of the kiwifruit industry has been severely hindered by the canker disease, which is caused by the bacterium Pseudomonas syringae pv. Actinidiae (Psa). However, endophytic fungi associated with healthy kiwi plants may protect host plants through the production of metabolites with potent anti-Psa activity. In the current study, four undescribed isobenzofuranones, namely sporulactones A‒D, two undescribed isocoumarins, namely sporulactones E and F, together with eight known analogs were isolated from the kiwi endophytic fungus Paraphaeosphaeria sporulosa. The structures with absolute configurations were established by extensive spectroscopic methods, quantum chemistry calculations, and X-ray diffraction experiments. In addition, five of the compounds exhibited anti-Psa activity, with minimum inhibitory concentration (MIC) values ranging from 25 to 100 µg/mL. These findings suggest that the small polyketide metabolites produced by P. sporulosa play an important role in the antibacterial properties of the endophyte.


Assuntos
Actinidia , Ascomicetos , Antibacterianos/farmacologia , Isocumarinas/farmacologia , Doenças das Plantas , Pseudomonas syringae
8.
J Fungi (Basel) ; 8(1)2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-35049949

RESUMO

Nine previously undescribed sesquiterpenoids, bipolarisorokins A-I (1-9); two new xanthones, bipolarithones A and B (10 and 11); two novel sativene-xanthone adducts, bipolarithones C and D (12 and 13); as well as five known compounds (14-18) were characterized from the kiwifruit-associated fungus Bipolaris sp. Their structures were elucidated by extensive spectroscopic methods, electronic circular dichroism (ECD), 13C NMR calculations, DP4+ probability analyses, and single crystal X-ray diffractions. Many compounds exhibited anti-pathogenic microorganism activity against the bacterium Pseudomonas syringae pv. actinidiae and four pathogenic microorganisms.

9.
Oncol Rep ; 42(1): 273-282, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115564

RESUMO

The present study aimed to construct conditionally replicative adenovirus (CRAds) carrying small hairpin (sh)RNA targeting enhancer of zeste homolog 2 (EZH2), in order to study its effect on inhibiting prostate cancer (PCa) cell growth and invasion. Immunohistochemical analyses of EZH2 was performed in tumor tissue samples from PCa and benign prostate hyperplasia (BPH). The human telomerase reverse transcriptase (hTERT) promoter was chosen to transcriptionally control EZH2 gene expression to obtain adenoviral replication (Ad­hTERT­EZH2shRNA) in human PCa cell lines. The inhibitory effect of Ad­hTERT­EZH2shRNA on EZH2 expression was evaluated by reverse transcription­-quantitative polymerase chain reaction and western blot analyses. Cell Counting Kit­8 assays were used to examine the effects of the Ad­hTERT­EZH2shRNA on cell proliferation. Transwell Matrigel invasion assays were used to detected cell invasion. Immunohistochemistry showed that EZH2 staining was stronger in castration­resistant prostate cancer (CRPC) samples, compared with androgen­dependent prostate cancer (ADPC) samples, and was absent in BPH. Furthermore, EZH2 expression knockdown suppressed PCa cell proliferation and invasion. In addition, it was found that Ad­hTERT­EZH2shRNA selectively replicated and significantly reduced the expression of EZH2 in PCa cells lines. The growth ability and invasion of DU145 and PC3 cells in vitro was effectively inhibited by Ad­hTERT­EZH2shRNA. Silencing the expression of EZH2 led to decreased expression of CCND1 and Ki67 and increased expression of E­cadherin, as determined by western blot analysis. Thus, it was shown that CRAds armed with EZH2 shRNA exhibited significant antitumor effects in human PCa cells. Ad­hTERT­EZH2shRNA may be developed as a treatment for hormone­refractory PCa.


Assuntos
Adenoviridae/fisiologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Neoplasias da Próstata/metabolismo , RNA Interferente Pequeno/farmacologia , Telomerase/genética , Adenoviridae/genética , Idoso , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Vetores Genéticos/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/terapia , Regiões Promotoras Genéticas , Neoplasias da Próstata/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/terapia , RNA Interferente Pequeno/genética , Replicação Viral
10.
Curr Genet ; 63(1): 131-144, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27306226

RESUMO

Ustilaginoidea virens is the causal agent of rice false smut disease resulting in quantitative and qualitative losses in rice. To gain insights into the pathogenic mechanisms of U. virens, we established a T-DNA insertion mutant library of U. virens through Agrobacterium tumefaciens-mediated transformation and selected an enhanced pathogenicity mutant (i.e., B3277). We analyzed the biological characteristics of the wild-type P1 and B3277. The growth rate and sporulation of B3277 were decreased compared with those of P1; the ferrous iron could be utilized by B3277, but inhibited the growth of P1. Southern blot analysis was performed to verify the copy number of the foreign gene inserted in the genomic DNA and only one copy of the T-DNA was found. The combined hiTAIL-PCR with RACE-PCR analysis showed the successful cloning of full length of the T-DNA flanking gene associated with pathogenicity, named Uvt3277. Gene expression was analyzed using real-time PCR. Results revealed that Uvt3277 was expressed at lower levels in B3277 than in P1. This gene was then subjected to bioinformatics analysis. The encoded protein of Uvt3277 exhibited high homology with low-affinity iron transporter proteins in some fungi. Transformation of the RNAi vector by constructing the hairpin RNA of the target gene was confirmed as successful. The pathogenicity of the transformant also increased. These results suggested that Uvt3277 may have an important function associated with the pathogenesis of U. virens. This study provides insights into the pathogenic mechanism of U. virens and a molecular target of disease control.


Assuntos
Ascomicetos/genética , Ascomicetos/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ferro/metabolismo , Doenças das Plantas/microbiologia , Sequência de Aminoácidos , Transporte Biológico , Clonagem Molecular , Análise por Conglomerados , DNA Bacteriano , Mutação , Oryza/microbiologia , Fenótipo , Característica Quantitativa Herdável , Interferência de RNA , Análise de Sequência de DNA
11.
Medicine (Baltimore) ; 95(44): e5307, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27858908

RESUMO

To evaluate the predictive value of neutrophil-to-lymphocyte ratio (NLR) in diagnosis of prostate cancer (PCa). Data of 662 patients who underwent prostate biopsy from January 2012 to June 2016 were retrospectively reviewed. The receiver operating characteristic-derived area under the curve analyses were performed to assess the predictive accuracy. Simultaneously, Youden's index was calculated to determine the optimal NLR cutoff. Furthermore, univariate and multivariate logistic regression analyses were performed to determine the association between NLR value and PCa detection. On account of an NLR value of 2.44 was shown with the maximal Youden's index on the receiver operating characteristic curve, the cutoff value of NLR was set at 2.44. Accordingly, patients were classified into high-NLR or low-NLR group. The patients in high-NLR group might have significant higher risk to be diagnosed with PCa (HR 1.640; P = 0.031), especially in the subgroup with prostate-specific antigen (PSA) ranged from 4 to 10 ng mL (hazard ratio [HR] 4.364; P = 0.003). The high-NLR was independent of age of diagnosis, PSA, prostate volume, abnormal digital rectal examination, and hypoechoic lesion on transrectal ultrasound for positive prostate biopsy. In the so-called gray area, combination of NLR value could raise 4.6% of the accuracy of the multivariate logistic model in PCa prediction, but not in advanced PCa prediction.The patients with high-NLR value may have significant higher risk to be diagnosed with PCa, especially among the patients with PSA ranged from 4 to 10 ng mL. In this subgroup, the adding of NLR value in the multivariate model can improve the accuracy of PCa prediction in a large degree. If validated, the NLR will become a promising, accessible, inexpensive biomarker for PCa prediction.


Assuntos
Linfócitos , Neutrófilos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Próstata , Neoplasias da Próstata/patologia , Estudos Retrospectivos
12.
World J Gastroenterol ; 22(14): 3769-76, 2016 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-27076761

RESUMO

AIM: To investigate the effect and mechanism of stimulation of the hypothalamic paraventricular nucleus with glutamate acid in rats with ulcerative colitis (UC). METHODS: The rats were anesthetized with 10% chloral hydrate via abdominal injection and treated with an equal volume of TNBS + 50% ethanol enema, injected into the upper section of the anus with the tail facing up. Colonic damage scores were calculated after injecting a certain dose of glutamic acid into the paraventricular nucleus (PVN), and the effect of the nucleus tractus solitarius (NTS) and vagus nerve in alleviating UC injury through chemical stimulation of the PVN was observed in rats. Expression changes of C-myc, Apaf-1, caspase-3, interleukin (IL)-6, and IL-17 during the protection against UC injury through chemical stimulation of the PVN in rats were detected by Western blot. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in colon tissues of rats were measured by colorimetric methods. RESULTS: Chemical stimulation of the PVN significantly reduced UC in rats in a dose-dependent manner. The protective effects of the chemical stimulation of the PVN on rats with UC were eliminated after chemical damage to the PVN. After glutamate receptor antagonist kynurenic acid was injected into the PVN, the protective effects of the chemical stimulation of the PVN were eliminated in rats with UC. After AVP-Vl receptor antagonist ([Deamino-penl, val4, D-Arg8]-vasopressin) was injected into NTS or bilateral chemical damage to NTS, the protective effect of the chemical stimulation of PVN on UC was also eliminated. After chemical stimulation of the PVN, SOD activity increased, MDA content decreased, C-myc protein expression significantly increased, caspase-3 and Apaf-1 protein expression significantly decreased, and IL-6 and IL-17 expression decreased in colon tissues in rats with UC. CONCLUSION: Chemical stimulation of the hypothalamic PVN provides a protective effect against UC injury in rats. Hypothalamic PVN, NTS and vagus nerve play key roles in this process.


Assuntos
Colite Ulcerativa/prevenção & controle , Colo/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/farmacologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colite Ulcerativa/fisiopatologia , Colo/inervação , Colo/metabolismo , Colo/patologia , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Mediadores da Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Núcleo Solitário/efeitos dos fármacos , Núcleo Solitário/fisiopatologia , Ácido Trinitrobenzenossulfônico , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiopatologia
13.
Oncotarget ; 7(18): 26247-58, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27028859

RESUMO

Mechanisms of stromal-epithelial crosstalk are essential for Prostate cancer (PCa) tumorigenesis and progression. Peripheral zone of the prostate gland possesses a stronger inclination for PCa than transition zone. We previously found a variety of genes that differently expressed among different prostate stromal cells, including LIM domain only 2 (LMO2) which highly expressed in peripheral zone derived stromal cells (PZSCs) and PCa associated fibroblasts (CAFs) compared to transition zone derived stromal cells (TZSCs). Studies on its role in tumors have highlighted LMO2 as an oncogene. Herein, we aim to study the potential mechanisms of stromal LMO2 in promoting PCa progression. The in vitro cells co-culture and in vivo cells recombination revealed that LMO2 over-expressed prostate stromal cells could promote the proliferation and invasiveness of either prostate epithelial or cancer cells. Further protein array screening confirmed that stromal LMO2 stimulated the secretion of Interleukin-11 (IL-11), which could promote proliferation and invasiveness of PCa cells via IL-11 receptor α (IL11Rα) - STAT3 signaling. Moreover, stromal LMO2 over-expression could suppress miR-204-5p which was proven to be a negative regulator of IL-11 expression. Taken together, results of our study demonstrate that prostate stromal LMO2 is capable of stimulating IL-11 secretion and by which activates IL11Rα - STAT3 signaling in PCa cells and then facilitates PCa progression. These results may make stromal LMO2 responsible for zonal characteristic of PCa and as a target for PCa microenvironment-targeted therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Interleucina-11/biossíntese , Proteínas com Domínio LIM/biossíntese , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas/biossíntese , Células Estromais/metabolismo , Animais , Progressão da Doença , Xenoenxertos , Humanos , Masculino , Camundongos , Comunicação Parácrina/fisiologia , Neoplasias da Próstata/metabolismo , Células Estromais/patologia , Regulação para Cima
14.
Curr Genet ; 62(3): 575-84, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26905382

RESUMO

Sexual reproduction of heterothallic clavicipitaceous fungus Villosiclava virens (anamorph: Ustilaginoidea virens) generates ascospores, which is considered as primary infection source of rice false smut disease. However, little is known about the molecular underpinnings of sexual reproduction in V. virens. In this study, transcriptomes of V. virens in fruiting body (FB) and sporulating mycelia (SM) were compared using Illumina paired-end sequencing technology. A total of 33,384,588 and 23,765,275 clean reads of FB and SM transcriptome profiles could be used to map cDNA of V. virens, respectively. We evaluated the gene expression variations between FB and SM, a total of 488 genes therein were significantly higher expressed in FB than SM, and 342 genes were significantly higher expressed genes in SM than FB. These differentially expressed genes were annotated using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases. Several genes were found to specifically function in sexual reproduction, involving in mating type, pheromone synthesis, signaling transduction, transcription factors, and meiosis; additionally, a few of genes were presumed to function in conidia sporulation and infection. Comparative transcriptome analysis of V. virens during FB and SM provided an overview of gene expression profiles at the transcriptional level and provided hints to better understand the molecular mechanisms of sexual development. Additionally, the data presented here also proved benefit for mining of essential genes contributing to sexual conidiation and infection.


Assuntos
Ascomicetos/fisiologia , Carpóforos , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Genes Fúngicos , Micélio , Transcriptoma , Biologia Computacional , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Anotação de Sequência Molecular
15.
FEMS Microbiol Lett ; 362(9)2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25682326

RESUMO

Ascospores of Villosiclava virens are a primary infection source of rice false smut. This phytopathogenic fungus exists in heterothallic form, and mating compatibility is regulated by mating-type locus 1 (MAT1). However, the MAT1 locus structure remains unknown. The MAT1-1 and MAT1-2 idiomorphs of V. virens were characterized and annotated on the basis of cDNA sequencing. A multiplex polymerase chain reaction (PCR) method was developed to identify the mating types of hyphae and sclerotia. The MAT1-1 locus of V. virens contains three mating-type genes: MAT1-1-1, MAT1-1-2 and MAT1-1-3, and a pseudogene similar to MAT1-2-1. The MAT1-2 locus harbors the MAT1-2-1 gene and a new mating-type gene MAT1-2-8. The mRNA of MAT1-1-1, MAT1-1-3 and MAT1-2-1, but not MAT1-1-2, was detectible by reverse transcription PCR in vegetative mycelia. However, the mRNA of MAT1-1-2 was detectible in the stroma, which is a sexual reproduction structure of V. virens. A multiplex PCR detection method was developed for the identification of the MAT1-1 and MAT1-2 idiomorphs. All 20 wild-type strains harbored either the MAT1-1 or MAT1-2 idiomorphs. Sclerotia that harbored both the MAT1-1 and MAT1-2 idiomorphs had potential to form fertile stromata, whereas those that harbored only the MAT1-1 idiomorph could not form mature stromata.


Assuntos
Genes Fúngicos Tipo Acasalamento , Loci Gênicos , Hypocreales/genética , Oryza/microbiologia , Hypocreales/fisiologia , Reação em Cadeia da Polimerase , Reprodução , Alinhamento de Sequência , Análise de Sequência de DNA , Esporos Fúngicos/genética , Esporos Fúngicos/fisiologia , Ustilaginales/genética
16.
Endocrine ; 48(1): 143-51, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24699882

RESUMO

Insulin resistance is a major feature and pathogenic factor of nonalcoholic fatty liver disease (NAFLD). Theoretically, genetic variation in candidate genes related to insulin resistance may contribute to the pathogenesis of NAFLD. The purpose of this study was to identify potentially pathogenic genes involved in NAFLD and insulin resistance that have not yet been discovered. This study yielded five important discoveries. 1. A total of 21 co-differentially expressed genes in both the NAFLD and insulin-resistance groups were identified from the pool containing thousands of genes via the significance analysis of microarrays method. 2. MAP kinase-interacting serine/threonine kinase 2 (Mknk2) was the unique gene to be identified that is involved in the insulin signaling pathway and Mitogen Activated Protein Kinase signaling pathway according to the Kyoto Encyclopedia of Genes and Genomes database. 3. Mknk2 mRNA and protein expression were dose-dependently up-regulated by palmitic acid (PA) in mouse primary hepatocytes. 4. Western blotting analysis and quantitative real-time PCR confirmed that Mknk2 affected the expression of acetyl-CoA carboxylases-1 and fatty acid synthase. 5. The inhibition of Mknk2 alleviated PA-induced insulin resistance, whereas the overexpression of Mknk2 resulted in the aggravation of insulin resistance in PA-treated hepatocytes. Therefore, we predict that MKNK2 may be a key protein related to NAFLD and insulin resistance.


Assuntos
Regulação da Expressão Gênica/genética , Resistência à Insulina/genética , Hepatopatia Gordurosa não Alcoólica/genética , Animais , Glucose/metabolismo , Teste de Tolerância a Glucose , Hepatócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasmídeos , Cultura Primária de Células , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética
17.
World J Gastroenterol ; 20(47): 17914-23, 2014 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-25548489

RESUMO

AIM: To assess the regulatory effect of microRNA-185 (miR-185) on lipid metabolism and the insulin signalling pathway in human HepG2 hepatocytes and a high-fat diet mouse model. METHODS: Quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA levels of lipogenic genes after loss or gain of miR-185. In addition, the amounts of insulin signalling intermediates were determined after transfection of HepG2 cells with pre-miR-185. RESULTS: MiR-185 levels decreased in a time- and dose-dependent manner in response to palmitic acid in human HepG2 hepatocytes. Transfection of HepG2 cells with miR-185 significantly decreased the mRNA levels of fatty acid synthase, 3-hydroxy-3-methylglutaryl-CoA reductase, sterol-regulatory element binding protein-2, and sterol-regulatory element binding protein-1c, whereas inhibition of miR-185 using an anti-miR-185 oligonucleotide produced the opposite effect in HepG2 cells. In a high-fat diet mouse model, the accumulation of lipids was significantly improved after treatment with miR-185, compared with control animals. Induction of miR-185 enhanced the insulin signalling pathway by up-regulating the insulin-receptor substrate-2. CONCLUSION: These findings suggest that miR-185 plays an important role in regulating fatty-acid metabolism and cholesterol homeostasis in hepatocytes, as well as in improving insulin sensitivity, both in vitro and in vivo.


Assuntos
Resistência à Insulina , Insulina/sangue , Metabolismo dos Lipídeos , Fígado/metabolismo , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Ácidos Graxos/sangue , Regulação da Expressão Gênica , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Metabolismo dos Lipídeos/genética , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , Oxirredução , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Tempo , Transfecção
18.
Med Oncol ; 31(4): 910, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24633705

RESUMO

The present study aimed to investigate the biological functions of miR-96 in the processes of proliferation and clonogenicity in the prostate cancer cells. miR-96 was identified to be markedly up-regulated in prostate cancer cell and cancer tissues compared with normal prostate cell and normal prostate tissues by microarray method and RT-PCR analysis. Down-regulation of miR-96 expression reduced the proliferation and colony formation ability of PC3 prostate cancer cells, while over-expression of miR-96 induced proliferation and colony formation ability of LNCaP prostate cancer cells. Forkhead box protein O1 (FOXO1) is key tumor suppressors and has been shown to play key roles in the regulation of diverse cellular processes, including cell proliferation, differentiation, cell cycle progression and apoptosis. The expression level of FOXO1 was strikingly up-regulated in PC3 cells after transfected with miR-96 inhibitor, and FOXO1 expression was down-regulated in LNCaP cells after transfected with miR-96 mimics. miR-96 may play a vital role in promoting cell proliferation in human prostate cancer cells. Inhibition of miR-96 caused expression increase of tumor suppressor gene FOXO1, thus manipulating miR-96 expression may be a promising approach in treatment of prostate cancer.


Assuntos
Regulação para Baixo , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/fisiologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Idoso , Apoptose , Ciclo Celular , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Proteína Forkhead Box O1 , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Resultado do Tratamento
19.
Lasers Med Sci ; 29(3): 957-63, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24026112

RESUMO

Thulium laser resection of the prostate-tangerine technique (TmLRP-TT) dissects whole prostatic lobes off the surgical capsule, similar to peeling a tangerine. The present study aimed to evaluate the safety and efficacy of TmLRP-TT for older symptomatic benign prostatic hyperplasia patients with large prostates during 18 months of follow-up. A prospective analysis of 95 consecutive patients with large prostates (>80 ml) who underwent surgical treatment using TmLRP-TT was carried out. All patients were evaluated preoperatively and at 1, 6, 12, and 18 months postoperatively by the International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Q max), postvoid residual urine volume (PVR), International Index of Erectile Function 5 (IIEF-5), urine analysis, and urine culture. Perioperative complications were recorded and graded by the modified Clavien classification system (CCS). Mean preoperative prostate volume was 106.81 ± 24.79 ml. TmLRP-TT was successfully completed in all patients. The mean operative duration, catheterization time, and hospital stay were 95.36 ± 27.06 min, 2.25 ± 0.9 days, and 5.39 ± 1.18 days, respectively. The decrease in mean hemoglobin level was 1.23 ± 0.72 g/dl, and that in mean serum sodium level was 0.71 ± 2.56 mmol/l. Within the observation period of 18 months, the patients showed an improvement in IPSS (20.01 ± 7.08 vs. 4.96 ± 3.68), QoL (4.10 ± 1.16 vs. 1.23 ± 1.30), Q max (8.14 ± 3.81 ml/s vs. 18.33 ± 2.56 ml/s) and PVR (102.70 ± 70.64 ml vs. 20.28 ± 30.02 ml), compared with baseline values (P < 0.001). IIEF-5 remained stable. Minor complications occurred in 10 (10.52 %) of 95 patients (Clavien grade 1, 9.47 % and grade 2, 1.05 %). There were no severe complications requiring reintervention (Clavien grade 3, 0 % and grade 4, 0 %). TmLRP-TT is a safe and effective surgical endoscopic technique associated with a low complication rate in large prostates as assessed during an 18-month follow-up period. It is a promising technology, which may be considered as one of the alternatives to open simple prostatectomy (OP) for large prostates in the future.


Assuntos
Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Lasers , Próstata/patologia , Próstata/cirurgia , Hiperplasia Prostática/cirurgia , Túlio/uso terapêutico , Idoso , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Cuidados Pré-Operatórios , Estudos Prospectivos , Prostatectomia/efeitos adversos , Hiperplasia Prostática/fisiopatologia , Resultado do Tratamento , Micção
20.
Chin Med J (Engl) ; 126(15): 2960-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23924475

RESUMO

OBJECTIVE: To discuss the novel biomarkers of microRNAs in prostate cancer. DATA SOURCES: The literatures about microRNAs and prostate cancer cited in this review were obtained mainly from Pubmed published in English from 2004 to 2012. STUDY SELECTION: Original articles regarding the novel role of microRNAs in prostate cancer were selected. RESULTS: MicroRNAs play an important role in prostate cancer such as cell differentiation, proliferation, apoptosis, and invasion. Especially microRNAs correlate with prostate cancer cell epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), drug sensitivity, cancer microenvironment, energy metabolism, androgen independence transformation, and diagnosis prediction. CONCLUSIONS: MicroRNAs are involved in various aspects of prostate cancer biology. The role of microRNA in the initiation and development of prostate cancer deserves further study.


Assuntos
MicroRNAs/fisiologia , Neoplasias da Próstata/patologia , Biomarcadores/análise , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , MicroRNAs/análise , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico
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