Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 90
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Genes (Basel) ; 11(2)2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32053967

RESUMO

The Apollo butterfly, Parnassius glacialis, is one of the most charming members of its genus and includes two subspecies locally distributed in montane areas of south-central China and Japan. In this study, we investigated the genetic structure and demographic history of P. glacialis by analyzing partial sequences of four mitochondrial genes and nuclear single nucleotide polymorphisms (SNPs) via genotyping-by-sequencing (GBS) of samples from nearly the entire known distributional range in China. The mitochondrial DNA (mtDNA) data demonstrated that a total of 39 haplotypes were present, and the species was estimated to have diverged about 0.95 million years ago during the middle Pleistocene transition into two main clades that likely formed during the Kunlun-Huanghe tectonic movement. The two clades then dispersed independently in distinct geographic areas alongside the mountainous routes in central and southern China, most likely driven by the Pleistocene glacial-interglacial cycles. Nuclear SNP analysis was generally congruent with mtDNA results at the individual level. A minor incongruence of genetic structures that was detected between mtDNA and nuclear SNP data from the Laojunshan and Tiantangzhai populations was likely due to secondary contact and male-biased dispersal. Our work demonstrates that complicated dispersal-vicariance evolutionary processes likely led to the current geographic distribution of P. glacialis in China, particularly the uplift of the Qinghai-Tibet Plateau and related climatic oscillations during the Quaternary period.

2.
Exp Gerontol ; 131: 110813, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31874191

RESUMO

OBJECTIVE: The aim of this study was to evaluate the influence of single nucleotide polymorphisms (SNPs) in interleukin-6 (IL-6) gene and the haplotype on late-onset Alzheimer's disease (LOAD). METHODS: A total of 896 participants were enrolled, including 446 LOAD patients and 450 controls. Total genomic DNA was extracted from the blood of participants and genotyping was then performed. Hardy-Weinberg equilibrium test was conducted in controls. Multivariate analysis was performed to determine the association between 4 SNPs (rs1800796, rs7802308, rs1800795 and rs13447446) in IL-6 gene and LOAD. Pairwise LD analysis was employed to identify the association between haplotype and LOAD. RESULTS: Multivariate logistic analysis showed that T allele of rs7802308 and G allele of rs1800796 were correlated with decreased risk of LOAD, adjusted ORs were 0.68 (95% CI: 0.50-0.91) and 0.71 (95% CI: 0.51-0.92), respectively. However, rs1800795 and rs13447446 were not associated with LOAD. Pairwise LD analysis among the 4 SNPs showed that only rs1800796 and rs1800795 in IL-6 gene was in heavy LD, the D' value was >0.75 (0.825). In all samples, the haplotype C-G was observed most frequently in two groups, with 55.79% and 49.46% in the LOAD patients and controls, respectively. The results also indicated that haplotype G-C was significantly associated with decreased LOAG risk. CONCLUSIONS: T allele of rs7802308 and G allele of rs1800796 were correlated with decreased risk of LOAD. The haplotype G-C were also correlated with decreased risk of LOAD.

3.
Technol Cancer Res Treat ; 18: 1533033819883633, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31684829

RESUMO

OBJECTIVE: To investigate the effect of long noncoding RNA GM16343 on interleukin 36ß promotion of CD8+T cells in tumor microenvironment regulation. METHODS: The differentially expressed long noncoding RNA in interleukin 36ß-stimulated mouse CD8+T cells was screened by gene chip technology, and the significant differentially expressed long noncoding RNAs were verified by real-time polymerase chain reaction. The lentiviral vector that overexpresses or knockdown GM16343 was constructed, transfected into CD8+T cells, and stimulated with interleukin 36ß, and the amount of interferon γ secreted was detected by enzyme-linked immunosorbent assay. A mouse subcutaneous xenograft model that stably express interleukin 36ß was established, and the tumor size and mouse survival time were observed by stimulation with CD8+T cells overexpression or knockdown of GM16343. RESULTS: A total of 12 long noncoding RNAs with significant differences were screened by gene chip analysis. Real-time polymerase chain reaction showed that the difference in GM16343 was larger, and the difference between the groups was observed to be the most significant. Compared to control group, CD8+T cells overexpressing GM16343 increased the secretion of interferon γ, and the tumor diameter of the mice after stimulation showed significant reduction, and the survival time showed significant prolongation. Compared to control group, the CD8+T cells after GM16343 were knocked down. The interferon γ secretion was decreased, and no significant change in tumor diameter and survival time was observed. CONCLUSION: Interleukin 36ß may enhance antitumor immune response of CD8+T cells by regulating GM16343.

4.
Cell Cycle ; 18(22): 3095-3110, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31564203

RESUMO

There is growing evidence of the position of microRNAs (miRs) in Alzheimer's disease (AD), thus our objective was to discuss the impact of miR-129-5p regulating nerve injury and inflammatory response in AD rats by modulating SOX6 expression. The AD rat model was established by injecting Aß25-35 into the brain. The pathological changes, ultrastructure, number of neurons, cell degeneration and apoptosis of hippocampal tissue were observed in vivo. MiR-129-5p, SOX6, IL-1ß, TNF-α, Bcl-2 and Bax expression in serum and hippocampal tissues were detected by ELISA, RT-qPCR or western blot analysis. The successfully modeled hippocampal neuronal cells of AD were transfected with miR-129-5p mimic, SOX6-siRNA or their controls to figure out their roles in proliferation, apoptosis and inflammatory reaction in vitro. Low expression of SOX6 and high expression of miR-129-5p in vivo of rats would shorten the escape latent period and increase the times of crossing platforms, alleviate the pathological injury, inhibit neuronal apoptosis and reduce the inflammatory reaction. Up-regulation of miR-129-5p and down-regulation of SOX6 promoted proliferation, suppressed apoptosis and degraded the inflammatory reaction of neuronal cells in vitro. Up-regulation of SOX6 reversed the expression of miR-129-5p to reduce the damage and inflammatory response of the cell model of AD. Our study presents that up-regulation of miR-129-5p or down-regulation of SOX6 can reduce nerve injury and inflammatory response in rats with AD. Thus, miR-129-5p may be a potential candidate for the treatment of AD.

5.
Anal Chem ; 91(10): 6746-6753, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31002238

RESUMO

Recent studies have indicated that circulating noncoding RNAs (ncRNAs) such as miRNAs are stable biomarkers for the diagnosis and prognosis of human diseases. However, due to low concentrations of circulating ncRNAs in blood, data normalization in plasma/serum ncRNA experiments using next-generation sequencing and quantitative real time RT-qPCR is a challenge. We found that the current normalization methods based on synthetic external spiked-in controls or published endogenous miRNA controls are inappropriate as they are not stably expressed and therefore fail to reliably detect differentially expressed ncRNAs. Using the alternative of individual ncRNAs as biomarkers, we considered a ratio-based normalization method calculated taking the ratio of any two ncRNAs in the same sample and used the resulting ratios as biomarkers. We mathematically verified the method to be independent of spiked-in and internal controls, and more robust than existing reference control based normalization methods to identify differentially expressed ncRNAs as potential biomarkers for human diseases. Thus, the ratio-based method can solve the difficult normalization problem for circuiting ncRNA data to identify reliable biomarkers to meet real clinical practice.

6.
Curr Neurovasc Res ; 16(2): 115-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30977447

RESUMO

OBJECTIVE: Paraoxonase (PON) family genes are closely related to the etiology and prognosis of cerebral infarction. This study explored the association of the promoter methylation of PON family genes (PON1, PON2 and PON3) with the risk of cerebral infarction. MATERIALS AND METHODS: In this study, 152 patients with confirmed cerebral infarction were selected as the case group, and 152 healthy controls were selected as the control group. The quantitative methylation-specific PCR (qMSP) was used to determine the promoter methylation levels of PON1, PON2 and PON3 genes. The methylation level was expressed as a methylation reference percentage (PMR). RESULTS: Our results indicated that PON1 methylation was significantly higher in the case group than in the control group (P = 0.0001). On the contrary, PON3 methylation was significantly lower in the case group than in the control group (P = 0.002). In addition, we found that PON2 gene had a very low level of methylation in both case and control groups (PMR = 0). Subgroup analysis showed that PON1 and PON3 methylation were associated with cerebral infarction only in males (PON1, P = 0.0002; PON3, P = 0.007). Interestingly, the methylation levels of PON1 and PON3 were correlated with each other (case: r = 0.418, P = 0.0001; control: r = 0.3, P = 0.0002). Further multiple regression analysis suggested that elevated methylation levels of PON3 were a protective factor for cerebral infarction [OR (95%CI) = 0.979 (0.96, 0.999), ß = -0.021, P = 0.035)], highdensity lipoprotein (HDL) and uric acid (UA) also were protective factors for cerebral infarction [HDL, OR (95% CI) = 0.01 (0.003, 0.033), P < 0.0001); UA, OR (95% CI) = 0.995 (0.991, 0.998), P = 0.003)]. The ROC curve analysis found that the combination of PON3, HDL, and UA had a good predictive power for cerebral infarction (AUC=0.878, 95% CI=0.839-0.918, sensitivity 73.7%, specificity 89.7%, P < 0.0001). CONCLUSION: PON1 and PON3 promoter methylation levels in peripheral blood were closely related. PON1 and PON3 methylation were associated with the risk of cerebral infarction in men. PON3 promoter methylation combined with HDL and UA could be used as potential biomarkers for the diagnosis of cerebral infarction.

7.
J Cancer Res Ther ; 15(2): 341-343, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30964108

RESUMO

Purpose: The purpose of this study is to evaluate the feasibility of percutaneous transauricular artery access for hepatic artery catheterization using a peripherally inserted central catheter (PICC) device and hepatic artery catheterization through auricular approach. Methods: Ten New Zealand White rabbits were used to establish a VX2 liver tumor model. Hepatic artery angiography and embolization were performed 3 weeks after inoculation. The rabbits were restrained in supine position under anesthesia. Intra-arterial access was accomplished with percutaneous Seldinger technique through the auricular artery using a PICC device. The hepatic artery catheterization was performed with a microcatheter and guide wire. The rate of technical success and procedure time was investigated. Results: Two rabbits failed initial percutaneous transauricular arterial access, with success in a contralateral attempt. Thus, percutaneous transauricular arterial access was achieved in 10 of 12 auricular arteries, with a technical success rate of 83.3%. The time needed to obtain intra-auricular access was 7.2 ± 3.1 min. Hepatic artery catheterization, angiography, and embolization were accomplished through the auricular approach in all 10 rabbits. Conclusion: Arterial access in rabbits can be achieved through the auricular artery. Hepatic artery catheterization, angiography, and embolization can be performed through auricular arterial access.


Assuntos
Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica/métodos , Artéria Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Angiografia/métodos , Animais , Carcinoma Hepatocelular/diagnóstico , Cateteres de Demora , Modelos Animais de Doenças , Humanos , Neoplasias Hepáticas/diagnóstico , Coelhos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Medicine (Baltimore) ; 98(7): e14593, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762812

RESUMO

BACKGROUND: Telomere length is closely related to the onset and prognosis of ischemic stroke. This study was to investigate the relationship between telomere length and the incidence of ischemic stroke in Han population of northern China. METHODS: In the present study, 152 patients with ischemic stroke were selected as the case group, and 152 healthy persons were used as the control group. Detection of telomere length was done by real-time polymerase chain reaction after extraction of genomic DNA from peripheral venous blood. RESULTS: Our results showed that the telomere length of the patients in the case group was significantly lower than that of the control group (Z = -11.843, P < .0001). Further analysis found that the telomere length of the control group was inversely correlated with age (r = -0.234, P = .004), and the telomere length and homocysteine (HCY) were inversely correlated in the case group (r = -0.176, P = .03), especially in women (r = -0.357, P = .024). Multivariate regression analysis showed that telomere length was a protective factor for ischemic stroke (odds ratio [OR] 95% confidence interval [95% CI] = 0.748 [0.681-0.823], ß = -0.29, P < .0001). The receiver operating characteristic curve showed that telomere length was a good diagnostic biomarker of ischemic stroke (area under the curve: 0.894, sensitivity: 84.7%, specificity: 93.4%). CONCLUSION: Our results indicate that shorter telomere length has some connection with the risk of ischemic stroke in the northern Chinese Han population. Telomere length might serve as a potential candidate biomarker for ischemic stroke. This requires a large sample to be further verified.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Acidente Vascular Cerebral/genética , Telômero , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , China/epidemiologia , Feminino , Homocisteína/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Acidente Vascular Cerebral/etnologia
9.
Eur J Pharmacol ; 843: 134-144, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30412727

RESUMO

Alzheimer's disease (AD) is a great threat for the health and life of elderly people. MicroRNA-128 (miR-128) has been reported to be abnormally expressed in the brain of AD patients and associated with the pathogenesis of AD. Our study aimed to have a deep insight into the roles and molecular basis of miR-128 in the development and progression of AD. The cognitive ability and exploratory behaviors were assessed by morris water maze and open-field tests, respectively. The concentrations of amyloid-ß (Aß) 40, Aß 42, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-10 and activity of ß-secretase and α-secretase were determined by corresponding ELISA commercial kits. RT-qPCR assay was performed to detect miR-128 level and the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARγ), ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP). Western blot assay was conducted to determine protein expression of PPARγ, amyloid precursor protein (APP), ß-APP cleaving enzyme (BACE1), sAPPα and sAPPß. The effect of miR-128 and PPARγ on amyloid plaque formation was assessed by immunohistochemistry assay. PPARγ mean optical density was determined by immunofluorescence assay. The interaction between miR-128 and PPARγ were validated by bioinformatics analysis and luciferase reporter assay. We found AD mice showed AD-like performance and an increased cerebral cortex Aß production. MiR-128 expression was upregulated and PPARγ expression was downregulated in cerebral cortex of AD mice. Moreover, PPARγ was a target of miR-128. Additionally, miR-128 knockout or PPARγ upregulation inhibited AD-like performances, amyloid plaque formation, Aß generation, APP amyloidogenic processing and inflammatory responses in AD mice, while these effects of miR-128 knockout were abrogated by PPARγ inhibitor. The results indicated MiR-128 knockout weakened AD-like performances, and reduced Aß production and inflammatory responses by targeting PPARγ in AD mice.


Assuntos
Doença de Alzheimer , MicroRNAs , PPAR gama , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Comportamento Animal , Linhagem Celular Tumoral , Córtex Cerebral/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Locomoção , Aprendizagem em Labirinto , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , MicroRNAs/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Regulação para Cima
10.
J Cell Biochem ; 119(12): 10327-10337, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30129142

RESUMO

Epidermal growth factor-like domain multiple 7 (EGFL7) is an important sport stimulating factor and motility related factors significantly enhanced the tumor cell metastasis and overexpressed in many cancers, including hepatocellular carcinoma (HCC), associated with tumorigenesis. However, the molecular mechanism by which EGFL7 regulates HCC cell proliferation and apoptosis and the correlation between EGFL7 and cyclin-dependent kinases regulatory subunit 2 (CKS2), which is essential for biological function, have not fully explained. In this study, EGFL7 and CKS2 expression in patients with HCC was measured by real-time polymerase chain reaction and immunohistochemistry. After HCC cells respectively transfected with pLKO.1-EGFL7-shRNA, pLVX-Puro-EGFL7 recombined vector or CKS2 small interfering RNA, cell counting kit-8 and flow cytometry was performed to examine the cell proliferation and apoptosis, respectively, and the expression of ß-catenin, CKS2, CDK2, and cleaved caspase-3 was measured by Western blot analysis. We found that EGFL7 and CKS2 were overexpressed in HCC tissues and a positive correlation was found between them. EGFL7 knockdown markedly inhibited proliferation and promoted apoptosis of HCC cells, along with decreased expression of CKS2 and CDK2, but increased cleaved caspase-3 expression, while EGFL7 overexpression showed an opposite effect. EGFL7 silencing in nude mice also showed decreased tumor growth and altered protein expression similar to its effect in HCC cells in vitro. Importantly, CKS2 silencing significantly inhibited EGFL7-induced HCC cell proliferation and protein expression, and Wnt/ß-catenin signaling pathway inhibitor IWR-1-endo significantly inhibited CKS2 expression in HCC cells. Taken together, EGFL7 promotes HCC cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/ß-catenin signaling.


Assuntos
CDC2-CDC28 Quinases/genética , Carcinoma Hepatocelular/genética , Proteínas de Transporte/genética , Proteínas de Ciclo Celular/genética , Fatores de Crescimento Endotelial/genética , Neoplasias Hepáticas/genética , Apoptose/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Via de Sinalização Wnt/genética
11.
J Cancer Res Ther ; 14(4): 867-872, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29970668

RESUMO

Objective: Epidermal growth factor-like domain-containing protein 7 (EGFL7) is an endothelial cell-derived secreted factor that regulates vascular tube formation. In human cancer, the specificity of expression is lost as EGFL7 has been detected in tumor cells, in addition to endothelial cells. This study evaluated the intricate relationship between hypoxia-inducible factor 1-alpha (HIF-1α) and EGFL7 under both hyperoxia and hypoxia states. Materials and Methods: In the present study, immunohistochemical staining and ELISA were applied to examine the relative level of EGFL7 in 182 cases of hepatocellular carcinoma (HCC) formalin-fixed and paraffin-embedded tissues and 110 cases of HCC serum samples. Quantitative polymerase chain reaction and Western blotting were applied to verify the correlation between serum EGFL7 level and anoxic microenvironment. Immunohistochemical staining was performed to determine the correlation between EGFL7 and HIF1-α. Results: The correlations between EGFL7 expression and patients' age, tumor size, gender, N-stage, history of cirrhosis, M-stage, history of hepatitis C, and history of hepatitis B were statistically insignificant (P = 0.28, 0.34, 0.71, 0.15, 0.8, 0.2, 0.052, and 0.14, respectively). High level of EGFL7 was significantly correlated with overall survival as well as disease-free survival in 182 HCC patients (P = 0.0016 and P < 0.001, respectively). The correlations between serum EGFL7 and vascular invasion and extrahepatic metastasis were statistically significant (P < 0.0001). Among the 35 HIF1-α-positive HCC patients, 69% were medium positive and 31% were strong positive. EGFL7 protein expression level was oxygen dependent in HCC line (P < 0.05). Conclusions: EGFL7 was found to be a potential predictor for HCC survival and metastasis state; EGFL7 may be a promising biomarker and therapeutic target in human HCC.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Fatores de Crescimento Endotelial/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Fatores de Crescimento Endotelial/genética , Feminino , Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Oxigênio/metabolismo , Prognóstico
12.
Cell Transplant ; 27(2): 310-324, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29637817

RESUMO

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Humanos , Regeneração Nervosa/fisiologia , Controle de Qualidade
13.
Sci Rep ; 8(1): 1756, 2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29379030

RESUMO

Multiple Sclerosis (MS), is a chronic inflammatory autoimmune disorder of the central nervous system that leads to chronic demyelination with axonal damage and neuronal loss. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for MS. In the current study, we investigated the effects of MSCs derived from the human umbilical cord (UCMSC) transfected by sphingosine kinase 1 (SPK1) gene. All the results showed that transplantation of UCMSCs gene modified by SPK1 (UCMSC-SPK1) dramatically reduce the severity of neurological deficits of the experimental autoimmune encephalomyelitis (EAE) mice, paralleling by reductions in demyelination, axonal loss, and astrogliosis. UCMSC-SPK1 transplantation also could inhibit the development of natural killer (NK) responses in the spleen of EAE mice, and increase the ratio of CD4+ CD25+ FoxP3+ (Treg) T cells. Furthermore, we described that a shift in the cytokine response from Th1/Th17 to Th2 was an underlying mechanism that suppressed CNS autoimmunity. UCMSCs transfected by SPK1 gene potentially offer a novel mode for the treatment of MS, and the specific mechanism of SPK1 in treating MS/EAE.


Assuntos
Encefalomielite Autoimune Experimental/terapia , Células-Tronco Mesenquimais/metabolismo , Esclerose Múltipla/terapia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Cordão Umbilical/metabolismo , Animais , Autoimunidade/fisiologia , Linfócitos T CD4-Positivos/metabolismo , Sistema Nervoso Central/metabolismo , Feminino , Humanos , Células Matadoras Naturais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Transfecção/métodos
14.
Exp Biol Med (Maywood) ; 243(4): 344-349, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29350066

RESUMO

It has been previously suggested that cytokeratins (CKs) are important diagnostic and prognostic biomarkers for urothelial lesions. Hence it is imperative to understand the expression pattern of cytokeratins during formation of papillary bladder cancer, which was the objective of the current study. Expression pattern of CK14 and CK18 were examined using immunohistochemical staining in a mice model of papillary bladder cancer. Twenty female mice were divided into two groups-group 1 (NT) and group 2, which received N-butyl- N-(4-hydroxybutyl) nitrosamine (BBN) for 20 weeks plus one week without treatment. Following histological classification of bladder lesions, CK14 and CK18 immunostaining was assessed according to its distribution and intensity. In NT animals, both basal cells and umbrella cells showed sporadic positive staining for CK14 and CK18, respectively. In BBN group, hyperplastic lesions showed significantly more CK14 and significantly less CK18 staining ( P < 0.05 in each case). Invasive carcinomas showed increased CK14 immunostaining in all epithelial layers. Cumulatively, our data indicate that altered CK14 (high) and CK18 (low) expression is perhaps an early event in bladder cancer tumorigenesis in females at least and is characteristic of both urothelial superficial pre-neoplastic and neoplastic lesions. Impact statement Studies have shown that expression of cytokeratins (CKs) or their altered distribution affects the bladder cancer pathogenesis and disease outcome, while the underlying mechanisms are not clear. The present study aims to explore the expression pattern of CK14 and CK18 during formation of papillary bladder cancer. The results showed that hyperplastic lesions showed significantly more CK14 and significantly less CK18 staining and invasive carcinomas showed increased CK14 immunostaining in all epithelial layers in N-butyl- N-(4-hydroxybutyl)nitrosamine (BBN)-induced mouse model. The results indicate that altered CK14 (high) and CK18 (low) expression is perhaps an early event in bladder cancer tumorigenesis and is characteristic of both urothelial superficial pre-neoplastic and neoplastic lesions, which may provide the early diagnosis index.


Assuntos
Carcinoma Papilar/patologia , Queratina-14/análise , Queratina-18/análise , Lesões Pré-Cancerosas/patologia , Neoplasias da Bexiga Urinária/patologia , Animais , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Camundongos Endogâmicos C57BL
15.
Artigo em Inglês | MEDLINE | ID: mdl-30671129

RESUMO

Gut microbiota play an important role in modulating energy contribution, metabolism, and inflammation, and disruption of the microbiome population is closely associated with chronic metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD). Gegen Qinlian decoction (GGQLD), a well-known traditional Chinese herbal medicine (CHM), was previously found to regulate lipid metabolism and attenuate inflammation during NAFLD pathogenesis. However, the underlying mechanism of this process, as well as how the gut microbiome is involved, remains largely unknown. In this study, we investigated the effect of varying doses of GGQLD on the total amount and distribution of gut bacteria in rats fed a high-fat diet (HFD) for 8 weeks. Our analysis indicates that Oscillibacter and Ruminococcaceae_g_unclassified are the dominant families in the HFD group. Further, HFD-dependent differences at the phylum, class, and genus levels appear to lead to dysbiosis, characterized by an increase in the Firmicutes/Bacteroidetes ratio and a dramatic increase in the Oscillibacter genus compared to the control group. Treatment with GGQLD, especially the GGQLL dose, improved these HFD-induced changes in intestinal flora, leading to increased levels of Firmicutes, Clostridia, Lactobacillus, bacilli, and Erysipelotrichales that were similar to the controls. Taken together, our data highlight the efficacy of GGQLD in treating NAFLD and support its clinical use as a treatment for NAFLD/NASH patients.

16.
Oncol Rep ; 39(2): 643-650, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29207139

RESUMO

Osteosarcoma (OS) is the most common primary malignancy of the bone affecting children and adolescents. Copine 1 (CPNE1) is a highly conserved calcium-dependent phospholipid-binding protein and may function in regulating signal transduction and membrane trafficking. In the present study, we investigated CPNE1 expression in osteosarcoma tissues and cells, and studied the effects of small interfering RNA (siRNA)-targeting CPNE1 on proliferation, metastasis and chemosensitivity of the osteosarcoma cells. The results demonstrated that CPNE1 was highly expressed in the osteosarcoma tissues and cell lines. Moreover, functional investigations confirmed that CPNE1 knockdown significantly inhibited cell proliferation, colony formation, invasion and metastasis in Saos-2 and HOS cells. Western blot analysis indicated that CPNE1 silencing downregulated the expression of many proteins associated with tumorigenesis and development, including Ras, MEK-1/2, WNT1, ß-catenin, cyclin A1, IRAK2 and cIAP2. In addition, CPNE1 downregulation enhanced the sensitivity of Saos-2 cells towards cisplatin and adriamycin. The present study provides deep insight into the clinical use of lentiviral-mediated CPNE1 silencing for osteosarcoma therapy.


Assuntos
Neoplasias Ósseas/genética , Proteínas de Ligação ao Cálcio/genética , Inativação Gênica , Osteossarcoma/genética , Adulto , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Transdução de Sinais
17.
Exp Ther Med ; 14(5): 4279-4287, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29104641

RESUMO

The present study aimed to explore the mechanism of action of Gegen Qinlian decoction (GGQLD) in experimental non-alcoholic fatty liver disease (NAFLD). A total of 30 rats were randomly divided into five groups: The chow, model, high- and low-dose GGQLD (GGQLD-H and GGQLD-L, respectively) and resveratrol (Resl) groups, and were treated with saline, GGQLD and Resl when a model of high-fat diet (HFD)-induced NAFLD was established. Blood lipid and liver enzymes were detected following treatment for 8 weeks and liver tissue pathology was observed using Oil Red O and haematoxylin and eosin staining. Furthermore, the liver protein and mRNA expression of sirtuin (Sirt)1, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) were measured using western blotting and reverse transcription-quantitative polymerase chain reaction. Compared with the chow group, the model group demonstrated significantly increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P<0.01). GGQLD doses and Resl attenuated the elevated serum ALT and AST levels. GGQLD-H and Resl significantly increased the serum high-density lipoprotein cholesterol level compared with that in the model group (P<0.01), while GGQLD-L and Resl significantly decreased serum low-density lipoprotein cholesterol levels (P<0.01). The GGQLDs and Resl groups revealed an evident improvement in Sirt1 protein and mRNA expression. Although GGQLD and Resl significantly decreased NF-κB gene expression compared with the model group (P<0.01), the effect on NF-κB protein expression was not significant. Furthermore, the PGC-1α gene and protein expression in the HFD rat group slightly decreased compared to the levels in the chow group, but the decrease was insignificant. However, an evident increase in PGC-1α mRNA expression was observed in the GGQLD-H group compared with the model group (P<0.01). Histological staining revealed that GGQLD and Resl decreased the lipid droplets in hepatocytes and normalized steatosis in rats fed with a HFD. The results indicated that GGQLD treatment may be a potent strategy for managing NAFLD by managing lipid metabolism and inflammatory and histological abnormalities by triggering the Sirt1 pathway.

18.
Oncotarget ; 8(44): 76279-76289, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-29100311

RESUMO

HADH is a key enzyme in fatty acid oxidation. The aim of this study was to identify the role of HADH in gastric cancer. We analyzed the expression of HADH in 102 pairs of gastric cancer samples. Western blot analysis revealed that HADH was decreased in stage I/II gastric cancer samples compared to matched adjacent normal gastric tissue, and its expression was further decreased in stage III/IV samples. Importantly, the reduced expression of HADH was associated with increased expression of p-Akt and reduced expression of PTEN in the gastric carcinoma tumor samples. To determine the significance of HADH downregulation in gastric cancer progression, we tested the impact of HADH knockdown or overexpression on the migration and invasion of the gastric cancer cells using a transwell assay. Knockdown of HADH significantly promoted gastric cancer cell migration and invasion, which was associated with increased expression of p-Akt. The PI3K inhibitor LY294002 inhibited HADH shRNA induced migration/invasion, and abolished the upregulation of p-Akt. By contrast, HADH overexpression inhibited the migration and invasion of MKN45 cells. Herein, for the first time, we demonstrate that downregulation of HADH promotes gastric cancer progression via activation of Akt signaling pathway.

19.
Oncotarget ; 8(45): 79157-79164, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29108295

RESUMO

Aims: To investigate the impact of Interleukin-16 (IL- 16) and Adiponectin (ANP) gene single nucleotide polymorphisms (SNPs), gene- gene interactions and haplotype on late-onset Alzheimer's disease (LOAD) risk. Methods: Hardy-Weinberg equilibrium (HWE), haplotype and pairwise linkage disequilibrium (LD) analysis were investigated by using SNPstats (available online at http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) was used to examine interaction among 4 SNPs, odds ratio (OR) and 95% confident interval (95%CI) were calculated by logistic regression model. Results: LOAD risk was significantly higher in carriers of rs266729- G allele than those with CC genotype (CG+ GG versus CC), OR (95%CI) =1.61 (1.26-1.96), and higher in carriers of rs1501299- T allele, OR (95%CI) = 1.62 (1.32-2.12), lower in carriers of rs4072111- T allele, adjusted OR (95%CI) =0.65 (0.44-0.93). We also found a significant gene- gene interaction between rs266729 and rs4072111. Participants with CG or GG of rs266729 and CC of rs4072111 genotype have the highest LOAD risk, OR (95%CI) = 2.62 (1.64 -3.58). Haplotype containing the rs266729- G and rs1501299- T alleles were associated with increased LOAD risk, OR (95%CI)= 1.83 (1.32- 2.43), and haplotype containing the rs1131445- C and rs4072111- T alleles were associated with decreased LOAD risk, OR (95%CI)= 0.53 (0.18- 0.95). Conclusions: We concluded that rs266729 and rs1501299 minor alleles were associated with increased LOAD risk, but rs4072111 minor allele was associated with decreased LOAD risk. We also found that interaction involving rs266729 and rs4072111, and haplotype combinations were associated with LOAD risk.

20.
Cell Physiol Biochem ; 43(6): 2226-2241, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29069652

RESUMO

BACKGROUND/AIMS: The study aimed to investigate the protective effect of curcumin against oxidative stress-induced injury of Parkinson's disease (PD) through the Wnt/ß-catenin signaling pathway in rats. METHODS: The successfully established PD rat models and normal healthy rats were randomly assigned into the 6-hydroxydopamine (6-OHDA), the curcumin (Cur) and the control groups. Immunohistochemistry was used to detect the positive expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and glial fibrillary acidic protein (GFAP). Deutocerebrum primary cells were extracted and classified into the control, 6-OHDA, Cur (5, 10, 15 µmol/L), Dickkopf-1 (DKK-1) and Cur + DKK-1 groups. MTT assays, adhesion tests and TUNEL staining were used to assess cell viability, adhesion and apoptosis, respectively. Western blotting and qRT-PCR were used to examine the protein and mRNA expressions of Wnt3a and ß-catenin and the c-myc and cyclinD1 mRNA expressions. RESULTS: TH and DAT expressions in the Cur group were elevated and GFAP was reduced compared with the 6-OHDA group. Curcumin enhanced viability, survival and adhesion and attenuated apoptosis of deutocerebrum primary cells by activating the Wnt/ß-catenin signaling pathway. Higher Wnt3a and ß-catenin mRNA and protein expressions and c-myc and cyclinD1 mRNA expressions, enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) contents, decreased malondialdehyde (MDA) content and elevated mitochondrial membrane potential (∆ψm) were found in the 10 and 15 µmol/L Cur groups compared with the 6-OHDA group. However, opposite tendencies were found in the Cur + DKK-1 group compared to the 10 µmol/L Cur group. CONCLUSION: This study suggests that curcumin could protect against oxidative stress-induced injury in PD rats via the Wnt/ß-catenin signaling pathway.


Assuntos
Curcumina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Comportamento Animal/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Ciclina D1/genética , Ciclina D1/metabolismo , Modelos Animais de Doenças , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Glutationa Peroxidase/metabolismo , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Oxidopamina/farmacologia , Doença de Parkinson/patologia , Doença de Parkinson/veterinária , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Proteína Wnt3/genética , Proteína Wnt3/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA