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1.
Ocul Immunol Inflamm ; 28(1): 133-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30395736

RESUMO

Purpose: To investigate whether there is an association between circulating S100A8/A9 levels and uveitis activity.Methods: A total of 549 plasma samples were collected from uveitis patients and non-uveitic controls.Results: S100A8/A9 plasma levels were elevated in uveitis patients compared to non-uveitic controls (P < 0.001). S100A8/A9 plasma levels in patients with active acute anterior uveitis (AAU) were significantly elevated and remarkably decreased in parallel with the severity of intraocular inflammation after corticosteroid treatment (P < 0.001). S100A8/A9 plasma levels were also higher in AAU patients with ankylosing spondylitis (AS) than in patients without AS (P = 0.02). S100A8/A9 plasma levels were significantly increased in uveitis patients with elevated C-reactive protein (CRP, P = 0.004) or erythrocyte sedimentation rates (ESR, P = 0.049) levels compared to uveitis patients with normal CRP or ESR values.Conclusion: Circulating S100A8/A9 might be a useful biomarker for the measurement of intraocular inflammation.

2.
Oncol Lett ; 18(4): 4262-4269, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31579424

RESUMO

Multidrug-resistant tumor cells can tolerate different structures, functions and antidrug action mechanisms, therefore, allowing these cells to respond to various structurally unrelated mechanisms of different chemotherapy drugs and to exhibit cross-resistance. The present study aimed to investigate the role of Multi-drug resistance gene (MDR1), Placental glutathione S-transferase-P1 (GSTP1), Lung resistance protein (LRP) and Ras association domain family member 1 (RASSF1A) in primary epithelial ovarian cancer (PEOC). The mRNA (protein) expression levels of MDR1, product P glycoprotein, LRP and GSTP1 were evaluated with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis in all tissue samples, ovarian cancer cell line A2780 and A2780/DDP. Methylation-specific PCR (MSP) was used to detect RASSF1A gene methylation in all tissue samples. The resistance genes/proteins were either poorly or not expressed in A2780, however were highly expressed in A2780/DDP cell line. The expression of resistance genes/proteins decreased following different concentrations of zebularine-stimulated A2780/DDP. Hypermethylation and low expression of RASSF1A gene were detected in PEOC and A2780/DDP. Subsequent to being exposed to different concentrations of zebularine-stimulated A2780/DDP, the RASSF1A methylation level was decreased, while the unmethylation level was increased. The expression of RASSF1A gene/protein was gradually restored, and the gene/protein expression was enhanced with the increase in drug concentration. Multivariate logistic regression indicated that the expression level of gene LRP and GSTP1 was a risk factor for PEOC prognosis. Furthermore, the expression of LRP and GSTP1 in the negative-group survival curves was higher compared with the positive group. High expression of resistance genes may serve an important role in cancer primary resistance. Low expression caused by hyper-methylation of RASSF1A gene may serve an important role in cancer-acquired resistance in PEOC. The present study suggested that resistant gene expression may be a potential prognostic biomarker.

3.
PLoS One ; 14(9): e0222338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31527891

RESUMO

Rhesus macaque is an important animal model in biomedical research, especially human disease, developmental, translational, and pre-clinical research. Blood physiological and biochemical parameters are important markers for physiology, pathology, and toxicology research. However, these parameters have not been systematically reported for Chinese rhesus macaques. To characterize the reference for these parameters, this study collected 1805 Chinese rhesus macaques living in Southwestern China. A total of 24 blood physiological indexes and 27 biochemical parameters were determined. Sex and age were found to affect these parameters. In conclusion, a comprehensive and systematic reference of hematological and biochemical parameters for Chinese rhesus macaque was established in this work on the basis of a large cohort. Such reference will benefit biomedical research employing rhesus macaques as animal models.

4.
Virol J ; 16(1): 105, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426820

RESUMO

BACKGROUND: The gut microbiome is closely associated with the health of the host; although the interaction between the bacterial microbiome and the whole virome has rarely been studied, it is likely of medical importance. Examination of the interactions between the gut bacterial microbiome and virome of rhesus monkey would significantly contribute to revealing the gut microbiome composition. METHODS: Here, we conducted a metagenomic analysis of the gut microbiome of rhesus monkeys in a longitudinal cohort treated with an antibiotic cocktail, and we documented the interactions between the bacterial microbiome and virome. The depletion of viral populations was confirmed at the species level by real-time PCR. We also detected changes in the gut metabolome by GC-MS and LC-MS. RESULTS: A majority of bacteria were depleted after treatment with antibiotics, and the Shannon diversity index decreased from 2.95 to 0.22. Furthermore, the abundance-based coverage estimator (ACE) decreased from 104.47 to 33.84, and the abundance of eukaryotic viruses also changed substantially. In the annotation, 6 families of DNA viruses and 1 bacteriophage family were present in the normal monkeys but absent after gut bacterial microbiome depletion. Intriguingly, we discovered that changes in the gut bacterial microbiome composition may promote changes in the gut virome composition, and tryptophan, arginine, and quinone may play roles in the interaction between the bacterial microbiome and virome. CONCLUSION: Our results indicated that the clearly altered composition of the virome was correlated with depletion in the bacterial community and that metabolites produced by bacteria possibly play important roles in the interaction.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal/efeitos dos fármacos , Interações Microbianas , Vírus/isolamento & purificação , Animais , Antibacterianos/administração & dosagem , Bactérias/classificação , Fezes/microbiologia , Fezes/virologia , Estudos Longitudinais , Macaca mulatta/microbiologia , Macaca mulatta/virologia , Redes e Vias Metabólicas , Metaboloma , Metagenômica , Vírus/classificação
5.
Am J Transl Res ; 11(4): 2516-2531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105859

RESUMO

Multiple sclerosis (MS) is a demyelinating disease affecting 2.5 million young people worldwide because of its immune-mediated pathological mechanisms. Recent studies have shown that stem cell transplantation is a new potential therapy for MS. There has been renewed interest in cell therapy to improve quality of life for MS patients. In this study, the experimental autoimmune encephalomyelitis (EAE) model, which is the most commonly model to mimic MS, was successfully established in cynomolgus monkeys. To evaluate the therapeutic effect of human umbilical cord mesenchymal stem cells (UCMSCs) on MS, we intravenously transplanted UCMSCs into cynomolgus monkeys with EAE. Our results showed that UCMSC transplantation significantly ameliorated the clinical symptoms of MS. Magnetic resonance imaging and clinical signs indicated that demyelination was obviously decreased after UCMSCs therapy. Moreover, the present study showed that the mechanisms, involved in the effects of UCMSCs on MS, included their immunomodulatory functions to regulate cytokine secretion and affect functional differentiation of the T cell lineage.

6.
Front Neurosci ; 13: 326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001081

RESUMO

Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Aberrations in several cytoskeletal proteins, such as tau have been implicated in the pathogenesis of neurodegenerative diseases, could be initiating factors in glaucoma progression and occurring prior to axon degeneration. Developmentally regulated brain protein (Drebrin or DBN1) is an evolutionarily conserved actin-binding protein playing a prominent role in neurons and is implicated in neurodegenerative diseases. However, the relationship between circulating DBN1 levels and RGC degeneration in glaucoma patients remains unclear. In our preliminary study, we detected drebrin protein in the plasma of glaucoma patients using proteomic analysis. Subsequently, we recruited a total of 232 patients including primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG) and Posner-Schlossman syndrome (PS) and measured its DBN1 plasma levels. We observed elevated DBN1 plasma levels in patients with primary glaucoma but not in patients with PS compared to nonaxonopathic controls. Interestingly, in contrast to tau plasma levels increased in all groups of patients, elevated drebrin plasma levels correlated with retinal nerve fiber layer defect (RNFLD) in glaucoma patients. To further explore the expression of DBN1 in neurodegeneration, we conducted experiment of optic nerve crush (ONC) models, and observed increased expression of DBN1 in the serum as well as in the retina and then decreased after ONC. This result reinforces the potentiality of circulating DBN1 levels are increased in glaucoma patients with neurodegeneration. Taken together, our findings suggest that circulating DBN1 levels correlated with RNFLD and may reflect the severity of RGCs injury in glaucoma patients. Combining measurement of circulating drebrin and tau levels may be a useful indicator for monitoring progression of neurodegenerative diseases.

7.
Biosci Rep ; 39(5)2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-30979828

RESUMO

Objective: In this work, the relationship between octamer binding transcription factor 4 (OCT-4) expression and the clinicopathological features of cervical cancer (CC) is evaluated in detail.Methods: The library databases Pubmed, Embase, Cochrane library, Wan Fang and Chinese National Knowledge Infrastructure (CNKI) were searched for research related to these concepts published from the time the databases were established until May 2018. The obtained studies are screened, extracted, and evaluated according to the inclusion and exclusion criteria, and meta-analysis is carried out via RevMan 5.3.Results: Ten case-control studies, including 408 cases of CC, 164 cases of cervical intraepithelial neoplasia (CIN), and 148 cases of normal cervix, are included in the analysis. Results show that OCT-4 levels are statistically significantly different between the CC and normal cervical tissue groups (odds ratio (OR) = 15.59, 95% confidence interval (CI): 8.70, 27.94), the CC and CIN groups (OR = 5.64, 95% CI: 3.23, 9.86), the CIN and normal cervical tissues groups (OR = 7.13, 95% CI: 2.41, 21.05), and the CC well/moderately differentiated and poorly differentiated groups (OR = 0.44, 95% CI: 0.24, 0.81). OCT-4 is not statistically significantly different between CIN I + II and CIN III tissues (OR = 0.40, 95% CI: -0.02, 0.81), the CC lymphatic and non-lymphatic metastasis groups (OR = 1.93, 95% CI: 0.83, 4.47), the FIGO I and FIGO II groups (OR = 0.79, 95% CI: 0.29, 2.13), and the adenocarcinoma and squamous cell carcinoma groups (OR = 1.55, 95% CI: 0.70, 3.44).Conclusions: The available evidence suggests that OCT-4 expression is associated with CC malignancy and histological differentiation. This finding, however, is subject to quantitative studies and quality tests.

8.
Front Pharmacol ; 10: 262, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30967778

RESUMO

Ventilator-associated pneumonia (VAP) infection caused by carbapenem-resistant Enterobacteriaceae (CRE) is becoming more prevalent, thus seriously affecting patient outcomes. In this paper, we studied the drug resistance mechanism and epidemiological characteristics of CRE, and analyzed the infection and prognosis factors of VAP caused by CRE, to provide evidence for effective control of nosocomial infection in patients with VAP. A total of 58 non-repetitive CRE strains of VAP were collected from January 2016 to June 2018. To explore the risk factors of CRE infection, 1:2 group case control method was used to select non CRE infection patients at the same period as the control group. Among the 58 CRE strains, the most common isolates included Klebsiella pneumoniae and Escherichia coli. All strains were sensitive to polymyxin B, which features better sensitivity to other antibiotics such as minocycline, trimethoprim/sulfamethoxazole, and amikacin. Multiple drug resistance genes were detected at the same time in most strains. KPC-2 was the most common carbapenemase-resistant gene in Klebsiella pneumoniae, whereas NDM-1 was more common in Escherichia coli. The risk factors correlated with CRE infection included intensive care unit (ICU) occupancy time >7 days (OR = 2.793; 95% CI 1.439~5.421), antibiotic exposure during hospital stay including those to enzyme inhibitors (OR = 1.977; 95% CI 1.025~3.812), carbapenems (OR = 3.268; 95% CI 1.671~6.392), antibiotic combination therapy(OR = 1.951; 95% CI 1.020~3.732), and nerve damage (OR = 3.013; 95% CI 1.278~7.101). Multivariable analysis showed that ICU stay >7 days (OR = 1.867; 95% CI 1.609~20.026), beta-lactamase inhibitor antibiotics (OR = 7.750; 95% CI 2.219~27.071), and carbapenem (OR = 9.143; 95% CI 2.259~37.01) are independent risk factors for VAP carbapenem caused by Carbapenem-resistant Enterobacteriaceae. A high resistance rate of CRE isolated from VAP indicated that the infected patients featured higher mortality and longer hospital stay time than the control group. Multiple risk factors for CRE infection and their control can effectively prevent the spread of VAP.

9.
Vet Microbiol ; 230: 244-248, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30827396

RESUMO

Rhesus and several other species of monkeys are susceptible to genotypes of hepatitis E virus (HEV), and these species are thus commonly used as animal models for experimental HEV infection. However, information regarding HEV infection in monkeys in nature or at monkey farms is limited. To investigate the status of HEV infection in rhesus monkeys at farms, we collected 548 serum and 48 fecal samples from a rhesus monkey farm in China, and analyzed their levels of anti-HEV IgG antibodies and HEV RNAs. An enzyme-linked immunosorbent assay using genotype 3 HEV-like particles as antigen revealed anti-HEV IgG-positivity in 388 (70.8%) monkeys. The antibody-positive rates in the 1-year-old and 2-year-old monkeys were significantly lower than those in monkeys >3 years old. The antibody-positive rate was greatly increased from 7.4% in the 2-year-old monkeys to 100% in the 3-year-olds, suggesting that the latter received HEV infection at a high frequency. HEV RNA was detected in one of 88 sera from 1- and 2-year-old monkeys and 10 of 48 fecal specimens from 3-year-old monkeys by reverse transcription-polymerase chain reaction. Phylogenetic analyses revealed that the HEV strain RmKM15 was present in a serum sample that belonged to subtype 4b in genotype 4, whereas 10 strains detected in the fecal specimens belonged to subtype 4 h, suggesting that two genetically different strains were circulating at the farm. However, no significant clinical signs were observed in these monkeys. Further studies are required to identify the source of infection and to evaluate the pathogenicity of HEV in rhesus monkeys.


Assuntos
Vírus da Hepatite E/patogenicidade , Hepatite E/veterinária , Macaca mulatta/virologia , Doenças dos Macacos/virologia , Alanina Transaminase/sangue , Animais , Anticorpos Antivirais/sangue , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Fazendas , Fezes/virologia , Genoma Viral , Genótipo , Hepatite E/diagnóstico , Vírus da Hepatite E/genética , Imunoglobulina G/sangue , Doenças dos Macacos/diagnóstico , Filogenia , RNA Viral/sangue
10.
Adv Mater ; 31(18): e1807557, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30803073

RESUMO

Central nervous system (CNS) diseases are the leading cause of morbidity and mortality; their treatment, however, remains constrained by the blood-brain barrier (BBB) that impedes the access of most therapeutics to the brain. A CNS delivery platform for protein therapeutics, which is achieved by encapsulating the proteins within nanocapsules that contain choline and acetylcholine analogues, is reported herein. Mediated by nicotinic acetylcholine receptors and choline transporters, such nanocapsules can effectively penetrate the BBB and deliver the therapeutics to the CNS, as demonstrated in mice and non-human primates. This universal platform, in general, enables the delivery of any protein therapeutics of interest to the brain, opening a new avenue for the treatment of CNS diseases.


Assuntos
Doenças do Sistema Nervoso Central/tratamento farmacológico , Portadores de Fármacos/química , Proteínas/química , Animais , Barreira Hematoencefálica/metabolismo , Doenças do Sistema Nervoso Central/veterinária , Camundongos , Nanocápsulas/química , Fator de Crescimento Neural/química , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/uso terapêutico , Células PC12 , Polímeros/química , Primatas , Proteínas/metabolismo , Proteínas/uso terapêutico , Ratos , Rituximab/química , Rituximab/metabolismo , Rituximab/uso terapêutico
11.
World J Gastroenterol ; 24(45): 5109-5119, 2018 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-30568388

RESUMO

AIM: To establish a rotavirus (RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines. METHODS: Neonatal rhesus monkeys with an average age of 15-20 d and an average weight of 500 g ± 150 g received intragastric administration of varying doses of SA11 RV ( 107 PFUs/mL, 106 PFUs/mL, or 105 PFUs/mL, 10 mL/animal) to determine whether the SA11 strain can effectively infect these animals by observing their clinical symptoms, fecal shedding of virus antigen by ELISA, distribution of RV antigen in the organs by immunofluorescence, variations of viral RNA load in the organs by qRT-PCR, histopathological changes in the small intestine by HE staining, and apoptosis of small intestinal epithelial cells by TUNEL assay. RESULTS: The RV monkey model showed typical clinical diarrhea symptoms in the 108 PFUs SA11 group, where we observed diarrhea 1-4 d post infection (dpi) and viral antigen shed in the feces from 1-7 dpi. RV was found in jejunal epithelial cells. We observed a viral load of approximately 5.85 × 103 copies per 100 mg in the jejunum at 2 dpi, which was increased to 1.09 × 105 copies per 100 mg at 3 dpi. A relatively high viral load was also seen in mesenteric lymph nodes at 2 dpi and 3 dpi. The following histopathological changes were observed in the small intestine following intragastric administration of SA11 RV: vacuolization, edema, and atrophy. Apoptosis in the jejunal villus epithelium was also detectable at 3 dpi. CONCLUSION: Our results indicate that we have successfully established a RV SA11 strain diarrhea model in neonatal rhesus monkeys. Future studies will elucidate the mechanisms underlying the pathogenesis of RV infection, and we will use the model to evaluate the protective effect of candidate vaccines.


Assuntos
Diarreia/imunologia , Modelos Animais de Doenças , Macaca mulatta , Infecções por Rotavirus/imunologia , Rotavirus/patogenicidade , Animais , Animais Recém-Nascidos , Diarreia/diagnóstico , Diarreia/virologia , Células Epiteliais/imunologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Fezes/virologia , Humanos , Intestino Delgado/citologia , Intestino Delgado/imunologia , Intestino Delgado/patologia , Intestino Delgado/virologia , RNA Viral/isolamento & purificação , Rotavirus/genética , Rotavirus/imunologia , Infecções por Rotavirus/diagnóstico , Infecções por Rotavirus/virologia , Eliminação de Partículas Virais
12.
Medicine (Baltimore) ; 97(41): e12364, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30313031

RESUMO

The sensitivity of tumor cells to chemotherapy drugs may become attenuated accounts for various reasons. Reduced drug sensitivity may cause the failure of chemotherapy and affect the prognosis of patients with cancer. This study investigates the relationship between the expression levels of lung resistance protein (LRP) and placental glutathione S-transferase-P1 (GSTP1), the resistance of primary epithelial ovarian cancer (PEOC) to chemotherapy, and the prognosis of patients with platinum drug-resistant PEOC.Quantitative PCR (QT-PCR) was used to detect the mRNA level of the resistance genes LRP, GSTP1 in all tissue and cell lines.The expression levels of resistance gene (LRP, GSTP1) in PEOC were the highest, followed by borderline adenoma tissues, and the lowest levels found in benign tumor tissues, the difference of genes expression between different tissues was statistically significant; the difference between the expression rates and relative expression level of drug resistance genes was statistically significant in platinum sensitive group compare with the platinum resistant group. The difference between resistant gene negative-expression and positive-expression of chemotherapy efficiency, disease free survival time, and recurrence time were statistically significant. The resistant genes expression in the PEOC patients of the negative-group survival curves was higher than that in the positive group. With ascites non-cellular component (ANCC) stimulated SKOV3 cells, the cell proliferation inhibition rate (CPIR) increased, and with ANCC stimulated SKOV3/DDP, the expression of LRP and GSTP1 also increased.ANCC may promote the expression of drug resistance genes, and the expression of genes may predict the poorly prognosis of epithelial ovarian cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Regulação Neoplásica da Expressão Gênica , Glutationa S-Transferase pi/metabolismo , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Partículas de Ribonucleoproteínas em Forma de Abóbada/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário , Feminino , Seguimentos , Glutationa S-Transferase pi/genética , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Compostos de Platina/uso terapêutico , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sobrevida , Partículas de Ribonucleoproteínas em Forma de Abóbada/genética
13.
Emerg Microbes Infect ; 7(1): 155, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30228270

RESUMO

Coxsackievirus A16 (CA16) is a member of the Picornaviridae family and causes mild and self-limiting hand, foot, and mouth disease (HFMD) in infants and young children. CA16 infection can also progress to central nervous system (CNS) complications; however, the underlying mechanism by which CA16 penetrates the blood-brain barrier (BBB) and then causes CNS damage remains unclear. This study aimed to explore the mechanism of CA16 neurotropic tropism by establishing an in vitro BBB model with CA16 infection and an in vivo CA16 rhesus monkey infant infection model. The results showed that CA16 infection induced increased permeability of the BBB accompanied by upregulation of matrix metalloproteinase 9 (MMP9) expression. Subsequently, high-throughput miRNA sequencing technology and bioinformatics analysis revealed that miR-1303 may regulate BBB permeability by targeting MMP9. Next, we used dual-luciferase, qRT-PCR, and western blot assays to provide evidence of MMP9 targeting by miR-1303. Further experiments revealed that CA16 infection promoted the degradation of junctional complexes (Claudin4, Claudin5, VE-Cadherin, and ZO-1), likely by downregulating miR-1303 and upregulating MMP9. Finally, EGFP-CA16 infection could enter the CNS by facilitating the degradation of junctional complexes, eventually causing neuroinflammation and injury to the CNS, which was confirmed using the in vivo rhesus monkey model. Our results indicate that CA16 might penetrate the BBB and then enter the CNS by downregulating miR-1303, which disrupts junctional complexes by directly regulating MMP9 and ultimately causing pathological CNS changes. These results provide new therapeutic targets in HFMD patients following CA16 infection.


Assuntos
Barreira Hematoencefálica/virologia , Doenças do Sistema Nervoso Central/enzimologia , Enterovirus Humano A/fisiologia , Doença de Mão, Pé e Boca/complicações , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/metabolismo , Animais , Barreira Hematoencefálica/enzimologia , Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/virologia , Claudina-4/genética , Claudina-4/metabolismo , Claudina-5/genética , Claudina-5/metabolismo , Enterovirus Humano A/genética , Doença de Mão, Pé e Boca/virologia , Humanos , Macaca mulatta , Metaloproteinase 9 da Matriz/genética , MicroRNAs/genética
14.
Viruses ; 10(5)2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29724057

RESUMO

Herpes simplex virus type 1(HSV-1) presents a conundrum to public health worldwide because of its specific pathogenicity and clinical features. Some experimental vaccines, such as the recombinant viral glycoproteins, exhibit the viral immunogenicity of a host-specific immune response, but none of these has achieved a valid epidemiological protective efficacy in the human population. In the present study, we constructed an attenuated HSV-1 strain M3 through the partial deletion of UL7, UL41, and the latency-associated transcript (LAT) using the CRISPR/Cas9 system. The mutant strain exhibited lowered infectivity and virulence in macaques. Neutralization testing and ELISpot detection of the specific T-cell responses confirmed the specific immunity induced by M3 immunization and this immunity defended against the challenges of the wild-type strain and restricted the entry of the wild-type strain into the trigeminal ganglion. These results in rhesus macaques demonstrated the potential of the attenuated vaccine for the prevention of HSV-1 in humans.


Assuntos
Antígenos Virais/imunologia , Herpes Simples/prevenção & controle , Herpesvirus Humano 1/genética , Vacinas contra Herpesvirus/imunologia , Animais , Antígenos Virais/genética , Sistemas CRISPR-Cas , Herpes Simples/imunologia , Vacinas contra Herpesvirus/genética , Imunogenicidade da Vacina , Macaca mulatta/virologia , Mutação , Testes de Neutralização , Fenótipo , Gânglio Trigeminal/virologia , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia , Replicação Viral
15.
Mol Med Rep ; 15(5): 2802-2806, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28447725

RESUMO

Tumor cells may develop multidrug resistance (MDR) to various chemotherapy regimens. Such resistance reduces the sensitivity of cells to chemotherapy drugs, leading to the failure of cervical cancer (CC) treatment and disease progression. The present study aimed to investigate the role of MDR1, lung resistance protein (LRP) and placental glutathione S­transferase π 1 (GSTP1) in CC and MDR, and the prognostic value of these genes. The mRNA expression levels of these resistance­associated genes were determined in 47 CC and 20 healthy cervical tissue samples. Subsequently, the data was analyzed alongside clinicopathological parameters. The mRNA expression levels of MDR1, LRP and GSTP1 in CC were 0.57±0.32, 0.58±0.29 and 0.44±0.24, respectively, whereas those in healthy cervical tissues were 0.19±0.10, 0.17±0.14 and 0.18±0.10, respectively. Therefore, the expression levels of these genes were significantly greater in CC compared with healthy cervical tissue (P<0.05). mRNA expression levels of MRD1 were increased in the well differentiated group (0.68±0.27) compared with the poorly differentiated group (0.38±0.33; P<0.05). No significant differences were observed between LRP and GSTP1 mRNA expression levels and tumor differentiation or clinical stage of the patients (P>0.05). Multivariate logistic regression indicated that the degree of differentiation and the MDR1 gene expression levels were predictors of CC prognosis (P<0.05). The survival rate of patients in the MDR1­negative group was significantly greater compared with the MDR1­positive group (P<0.05). The results of the present study therefore suggested that MDR1 gene expression is a predictor of poor survival in CC.


Assuntos
Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Neoplasias do Colo do Útero , Subfamília B de Transportador de Cassetes de Ligação de ATP/biossíntese , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Taxa de Sobrevida , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
16.
Viruses ; 9(2)2017 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-28146109

RESUMO

As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1.Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection,and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG)on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues.


Assuntos
Modelos Animais de Doenças , Herpes Simples/patologia , Herpes Simples/virologia , Herpesvirus Humano 1/isolamento & purificação , Estruturas Animais/virologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , ELISPOT , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Macaca mulatta , Testes de Neutralização , Linfócitos T/imunologia
17.
Int J Clin Exp Pathol ; 8(6): 6995-7001, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26261589

RESUMO

OBJECTIVE: By the detection of HBV infection, AFP and AST, the targets of biological behavior and the gene expression of multi-drug resistance gene 1 (MDR1) in hepatocellular carcinoma (HCC), we investigate characteristics of the expression of MDR1 in HCC and its relationship with HCC biological behavior. METHODS: Using real-time fluorescence quantitative PCR (FQ-PCR) to detect the expressions of MDR1 in 102 samples of HCC tissue and 20 samples of non-cancerous tissue, we analyze the relationship between expressions of MDR1 and biological characteristics of HCC. RESULTS: The expression of MDR1 in HCC is 0.55 ± 0.27, and in normal liver tissues is 0.23 ± 0.10, respectively. The expression in HCC is higher than it in normal liver tissue, the difference is statistically significant (P<0.05) and the difference between the expression and the HCC envelopes is statistically significant, and the expression increases along with the increase of Edmondson classification (P<0.05). HBV infection, AFP positive, the rise of AST, all these factors have positive correlations with the expression (r=0.463, 0.473, 0.299). In MDR1 expressions of HCC patients, the survival curve of the negative is higher than that of the positive, but the difference is not statistically significant. CONCLUSION: There are drug resistance phenomena in HCC, MDR1 expression may play an important role in primary HCC drug resistance. HBV infection can be detected as a reference indicator of HCC chemotherapy resistance, plasma levels of AFP, AST can be used as a reference index change dynamic monitoring of MDR1 expression.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Idoso , Aspartato Aminotransferases/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B/complicações , Hepatite B/virologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Regulação para Cima , alfa-Fetoproteínas/análise
18.
Int J Clin Exp Med ; 8(3): 4175-85, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26064328

RESUMO

PURPOSE: Our previous research identified that Hepatitis B virus (HBV) infection results in the increased methylation of p16; however, the mechanism(s) of the methylation changes observed following HBV infection are yet to be deduced. DNA methylation is governed by the interaction of DNA methyltransferases (DNMT). To investigate the expression of DNMT in cancerous tissue, cirrhotic tissues and non-cancerous tissue, we examined the relationship between HBV infection and DNMT expression. METHODS: We compared the mRNA expression levels of the four DNMTs in cancerous, cirrhotic and matched non-cancerous tissues of HCC with HBV infection by real-time PCR. RESULTS: The results showed that compared with the level in the corresponding non-cancerous liver tissues, the levels of DNMT1, DNMT3A and DNMT3B were elevated in 54.5%, 68.2% and 38.6% of cancerous tissues and 31.4%, 40% and 25.8% of cirrhotic tissues, respectively. The average mRNA expression for DNMT2 in cancerous and cirrhotic tissues of HCC was not significantly different from that in the corresponding non-cancerous liver tissues. In HBV-associated tissue samples, both the average level and the elevated frequency of DNMT1, DNMT3A and DNMT3B mRNA expression were significantly higher than in non-HBV-associated cirrhotic and cancerous tissues; even in non-cancerous tissues, the mRNA levels of DNMT1 and DNMT3A in HBV-associated samples were significantly higher than in the non-HBV-associated samples. Correlations analysis demonstrated a significant association between HBV infection and the overexpression of DNMTs and p16 methylation. CONCLUSIONS: The results of our current study suggest that persistent HBV infection can stimulate the overexpression of DNMTs, particularly DNMT1, DNMT3A and DNMT3B, which may result in the hyper-methylation/inactivation of p16, thus indirectly regulating the progression of hepatocellular carcinogenesis.

20.
Exp Clin Endocrinol Diabetes ; 123(1): 19-26, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25314651

RESUMO

To build an ideal animal model for studying the mechanism of occurrence, developing and treating of diabetes become a more important issue, facing with the fact that the big threat of diabetes to human health has been worsen. First, we used the normal control diets or the high-fat/high-sucrose diets to feed the adult rhesus monkeys and the macaques induced by the high-fat/high-sucrose diets in the high-fat/high-sucrose group and the type 2 diabetes mellitus (T2DM) group developed the hyperglycemia, hyperinsulinemia at 6 months in accordance with the precious researches that reported that minipigs, rats and mice could develop hyperglycemia, hyperinsulinemia, hyperlipidemia and obesity after being induced with high-fat/high-carbohydrate diets. Second, the rhesus monkeys in T2DM group were injected STZ at a low dosage of 35 mg/kg BW to induce glucose persistent elevation which maintained pretty well after 12 months. Third, we took the assay of glucose tolerance test and insulin resistance index, assessed the changing tendency of serum resistin and analysed the pathological characteristics of the tissues like pancreas and liver by staining in different ways. The results indicate the rhesus monkeys in T2DM group have lots of clinical features of T2DM. The experimental non-genetic T2DM rhesus monkeys model not only contribute to simulating of clinical manifestations and pathological features of human T2DM, but also may be a good kind of model for research on the treatment of T2DM and for new drugs evaluation.


Assuntos
Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Carboidratos da Dieta/efeitos adversos , Gorduras na Dieta/efeitos adversos , Sacarose/efeitos adversos , Edulcorantes/efeitos adversos , Animais , Glicemia/metabolismo , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Feminino , Humanos , Macaca mulatta , Masculino , Camundongos , Ratos , Sacarose/farmacologia , Edulcorantes/farmacologia
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