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1.
J Neurointerv Surg ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34857667

RESUMO

BACKGROUND: Mechanical thrombectomy is the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the anterior circulation. This trial aimed to indicate whether Skyflow, a new thrombectomy device, could achieve the same safety and efficacy as Solitaire FR in the treatment of AIS. METHODS: This study was a prospective, multicenter, randomized, single blind, parallel, positive controlled, non-inferiority clinical trial. Patients with intracranial anterior circulation LVO within 8 hours from onset were included to receive thrombectomy treatment with either the Skyflow or Solitaire FR stent retriever. The primary endpoint was the rate of successful reperfusion (modified Treatment In Cerebral Infarction (mTICI) ≥2b) after the operation. The safety endpoints were the rate of symptomatic intracranial hemorrhage (sICH) and subarachnoid hemorrhage (SAH) at 24 hours after operation. RESULTS: A total of 95 and 97 patients were involved in the Skyflow group and Solitaire FR group, respectively. A successful reperfusion (mTICI ≥2b) was finally achieved in 84 (88.4%) patients in the Skyflow group and 80 (82.5%) patients in the Solitaire FR group. Skyflow was non-inferior to Solitaire FR in regard to the primary outcome, with the criterion of a non-inferiority margin of 12.5% (p=0.0002) after being adjusted for the combined center effect and the National Institutes of Health Stroke Scale (NIHSS) score. The rate of periprocedural sICH and SAH did not differ significantly between the two groups. CONCLUSION: Endovascular thrombectomy with the Skyflow stent retriever was non-inferior to Solitaire FR with regard to successful reperfusion in AIS due to LVO (with a pre-specified non-inferiority margin of 12.5%).

2.
BMC Infect Dis ; 20(1): 935, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33297990

RESUMO

BACKGROUND: This study aims to investigate the comparative clinical characteristics of Covid-19 and non-Covid-19 patients. METHODS: Fifteen Covid-19 and 93 non-Covid-19 patients were included in RNA testing. All epidemiological and clinical data were collected and analyzed, and then comparative results were carried out. RESULTS: Covid-19 patients were older (46.40 ± 18.21 years vs 34.43 ± 18.80 years) and had a higher body weight (70.27 ± 10.67 kg vs 60.54 ± 12.33 kg, P < 0.05). The main symptoms that were similar between Covid-19 and non-Covid-19 patients, and Covid-19 patients showed a lower incidence of sputum production (6.67% vs 45.16%, P < 0.01) and a lower white-cell count (4.83 × 109/L vs 7.43 × 109/L) and lymphocyte count (0.90 × 109/L vs 1.57 × 109/L, P < 0.01). Although there were no differences, C-reactive protein and interleukin-6 were elevated in Covid-19 patients. The sensitivity and negative predictive value of CT images were 0.87 and 0.97, respectively. Covid-19 patients showed a higher contact history of Wuhan residents (80% vs 30.11%) and higher familial clustering (53.33% vs 8.60%, P < 0.001). Covid-19 patients showed a higher major adverse events (ARDS, 13.33%; death, 6.67%; P < 0.05). CONCLUSION: Our results suggested that Covid-19patients had a significant history of exposure and familial clustering and a higher rate of severe status; biochemical indicators showed lymphocyte depletion.


Assuntos
COVID-19/sangue , COVID-19/epidemiologia , Surtos de Doenças , SARS-CoV-2/genética , Adolescente , Adulto , Peso Corporal , Proteína C-Reativa/análise , COVID-19/virologia , China/epidemiologia , Testes Diagnósticos de Rotina , Feminino , Humanos , Incidência , Interleucina-6/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/genética , Estudos Retrospectivos , Adulto Jovem
3.
J Neurol ; 267(11): 3392-3399, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32601755

RESUMO

BACKGROUND: The aim of this study was to investigate differences in the dynamic changes and risk factors of hemodynamic depression (HD) between straight and tapered carotid stenting (SCS and TCS, respectively). METHODS: A total of 148 and 167 patients were included in TCS and SCS groups in this study, respectively. All clinical data were collected and analyzed for differences in HD and primary endpoint events at 12 months. RESULTS: The SCS procedure had a lower predilation rate and a higher incidence of intra- and postprocedure HD; furthermore, the decline in heart rate in the SCS procedure was higher in patients with intra- and postprocedure HD (P < 0.05). Right stenosis [odds ratio (OR) 1.67] and stent type (ev3) (OR 2.31) were confirmed as risk factors, and older age (> 70 years) was accompanied by a lower risk (OR 0.58; P < 0.05). The SCS procedure had a higher incidence of bradycardia and hypotension after 24 h and a longer duration of hypotension (P < 0.05). Stenosis (> 80%) (OR 1.68), the SCS procedure (OR 1.72), and alcohol intake (OR 2.38) were defined as risk factors. There was no difference in the complications or clinical endpoint events in either procedure, and the restenosis rate was lower in the TCS procedure (1.35% vs 5.42%). CONCLUSION: Our results reveal that TCS has a lower incidence of HD and that intra- and postprocedure HD have different manifestations and risk factors.


Assuntos
Estenose das Carótidas , Hipotensão , Idoso , Estenose das Carótidas/cirurgia , Hemodinâmica , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Stents/efeitos adversos , Resultado do Tratamento
4.
Nutr Metab (Lond) ; 17: 29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32322287

RESUMO

OBJECTIVE: Resveratrol is a natural polyphenolic compound that ameliorates postmenopausal osteoporosis by activating the estrogen receptor. Research has shown that resveratrol exhibits some type of estrogen receptor agonist activity, reducing the risk of breast cancer. However, its mechanism of action remains largely unknown. This study aims to investigate the effect of resveratrol on osteoblastic and osteoclastic differentiation and its potential role in the regulation of autophagy. METHODS: Sprague Dawley (SD) rats underwent ovariectomies (OVX) and were administered resveratrol (at 10, 20 or 40 mg/kg/d) for 8 weeks. The calcium content and the bone mineral density (BMD) were measured in the lumbar vertebrae (L3) and the right distal femur-tibia bone region. The osteoblasts and osteoclasts were isolated from rat lumbar vertebrae by enzyme digestion and bone marrow induction, respectively. The cells were then cultured with resveratrol in combination with bafilomycin or leupeptin to inhibit or activate autophagy, respectively. Western blotting was used to assess the differentiation markers and autophagy-related genes in the osteoblasts and osteoclasts. RESULTS: Compared to the sham group, the bone calcium content and BMD were significantly decreased in the OVX group (p < 0.05), while resveratrol attenuated these in a dose-dependent manner. In the osteoblasts, vascular endothelial growth factor (VEGF), and alpha-1 type I collagen (COL1A1) were markedly decreased, and in osteoclasts, the receptor activator of nuclear factor-κB ligand (RANKL) was increased in the OVX group, while resveratrol reversed this pattern in a dose-dependent manner. The inhibition of autophagy in osteoblasts and its activation in osteoclasts was observed in the OVX group. However, with resveratrol, this was reversed in a dose-dependent manner. CONCLUSION: Overall, resveratrol promotes osteoblastic differentiation and suppresses osteoclastic differentiation in a rat model with postmenopausal osteoporosis by regulating autophagy.

5.
J Vet Diagn Invest ; 31(6): 909-912, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31650901

RESUMO

Swine diarrhea can be caused by multiple agents, including porcine epidemic diarrhea virus (PEDV), porcine sapelovirus (PSV), and porcine sapovirus (SaV). We designed a one-step triplex reverse-transcription PCR (RT-PCR) detection method including 3 pairs of primers that focused on the S1 gene of PEDV, a conserved gene of PSV, and the VP1 gene of SaV. The optimal concentrations of upstream and downstream primers in the triplex RT-PCR were 0.24 µM for PEDV, 0.15 µM for PSV, and 0.2 µM for SaV, and the optimal annealing temperature was 55.5°C. Triplex RT-PCR assessment of 402 piglet diarrhea samples was compared with conventional individual RT-PCR. Concordance rates in both tests for individual viruses were 100%, 97.6%, and 94.4% for PEDV, PSV, and SaV, respectively. PEDV, PSV, and SaV were detected in 57.2%, 10.4%, and 9.0% of the samples, respectively. The high sensitivity and specificity of this triplex RT-PCR-based detection method for PEDV, PSV, and SaV could allow rapid detection and analysis of mixed infections by these 3 viruses.


Assuntos
Infecções por Caliciviridae/veterinária , Infecções por Coronavirus/veterinária , Diarreia/veterinária , Reação em Cadeia da Polimerase Multiplex/veterinária , Infecções por Picornaviridae/veterinária , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Doenças dos Suínos/diagnóstico , Animais , Infecções por Caliciviridae/diagnóstico , Infecções por Coronavirus/diagnóstico , Diarreia/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Picornaviridae/isolamento & purificação , Infecções por Picornaviridae/diagnóstico , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sapovirus/isolamento & purificação , Suínos , Doenças dos Suínos/virologia
7.
Nat Biotechnol ; 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30475349

RESUMO

The efficacy of oncolytic herpes simplex virus (oHSV) is limited by rapid viral clearance by innate immune effector cells and poor intratumoral viral spread. We combine two approaches to overcome these barriers: inhibition of natural killer (NK) cells and enhancement of intratumoral viral spread. We engineered an oHSV to express CDH1, encoding E-cadherin, an adherent molecule and a ligand for KLRG1, an inhibitory receptor expressed on NK cells. In vitro, infection with this engineered virus, named OV-CDH1, induced high surface E-cadherin expression on infected glioblastoma (GBM) cells, which typically lack endogenous E-cadherin. Ectopically expressed E-cadherin enhanced the spread of OV-CDH1 by facilitating cell-to-cell infection and viral entry and reduced viral clearance by selectively protecting OV-CDH1-infected cells from KLRG1+ NK cell killing. In vivo, OV-CDH1 treatment substantially prolonged the survival in GBM-bearing mouse models, primarily because of improved viral spread rather than inhibition of NK cell activity. Thus, virus-induced overexpression of E-cadherin may be a generalizable strategy for improving cancer virotherapy.

8.
J Endovasc Ther ; 25(6): 765-770, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30296887

RESUMO

PURPOSE: To investigate the short-term outcomes and complications of straight vs tapered carotid stent placement for patients with symptomatic carotid stenosis. METHODS: A prospective study was conducted to examine if tapered carotid stents (TCS) performed better than straight carotid stents (SCS) in terms of complications and outcomes in patients with a unilateral, symptomatic, internal carotid artery stenosis ⩾70%. Between January 2014 and January 2016, 236 patients were screened; 88 were excluded, leaving 148 patients for 1:1 randomization to carotid artery stenting with either SCS or TCS. The data were analyzed for differences between the groups in terms of complications (hemodynamic depression, cerebral hyperperfusion syndrome, puncture site sequelae) and endpoint events (stroke, myocardial infarction, and death) at 30 days and 6 months. RESULTS: Two patients in the TCS group underwent endarterectomy after allocation, leaving 72 patients (mean age 65.1±8.8 years; 59 men) in the TCS group for analysis vs 74 (mean age 65.0±7.9 years; 58 men) in the SCS group. The technical success was 100% in both groups. The incidence of hemodynamic depression (hypotension and bradycardia) after the procedures were higher in the SCS group (p=0.04), and the patients who underwent SCS procedures had longer hospital stays (p=0.01). There was no difference in the incidences of complications, myocardial infarction, mortality, or stroke at 30 days or 6 months between the SCS and TCS groups. The rates of restenosis (4% SCS vs 1% TCS) were similar (p=0.63); all restenoses were moderate (50%-70%). CONCLUSION: When compared to straight stents, tapered carotid stents significantly decreased hemodynamic complications and hospital stay.


Assuntos
Angioplastia com Balão/instrumentação , Artéria Carótida Interna , Estenose das Carótidas/terapia , Stents , Idoso , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/mortalidade , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/complicações , Estenose das Carótidas/mortalidade , Estenose das Carótidas/fisiopatologia , Feminino , Hemodinâmica , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Estudos Prospectivos , Desenho de Prótese , Recidiva , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
9.
Neuropsychiatr Dis Treat ; 14: 2233-2239, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214213

RESUMO

Purpose: The platelet distribution width (PDW) reflects the status of platelet activity and may be useful for early predictions of the clinical outcome of stroke patients. The purpose of the study was to determine the associations between PDW and clinical outcomes after intravenous thrombolysis in stroke patients. Patients and methods: Acute ischemic stroke patients who received intravenous treatment with recombinant tissue-type plasminogen activator were selected for inclusion in the retrospective cohort of this study. The relations between PDW at admission and clinical outcomes were analyzed, including a poor outcome as assessed using the modified Rankin Scale at 3 months, early neurological improvement, and any hemorrhage. The effect of PDW at admission on a poor outcome at 3 months was analyzed using a multivariable logistic regression model with adjustment for potential confounders. The optimal PDW cutoff for predicting poor outcome at 3 months was determined by analyzing the receiver operating characteristics curve. Results: PDW was significantly higher for a good outcome than a poor outcome (p=0.005), with median (interquartile range) values of 16.2 (13.2-17.2) and 13.6 (12.5-15.9), respectively. PDW was also higher in patients with early neurological improvement than in patients without improvement (p=0.020) and did not differ between hemorrhage and nonhemorrhage patients. The association between PDW <16.05% and poor outcome remained in a multivariable logistic regression analysis, with an OR of 6.68 and a 95% CI of 1.69-26.49 (p=0.007). Conclusion: Results suggest a novel hypothesis that a lower PDW may be related with a poor outcome at 3 months after intravenous thrombolysis in acute ischemic stroke patients.

10.
World Neurosurg ; 120: 249-255, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30165234

RESUMO

BACKGROUND: Cerebral fat embolism (CFE) is a rare complication that usually occurs after trauma injury. The incidence of CFE due to aesthetic surgery is extremely rare and can lead to fatal outcome. Due to the rarity of this complication, there is still lack of knowledge and standardization of the treatment. CASE DESCRIPTION: Herein, we reported 6 cases of CFE that occurred in patients who underwent cosmetic surgery. Among 5 patients who had large artery occlusion, 3 patients survived and 2 patients died due to progression of the disease. One patient had the ophthalmic artery occlusion. In addition, embolectomy was performed in 5 patients and 3 patients had decompressive craniectomy following endovascular treatment due to severe brain edema. CONCLUSIONS: CFE is associated with high morbidity and mortality, and early surgical intervention can improve the prognosis.


Assuntos
Tecido Adiposo/transplante , Técnicas Cosméticas/efeitos adversos , Embolia Gordurosa/etiologia , Embolia Gordurosa/cirurgia , Embolia Intracraniana/etiologia , Embolia Intracraniana/cirurgia , Complicações Pós-Operatórias/etiologia , Adulto , Angiografia Digital , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/cirurgia , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/etiologia , Edema Encefálico/cirurgia , Doenças Arteriais Cerebrais/diagnóstico por imagem , Doenças Arteriais Cerebrais/etiologia , Doenças Arteriais Cerebrais/cirurgia , Terapia Combinada , Craniectomia Descompressiva , Progressão da Doença , Embolectomia , Embolia Gordurosa/diagnóstico , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
11.
J Photochem Photobiol B ; 181: 106-114, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29549803

RESUMO

The present study aimed to investigate the neuroprotective effect of Annona glabra extract (AGE) against ethanol-induced neurodegeneration in neonatal rats. AGE is known to contain various pharmacological and therapeutic properties. Phytochemical analysis of AGE was performed to understand the presence of vital therapeutic components. Neonatal rats were assigned to the following groups: group I (normal control rats receiving normal saline), group II (control rats receiving ethanol), and group III (treated rats receiving ethanol-AGE). The lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (Gpx), superoxide dismutase (SOD), catalase, and acetylcholine esterase (AChE) levels were determined. Behavioral parameters, histological features, neuronal cell viability, and apoptosis were also investigated. The presence of flavonoids, terpenoid, glycosides, steroids, saponins, tannins, anthraquinones, and acidic compounds was noted in the AGE. Ethanol supplementation drastically increased the malondialdehyde (MDA) content to 52.17 nmol/g in the control rats (group II). However, the MDA content was reduced to 27.34 nmol/g in ethanol-AGE-treated neonatal rats (group III) compared with control rats. The GSH content was substantially reduced, to 33.68 mg/g, in control rats compared with in normal control rats. However, the GSH content was significantly increased, to 59.32 mg/g, following ethanol-AGE supplementation. Gpx, SOD, catalase, and AChE enzyme activities were increased in treated neonatal rats compared with their respective controls. Locomotor activities, such as crossing, grooming, rearing, and sniffing, were increased in ethanol-AGE-treated neonatal rats compared with controls. Reduced levels of intact pyramidal cells and cells with degenerative alterations appeared in the control rats. However, ethanol-AGE supplementation reduced degenerative alterations and hippocampal damage. Reduced cultured hippocampal neuron cell viability and increased apoptosis were noted in the control rats, whereas these impacts were significantly recovered following ethanol-AGE supplementation. Based on all these data, we concluded that the supplementation of AGE was very effective against ethanol-induced neurodegeneration in neonatal rats.


Assuntos
Annona/química , Apoptose/efeitos dos fármacos , Etanol/toxicidade , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/química , Acetilcolinesterase/metabolismo , Animais , Animais Recém-Nascidos , Annona/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Catalase/metabolismo , Células Cultivadas , Glutationa/química , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Ratos , Superóxido Dismutase/metabolismo
12.
J Infect Dev Ctries ; 12(12): 1124-1133, 2018 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-32027615

RESUMO

INTRODUCTION: Porcine epidemic diarrhea virus (PEDV) is one of the most common viral pathogens causing swine diarrhea. METHODOLOGY: We performed a genetic evolution analysis of the S1 gene of endemic PEDV strains in Eastern China. The S1 genes of 37 PEDV-positive samples were amplified and sequenced, and compared to the standard CV777 strain, 120 nucleotides were found to have mutations. RESULTS: The nucleotide and deduced amino acid homologies between the sequences and those of the CV777 strain were 90%-91% and 88.2%-90%, respectively, and their homologies to the vaccine strain were 88.6%-89.7% and 86.2%-87.8%, respectively. Genetic evolution and variation analyses indicated that the 37 PEDV strains belonged to genogroup 2-1, while the CV777 strain, vaccine strain, and earlier Chinese strains all belonged to genogroup 1-1. CONCLUSIONS: The newly emerged clinical PEDV strains indicate that the PEDV CV777 vaccine currently used in China may not fully protect pigs from infection with recent epidemic strains, and will require the development of new vaccine strains.


Assuntos
Filogenia , Vírus da Diarreia Epidêmica Suína/genética , Proteínas Virais/genética , Animais , China , Infecções por Coronavirus/virologia , Epitopos , Evolução Molecular , Variação Genética , Glicosilação , Mutação , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , Suínos , Proteínas Virais/metabolismo
13.
J BUON ; 22(5): 1272-1277, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29135113

RESUMO

PURPOSE: The minichromosomal maintenance (MCM) proteins are involved in the initiation and DNA replication. The role of MCM4 remains to be elucidated. The purpose of this study was to investigate the effects of MCM4 in laryngeal squamous cell carcinoma (LSCC) cell growth and apoptosis. METHODS: LSCC cell line UMSCC 5 was used in this study. The small interfering RNA (siRNA) of MCM 4 gene was used to identify the effects of MCM4 on the proliferation and apoptosis using methylimidazole tetrazolium (MTT) assay and flow-cytometry, respectively. Confirmed LSCC and adjacent non-tumor tissues were collected from 34 patients who were willing to participate in the study, from 2010 through 2015, from 163 patients undergoing treatment in the Department of Otorhinolaryngology/Head and Neck Surgery of Beijing Tongren Hospital in Capital Medical University of P.R. China. Immunohistochemical staining of MCM4 expression in the resected tissues was performed to analyze the correlation between its expression and the clinicopathological characteristics. RESULTS: The results showed that siRNA of MCM4 could significantly inhibit LSCC cell line UMSCC 5 proliferation and induce apoptosis. MCM4 mRNA was higher expressed in carcinoma tissues than in adjacent normal tissues. MCM4 expression was correlated with male gender, smoking history and poor differentiation. CONCLUSIONS: We noticed a significant role for MCM4 overexpression in human LSCC tissues and their corresponding adjacent non-neoplastic tissues and found that siRNA of MCM4 can significantly decrease the proliferation of cancer cells. It is suggested that MCM4 profiling could potentially be used to predict response to treatment and prognosis in LSCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma de Células Escamosas/genética , Neoplasias Laríngeas/genética , Proteínas Nucleares/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Feminino , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
14.
Oncol Rep ; 38(5): 3019-3029, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29048627

RESUMO

Solute carrier family 7, membrane 11 (SLC7A11) or (xCT) is a component of the cysteine-glutamate transporter, which plays a critical role in glutathione homeostasis which is important to protect cells from oxidative stress. SLC7A11 is distributed in various tissues and participates in the occurrence of a number of diseases, particularly in the pathogenesis of malignant tumors, but its role in laryngeal cancer development has not yet been clearly defined. The objective of the present study was to investigate the role of SLC7A11 in laryngeal squamous cell carcinoma (LSCC). We conducted immunohistochemistry and RT-PCR to evaluate the protein and mRNA levels of SLC7A11 in LSCC and in control tissues, respectively. The knockdown experiments were conducted with SLC7A11 short hairpin RNA (shRNA) lentivirus, and the protein and mRNA levels of SLC7A11 were assessed by RT-PCR and western blotting. The functional study of SLC7A11 in vitro was conducted by MTT assay, and the effects on the cell cycle were detected using flow cytometry. Immunohistochemical results revealed that the expression levels of SLC7A11, Ki-67 and p53 in LSCC tissues were higher than those in laryngeal dysplasia tissues. The Spearman rank correlation analysis revealed that the expression of SLC7A11 was positively correlated with the expression of p53 and Ki-67. Cox regression analysis and Kaplan-Meier plots confirmed that the expression levels of SLC7A11 were a prognostic factor for overall survival (OS) rates and postoperative recurrence of LSCC. Moreover, the functional study of SLC7A11 in vitro revealed that knockdown of SLC7A11 using shRNA inhibited cell proliferation by inducing cell cycle arrest at the G1 phase. Immunohistochemical and RT-PCR results and knockdown experiments of SLC7A11 revealed that SLC7A11 was involved in the progression of LSCC, and may provide clinical information for the evaluation of OS rates and postoperative recurrence of LSCC. Collectively, these observations suggest that SLC7A11 may be a vital biomarker for the diagnosis and prognosis in human LSCC, and targeting SLC7A11 appears to be a potentially significant method for LSCC treatment.


Assuntos
Sistema y+ de Transporte de Aminoácidos/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Laríngeas/genética , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Sistema X-AG de Transporte de Aminoácidos/genética , Apoptose/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células/genética , Cisteína/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço
15.
Sci China Life Sci ; 60(12): 1331-1339, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29019145

RESUMO

Pathogenic H7N9 influenza viruses continue to pose a public health concern. The H7N9 virus has caused five outbreak waves of human infections in China since 2013. In the present study, a novel H7N9 strain (A/Guangdong/8H324/2017) was isolated from a female patient with severe respiratory illness during the fifth wave of the 2017 H7N9 epidemic. Phylogenetic analysis showed that the H7N9 viruses collected during the fifth wave belong to two different lineages: the Pearl River Delta lineage and the Yangtze River Delta lineage. The novel isolate is closely related to the Pearl River Delta H7N9 viruses, which were isolated from patients in Guangdong Province. The novel H7N9 isolate has an insertion of three basic amino acids in the cleavage site of hemagglutinin (HA), which may enhance virulence in poultry. The 2017 isolate also possesses an R292K substitution in the neuraminidase (NA) protein, which confers oseltamivir resistance. This study highlights the pandemic potential of the novel H7N9 virus in mammals; thus, future characterization and surveillance is warranted.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/classificação , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Humana/virologia , Filogenia , Adulto , Substituição de Aminoácidos , Animais , China/epidemiologia , Surtos de Doenças , Farmacorresistência Viral , Feminino , Genoma Viral/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Neuraminidase/genética , Aves Domésticas , Análise de Sequência de RNA , Proteínas Virais/genética
16.
Sci Rep ; 7(1): 10047, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28855646

RESUMO

The global spread of Zika virus (ZIKV) as well as its unexpected link to infant microcephaly have resulted in serious public health concerns. No antiviral drugs against ZIKV is currently available, and vaccine development is of high priority to prepare for potential ZIKV pandemic. In the present study, a truncated E protein with the N-terminal 90% region reserved (E90) from a contemporary ZIKV strain was cloned and expressed in Escherichia coli, purified by a Ni-NTA column, and characterized by Western blotting assays. Immunization with recombinant E90 induced robust ZIKV-specific humoral response in adult BALB/c mice. Passive transfer of the antisera from E90-immunized mice conferred full protection against lethal ZIKV challenge in a neonatal mice model. Our results indicate that recombinant ZIKV E90 described here represents as a promising ZIKV subunit vaccine that deserves further clinical development.


Assuntos
Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Proteínas do Envelope Viral/imunologia , Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Clonagem Molecular , Modelos Animais de Doenças , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Expressão Gênica , Humanos , Soros Imunes/administração & dosagem , Imunidade Humoral/efeitos dos fármacos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Análise de Sobrevida , Vacinas de Subunidades , Proteínas do Envelope Viral/administração & dosagem , Proteínas do Envelope Viral/genética , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Zika virus/química , Infecção por Zika virus/imunologia , Infecção por Zika virus/mortalidade , Infecção por Zika virus/virologia
17.
J Virol ; 91(21)2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28814522

RESUMO

Zika virus (ZIKV) has caused significant outbreaks and epidemics in the Americas recently, raising global concern due to its ability to cause microcephaly and other neurological complications. A stable and efficient infectious clone of ZIKV is urgently needed. However, the instability and toxicity of flavivirus cDNA clones in Escherichia coli hosts has hindered the development of ZIKV infectious clones. Here, using a novel self-splicing ribozyme-based strategy, we generated a stable infectious cDNA clone of a contemporary ZIKV strain imported from Venezuela to China in 2016. The constructed clone contained a modified version of the group II self-splicing intron P.li.LSUI2 near the junction between the E and NS1 genes, which were removed from the RNA transcripts by an easy-to-establish in vitro splicing reaction. Transfection of the spliced RNAs into BHK-21 cells led to the production of infectious progeny virus that resembled the parental virus. Finally, potential cis-acting RNA elements in ZIKV genomic RNA were identified based on this novel reverse genetics system, and the critical role of 5'-SLA promoter and 5'-3' cyclization sequences were characterized by a combination of different assays. Our results provide another stable and reliable reverse genetics system for ZIKV that will help study ZIKV infection and pathogenesis, and the novel self-splicing intron-based strategy could be further expanded for the construction of infectious clones from other emerging and reemerging flaviviruses.IMPORTANCE The ongoing Zika virus (ZIKV) outbreaks have drawn global concern due to the unexpected causal link to fetus microcephaly and other severe neurological complications. The infectious cDNA clones of ZIKV are critical for the research community to study the virus, understand the disease, and inform vaccine design and antiviral screening. A panel of existing technologies have been utilized to develop ZIKV infectious clones. Here, we successfully generated a stable infectious clone of a 2016 ZIKV strain using a novel self-splicing ribozyme-based technology that abolished the potential toxicity of ZIKV cDNA clones to the E. coli host. Moreover, two crucial cis-acting replication elements (5'-SLA and 5'-CS) of ZIKV were first identified using this novel reverse genetics system. This novel self-splicing ribozyme-based reverse genetics platform will be widely utilized in future ZIKV studies and provide insight for the development of infectious clones of other emerging viruses.


Assuntos
Splicing de RNA , RNA Catalítico/metabolismo , Sequências Reguladoras de Ácido Ribonucleico/genética , Infecção por Zika virus/virologia , Zika virus/genética , Animais , Células Cultivadas , Clonagem Molecular , Cricetinae , DNA Complementar , Regulação Viral da Expressão Gênica , Rim/metabolismo , Rim/virologia , Camundongos Endogâmicos BALB C , RNA Catalítico/genética , Genética Reversa , Carga Viral , Replicação Viral
18.
PLoS One ; 12(7): e0181175, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28746340

RESUMO

This study was aimed to explore the role of tanshinol in osteoblastic cells, and the role in vivo using an ovariectomized (OVX) rat model of osteoporosis. MC3T3-E1 cells were pretreated with 0-400 µg/mL tanshinol, and then cell viability, apoptosis, alkaline phosphatase (ALP) activity and the expressions of Collagen Type I Alpha 1 (Col1A1), Runt Related Transcription Factor 2 (Runx2) and osteocalcin (OCN) were respectively detected. Rats underwent OVX surgery was intervened with 5 mg/kg tanshinol or 25 µg/kg ß-estradiol (E2) for 12 weeks. The triglycerides (TG), total cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C and LDL-C), ALP, OCN and Tartrate-resistant acid phosphatase-5b (TRACP-5b) contents were measured. Besides, the expressions of main factors in nuclear factor-kappa B (NF-κB) pathway were detected. The results showed that tanshinol significantly promoted MC3T3-E1 cells viability and ALP activity, while inhibited apoptosis (P < 0.05); Col1A1, Runx2 and OCN were all up-regulated by tanshinol (P < 0.05). In OVX rats, the contents of TG, TC, LDL-C, ALP, OCN and TRACP-5b were all increased (P < 0.05), while HDL-C was decreased (P < 0.05). Tanshinol significantly alleviated these aberrant regulations (P < 0.05). Inhibitory subunit of NF-κB (IκBα) and p65 were both remarkably phosphorylated by OVX, while this phosphorylation was partially neutralized by tanshinol (P < 0.05). In conclusion, we demonstrated that tanshinol exerted a bone-protective function by modulating the markers of bone turnover possibly via blocking NF-κB pathway. This study will provide new evidence that tanshinol is a potential therapeutic option for the relief of estrogen deficiency-induced osteoporosis.


Assuntos
Biomarcadores/metabolismo , Osso e Ossos/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Osteoblastos/efeitos dos fármacos , Ovariectomia , Fosfatase Alcalina/sangue , Fosfatase Alcalina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/sangue , Western Blotting , Osso e Ossos/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteocalcina/sangue , Osteocalcina/genética , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fosfatase Ácida Resistente a Tartarato/sangue , Triglicerídeos/sangue
19.
Neuropsychiatr Dis Treat ; 13: 1551-1557, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28670124

RESUMO

PURPOSE: The aspartate transaminase/alanine transaminase ratio (De Ritis ratio, AAR) was reported to be associated with patients' prognosis in certain diseases recently. The objective of the current study was to determine the association between the AAR at admission and poor outcome at 3 months in acute ischemic stroke (AIS) patients. PATIENTS AND METHODS: This retrospective cohort study included patients who experienced their first-ever AIS between June 2015 and March 2016. The primary outcome measure was a poor outcome at 3 months (modified Rankin Scale score >2). Multivariate logistic regression models were used to assess the relationship between AAR quartiles and clinical outcomes among the AIS patients. Receiver operating characteristic curve analysis was applied to identify the optimal cutoff for AAR in predicting the prognosis of AIS. RESULTS: In terms of the relationship between poor outcome and AAR, the adjusted odds ratio comparing the highest and lowest AAR quartiles was 2.15 (95% confidence interval =1.14-4.05). An AAR of 1.53 was identified as the optimal cutoff. In a prespecified subgroup analysis according to the time from symptom onset to treatment (>24 vs ≤24 hours), there was no significant difference in the effect of AAR >1.53 between the two groups. CONCLUSION: An increased AAR at admission is significantly associated with a poor outcome at 3 months in AIS patients.

20.
Med Sci Monit ; 23: 2825-2832, 2017 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-28600907

RESUMO

BACKGROUND Hypokalemia has been confirmed to be a predictor of adverse cardiovascular and renal outcomes. There is a paucity of studies focusing on the potential connection between the serum K+ level and the outcome after acute ischemic stroke (AIS). This study investigated whether hypokalemia in the acute stroke stage contributes to worse functional outcome in AIS patients. MATERIAL AND METHODS This retrospective cohort study included consecutive patients with first-ever AIS admitted between June 2015 and March 2016. Patients were divided into 2 groups: hypokalemia (K+ <3.5 mmol/L) and normokalemia (3.5 mmol/L ≤K+ ≤5.5 mmol/L). Primary outcome measure was poor outcome at 3 months (modified Rankin scale >2). Univariate and multivariate logistic regression analyses were used to assess the association between hypokalemia and poor outcome. Receiver operating curve (ROC) analysis was performed to determine the optimal cutoff point of serum K+ level for predicting poor outcome. RESULTS The percent of patients with poor outcome at 3 months was higher in the hypokalemic group (62.9%) than in the normokalemic group (45.5%). Hypokalemic patients tended to have lower fasting glucose at admission, lower Glasgow coma scale score, and longer time from symptom onset to treatment compared with normokalemic patients. Hypokalemia was associated with poor outcome at 3 months after adjusting for potential confounders (odds ratio=2.42, 95% confidence interval=1.21-4.86, P=0.013). ROC analysis showed that the optimal threshold for serum K+ level was 3.7 mmol/L. CONCLUSIONS Hypokalemia at the initial admission is associated with poor prognosis at 3 months in first-ever AIS patients.


Assuntos
Isquemia Encefálica/complicações , Hipopotassemia/complicações , Acidente Vascular Cerebral/complicações , Demografia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances
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