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1.
Chin Med ; 16(1): 116, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758851

RESUMO

BACKGROUND: Arsenic (As3+) is a carcinogen with considerable environmental and occupational relevancy. Its mechanism of action and methods of prevention remain to be investigated. Previous studies have demonstrated that ROS is responsible for As3+-induced cell transformation, which is considered as the first stage of As3+ carcinogenesis. The NF-E2 p45-related factor-2 (Nrf2) signaling pathway regulates the cellular antioxidant response, and activation of Nrf2 has recently been shown to limit oxidative damage following exposure to As3+ METHODS AND RESULTS: In this study, molecular docking was used to virtually screen natural antioxidant chemical databases and identify molecules that interact with the ligand-binding site of Keap1 (PDB code 4L7B). The cell-based assays and molecular docking findings revealed that curcumin has the best inhibitory activity against Keap1-4L7B. Co-immunoprecipitation (Co-IP) results indicated that curcumin is a potent Keap1 Kelch domain-dependent Nrf2 activator that stabilizes Nrf2 by hindering its ubiquitination. The increased activation of Nrf2 and its target antioxidant genes by curcumin could significantly decrease As3+-generated ROS. Moreover, curcumin induced autophagy in As3+-treated BEAS-2B via inducing autophagy by the formation of a p62/LC-3 complex and increasing autophagic flux by promoting transcription factor EB (TFEB) and lysosome-associated membrane protein 1 (LAMP1) expression. Knockdown of Nrf2 abolished curcumin-induced autophagy and downregulated ROS. Further studies showed that inhibition of autophagosome and lysosome fusion with bafilomycin a1 (BafA1) could block curcumin and prevented As3+-induced cell transformation. These results demonstrated that curcumin prevents As3+-induced cell transformation by inducing autophagy via the activation of the Nrf2 signaling pathway in BEAS-2B cells. However, overexpression of Keap-1 showed a constitutively high level of Nrf2 in As3+-transformed BEAS-2B cells (AsT) is Keap1-independent regulation. Overexpression of Nrf2 in AsT demonstrated that curcumin increased ROS levels and induced cell apoptosis via the downregulation of Nrf2. Further studies showed that curcumin decreased the Nrf2 level in AsT by activating GSK-3ß to inhibit the activation of PI3K/AKT. Co-IP assay results showed that curcumin promoted the interaction of Nrf2 with the GSK-3ß/ß-TrCP axis and ubiquitin. Moreover, the inhibition of GSK-3ß reversed Nrf2 expression in curcumin-treated AsT, indicating that the decrease in Nrf2 is due to activation of the GSK-3ß/ß-TrCP ubiquitination pathway. Furthermore, in vitro and in vivo results showed that curcumin induced cell apoptosis, and had anti-angiogenesis and anti-tumorigenesis effects as a result of activating the GSK-3ß/ß-TrCP ubiquitination pathway and subsequent decrease in Nrf2. CONCLUSIONS: Taken together, in the first stage, curcumin activated Nrf2, decreased ROS, and induced autophagy in normal cells to prevent As3+-induced cell transformation. In the second stage, curcumin promoted ROS and apoptosis and inhibited angiogenesis via inhibition of constitutive expression of Nrf2 in AsT to prevent tumorigenesis. Our results suggest that antioxidant natural compounds such as curcumin can be evaluated as potential candidates for complementary therapies in the treatment of As3+-induced carcinogenesis.

2.
J Asthma Allergy ; 14: 1197-1207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616159

RESUMO

Background: Asthma belongs to chronic inflammatory respiratory diseases characterized by airway inflammation and remodeling. Circular RNAs (circRNAs) are promising therapeutic targets for various diseases, including asthma. In this work, we aim to investigate the role of circular RNA Erb-B2 receptor tyrosine kinase 2 (circERBB2) during progression of asthma. Methods: Human airway smooth muscle cells (ASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) to mimic cell remodeling. The expression of circERBB2, microRNA-98-5p (miR-98-5p), and insulin-like growth factor 1 receptor (IGF1R) was measured by qRT-PCR. Cell proliferation, migration and apoptosis were determined by cell counting-8 (CCK-8), transwell, and flow cytometry. Protein levels of PCNA, MMP-9, IGF1R were evaluated using Western blotting. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Luciferase reporter gene experiment was adopted to evaluate the targeting relationship between miR-98-5p with circERBB2 and IGF1R. Interaction between RNAs was determined by RNA pulldown and RIP assay. Results: The depletion of circERBB2 attenuated the proliferation, migration, and levels of inflammatory factors induced by PDGF-BB and cell apoptosis. CircERBB2 was identified to directly interact with miR-98-5p, and overexpression of miR-98-5p abolished the function of circERBB2 on PDGF-BB-stimulated ASMCs. IGF1R was identified as a target of miR-98-5p, and knockdown of IGF1R relieved the PDGF-BB-induced ASMCs proliferation and migration. Conclusion: Our work disclosed that knockdown of circERBB2 suppressed PDGF-BB-caused proliferation, migration and inflammatory response of ASMCs, through regulating miR-98-5p/IGF1R signaling, presented circERBB2 as a promising therapeutic target for asthma.

3.
J Orthop Surg Res ; 16(1): 273, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879213

RESUMO

BACKGROUND: The purpose of present study was to identify the differentially expressed genes (DEGs) associated with BMP-9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) by using bioinformatics methods. METHODS: Gene expression profiles of BMP-9-induced MSCs were compared between with GFP-induced MSCs and BMP-9-induced MSCs. GSE48882 containing two groups of gene expression profiles, 3 GFP-induced MSC samples and 3 from BMP-9-induced MSCs, was downloaded from the Gene Expression Omnibus (GEO) database. Then, DEGs were clustered based on functions and signaling pathways with significant enrichment analysis. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that the identified DEGs were potentially involved in cytoplasm, nucleus, and extracellular exosome signaling pathway. RESULTS: A total of 1967 DEGs (1029 upregulated and 938 downregulated) were identified from GSE48882 datasets. R/Bioconductor package limma was used to identify the DEGs. Further analysis revealed that there were 35 common DEGs observed between the samples. GO function and KEGG pathway enrichment analysis, among which endoplasmic reticulum, protein export, RNA transport, and apoptosis was the most significant dysregulated pathway. The result of protein-protein interaction (PPI) network modules demonstrated that the Hspa5, P4hb, Sec61a1, Smarca2, Pdia3, Dnajc3, Hyou1, Smad7, Derl1, and Surf4 were the high-degree hub nodes. CONCLUSION: Taken above, using integrated bioinformatical analysis, we have identified DEGs candidate genes and pathways in BMP-9 induced MSCs, which could improve our understanding of the key genes and pathways for BMP-9-induced osteogenic of MSCs.


Assuntos
Diferenciação Celular/genética , Biologia Computacional/métodos , Bases de Dados Genéticas , Fator 2 de Diferenciação de Crescimento/genética , Fator 2 de Diferenciação de Crescimento/fisiologia , Células-Tronco Mesenquimais/fisiologia , Osteogênese/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Transcriptoma , Estudos de Associação Genética/métodos , Fator 2 de Diferenciação de Crescimento/metabolismo , Proteínas de Choque Térmico , Humanos , Pró-Colágeno-Prolina Dioxigenase , Isomerases de Dissulfetos de Proteínas , Canais de Translocação SEC
5.
Acta Pharmacol Sin ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767379

RESUMO

Urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) are important targets for the development of uric acid-lowering drugs. We previously showed that the flexible linkers of URAT1 inhibitors could enhance their potency. In this study we designed and synthesized CDER167, a novel RDEA3710 analogue, by introducing a linker (methylene) between the naphthalene and pyridine rings to increase flexibility, and characterized its pharmacological and pharmacokinetics properties in vitro and in vivo. We showed that CDER167 exerted dual-target inhibitory effects on both URAT1 and GLUT9: CDER167 concentration-dependently inhibited the uptake of [14C]-uric acid in URAT1-expressing HEK293 cells with an IC50 value of 2.08 ± 0.31 µM, which was similar to that of RDEA3170 (its IC50 value was 1.47 ± 0.23 µM). Using site-directed mutagenesis, we demonstrated that CDER167 might interact with URAT1 at S35 and F365. In GLUT9-expressing HEK293T cells, CDER167 concentration-dependently inhibited GLUT9 with an IC50 value of 91.55 ± 15.28 µM, whereas RDEA3170 at 100 µM had no effect on GLUT9. In potassium oxonate-induced hyperuricemic mice, oral administration of CDER167 (10 mg·kg-1 · d-1) for 7 days was more effective in lowering uric acid in blood and significantly promoted uric acid excretion in urine as compared with RDEA3170 (20 mg·kg-1 · d-1) administered. The animal experiment proved the safety of CDER167. In addition, CDER167 displayed better bioavailability than RDEA3170, better metabolic stability and no hERG toxicity at 100 µM. These results suggest that CDER167 deserves further investigation as a candidate antihyperuricemic drug targeting URAT1 and GLUT9.

7.
Medicine (Baltimore) ; 99(51): e23757, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371137

RESUMO

BACKGROUND: Total knee arthroplasty is a common surgery for end-stage of knee osteoarthritis. Proprioceptive training has become an important part in athletes training programmes in different sports. However, the effects of proprioceptive training on the recovery of total knee arthroplasty were unknown. This meta-analysis, with its comprehensive and rigorous methodology, will provide better insight into this problem. METHODS AND ANALYSIS: Electronic databases including PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI) database, Wanfang Database and Chinese Biomedical Literature Database (CBM) were searched from its inception to October 21, 2020. We only included proprioceptive training vs placebo in patients after total knee arthroplasty and pooled results were summarized by STATA 12.0 software. Two researchers independently selected the study and assessed the quality of the included studies. The heterogeneity was measured by I2 tests (I2 < 50 indicates little heterogeneity, I2 ≥ 50 indicates high heterogeneity). Publication bias was ruled out by funnel plot and statistically assessed by Beggs test (P > .05 as no publication bias). RESULTS: Results will be published in relevant peer-reviewed journals. CONCLUSION: Our study aims to systematically present the clinical effects of proprioceptive training after total knee arthroplasty patients, which will be provide clinical guidance for total knee arthroplasty patients.


Assuntos
Osteoartrite do Joelho/cirurgia , Propriocepção/fisiologia , Reabilitação/educação , Reabilitação/métodos , Humanos , Reabilitação/tendências
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 489-493, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642224

RESUMO

OBJECTIVE: To determine segmental myocardial changes in cardiovascular magnetic resonance feature-tracking (CMR-FT) in the early phase of reperfused myocardial infarction in patients and rats. METHODS: Ten patients receiving percutaneous coronary interventions (2-10 d) and 10 rats with 60 min induced myocardial ischemia followed by reperfusions (48 h and 7 d) were investigated by MRI. The steady state free precession cine and late gadolinium enhancement (LGE) sequences were measured to evaluate the standard short axis of the whole heart after an injection of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, Magnevist, Bayer Health Care Pharmaceuticals) at a dose of 0.1 mmol/kg. The infarction sizes (all areas were expressed as a percentage of the whole myocardial tissues of left ventricle (LV), end-diastolic volume (EDV) and ejection fractions (EF) were calculated. The MRI cine images were analyzed using the myocardial feature tracking software CVI, estimating the peak value of radial strains (RS) and circumferential strains (CS) of the 16 AHA segments excluding apex cordis. The complete myocardial infarction (CMI) segments, partial myocardial infarction (PMI) segments and non-myocardial infarction (NMI) segments were identified and compared. RESULTS: Patients: The radial strain and circumferential strain of the CMI and PMI segments were smaller than the NMI segment (both P < 0.01). However, there was no significant difference between the CMI and the PMI segment (P>0.05). Rats: No significance differences were found in EF and EDV between the two time period 48 h and 7 d (both P>0.05). The radial strain and circumferential strain of the CMI and PMI segments were smaller than the NMI segment (all P < 0.01). But there was no significance difference between the CMI segment and the PMI segment (P>0.05). No significant changes in the global radial strain and the circumferential strain were found over time (both P>0.05). But the segmental radial strain and circumferential strain became larger over time (all P < 0.05). CONCLUSIONS: The systolic ability of myocardium decreases as a result of reperfusion injury in the early phase of reperfused myocardial infarction. But it can gradually recover over time with reperfusion.


Assuntos
Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Animais , Meios de Contraste , Gadolínio , Gadolínio DTPA , Humanos , Ratos
9.
Chin Med J (Engl) ; 131(24): 2930-2937, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30539905

RESUMO

Background: The incidence of cryptococcal meningitis among immunocompetent patients increases, especially in China and imaging plays an important role. The current study was to find the correlation between magnetic resonance imaging (MRI) manifestation and clinical severity in nonhuman immunodeficiency virus patients with cryptococcal infection of central nervous system (CNS). Methods: A total of 65 patients with CNS cryptococcal infection from August 2014 to October 2016 were retrospectively included in this study. All the patients had MRI data and clinical data. The patients were divided into two groups according to whether the patients were confirmed with identifiable underlying disease. Comparison and correlation of MRI and clinical data in both groups were investigated using independent sample t- test, Chi-square test, Mann-Whitney test and Spearman rank correlation analysis. Results: In all 65 patients, 41 cases (41/65, 63.1%; Group 1) had normal immunity and 24 cases (24/65, 36.9%; Group 2) had at least one identifiable underlying disease. Fever, higher percentage of neutrophil (NEUT) in white blood cell (WBC), and increased cell number of cerebral spinal fluid (CSF) were much common in patients with underlying disease (Group 1 vs. Group 2: Fever: 21/41 vs. 21/24, χ2 = 8.715, P = 0.003; NEUT in WBC: 73.15% vs. 79.60%, Z = -2.370, P = 0.018; cell number of CSF: 19 vs. 200, Z = -4.298, P < 0.001; respectively). Compared to the patients with normal immunity, the lesions are more common in the basal ganglia among patients with identifiable underlying disease (Group 1 vs. Group 2: 20/41 vs. 20/24, χ2 = 7.636, P = 0.006). The number of the involved brain areas in patients with identifiable underlying disease were well correlated with the number of cells and pressure of CSF (r = -0.472, P = 0.031; r = 0.779, P = 0.039; respectively). Conclusions: With the increased number of the involved brain areas in patients with identifiable underlying disease, the body has lower immunity against the organism which might result in higher intracranial pressure and more severe clinical status.


Assuntos
Encefalite/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Meningite Criptocócica/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Huan Jing Ke Xue ; 39(1): 219-226, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965685

RESUMO

The anaerobic-anoxic-oxic (AAO) process was used to investigate the variation of the parameters of water quality when the dissolved oxygen (DO) in the aerobic tank was controlled at a low concentration. The results indicated the system still had good phosphorus and nitrogen removal efficiencies when the DO concentration in the aerobic tank was decreased from 2.00 mg·L-1 to 1.00 mg·L-1 and 0.50 mg·L-1, and the effluent indexes could meet the first class A standard for the "discharge standard of pollutants for municipal wastewater treatment plant" (GB18918-2002) of China. The activated sludge model of the AAO process was developed by BioWin 4.1 software. The sensitivities of the model parameters were analyzed, and the model parameters, such as amount of polyhydroxyalkanoate (PHA) stored per unit of acetate or the propionate sequestered by phosphorus accumulating bacteria (YP/PHA,seq), the amount of phosphorus stored per unit of PHA oxidized in aerobic conditions by phosphorus accumulating bacteria (YP/PHA,aerobic), the maximum specific growth rate of ammonia oxidizing bacteria (µmax,A), and the maximum specific growth rate of nitrite oxidizing bacteria (µmax,N), were calibrated and validated by the dynamic simulation. In addition, the energy consumption of the aeration was simulated and evaluated. The results showed that when the DO concentration in the aerobic tank was decreased from 2.00 mg·L-1 to 1.00 mg·L-1 and 0.50 mg·L-1, the air flow could be reduced by 23.8% and 38.1%, and the oxygen transfer efficiency could be increased by 7.2% and 11.7%, respectively.


Assuntos
Reatores Biológicos , Nitrogênio/isolamento & purificação , Oxigênio/química , Fósforo/isolamento & purificação , Eliminação de Resíduos Líquidos , Bactérias/metabolismo , China , Esgotos
11.
Front Neurosci ; 12: 928, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30618557

RESUMO

Spontaneous intracerebral hemorrhage (ICH) is one of the most lethal forms of stroke. From the limited previous studies and our preliminary data, white matter is considered a key predictor of the outcome and potential target of recovery. The traditional ICH model induced by injection of autologous blood or bacterial collagenase into striatum (ST) demonstrated a spontaneous functional recovery within one or 2 months. We hypothesis that an internal capsule (IC) lesion might lead to long-term axonal damage and long lasting functional deficits. Thus in this study, a modified internal capsule ICH model was conducted in rats, and the axonal damage, neurological deficits, histopathology as well as electrophysiology were characterized. The finding demonstrated that compared to ST group, the modified IC lesioned model exhibited a relatively smaller lesion volume with consistent axonal loss/degeneration and long-lasting neurological dysfunction at 2 months after ICH. Functionally, the impairment of the mNSS, ratio of contralateral forelimb usage, four limb stand index, contralateral duty cycle and ipsilateral SSEPs amplitude remained significant at 56 days. Structurally, the significant loss of PKCγ in ipsilateral cortical spinal tracts of IC group and the consistent axonal degeneration with several axonal retraction bulbs and enlarged tubular space was observed at 56 days after ICH. This study suggested that a modified IC lesioned model was proved to have long lasting neurological deficits. A comprehensive understanding of the dynamic progression after experimental ICH should aid further successful clinic translation in animal ICH studies, and provide new insights into the role of whiter matter injury in the mechanism and therapeutic targets of ICH.

12.
Int J Surg ; 46: 27-36, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28797918

RESUMO

OBJECTIVE: The aim of the present study was to compare the efficacy and safety of oral tranexamic acid (TXA) with controls or intravenous TXA in patients undergoing total joint arthroplasty (TJA) in a systematic review and meta-analysis. METHODS: We systematically searched randomized controlled trials (RCTs) from PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and Google databases. Any studies comparing oral TXA versus a control group or intravenous TXA for patients prepared for TJA were included. The outcomes included the need for transfusion, hemoglobin drops, length of hospital stay and drain volume. We calculated the risk ratio (RR) with a 95% confidence interval (CI) for the need of transfusion and the weighted mean difference (WMD) with a 95% CI for hemoglobin drop, length of hospital stay and drain blood loss. Stata 12.0 was used for the meta-analysis. RESULTS: Five clinical trials (5 RCTs) involving 333 patients were finally included in this meta-analysis. When compared with the control group, oral TXA was associated with less need for transfusion, fewer hemoglobin drops, less drain volume and a shorter length of hospital stay (P < 0.05). When compared with IV TXA, oral TXA was associated with more hemoglobin drops (P < 0.05). However, there was no significant difference between the need for transfusion, drain volume and the length of hospital stay between oral TXA and IV TXA. CONCLUSION: Oral TXA has comparable hemostatic effects with IV TXA and may reduce the costs for patients prepared for TJA. However, considering the limited quality and number of the included studies, more high-quality and multi-center RCTs are still needed to recommend oral TXA for routine administration.


Assuntos
Antifibrinolíticos/administração & dosagem , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Transfusão de Sangue/estatística & dados numéricos , Hemorragia Pós-Operatória/tratamento farmacológico , Ácido Tranexâmico/administração & dosagem , Administração Intravenosa , Administração Oral , Idoso , Feminino , Hemostáticos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Sci Rep ; 7(1): 6831, 2017 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-28754954

RESUMO

This study aimed to investigate the effects of subpressure on the bond properties of total-etching adhesive to dentin. Thirty-six caries-free premolars were sectioned parallel to the occlusal plane and randomly divided into four groups (n = 9): a control group (C, no treatment) and three subpressure groups, which were treated under 0.8, 0.6 or 0.4 bar after applying adhesives, named S8, S6 and S4, respectively. Afterward, resin was bonded to the dentin surface, and 27 beams (1.0 mm × 1.0 mm) of each group were sectioned. One was selected to observe the bonding interface from each group by SEM. Each group was divided into two subgroups (n = 13): 24 hours of water storage (I) and 10,000 thermocycling (A). The microtensile bond strength (µTBS), failure modes and nanoleakage expression were evaluated. SEM results showed that the subpressure groups had longer and denser resin tags. The µTBS of the subpressure groups was higher than that of the control group (p < 0.05). The subpressure groups were dominated by mixed failure, whereas main interfacial failure appeared in group C. The subpressure groups showed less silver deposition than the control group (p < 0.05). The subpressure technique may remarkably improve bonding strength and decrease nanoleakage on total-etching bonding.


Assuntos
Colagem Dentária/métodos , Dente Pré-Molar/efeitos dos fármacos , Dente Pré-Molar/ultraestrutura , Colagem Dentária/instrumentação , Dentina/efeitos dos fármacos , Dentina/ultraestrutura , Humanos , Pressão , Cimentos de Resina/farmacologia
14.
PLoS One ; 12(6): e0179668, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28640855

RESUMO

OBJECTIVE: This study was conducted to investigate the effect of subpressure on the bond strength of resin to zirconia ceramic. The subpressure would create a pressure gradient which could clean out the bubbles in the adhesives or bonding interface. METHODS: Twenty-eight pre-sintered zirconia discs were fabricated. Half of them were polished (group P, n = 14), and the rest were sandblasted (group S, n = 14). After sintered,the surface roughness of the zirconia discs was measured. Then, they were randomly divided into two subgroups (n = 7). The groups were named as follows: PC: P + no additional treatments; PP: P + 0.04 MPa after application of adhesives; SC: S + no additional treatments; and SP: S + 0.04 MPa after application of adhesives. Resin columns were bonded to the zirconia specimens to determine shear bond strength (SBS). The bonding interfaces were observed and the fracture modes were evaluated. Statistical analysis was performed on all data. RESULTS: The surface roughness of group S was significantly higher than that of group P (P<0.05). The SBS values were PC = 13.48 ± 0.7 MPa, PP = 15.22 ± 0.8 MPa, SC = 17.23 ± 0.7 MPa and SP = 21.68 ± 1.4 MPa. There were significant differences among the groups (P<0.05). Scanning electron microscopy (SEM) results showed that the adhesives of group SP and PP were closer and denser to the zirconia ceramic than that of group PC and SC. The proportion of the mixed fracture mode significantly increased after adding subpressure (P< 0.05). CONCLUSION: Subpressure can improve the shear bond strength of resin to zirconia ceramics and increase micro-infiltration between the adhesives and the zirconia ceramics, especially on the rough surfaces.


Assuntos
Cerâmica/química , Pressão , Cimentos de Resina/química , Zircônio/química , Resistência ao Cisalhamento , Propriedades de Superfície
15.
Oncol Lett ; 13(5): 3608-3616, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28521461

RESUMO

The efficacy of epidermal growth factor receptor- targeted therapy is significantly associated with Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-raf serine/threonine kinase proto-oncogene (BRAF) mutation in patients with colorectal cancer (CRC), for which the standard gene testing is currently performed using tumor tissue DNA. The aim of the present study was to compare the presence of KRAS and BRAF mutations in the serum exosome and primary tumor tissue from patients with CRC. Genomic DNA were extracted from the tumor tissues of 35 patients with histologically-confirmed CRC and exosomal mRNA were obtained from peripheral blood, which were collected from the corresponding patients prior to surgery. Three mutations in the KRAS gene (codons 12, 13 and 61) and a mutation in the BRAF gene (codon 600) were detected using a polymerase chain reaction-based sequencing method and their presence were compared between tumor tissues and the matched serum exosomes. The KRAS mutation rates in tumor tissues and the matched serum exosomes were 57.6 and 42.4%, respectively, which was not significantly different (P=0.063). The detection rate of the BRAF mutation was 24.2 and 18.2% in tumor tissues and the matched serum exosomes, respectively, and there was no significant difference (P=0.500). The patients with CRC that had a KRAS mutation of codon 12 in exon 2 in their tumor tissues and serum exosomes were significantly older compared with those without this mutation (tumor tissue, P=0.002; serum exosome, P=0.022). The sensitivity of KRAS and BRAF mutation detection using exosomal mRNA was 73.7 and 75%, respectively. The specificity of the detected mutations exhibited an efficiency of 100%, and the total consistency rate was 94.9 and 93.9% for KRAS and BRAF mutations, respectively. These results suggested that serum exosomal mRNA may be used as a novel source for the rapid and non-invasive genotyping of patients with CRC.

16.
Oncotarget ; 8(8): 12775-12783, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28061443

RESUMO

Ultra Violet (UV)-caused skin cell damage is a main cause of skin cancer. Here, we studied the activity of MHY1485, a mTOR activator, in UV-treated skin cells. In primary human skin keratinocytes, HaCaT keratinocytes and human skin fibroblasts, MHY1485 ameliorated UV-induced cell death and apoptosis. mTOR activation is required for MHY1485-induced above cytoprotective actions. mTOR kinase inhibitors (OSI-027, AZD-8055 and AZD-2014) or mTOR shRNA knockdown almost abolished MHY1485-induced cytoprotection. Further, MHY1485 treatment in skin cells activated mTOR downstream NF-E2-related factor 2 (Nrf2) signaling, causing Nrf2 Ser-40 phosphorylation, stabilization/upregulation and nuclear translocation, as well as mRNA expression of Nrf2-dictated genes. Contrarily, Nrf2 knockdown or S40T mutation almost nullified MHY1485-induced cytoprotection. MHY1485 suppressed UV-induced reactive oxygen species production and DNA single strand breaks in skin keratinocytes and fibroblasts. Together, we conclude that MHY1485 inhibits UV-induced skin cell damages via activating mTOR-Nrf2 signaling.


Assuntos
Citoproteção , Morfolinas/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Pele/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Triazinas/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Western Blotting , Células Cultivadas , Quebras de DNA de Cadeia Simples , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Técnicas de Silenciamento de Genes , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Serina-Treonina Quinases TOR/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos
17.
Pharm Biol ; 55(1): 554-559, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27937684

RESUMO

CONTEXT: Yinzhihuang oral liquid, a well-known Chinese herbal formula, is a clinical drug for the treatment of neonatal jaundice, and a number of clinical trials have been published addressing this issue, but there is no comprehensive analysis that evaluates its efficacy for the treatment of newborn with hyperbilirubinaemia. OBJECTIVE: A meta-analysis was conducted to evaluate the efficacy of Yinzhihuang oral liquid on neonatal jaundice. METHODS: Search was performed throughout PubMed, Cochrane Library, EMBASE, Ovid, Wanfang, VIP Medicine Information System (VMIS) and China National Knowledge Infrastructure (CNKI) databases up to December 2015. The search terms were (Yinzhihuang oral liquid or Yinzhihuang oral solution), (neonatal jaundice or neonatal hyperbilirubinaemia), and (efficacy). Review Manager 5.2 software was used for analyzing the data. Data were pooled by using the random-effects models and expressed as relative ratio (RR), standardized mean difference (SMD) or mean difference (MD) with a 95% confidence interval (CI). The Cochrane tool was applied to assess the risk of bias of the trials. RESULTS: Yinzhihuang oral liquid in conjunction with other therapy increased effective rate of neonatal jaundice therapy (RR =1.14, 95%CI: 1.08-1.20). Yinzhihuang oral liquid significantly eliminated overproduced bilirubin which was measured by TSB or TCB at the third day and fifth day during the treatment {[third day, SMD = -1.63, 95%CI: -2.20 to (-1.06)], [fifth day, SMD = -5.00, 95%CI: -7.88 to (-2.12)]}; Yinzhihuang oral liquid significantly shortened jaundice subsiding time [MD = -3.20, 95%CI: -6.01to (-0.39)]. CONCLUSION: Yinzhihuang oral liquid can be considered as an effective treatment option for neonatal jaundice.


Assuntos
Bilirrubina/sangue , Medicamentos de Ervas Chinesas/uso terapêutico , Hiperbilirrubinemia Neonatal/tratamento farmacológico , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Hiperbilirrubinemia Neonatal/sangue , Hiperbilirrubinemia Neonatal/diagnóstico , Recém-Nascido , Razão de Chances , Fitoterapia , Plantas Medicinais , Resultado do Tratamento
18.
J Hepatol ; 66(3): 601-609, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27871879

RESUMO

BACKGROUND & AIMS: Aging is known to exacerbate the progression of alcoholic liver disease (ALD), but the underlying mechanisms remain obscure. The aim of this study was to use a chronic plus binge ethanol feeding model in mice to evaluate the effects of aging on alcohol-induced liver injury. METHODS: C57BL/6 mice were subjected to short-term (10days) ethanol plus one binge or long-term (8weeks) ethanol plus multiple binges of ethanol. Liver injury and fibrosis were determined. Hepatic stellate cells (HSCs) were isolated and used in in vitro studies. RESULTS: Middle-aged (12-14months) and old-aged (>16months) mice were more susceptible to liver injury, inflammation, and oxidative stress induced by short-term plus one binge or long-term plus multiple binges of ethanol feeding when compared to young (8-12weeks) mice. Long-term plus multiple binges of ethanol feeding induced greater liver fibrosis in middle-aged mice than that in young mice. Hepatic expression of sirtuin 1 (SIRT1) protein was downregulated in the middle-aged mice compared to young mice. Restoration of SIRT1 expression via the administration of adenovirus-SIRT1 vector ameliorated short-term plus binge ethanol-induced liver injury and fibrosis in middle-aged mice. HSCs isolated from middle-aged mice expressed lower levels of SIRT1 protein and were more susceptible to spontaneous activation in in vitro culture than those from young mice. Overexpression of SIRT1 reduced activation of HSCs from middle-aged mice in vitro with downregulation of PDGFR-α and c-Myc, while deletion of SIRT1 activated HSCs isolated from young mice in vitro. Finally, HSC-specific SIRT1 knockout mice were more susceptible to long-term chronic-plus-multiple binges of ethanol-induced liver fibrosis with upregulation of PDGFR-α expression. CONCLUSIONS: Aging exacerbates ALD in mice through the downregulation of SIRT1 in hepatocytes and HSCs. Activation of SIRT1 may serve as a novel target for the treatment of ALD. LAY SUMMARY: Aged mice are more susceptible to alcohol-induced liver injury and fibrosis, which is, at least in part, due to lower levels of sirtuin 1 protein in hepatocytes and hepatic stellate cells. Our findings suggest that sirtuin 1 activators may have beneficial effects for the treatment of alcoholic liver disease in aged patients.


Assuntos
Envelhecimento/genética , Envelhecimento/patologia , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/patologia , Sirtuína 1/genética , Envelhecimento/metabolismo , Animais , Consumo Excessivo de Bebidas Alcoólicas , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatopatias Alcoólicas/etiologia , Regeneração Hepática , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo , Sirtuína 1/deficiência
19.
Int J Clin Exp Med ; 8(7): 11490-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26379968

RESUMO

OBJECTIVE: To analyze the distribution of HLA-DRB1 and HLA-DQB1 alleles and its correlation with IFN-γ, IL-2, IL-6, IL-10 in HPV16 infected women with advanced cervical carcinoma. METHODS: We collected 137 blood samples of cervical carcinoma patients diagnosed by pathology as cervical cancer in stage IIb-IVb before the treatment, and we gathered 175 blood samples of healthy women living in the local. We determined the genetic subtypes of HLA-DRB1 and HLA-DQB1, and we measured the concentration of IFN-γ, IL-2, IL-6 and IL-10. We compared the difference of cytokines in patients with different clinical stages and the healthy in the control group. According to genetic subtypes of HLA-DRB1 and HLA-DQB1, we also compared the concentration of cytokine (CK) in different genetic subtypes. RESULTS: Eight HLA-DRB1 alleles and four HLA-DQB1 alleles were found. There were not significant differences between each allele in the concentration of IFN-γ, IL-2, IL-6, and IL-10. CONCLUSION: HLA-DRB1*07, HLA-DQB1*02 and HLA-DQB1*03 were the differentially expressed gene in HPV16 infected patients with advanced cervical cancer. There may be correlations between the occurrence, development of cervical cancer and IFN-γ, IL-2, IL-6, IL-10.

20.
Asian Pac J Cancer Prev ; 16(8): 3325-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25921139

RESUMO

Pim kinase-3(Pim-3), a member of serine/threonine protein kinases, has been implicated in multiple human cancers and involved in Myc-induced tumorigenesis. However, little is known regarding its expression and biological function in human ovarian cancer. In this study we showed that the clinical significance and biological functions of Pim-3 in ovarian cancer and found that higher Pim-3 mRNA level are detected in ovarian cancer tissues than those in normal ovarian tissues. There are significant correlations between higher Pim-3 expression levels with the FIGO stage, histopathological subtypes, and distant metastasis in ovarian cancer patients. Lentivirus-mediated gene overexpression of Pim-3 significantly promotes the proliferation and migration of SKOV3 cell lines. Furthermore, MACC1 and Pim-3 expression were significantly correlated in human ovarian cancer cells, and overexpression of Pim-3 in ovary cancer cells increased MACC1 mRNA and protein expression. The data indicate that Pim-3 acts as a putative oncogene in ovary cancer and could be a viable diagnostic and therapeutic target for ovarian cancer.


Assuntos
Adenocarcinoma/genética , Disgerminoma/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/genética , Ovário/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cistadenocarcinoma Mucinoso/genética , Cistadenocarcinoma Mucinoso/metabolismo , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Disgerminoma/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transativadores , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
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