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1.
Trials ; 21(1): 69, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924256

RESUMO

BACKGROUND: The loss of functional ability of patients after stroke is mostly caused by dysfunction of the upper limbs, especially the hands. Hand functional exercise is the premise of alleviating hand dysfunction, and the relief of hand spasm is the basis of timely and effective hand functional exercise. Previous clinical observation have shown that fascial-point needling can effectively alleviate hand spasm immediately after stroke, but further evidence from large-sample studies is needed. The overall objective of this trial is to further evaluate the clinical efficacy of fascial-point acupuncture on hand spasm after stroke. METHODS/DESIGN: This multicenter randomized controlled trial will compare the efficacy of fascial-point acupuncture versus sham acupuncture and routine rehabilitation therapy in stroke patients with hand spasm. Patients will be randomized to undergo either the fascial-point acupuncture, the sham acupuncture or the control (routine rehabilitation therapy). We will recruit 210 stroke inpatients who meet the trial criteria and observe the remission of hand spasm and improvement of limb function after 4 weeks of intervention. The first evaluation indices are the remission of hand spasm and the duration of spasm remission. The second evaluation indices are the hand function of the affected limbs and the activities of daily living. When the accumulative total number of cases included reaches 120, a mid-term analysis will be conducted to determine any evidence that experimental intervention does have an advantage. DISCUSSION: Our aim is to evaluate the efficacy of fascial-point acupuncture in relieving hand spasm after stroke. The results should provide more evidence for the clinical application of this therapy in the future. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ID: ChiCTR1900022379. Registered on 9 April 2019.

2.
Acta Pharmacol Sin ; 41(1): 93-100, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31285534

RESUMO

PARK2, which encodes Parkin, is a disease-causing gene for both neurodegenerative disorders and cancer. Parkin can function as a neuroprotector that plays a crucial role in the regulation of mitophagy, and germline mutations in PARK2 are associated with Parkinson's disease (PD). Intriguingly, recent studies suggest that Parkin can also function as a tumor suppressor and that somatic and germline mutations in PARK2 are associated with various human cancers, including lung cancer. However, it is presently unknown how the tumor suppressor activity of Parkin is affected by these mutations and whether it is associated with mitophagy. Herein, we show that wild-type (WT) Parkin can rapidly translocate onto mitochondria following mitochondrial damage and that Parkin promotes mitophagic clearance of mitochondria in lung cancer cells. However, lung cancer-linked mutations inhibit the mitochondrial translocation and ubiquitin-associated activity of Parkin. Among all lung cancer-linked mutants that we tested, A46T Parkin failed to translocate onto mitochondria and could not recruit downstream mitophagic regulators, including optineurin (OPTN) and TFEB, whereas N254S and R275W Parkin displayed slower mitochondrial translocation than WT Parkin. Moreover, we found that deferiprone (DFP), an iron chelator that can induce mitophagy, greatly increased the death of A46T Parkin-expressing lung cancer cells. Taken together, our results reveal a novel mitophagic mechanism in lung cancer, suggesting that lung cancer-linked mutations in PARK2 are associated with impaired mitophagy and identifying DFP as a novel therapeutic agent for PARK2-linked lung cancer and possibly other types of cancers driven by mitophagic dysregulation.

3.
Lipids Health Dis ; 18(1): 210, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801554

RESUMO

BACKGROUND: It has been confirmed that the triglyceride to high-density lipoprotein cholesterol ratio (THR) is associated with insulin resistance and metabolic syndrome. However, to the best of our knowledge, only a few studies with small sample sizes have investigated the relationship between THR and coronary artery disease (CAD). Therefore, we aimed to assess the correlation between the THR and long-term mortality in patients with CAD after undergoing percutaneous coronary intervention (PCI) in our study that enrolled a large number of patients. METHODS: A total of 3269 post-PCI patients with CAD were enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The mean follow-up time was 37.59 ± 22.24 months. Patients were divided into two groups according to their THR value: the lower group (THR < 2.84, n = 1232) and the higher group (THR ≥ 2.84, n = 2037). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: In our study, ACM occurred in 124 patients: 30 (2.4%) in the lower group and 94 (4.6%) in the higher group (P = 0.002). MACEs occurred in 362 patients: 111 (9.0%) in the lower group and 251 (12.3%) in the higher group (P = 0.003). The number of MACCEs was 482: 152 (12.3%) in the lower group and 320 (15.7%) in the higher group (P = 0.008). Heart failure occurred in 514 patients: 89 (7.2%) in the lower group and 425 (20.9%) in the higher group (P < 0.001). Kaplan-Meier analyses showed that elevated THR was significantly related to long-term ACM (log-rank, P = 0.044) and the occurrence of heart failure (log-rank, P < 0.001). Multivariate Cox regression analyses showed that the THR was an independent predictor of long-term ACM (adjusted HR = 2.042 [1.264-3.300], P = 0.004) and heart failure (adjusted HR = 1.700 [1.347-2.147], P < 0.001). CONCLUSIONS: An increased THR is an independent predictor of long-term ACM and heart failure in post-PCI patients with CAD.

4.
Medicine (Baltimore) ; 98(46): e17403, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725603

RESUMO

Studies investigating the association between gene variants and depression susceptibility found inconsistent data. The present study aimed to clarify whether CNR1rs1049353, CNR1 AAT triplet repeat, and CNR2rs2501432 polymorphisms confer higher risk for depressive disorder.Literature from PubMed, Medline, Embase, Scopus, Cochrance Library, and Wanfang databases was searched (up to August 20, 2018). Seven case-control studies with various comorbidities were eligible. We targeted CNR single-nucleotide polymorphisms (SNPs) that have been reported by 2 or more studies to be involved in the current meta-analysis, resulting in a final list of 3 SNPs: CNR1rs1049353, CNR1 AAT triplet repeat polymorphism, and CNR2rs2501432. Odds ratios (ORs) and 95% confidence intervals (CIs) for allele and homozygote comparisons, dominant and recessive models, and triplet repeat polymorphism ((AAT)n≥5, ≥5 vs (AAT)n<5, <5 or <5, ≥5) were assessed using a random effect model as measures of association. Heterogeneity among included studies was analyzed using sensitivity test. Publication bias was also explored by Egger and rank correlation test.overall, no significant association was found between depression and CNR1rs1049353 (G vs A: OR [95% CI] = 1.09 [0.61-1.95]; GG vs AA: 1.29 [0.73-2.26]; GG vs GA+AA: 1.10 [0.57-2.10]; GG+GA vs AA: 1.25 [0.72-2.18]; and AAT triplet repeat polymorphism ((AAT)n≥5, ≥5 vs (AAT)n<5, <5 or <5, ≥5): 1.92 [0.59-6.27]. In contrast, a significant association between CNR2rs2501432 and depression was detected, and the ORs and 95% CIs are as follows: allele contrast (OR = 1.39, 95% CI = [1.12-1.72], P = .003); homozygous (OR = 2.19, 95% CI = [1.34-3.59], P = .002); dominant (OR = 1.93,95% CI = [1.23-3.04], P = .005); and recessive (OR = 1.41, 95% CI = [1.04-1.92], P = .03).This meta-analysis revealed that CNR1rs1049353 or AAT triplet repeat polymorphism had no association with susceptibility to depression, while CNR2rs2501432 polymorphism was a remarkable mark for depression patients.


Assuntos
Depressão/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Receptor CB1 de Canabinoide/genética , Receptor CB2 de Canabinoide/genética , Alelos , Estudos de Casos e Controles , Humanos , Razão de Chances , Fatores de Risco
5.
Neurochem Res ; 44(12): 2821-2831, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31728857

RESUMO

Paeoniflorin (PF) has been reported to possess neuroprotective influences on cognitive dysfunction illness. In current research, we attempted to probe into the protective influences of PF against H2O2-induced damage and the underlying regulating mechanisms on hippocampal HT-22 cells. HT-22 cells were pretreated with PF, and then induced by H2O2. Afterwards, the influences of PF pretreatment were examined using CCK-8 assay, apoptosis assay, western blot and ROS assay, respectively. In addition, the expression of microRNA-135a (miR-135a) was analyzed and altered by qRT-PCR and cell transfection, respectively. After overexpression of miR-135a, the effects of miR-135a mimic on cell functions were detected again. Moreover, influences of H2O2, PF and miR-135a overexpression on JAK2/STAT3 and ERK1/2 signal pathways were further investigated. Further experiments verified that PF pretreatment alleviated H2O2-induced oxidative stress through increasing cell viability, inhibiting cell apoptosis, reducing ROS generation and activating JAK2/STAT3 and ERK1/2 pathways. Besides, expression of miR-135a was declined by PF pretreatment. Whereas, miR-135a mimic abrogated the protective effects triggered by PF pretreatment. These results indicated that PF can alleviate H2O2-induced oxidative stress by down-regulation of miR-135a via activation of JAK2/STAT3 and ERK1/2 pathways.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31725126

RESUMO

STUDY DESIGN: To evaluate the effect of p38 pathway on spinal cord injury (SCI), a rat model of SCI was performed. OBJECTIVE: We determined the effect of p38 on SCI and SCI related inflammation, apoptosis and autophagy. SUMMARY OF BACKGROUND DATA: SCI is a severe clinical problem worldwide. It is difficult to prevent cell necroptosis and promote the survival of residual neurons after SCI. p38, a class of mitogen-activated protein kinases (MAPKs), its effect on SCI and SCI related inflammation, apoptosis and autophagy have not been studied very well. METHODS: The rats were randomly divided into the following 4 groups: the sham-operated (sham) group, the SCI group, the SCI + vehicle group, and the SCI + SB203580 (10 mg/kg) group. The p38 inhibitor SB203580 was administered by oral (10 mg/kg/d) gavage once per day for 14 d. Neurological recovery was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotion rating scale. Apoptosis, autophagy and inflammation related proteins were measured by ELISA kits or western blotting. RESULTS: Our results showed that p38 was upregulated after SCI from day 3, which was paralleled with the levels of its proteins ATF-2, suggesting an increase in p38 activity. Our results showed administration of SB203580 attenuated histopathology and promoted locomotion recovery in rats after SCI. SB203580 administration significantly inhibited inflammatory cytokines levels as well as the inflammation signaling pathway. SB203580 administration also modulated the apoptosis and autophagy signaling pathway. CONCLUSION: Our findings suggest that p38 inhibitor SB203580 treatment alleviates secondary SCI by inhibiting inflammation and apoptosis, thereby promoting neurological and locomoter functional recovery, thus suggest the important role of p38 in neuronal protection after SCI. LEVEL OF EVIDENCE: N/A.

7.
Mol Hum Reprod ; 25(12): 773-786, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31633178

RESUMO

Male 'blind sterile' mice with the causative TBC1 domain family member 20 (TBC1D20) deficiency are infertile with excessive germ cell apoptosis and spermatogenesis arrest at the spermatid stage. Sertoli cells are characterised as 'nurse cells' essential for normal spermatogenesis, but the role and corresponding molecular mechanisms of TBC1D20 deficiency in Sertoli cells of mice are not clear to date. In the present study, the histopathology of the testis and Sertoli cell proliferation and apoptosis were determined, and the corresponding molecular mechanisms were investigated by western blotting. Our data showed that TBC1D20 exhibits a testis-abundant expression pattern, and its expression level is positively associated with spermatogenesis. TBC1D20 is assembled in the Golgi and endoplasmic reticulum and is widely expressed by various germ cell subtypes and Sertoli cells. TBC1D20 deficiency in Sertoli cells led to an excessive apoptosis ratio and G1/S arrest. The increased apoptosis of TBC1D20-deficient Sertoli cells resulted from caspase-12 activation. TBC1D20-deficient Sertoli cells had an abnormal Golgi-endoplasmic reticulum structure, which led to endoplasmic reticulum stress, resulting in cell cycle arrest and excessive apoptosis. It suggested that TBC1D20 deficiency triggers irreversible endoplasmic reticulum stress resulting in G1/S arrest and excessive apoptosis in TBC1D20-deficient Sertoli cells, and TBC1D20 deficiency in Sertoli cells may also contribute to the infertility phenotype in 'blind sterile' male mice.

8.
Neurochem Int ; 131: 104543, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31491493

RESUMO

Prolonged administration of Levodopa (L-dopa) therapy can generate L-dopa-induced dyskinesia (LID). Accumulating evidence indicates that hyper-activation of the dopamine D1 receptor (D1R) and the cAMP signaling cascade in the medium spiny neurons (MSNs) of the striatum are involved in LID. Previous studies have shown that striatal ß-arrestin2 overexpression significantly reduces LID severity and have indicated that ß-arrestin2 may play a causal role in the dyskinesia sensitization process. L-dopa-induced changes in the expression of signaling molecules and other proteins in the striatum were examined immunohistochemically and by western blot. A rAAV (recombinant adeno-associated virus) vector was used to overexpress and ablate ß-arrestin2. We found that striatal overexpression of AAV-mediated ß-arrestin2 produced less severe AIMs (abnormal involuntary movements) in response to L-dopa, whereas selective deletion of ß-arrestin2 in the striatal neurons dramatically enhanced the severity of dyskinesia induced by L-dopa. Furthermore, no significant improvements in motor behavior (FFT: forelimb functional test) were seen with the inhibition or overexpression of ß-arrestin2. Finally, overexpression of ß-arrestin2 diminished L-dopa-induced D1R and phosphor-DARPP32/ERK levels. Viral deletion of ß-arrestin2 markedly enhanced the key biochemical markers in the direct pathway. We found that increased availability of ß-arrestin2 ameliorated dyskinesia severity with no influence on the anti-Parkinsonian action of L-dopa, suggesting a promising approach for controlling LID in Parkinson's disease. In addition, overexpression of ß-Arrestin2 prevented the development of LID by inhibiting G protein-dependent D1R and phosphor-DARPP32/ERK signaling in dyskinetic rats.

9.
Front Pharmacol ; 10: 660, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275144

RESUMO

Prolonged pulsatile administration of Levodopa (L-dopa) can generate L-dopa-induced dyskinesia (LID). Numerous research has reported that continuous dopamine delivery (CDD) was useful in reducing the severity of LID. 6-OHDA lesioned rats were divided into two groups to receive intermittent L-dopa stimulation (L-dopa/benserazide) or Levodopa/benserazide PLGA microsphere (LBPM) for 3 weeks. rAAV (recombinant adeno-associated virus) vector was used to overexpress and ablation of ß-arrestin2. We found that LBPM developed less AIM severity compared with standard L-dopa administration, whereas selective deletion of ß-arrestin2 in striatum neurons dramatically enhanced the severity of dyskinesia by LBPM. On the contrary, the effects of LBPM in terms of ALO AIM were further relieved by ß-arrestin2 overexpression. Furthermore, no significant change in motor behavior was seen either in inhibition or overexpression of ß-arrestin2. In short, our experiments provided evidence that LBPM's prevention of LID behavior was likely due to ß-arrestin2, suggesting that a therapy modulating ß-arrestin2 may offer a more efficient anti-dyskinetic method with a low risk of untoward effects.

10.
3 Biotech ; 9(5): 203, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31065503

RESUMO

Coat color genetics successfully adapted and applied to different animal species, which provides a good demonstration of the concept of comparative genetics. In this study, we sequenced 945 bp fragments of melanocortin 1 receptor (MC1R) gene, 421 bp fragments of exon 1 of tyrosinase (TYR) gene and 266 bp fragments of exon 3 of agouti signaling protein (ASIP) gene for 250 individuals with five plumage color patterns. We detected a total of three SNPs (T398A, T637C, and G920C) in MC1R and built six haplotypes (H1-H6) based on the three SNPs. H5 and H6 haplotypes were mainly concentrated in white and grey chicken. And diplotypes H2H3 occurred in white feather and black-speckle feather with the same frequency. Moreover, a total of three SNPs (C47G, T120C, and T172C) in TYR were found and built six haplotypes (P1-P6) based on the three SNPs. Among them, haplotype P2, P3 and P6 were not occurred in black chicken, the diplotypes P1P6 and P4P6 were only distributed in white, gray and black-speckled feather. We only detected one SNP (T168C) in ASIP gene and found that genotype TT was advantage genotype in the different plumage color groups of chickens. Collectively, our study suggested an association between plumage color and genetic variation of MC1R, TYR and ASIP in chicken.

11.
Environ Sci Pollut Res Int ; 26(19): 19272-19281, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31069655

RESUMO

As cadmium levels are increasing in the environment, the adverse effects of cadmium exposure specifically associated with chronic diseases are receiving increasing attention. Several population-based studies have been conducted on the association between cadmium and diabetes mellitus (DM) but have reported controversial results. Here, we aimed to evaluate the association between cadmium exposure and DM. In this meta-analysis, a random effects model was used because there was evidence of heterogeneity among studies. A dose-response relationship was assessed through a restricted cubic spline model with three knots. The results showed a positive association between cadmium levels in the body and DM (OR = 1.27; 95% CI, 1.07-1.52). The cadmium levels in the body were defined on the basis of combined urinary and blood cadmium. Subgroup analysis further indicated a positive association between urinary cadmium levels and DM (OR = 1.31; 95% CI, 1.02-1.69). The dose-response analysis results showed a positive association between levels of urinary cadmium above 2.43 µg/g creatinine and DM, and the risk of DM increased by 16% for each l µg/g creatinine increase in urinary cadmium levels. The results from our meta-analysis indicate that cadmium levels in the body are positively associated with DM, and urinary cadmium levels above 2.43 µg/g creatinine are associated with an increased risk of DM.


Assuntos
Cádmio/urina , Diabetes Mellitus/epidemiologia , Exposição Ambiental/análise , Poluentes Ambientais/urina , Cádmio/toxicidade , Creatinina/urina , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/urina , Relação Dose-Resposta a Droga , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Feminino , Humanos , Masculino
12.
Am J Transl Res ; 11(4): 2207-2218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105829

RESUMO

Renal cell carcinoma (RCC) is a common cancer that accounts for about 1.6% of all malignancies. Accumulating evidence has shown that miRNAs may play important roles in the development of cancers and that these same miRNAs may serve as diagnostic and prognostic biomarkers. The role of the miRNA miR-378a-5p in RCC, however, has been largely unexplored. In our study, we have demonstrated that miR-378a-5p expression was decreased in renal tissues and in RCC cell lines compared with corresponding expression levels in normal renal tissues and in the 293-T cell line. Functional studies in two RCC cell lines (ACHN and 786-O) have indicated that miR-378a-5p overexpression attenuated cell proliferation, migration, and invasion while promoting cell apoptosis. Inhibition of miR-378a-5p expression, on the other hand, promoted cell proliferation, migration, and invasion while reducing cell apoptosis. Additionally, in 42 cases of renal cancer formalin-fixed paraffin-embedded specimens, patients with higher expression levels of miR-378a-5p had significantly longer overall survival rates (P<0.05) than patients with lower miR-378a-5p expression levels. Thus, in this study, we have shown that miR-378a-5p can serve as a tumor suppressor and a potential prognostic biomarker in RCC.

13.
J Clin Neurosci ; 63: 110-115, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30737090

RESUMO

To investigate the prognostic value of platelet-to-neutrophil ratio (PNR) in acute ischemic stroke (AIS) patients. In this study, a total of 400 AIS patients were included. Demographic, clinical, laboratory data were collected on admission, and PNR was calculated according to platelet and neutrophil counts on admission. The prognosis after 3 months was evaluated by the Barthel index (BI), where BI ≤85 was defined as poor prognosis and BI >85 was defined as good prognosis. Regression analyses were performed, adjusting for confounders. (1) Compared with good prognosis group, PNR level on admission in poor prognosis group was significantly lower, the difference between the two groups was statistically significant (P < 0.05). (2) The difference in PNR level between the large infarct volume group and small infarct volume group was no statistically significant, nor between the moderate to severe group and the mild group (all P > 0.05). (3) In multivariate logistic regression analysis, PNR, platelet-to-lymphocyte ratio (PLR), platelet-to-white blood cell ratio (PWR) level were correlated with the 3 month prognosis of AIS. PNR may be an independent protective factor for predicting the prognosis of AIS. PNR level has a higher accuracy in the 3 month prognosis of acute ischemic cerebral infarction than the level of PLR and PWR. The level of PNR is correlated with the 3 month prognosis of acute ischemic cerebral infarction. The level of PNR may be an independent protective factor for predicting the prognosis of AIS.


Assuntos
Plaquetas/patologia , Isquemia Encefálica/sangue , Neutrófilos/patologia , Acidente Vascular Cerebral/sangue , Doença Aguda , Idoso , Isquemia Encefálica/diagnóstico , Feminino , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Acidente Vascular Cerebral/diagnóstico
14.
World Neurosurg ; 125: e348-e352, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30703596

RESUMO

OBJECTIVE: To evaluate the safety and accuracy of use of a 3-dimensional printed navigation template in the placement of a cortical bone trajectory (CBT) screw in the middle-upper thoracic spine. METHODS: Ten human cadavers were included in the study. Sixty CBT screws were placed on 1 side, using the free-hand technique, and 60 CBT screws were placed on the other side, using the navigation template that was designed and printed using data from 10 cadavers. The safety and accuracy of use of the CBT screws were directly evaluated by radiography and computed tomography. RESULTS: Computed tomography revealed that 2 and 3 of 60 screws, placed using the navigation template, were broken in the medial or lateral areas and in the superior or inferior pedicle wall, respectively. Furthermore, 8 screws were broken in the medial or lateral areas and 11 screws were broken in the superior or inferior pedicle wall when the free-hand technique was used. Radiography revealed that 3 screws in zone I, 55 screws in zone II, and 2 screws in zone III were placed using the navigation template. Furthermore, 7 screws in zone I, 45 screws in zone II, and 8 screws in zone III were placed using the free-hand technique. CONCLUSIONS: In this cadaver study, insertion of the CBT screws in the middle-upper thoracic spine with the assistance of the navigation template was safe and convenient.


Assuntos
Osso Cortical/cirurgia , Parafusos Pediculares , Impressão Tridimensional , Vértebras Torácicas/cirurgia , Adolescente , Adulto , Idoso , Cadáver , Osso Cortical/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto Jovem
15.
Biomed Pharmacother ; 111: 517-526, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30597305

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) accounts for more than 90% of cancers in the kidney. RCC is often asymptomatic, as a result people with RCC generally have advanced disease by the time it is discovered and has a poor prognosis compared to other cancers. Therefore, it is necessary to explore its pathogenesis and identify some reliable prognostic biomarker of RCC. miRNAs are emerging as important players in the development and progression of RCC. miR-31-5p has been reported to act as a tumor suppressor in hepatocellular carcinoma (HCC). The aim of this study is to determine the detailed molecular mechanism of miR-31-5p in the progression of RCC and to investigate its potential clinical value. METHODS: In this study, RT-qPCR, EdU assay, CCK-8 assay, wound scratch assay, transwell assay, flow cytometry assay and cell cycle assay were performed to detect miR-31-5p expression and its functions in RCC. Moreover, 42 formalin-fixed paraffin-embedded (FFPE) RCC samples were used to analyze the relationship between miR-31-5p expression and patients' overall survival. Finally, luciferase reporter assay, RT-qPCR assay and western blot were used to explore the association between miR-31-5p and its potential targets. RESULTS: miR-31-5p was significantly down-regulated in RCC tissues and RCC cell lines compared with paired adjacent normal tissues and normal cell lines. miR-31-5p downregulation was associated with poor prognosis in RCC patients. Overexpression of miR-31-5p inhibited RCC cell proliferation, migration and invasion and cell cycle. Conversely, down-regulation of miR-31-5p promoted cell proliferation, migration and invasion. Furthermore, cyclin-dependent kinasec1 (CDK1), a key player in cell cycle regulation, was identified as a functional target of miR-31-5p. CONCLUSIONS: Our results suggest that miR-31-5p serves as a tumor suppressor in RCC and is expected to be a molecular biomarker for poor prognosis of RCC.


Assuntos
Proteína Quinase CDC2/biossíntese , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , MicroRNAs/biossíntese , Proteínas Supressoras de Tumor/biossíntese , Idoso , Proteína Quinase CDC2/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/prevenção & controle , Feminino , Células HEK293 , Humanos , Neoplasias Renais/genética , Neoplasias Renais/prevenção & controle , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Supressoras de Tumor/genética
16.
J Nanosci Nanotechnol ; 19(1): 119-124, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30327010

RESUMO

The K-doped Li1-xKxFePO4 (x = 0, 0.005, 0.01, and 0.02) samples were synthesized successfully via a solid-state method, and the electronic structures of the samples were calculated by the first-principles based on density functional theory. Theoretical calculations show that the bandwidth of Li1-xKxFePO4 decreases with the increase in K+ doping, which is consistent with the experimental results. It was demonstrated that Li0.995K0.005FePO4 delivers higher capacity retention with 92.7% after 100 cycles compared with LiFePO4 (86.3%) at 1 C and shows better high-rate performance with capacities of 151.9, 151.8, 149.2, 128.3, and 84.6 mAh·g-1 at current densities of 0.1 C, 0.2 C, 0.5 C, 1 C, and 3 C; the corresponding values for LiFePO4 were 153.2, 136.5, 125.9, 111.5, and 66.0 mAh·g-1. Owing to the expanded Li ion diffusion pathway, EIS analysis showed that the lithium ion diffusion coefficient of LiFePO4 doped with K ion was significantly improved compared to LiFePO4; the values were 1.934×10-13 and 1.658×10-12 cm²·s-1, respectively. Additionally, Li0.995K0.005FePO4 showed a lower charge transfer resistance (300.2 Ω compared to 407.1 Ω of LiFePO4).

17.
Phytother Res ; 33(3): 524-533, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30575152

RESUMO

Curcumin is a polyphenolic natural compound with diverse and attractive biological activities, which may prevent or ameliorate pathological processes underlying age-related cognitive decline, dementia, or mood disorders. However, clinical trials and animal studies have yielded conflicting conclusions regarding its effectiveness for cognition in different individuals. The aim of this review is to meta-analytically assess the effectiveness of curcumin for cognitive function in different types of people. A preliminary search on PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese National Knowledge Infrastructure, and Wanfang Data and China Biology Medicine disc was performed to identify randomized controlled trials investigating the effect of curcumin on cognition. Six clinical trials with a total of 289 subjects met inclusion criteria for this review. We used a random-effects model to calculate the pooled standardized difference of means (SMD). For older adults who received curcumin, scores on measures of cognitive function (SMD = 0.33, 95% confidence interval [CI] [0.05, 0.62]; p = 0.02), occurrence of adverse events (odds ratio [OR] = 5.59, 95% CI [0.96, 36.80]; p = 0.05), and measures of depression (SMD = -0.29, 95% CI [0.64, 0.05]; p = 0.09) indicated significant memory improvement. In patients with Alzheimer's disease (AD), scores in measures of cognition status (SMD = -0.90, 95% CI [1.48, -0.32]; p = 0.002) indicated that there was a trend for treated subjects to do worse than placebo-treated subjects on the Mini-Mental State Examination. The occurrence of adverse events (OR = 0.87, 95% CI [0.10, 7.51]; p = 0.90) was similar to those who received placebo. Due to insufficient data, it was impossible to provide a narrative account of only the outcomes for schizophrenia. Curcumin appears to be more effective in improving cognitive function in the elderly than in improving symptoms of AD and schizophrenia. Curcumin is also safe and tolerated among these individuals. Because of the small number of studies available, a funnel plot or sensitivity analysis was not possible. Further high-quality trials with larger sample sizes or bioavailability-improved curcumin formulations may be considered for reliable assessment.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Curcumina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/psicologia , China , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Curcumina/farmacologia , Depressão/tratamento farmacológico , Depressão/epidemiologia , Depressão/psicologia , Humanos
18.
Aging (Albany NY) ; 11(24): 12315-12327, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31891566

RESUMO

The cause of the L-dopa-induced dyskinesia (LID) has been ascribed to G-protein coupled receptor (GPCR) supersensitivity and uncontrolled downstream signaling. It is now supposed that ß-arrestin2 affects GPCR signaling through its ability to scaffold various intracellular molecules. We used the rAAV (recombinant adeno-associated virus) vectors to overexpress and ablation of ß-arrestin2. L-dopa-induced changes in expression of signaling molecules and other proteins in the striatum were examined by western blot and immunohistochemically. Our data demonstrated that via AAV-mediated overexpression of ß-arrestin2 attenuated LID performance in 6-OHDA-lesioned rodent models. ß-arrestin2 suppressed LID behavior without compromising the antiparkinsonian effects of L-dopa. Moreover, we also found that the anti-dyskinetic effect of ß-arrestin2 was reversed by SKF38393, a D1R agonist. On the contrary, the rat knockdown study demonstrated that reduced availability of ß-arrestin2 deteriorated LID performance, which was counteracted by SCH23390, a D1R antagonist. These data not only demonstrate a central role for ß-arrestin2/GPCR signaling in LID, but also show the D1R signal pathway changes occurring in response to dopaminergic denervation and pulsatile administration of L-dopa.

19.
Br J Neurosurg ; : 1-4, 2018 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-30526115

RESUMO

OBJECT: Autism spectrum disorders (ASD) is characterized by stereotyped behavior, attention deficit and/or impaired sensory perception to external stimuli. Its neurobiological mechanisms remain unclear. In this study we examined the resting-state functional connectivity of the premotor area and investigated its correlation with behavioral variables to determine whether connectivity alterations can distinguish ASD from healthy controls. METHODS: 39 children with ASD and 42 healthy children with matched age, sex and intelligence were recruited. All the 81 subjects had behavioral index evaluation and underwent resting-state functional magnetic resonance imaging (fMRI) scans. After MRI data preprocessing, the left and right premotor areas were selected as region of interest (ROI) seeds to perform functional connectivity. Groups were compared, and the correlation between functional connectivity and behavioral indicators was analyzed. RESULTS: Compared with healthy controls, ASD children showed significantly increased functional connectivity between the left premotor area and the posterior cingulate gyrus or anterior lobe of wedge, but functional connectivity between the left premotor area and the left insular lobe was decreased (p < 0.05, FDR correction). In addition, the connectivity between the left premotor area and the left insular lobe was negatively correlated with the behavioral scores (p < 0.05). CONCLUSION: Imbalanced premotor functional connectivity may be one possible mechanism of stereotyped behavior in ASD.

20.
Front Aging Neurosci ; 10: 262, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271338

RESUMO

Background: Modulation of Metabotropic glutamate receptor 5 (mGluR5) may be a novel therapeutic approach to manage Parkinson's disease (PD) Patients with L-dopa-induced dyskinesia (LID). Objectives: The objective of this meta-analysis was to evaluate the effects of mGluR5 antagonists for the treatment of LID patients. Methods: Several electronic databases were consulted up to July 30, 2017. Randomized clinical trials (RCTs) that compared mGluR5 antagonists vs. placebo in LID patients were included. Pooled weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using random-effects models. Results: Nine trials including 776 patients met all inclusion criteria. We pooled the whole data and found apparent difference between mGluR5 antagonists and placebo in terms of mAIMS (p = 0.010). However, there was no significant improvements on antidyskinetic in terms of LFADLDS (p = 0.42) and UPDRS Part IV (p = 0.20). Meanwhile, the effect size of UPDRS part III was similar in mGluR5 antagonist groups with in placebo groups (p = 0.25). Adverse events incidence was higher with mGluR5 antagonists than with placebo, especially at the expense of increased dizziness (16.3 vs. 4.3%), visual hallucination (10.1 vs. 1.1%), or fatigue (10.1 vs. 4.8%). Conclusions: mGluR5 antagonists had a greater treatment effect on the mAIMS in LID patients, however, there was no improvements on antidyskinetic in terms of LFADLDS and UPDRS Part IV compared with placebo. According to these results, we unable to recommend mGluR5 antagonists for the routine treatment of LID patients right now.

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