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1.
Nat Commun ; 15(1): 5985, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013850

RESUMO

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates ß-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-ß signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.


Assuntos
Envelhecimento , Aneurisma Aórtico , Dissecção Aórtica , Senescência Celular , MicroRNAs , Músculo Liso Vascular , Quinase de Cadeia Leve de Miosina , Transdução de Sinais , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos , Quinase de Cadeia Leve de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Masculino , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Dissecção Aórtica/metabolismo , Dissecção Aórtica/genética , Dissecção Aórtica/patologia , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Miócitos de Músculo Liso/metabolismo , Camundongos Endogâmicos C57BL , Feminino , Fator de Crescimento Transformador beta/metabolismo , Modelos Animais de Doenças , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Angiotensina II/metabolismo , Proteínas de Ligação ao Cálcio
2.
Aging (Albany NY) ; 15(22): 13384-13410, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38015723

RESUMO

A ketogenic diet (KD) and ß-hydroxybutyrate (ßOHB) have been widely reported as effective therapies for metabolic diseases. ß-Hydroxybutyrate dehydrogenase 1 (BDH1) is the rate-limiting enzyme in ketone metabolism. In this study, we examined the BDH1-mediated ßOHB metabolic pathway in the pathogenesis of diabetic kidney disease (DKD). We found that BDH1 is downregulated in the kidneys in DKD mouse models, patients with diabetes, and high glucose- or palmitic acid-induced human renal tubular epithelial (HK-2) cells. BDH1 overexpression or ßOHB treatment protects HK-2 cells from glucotoxicity and lipotoxicity by inhibiting reactive oxygen species overproduction. Mechanistically, BDH1-mediated ßOHB metabolism activates NRF2 by enhancing the metabolic flux of ßOHB-acetoacetate-succinate-fumarate. Moreover, in vivo studies showed that adeno-associated virus 9-mediated BDH1 renal expression successfully reverses fibrosis, inflammation, and apoptosis in the kidneys of C57 BKS db/db mice. Either ßOHB supplementation or KD feeding could elevate the renal expression of BDH1 and reverse the progression of DKD. Our results revealed a BDH1-mediated molecular mechanism in the pathogenesis of DKD and identified BDH1 as a potential therapeutic target for DKD.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Animais , Humanos , Camundongos , Ácido 3-Hidroxibutírico/farmacologia , Antioxidantes/uso terapêutico , Nefropatias Diabéticas/metabolismo , Rim/patologia , Fator 2 Relacionado a NF-E2/genética , Hidroxibutirato Desidrogenase/metabolismo
3.
Opt Express ; 31(19): 30639-30649, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710603

RESUMO

Broadband wavelength tunable Laguerre-Gaussian (LG) mode with flexibly manipulated topological charge is greatly desired for large-capacity optical communication. However, the operating wavelengths achieved for the current LG modes are significantly restricted either by the emission spectrum of the intracavity gain medium or by the operation wavelengths of mode-conversion or modulation components. Here, broadband wavelength-tunable LG modes with a controllable topological charge are generated based on a random fiber laser (RFL) and a digital micromirror device (DMD). The RFL can produce broadly wavelength-tunable laser emissions spanning from 1044 to 1403 nm with a high spectral purity and an excellent beam quality, benefiting from the cascaded random Raman gain starting from a ytterbium fiber based active gain. A commercially available broadband DMD is then utilized to excite the LG modes with a flexibly tunable topological charge of up to 100 order through the super-pixel wavefront shaping technique. The combination of the RFL and the DMD greatly broadens the operating wavelength region of the LG modes to be achieved, which facilitates the capacity scaling-up in the orbital angular momentum multiplexed optical communication application.

4.
Front Plant Sci ; 14: 1164451, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37457345

RESUMO

To fully exploit the economic value of the Chinese endemic species Pteroceltis tatarinowii and provide new resources for forage production, the forage nutritional value of P. tatarinowii leaves from different populations was analyzed and evaluated. The results were as follows: 1) There were significant differences in the forage nutrient indices of leaves from different populations. The crude protein content was 10.77%-18.65%, with an average of 14.58%, and the SDJN population had the highest crude protein content. The average crude fat, crude fiber content was 7.62%; the average neutral detergent fiber content was 25.33%; and the average acid detergent fiber contents were 6.79%, 7.62%, 25.33%, and 17.52%, respectively. The average phosphorus and calcium content in the leaves was 0.785 g·kg-1 and 58.01 g·kg-1, respectively. The tannin content was much lower than the antifeedant standard, at an average of 4.97 g·kg-1. The average total amounts of hydrolyzed and free amino acids in the leaves were 108.20 mg·g-1 and 47.87 mg·g-1, respectively. Thus, P. tatarinowii leaves have high crude protein, crude fat, and calcium contents, and low fiber, tannin contents, and are protein-rich. These results provide evidence that this species can be developed into an excellent woody forage tree. 2) There were significant differences in the forage quality evaluation indices among the populations. The forage indices of NDP, ADP, DMI, DDM, and RFV of 21 populations all met the super standard of the American Grass and Grassland Association (AFGC) for hay, two crude protein indices met the grade 1 standard, and 12 crude protein indices met the grade 2 standard. Four high-protein and high-RFV forage populations (SDJN, SDZZ, SXLQ, and AHXX) were selected. 3) The results of the correlation analysis showed that there was no significant correlation between the forage characteristics of P. tatarinowii leaves and latitude and longitude, indicating no significant geographical variation. However, the forage characteristics were strongly correlated with elevation, average annual temperature, and annual precipitation. Thus, high elevation, low temperatures, and rainy weather can improve the forage value of the leaves. P. tatarinowii can be planted to provide leaf forage in cold and wet areas at a specific elevation. Moreover, the forage value of P. tatarinowii leaves can be further improved by increasing nitrogen fertilizer and reducing K and Ca fertilizers during cultivation. 4) Cluster analysis revealed obvious regionalism. Taking the Yangtze River Basin as the limit, cluster analysis divided the species into four population groups: the Yangtze River Basin and northern, southwestern, and eastern coastal populations.

5.
PeerJ Comput Sci ; 9: e1227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37346676

RESUMO

3D (three-dimensional) models are widely applied in our daily life, such as mechanical manufacture, games, biochemistry, art, virtual reality, and etc. With the exponential growth of 3D models on web and in model library, there is an increasing need to retrieve the desired model accurately according to freehand sketch. Researchers are focusing on applying machine learning technology to 3D model retrieval. In this article, we combine semantic feature, shape distribution features and gist feature to retrieve 3D model based on interactive attention convolutional neural networks (CNN). The purpose is to improve the accuracy of 3D model retrieval. Firstly, 2D (two-dimensional) views are extracted from 3D model at six different angles and converted into line drawings. Secondly, interactive attention module is embedded into CNN to extract semantic features, which adds data interaction between two CNN layers. Interactive attention CNN extracts effective features from 2D views. Gist algorithm and 2D shape distribution (SD) algorithm are used to extract global features. Thirdly, Euclidean distance is adopted to calculate the similarity of semantic feature, the similarity of gist feature and the similarity of shape distribution feature between sketch and 2D view. Then, the weighted sum of three similarities is used to compute the similarity between sketch and 2D view for retrieving 3D model. It solves the problem that low accuracy of 3D model retrieval is caused by the poor extraction of semantic features. Nearest neighbor (NN), first tier (FT), second tier (ST), F-measure (E(F)), and discounted cumulated gain (DCG) are used to evaluate the performance of 3D model retrieval. Experiments are conducted on ModelNet40 and results show that the proposed method is better than others. The proposed method is feasible in 3D model retrieval.

6.
Math Biosci Eng ; 20(5): 9062-9079, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37161234

RESUMO

With the development of multimedia technology, the number of 3D models on the web or in databases is becoming increasingly larger and larger. It becomes more and more important to classify and retrieve 3D models. 3D model classification plays important roles in the mechanical design field, education field, medicine field and so on. Due to the 3D model's complexity and irregularity, it is difficult to classify 3D model correctly. Many methods of 3D model classification pay attention to local features from 2D views and neglect the 3D model's contour information, which cannot express it better. So, accuracy the of 3D model classification is poor. In order to improve the accuracy of 3D model classification, this paper proposes a method based on EfficientNet and Convolutional Neural Network (CNN) to classify 3D models, in which view feature and shape feature are used. The 3D model is projected into 2D views from different angles. EfficientNet is used to extract view feature from 2D views. Shape descriptors D1, D2, D3, Zernike moment and Fourier descriptors of 2D views are adopted to describe the 3D model and CNN is applied to extract shape feature. The view feature and shape feature are combined as discriminative features. Then, the softmax function is used to determine the 3D model's category. Experiments are conducted on ModelNet 10 dataset. Experimental results show that the proposed method achieves better than other methods.

8.
Shanghai Kou Qiang Yi Xue ; 31(4): 429-434, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36710560

RESUMO

PURPOSE: To investigate the characteristics of condylography of masticatory movement in patients of Class Ⅱ division 1 malocclusion with temporomandibular disorders (TMD), and the effects of TMD and Angle Ⅱ1 malocclusion factors on the condylography of masticatory movement. METHODS: According to the inclusion criteria of the experiment, ten normal occlusion subjects without TMD(nTMD-N), ten Angle Ⅱ1 patients without TMD(nTMD-Ⅱ1)and 14 Angle Ⅱ1 patients with TMD(TMD-Ⅱ1)were included. Cadiax IV was used to record the condylography of the subjects during mastication, and the data of condylography was measured and analyzed by GDSW software. The results were analyzed with SPSS 26.0 software package. RESULTS: The characteristics of condylography in nTMD-Ⅱ1 and TMD-Ⅱ1 groups were different from those of nTMD-N group. During unilateral mastication on the left or right side, there was no significant difference among nTMD-N group, nTMD-Ⅱ1 group and TMD-Ⅱ1 group. During bilateral mastication, the SCI value of nTMD-Ⅱ1 group was significantly higher than that of nTMD-N group, and the S value of nTMD-N group was significantly higher than that of nTMD-Ⅱ1 group (P<0.05). CONCLUSIONS: During unilateral masticatory movement, TMD and Angle Ⅱ1 malocclusion has little effect on the masticatory movement trajectory. Angle Ⅱ1 malocclusion has influence on bilateral masticatory movement, and the amplitude of condylar movement in patients with ClassⅡdivision 1 malocclusion is smaller than that in normal mastication. TMD has no significant effect on the masticatory movement condylography of the patients.


Assuntos
Má Oclusão Classe II de Angle , Má Oclusão , Transtornos da Articulação Temporomandibular , Humanos , Mastigação , Transtornos da Articulação Temporomandibular/diagnóstico por imagem
9.
Ying Yong Sheng Tai Xue Bao ; 32(8): 2791-2799, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34664452

RESUMO

The variations in plant growth of 32 Quercus acutissima provenances in three sites (Yongfeng, Jiangxi; Kaihua, Zhejiang and Chuzhou, Anhui) were studied. The AMMI model was used to analyze the stability of growth traits and to select the best provenances. The results showed that tree height, diameter at breast (ground) height, and aboveground biomass (AGB) per individual of the provenances were significantly different in the three sites. The AGB per individual was significantly affected by site, provenance, and the interaction of provenance × site. Site had the greatest impact on the variation of tree growth, followed by provenance and provenance × site. The growth performance of these superior provenances in different sites varied greatly in the seedling stage (1-3 years old) and young forest stage (4-11 years old). Based on the AGB per individual in the 11st year, the best provenances were selected in each site. Seven superior provenances of Yongfeng, Jiangxi were selected, with the average AGB per individual increased by 15.6%-57.8% compared with the ave-rage value. Seven superior provenances of Kaihua, Zhejiang were selected, with the average AGB per individual increased by 19.2%-45.2%. Eight superior provenances of Chuzhou, Anhui were selected,with the average AGB per individual increased by 24.9%-63.3%. According to the growth performance and stability, four superior provenances were selected to develop short-rotation charcoal forest cultivation across three sites, with an average AGB per individual of 36.55 kg and an average stability parameter of 0.97.


Assuntos
Quercus , China , Florestas , Geografia , Fenótipo , Quercus/crescimento & desenvolvimento , Árvores/crescimento & desenvolvimento
10.
Acta Pharmacol Sin ; 41(11): 1377-1386, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32968208

RESUMO

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and an ongoing severe pandemic. Curative drugs specific for COVID-19 are currently lacking. Chloroquine phosphate and its derivative hydroxychloroquine, which have been used in the treatment and prevention of malaria and autoimmune diseases for decades, were found to inhibit SARS-CoV-2 infection with high potency in vitro and have shown clinical and virologic benefits in COVID-19 patients. Therefore, chloroquine phosphate was first used in the treatment of COVID-19 in China. Later, under a limited emergency-use authorization from the FDA, hydroxychloroquine in combination with azithromycin was used to treat COVID-19 patients in the USA, although the mechanisms of the anti-COVID-19 effects remain unclear. Preliminary outcomes from clinical trials in several countries have generated controversial results. The desperation to control the pandemic overrode the concerns regarding the serious adverse effects of chloroquine derivatives and combination drugs, including lethal arrhythmias and cardiomyopathy. The risks of these treatments have become more complex as a result of findings that COVID-19 is actually a multisystem disease. While respiratory symptoms are the major clinical manifestations, cardiovascular abnormalities, including arrhythmias, myocarditis, heart failure, and ischemic stroke, have been reported in a significant number of COVID-19 patients. Patients with preexisting cardiovascular conditions (hypertension, arrhythmias, etc.) are at increased risk of severe COVID-19 and death. From pharmacological and cardiovascular perspectives, therefore, the treatment of COVID-19 with chloroquine and its derivatives should be systematically evaluated, and patients should be routinely monitored for cardiovascular conditions to prevent lethal adverse events.


Assuntos
Doenças Cardiovasculares/complicações , Cloroquina/análogos & derivados , Cloroquina/uso terapêutico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Antivirais/farmacologia , COVID-19 , Cloroquina/farmacologia , Humanos , Pandemias , Tratamento Farmacológico da COVID-19
11.
Int J Cardiol ; 303: 69-73, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31748188

RESUMO

BACKGROUND: Older age, renal and cardiac dysfunction are predictors of poor outcome in aortic dissection. The aim of this study was to evaluate the association of the age, creatinine and ejection fraction (ACEF) score with adverse events in patients with type B aortic dissection (TBAD) undergoing thoracic endovascular aortic repair (TEVAR). METHODS: The study enrolled 605 patients from January 2010 to July 2015, who were classified into three groups according to the tertiles of ACEF score: Tertile 1 (≤0.77, n = 204), Tertile 2 (0.77-0.96, n = 205) and Tertile 3 (>0.96, n = 196). The association between ACEF, AGEF (age, glomerular filtration rate and ejection fraction) and the updated version of the ACEF (ACEF II) score with adverse events was analyzed. RESULTS: After a median 3.4 years follow-up, 63 (10.4%) patients died. Multivariable analysis revealed that ACEF score was independently associated with long-term mortality (adjusted hazard ratio = 3.54; 95% confidence interval, 2.09-6.01; p < 0.001). ACEF, AGEF and ACEF II score had similar predictive ability for both in-hospital and long-term death. The in-hospital mortality (1.5% vs. 1.0% vs. 6.6%, p = 0.001) were significantly higher in Tertile 3. In addition, cumulative long-term mortality in Tertile 3 was significantly higher than that in Tertile 1 and 2 (Log-Rank = 23.74; p < 0.001). CONCLUSION: ACEF score could be served as an useful and relatively simple tool for pre-TEVAR risk stratification in TBAD patients.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/sangue , Creatinina/sangue , Procedimentos Endovasculares/métodos , Medição de Risco/métodos , Volume Sistólico/fisiologia , Adulto , Dissecção Aórtica/mortalidade , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/sangue , Aneurisma da Aorta Torácica/mortalidade , Biomarcadores/sangue , China/epidemiologia , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
BMC Cardiovasc Disord ; 19(1): 297, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847835

RESUMO

BACKGROUND: Blood glucose (BG) is a risk factor of adverse prognosis in non-diabetic patients in several conditions. However, a limited number of studies were performed to explore the relationship between postoperative BG and adverse outcomes in non-diabetic patients with rheumatic heart disease (RHD). METHODS: We identified 1395 non-diabetic patients who diagnosed with having RHD, and underwent at least one valve replacement and preoperative coronary angiography. BG was measured at admission to the intensive care unit (ICU) after surgery. The association of postoperative BG level with in-hospital and one-year mortality was accordingly analyzed. RESULTS: Included patients were stratified into four groups according to postoperative BG level's (mmol/L) quartiles: Q1 (< 9.3 mmol/L, n = 348), Q2 (9.3-10.9 mmol/L, n = 354), Q3 (10.9-13.2 mmol/L, n = 341), and Q4 (≥ 13.2 mmol/L, n = 352). The in-hospital death (1.1% vs. 2.3% vs. 1.8% vs. 8.2%, P < 0.001) and MACEs (2.0% vs. 3.1% vs. 2.6% vs. 9.7%, P < 0.001) were significantly higher in the upper quartiles. Postoperative BG > 13.0 mmol/L was the best threshold for predicting in-hospital death (area under the curve (AUC) = 0.707, 95% confidence interval (CI): 0.634-0.780, P < 0.001). Multivariate logistic regression analysis indicated that postoperative BG > 13.0 mmol/L was an independent predictor of in-hospital mortality (adjusted odds ratio (OR) = 3.418, 95% CI: 1.713-6.821, P < 0.001). In addition, Kaplan-Meier curve analysis showed that the risk of one-year death was increased for a postoperative BG > 13.2 (log-rank = 32.762, P < 0.001). CONCLUSION: Postoperative BG, as a routine test, could be served as a risk measure for non-diabetic patients with RHD.


Assuntos
Glicemia/metabolismo , Implante de Prótese de Valva Cardíaca/efeitos adversos , Cardiopatia Reumática/cirurgia , Biomarcadores/sangue , Angiografia Coronária , Feminino , Implante de Prótese de Valva Cardíaca/mortalidade , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Cardiopatia Reumática/sangue , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
13.
Exp Mol Med ; 50(10): 1-14, 2018 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-30369596

RESUMO

Ketamine has a rapid, obvious, and persistent antidepressant effect, but its underlying molecular mechanisms remain unknown. Recently, microRNAs (miRNAs) have emerged as important modulators of ketamine's antidepressant effect. We investigated the alteration in miR-29b-3p in the brain of rats subjected to ketamine administration and chronic unpredictable mild stress (CUMS), and a sucrose preference test and forced swimming test were used to evaluate the rats' depressive-like state. We used recombination adeno-associated virus (rAAV) or lentivirus-expressing miR-29b-3p to observe the change in metabotropic glutamate receptor 4 (GRM4). Cell culture and electrophysiological recordings were used to evaluate the function of miR-29b-3p. Ketamine dramatically increased miR-29b-3p expression in the prefrontal cortex of the normal rats. The dual luciferase reporter test confirmed that GRM4 was the target of miR-29b-3p. The miR-29b-3p levels were downregulated, while the GRM4 levels were upregulated in the prefrontal cortex of the depressive-like rats. The ketamine treatment increased miR-29b-3p expression and decreased GRM4 expression in the prefrontal cortex of the depressive-like rats and primary neurons. By overexpressing and silencing miR-29b-3p, we further validated that miR-29b-3p could negatively regulate GRM4. The silencing of miR-29b-3p suppressed the Ca2+ influx in the prefrontal cortex neurons. The miR-29b-3p overexpression contributed to cell survival, cytodendrite growth, increases in extracellular glutamate concentration, and cell apoptosis inhibition. The overexpression of miR-29b-3p by rAAV resulted in a noticeable relief of the depressive behaviors of the CUMS rats and a lower expression of GRM4. The miR-29b-3p/GRM4 pathway acts as a critical mediator of ketamine's antidepressant effect in depressive-like rats and could be considered a potential therapeutic target for treating major depression disorder.


Assuntos
Antidepressivos/farmacologia , Ketamina/farmacologia , MicroRNAs/genética , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Regiões 3' não Traduzidas , Animais , Apoptose/genética , Cálcio/metabolismo , Sobrevivência Celular/genética , Modelos Animais de Doenças , Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Ácido Glutâmico/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Interferência de RNA , Ratos , Estresse Psicológico
14.
J Cardiovasc Pharmacol ; 72(4): 176-185, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29985281

RESUMO

Simvastatin treatment is cardioprotective in patients undergoing noncoronary artery cardiac surgery. However, the mechanisms by which simvastatin treatment protects the myocardium under these conditions are not fully understood. Seventy patients undergoing noncoronary cardiac surgery, 35 from a simvastatin treatment group and 35 from a control treatment group, were enrolled in our clinical study. Simvastatin (20 mg/d) was administered preoperatively for 5-7 days. Myocardial tissue biopsies were taken before and after surgery. Apoptosis was detected by TUNEL staining. The expressions of Bcl-2 and Bak in myocardial tissue were detected by immunoblotting. The expressions of miRNA and Bcl-2 mRNA were detected by quantitative real-time polymerase chain reaction assays. Cardiomyocytes were isolated from rat and cultured cells. MiR-15a-5p mimic was transfected into cardiomyocytes, and the Bcl-2 was detected by immunoblotting. TUNEL staining showed significantly less myocardial apoptosis in the simvastatin treatment group when compared with the control treatment group. Protein expression of Bcl-2 was increased in the simvastatin treatment group before surgery, and Bak expression was increased in the control treatment group after surgery. Further comparisons showed that Bcl-2/Bak ratios were reduced in the control treatment group but were not significantly changed in the simvastatin treatment group after surgery. Furthermore, microarray assays revealed that miR-15a-5p was significantly decreased by simvastatin treatment. This was validated by quantitative real-time polymerase chain reaction analysis. MiR-15a-5p was predicted to target Bcl-2 mRNA at nucleotide positions 2529-2536. This was validated by luciferase binding assays. Coincident with the change in miR-15a-5p, the mRNA expression of Bcl-2 was increased in the simvastatin treatment group. MiR-15a-5p mimic significantly inhibited Bcl-2 expression in cardiomyocytes. Our findings strongly suggest that simvastatin treatment preoperatively protected the myocardium in patients undergoing noncoronary artery cardiac surgery, at least in part, by inhibiting apoptosis via suppressing miR-15a-5p expression, leading to increasing expression of Bcl-2 and decreasing expression of Bak.


Assuntos
Apoptose/efeitos dos fármacos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Cardiopatias/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , MicroRNAs/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Sinvastatina/administração & dosagem , Adulto , Animais , Células Cultivadas , China , Esquema de Medicação , Feminino , Cardiopatias/genética , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sinvastatina/efeitos adversos , Resultado do Tratamento , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo
15.
Acta Pharmacol Sin ; 39(5): 885-892, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29698390

RESUMO

Contact inhibition and its disruption of vascular smooth muscle cells (VSMCs) are important cellular events in vascular diseases. But the underlying molecular mechanisms are unclear. In this study we investigated the roles of microRNAs (miRNAs) in the contact inhibition and its disruption of VSMCs and the molecular mechanisms involved. Rat VSMCs were seeded at 30% or 90% confluence. MiRNA expression profiles in contact-inhibited confluent VSMCs (90% confluence) and non-contact-inhibited low-density VSMCs (30% confluence) were determined. We found that multiple miRNAs were differentially expressed between the two groups. Among them, miR-145 was significantly increased in contact-inhibited VSMCs. Serum could disrupt the contact inhibition as shown by the elicited proliferation of confluent VSMCs. The contact inhibition disruption accompanied with a down-regulation of miR-145. Serum-induced contact inhibition disruption of VSMCs was blocked by overexpression of miR-145. Moreover, downregulation of miR-145 was sufficient to disrupt the contact inhibition of VSMCs. The downregulation of miR-145 in serum-induced contact inhibition disruption was related to the activation PI3-kinase/Akt pathway, which was blocked by the PI3-kinase inhibitor LY294002. KLF5, a target gene of miR-145, was identified to be involved in miR-145-mediated effect on VSMC contact inhibition disruption, as it could be inhibited by knockdown of KLF5. In summary, our results show that multiple miRNAs are differentially expressed in contact-inhibited VSMCs and in non-contact-inhibited VSMCs. Among them, miR-145 is a critical gene in contact inhibition and its disruption of VSMCs. PI3-kinase/Akt/miR-145/KLF5 is a critical signaling pathway in serum-induced contact inhibition disruption. Targeting of miRNAs related to the contact inhibition of VSMCs may represent a novel therapeutic approach for vascular diseases.


Assuntos
Inibição de Contato/fisiologia , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Animais , Contagem de Células , Proliferação de Células/fisiologia , Cromonas/farmacologia , Regulação para Baixo , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , MicroRNAs/genética , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia
16.
Cell Physiol Biochem ; 43(3): 1152-1167, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28977802

RESUMO

BACKGROUND/AIMS: ALT1 is a novel long non-coding RNA derived from the alternatively spliced transcript of the deleted in lymphocytic leukemia 2 (DLEU2). To date, ALT1 biological roles in human vascular endothelial cells have not been reported. METHODS: ALT1 was knocked down by siRNAs. Cell proliferation was analyzed by cck-8. The existence and sequence of human ALT1 were identified by 3' rapid amplification of cDNA ends. The interaction between lncRNA and proteins was analyzed by RNA-Protein pull down assay, RNA immunoprecipitation, and mass spectrometry analysis. RESULTS: ALT1 was expressed in human umbilical vein endothelial cells (HUVECs). The expression of ALT1 was significantly downregulated in contact-inhibited HUVECs and in hypoxia-induced, growth-arrested HUVECs. Knocking down of ALT1 inhibited the proliferation of HUVECs by G0/G1 cell cycle arrest. We observed that angiotensin converting enzyme Ⅱ(ACE2) was a direct target gene of ALT1. Knocking-down of ALT1 or its target gene ACE2 could efficiently decrease the expression of cyclin D1 via the enhanced ubiquitination and degradation, in which HIF-1α and protein von Hippel-Lindau (pVHL) might be involved. CONCLUSION: The results suggested the human long non-coding RNA ALT1 is a novel regulator for cell cycle of HUVECs via ACE2 and cyclin D1 pathway.


Assuntos
Peptidil Dipeptidase A/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Enzima de Conversão de Angiotensina 2 , Apoptose , Proteínas de Transporte/metabolismo , Hipóxia Celular , Proliferação de Células , Proteínas Culina/antagonistas & inibidores , Proteínas Culina/genética , Proteínas Culina/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Proteínas do Citoesqueleto , Regulação para Baixo , Pontos de Checagem da Fase G1 do Ciclo Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imunoprecipitação , MicroRNAs/metabolismo , Chaperonas Moleculares , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/genética , Interferência de RNA , RNA Longo não Codificante , RNA Interferente Pequeno/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Transferases , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Ubiquitinação
17.
J Oral Maxillofac Surg ; 74(11): 2286.e1-2286.e11, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27542550

RESUMO

PURPOSE: To evaluate transverse displacement of the proximal segment after bilateral sagittal split ramus osteotomy (BSSO) advancement with different lingual split patterns and advancement amounts and to determine the influential factors related to mandibular width. MATERIALS AND METHODS: A 3-dimensional finite element model of the mandible including the temporomandibular joint was created for a presurgical simulation and for BSSO with lingual split patterns I (T1; Hunsuck split) and II (T2; Obwegeser split). The mandible was advanced 3 mm (A3) and 8 mm (A8) and fixated with a conventional titanium plate. Ansys software was used to measure the linear distances of the interproximal segments and to analyze the transverse displacement distribution of proximal segments after applying the load of masticatory muscle force groups. RESULTS: After surgical simulation, T1A3, T1A8, T2A3, and T2A8 showed increased transverse widths (mean, 2.99, 4.70, 2.36, and 4.42 mm, respectively). For transverse augmentation, there was a statistically significant difference between the 2 different mandibular advancement amounts in T1 and in T2 (P ≤ .000), but no significant differences was observed between T1 and T2 (P ≥ .058). The maximum transverse displacement distribution in the proximal segment was measured around the gonial area, and the early contact area was found near the border between the horizontal and sagittal osteotomy lines. CONCLUSION: Transverse displacements of proximal segments occur after BSSO advancement with T1 and T2 and transverse augmentation has statistically meaningful effects depending on the amount of advancement; however, no differences in transverse augmentation between T1 and T2 were identified. The fulcrum caused by the early contact between the proximal and distal segments could be an influential factor related to mandibular width.


Assuntos
Mandíbula/anatomia & histologia , Mandíbula/cirurgia , Avanço Mandibular/métodos , Osteotomia Sagital do Ramo Mandibular/métodos , Simulação por Computador , Análise de Elementos Finitos , Humanos , Imageamento Tridimensional , Mandíbula/diagnóstico por imagem , Modelos Anatômicos , Avaliação de Resultados em Cuidados de Saúde , Período Pré-Operatório
18.
J Anesth ; 30(2): 232-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26582047

RESUMO

PURPOSE: A depressed mood frequently occurs in perioperative patients, negatively impacting patient recovery. Recent studies suggested that ketamine has a rapid, obvious, and persistent antidepressant effect. The purpose of this study was to investigate the impact of intraoperative application of ketamine on postoperative depressive mood in patients undergoing elective orthopedic surgery. METHODS: This was a randomized, double-blind, controlled study. A total of 120 patients (ASA grade I-II) undergoing elective orthopedic surgery were divided randomly into a ketamine group (group K) and a control group (group C). In the K group, 0.5 mg/kg (0.05 ml/kg) ketamine was given at induction of anesthesia, followed by 0.25 mg/kg/h (0.025 ml/kg/h) continuous infusion for 30 min. In the C group, 0.05 ml/kg 0.9 % saline was used at induction of anesthesia, followed by 0.025 ml/kg/h continuous infusion of saline for 30 min. PHQ-9 score was recorded preoperatively (1 day before surgery) and postoperatively (on day 1 and day 5 following surgery). Blood at these time points was drawn for serum brain-derived neurotrophic factor (BDNF) level analysis. Intraoperative blood loss, surgery time, postoperative visual analog scale pain scores and perioperative complications were also recorded. RESULTS: There were no differences in age, sex, surgery time, blood loss, and preoperative PHQ-9 scores between the two groups (P > 0.05). There were no differences in PHQ-9 scores preoperatively and postoperatively for the C group (P > 0.05); however, the PHQ-9 postoperative scores were lower than the preoperative PHQ-9 scores in the K group (P < 0.01). Postoperative PHQ-9 scores of K group were lower than those of C group (P < 0.05). There were no differences in serum BDNF levels in C group pre- to postoperatively (P > 0.05). Compared with the preoperative BDNF levels of K group, postoperative BDNF levels in K group increased significantly (P < 0.01). An inverse correlation between PHQ-9 score and serum BDNF level was shown. CONCLUSION: Intraoperative application of ketamine was associated with improved scores for depressed mood and increased serum BDNF levels in patients undergoing elective orthopedic surgery.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Ketamina/uso terapêutico , Procedimentos Ortopédicos/métodos , Adulto , Método Duplo-Cego , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Masculino , Dor Pós-Operatória/tratamento farmacológico , Período Pós-Operatório
19.
Cell Physiol Biochem ; 36(4): 1359-70, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26159387

RESUMO

AIMS: To explore the expression of miR-24-3p in human arteries with arteriosclerosis obliterans (ASO) as well as the role of miR-24-3p in the pathogenesis of ASO. METHODS: We used quantitative real-time PCR (qRT-PCR) and in situ hybridization to monitor miR-24-3p expression in human arteries. To investigate the effect of miR-24-3p on human arterial smooth muscle cells (HASMCs), we applied cell counting and EdU assays to monitor proliferation and transwell and wound healing assays to investigate migration and flow cytometry to investigate apoptosis. Furthermore, we applied 3'-untranslated region (3'-UTR) luciferase assays to investigate the role of miR-24-3p in targeting platelet-derived growth factor receptor B (PDGFRB) and c-Myc. RESULTS: MiR-24-3p was mainly located in the media of arteries and was downregulated in ASO arteries compared with normal arteries. Platelet-derived growth factor BB (PDGF-BB) treatment reduced the expression of miR-24-3p in primary cultured HASMCs. MiR-24-3p mimic oligos inhibited the proliferation and migration, and promotes apoptosis of HASMCs. Our 3'-UTR luciferase assays confirmed that PDGFRB and c-Myc were targets of miR-24-3p. CONCLUSION: The results suggest that miR-24-3p regulates the proliferation and migration of HASMCs by targeting PDGFRB and c-Myc. The PDGF/miR-24-3p/PDGFRB and PDGF/miR-24-3p/c-Myc pathways may play critical roles in the pathogenesis of ASO. These findings highlight the potential for new therapeutic targets for ASO.


Assuntos
Apoptose , Arteriosclerose Obliterante/genética , Movimento Celular , Proliferação de Células , Regulação da Expressão Gênica , MicroRNAs/genética , Miócitos de Músculo Liso/patologia , Arteriosclerose Obliterante/patologia , Sequência de Bases , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética
20.
J Mol Cell Cardiol ; 74: 209-19, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24887036

RESUMO

Normal high density lipoprotein (HDL) protects vascular function; however these protective effects of HDL may absent in valvular heart disease (VHD). Because vascular function plays an important role in maintaining the circulation post-cardiac surgery and some patients are difficult to stabilize, we hypothesized that a deleterious vascular effect of HDL may contribute to vascular dysfunction in VHD patients following surgery. HDL was isolated from age-match 28 healthy subjects and 84 patients with VHD and during cardiac surgery. HDL pro-inflammation index was measured and the effects of HDL on vasodilation, protein interaction, generation of nitric oxide (NO) and superoxide were determined. Patients with VHD received either simvastatin (20mg/d) or routine medications, and endothelial effects of HDL were characterized. HDL inflammation index significantly increased in VHD patients and post-cardiac surgery. HDL from VHD patients and post-cardiac surgery significantly impaired endothelium-dependent vasodilation, inhibited both Akt and endothelial nitric oxide synthase (eNOS) phosphorylation at S1177, eNOS associated with heat shock protein 90 (HSP90), NO production and increased eNOS phosphorylation at T495 and superoxide generation. Simvastatin therapy partially reduced HDL inflammation index, improved the capacity of HDL to stimulate eNOS and Akt phosphorylation at S1177, eNOS associated with HSP90, NO production, reduced eNOS phosphorylation at T495 and superoxide generation, and improved endothelium-dependent vasodilation. Our data demonstrated that HDL from VHD patients and cardiac surgery contributed to endothelial dysfunction through uncoupling of eNOS. This deleterious effect can be reversed by simvastatin, which improves the vasoprotective effects of HDL. Targeting HDL may be a therapeutic strategy for maintaining vascular function and improving the outcomes post-cardiac surgery.


Assuntos
Doenças das Valvas Cardíacas/metabolismo , Valvas Cardíacas/metabolismo , Lipoproteínas HDL/metabolismo , Adulto , Idoso , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Estudos de Casos e Controles , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Feminino , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Valvas Cardíacas/efeitos dos fármacos , Valvas Cardíacas/patologia , Humanos , Hipolipemiantes/uso terapêutico , Lipoproteínas HDL/farmacologia , Masculino , Camundongos , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sinvastatina/uso terapêutico , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismo , Vasodilatação/efeitos dos fármacos
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