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1.
Angew Chem Int Ed Engl ; 63(6): e202313859, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38055195

RESUMO

Exploitation of key protected wild plant resources makes great sense, but their limited populations become the major barrier. A particular strategy for breaking this barrier was inspired by the exploration of a resource-saving fungal endophyte Penicillium sp. DG23, which inhabits the key protected wild plant Schisandra macrocarpa. Chemical studies on the cultures of this strain afforded eight novel indole diterpenoids, schipenindolenes A-H (1-8), belonging to six diverse skeleton types. Importantly, semisyntheses suggested some key nonenzymatic reactions constructing these molecules and provided targeted compounds, in particular schipenindolene A (Spid A, 1) with low natural abundance. Remarkably, Spid A was the most potent HMG-CoA reductase (HMGCR) degrader among the indole diterpenoid family. It degraded statin-induced accumulation of HMGCR protein, decreased cholesterol levels and acted synergistically with statin to further lower cholesterol. Mechanistically, transcriptomic and proteomic profiling suggested that Spid A potentially activated the endoplasmic reticulum-associated degradation (ERAD) pathway to enhance the degradation of HMGCR, while simultaneously inhibiting the statin-activated expression of many key enzymes in the cholesterol and fatty acid synthesis pathways, thereby strengthening the efficacy of statins and potentially reducing the side effects of statins. Collectively, this study suggests the potential of Spid A for treating cardiovascular disease.


Assuntos
Acil Coenzima A , Inibidores de Hidroximetilglutaril-CoA Redutases , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Degradação Associada com o Retículo Endoplasmático , Proteômica , Colesterol/metabolismo , Indóis
2.
Diagnostics (Basel) ; 13(16)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37627940

RESUMO

Chronic diseases are increasingly major threats to older persons, seriously affecting their physical health and well-being. Hospitals have accumulated a wealth of health-related data, including patients' test reports, treatment histories, and diagnostic records, to better understand patients' health, safety, and disease progression. Extracting relevant information from this data enables physicians to provide personalized patient-treatment recommendations. While collaborative filtering techniques and classical algorithms such as naive Bayes, logistic regression, and decision trees have had notable success in health-recommendation systems, most current systems primarily inform users of their likely preferences without providing explanations. This paper proposes an approach of deep learning with a local interpretable model-agnostic explanations (LIME)-based interpretable recommendation system to solve this problem. Specifically, we apply the proposed approach to two chronic diseases common in older adults: heart disease and diabetes. After data preprocessing, we use six deep-learning algorithms to form interpretations. In the heart-disease data set, the actual model recommendation of multi-layer perceptron and gradient-boosting algorithm differs from the local model's recommendation of LIME, which can be used as its approximate prediction. From the feature importance of these two algorithms, it can be seen that the CholCheck, GenHith, and HighBP features are the most important for predicting heart disease. In the diabetes data set, the actual model predictions of the multi-layer perceptron and logistic-regression algorithm were little different from the local model's prediction of LIME, which can be used as its approximate recommendation. Moreover, from the feature importance of the two algorithms, it can be seen that the three features of glucose, BMI, and age were the most important for predicting heart disease. Next, LIME is used to determine the importance of each feature that affected the results of the calculated model. Subsequently, we present the contribution coefficients of these features to the final recommendation. By analyzing the impact of different patient characteristics on the recommendations, our proposed system elucidates the underlying reasons behind these recommendations and enhances patient trust. This approach has important implications for medical recommendation systems and encourages informed decision-making in healthcare.

3.
Infect Drug Resist ; 16: 3761-3765, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333679

RESUMO

Infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus (MRSA) is usually life threatening and difficult to treat. Contezolid is a newly approved oxazolidinone antimicrobial agent showing potent activity against MRSA. We successfully treated a case of refractory IE caused by MRSA with contezolid in a 41-year-old male patient. The patient was admitted due to recurrent fever and chills for more than 10 days. He had chronic renal failure for more than 10 years and under ongoing hemodialysis. The diagnosis of IE was confirmed by echocardiography and positive blood culture of MRSA. Antimicrobial therapy with vancomycin combined with moxifloxacin, and daptomycin combined with cefoperazone-sulbactam failed in the first 27 days. Moreover, the patient had to take oral anticoagulant after removal of tricuspid valve vegetation and tricuspid valve replacement. Contezolid 800 mg was added orally every 12 hours, to replace vancomycin, for its anti-MRSA activity and good safety profile. Temperature normalized after the contezolid add-on treatment for 15 days. No relapse of infection or drug-related adverse reaction was reported at 3-month follow-up since the diagnosis of IE. This successful experience serves as motivation for a well-designed clinical trial to confirm the utility of contezolid in managing IE.

4.
Materials (Basel) ; 16(12)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37374552

RESUMO

Hydraulic structures are typically subjected to long-term hydraulic loading, and concrete-the main material of structures-may suffer from cracking damage and seepage failure, which can threaten the safety of hydraulic structures. In order to assess the safety of hydraulic concrete structures and realize the accurate analysis of the whole failure process of hydraulic concrete structures under the coupling effect of seepage and stress, it is vital to comprehend the variation law of concrete permeability coefficients under complex stress states. In this paper, several concrete samples were prepared, designed for loading conditions of confining pressures and seepage pressures in the first stage, and axial pressures in the later stage, to carry out the permeability experiment of concrete materials under multi-axial loading, followed by the relationships between the permeability coefficients and axial strain, and the confining and seepage pressures were revealed accordingly. In addition, during the application of axial pressure, the whole process of seepage-stress coupling was divided into four stages, describing the permeability variation law of each stage and analyzing the causes of its formation. The exponential relationship between the permeability coefficient and volume strain was established, which can serve as a scientific basis for the determination of permeability coefficients in the analysis of the whole failure process of concrete seepage-stress coupling. Finally, this relationship formula was applied to numerical simulation to verify the applicability of the above experimental results in the numerical simulation analysis of concrete seepage-stress coupling.

5.
J Mater Chem A Mater ; 10(26): 13884-13894, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35872702

RESUMO

Two-dimensional (2D) anatase titanium dioxide (TiO2) is expected to exhibit different properties as compared to anatase nanocrystallites, due to its highly reactive exposed facets. However, access to 2D anatase TiO2 is limited by the non-layered nature of the bulk crystal, which does not allow use of top-down chemical exfoliation. Large efforts have been dedicated to the growth of 2D anatase TiO2 with high reactive facets by bottom-up approaches, which relies on the use of harmful chemical reagents. Here, we demonstrate a novel fluorine-free strategy based on topochemical conversion of 2D 1T-TiS2 for the production of single crystalline 2D anatase TiO2, exposing the {001} facet on the top and bottom and {100} at the sides of the nanosheet. The exposure of these faces, with no additional defects or doping, gives rise to a significant activity enhancement in the hydrogen evolution reaction, as compared to commercially available Degussa P25 TiO2 nanoparticles. Because of the strong potential of TiO2 in many energy-based applications, our topochemical approach offers a low cost, green and mass scalable route for production of highly crystalline anatase TiO2 with well controlled and highly reactive exposed facets.

6.
Bioengineered ; 13(5): 11907-11922, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35546067

RESUMO

Hepatocellular carcinoma (HCC) is a malignant tumor originating from liver epithelial cells with a high clinical mortality rate. ß-Patchoulene (ß-PAE) is a compound extracted from patchouli, which has analgesic, anti-inflammatory and antioxidant effects. This research aims to probe the impacts of ß-PAE on hypoxia-induced HCC cell proliferation and epithelial-mesenchymal transition (EMT). Firstly, hypoxic injury models were constructed in HCC Huh-7 and MHCC97 cells, and the hypoxic injury cell models were then treated with different concentrations of ß-PAE. The cell viability, proliferation, migration, invasion and apoptosis were checked by the cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell assay, flow cytometry and terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression of Survivin protein, EMT markers and the NF-κB/HIF-1α pathway was gauged by Western blot (WB) or cellular immunofluorescence or reverse transcription-polymerase chain reaction (RT-PCR). The in-vivo experiment was conducted to confirm the anti-tumor role of ß-PAE. As a result, ß-PAE abated hypoxia-induced HCC cell growth, proliferation, migration, invasion and EMT and facilitated apoptosis in vitro and in vivo dose-dependently. Further mechanism studies displayed that ß-PAE inactivated the NF-κB/HIF-1α pathway, and HIF-1α activation significantly reversed the ß-PAE-mediated tumor inhibition. ß-PAE repressed the proliferation and EMT of hypoxia-induced HCC cells by choking the NF-κB/HIF-1α pathway, suggesting that ß-PAE was a potential drug for HCC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Humanos , Hipóxia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , NF-kappa B/metabolismo , Sesquiterpenos de Guaiano , Transdução de Sinais
7.
Bioengineered ; 12(1): 8217-8232, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34596006

RESUMO

Accumulating signs have found that long noncoding RNAs (lncRNAs) contribute to hepatocellular carcinoma (HCC). Here, we probed the effect and mechanism of lncRNA DARS-AS1 in HCC. The profiles of DARS-AS1 and Cytoskeleton associated protein 2 (CKAP2) in 50 HCC tissues and non-tumor tissues were examined by real-time quantitative polymerase chain reaction (RT-qPCR). DARS-AS1 and CKAP2 overexpression and/or knockdown cell models were established. The proliferation, apoptosis, invasion and epithelial-mesenchymal transition (EMT) were determined. CKAP2, and focal adhesion kinase (FAK)-extracellular signal-regulated kinase (ERK) was tested by Western blot (WB). The relationship between DARS-AS1 and CKAP2 was predicted by Bioinformatics, and the dual-luciferase reporter assay was applied to verify the targeting association between miR-3200-5p and DARS-AS1 and CKAP2. DARS-AS1 was overexpressed in HCC tissues (vs. that in non-tumor tissues) and was closely correlated with the patients' tumor stage. DARS-AS1 facilitated HCC cell proliferation and hampered apoptosis. HCC cell migration and EMT were enhanced by DARS-AS1. DARS-AS1 up-regulated CKAP2, which aggravated HCC. Further investigation illustrated that either DARS-AS1 or CKAP2 activated FAK-ERK pathway, and miR-3200-5p was competitively restrained by DARS-AS1. miR-3200-5p exerted tumor-suppressive effects in HCC and inactivated CKAP2 and FAK-ERK pathway. All in all, this study corroborates that DARS-AS1 facilitates HCC proliferation and metastasis by regulating miR-3200-5p-mediated CKAP2, which provides a potential target for HCC diagnosis and treatment.Abbreviations: CCK-8: cell counting kit-8; CKAP2: Cytoskeleton associated protein 2; cDNA:complementary DNA; DAPI: 4',6-diamidino-2-phenylindole; DARS-AS1: DARS1 antisense RNA 1; DEPC: diethyl pyrocarbonate; DMEM-F12: Dulbecco's minimal essential medium/Ham's-F12; EMT: epithelial-mesenchymal transition; ERK: extracellular signal-regulated kinase; FAK: focal adhesion kinase; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HCC: hepatocellular carcinoma; HE: hematoxylin-eosin; IHC: Immunohistochemistry; LIHC: Liver hepatocellular carcinoma; lncRNAs: long noncoding RNAs; MIAT: lncRNA myocardial infarction-related transcripts; MT: Mutant; NC: negative control; PBS: phosphate-buffered saline; PMSF: Phenylmethylsulfonyl fluoride; PVDF: polyvinylidene difluoride; RT: room temperature; RT-qPCR: real-time quantitative polymerase chain reaction; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SPF: specific pathogen-free; TMAP: tumor-associated microtubule-associated protein; TUNEL: TdT-mediated dUTP nick end labeling; V: volume; WT: wild type.


Assuntos
Carcinoma Hepatocelular/patologia , Proteínas do Citoesqueleto/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas do Citoesqueleto/metabolismo , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Regulação para Cima
8.
Chem Biodivers ; 18(1): e2000870, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33289245

RESUMO

Pleiones are popular ornamental orchids and different species of Pleione are long being used as traditional medicine in many Asian countries. However, previous chemical investigations of the genus Pleione are restricted to only a few species. In the present study, high performance liquid chromatography (HPLC) fingerprint of Pleione plants was established, which in particular, eight common peaks were confirmed in 16 species/hybrids. Three of the compounds corresponding to the chromatographic peaks were identified by electrospray ionization tandem mass spectrometry (ESI-tandem-MS). HPLC analysis confirmed the studied taxa shared most of chemical compounds but the content of chemical compounds was significantly different between species. Comparison of hierarchical clustering result with phylogenetic tree revealed that closely related species have higher similarities in chemical constituents. In consideration of low chemical similarity between spring-flowering and autumn-flowering species, we suggest a discrimination of these two groups during medicinal use of the genus Pleione. Species with a large pseudobulb and with high content of a certain compound should be given priority in future artificial cultivation and medicinal cultivar breeding. We hope our findings will contribute to the quality control and promote conservation of such endangered plant group.


Assuntos
Orchidaceae/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Flores/anatomia & histologia , Flores/química , Flores/metabolismo , Orchidaceae/classificação , Orchidaceae/metabolismo , Filogenia , Plantas Medicinais/química , Plantas Medicinais/classificação , Plantas Medicinais/metabolismo , Análise de Componente Principal , Estações do Ano , Espectrometria de Massas por Ionização por Electrospray
9.
ACS Nano ; 14(5): 5600-5608, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32320212

RESUMO

Enhancing catalytic activity by decorating noble metals in catalysts provides an opportunity for promoting the electrocatalytic hydrogen evolution reaction (HER) application. However, there are few systematic studies on regulating the structures of noble metals in catalytic materials and investigating their influence on HER. Herein, Pt catalysts with different structures including single atoms (SAs), clusters, and nanoparticles well-controllably anchored on VS2 nanosheets through a cost-effective optothermal method are reported, and their HER performance is studied. The most efficient Pt-decorated VS2 catalyst (with both Pt SAs and clusters) delivers an overpotential of 77 mV at 10 mA cm-2, close to that of Pt/C (48 mV). However, the optimal mass activity of Pt (normalizing to Pt content) is obtained from only SA Pt-decorated VS2 (i.e., 22.88 A mgPt-1 at 200 mV) and is 12 times greater than that of the Pt/C (1.87 A mgPt-1), attributed to the greatly enhanced Pt utilization. Additionally, the theoretical simulations reveal that Pt SA decoration makes the adsorption free energy of H* closer to the thermoneutral value and improves the charge-transfer kinetics, significantly enhancing HER activity. This work offers a pathway to prepare the desired catalyst based on synergy of Pt structures and VS2 and reveals the intrinsic mechanism for enhancing catalytic activity, which is important for HER applications.

10.
RSC Adv ; 10(23): 13838-13847, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35492991

RESUMO

The 3D hierarchical structure in catalysts not only the preserves intrinsic characteristics of each component, but also achieves increased specific surface area and active sites for the hydrogen evolution reaction (HER). Herein, we report a new strategy to synthesize efficient 3D hierarchical catalysts composed of Mo2C nanosheets and Co nanoparticles (H-Mo2C@Co). It was realized by using raw materials, defect-rich MoO x , Co(NO3)2·6H2O and 2-methylimidazole, to design Mo/Co bimetallic metal-organic frameworks (BMOFs), followed by pyrolysis at 800 °C. The defects in MoO x induced preferential nucleation and growth of the BMOFs so that they can ensure the construction of a stable 3D hierarchical structure. Mo2C and Co have a synergistic effect in improving the HER via providing large surface areas (351.5 m2 g-1), more active sites and optimizing charge transfer. It can achieve 10 mA cm-2 at low overpotential over a wide pH range (144 mV in 0.5 M H2SO4 and 103 mV in 1.0 M KOH) and the properties can be well maintained in both acid and alkaline electrolyte after 2000 cycles. The hierarchical catalyst contains no noble metal, can be synthesized on a large scale and recycled by magnetic stirring, demonstrating great potential in water splitting, wastewater treatment, dye adsorption and other fields.

11.
Oncol Lett ; 18(4): 3443-3452, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31516562

RESUMO

MicroRNAs (miRNAs) serve a pivotal role in tumor development and progression, in which miRNA (miR)-139-5p functions as a tumor suppressor. However, the functions and mechanisms of miR-139-5p in pancreatic ductal adenocarcinoma (PDAC) remain unclear. In the present study, it was found that miR-139-5p was markedly decreased in PDAC tissues and cell lines. Noticeably, thymopoietin (TMPO) was predicted and confirmed as a direct target of miR-139-5p using a luciferase reporter system. The expression level of miR-139-5p was inversely associated with the expression of TMPO in PDAC specimens. A series of gain-of-function assays elucidated that the overexpression of miR-139-5p suppressed cell proliferation, and induced cell cycle arrest and cell apoptosis, determined with a Cell Counting Kit-8, colony formation assays and flow cytometry, respectively. Furthermore, the re-expression of TMPO eliminated the effects of miR-139-5p on cell proliferation, cell cycle progression and apoptosis. In summary, these findings demonstrated that miR-139-5p may be a tumor suppressor in PDAC, which may be useful in developing promising therapies for PDAC.

12.
J Am Heart Assoc ; 8(4): e010254, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30757948

RESUMO

Background Chronic intermittent hypoxia ( CIH ) is a distinct pathological mechanism of obstructive sleep apnea ( OSA ), which is recognized as an independent risk factor for cardiovascular diseases. The aims of this study were to ascertain whether CIH induces atrial fibrillation ( AF ), to determine whether cardiac sympathetic denervation ( CSD ) can prevent it and suppress blood pressure, and to explore the potential molecular mechanisms involved. Methods and Results Sixty Sprague-Dawley male rats were randomly divided into 4 groups: sham, CSD , CIH , CIH + CSD . The rats were exposed either to CIH 8 hours daily or normoxia for 6 weeks. Cardiac pathology and structure were analyzed by hematoxylin and eosin staining and echocardiogram. ECG, blood pressure, body weight, and blood gas were recorded. Connexin 43 and tyrosine hydroxylase were detected by western blot, immunohistochemistry, and immunofluorescence. CIH induced atrial remodeling, and increased AF inducibility. CSD treatment reduced postapneic blood pressure rises and AF susceptibility, which could attenuate CIH -associated structural atrial arrhythmogenic remodeling. In addition, CIH -induced sympathetic nerve hyperinnervation and CSD treatment reduced sympathetic innervation, which may affect CIH -induced AF -associated sympathovagal imbalance. Connexin 43 was specifically downregulated in CIH , whereas CSD treatment increased its expression. Conclusions These results suggested CIH induces atrial remodeling, increases AF inducibility, results in sympathetic nerve hyperinnervation, and decreases connexin 43 expression, but CSD treatment reduces AF susceptibility, postapneic blood pressure increase, sympathetic innervation, and the alteration of Cx43, which may be a key point in the genesis of CIH -induced AF .


Assuntos
Fibrilação Atrial/terapia , Pressão Sanguínea/fisiologia , Hipóxia/complicações , Apneia Obstrutiva do Sono/complicações , Simpatectomia/métodos , Animais , Fibrilação Atrial/etiologia , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial/fisiologia , Western Blotting , Doença Crônica , Conexina 43/biossíntese , Modelos Animais de Doenças , Eletrocardiografia , Hipóxia/sangue , Imuno-Histoquímica , Masculino , Ratos , Ratos Sprague-Dawley , Apneia Obstrutiva do Sono/sangue
13.
Int J Clin Exp Pathol ; 12(4): 1163-1173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933931

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC), is the third leading cause of cancer-related death. MicroRNA-506 (miR-506) has been reported to exhibit abnormal expression in HCC; however, the role of miR-506 in HCC and the molecular mechanisms underlying miR-506 in HCC remain unclarified. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay was performed to detect the expression of miR-506 and Rho associated coiled-coil containing protein kinase 2 (ROCK2). Cell proliferation and apoptosis were evaluated by MTT assay and flow cytometry, respectively. Bioinformatics analysis and luciferase reporter assays were performed to identify the regulation between miR-506 and ROCK2. Western blot assay was performed to detect the expression of ROCK2, RhoA, and Ras-related C3 botulinum toxin substrate 1 (Rac1). The tumor growth in vivo was evaluated in a HCC xenograft mice model. RESULTS: The mRNA levels of ROCK2 were significantly upregulated, while miR-506 levels were significantly downregulated in HCC tissues and cells. The expression of ROCK2 was negatively correlated with miR-506 in HCC tissues. In vitro, upregulation of miR-506 inhibited proliferation and induced apoptosis, and downregulation of miR-506 promoted proliferation and blocked apoptosis in HepG2 and Hep3B cells. ROCK2 was a target gene of miR-506 and miR-506 regulated the expression of ROCK2 in HepG2 and Hep3B cells. Furthermore, downregulation of miR-506 partially attenuated the tumor-suppressive effect of ROCK2 knockout on HepG2 and Hep3B cells, and upregulation of miR-506 partially attenuated the oncogenic effect of ROCK2 overexpression on HepG2 and Hep3B cells; Overexpression of ROCK2 increased and ROCK2 knockdown decreased the expression of Rac1, which were attenuated by upregulation of miR-506 or downregulation of miR-506, respectively. In addition, ROCK2 overexpression or knockdown hadno significant effect on RhoA expression. In vivo, upregulation of miR-506 suppressed tumor growth, while downregulation of miR-506 promoted tumor growth. CONCLUSION: miR-506 was involved in cell proliferation and apoptosis by affecting RhoA/ROCK signaling pathway in HCC cells. Our results provide a novel mechanism of miR-506-mediated suppressive effects on HCC tumorigenesis.

14.
Sleep Breath ; 23(2): 493-502, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30194514

RESUMO

PURPOSE: Chronic intermittent hypoxia (CIH) is key pathological mechanism of obstructive sleep apnea (OSA), which induced cardiac dysfunction. Filamin c (FLNC) is a muscle-restricted isoform and predominantly expressed in muscle tissue. In this study, we utilized a recently developed CIH rat model to mimic OSA, investigated the expression of FLNC in cardiomyocytes, and examined the correlations of FLNC with active caspase-3 to ascertain whether FLNC regulates the survival of cardiomyocytes. METHODS: Forty Sprague-Dawley rats were randomly divided into normoxia and CIH groups. All rats were exposed either to normoxia or CIH 8 h daily for 6 weeks. Echocardiogram and HE staining were used to examine cardiac pathology, structure, and function. Body weight, heart weight, and blood gas values were recorded, respectively. The FLNC, Bax, Bcl-2, BNIP 3, and active caspase-3 proteins were detected by western blot; FLNC was examined by immunohistochemistry and immunofluorescence. Association of FLNC with cardiomyocyte apoptosis was detected by immunofluorescence. RESULTS: CIH induced cardiac injuries and caused arterial blood gas disorder. FLNC significantly increased in CIH-induced cardiomyocytes than that in normoxia tissues. Pro-apoptotic BNIP 3 and Bax proteins were significantly increased in CIH, whereas anti-apoptotic member Bcl-2 was decreased. Active caspase-3, a universal marker of apoptosis, was significantly increased in CIH group. Co-localizations of FLNC and active caspase-3 were observed in CIH group. CONCLUSIONS: These results suggested FLNC is implicated in the pathogenesis of CIH-induced cardiomyocyte apoptosis, and FLNC may serve as a novel cardioprotective target for OSA patients.


Assuntos
Apoptose/genética , Cardiotônicos , Filaminas/genética , Regulação da Expressão Gênica/genética , Hipóxia/genética , Miócitos Cardíacos/metabolismo , Apneia Obstrutiva do Sono/genética , Animais , Correlação de Dados , Imunofluorescência , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-Dawley , Apneia Obstrutiva do Sono/patologia
15.
Life Sci ; 193: 200-206, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29104105

RESUMO

AIMS: Aortic dissection (AD) represents one of the most common aortic emergencies with high incidence of morbidity and mortality. Clinical studies have shown that the increased excitability of the sympathetic nerve may be associated with the formation of AD. In this study, we examined the effects of bilateral superior cervical sympathectomy (SCGx) on the progression of ß-aminopropionitrile (BAPN)-induced AD in rats. MAIN METHODS: Sprague-Dawley rats were randomly divided into three groups, including BAPN, BAPN+SCGx and control groups. For terminal measurements, the mean arterial pressure (MAP) and heart rate (HR) were monitored and the basal sympathetic nerve activity (SNA) was assessed through recording the variation in arterial pressure in response to hexamethonium application. Pathological changes in the aortic wall were observed by histological staining. Matrix metalloproteinase-2 (MMP-2) and MMP-9 concentrations within the aortic wall were analyzed by western blot. KEY FINDINGS: The results show that BAPN administration could elevate SNA and cause the formation of AD in rats with a high incidence (67.7%), while SCGx treatment inhibited the elevation of SNA and significantly reduced the incidence (20%). SCGx may suppress the formation of BAPN-induced AD via restraining the rise of HR and reducing the MMP-9 concentration in aortic wall. SIGNIFICANCE: These results indicate that surgical techniques such as sympathetic nerve block may be a potentially useful therapy for the prevention of AD.


Assuntos
Dissecção Aórtica/cirurgia , Gânglios Simpáticos/fisiopatologia , Aminopropionitrilo/metabolismo , Dissecção Aórtica/terapia , Animais , Aorta/fisiopatologia , Pressão Arterial/fisiologia , Modelos Animais de Doenças , Progressão da Doença , Ganglionectomia/métodos , Frequência Cardíaca/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Sistema Nervoso Simpático/fisiopatologia
16.
Sci Rep ; 6: 33597, 2016 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-27677326

RESUMO

The superior performance of metal oxide nanocomposites has introduced them as excellent candidates for emerging energy sources, and attracted significant attention in recent years. The drawback of these materials is their inherent structural pulverization which adversely impacts their performance and makes the rational design of stable nanocomposites a great challenge. In this work, functional V2O5-C-SnO2 hybrid nanobelts (VCSNs) with a stable structure are introduced where the ultradispersed SnO2 nanocrystals are tightly linked with glucose on the V2O5 surface. The nanostructured V2O5 acts as a supporting matrix as well as an active electrode component. Compared with existing carbon-V2O5 hybrid nanobelts, these hybrid nanobelts exhibit a much higher reversible capacity and architectural stability when used as anode materials for lithium-ion batteries. The superior cyclic performance of VCSNs can be attributed to the synergistic effects of SnO2 and V2O5. However, limited data are available for V2O5-based anodes in lithium-ion battery design.

17.
Sci Rep ; 6: 22494, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26931057

RESUMO

Y-shaped ZnO nanobelts are fabricated by a simple thermal evaporation method. Transmission Electron Microscopy (TEM) investigation shows that these ZnO nanobelts are crystals with twinned planes {11-21}. Convergent Beam Electron Diffraction studies show that the two sides of twinned nanobelts are O-terminated towards the twinned boundary and Zn-terminated outwards. The two branches of twinned ZnO nanobelts grow along [11-26] from the trunk and then turn to the polarization direction [0001]. The featured Y-shape morphology and TEM characterizations indicate that the growth of these novel nanostructures is driven by an unusual twinned dislocation growth mechanism.

18.
Sci Rep ; 6: 18886, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26729069

RESUMO

Ordered nanoarchitectures have attracted an intense research interest recently because of their promising device applications. They are always fabricated by self-assembling building blocks such as nanowires, nanodots. This kind of bottom up approaches is limited in poor control over height, lateral resolution, aspect ratio, and patterning. Here, we break these limits and realize 3D sculpturing of vertical ZnO nanowire arrays (NAs) based on the conventional photolithography approach. These are achieved by immersing nanowire NAs in thick photoresist (PR) layers, which enable the cutting and patterning of ZnO NAs as well as the tailoring of NAs. Our strategy of 3D sculpturing of NAs promisingly paves the way for designing novel NAs-based nanoarchitectures.

19.
Onco Targets Ther ; 8: 2227-35, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26347321

RESUMO

MircroRNA-212 (miR-212) is proposed as a novel tumor-related miRNA and has been found to be significantly deregulated in human cancers. In this study, the miR-212 expression was found to be obviously downregulated in hepatocellular carcinoma (HCC) tissues as compared with adjacent nontumor tissues. Clinical association analysis indicated that low expression of miR-212 was prominently correlated with poor prognostic features of HCC, including high AFP level, large tumor size, high Edmondson-Steiner grading, and advanced tumor-node-metastasis tumor stage. Furthermore, the miR-212 expression was an independent prognostic marker for predicting both 5-year overall survival and disease-free survival of HCC patients. Our in vitro studies showed that upregulation of miR-212 inhibited cell proliferation and induced apoptosis in HepG2 cells. On the contrary, downregulation of miR-212 promoted cell proliferation and suppressed apoptosis in Huh7 cells. Interestingly, we found that upregulation of miR-212 decreased FOXA1 expression in HepG2 cells. Significantly, FOXA1 was identified as a direct target of miR-212 in HCC. FOXA1 was downregulated in HCC tissues as compared with noncancerous tissues. An inverse correlation between FOXA1 and miR-212 expression was observed in HCC tissues. Notably, FOXA1 knockdown inhibited cell proliferation and induced apoptosis in HepG2 cells. In conclusion, miR-212 is a potent prognostic marker and may suppress HCC tumor growth by inhibiting FOXA1 expression.

20.
Sci Rep ; 5: 8226, 2015 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-25648112

RESUMO

Hierarchical ZnO nanostructures with a large yield were fabricated by a simple thermal evaporation method. For the first time, novel ZnO flowers were observed blooming at certain sites of a variety of spines, identified as Zn-terminated polar (0001) planes or tips. The spines for as-synthesized hierarchical structures can be nanowires, nanobelts, nanodendrites, nanobrushes, etc. This growth phenomenon determines the key role of polar sites in the fabrication of hierarchical structures. The spiral feature of ZnO flowers indicates an unusual screw dislocation driven growth mechanism, which is attributed to a high concentration of Zn vapor.

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