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1.
Front Chem ; 12: 1402502, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39036657

RESUMO

Biomass and its derivatives have broad applications in the fields of bio-catalysis, energy storage, environmental remediation. The structure and components of biomass, which are vital parameters affecting corresponding performances of derived products, need to be fully understood for further regulating the biomass and its derivatives. Herein, tobacco is taken as an example of biomass to introduce the typical characterization techniques in unraveling the structural information, chemical components, and properties of biomass and its derivatives. Firstly, the structural information, chemical components and application for biomass are summarized. Then the characterization techniques together with the resultant structural information and chemical components are introduced. Finally, to promote a wide and deep study in this field, the perspectives and challenges concerning structure and composition charaterization in biomass and its derivatives are put forward.

2.
Heliyon ; 10(13): e33920, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39055830

RESUMO

Tobacco, a widely cultivated crop, has been extensively utilized by humans for an extended period. However, the tobacco industry generates a significant amount of organic waste, and the effective utilization of this tobacco waste has been limited. Currently, most tobacco waste is either recycled as reconstituted tobacco sheets or disposed of in landfills. However, tobacco possesses far more potential value than just these applications. This article provides an overview of the diverse uses of tobacco waste in agriculture, medicine, chemical engineering, and energy sectors. In the realm of agriculture, tobacco waste finds primary application as fertilizers and pesticides. In medical applications, the bioactive compounds present in tobacco are fully harnessed, resulting in the production of phenols, solanesol, polysaccharides, proteins, and even alkaloids. These bioactive compounds exhibit beneficial effects on human health. Additionally, the applications of tobacco waste in chemical engineering and energy sectors are centered around the utilization of lignocellulosic compounds and certain fuels. Chemical platform compounds derived from tobacco waste, as well as selected fuel sources, play a significant role in these areas. The rational utilization of tobacco waste represents a promising prospect, particularly in the present era when sustainable development is widely advocated. Moreover, this approach holds significant importance for enhancing energy utilization.

3.
Chin J Integr Med ; 30(3): 267-276, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38221564

RESUMO

Chinese medicine (CM) diagnosis intellectualization is one of the hotspots in the research of CM modernization. The traditional CM intelligent diagnosis models transform the CM diagnosis issues into classification issues, however, it is difficult to solve the problems such as excessive or similar categories. With the development of natural language processing techniques, text generation technique has become increasingly mature. In this study, we aimed to establish the CM diagnosis generation model by transforming the CM diagnosis issues into text generation issues. The semantic context characteristic learning capacity was enhanced referring to Bidirectional Long Short-Term Memory (BILSTM) with Transformer as the backbone network. Meanwhile, the CM diagnosis generation model Knowledge Graph Enhanced Transformer (KGET) was established by introducing the knowledge in medical field to enhance the inferential capability. The KGET model was established based on 566 CM case texts, and was compared with the classic text generation models including Long Short-Term Memory sequence-to-sequence (LSTM-seq2seq), Bidirectional and Auto-Regression Transformer (BART), and Chinese Pre-trained Unbalanced Transformer (CPT), so as to analyze the model manifestations. Finally, the ablation experiments were performed to explore the influence of the optimized part on the KGET model. The results of Bilingual Evaluation Understudy (BLEU), Recall-Oriented Understudy for Gisting Evaluation 1 (ROUGE1), ROUGE2 and Edit distance of KGET model were 45.85, 73.93, 54.59 and 7.12, respectively in this study. Compared with LSTM-seq2seq, BART and CPT models, the KGET model was higher in BLEU, ROUGE1 and ROUGE2 by 6.00-17.09, 1.65-9.39 and 0.51-17.62, respectively, and lower in Edit distance by 0.47-3.21. The ablation experiment results revealed that introduction of BILSTM model and prior knowledge could significantly increase the model performance. Additionally, the manual assessment indicated that the CM diagnosis results of the KGET model used in this study were highly consistent with the practical diagnosis results. In conclusion, text generation technology can be effectively applied to CM diagnostic modeling. It can effectively avoid the problem of poor diagnostic performance caused by excessive and similar categories in traditional CM diagnostic classification models. CM diagnostic text generation technology has broad application prospects in the future.


Assuntos
Medicina Tradicional Chinesa , Reconhecimento Automatizado de Padrão , Humanos , Povo Asiático , Idioma , Aprendizagem
5.
PLoS One ; 18(11): e0288315, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37939023

RESUMO

Although the literature has assessed the impact of Intellectual property protection on urban innovation, there is still a gap in the assessment of the impact of green innovation at the firm level. This study constructs a multi-period differences-in-differences (DID) model using China's Intellectual Property Demonstration Cities (IPDC) as a quasi-natural experiment to investigate the impact of IPDC on corporate green innovation. The findings indicate that (1) the IPDC program significantly stimulates corporate green innovation and has long-term effects. This finding still holds after using PSM-DID as well as robust IW estimators. (2) Mechanism analysis suggests that IPDC can promote firms' green innovation by reducing R&D spillover losses and alleviating financing constraints. (3) Heterogeneity tests show that the IPDC program has a more significant promotion effect on small, state-owned, growth-stage firms. Based on the above findings, this study provides policy implications for enhancing intellectual property protection to stimulate corporate green innovation.


Assuntos
Políticas , Cidades , China
6.
Herz ; 48(6): 470-473, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37566118

RESUMO

A 71 year old male patient who experienced acute myocardial infarction (AMI) 4 years ago and had a history of polycythemia vera and thrombocythemia was admitted because acute attack of chronic heart failure. Coronary angiography revealed an unusual filling defect in the middle segment of the left anterior descending (LAD) coronary artery and IVUS showed it is a HLS which is different from dissection or woven coronary artery. We review the recent literature of HLS in this article and further investigations are warranted for the optimal management of HLS.


Assuntos
Policitemia Vera , Trombocitose , Trombose , Masculino , Humanos , Idoso , Vasos Coronários/diagnóstico por imagem , Policitemia Vera/complicações , Policitemia Vera/diagnóstico por imagem , Angiografia Coronária , Ultrassonografia de Intervenção
7.
BMJ Open ; 13(2): e066474, 2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36731927

RESUMO

OBJECTIVES: The initial medical contact of patients with atrial fibrillation (AF) and ischaemic stroke is often performed by neurologists. However, when stand care with oral anticoagulants (OACs) adherence and persistence was emphasised by cardiologists, data regarding the gap between current neurology care and standard care from Chinese tertiary hospitals is scarce and the long-term outcome is unknown. This study was to investigate the AF detection rate, the use of anticoagulation therapy and posthospital clinical outcomes associated with neurology care in patients with AF and ischaemic stroke in China. DESIGN: A retrospective cohort study. SETTING: Clinical data of all patients who had an ischaemic stroke discharged from the neurologic department of a high-volume academic hospital from 1 January 2013 to 31 December 2017 were analysed and patients were followed. PARTICIPANTS: Patients diagnosed with ischaemic stroke and AF were included. MAIN OUTCOME MEASURES: The usage of anticoagulation at discharge, the posthospital restroke rate and all-cause mortality. RESULTS: Among 5797 patients who had an ischaemic stroke, 373 (6.43%) patients were diagnosed with AF during hospitalisation. Among them, only 198 (53.66%) patients were on anticoagulation therapy at discharge. A total of 325 (88.08%) patients were accessible and received follow-up. After a median 3-year follow-up, 103 (31.69%) patients died due to all causes. Among them, 53 (16.31%) patients died from recurrent stroke. And 86 (26.46%) patients restroked. In multivariable analysis, patients without anticoagulation therapy, muscle strength

Assuntos
Fibrilação Atrial , Isquemia Encefálica , AVC Isquêmico , Neurologia , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/diagnóstico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Estudos Retrospectivos , Centros de Atenção Terciária , Anticoagulantes/uso terapêutico , AVC Isquêmico/complicações , Fatores de Risco , Administração Oral
8.
Abdom Radiol (NY) ; 48(1): 236-243, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36242605

RESUMO

PURPOSE: To explore the multi-slice spiral computed tomography (MSCT) imaging characteristics of patients with bezoars-induced small bowel obstruction (BI-SBO) to evaluate the risk of conservative treatment. MATERIALS AND METHODS: This retrospective study included 72 patients with BI-SBO who underwent whole-abdominal MSCT scan within 1 day before treatment. The patients were classified as the non-pass group and pass group depending on whether bezoar can pass after conservative treatment. The CT images were observed and measured by two radiologists. Statistical analysis was performed by using Student's t test, Pearson's chi-squared test, Fisher's exact test, Logistic linear regression, and receiver operating characteristic curve (ROC). RESULTS: The study population consisted of 72 patients with a mean age of 52.2 ± 16.2 years (32 men and 40 women with an age range of 13-81 years). There were statistical differences between the two groups in the bezoar appearance, maximum HU of bezoar, thickness of intestinal wall, mesenteric haziness, mesenteric fluid, and peritoneal fluid (P = 0.002, 0.024, 0.017, 0.006, 0.021, and 0.030). The appearance of bezoar and mesenteric haziness is independent risk factors affecting whether bezoar can be passed by the conservative treatment. Sensitivity (41.7%) was decreased, NPV (76.3%) was not significantly changed, specificity (93.8%) and PPV (76.9%) were improved when both parameters were met to assess failure of conservative treatment. CONCLUSION: The observation of important signs by MSCT and its reconstruction technology is of great clinical value in evaluating the passability of bezoar by conservative treatment, and which can provide radiographic basis for clinical treatment selection.


Assuntos
Bezoares , Obstrução Intestinal , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Bezoares/diagnóstico por imagem , Bezoares/terapia , Estudos Retrospectivos , Tratamento Conservador/efeitos adversos , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/cirurgia , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia , Tomografia Computadorizada Espiral
9.
Pacing Clin Electrophysiol ; 46(1): 34-38, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35962617

RESUMO

BACKGROUND: Ablation of the vein of Marshall (VOM) by dehydrated ethanol (DE) is an important method for completely blocking the mitral isthmus (MI). Before DE ablation of the VOM, Marshall angiography should be performed so that the contrast medium is inevitably exposed to DE. METHOD: We present a case of DE ablation of the VOM. When iodixanol was exposed to DE, some floccule embolized the lumen of the over-the-wire (OTW) balloon dilatation catheter and led to the impossibility of DE ablation. Then, we performed in vitro experiments: iodixanol, not iomeprol, produced many stable white floccules when it encountered DE. CONCLUSION: Iodixanol is not an appropriate contrast for DE ablation of the VOM. However, if there is no other alternative contrast, the following methods might be used to address the problem: ⑴ diluted iodixanol (iodixanol:normal saline 1:1) could be used for VOM ablation; or ⑵ the lumen of the OTW could be flushed by NS after VOM angiography, and then DE injection could be performed.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/cirurgia , Vasos Coronários/cirurgia , Ablação por Cateter/métodos , Etanol
11.
J Zhejiang Univ Sci B ; 23(3): 204-217, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35261216

RESUMO

It has been revealed that hypoxia is dynamic in hypertrophic scars; therefore, we considered that it may have different effects on hypoxia-inducible factor-1α (HIF-1α) and p53 expression. Herein, we aimed to confirm the presence of a teeterboard-like conversion between HIF-1α and p53, which is correlated with scar formation and regression. Thus, we obtained samples of normal skin and hypertrophic scars to identify the differences in HIF-1α and autophagy using immunohistochemistry and transmission electron microscopy. In addition, we used moderate hypoxia in vitro to simulate the proliferative scar, and silenced HIF-1α or p53 gene expression or triggered overexpression to investigate the changes of HIF-1α and p53 expression, autophagy, apoptosis, and cell proliferation under this condition. HIF-1α, p53, and autophagy-related proteins were assayed using western blotting and immunofluorescence, whereas apoptosis was detected using flow cytometry analysis, and cell proliferation was detected using cell counting kit-8 (CCK-8) and 5-bromo-2'-deoxyuridine (BrdU) staining. Furthermore, immunoprecipitation was performed to verify the binding of HIF-1α and p53 to transcription cofactor p300. Our results demonstrated that, in scar tissue, HIF-1α expression increased in parallel with autophagosome formation. Under hypoxia, HIF-1α expression and autophagy were upregulated, whereas p53 expression and apoptosis were downregulated in vitro. HIF-1α knockdown downregulated autophagy, proliferation, and p300-bound HIF-1α, and upregulated p53 expression, apoptosis, and p300-bound p53. Meanwhile, p53 knockdown induced the opposite effects and enhanced HIF-1α, whereas p53 overexpression resulted in the same effects and reduced HIF-1α. Our results suggest a teeterboard-like conversion between HIF-1α and p53, which is linked with scar hyperplasia and regression.


Assuntos
Apoptose , Autofagia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Proteína Supressora de Tumor p53 , Hipóxia Celular , Fibroblastos/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteína Supressora de Tumor p53/metabolismo
12.
Front Med (Lausanne) ; 9: 1060815, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36703883

RESUMO

Objective: The objective of this study was to compare the efficacy and safety of fractional CO2 laser and 1,550 nm Er: glass laser in the treatment for the patients with striae albae. Methods: The female adults with striae albae in the abdomen for at least 12 months were recruited. After informed consent obtained, the patient received three treatments at 2-month intervals. The lesions on the left abdomen were treated with 10,600 nm CO2 fractional laser and right side treated with 1,550 nm Er: glass fractional laser. The pictures were taken before each visit and 3 months after the final treatment. The criteria for the evaluations using a quartile grading scale were excellent (76-100%), good (51-75%), fair (26-50%), poor (1-25%), and no improvement (0%). The safety and efficacy of the two lasers were independently evaluated using before and after photographs by two dermatologists. In addition, the self-reports to investigate the pain and satisfaction from patients were also recorded. Results: Totally, 27 cases were recruited, and 25 patients completed the treatments and follow-up. The excellent and good results (improvement of 51-100%) were achieved on the right abdomen in 84% of the patients, while 48% on the left site (p < 0.05). Hyper-pigmentation was seen in 20% of the patients assessed on the left abdomen and only in 8% on the right abdomen. During the treatments, average score of the pain on the right abdomen was 5.41 ± 2.13, which was higher than that on the left (4.19 ± 2.12) (p < 0.001). No permanent hyper-pigmentation was found on the both sides. Considering the whole treatments, the patients favored the modality used on the right side (80 vs. 68%, p < 0.05). Conclusion: Compared with CO2 fractional laser, 1,550 nm Er: glass fractional laser therapy provides the significantly better clinical outcomes and fewer side effects in the treatment of striae albae. Limitations: The sample size and follow-up time were limited.

13.
Open Med (Wars) ; 16(1): 1134-1142, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34435138

RESUMO

BACKGROUND: Heart failure (HF) is a serious and advanced stage of various cardiac diseases with high mortality and rehospitalization rates. Phosphoglycerate mutase 2 (PGAM2) overexpression was identified in the serum of patients with HF. MATERIAL/METHODS: One hundred and fifty-three cases of HF were included in the present work. According to New York Heart Association (NYHA) classification, 22 were grade II, 84 were grade III, and 47 were grade IV. Serum PGAM2, NT-proBNP, B-type natriuretic peptide (BNP), troponin T (TNT), and Cys-C of HF patients were detected using ELISA assay. Left ventricular ejection fraction, left ventricular end-diastolic inner diameter, and left atrium (LA) inner diameter of the included cases were also detected by the cardiac color Doppler. RESULTS: The number of patients with atrial fibrillation was significantly higher in NYHA IV group than in groups II and III with statistical difference (p < 0.05). The serum PGAM2, NT-proBNP, and Cys-C were significantly higher in NYHA IV group than in NYHA II and NYHA III groups (p all < 0.05). NT-proBNP had the highest prediction efficacy of HF severity and PGAM2 was also a potential biomarker for HF severity evaluation with relatively high sensitivity, specificity, and area under the ROC. The overall survival among NYHA II, III, and IV groups were statistically different (p = 0.04) with the median survival time of 25 months for NYHA III and IV groups. CONCLUSION: PGAM2 is a new promising biomarker for evaluation of the severity of HF. Combination detection using multiple serum factors such as PGAM2, NT-proBNP, BNP, TNT, and Cys-C can improve the HF severity differential diagnosis performance.

15.
Opt Express ; 27(16): 22855-22867, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510570

RESUMO

We present a scheme for the electromagnetically induced transparency (EIT)-like nonlinear ground-state cooling in a double-cavity optomechanical system in which an optical cavity mode is coupled parametrically to the square of the position of a mechanical oscillator, an additional auxiliary cavity is coupled to the optomechanical cavity. The optimum cooling conditions is derived, based on which the heating process can be well suppressed and the mechanical resonator can be cooled with an optimal effect to near its ground state through EIT-like cooling mechanism even in unresolved sideband regime. It is demonstrated by numerical simulations that not only the average phonon number of steady state is lower than that of single-cavity optomechanical system, but also the cooling rate is greatly faster than that of the linear optomechanical coupling due to the two-phonon cooling process in the quadratic coupling. Also, the ground-state cooling is achievable even with a relatively weak quadratic coupling strengthby tunning the coupling between two cavities to reach the optimum cooling conditions, thus provides an solution for overcoming the limitations of weak quadratic coupling rate in experiments. The proposed approach provides a platform for quantum manipulation of macroscopic mechanical devices beyond the resolved sideband limit and linear coupling regime.

16.
J Cancer Res Clin Oncol ; 144(11): 2207-2218, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30094537

RESUMO

PURPOSE: Pathologic response to neoadjuvant chemotherapy is a prognostic factor in many cancer types. However, the existing evaluative criteria are deficient. We sought to prospectively evaluate the total iodine uptake derived from dual-energy computed tomography (DECT) in predicting treatment efficacy and progression-free survival (PFS) time in gastric cancer after neoadjuvant chemotherapy. METHODS: From October 2012 to December 2015, 44 patients with locally advanced gastric cancer were examined with DECT 1 week before and three cycles after neoadjuvant chemotherapy. The percentage changes in tumor area (%ΔS), diameter (%ΔD), and density (%ΔHU) were calculated to evaluate the WHO, RESCIST, and Choi criteria. The percentage changes in tumor volume (%ΔV) and total iodine uptake of portal phase (%ΔTIU-p) were also calculated to determine cut-off values by ROC curves. The correlation between the different criteria and histopathologic tumor regression grade (Becker score) or PFS were statistically analyzed. RESULTS: Forty-four patients were divided into responders and non-responders according to 43.34% volume reduction (P = 0.002) and 63.87% (P = 0.002) TIU-p reduction, respectively. The %ΔTIU-p showed strong (r = 0.602, P = 0.000) and %ΔV showed moderate (r = 0.416, P = 0.005), while the WHO (r = 0.075, P = 0.627), RECIST (r = 0.270, P = 0.077) and Choi criteria (r = 0.238, P = 0.120) showed no correlation with the Becker score. The differences in PFS time between the responder and non-responder groups were significant according to %ΔTIU-p and Choi criteria (P = 0.001 and P = 0.013, respectively). CONCLUSIONS: The TIU-p can help predict pathological regression in advanced gastric cancer patients after neoadjuvant chemotherapy. In addition, the %ΔTIU-p could be one of the potentially valuable predictive parameters of the PFS time.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Iodo/farmacocinética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Avaliação de Resultados em Cuidados de Saúde/métodos , Estudos Prospectivos , Critérios de Avaliação de Resposta em Tumores Sólidos , Neoplasias Gástricas/metabolismo
17.
PLoS One ; 11(2): e0148482, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26845040

RESUMO

Adiponectin and miR-133a are key regulators in cardiac hypertrophy. However, whether APN has a potential effect on miR-133a remains unclear. In this study, we aimed to investigate whether APN could regulate miR-133a expression in Angiotensin II (Ang II) induced cardiac hypertrophy in vivo and in vitro. Lentiviral-mediated adiponectin treatment attenuated cardiac hypertrophy induced by Ang II infusion in male wistar rats as determined by reduced cell surface area and mRNA levels of atrial natriuretic peptide (ANF) and brain natriuretic peptide (BNP), also the reduced left ventricular end-diastolic posterior wall thickness (LVPWd) and end-diastolic interventricular septal thickness (IVSd). Meanwhile, APN elevated miR-133a level which was downregulated by Ang II. To further investigate the underlying molecular mechanisms, we treated neonatal rat ventricular myocytes (NRVMs) with recombinant rat APN before Ang II stimulation. Pretreating cells with recombinant APN promoted AMP-activated protein kinase (AMPK) phosphorylation and inhibited ERK activation. By using the inhibitor of AMPK or a lentiviral vector expressing AMPK short hairpin RNA (shRNA) cancelled the positive effect of APN on miR-133a. The ERK inhibitor PD98059 reversed the downregulation of miR-133a induced by Ang II. These results indicated that the AMPK activation and ERK inhibition were responsible for the positive effect of APN on miR-133a. Furthermore, adiponectin receptor 1 (AdipoR1) mRNA expression was inhibited by Ang II stimulation. The positive effects of APN on AMPK activation and miR-133a, and the inhibitory effect on ERK phosphorylation were inhibited in NRVMs transfected with lentiviral AdipoR1shRNA. In addition, APN depressed the elevated expression of connective tissue growth factor (CTGF), a direct target of miR-133a, through the AMPK pathway. Taken together, our data indicated that APN reversed miR-133a levels through AMPK activation, reduced ERK1/2 phosphorylation in cardiomyocytes stimulated with Ang II, revealing a previously undemonstrated and important link between APN and miR-133a.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/metabolismo , Cardiomegalia/genética , Cardiomegalia/metabolismo , Regulação da Expressão Gênica , MicroRNAs/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Adiponectina/genética , Angiotensina II/efeitos adversos , Animais , Cardiomegalia/induzido quimicamente , Cardiomegalia/diagnóstico , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Modelos Animais de Doenças , Ecocardiografia/métodos , Expressão Gênica , Vetores Genéticos/genética , Lentivirus/genética , Masculino , Miócitos Cardíacos/metabolismo , Fosforilação , Ratos , Receptores de Adiponectina/metabolismo , Transdução de Sinais , Transdução Genética , Regulação para Cima
18.
Iran Red Crescent Med J ; 16(4): e14914, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24910802

RESUMO

BACKGROUND: PI3K/AKT pathway plays major roles in regulating cardiomyocyte metabolism. The roles of PI3K/AKT pathway and FOXO3a in mediating high glucose-induced apoptosis in cardiomyocytes remain unclear. OBJECTIVES: In this experimental study, we investigated the mechanisms of the PI3K/AKT pathway and FOXO3a in mediating hyperglycemia-induced apoptosis in neonatal rat ventricular myocytes (NRVMs). MATERIALS AND METHODS: NRVMs were adopted as the cell model to investigate the roles of PI3K/AKT and FOXO3a in mediating hyperglycemia-induced apoptosis in cardiomyocytes. Annexin-V-FITC staining and PI staining were used to evaluate the apoptosis in NRVMs under indicated conditions of serum starvation, high glucose exposure, and pharmacological or genetic manipulations on the expressions of PI3K/AKT and FOXO3a. Western blotting was conducted to evaluate the cytoplasmic/nuclear localization of FOXO3a in NRVMs exposed to high glucose. FOXO3a transcriptional activity was measured by luciferase reporter assay. RESULTS: High glucose (30 mM) induced significant apoptosis in serum-starved NRVMs as compared with normal glucose (5 mM) control (12.01 ± 0.76% vs. 2.86 ± 0.55%; P < 0.001). Treatment with IGF1 attenuated hyperglycemia-induced apoptosis by 68% (3.23 ± 0.76% vs. 9.97 ± 1.29%; P < 0.001; n = 3) in comparison with the non-treated control. Treatment with PI3K inhibitor LY294002 enhanced hyperglycemia-induced apoptosis by 109% (20.83 ± 1.87% vs. 9.97 ± 1.29%; P < 0.001; n = 3) in comparison with the non-treated control. Over-expression of AKT by transduction with CA-AKT attenuated hyperglycemia-induced apoptosis by 47% (5.48 ± 0.35% vs.10.31 ± 0.94%; P < 0.001; n = 3) in comparison with the empty-vector control. Transduction with DN-AKT enhanced high glucose-induced apoptosis by 105% (21.13 ± 1.11% vs. 10.31 ± 0.94%; P < 0.001; n = 3) in comparison with the empty-vector control. Western blotting showed that high glucose induced a significant increase in FOXO3a nuclear localization. Luciferase reporter assay showed that high glucose induced a significant increase of 310% (P < 0.001; n = 3) in FOXO3a transcriptional activity against Fas ligand when NRVMs were transducted with TM-FOXO3a in comparison with the empty-vector control. CONCLUSIONS: The PI3K/AKT pathway mediated hyperglycemia-induced apoptosis of NRVMs through the translocation of FOXO3a to nuclei and the resultant enhanced transcriptional activity of FOXO3.

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