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1.
Lipids Health Dis ; 22(1): 90, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37391821

RESUMO

BACKGROUND: The Chinese visceral adiposity index (CVAI), a simple surrogate measure of visceral fat, is significantly associated with cardiovascular disease (CVD) risk in the general population. This study aimed to evaluate the association of cumulative CVAI (cumCVAI) exposure and its accumulation time course with CVD risk among patients with hypertension. METHODS: This prospective study involved 15,350 patients with hypertension from the Kailuan Study who were evaluated at least three times in the observation period of 2006 to 2014 (2006-2007, 2010-2011, and 2014-2015) and who were free of myocardial infarction and stroke before 2014. The cumCVAI was calculated as the weighted sum of the mean CVAI for each time interval (value × time). The time course of CVAI accumulation was categorized by splitting the overall accumulation into early (cumCVAI06 - 10) and late (cumCVAI10 - 14) accumulation, or the slope of CVAI versus time from 2006 to 2014 into positive and negative. RESULTS: During the 6.59-year follow-up period, 1,184 new-onset CVD events were recorded. After adjusting for confounding variables, the hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD were 1.35 (1.13-1.61) in the highest quartile of cumCVAI, 1.35 (1.14-1.61) in the highest quartile of the time-weighted average CVAI, 1.26 (1.12-1.43) in those with a cumulative burden > 0, and 1.43 (1.14-1.78) for the group with a 10-year exposure duration. When considering the time course of CVAI accumulation, the HR (95% CI) for CVD was 1.33 (1.11-1.59) for early cumCVAI. When considering the combined effect of cumCVAI accumulation and its time course, the HR (95% CI) for CVD was 1.22 (1.03-1.46) for cumCVAI ≥ median with a positive slope. CONCLUSIONS: In this study, incident CVD risk depended on both long-term high cumCVAI exposure and the duration of high CVAI exposure among patients with hypertension. Early CVAI accumulation resulted in a greater risk increase than later CVAI accumulation, emphasizing the importance of optimal CVAI control in early life.


Assuntos
Adiposidade , Hipertensão , Humanos , População do Leste Asiático , Hipertensão/complicações , Estudos Prospectivos
2.
BMC Public Health ; 23(1): 2528, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110944

RESUMO

BACKGROUND: High cardiovascular health (CVH) was associated with lower risk of cardiovascular disease (CVD) and longer life expectancy. However, whether life years lived without CVD could increase faster than or at least at the same pace as total lifespan remains unknown. We aimed to explore the associations of CVH status with total life expectancy and life years lived with and without CVD among middle-aged and elderly men and women. METHODS: We included 65,587 participants aged ≥ 45 years from Kailuan study, who were recruited during June 2006 to October 2007. CVH was scored and classified (low [0-49 points], moderate [50-79 points] and high [80-100 points]) with Life's Essential 8, incorporating evaluations of health behaviors and factors. All-cause mortality and incident non-fatal CVD were recorded from baseline to December 31, 2020. The multi-state life table was adopted to explore the associations of CVH status with total life expectancy and life years lived with and without CVD. RESULTS: Six thousand fifty eight cases of incident non-fatal CVD and 10,580 cases of deaths were identified. Men aged 45 years with low, moderate, and high CVH had a life expectancy of 33.0, 36.5 and 38.5 years, of which 7.8 (23.6%), 6.0 (16.3%) and 3.7 years (9.6%) were spent with CVD. For women, the corresponding life expectancy was 36.6, 43.6 and 48.6 years, and the remaining life years lived with CVD were 7.8 (21.3%), 6.0 (13.7%) and 4.5 years (9.3%), respectively. The benefits of high CVH were persistent across lifespan from age 45 to 85 years and consistent when CVH was evaluated with health behaviors and factors alone. CONCLUSIONS: High CVH compared with low CVH was associated with longer total life expectancy and fewer years spent with CVD, indicating that promoting CVH is of great importance for CVD prevention and healthy ageing in China.


Assuntos
Doenças Cardiovasculares , Masculino , Pessoa de Meia-Idade , Idoso , Humanos , Feminino , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco , Comportamentos Relacionados com a Saúde , Expectativa de Vida , China/epidemiologia , Nível de Saúde
3.
J Vasc Res ; 58(4): 267-276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33946068

RESUMO

AIM: To explore the protective effects and related mech-anisms of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) on en-dothelial dysfunction under hyperglycemic conditions. METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were treated with normal glucose (glucose concentration of 5.5 mmol/L), high glucose (glucose concentration of 33 mmol/L), and high glucose plus 1,25(OH)2D3, respectively. Cell viability and apoptosis, intracellular reactive oxygen species (ROS) and nitric oxide (NO) contents, antioxidant enzyme activities, proinflammatory cytokine mRNA levels, and expression levels of proteins involved were measured. RESULTS: High glucose decreased HUVEC viability, promoted ROS production and apoptosis, and reduced NO generation, which was associated with decreased activities of antioxidant enzymes and increased levels of proinflam-matory cytokines. 1,25(OH)2D3 treatment enhanced HUVEC viability, attenuated ROS generation and apoptosis, and -increased NO production, which was accompanied by -enhanced antioxidant enzyme activities and reduced -proinflammatory factors. Mechanically, 1,25(OH)2D3 promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in a vitamin D receptor (VDR)-dependent manner, and Nrf2 siRNA abolished the antioxidative and -anti-inflammatory effects of 1,25(OH)2D3. CONCLUSIONS: 1,25(OH)2D3 attenuates high-glucose-induced endothelial oxidative injury through upregulation of the Nrf2 antioxidant pathway in a VDR-dependent manner.


Assuntos
Antioxidantes/farmacologia , Calcitriol/farmacologia , Glucose/toxicidade , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptores de Calcitriol/agonistas , Apoptose/efeitos dos fármacos , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Fator 2 Relacionado a NF-E2/genética , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transdução de Sinais
4.
Ann Hematol ; 100(2): 529-540, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33420575

RESUMO

Graft-versus-host disease (GVHD) prophylaxis based on post-transplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantations (allo-HCT). The differential impacts of PTCy and ATG on transplantation outcomes are not well characterized. Here we report a meta-analysis of PTCy versus ATG in allo-HCT. Ten studies were eligible, and a total of 1871 patients were included. The incidence of II-IV aGVHD, III-IV aGVHD, and NRM were significantly lower in PTCy arm (HR = 0.63, 95% CI 0.45-0.89; HR = 0.35, 95% CI 0.16-0.77; HR = 0.59, 95% CI 0.48-0.73). PTCy was associated with a better OS and PFS (HR = 0.62, 95% CI = 0.53-0.73; HR = 0.76, 95% CI 0.62-0.93). The relapse rate and cGVHD incidence were not significantly different between PTCy and ATG (HR = 0.85, 95% CI 0.68-1.07; HR = 0.65, 95% CI 0.38-1.12). Thus, compared with ATG, PTCy has a better aGVHD control and OS benefit, without increasing relapse risk, which needs further validation in prospective randomized trials.


Assuntos
Soro Antilinfocitário/uso terapêutico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Aloenxertos , Humanos , Recidiva , Fatores de Risco
5.
Water Sci Technol ; 76(3-4): 633-641, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28759445

RESUMO

The aim of this study is to investigate the potential of ultraviolet/visible (UV/Vis) spectrometry as a complementary method for routine monitoring of reclaimed water production. Robustness of the models and compliance of their sensitivity with current quality limits are investigated. The following indicators are studied: total suspended solids (TSS), turbidity, chemical oxygen demand (COD) and nitrate. Partial least squares regression (PLSR) is used to find linear correlations between absorbances and indicators of interest. Artificial samples are made by simulating a sludge leak on the wastewater treatment plant and added to the original dataset, then divided into calibration and prediction datasets. The models are built on the calibration set, and then tested on the prediction set. The best models are developed with: PLSR for COD (Rpred2 = 0.80), TSS (Rpred2 = 0.86) and turbidity (Rpred2 = 0.96), and with a simple linear regression from absorbance at 208 nm (Rpred2 = 0.95) for nitrate concentration. The input of artificial data significantly enhances the robustness of the models. The sensitivity of the UV/Vis spectrometry monitoring system developed is compatible with quality requirements of reclaimed water production processes.


Assuntos
Reciclagem , Espectrofotometria Ultravioleta/métodos , Águas Residuárias/química , Poluentes Químicos da Água/química , Qualidade da Água , Análise da Demanda Biológica de Oxigênio , Calibragem , Análise dos Mínimos Quadrados , Nitratos/análise , Esgotos/análise , Água/análise
6.
Eur J Gynaecol Oncol ; 37(4): 499-503, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-29894074

RESUMO

PURPOSE: To assess the complications and clinical outcomes of concurrent chemoradiotherapy (CCRT) or pure radiotherapy (RT) in local advanced cervical carcinoma (LACC) patients. MATERIALS AND METHODS: A retrospective study was carried out in 113 consecutive LACC (FIGO Stage IB2-IIIB) patients, of whom 68 received CCRT; the others received pure RT. Five-year overall survival (OS) and the incidence, type, and severity of postoperative complications were analyzed. RESULTS: The five-year survival rate for CCRT and pure RT were 67.7% and 46.8%, respectively (p = 0.018). The incidences of bone marrow suppression and gastrointestinal reaction for CCRT and pure RT were 100% vs. 88.89% (p < 0.001) and 70.6% vs. 33.33% (p < 0.001). Only 16.18% patients received CCRT developed chronic radiation enteritis, and 4.35% developed chronic radiation cystitis. While 11.11% patients received pure RT experienced chronic radiation enteritis (p = 0.449), 4.44% experienced chronic radiation cystitis (p = 0.312). CONCLUSIONS: This retrospective study demonstrated that CCRT followed by radical surgery achieved a better outcome compared with pure RT in LACC patients, but could apparently rise the incidence and severity of hematologic and gastrointestinal toxicity.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia/métodos , Lesões por Radiação/etiologia , Neoplasias do Colo do Útero/radioterapia , Adulto , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Terapia Combinada , Cistite/etiologia , Intervalo Livre de Doença , Enterite/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 42(9): 778-83, 2014 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-25511100

RESUMO

OBJECTIVE: To investigate the impact of ideal cardiovascular health behaviors and factors on resting heart rate (RHR). METHODS: A cross-sectional study method was used in our study.83 824 workers who had participated in the 2006-2007 Kailuan health examination were included, individuals with arrhythmia, hemoglobin ≤ 90g/L, taking drugs which might affect RHR, history of cerebral infarction or myocardial infarction or cancer were excluded.Related information was obtained from the unified questionnaire, blood biochemistry was performed. Multivariate logistic regression was used to analyze the impact of ideal cardiovascular health behaviors and factors on the RHR. RESULTS: (1) The RHR was (76.4 ± 10.3), (75.2 ± 10.3), (74.3 ± 9.9), (73.6 ± 10.0), (72.6 ± 9.9), (72.1 ± 9.7) and (71.8 ± 9.2) beats/min in workers whose number of ideal cardiovascular health behaviors and factors was 1, 2, 3, 4, 5 and ≥ 6 respectively (P < 0.01). (2) Multivariate logistic regression showed that, after adjusted by gender, age, triglyceride, high density lipoprotein cholesterol, high-sensitive C-reactive protein, tea drinking, alcohol drinking, the risk of RHR ≥ 80 beats/min gradually reduces along with the increasing of number of ideal cardiovascular health behaviors and factors (1, 2, 3, 4, 5 and ≥ 6) compared with those who did not have ideal cardiovascular health behaviors and factors, the value of OR (95%CI) was 0.79 (0.71-0.87), 0.68 (0.62-0.75), 0.61 (0.55-0.67), 0.52 (0.47-0.58), 0.50 (0.44-0.56), 0.49 (0.40-0.60) respectively. CONCLUSION: Ideal cardiovascular health behavior and factors is related to lower RHR in individuals without cardiovascular diseases.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Comportamentos Relacionados com a Saúde , Frequência Cardíaca , Proteína C-Reativa , HDL-Colesterol , Estudos Transversais , Humanos , Modelos Logísticos , Infarto do Miocárdio , Fatores de Risco , Inquéritos e Questionários , Triglicerídeos
8.
Acta Cardiol Sin ; 30(4): 316-24, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27122805

RESUMO

BACKGROUND: The purpose of this study was to evaluate the effects of prehypertensive losartan and amlodipine administration on left ventricular (LV) remodeling and function in spontaneously hypertensive rats-stroke prone (SHRSP). METHODS: Spontaneously hypertensive rats-stroke prone were prehypertensively administered losartan, amlodipine, or vehicle. Wistar-Kyoto rats were used as a control. Blood pressure of the rats was determined by tail-cuff method, and LV structure and function were measured by echocardiography and LV cannulation. Collagen volume fraction was analyzed by picrosirius red staining. Protein expressions of brain natriuretic peptide (BNP) and angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors were determined by use of the Western blotting method. RESULTS: Although both drugs downregulated BNP protein expression, the LV remodeling and function were more improved with losartan than with amlodipine treatment. Losartan upregulated AT1R and downregulated AT2R protein expression. CONCLUSIONS: Both drugs inhibited LV remodeling and improved LV function in prehypertensively treated SHRSP. Losartan provided better continued heart protection, potentially due to its persistent inhibition of AT1R and activation of AT2R in the myocardium. KEY WORDS: Amlodipine; Blood pressure; Heart; Losartan; Prehypertension.

9.
ESC Heart Fail ; 11(1): 13-27, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37986663

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is a group of clinical syndromes that exhibit a remarkably heterogeneous phenotype, characterized by symptoms and signs of heart failure, left ventricular diastolic dysfunction, elevated levels of natriuretic peptides, and an ejection fraction greater than or equal to 50%. With the aging of the population and the escalating prevalence of hypertension, obesity, and diabetes, the incidence of HFpEF is progressively rising. Drug therapy options for HFpEF are currently limited, and the associated high risk of cardiovascular mortality and heart failure rehospitalization significantly impact patients' quality of life and longevity while imposing a substantial economic burden on society. Recent research indicates that certain device-based therapies may serve as valuable adjuncts to drug therapy in patients with specific phenotypes of HFpEF, effectively improving symptoms and quality of life while reducing the risk of readmission for heart failure. These include inter-atrial shunt and greater splanchnic nerve ablation to reduce left ventricular filling pressure, implantable heart failure monitor to guide diuresis, left atrial pacing to correct interatrial dyssynchrony, cardiac contractility modulation to enhance cardiac calcium handling, as well as renal denervation, baroreflex activation therapy, and vagus nerve stimulation to restore the autonomic imbalance. In this review, we provide a comprehensive overview of the mechanisms and clinical evidence pertaining to these devices, with the aim of enhancing therapeutic strategies for HFpEF.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Átrios do Coração , Qualidade de Vida , Volume Sistólico/fisiologia , Ensaios Clínicos como Assunto
10.
Bioresour Technol ; 396: 130433, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342281

RESUMO

Cassava (Manihot esculenta Crantz) leaves, the primary by-product of cassava processing, constitute a significant protein source, accounting for 18 to 38 percent on a dry weight basis. Despite their nutritional value, a substantial portion of these leaves is often discarded post-harvest, resulting in notable resource waste. This study employs metagenomic technology to investigate the protein degradation mechanism in cassava leaves, aiming to provide a technical reference for value-added of this by-product. Following a 36-hour period of natural fermentation, the protein degradation rate reached 58%, a phenomenon intricately linked to both the microbial community structure and its functional properties. Notably, Lactococcus and Enterobacter, recognized for their abundant protease activity, were predominant. Metagenomically assembled genomes further revealed Lactococcus's substantial role in producing flavors and active compounds, including amino acids and peptides. This study offers novel perspectives to the foodization and high-value utilization of cassava by-products, emphasizing the sustainable exploitation of biomass resources.


Assuntos
Manihot , Fermentação , Manihot/química , Manihot/metabolismo , Proteólise , Folhas de Planta/química
11.
ACS Appl Mater Interfaces ; 16(22): 28482-28492, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38771938

RESUMO

Uneven lithium plating and low ionic conductivity currently impede the realization of high-capacity rechargeable lithium metal batteries. And the conventional poly(ethylene oxide) (PEO) solid-state electrolytes are unsuitable for high-energy-density Li anode applications due to their low lithium-ion transference number and high reactivity with Li metal, leading to detrimental dendrite formation and potentially hazardous exothermic reactions with the electrolyte. In this study, we employ a supramolecular approach to develop a novel polymer solid-state electrolyte based on poly(vinylidene fluoride) (PVDF) and a novel triblock polymer nanomicrosphere, (poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone), (PCL-PEG-PCL). The abundance of carbonyl and ether-oxygen functional groups in PCL-PEG-PCL enhances the lithium coordination environment within the polymer solid-state electrolyte. Additionally, the original C-F moieties of PVDF form hydrogen bonds with C-H and terminal hydroxyl groups in PCL-PEG-PCL, collectively creating a multichannel fast Li+-conducting supramolecular cross-linked network. The resulting electrolyte demonstrates a high ionic conductivity of 1.4 × 10-3 S cm-1 and an extended electrochemical window of 5.2 V. Moreover, the electrolyte exhibits a high lithium-ion transference number (tLi+ = 0.63) at room temperature and exhibits excellent interfacial compatibility with the lithium metal anode. For the resulting electrolyte utilized in LiFePO4 batteries, the capacity retention of the cells assembled with this electrolyte exceeds 91.3% after 1000 cycles at 25 °C and 2 C (0.281 mA cm-2).

12.
Int Immunopharmacol ; 128: 111554, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38262162

RESUMO

Macrophage is a vital factor in determining the fate of abdominal aortic aneurysm (AAA). The crosstalk between macrophage and other cells plays a crucial role in the development of aneurysm. Gasdermin D (GSDMD) is a vital executive protein of pyroptosis, which is a novel programmed cell death associated with inflammation. In this study, we identified aortic macrophage as the main expressing cell of GSDMD in AAA. Using Gsdmd-/-ApoE-/- mouse and AAV-F4/80-shGSDMD, we demonstrated the potential role of macrophage-derived GSDMD in AAA and aortic pyroptosis induced by Ang II in vivo. In vitro experiments showed that GSDMD promotes the pyroptosis of mouse primary peritoneal macrophages (MPMs), murine aortic vascular smooth muscle cells (MOVAS) and primary smooth muscle cells. Mechanistically, a mouse cytokine antibody array showed that Gsdmd-/- inhibited LPS + nigericin (LN)- induced secretion of multiple cytokines from MPMs. Furthermore, GSDMD is involved in the crosstalk between MPMs and MOVAS via cytokine secretion. This study provides a novel fundamental insight into macrophage-derived GSDMD in AAA and showed that GSDMD could be a promising therapeutic target for AAA.


Assuntos
Aneurisma da Aorta Abdominal , Piroptose , Animais , Camundongos , Angiotensina II/metabolismo , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Macrófagos Peritoneais/metabolismo , Miócitos de Músculo Liso/metabolismo
13.
Nat Commun ; 15(1): 5441, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937512

RESUMO

Recent studies have shown the crucial role of podocyte injury in the development of diabetic kidney disease (DKD). Deubiquitinating modification of proteins is widely involved in the occurrence and development of diseases. Here, we explore the role and regulating mechanism of a deubiquitinating enzyme, OTUD5, in podocyte injury and DKD. RNA-seq analysis indicates a significantly decreased expression of OTUD5 in HG/PA-stimulated podocytes. Podocyte-specific Otud5 knockout exacerbates podocyte injury and DKD in both type 1 and type 2 diabetic mice. Furthermore, AVV9-mediated OTUD5 overexpression in podocytes shows a therapeutic effect against DKD. Mass spectrometry and co-immunoprecipitation experiments reveal an inflammation-regulating protein, TAK1, as the substrate of OTUD5 in podocytes. Mechanistically, OTUD5 deubiquitinates K63-linked TAK1 at the K158 site through its active site C224, which subsequently prevents the phosphorylation of TAK1 and reduces downstream inflammatory responses in podocytes. Our findings show an OTUD5-TAK1 axis in podocyte inflammation and injury and highlight the potential of OTUD5 as a promising therapeutic target for DKD.


Assuntos
Nefropatias Diabéticas , Inflamação , MAP Quinase Quinase Quinases , Camundongos Knockout , Podócitos , Ubiquitinação , Podócitos/metabolismo , Podócitos/patologia , Animais , MAP Quinase Quinase Quinases/metabolismo , MAP Quinase Quinase Quinases/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/genética , Camundongos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/genética , Humanos , Masculino , Camundongos Endogâmicos C57BL , Fosforilação , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/complicações , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genética , Células HEK293 , Enzimas Desubiquitinantes/metabolismo , Enzimas Desubiquitinantes/genética
14.
Int Immunopharmacol ; 134: 112143, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38692016

RESUMO

Chronic inflammation is a significant contributor to hypertensive heart failure. Carnosol (Car), primarily derived from the sage plant (Salvia carnosa), exhibits anti-inflammatory properties in a range of systems. Nevertheless, the influence of angiotensin II (Ang II) on cardiac remodeling remains uncharted. Car was shown to protect mice's hearts against Ang II-induced heart damage at dosages of 20 and 40 mg/kg/d. This protection was evident in a concentration-related decrease in the remodeling of the heart and dysfunction. Examination of the transcriptome revealed that the pivotal roles in mediating the protective effects of Car involved inhibiting Ang II-induced inflammation and the activation of the mitogen-activated protein kinase (MAPK) pathway. Furthermore, Car was found to inhibit p38 phosphorylation, therefore reducing the level of inflammation in cultured cardiomyocytes and mouse hearts. This effect was attributed to the direct binding to p38 and inhibition of p38 protein phosphorylation by Car both in vitro and in vivo. In addition, the effects of Car on inflammation were neutralized when p38 was blocked in cardiomyocytes.


Assuntos
Abietanos , Angiotensina II , Anti-Inflamatórios , Camundongos Endogâmicos C57BL , Miócitos Cardíacos , Remodelação Ventricular , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Angiotensina II/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Masculino , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Camundongos , Abietanos/farmacologia , Abietanos/uso terapêutico , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Remodelação Ventricular/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/induzido quimicamente , Fosforilação/efeitos dos fármacos , Células Cultivadas
15.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167061, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342418

RESUMO

BACKGROUND: Cardiac hypertrophy is a crucial pathological characteristic of hypertensive heart disease and subsequent heart failure. Deubiquitinating enzymes (DUBs) have been found to be involved in the regulation of myocardial hypertrophy. OTU Domain-Containing Protein 6a (OTUD6a) is a recently identified DUB. To date, the potential role of OTUD6a in myocardial hypertrophy has not yet been revealed. METHODS AND RESULTS: We examined the up-regulated level of OTUD6a in mouse or human hypertrophic heart tissues. Then, transverse aortic constriction (TAC)- or angiotensin II (Ang II)- induced ventricular hypertrophy and dysfunction were significantly attenuated in OTUD6a gene knockout mice (OTUD6a-/-). In mechanism, we identified that the Stimulator of Interferon Genes (STING) is a direct substrate protein of OTUD6a via immunoprecipitation assay and mass spectrometry. OTUD6a maintains STING stability via clearing the K48-linked ubiquitin in cardiomyocytes. Subsequently, OTUD6a regulates the STING-downstream NF-κB signaling activation and inflammatory gene expression both in vivo and in vitro. Inhibition of STING blocked OTUD6a overexpression-induced inflammatory and hypertrophic responses in cardiomyocytes. CONCLUSION: This finding extends our understanding of the detrimental role of OTUD6a in myocardial hypertrophy and identifies STING as a deubiquinating substrate of OTUD6a, indicating that targeting OTUD6a could be a potential strategy for the treatment of cardiac hypertrophy.


Assuntos
Cardiomegalia , Insuficiência Cardíaca , Animais , Humanos , Camundongos , Cardiomegalia/metabolismo , Enzimas Desubiquitinantes/genética , Enzimas Desubiquitinantes/metabolismo , Insuficiência Cardíaca/metabolismo , Inflamação/metabolismo , Camundongos Knockout , Miócitos Cardíacos/metabolismo
16.
Int J Biol Macromol ; 266(Pt 2): 131383, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580030

RESUMO

The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 µg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.


Assuntos
Antibacterianos , Doxiciclina , Nanopartículas , Agulhas , Polilisina , Polilisina/química , Doxiciclina/administração & dosagem , Doxiciclina/farmacologia , Doxiciclina/química , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/química , Animais , Pseudomonas aeruginosa/efeitos dos fármacos , Camundongos , Sistemas de Liberação de Medicamentos , Administração Cutânea , Pele/efeitos dos fármacos , Pele/microbiologia , Infecções por Pseudomonas/tratamento farmacológico
17.
Nat Metab ; 6(6): 1092-1107, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38773347

RESUMO

Lipid droplet tethering with mitochondria for fatty acid oxidation is critical for tumor cells to counteract energy stress. However, the underlying mechanism remains unclear. Here, we demonstrate that glucose deprivation induces phosphorylation of the glycolytic enzyme phosphofructokinase, liver type (PFKL), reducing its activity and favoring its interaction with perilipin 2 (PLIN2). On lipid droplets, PFKL acts as a protein kinase and phosphorylates PLIN2 to promote the binding of PLIN2 to carnitine palmitoyltransferase 1A (CPT1A). This results in the tethering of lipid droplets and mitochondria and the recruitment of adipose triglyceride lipase to the lipid droplet-mitochondria tethering regions to engage lipid mobilization. Interfering with this cascade inhibits tumor cell proliferation, promotes apoptosis and blunts liver tumor growth in male mice. These results reveal that energy stress confers a moonlight function to PFKL as a protein kinase to tether lipid droplets with mitochondria and highlight the crucial role of PFKL in the integrated regulation of glycolysis, lipid metabolism and mitochondrial oxidation.


Assuntos
Proliferação de Células , Glicólise , Gotículas Lipídicas , Lipólise , Mitocôndrias , Oxirredução , Gotículas Lipídicas/metabolismo , Animais , Mitocôndrias/metabolismo , Camundongos , Humanos , Masculino , Metabolismo dos Lipídeos , Perilipina-2/metabolismo , Fosforilação , Carnitina O-Palmitoiltransferase/metabolismo , Linhagem Celular Tumoral
18.
Zhonghua Xin Xue Guan Bing Za Zhi ; 41(11): 968-73, 2013 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-24370229

RESUMO

OBJECTIVE: To investigate the impact of resting heart rate (RHR) on new-onset diabetes (NOD) in population without hypertension. METHODS: This prospective cohort study was performed in 2006 and 2007 and screened 101 510 participants. All subjects were employees of the Kailuan Group, a state-run coal mining company. The observation cohort included 48 926 subjects with normal fasting blood glucose (FBG) <7.0 mmol/L, no history of diabetes, complete FBG and RHR examination data, systolic blood pressure <140 mm Hg (1 mm Hg = 0.133 kPa) , diastolic blood pressure <90 mm Hg, no history of hypertension, and no use of hypoglycemic agents or antihypertensive drugs.We excluded participants without a health examination in 2008-2009 or 2010-2011 and those with incomplete examination data. A total of 29 910 participants were included in the final analysis. The observation population was divided into four groups according to RHR data collected during 2006-2007 health examinations: quartile 1 (RHR<63 beats/min) ; quartile 2 (63 beats/min ≤ RHR<70 beats/min) ; quartile 3 (70 beats/min ≤ RHR<75 beats/min) ; quartile 4 ( RHR ≥ 75 beats/min). Kaplan-Meier analysis was used to calculate the incidence of NOD. The relationship between RHR and NOD was estimated using Cox proportional hazard analysis. RESULTS: The incidences of NOD/1000 person-years for the above quartiles of RHR were 11.22, 13.58, 13.96, and 17.55, respectively in the total observational population; the corresponding incidences were 12.17, 15.20, 16.08, 20.44, and 8.29, 9.38, 8.86, and 9.60 in men and women, respectively. Compared with quartile 1, Cox proportional hazard regression analysis showed that the other three RHR groups had an increased risk of NOD after adjusting for age, gender, systolic blood pressure, diastolic blood pressure, and other risk factors. The hazard ratio values for these groups were 1.20 (95%CI:1.04-1.40, P < 0.05), 1.25 (95%CI:1.07-1.45, P < 0.01) and 1.58 (95%CI:1.36-1.82, P < 0.01), respectively. Furthermore, after adjusted the FBG, risk of NOD was significantly higher in quartile 2 (HR = 1.21, 95%CI:1.04-1.40, P < 0.01) and quartile 4 (HR = 1.22, 95%CI:1.06-1.41, P < 0.01 compared that in quartile 1. After adjusting for the factors listed above, the influence of RHR on NOD was not significant in women (P > 0.05) , but there was still an increased risk of NOD in men compared with quartile 1 with hazard ratio values of 1.21 (95%CI:1.02-1.43, P < 0.05) , and 1.27 (95%CI:1.09-1.49, P < 0.01) for quartile 2 and quartile 4, respectively. CONCLUSION: Higher RHR is linked with higher risk of NOD in population without hypertension.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Frequência Cardíaca , Feminino , Humanos , Hipertensão , Masculino , Estudos Prospectivos , Análise de Regressão , Fatores de Risco
19.
Neural Comput Appl ; 35(3): 2103-2117, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35496654

RESUMO

Public health machinery learning platform based on cloud-native is a system platform that combines machine learning frameworks and cloud-native technology for public health services. The problem of how its flexible value is realized has been widely concerned by all public health network intelligent researchers. Thus, this article examines the relationship between cloud-native architecture flexibility and cloud provider value and the processes and the boundary condition by which cloud-native architecture flexibility affects cloud provider value based on innovation theory and dynamic capability theory. The results of a survey of 509 platform-related respondents in China show that cloud-native architecture flexibility is positively related to cloud provider value, and both absorptive capacity and supply chain agility mediate the above-mentioned effect. Moreover, R&D subsidies strengthen both the positive relationship between absorptive capacity and cloud provider value and the relationship between supply chain agility and cloud provider value. In this study, cloud-native architecture flexibility, unit absorptive capacity, supply chain agility and R&D subsidies are considered into a flexible value generation mechanism model that extend the relevant research on the value generation mechanism of information system under the background of network intelligence, and to provide relevant enterprises with suggestions on upgrade strategies.

20.
Materials (Basel) ; 16(17)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37687505

RESUMO

To further improve the operational performance of a phononic crystal air-coupled ultrasonic transducer while reducing the number of simulations, an intelligent optimization design strategy is proposed by combining finite element simulation analysis and artificial intelligence (AI) methods. In the proposed strategy, the structural design parameters of 1-3 piezoelectric composites and acoustic impedance gradient matching layer are sampled using the optimal Latin hypercube sampling (OLHS) method. Moreover, the COMSOL software is utilized to calculate the performance parameters of the transducer. Based on the simulation data, a radial basis function neural network (RBFNN) model is trained to establish the relationship between the design parameters and the performance parameters. The accuracy of the approximation model is verified through linear regression plots and statistical methods. Finally, the NSGA-II algorithm is used to determine the design parameters of the transducer. After optimization, the band gap widths of the piezoelectric composites and acoustic impedance gradient matching layer are increased by 16 kHz and 13.5 kHz, respectively. Additionally, the -6 dB bandwidth of the transducer is expanded by 11.5%. The simulation results and experimental results are consistent with the design objectives, which confirms the effectiveness of the design strategy. This work provides a feasible strategy for the design of high-performance air-coupled ultrasonic transducers, which is of great significance for the development of non-destructive testing technology.

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