RESUMO
OBJECTIVE: Endothelial function may improve with enhanced external counterpulsation (EECP) or acupuncture. This study aimed to evaluate the feasibility of acupoint stimulation combined with EECP (acupoint-EECP) for endothelial cell function in patients with essential hypertension. METHODS: Thirty essential hypertensive patients were, randomly divided into two groups, with 15 patients in the acupoint-EECP group, and 15 patients in the control group, of which 3 cases were lost by week 6. Both groups were treated with continued medicine. The participants in the acupoint-EECP group received acupoint stimulation combined with EECP therapy, 45 min for each time, 5 times weekly for 6 weeks for a total of 22.5 hours. The selected acupoints are Zusanli (ST36), Fenglong (ST40) and Sanyinjiao (SP6). The curative effects of the two groups were compared. RESULTS: The acupoint-EECP group (n=15) showed significant improvement in endothelial function [nitric oxide (NO) ï¼endothelin-1 (ET-1) and carotid-femoral pulse wave velocity (cf-PWV), respectively] values compared to the control group (n=12). Multiple imputation (n = 20 imputations) was performed to account for potential bias due to missing data. In stratified analyses, SBP and DBP values decreased when the baseline SBP was ≥120 mmHg and DBP was ≥80 mmHg. CONCLUSIONS: These findings suggest the feasibility of acupoint-EECP in improving endothelial function and treating hypertension. (The Chinese clinical trial registration number is ChiCTR2100053795.).
Assuntos
Terapia por Acupuntura , Contrapulsação , Hipertensão , Humanos , Projetos Piloto , Análise de Onda de PulsoRESUMO
It has been recently reported that CD38 was highly expressed in adipose tissues from obese people and CD38-deficient mice were resistant to high-fat diet (HFD)-induced obesity. However, the role of CD38 in the regulation of adipogenesis and lipogenesis is unknown. In this study, to explore the roles of CD38 in adipogenesis and lipogenesis in vivo and in vitro, obesity models were generated with male CD38-/- and WT mice fed with HFD. The adipocyte differentiations were induced with MEFs from WT and CD38-/- mice, 3T3-L1 and C3H10T1/2 cells in vitro. The lipid accumulations and the alternations of CD38 and the genes involved in adipogenesis and lipogenesis were determined with the adipose tissues from the HFD-fed mice or the MEFs, 3T3-L1 and C3H10T1/2 cells during induction of adipocyte differentiation. The results showed that CD38-/- male mice were significantly resistant to HFD-induced obesity. CD38 expressions in adipocytes were significantly increased in WT mice fed with HFD, and the similar results were obtained from WT MEFs, 3T3-L1 and C3H10T1/2 during induction of adipocyte differentiation. The expressions of PPARγ, AP2 and C/EBPα were markedly attenuated in adipocytes from HFD-fed CD38-/- mice and CD38-/- MEFs at late stage of adipocyte differentiation. Moreover, the expressions of SREBP1 and FASN were also significantly decreased in CD38-/- MEFs. Finally, the CD38 deficiency-mediated activations of Sirt1 signalling were up-regulated or down-regulated by resveratrol and nicotinamide, respectively. These results suggest that CD38 deficiency impairs adipogenesis and lipogenesis through activating Sirt1/PPARγ-FASN signalling pathway during the development of obesity.
Assuntos
ADP-Ribosil Ciclase 1/deficiência , Adipogenia , Tecido Adiposo/metabolismo , Lipogênese , PPAR gama/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , ADP-Ribosil Ciclase 1/metabolismo , Adipócitos/metabolismo , Animais , Diferenciação Celular , Embrião de Mamíferos/citologia , Fibroblastos/metabolismo , Camundongos , NAD/metabolismoRESUMO
BACKGROUND/AIMS: Previous studies showed that CD38 deficiency protected heart from ischemia/reperfusion injury and high fat diet (HFD)-induced obesity in mice. However, the role of CD38 in HFD-induced heart injury remains unclear. In the present study, we have investigated the effects and mechanisms of CD38 deficiency on HFD-induced heart injury. METHODS: The metabolites in heart from wild type (WT) and CD38 knockout (CD38-/-) mice were examined using metabolomics analysis. Cell viability, lactate hydrogenase (LDH) release, super oxide dismutase (SOD) activity, reactive oxygen species (ROS) production, triglyceride concentration and gene expression were examined by biochemical analysis and QPCR. RESULTS: Our results revealed that CD38 deficiency significantly elevated the intracellular glutathione (GSH) concentration and GSH/GSSG ratio, decreased the contents of free fatty acids and increased intracellular NAD+ level in heart from CD38-/- mice fed with HFD. In addition, in vitro knockdown of CD38 significantly attenuated OA-induced cellular injury, ROS production and lipid synthesis. Furthermore, the expression of mitochondrial deacetylase Sirt3 as well as its target genes FOXO3 and SOD2 were markedly upregulated in the H9C2 cell lines after OA stimulation. In contrast, the expressions of NOX2 and NOX4 were significantly decreased in the cells after OA stimulation. CONCLUSION: Our results demonstrated that CD38 deficiency protected heart from HFD-induced oxidative stress via activating Sirt3/FOXO3-mediated anti-oxidative stress pathway.
Assuntos
ADP-Ribosil Ciclase 1/genética , Dieta Hiperlipídica , Proteína Forkhead Box O3/metabolismo , Glicoproteínas de Membrana/genética , Estresse Oxidativo , Sirtuína 3/metabolismo , ADP-Ribosil Ciclase 1/antagonistas & inibidores , ADP-Ribosil Ciclase 1/metabolismo , Animais , Linhagem Celular , Glutationa/metabolismo , Masculino , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Nonalcoholic fatty liver disease is one of the most common liver diseases in the world and is a typical hepatic manifestation of metabolic syndrome which is characterized with lipid accumulation in liver. Nicotinamide phosphoribosyltransferase (NAMPT) has been recently identified as an enzyme involved in nicotinamide adenine dinucleotide (NAD+) biosynthesis and plays an important role in cellular metabolism in variety of organs in mammals. The aim of this study was to investigate the effects of NAMPT on high fat diet-induced hepatic steatosis. METHODS: Hepatic steatosis model was induced by high fat diet (HFD) in C57BL/6 mice in vivo. HepG2 and Hep1-6 hepatocytes were transfected with NAMPT vector plasmid or treated with NAMPT inhibitor FK866 and then incubated with oleic acid. Lipids accumulation was examined by HE staining or oil red staining. Quantitative RT-PCR and Western blot were used to measure expressions of the genes involved in lipogenic synthesis. RESULTS: FK866 significantly promoted liver steatosis in the mice fed with HFD and hepatic lipid accumulation in vitro, accompanied by the increases of the expressions of lipogenic genes such as sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN). Nicotinamide mononucleotide (NMN) and NAD+ significantly rescued the actions of FK866 in vitro. In contrast, overexpression of NAMPT in HepG2 and Hep1-6 hepatocytes ameliorated hepatic lipid accumulation. In addition, FK866 decreased the protein levels of Sirt1 and phospho-AMPKα in liver of the HFD fed mice. Furthermore, Resveratrol, a Sirt1 activator, significantly reduced lipogenic gene expressions, while EX-527, a Sirt1 specific inhibitor, had the opposite effects. CONCLUSION: Our results demonstrated that inhibition of NAMPT aggravated the HFD- or oleic acid-induced hepatic steatosis through suppressing Sirt1-mediated signaling pathway. On the one hand, the inhibition of NAMPT reduced the production of NAD+ through inhibiting the NAD+ salvage pathway, resulting in the decrease of Sirt1 activity, and then attenuated the deacetylation of SREBP1 in which the inhibition of SREBP1 activity promoted the expressions of FASN and ACC. On the other hand, the reduced Sirt1 activity alleviated the activation of AMPKα to further enhance SREBP1 activities.
Assuntos
Proteínas Quinases Ativadas por AMP/genética , Citocinas/genética , Fígado/enzimologia , Nicotinamida Fosforribosiltransferase/genética , Hepatopatia Gordurosa não Alcoólica/genética , Sirtuína 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Acrilamidas/farmacologia , Animais , Carbazóis/farmacologia , Linhagem Celular , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Hepatócitos/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NAD/farmacologia , Mononucleotídeo de Nicotinamida/farmacologia , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Nicotinamida Fosforribosiltransferase/metabolismo , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Ácido Oleico/farmacologia , Piperidinas/farmacologia , Resveratrol , Transdução de Sinais , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Estilbenos/farmacologiaRESUMO
OBJECTIVE: To evaluate the therapeutic efficacy of Shexiang Baoxin Pill combined with exercise in heart failure patients with preserved ejection fraction (HFpEF). METHODS: Sixty patients with HFpEF were randomly divided into group A (n=20), receiving Shexiang Baoxin Pill combined with home-based exercise training based on conventional drugs for 12 weeks; group B (n=20), receiving conventional drugs combined with home-based exercise training for 12 weeks; and group C (n=20), receiving conventional drug treatment only. Peak oxygen uptake (peakVO2), anaerobic threshold (AT), 6-min walking test (6MWT), Pittsburgh Sleep Quality Index (PSQI), and SF-36 questionnaire (SF-36) results before and after treatment were compared among groups. RESULTS: After the 12-week intervention, patients in group C showed significant declines in peakVO2, AT, 6MWT, PSQI, and SF-36 compared with pre-treatment (P<0.01), while groups A and B both showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 results compared with pre-treatment (P<0.01). Compared with group C, patients in groups A and B showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 (P<0.01). In addition, patients in group A showed more significant improvements in physical function, role-physical, vitality, and mental health scores on the SF-36 questionnaire, and PSQI scores than those in group B (P<0.01). CONCLUSIONS: Exercise training improved exercise tolerance, sleep quality and quality of life (QoL) in patients with HFpEF. Notably, Shexiang Baoxin Pill played an active role in sleep quality and QoL of patients with HFpEF. (The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100054322)).
Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/terapia , Qualidade de Vida , Volume Sistólico , Exercício FísicoRESUMO
Litter size has increased and farrowing duration has also prolonged in recent years. The aim of this study was to analyze the effect of litter size and parity on farrowing duration (FAR) to estimate the possibility of selecting a short farrowing duration. We recorded 32,200 parturitions of 8420 Landrace × Yorkshire sows, determined farrowing duration, litter size, parity, gestation length. Results showed that total number of born (TNB) and parity obeyed a cubic (p = 0.0004, p = 0.004) relationship while number born alive (NBA) and number born dead (NBD) obeyed a linear (p = 0.0239, p = 0.0035) relationship with FAR. Gestation length obeyed a linear (p = 0.02) relationship with FAR. FAR of sows with stillbirth was longer than that of sows without stillbirth. Stillbirth rate increased rapidly from about 2% to 4%, especially when FAR was over 240 min. FAR gradually prolonged with the parities. FAR of 7th parity sows was longer than that of 1st~6th parity sows (p < 0.05), but different parity sows had little difference in the same FAR interval except for gilts. Results indicated it was possible and necessary to consider FAR into pig breeding without worrying about decreasing of live litter size or negative effect of parity if FAR was shorter than 300 min.