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1.
Nutr Metab Cardiovasc Dis ; 31(10): 2792-2799, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34332862

RESUMO

AIMS: A comprehensive assessment of the association of shift work with risk of metabolic syndrome (MetS) through a systematic review and meta-analysis has not been reported. We aimed to evaluate the relationship from observational studies. DATA SYNTHESIS: We searched PubMed, Embase, and Web of Science databases from inception to December 16, 2020. Articles were chosen according to established inclusion criteria. Studies with data on men and women and different types of shift work were treated as independent studies. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled by using random-effects models with heterogeneity (I2) > 50%; otherwise, a fixed-effects model was used. A total of 7192 articles was searched from PubMed, Embase and Web of science. Finally, we included 23 articles (38 studies) in this meta-analysis. The pooled RRs and 95% CI of MetS risk with shift work, 1-shift work, 2-shift work, and 3-shift work versus non-shift work were 1.30 (95% CI 1.19-1.41), 0.95 (95% CI 0.82-1.11), 1.19 (95% CI 0.91-1.56) and 1.17 (95% CI 1.00-1.37), respectively. The results from subgroup analyses stratified by sex, age, and region supported our overall findings that shift work is a risk factor for MetS. CONCLUSIONS: This meta-analysis suggests that shift work increases risk of MetS. Higher risk of MetS was found in the shift workers who were 2-shift or 3-shift or women or Asian workers.


Assuntos
Síndrome Metabólica/epidemiologia , Jornada de Trabalho em Turnos/efeitos adversos , Adulto , Fatores de Risco Cardiometabólico , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Medição de Risco , Fatores de Tempo
2.
Acta Pharmacol Sin ; 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34040166

RESUMO

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that is present in almost all cells and regulates the activity of innate immune responses in both intracellular and extracellular settings. Current evidence suggests that HMGB1 plays a pivotal role in human pathological and pathophysiological processes such as the inflammatory response, immune reactions, cell migration, aging, and cell death. Sepsis is a systemic inflammatory response syndrome (SIRS) that occurs in hosts in response to microbial infections with a proven or suspected infectious etiology and is the leading cause of death in intensive care units worldwide, particularly in the aging population. Dysregulated systemic inflammation is a classic characteristic of sepsis, and suppression of HMGB1 may ameliorate inflammation and improve patient outcomes. Here, we focus on the latest breakthroughs regarding the roles of HMGB1 in sepsis and sepsis-related organ injury, the ways by which HMGB1 are released, and the signaling pathways and therapeutics associated with HMGB1. This review highlights recent advances related to HMGB1: the regulation of HMBG1 might be helpful for both basic research and drug development for the treatment of sepsis and sepsis-related organ injury.

3.
Eur J Pharmacol ; 882: 173228, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502492

RESUMO

The current study was designed to examine the protection of RAGE-specific inhibitor FPS-ZM1 against renal injury in spontaneously hypertensive rats (SHR) and investigate the underlying mechanism. The adult male SHR were treated with FPS-ZM1 via oral gavages for 12 weeks, and age-matched male Wistar-Kyoto rats (WKY) were used as control. Treatment of SHR with FPS-ZM1 slightly reduced blood pressure, and significantly improved baroreflex sensitivity in SHR. Treatment of SHR with FPS-ZM1 improved renal function, evidenced by increased glomerular filtration rate and renal blood flow, and reduced plasma creatinine, blood urea nitrogen and urine albumin excretion rate. Histology results revealed that treatment of SHR with FPS-ZM1 alleviated renal injury and reduced tubulointerstitial fibrosis. Treatment of SHR with FPS-ZM1 suppressed activation of NF-κB and reduced expression of pro-inflammatory cytokines including Tnf, Il6, and Il1b. Treatment of SHR with FPS-ZM1 abated oxidative stress and downregulated mRNA levels of components of NADPH oxidase (Nox) including Cyba, Nox1, Nox2, Nox4 and Ncf1 in kidneys. In addition, treatment of SHR with FPS-ZM1 reduced renal AngII levels, downregulated mRNA expression of Ace and upregulated expression of Agtr2. In conclusion, treatment with FPS-ZM1 alleviated hypertension-related renal dysfunction, possibly by suppressing NF-κB-mediated inflammation, abating Nox-mediated oxidative stress, and improving local renal renin-angiotensin system (RAS).


Assuntos
Benzamidas/uso terapêutico , Hipertensão Essencial/tratamento farmacológico , Nefropatias/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Animais , Benzamidas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão Essencial/patologia , Hipertensão Essencial/fisiopatologia , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiologia , Nefropatias/patologia , Nefropatias/fisiopatologia , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sistema Renina-Angiotensina/efeitos dos fármacos
4.
Clin Cardiol ; 43(7): 796-802, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32562427

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could cause virulent infection leading to Corona Virus Disease 2019 (COVID-19)-related pneumonia as well as multiple organ injuries. HYPOTHESIS: COVID-19 infection may result in cardiovascular manifestations leading to worse clinical outcome. METHODS: Fifty four severe and critical patients with confirmed COVID-19 were enrolled. Risk factors predicting the severity of COVID-19 were analyzed. RESULTS: Of the 54 patients (56.1 ± 13.5 years old, 66.7% male) with COVID-19, 39 were diagnosed as severe and 15 as critical cases. The occurrence of diabetes, the level of D-dimer, inflammatory and cardiac markers in critical cases were significantly higher. Troponin I (TnI) elevation occurred in 42.6% of all the severe and critical patients. Three patients experienced hypotension at admission and were all diagnosed as critical cases consequently. Hypotension was found in one severe case and seven critical cases during hospitalization. Sinus tachycardia is the most common type of arrythmia and was observed in 23 severe patients and all the critical patients. Atrioventricular block and ventricular tachycardia were observed in critical patients at end stage while bradycardia and atrial fibrillation were less common. Mild pericardial effusion was observed in one severe case and five critical cases. Three critical cases suffered new onset of heart failure. Hypotension during treatment, severe myocardial injury and pericardial effusion were independent risk factors predicting the critical status of COVID-19 infection. CONCLUSION: This study has systemically observed the impact of COVID-19 on cardiovascular system, including myocardial injury, blood pressure, arrythmia and cardiac function in severe and critical cases. Monitoring of vital signs and cardiac function of COVID-19 patients and applying potential interventions especially for those with hypotension during treatment, severe myocardial injury or pericardial effusion, is of vital importance.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Adulto , Idoso , COVID-19 , Doenças Cardiovasculares/terapia , China/epidemiologia , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/terapia , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Análise Multivariada , Pandemias , Pneumonia Viral/terapia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida
5.
Emerg Microbes Infect ; 9(1): 757-760, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32228222

RESUMO

The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood. In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs. This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Infecções por Coronavirus/complicações , Hipertensão/tratamento farmacológico , Pneumonia Viral/complicações , Sistema Renina-Angiotensina , Idoso , Betacoronavirus , Proteína C-Reativa/análise , Complexo CD3 , Linfócitos T CD8-Positivos/citologia , COVID-19 , China , Infecções por Coronavirus/tratamento farmacológico , Feminino , Humanos , Hipertensão/complicações , Hipertensão/virologia , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento , Carga Viral
6.
BMC Cardiovasc Disord ; 19(1): 138, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182014

RESUMO

BACKGROUND: Catheter ablation (CA) and left atrial appendage closure (LAAC) have been combined into a novel one-stop procedure for patients with atrial fibrillation (AF). However, postoperative complications are relatively common in patients undergoing LAAC; the complications, including residual flow, increase in the risk of bleeding, or other adverse events, are unknown in patients receiving one-stop therapy. Therefore, we tried to evaluate the adverse events of CA and LAAC hybrid therapy in patients with nonvalvular AF. METHODS: We performed a meta-analysis and computer-based literature search to identify publications listed in the PubMed, Embase, and Cochrane library databases. Studies were included if patients received CA and LAAC hybrid therapy and reported adverse events. RESULTS: Overall 13 studies involving 952 patients were eligible based on the inclusion criteria. In the periprocedural period, the pooled incidence of pericardial effusion was 3.15%. The rates of bleeding events and residual flow were 5.02 and 9.11%, respectively. During follow-up, the rates of all-cause mortality, embolism events, bleeding events, AF recurrence, and residual flow were 2.15, 5.24, 6.95, 32.89, and 15.35%, respectively. The maximum occurrence probability of residual flow events was 21.87%. Bleeding events were more common in patients with a higher procedural residual flow event rate (P = 0.03). A higher AF recurrence rate indicated higher rates of embolism events (P = 0.04) and residual flow (P = 0.03) during follow-up. CONCLUSIONS: Bleeding events were more common in patients with a higher procedural residual flow event rate. However, combined CA and LAAC therapy is reasonably safe and efficacious in patients with nonvalvular AF. Further studies on the safety and efficacy of CA or LAAC alone are necessary in future.


Assuntos
Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Ablação por Cateter , Frequência Cardíaca , Potenciais de Ação , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Causas de Morte , Feminino , Humanos , Masculino , Hemorragia Pós-Operatória/induzido quimicamente , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
7.
FASEB J ; 33(4): 5366-5376, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30759345

RESUMO

The voltage-gated cardiac sodium channel, Nav1.5, is the key component that controls cardiac excitative electrical impulse and propagation. However, the dynamic alterations of Nav1.5 during cardiac ischemia and reperfusion (I/R) are seldom reported. We found that the protein levels of rat cardiac Nav1.5 were significantly decreased in response to cardiac I/R injury. By simulating I/R injury in cells through activating AMPK by glucose deprivation, AMPK activator treatment, or hypoxia and reoxygenation (H/R), we found that Nav1.5 was down-regulated by AMPK-mediated autophagic degradation. Furthermore, AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule-associated protein 1 light chain 3 (LC3), by exposing the LC3-interacting region adjacent to T101 in Nav1.5. This study highlights an instrumental role of AMPK in mediating the autophagic degradation of Nav1.5 during cardiac I/R injury.-Liu, X., Chen, Z., Han, Z., Liu, Y., Wu, X., Peng, Y., Di, W., Lan, R., Sun, B., Xu, B., Xu, W. AMPK-mediated degradation of Nav1.5 through autophagy.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Células Musculares/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Animais , Animais Recém-Nascidos , Autofagia/fisiologia , Imunoprecipitação , Masculino , Miócitos Cardíacos/metabolismo , Fosforilação , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais
8.
Cell Mol Life Sci ; 75(14): 2681, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29691591

RESUMO

In the original publication, affiliations were incorrectly published for the authors.

9.
Curr Issues Mol Biol ; 28: 29-46, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29388552

RESUMO

The peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1s (PGC-1s) can induce the expression of several downstream genes that play pivotal roles in the regulation of mitochondrial biogenesis and metabolism in the heart. Moreover, PGC-1 signaling pathways have also been reported to play a critical role in cardioprotection. Given the significance of PGC-1 coactivators, we summarize the current literature on the molecular mechanisms and roles of PGC-1s in cardiac metabolism. Thus, in this review, we first introduce the basic knowledge regarding PGC-1 signaling pathways. We then discuss their roles in heart metabolism. Moreover, we describe several significant treatments that target the PGC-1 signaling pathway. This review presents the significant roles of PGC-1s in cardiac metabolism and may contribute to the promotion of PGC-1 signaling pathway as a novel therapeutic target.


Assuntos
Doenças Cardiovasculares/genética , Metabolismo Energético/genética , PPAR gama/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Doenças Cardiovasculares/patologia , Humanos , Miocárdio/metabolismo , Miocárdio/patologia , Biogênese de Organelas , Transdução de Sinais/genética
10.
Br J Pharmacol ; 175(16): 3251-3262, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28880375

RESUMO

Melatonin, discovered in 1958 in the bovine pineal tissue, is an indoleamine that modulates circadian rhythms and has a wide variety of other functions. Haematological neoplasms are the leading cause of death in children and adolescents throughout the world. Research has demonstrated that melatonin is a low-toxicity protective molecule against experimental haematological neoplasms, but the mechanisms remain poorly defined. Here, we provide an introduction to haematological neoplasms and melatonin, especially as they relate to the actions of melatonin on haematological carcinogenesis. Secondly, we summarize what is known about the mechanisms of action of melatonin in the haematological system, including its pro-apoptotic, pro-oxidative, anti-proliferative and immunomodulatory actions. Thirdly, we discuss the advantages of melatonin in combination with other drugs against haematological malignancy, as well as its other benefits on the haematological system. Finally, we summarize the findings that are contrary to the suppressive effects of melatonin on cancers of haematological origin. We hope that this information will be helpful in the design of studies related to the therapeutic efficacy of melatonin in haematological neoplasms. LINKED ARTICLES: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc.


Assuntos
Neoplasias Hematológicas/tratamento farmacológico , Melatonina/uso terapêutico , Animais , Antineoplásicos/efeitos adversos , Neoplasias Hematológicas/metabolismo , Humanos , Melatonina/metabolismo
11.
Free Radic Biol Med ; 115: 18-30, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29129519

RESUMO

Silent information regulator 6 (SIRT6), a class III histone deacetylase, has been revealed to participate in multiple metabolic processes in the liver, and it plays important roles in protecting against ischemia/reperfusion (I/R) injury in multiple organs. In this study, we explored whether SIRT6 is protective against hepatic I/R injury and elucidated the underlying mechanisms. The expression of SIRT6 was significantly decreased during reperfusion compared with the control group. SIRT6-LKO mice exhibited significantly aggravated oxidative stress, mitochondrial dysfunction, inflammatory responses, mitogen-activated protein kinase (MAPK) signaling activation, and apoptosis and autophagy related hepatocyte death compared with control mice. In vitro studies in SIRT6-KO hepatocytes exhibited similar results. In contrast, SIRT6 upregulation alleviated liver damage during hepatic I/R injury. Our study demonstrated for the first time that SIRT6 upregulation effectively protects against hepatic I/R injury. The underlying mechanisms involve the maintenance of oxidative homeostasis and mitochondrial function, which subsequently inhibit the inflammatory responses and MAPK signaling, and finally attenuate apoptosis and autophagy related hepatocyte death. These results suggest that the activation of SIRT6 exerts multifaceted protective effects during hepatic I/R injury, which can provide a novel therapeutic target for hepatic I/R injury.


Assuntos
Fígado/metabolismo , Traumatismo por Reperfusão/metabolismo , Sirtuínas/metabolismo , Animais , Apoptose , Autofagia , Morte Celular , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fígado/patologia , Masculino , Camundongos , Camundongos Knockout , Transdução de Sinais , Sirtuínas/genética , Transcriptoma
12.
Biochim Biophys Acta Mol Basis Dis ; 1864(2): 563-578, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29196237

RESUMO

It has been demonstrated that the anti-oxidative and cardioprotective effects of melatonin are, at least in part, mediated by its membrane receptors. However, the direct downstream signaling remains unknown. We previously found that melatonin ameliorated myocardial ischemia-reperfusion (MI/R) injury in diabetic animals, although the underlying mechanisms are also incompletely understood. This study was designed to determine the role of melatonin membrane receptors in melatonin's cardioprotective actions against diabetic MI/R injury with a focus on cGMP and its downstream effector PKG. Streptozotocin-induced diabetic Sprague-Dawley rats and high-glucose medium-incubated H9c2 cardiomyoblasts were utilized to determine the effects of melatonin against MI/R injury. Melatonin treatment preserved cardiac function and reduced oxidative damage and apoptosis. Additionally, melatonin increased intracellular cGMP level, PKGIα expression, p-VASP/VASP ratio and further modulated myocardial Nrf-2-HO-1 and MAPK signaling. However, these effects were blunted by KT5823 (a selective inhibitor of PKG) or PKGIα siRNA except that intracellular cGMP level did not changed significantly. Additionally, our in vitro study showed that luzindole (a nonselective melatonin membrane receptor antagonist) or 4P-PDOT (a selective MT2 receptor antagonist) not only blocked the cytoprotective effect of melatonin, but also attenuated the stimulatory effect of melatonin on cGMP-PKGIα signaling and its modulatory effect on Nrf-2-HO-1 and MAPK signaling. This study showed that melatonin ameliorated diabetic MI/R injury by modulating Nrf-2-HO-1 and MAPK signaling, thus reducing myocardial apoptosis and oxidative stress and preserving cardiac function. Importantly, melatonin membrane receptors (especially MT2 receptor)-dependent cGMP-PKGIα signaling played a critical role in this process.


Assuntos
Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Coração/efeitos dos fármacos , Melatonina/farmacologia , Traumatismo por Reperfusão/metabolismo , Acetilcisteína/metabolismo , Animais , Apoptose , Membrana Celular/metabolismo , Sobrevivência Celular , Diabetes Mellitus Experimental , Ativação Enzimática , Regulação da Expressão Gênica , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais , Triptaminas/farmacologia
13.
Semin Cancer Biol ; 50: 124-131, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28965871

RESUMO

Digestive malignancies are the leading cause of mortality among all neoplasms, contributing to estimated 3 million deaths in 2012 worldwide. The mortality rate hassurpassed lung cancer and prostate cancer in recent years. The transcription factor Forkhead Box O1 (FOXO1) is a key member of Forkhead Box family, regulating diverse cellular functions during tumor initiation, progression and metastasis. In this review, we focus on recent studies investigating the antineoplastic role of FOXO1 in digestive malignancy. This review aims to serve as a guide for further research and implicate FOXO1 as a potent therapeutic target in digestive malignancy.


Assuntos
Carcinogênese/genética , Proteína Forkhead Box O1/genética , Neoplasias Gastrointestinais/genética , Neoplasias Hepáticas/genética , Progressão da Doença , Neoplasias Gastrointestinais/patologia , Humanos , Neoplasias Hepáticas/patologia , Metástase Neoplásica
14.
Oncotarget ; 8(43): 74791-74805, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088824

RESUMO

Diallyl trisulfide (DATS), the major active ingredient in garlic, has been reported to confer cardioprotective effects. However, its effect on myocardial ischemia-reperfusion (MI/R) injury in diabetic state and the underlying mechanism are still unknown. We hypothesize that DATS reduces MI/R injury in diabetic state via AMPK-mediated AKT/GSK-3ß/HIF-1α activation. Streptozotocin-induced diabetic rats received MI/R surgery with or without DATS (20mg/kg) treatment in the presence or absence of Compound C (Com.C, an AMPK inhibitor, 0.25mg/kg) or LY294002 (a PI3K inhibitor, 5mg/kg). We found that DATS significantly improved heart function and reduced myocardial apoptosis. Additionally, in cultured H9c2 cells, DATS (10µM) also attenuated simulated ischemia-reperfusion injury. We found that AMPK and AKT/GSK-3ß/HIF-1α signaling were down-regulated under diabetic condition, while DATS markedly increased the phosphorylation of AMPK, ACC, AKT and GSK-3ß as well as HIF-1α expression in MI/R-injured myocardium. However, these protective actions were all blunted by Com.C administration. Additionally, LY294002 abolished the stimulatory effect of DATS on AKT/GSK-3ß/HIF-1α signaling without affecting AMPK signaling. While 2-methoxyestradiol (a HIF-1α inhibitor) reduced HIF-1α expression without affecting AKT/GSK-3ß signaling. Taken together, these data showed that DATS protected against MI/R injury in diabetic state by attenuating cellular apoptosis via AMPK-mediated AKT/GSK-3ß/HIF-1α signaling. Its cardioprotective effect deserves further study.

15.
Oncotarget ; 8(37): 62780-62792, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-28977988

RESUMO

Fibrosis is a common process of excessive extracellular matrix (ECM) accumulation following inflammatory injury. Fibrosis is involved in the pathogenesis of almost all liver diseases for which there is no effective treatment. 5'-AMP-activated protein kinase (AMPK) is a cellular energy sensor that can ameliorate the process of hepatic fibrogenesis. Given the existing evidence, we first introduce the basic background of AMPK and hepatic fibrosis and the actions of AMPK in hepatic fibrosis. Second, we discuss the three phases of hepatic fibrosis and potential drugs that target AMPK. Third, we analyze possible anti-fibrosis mechanisms and other benefits of AMPK on the liver. Finally, we summarize and briefly explain the current objections to targeting AMPK. This review may aid clinical and basic research on AMPK, which may be a novel drug candidate for hepatic fibrosis.

16.
Cell Mol Life Sci ; 74(21): 3989-3998, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28795196

RESUMO

Ischemia/reperfusion (IR) injury occurs in many organs and tissues, and contributes to morbidity and mortality worldwide. Melatonin, an endogenously produced indolamine, provides a strong defense against IR injury. Mitochondrion, an organelle for ATP production and a decider for cell fate, has been validated to be a crucial target for melatonin to exert its protection against IR injury. In this review, we first clarify the mechanisms underlying mitochondrial dysfunction during IR and melatonin's protection of mitochondria under this condition. Thereafter, special focus is placed on the protective actions of melatonin against IR injury in brain, heart, liver, and others. Finally, we explore several potential future directions of research in this area. Collectively, the information compiled here will serve as a comprehensive reference for the actions of melatonin in IR injury identified to date and will hopefully aid in the design of future research and increase the potential of melatonin as a therapeutic agent.


Assuntos
Antioxidantes/farmacologia , Melatonina/farmacologia , Mitocôndrias/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Animais , Humanos , Mitocôndrias/efeitos dos fármacos , Traumatismo por Reperfusão/metabolismo
17.
PLoS One ; 12(7): e0180513, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28683134

RESUMO

BACKGROUND: Recent studies have reported prognosis differences between male and female heart failure patients following cardiac resynchronization therapy (CRT). However, the potential clinical factors that underpin these differences remain to be elucidated. METHODS: A meta-analysis was performed to investigate the factors that characterize sex-specific differences following CRT. This analysis involved searching the Medline (Pubmed source) and Embase databases in the period from January 1980 to September 2016. RESULTS: Fifty-eight studies involving 33445 patients (23.08% of whom were women) were analyzed as part of this study. Only patients receiving CRT with follow-up greater than six months were included in our analysis. Compared with males, females exhibited a reduction of 33% (hazard ratio, 0.67; 95% confidence interval, 0.62-0.73; P < 0.0001) and 42% (hazard ratio, 0.58; 95% confidence interval, 0.46-0.74; P = 0.003) in all-cause mortality and heart failure hospitalization or heart failure, respectively. Following a stratified analysis of all-cause mortality, we observed that ischemic causes (p = 0.03) were likely to account for most of the sex-specific differences in relation to CRT. CONCLUSION: These data suggest that women have a reduced risk of all-cause mortality and heart failure hospitalization or heart failure following CRT. Based on the results from the stratified analysis, we observed more optimal outcomes for females with ischemic heart disease. Thus, ischemia are likely to play a role in sex-related differences associated with CRT in heart failure patients. Further studies are required to determine other indications and the potential mechanisms that might be associated with sex-specific CRT outcomes.


Assuntos
Terapia de Ressincronização Cardíaca/métodos , Insuficiência Cardíaca/mortalidade , Isquemia Miocárdica/mortalidade , Fatores Sexuais , Feminino , Insuficiência Cardíaca/terapia , Humanos , Masculino , Isquemia Miocárdica/terapia
18.
Pharmacol Res ; 119: 373-383, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28274852

RESUMO

Curcumin, which was first used 3000 years ago as an anti-inflammatory agent, is a well-known bioactive compound derived from the active ingredient of turmeric (Curcuma longa). Previous research has demonstrated that curcumin has immense therapeutic potential in a variety of diseases via anti-oxidative, anti-apoptotic, and anti-inflammatory pathways. Cardiac diseases are the leading cause of mortality worldwide and cause considerable harm to human beings. Numerous studies have suggested that curcumin exerts a protective role in the human body whereas its actions in cardiac diseases remain elusive and poorly understood. On the basis of the current evidence, we first give a brief introduction of cardiac diseases and curcumin, especially regarding the effects of curcumin in embryonic heart development. Secondly, we analyze the basic roles of curcumin in pathways that are dysregulated in cardiac diseases, including oxidative stress, apoptosis, and inflammation. Thirdly, actions of curcumin in different cardiac diseases will be discussed, as will relevant clinical trials. Eventually, we would like to discuss the existing controversial opinions and provide a detailed analysis followed by the remaining obstacles, advancement, and further prospects of the clinical application of curcumin. The information compiled here may serve as a comprehensive reference of the protective effects of curcumin in the heart, which is significant to the further research and design of curcumin analogs as therapeutic options for cardiac diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Cardiotônicos/uso terapêutico , Curcumina/uso terapêutico , Cardiopatias/tratamento farmacológico , Coração/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Cardiotônicos/química , Cardiotônicos/farmacologia , Curcuma/química , Curcumina/química , Curcumina/farmacologia , Coração/embriologia , Cardiopatias/imunologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Miocárdio/imunologia , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos
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