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Myeloid-derived growth factor (MYDGF) is a novel secreted protein with potent antiapoptotic and tissue-repairing properties that is present in nearly 140 human tissues and cell lines, with the highest abundance in the oral epithelium and skin. Initially, MYDGF was found in bone marrow-derived monocytes and macrophages for cardioprotection and repair after myocardial infarction. Subsequent studies have shown that MYDGF plays an important role in other cardiovascular diseases (e.g., atherosclerosis and heart failure), metabolic disorders, renal disease, autoimmune/inflammatory disorders, and cancers. Although the underlying mechanisms have not been fully explored, the role of MYDGF in health and disease may involve cell apoptosis and proliferation, tissue repair and regeneration, anti-inflammation, and glycolipid metabolism regulation. In this review, we summarize the current progress in understanding the role of MYDGF in health and disease, focusing on its structure, function and mechanisms. The graphical abstract shows the current role of MYDGF in different organs and diseases (Fig. 1).
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Doenças Cardiovasculares , Humanos , Animais , Doenças Cardiovasculares/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Apoptose , Suscetibilidade a DoençasRESUMO
INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with a wide range of unfavorable cardiometabolic risk factors, including obesity, hypertension, insulin resistance, impaired glucose metabolism, dyslipidemia, and metabolic syndrome. Compared with women with regular menstrual cycles, women with a history of irregular menstrual periods have an increased unfavorable cardiometabolic risk. Recently, the association between the severity of oligomenorrhea and hyperinsulinemia and insulin resistance has been demonstrated. However, evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is scarce. MATERIAL AND METHODS: This work was a prospective cross-sectional study. A total of 154 women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. PCOS women with eumenorrheic (eumeno group), oligomenorrhea (oligo group), and amenorrhea (ameno group) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test, and homeostasis model assessment of insulin resistance. RESULTS: A trend toward an increase in unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of insulin resistance, prediabetes, dyslipidemia, and metabolic syndrome was observed in the ameno group (n = 57) as compared with the eumeno (n = 24) or oligo group (n = 73). A higher prevalence of insulin resistance (odds ratio [OR]: 3.02; 95% confidence interval [CI]: 1.03-8.81) and prediabetes (OR: 3.94; 95% CI: 1.01-15.40) was observed in the ameno group than in the eumeno group, and a higher proportion of dyslipidemia (OR: 2.44; 95% CI: 1.16-5.15) was observed in the ameno group than in the oligo group in the binary logistic regression analysis after adjusting for confounding factors. CONCLUSIONS: PCOS women with amenorrhea show a higher prevalence of insulin resistance, prediabetes, and dyslipidemia compared with those with oligomenorrhea or eumenorrhea. The severity of menstrual dysfunction could be used as a readily obtainable marker for the identification of PCOS women at greatest risk of cardiometabolic diseases.
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Fatores de Risco Cardiometabólico , Distúrbios Menstruais , Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/epidemiologia , Adulto , Estudos Transversais , Estudos Prospectivos , Distúrbios Menstruais/epidemiologia , Resistência à Insulina , Síndrome Metabólica/epidemiologia , Oligomenorreia/epidemiologia , Índice de Gravidade de Doença , Dislipidemias/epidemiologia , Biomarcadores/sangue , Adulto Jovem , Fatores de RiscoRESUMO
BACKGROUND: The use of cardiac implantable electronic devices has grown substantially over the past two decades, lead-related vascular issues are commonly encountered in clinical practice. Superior vena cava (SVC) syndrome due to pacemaker leads is an uncommon complication. Anticoagulation remains the mainstay of therapy to restore some degree of patency and relieve swelling. However, there are limited clinical trials on direct oral anticoagulants (DOACs). CASE PRESENTATION: We report a case of an 80-year-old man who developed SVC syndrome after transvenous pacemaker implantation with symptoms of obstruction that were significantly relieved after four months of DOACs. His symptoms had completely resolved nine months later. CONCLUSIONS: DOACs are effective in the treatment of SVC syndrome after pacemaker implantation, representing an important new approach. It is a very good choice for patients who do not want to undergo interventional therapy.
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BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a common complication in patients undergoing coronary angiography (CAG). However, few studies demonstrate the association between the prognosis and developed CA-AKI in the different periods after the operation. METHODS: We retrospectively enrolled 3206 patients with preoperative serum creatinine (Scr) and at least twice SCr measurement after CAG. CA-AKI was defined as an increase ≥50% or ≥0.3 mg/dL from baseline in the 72 hours after the procedure. Early CA-AKI was defined as having the first increase in SCr within the early phase (<24 hours), and late CA-AKI was defined as an increase in SCr that occurred for the first time in the late phase (24-72 hours). The first endpoint of this study was long-term all-cause mortality. Kaplan-Meier analysis was used to count the cumulative mortality, and the log-rank test was used to assess differences between curves. Univariate and multivariate cox regression analyses were performed to assess whether patients who developed different type CA-AKI were at increased risk of long-term mortality. RESULTS: The number of deaths in the 3 groups was 407 for normal (12.7%), 106 for early CA-AKI (32.7%) and 57 for late CA-AKI (17.7%), during a median follow-up period of 3.95 years. After adjusting for important clinical variables, early CA-AKI (HR = 1.33, 95% CI: 1.02-1.74, P=0.038) was significantly associated with mortality, while late CA-AKI (HR = 0.92, 95% CI: 0.65-1.31, P=0.633) was not. The same results were found in patients with coronary artery disease, chronic kidney disease, diabetes mellitus, and percutaneous coronary intervention. CONCLUSIONS: Early increases in Scr, i.e., early CA-AKI, have better predictive value for long-term mortality. Therefore, in clinical practice, physicians should pay more attention to patients with early renal injury related to long-term prognosis and give active treatment.
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Injúria Renal Aguda , Meios de Contraste/efeitos adversos , Angiografia Coronária , Doença da Artéria Coronariana , Efeitos Adversos de Longa Duração , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , China/epidemiologia , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Angiografia Coronária/mortalidade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Creatinina/sangue , Feminino , Humanos , Efeitos Adversos de Longa Duração/etiologia , Efeitos Adversos de Longa Duração/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Risco Ajustado/métodos , Fatores de RiscoRESUMO
Despite significant advances in therapies in past decades, the mortality rate of septic cardiomyopathy remains high. The aim of this study is to explore the therapeutic effects of combined treatment using melatonin and irisin in a mouse model of lipopolysaccharide (LPS)-mediated septic cardiomyopathy. Our data found that melatonin and irisin could further attenuate LPS-induced myocardial depression. Molecular investigation illustrated that melatonin and irisin cotreatment sustained cardiomyocyte viability and improved mitochondrial function under LPS stress. Pathway analysis demonstrated that macrophage-stimulating 1 (Mst1), which was significantly activated by LPS, was drastically inhibited by melatonin/irisin cotreatment. Mechanically, Mst1 activated c-Jun N-terminal kinase (JNK) pathway and the latter induced oxidative stress, adenosine triphosphate metabolism disorder, mitochondrial membrane potential reduction, and cardiomyocyte death activation. Melatonin and irisin cotreatment effectively inhibited the Mst1-JNK pathway and, thus, promoted cardiomyocyte survival and mitochondrial homeostasis. Interestingly, Mst1 overexpression abolished the beneficial effects of melatonin and irisin in vivo and in vitro. Altogether, our results confirmed that melatonin and irisin combination treatment could protect heart against sepsis-induced myocardial depression via modulating the Mst1-JNK pathways.
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Cardiomiopatias/induzido quimicamente , Cardiomiopatias/tratamento farmacológico , Fibronectinas/farmacologia , Fator de Crescimento de Hepatócito/metabolismo , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melatonina/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cardiomiopatias/metabolismo , Células Cultivadas , Coração/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Sepse/tratamento farmacológico , Sepse/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The underlying mechanisms that mediate the effects of vitamin C on endothelial cell aging are widely unknown. To investigate whether Piwi-interacting RNAs (piRNAs) are involved in this process, an endothelial aging model was induced in vitro using H2O2 in human umbilical vein endothelial cells (HUVECs) and then treated with vitamin C (VC). Untreated HUVECs without H2O2 exposure were used to serve as the negative control group. Cell cycle, cell viability, and aging-associated protein expression were assessed, and RNA sequencing was performed to reveal the piRNA profile. Functional and regulatory networks of the different piRNA target genes were predicted by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis. H2O2 induced G1 phase cell arrest, decreased cell viability, and upregulated the senescence marker p16 in HUVECs. We found that VC treatment inhibited G1 phase cell arrest, increased the number of cells in the S and G2/M phases, increased cell viability, and decreased p16 expression. The piRNA expression profiles revealed that a large proportion of piRNAs that were differentially expressed in H2O2-treated HUVECs were partly normalized by VC. Furthermore, a number of piRNAs associated with the response to VC in H2O2-treated HUVECs were linked with senescence and cell cycle-related pathways and networks. These results indicate that the ability of VC to attenuate H2O2-mediated endothelial cell senescence may be associated with changes in expression of piRNAs that are linked to the cell cycle.
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Ácido Ascórbico/farmacologia , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , RNA Interferente Pequeno/genética , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio/farmacologiaRESUMO
BACKGROUND: Effects of ß-blockers on outcomes in patients with chronic heart failure (CHF) and atrial fibrillation (AF) is still in controversy. METHODS: Searching was conducted by using keywords "atrial fibrillation", and "heart failure" in PubMed, MEDLINE and Embase databases before November 30, 2017. Prospective studies [i.e. randomized control trials (RCTs), post-hoc analysis of RCTs, prospective cohort studies and registry studies] that studied the effect of ß-blockers and all-cause mortality in patients with CHF and AF were included. The analysis was stratified by study design. RESULTS: We identified 12 studies, including 6 post-hoc analysis of RCTs and 6 observational studies (including prospective registry studies and prospective cohort studies), which enrolled 38,133 patients with CHF and AF. Overall, ß-blockers treatment was associated with significant decrease in all-cause mortality [Risk Ratio (RR) =0.73; 95% Confidence Interval (CI) 0.65-0.82, P < 0.001]. When stratified by study design, ß-blockers treatment was associated with 34% reduction in patients with CHF and AF in observational study (RR = 0.66; 95% CI 0.58-0.76, P < 0. 001), but not in post-hoc analysis of RCT (RR = 0.87; 95% CI 0.74-1.02, P = 0.09). CONCLUSIONS: ß-blockers treatment was associated with significantly decrease the risk of all-cause mortality in patients with AF-CHF and it was only seen in observational study group, but not in subgroup analysis of RCT group. Further large RCTs are required to verify the effect of ß-blockers treatment on patients with CHF and AF. The main limitation of this study is the lack of individual data on patients in each study.
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Antagonistas Adrenérgicos beta/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Antagonistas Adrenérgicos beta/efeitos adversos , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Causas de Morte , Doença Crônica , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
AIMS/HYPOTHESIS: The results from prospective cohort studies of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and risk of cancer are controversial. We conducted a meta-analysis to evaluate the risk of cancer in association with impaired fasting glucose and impaired glucose tolerance. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched for prospective cohort studies with data on prediabetes and cancer. Two independent reviewers assessed the reports and extracted the data. Prospective studies were included if they reported adjusted RRs with 95% CIs for the association between cancer and prediabetes. Subgroup analyses were conducted according to endpoint, age, sex, ethnicity, duration of follow-up and study characteristics. RESULTS: Data from 891,426 participants were derived from 16 prospective cohort studies. Prediabetes was associated with an increased risk of cancer overall (RR 1.15; 95% CI 1.06, 1.23). The results were consistent across cancer endpoint, age, duration of follow-up and ethnicity. There was no significant difference for the risk of cancer with different definitions of prediabetes. In a site-specific cancer analysis, prediabetes was significantly associated with increased risks of cancer of the stomach/colorectum, liver, pancreas, breast and endometrium (all p < 0.05), but not associated with cancer of the bronchus/lung, prostate, ovary, kidney or bladder. The risks of site-specific cancer were significantly different (p = 0.01) and were highest for liver, endometrial and stomach/colorectal cancer. CONCLUSIONS/INTERPRETATION: Overall, prediabetes was associated with an increased risk of cancer, especially liver, endometrial and stomach/colorectal cancer.
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Neoplasias/epidemiologia , Neoplasias/etiologia , Estado Pré-Diabético/complicações , Feminino , Humanos , Masculino , Estado Pré-Diabético/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Studies of prehypertension and mortality are controversial after adjusting for other cardiovascular risk factors. This meta-analysis sought to evaluate the association of prehypertension with all-cause and cardiovascular disease (CVD) mortality. METHODS: The PubMed, EMBASE, Cochrane Library databases, and conference proceedings were searched for studies with data on prehypertension and mortality. The relative risks (RRs) of all-cause, CVD, coronary heart disease (CHD), and stroke mortality were calculated and presented with 95% CIs. Subgroup analyses were conducted according to blood pressure, age, gender, ethnicity, follow-up duration, participant number, and study characteristics. RESULTS: Data from 1,129,098 participants were derived from 20 prospective cohort studies. Prehypertension significantly increased the risk of CVD, CHD, and stroke mortality (RR 1.28, 95% CI 1.16-1.40; RR 1.12, 95% CI 1.02-1.23; and RR 1.41, 95% CI 1.28-1.56, respectively), but did not increase the risk of all-cause mortality after multivariate adjustment (RR 1.03, 95% CI 0.97-1.10). The difference between CHD mortality and stroke mortality was significant (P < .001). Subgroup analyses showed that CVD mortality was significantly increased in high-range prehypertension (RR 1.28, 95% CI 1.16-1.41) but not in low-range prehypertension (RR 1.08, 95% CI 0.98-1.18). CONCLUSION: Prehypertension is associated with CVD mortality, especially with stroke mortality, but not with all-cause mortality. The risk for CVD mortality is largely driven by high-range prehypertension.
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Pressão Sanguínea/fisiologia , Pré-Hipertensão/mortalidade , Doenças Cardiovasculares/mortalidade , Causas de Morte/tendências , Humanos , Fatores de Risco , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Studies of the association of prehypertension with the incidence of end-stage renal disease (ESRD) after adjusting for other cardiovascular risk factors have shown controversial results. STUDY DESIGN: Systematic review and meta-analysis of prospective cohort studies. SETTING & POPULATION: Adults with prehypertension. SELECTION CRITERIA FOR STUDIES: Studies evaluating the association of prehypertension with the incidence of ESRD identified by searches in PubMed, EMBASE, and Cochrane Library databases and conference proceedings, without language restriction. PREDICTOR: Prehypertension. OUTCOMES: The relative risks (RRs) of ESRD were calculated and reported with 95% CIs. Subgroup analyses were conducted according to blood pressure (BP), age, sex, ethnicity, and study characteristics. RESULTS: Data from 1,003,793 participants were derived from 6 prospective cohort studies. Compared with optimal BP, prehypertension significantly increased the risk of ESRD (RR, 1.59; 95% CI, 1.39-1.91). In subgroup analyses, prehypertension significantly predicted higher ESRD risk across age, sex, ethnicity, and study characteristics. Even low-range (BP, 120-129/80-84 mm Hg) prehypertension increased the risk of ESRD compared with optimal BP (RR, 1.44; 95% CI, 1.19-1.74), and the risk increased further with high-range (BP, 130-139/85-89 mm Hg) prehypertension (RR, 2.02; 95% CI, 1.70-2.40). The RR was significantly higher in the high-range compared with the low-range prehypertensive population (P = 0.01). LIMITATIONS: No access to individual patient-level data. CONCLUSIONS: Prehypertension is associated with incident ESRD. The increased risk is driven largely by high-range prehypertension.
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Falência Renal Crônica , Pré-Hipertensão , Adulto , Idoso , Pressão Sanguínea , Determinação da Pressão Arterial/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Incidência , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pré-Hipertensão/complicações , Pré-Hipertensão/diagnóstico , Pré-Hipertensão/epidemiologia , Pré-Hipertensão/fisiopatologia , Risco , Medição de RiscoRESUMO
OBJECTIVE: To assess the diagnostic value of cardiac magnetic resonance (CMR) in patients with acute viral myocarditis. METHODS: Thirty patients with suspected acute viral myocarditis admitted in first people's hospital of Shunde from June 2011 to June 2013 were included in this prospective study. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of acute viral myocarditis were evaluated by clinical diagnosis. Diagnostic value among different scan methods and Lake Louise criteria were compared. RESULTS: Acute viral myocarditis was diagnosed in 63.33% (19/30) patients.Values for sensitivity, specificity, PPV, NPV, and diagnostic accuracy within the overall cohort were 57.89%, 72.73%, 78.57%, 50.00%, 63.33%, respectively by edema imaging (ER).Values for sensitivity, specificity, PPV, NPV, and diagnostic accuracy within the overall cohort were 78.95%, 63.64%, 78.95%, 63.64%, 73.33%, respectively using global relative enhancement (gRE).Values for sensitivity, specificity, PPV, NPV, and diagnostic accuracy within the overall cohort were 78.95%, 54.55%, 75.00%, 60.00%, 70.00%, respectively using late gadolinium enhancement (LGE) criteria.Values for sensitivity, specificity, PPV, NPV, and diagnostic accuracy within the overall cohort were 84.21%, 81.82%, 88.89%, 75.00%, 83.33% using Lake Louise criteria. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy using Lake Louise criteria were significantly higher than using ER, gRE, LGE alone(all P < 0.05).Specificity was higher using ER than using gRE and LGE (both P < 0.05). The sensitivity, NPV, and diagnostic accuracy were significantly higher using gRE than using ER (all P < 0.05) and was similar as using LGE (all P > 0.05). CONCLUSION: Cardiac magnetic resonance is an excellent imaging modality for the diagnosis of acute viral myocarditis.
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Espectroscopia de Ressonância Magnética , Miocardite/diagnóstico , Miocardite/virologia , Doença Aguda , Meios de Contraste , Gadolínio , Coração , Humanos , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The triglyceride glucose index (TyG) has previously been considered a reliable indicator of insulin resistance (IR) and an independent prognostic predictor in heart failure (HF). OBJECTIVES: To clarify the association between the TyG and short-term death in non-diabetic patients admitted for acute heart failure (AHF). MATERIAL AND METHODS: We examined 886 out of 1620 consecutive AHF patients who were admitted to Shunde Hospital, Southern Medical University, Foshan, China, from June 1, 2014, to June 1, 2022. The median of the patientsf TyG values was used to divide them into 2 groups. The following formula was used to calculate the TyG: ln [fasting triglycerides (mg/dL) ~ fasting glucose (mg/dL)/2]. The data on all-cause mortality of AHF patients during their hospital stay were collected. The 30-day Enhanced Feedback for Effective Cardiac Treatment (EFFECT) death risk score was used to assess the risk of death. RESULTS: The TyG level was positively correlated with a poor AHF prognostic marker (N-terminal B-type natriuretic peptide (NT-proBNP)) (D = 0.207, p < 0.001) and negatively correlated with a protective marker (serum albumin) (D = .0.43, p < 0.001). Higher TyG values were associated with an elevated EFFECT score and hospital mortality (p < 0.001). According to multivariate logistic regression analysis, higher TyG levels raised the risk of death in hospital (odds ratio (OR) = 1.73; 95% confidence interval (95% CI): 1.03.3.27; p = 0.031) after adjusting for multiple variables, including age, EFFECT score and NT-proBNP. The TyG had a greater area under the receiver operating characteristic (ROC) curve (AUC: 0.688) for predicting hospital death compared to NT-proBNP (AUC: 0.506). CONCLUSIONS: Our findings show that the TyG is associated with the short-term mortality rate of non-diabetic patients admitted to the hospital for AHF. The TyG testing could be a useful prognostic indicator for these patients.
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Glucose , Insuficiência Cardíaca , Humanos , Triglicerídeos , Biomarcadores , Prognóstico , Fatores de Risco , Glicemia , Insuficiência Cardíaca/diagnósticoRESUMO
OBJECTIVES: Secreted frizzled-related protein 2 (SFRP2), a novel adipokine that used to be considered an inhibitor of the canonical Wnt pathway, may play a protective role in metabolic disorders. However, its effect on diabetic cardiomyopathy was still unclear. Accumulating evidence indicates that mitophagy can protect cardiac function in the diabetic heart. The present study aimed to explore the roles of SFRP2 on diabetic cardiomyopathy, focusing on the effects and mechanisms for regulating mitophagy. METHODS: Wild-type H9c2 cells, Sfrp2 overexpression and knockdown H9c2 cells were exposed to a glucolipotoxic milieu. Reactive oxygen species (ROS) production, cell viability, apoptosis, mitophagy and lysosomal activity were detected. The interaction of SFRP2 with frizzled 5 (FZD5), and its effect on expression and intracellular localization of transcription factor EB (TFEB) and ß-catenin were also explored. Diabetic rats and Sfrp2 overexpression diabetic rats were constructed to further document the findings from the in vitro study. RESULTS: The expression of SFRP2 was low and mitophagy was inhibited in H9c2 cells in a glucolipotoxic milieu. Sfrp2 overexpression activated mitophagy and reduced H9c2 cells injury, whereas Sfrp2 deficiency inhibited mitophagy and worsened this injury. Consistent with the in vitro findings, Sfrp2 overexpression ameliorated the impairment in cardiac function of diabetic rats by activating mitophagy. Sfrp2 overexpression upregulated the expression of calcineurin and TFEB, but did not affect ß-catenin in vitro and in vivo. The calcineurin inhibitor tacrolimus can inhibit mitophagy and worsen cell injury in Sfrp2 overexpression H9c2 cells. Furthermore, we found that FZD5 is required for the SFRP2-induced activation of the calcineurin/TFEB pathway and interacts with SFRP2 in H9c2 cells. Transfection with small interfering RNA targeting FZD5 opposed the effects of Sfrp2 overexpression on mitophagy and cell survival in a glucolipotoxic environment. CONCLUSIONS: SFRP2 can protect the diabetic heart by interacting with FZD5 and activating the calcineurin/TFEB pathway to upregulate mitophagy in H9c2 cells.
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Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Ratos , Animais , beta Catenina/metabolismo , Proteínas Secretadas Relacionadas a Receptores Frizzled , Mitofagia , Cardiomiopatias Diabéticas/genética , Diabetes Mellitus Experimental/genética , Calcineurina/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismoRESUMO
BACKGROUND: Prospective cohort studies of prehypertension and the incidence of cardiovascular disease (CVD) are controversial after adjusting for other cardiovascular risk factors. This meta-analysis evaluated the association between prehypertension and CVD morbidity. METHODS: Databases (PubMed, EMBASE and the Cochrane Library) and conference proceedings were searched for prospective cohort studies with data on prehypertension and cardiovascular morbidity. Two independent reviewers assessed the reports and extracted data. The relative risks (RRs) of CVD, coronary heart disease (CHD) and stroke morbidity were calculated and reported with 95% confidence intervals (95% CIs). Subgroup analyses were conducted on blood pressure, age, gender, ethnicity, follow-up duration, number of participants and study quality. RESULTS: Pooled data included the results from 468,561 participants from 18 prospective cohort studies. Prehypertension elevated the risks of CVD (RR = 1.55; 95% CI = 1.41 to 1.71); CHD (RR = 1.50; 95% CI = 1.30 to 1.74); and stroke (RR = 1.71; 95% CI = 1.55 to 1.89). In the subgroup analyses, even for low-range prehypertension, the risk of CVD was significantly higher than for optimal BP (RR = 1.46, 95% CI = 1.32 to 1.62), and further increased with high-range prehypertension (RR = 1.80, 95% CI = 1.41 to 2.31). The relative risk was significantly higher in the high-range prehypertensive populations than in the low-range populations (χ2= 5.69, P = 0.02). There were no significant differences among the other subgroup analyses (P>0.05). CONCLUSIONS: Prehypertension, even in the low range, elevates the risk of CVD after adjusting for multiple cardiovascular risk factors.
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Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Pré-Hipertensão/epidemiologia , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Incidência , Pré-Hipertensão/diagnóstico , Pré-Hipertensão/fisiopatologia , Estudos ProspectivosRESUMO
OBJECTIVE: To investigate the effects of hydrogen sulfide (H2S) on H2O2-stimulated primary neonatal rat cardiomyocytes and related mechanism. METHODS: Primary neonatal rat cardiomyocytes were treated with various concentrations of H2O2 (10, 100, 1000 µmol/L) for 24 h to establish the oxidative stress-induced cell injury model after 3 days' conventional culture. In addition, different concentrations of NaHS (1, 10, 100 µmol/L) were added to cardiomyocytes in the absence and presence of 100 µmol/L H2O2 for 24 h. The viability of cardiomyocytes was measured by MTT assay. The SOD vitality was measured by xanthine oxidase method and MDA content was determined by thiobarbituric acid colorimetric method. LDH activity was measured by chemical colorimetric method. The percentage of apoptotic cells was assessed by flow cytometry (FCM). The mitochondrial membrane potential (MMP) was analyzed by rhodamine 123 (Rh123) staining and photofluorography. The level of reactive oxygen species (ROS) in cardiomyocytes was measured by DCFH-DA staining and photofluorography. RESULTS: Cell viability and SOD vitality were significantly reduced while MDA content and LDH activity were significantly increased with increasing H2O2 concentrations. These effects could be partly reduced by cotreatment with H2O2 in a concentration-dependent manner (all P < 0.05). Compared with control group, the DCF fluorescence intensity significantly increased in the 100 µmol/L H2O2 group (P = 0.003), which could be attenuated by NaHS in a dose-dependent manner. Compared with control group, the MMP significantly decreased in the 100 µmol/L H2O2 group (P = 0.000), which could be partly reversed by cotreatment with NaHS in a dose-dependent manner. Moreover, H2O2 treatment also significantly reduced 100 µmol/L H2O2 induced apoptosis in a dose-dependent manner. CONCLUSION: H2S protects primary neonatal rat cardiomyocytes against H2O2-induced oxidative stress injury through inhibition of H2O2 induced overproduction of ROS, dissipation of MMP and apoptosis.
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Peróxido de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial , Miócitos Cardíacos/metabolismo , Ratos , Superóxido Dismutase/metabolismoRESUMO
Background and aims: Non-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of heart failure (HF) than those without NAFLD. However, the prognostic impact of NAFLD in HF is still controversial. This meta-analysis aimed to explore the association between NAFLD and the risk of adverse outcomes in patients with HF. Methods: We searched multiple electronic databases (Embase, PubMed, and Google Scholar) for potentially related studies up to June 30, 2022. Cohort studies reported multivariable adjusted relative risks and 95% confidence intervals (CIs) of adverse outcomes in HF patients with NAFLD comparing those without NAFLD were included for analysis. Results: A total of six studies involving 12,374 patients with HF were included for analysis, with a median follow-up duration of 2.5 years. The pooled analysis showed that HF patients with NAFLD were associated with a significantly increased risk of major composite adverse outcomes (HR 1.61, 95% CI 1.25-2.07), all-cause mortality (HR 1.66, 95% CI 1.39-1.98), and HF hospitalization or re-hospitalization (HR 1.71, 95% CI 1.03-2.86). Conclusion: NAFLD is associated with a worse prognosis in patients with HF. Effective screening and treatment strategies are needed to improve the prognosis in HF patients with NAFLD.
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Insuficiência Cardíaca , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Prognóstico , Estudos de Coortes , HospitalizaçãoRESUMO
Background: With the refinement of cryopreservation technology, the number of frozen-warmed embryo transfer (FET) cycles and cryopreserved embryos has increased rapidly. However, studies investigating the effect of storage duration on pregnancy outcomes after vitrification are limited and their results are controversial. Furthermore, the available studies did not take patients' demographic nor clinical treatment characteristics into account and the cryo-storage duration was short. So this study aimed to explore the effect of storage duration of vitrified warmed embryos on pregnancy and neonatal outcomes in patients with good prognosis and long storage duration of vitrified embryos. Methods: This study was a bi-centre, retrospective study including 1037 women undergoing their first FET cycles following a fresh cycle from January 2012 until December 2021. Patients were divided into four storage groups in accordance with the storage duration of transferred embryos (612 patients in group I, with storage duration between 1 and 6 months; 202 patients in group II, with storage duration between 7 and 12 months; 141 patients in group III, with storage duration between 13 and 36 months; and 76 patients in group IV, with storage duration between 37 and 84 months). The pregnancy and neonatal outcomes were compared amongst different storage duration groups. Results: Amongst the different groups, no significant differences were observed in the pregnancy outcomes, including biochemical pregnancy rate, implantation rate, clinical pregnancy rate, ongoing pregnancy rate and live birth rate. In addition, no evidence of differences amongst different storage duration groups was observed in terms of preterm birth, birth length and low birthweight. Conclusions: The pregnancy and neonatal outcomes of embryos after vitrification were not impaired by storage duration up to 7 years.
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Nascimento Prematuro , Gravidez , Recém-Nascido , Humanos , Feminino , Estudos Retrospectivos , Nascimento Prematuro/etiologia , Transferência Embrionária/métodos , Criopreservação/métodos , VitrificaçãoRESUMO
BACKGROUND AIMS: We investigated bone marrow stromal cell (BMSC) transplantation combined with angiotensin-converting enzyme inhibitor (ACEI) treatment in acute myocardial infarction (AMI) and the role of insulin-like growth factor-1 (IGF-1). METHODS: AMI models were established in Sprague-Dawley rats by ligation of the left anterior descending coronary artery and grouped into blank control (BC), ACEI treatment (ACEI), BMSC transplantation (BMSC) and BMSC transplantation plus ACEI (combined). Perindopril (2.5 mg/kg) was administered by gavage to ACEI and combined groups from the day after AMI. BMSC (2 × 10(8)) were injected into the border of the MI area a week later in the BMSC and combined groups. RESULTS: After 4 weeks, hemodynamics in the BMSC and combined groups were significantly improved (P < 0.05 versus BC), with the greatest improvement in the combined group (P < 0.05). In addition, an increased number of BMSC survived in the combined group (P < 0.05 versus BMSC). A proportion of BMSC was positive for troponin T, as detected by immunofluorescence. The number of apoptotic cardiomyocytes was decreased in the BMSC and ACEI groups, and even further in the combined group (P < 0.05). IGF-1 expression was up-regulated in the BMSC and combined groups (P < 0.05 versus BC), but not in the ACEI group. B cell lymphoma-2 (Bcl-2) expression was up-regulated in the ACEI, BMSC and combined groups, with the highest expression in the combined group (P < 0.05). CONCLUSIONS: Our results show that BMSC engrafted in AMI can survive well and secrete IGF-1 and preserve cardiac function significantly. These data suggest that BMSC transplantation inhibits apoptosis of cardiomyocytes by up-regulation of Bcl-2 expression in the myocardium, and this effect might be sensitized by ACEI.
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Transplante de Medula Óssea , Terapia Baseada em Transplante de Células e Tecidos , Fator de Crescimento Insulin-Like I/metabolismo , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/terapia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Vasos Coronários/cirurgia , Expressão Gênica/efeitos dos fármacos , Humanos , Miócitos Cardíacos/citologia , Perindopril/administração & dosagem , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Cardiorenal syndrome (CRS), defined as acute or chronic damage to the heart or kidney triggering impairment of another organ, has a poor prognosis. However, the molecular mechanisms underlying CRS remain largely unknown. The RNA-sequencing data of the left ventricle tissue isolated from the sham-operated and CRS model rats at different time points were downloaded from the Gene Expression Omnibus (GEO) database. Genomic differences, protein-protein interaction networks, and short time-series analyses, revealed fibronectin 1 (FN1) and periostin (POSTN) as hub genes associated with CRS progression. The transcriptome sequencing data of humans obtained from the GEO revealed that FN1 and POSTN were both significantly associated with many different heart and kidney diseases. Peripheral blood samples from 20 control and 20 CRS patients were collected from the local hospital, and the gene expression levels of FN1 and POSTN were detected by real-time quantitative polymerase chain reaction. FN1 (area under the curve [AUC] = 0.807) and POSTN (AUC = 0.767) could distinguish CRS in the local cohort with high efficacy and were positively correlated with renal and heart damage markers, such as left ventricular ejection fraction. To improve the diagnostic ability, diagnosis models comprising FN1 and POSTN were constructed by logistic regression (F-Score = 0.718), classification tree (F-Score = 0.812), and random forest (F-Score = 1.000). Overall, the transcriptome data of CRS rat models were systematically analyzed, revealing that FN1 and POSTN were hub genes, which were validated in different public datasets and the local cohort.
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Síndrome Cardiorrenal , Animais , Biomarcadores Tumorais/genética , Síndrome Cardiorrenal/genética , Humanos , Mapas de Interação de Proteínas , Ratos , Volume Sistólico , Função Ventricular EsquerdaRESUMO
The de Winter electrocardiography (ECG) pattern is a sign that implies proximal left anterior descending coronary artery occlusion in patients with chest pain. We report a case of a 34-year-old man with a history of smoking who presented to the local emergency department with a 49 min history of chest pain. The first ECG of the patient indicated that ST-segment elevation was noted in the lead V2-V4; 57 min later, a second ECG revealed a typical de Winter syndrome when the patient was transferred to the emergency chest pain centre of our hospital. A percutaneous coronary intervention (PCI) was performed approximately 8 h later because the patient initially refused the PCI. Acute coronary artery angiography showed that the proximal left anterior descending coronary artery was completely occluded. Our case suggests that ST-segment elevation myocardial infarction may evolve in the direction of de Winter, which reflects a coronary thrombus in formation, so the de Winter ECG pattern should not be considered static.