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BACKGROUND: Researches have found that alteration of intestinal flora may be closely related to the development of autism spectrum disorder (ASD). However, whether probiotics supplementation has a protective effect on ASD remains controversial. This meta-analysis aimed to analyze the outcome of probiotics in the treatment of ASD children. METHODS: The Pubmed, Cochrane Library, Web of Science and Embase were searched until Sep 2022. Randomized controlled trials (RCTs) relevant to the probiotics and placebo treatment on ASD children were screened. Quality assessment of the included RCTs was evaluated by the Cochrane collaboration's tool. The primary outcomes were ASD assessment scales, including ABC (aberrant behavior checklist) and CBCL (child behavior checklist) for evaluating the behavior improvement, SRS (social responsiveness scale) for social assessment, DQ (developmental quotient) for physical and mental development and CGI-I (clinical global impression improvement) for overall improvement. The secondary outcome was total 6-GSI (gastrointestinal severity index). RESULTS: In total, 6 RCTs from 6 studies with 302 children were included in the systemic review. Total 6-GSI (MD=-0.59, 95%CI [-1.02,-0.17], P < 0.05) decreased significantly after oral administration of probiotics. Whereas, there was no statistical difference in ABC, CBCL, SRS, DQ and CGI-I between probiotics and placebo groups in ASD children. CONCLUSION: Probiotics treatment could improve gastrointestinal symptoms, but there was no significant improvement in ASD.
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Transtorno do Espectro Autista , Probióticos , Humanos , Probióticos/uso terapêutico , Transtorno do Espectro Autista/terapia , Criança , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Microbioma GastrointestinalRESUMO
The purpose of this study was to investigate the relationship between oxidative stress and cognitive function, encompassing cognitive performance, intelligence, memory, reaction time, speech and vision by a bidirectional Mendelian randomisation study. Independent genetic variants associated with glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), peroxiredoxin (PRDX), sulfhydryl oxidase (SOX) and thyroid peroxidase (TPO) were explored using a genome-wide association study (GWAS). The inverse variance weighted (IVW) or Wald ratio method was employed to ascertain the relationship between antioxidant enzymes and cognitive function. The MR analyses indicated that the MR effect estimates of GST (ß = 0.0352, P = 0.0047, FDR = 0.0164) and TPO (ß = 0.0531, P = 0.0003, FDR = 0.0021) were significantly associated with cognitive performance elevation. Furthermore, genetically predicted GST (ß = 0.0334, P = 0.0043, FDR = 0.0151) and TPO (ß = 0.0496, P = 0.0031, FDR = 0.0151) were found to be associated with high intelligence. Additionally, there were also some associations of SOX (ß = 0.0243, P = 0.0283, FDR = 0.066) on high cognitive performance, TPO (ß = 0.1189, P = 0.0315, FDR = 0.2205) on larger maximum digits remembered correctly, and SOX (ß = - 0.2435, P = 0.0395, FDR = 0.1185) on reaction time. Nevertheless, the associations between antioxidant enzymes and speech and linguistic disorders, as well as visual disturbances, were not significant. We did not find reverse causation between antioxidant enzymes and cognitive function traits. This study provides evidence of potential causal relationships between oxidative stress and cognitive function.
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BACKGROUND: There are numerous complex barriers and facilitators to continuously wearing hearing protection devices (HPDs) for noise-exposed workers. Therefore, the present study aimed to investigate the relationship between HPD wearing behavior and hearing protection knowledge and attitude, HPD wearing comfort, and work-related factors. METHOD: A cross-sectional study was conducted with 524 noise-exposed workers in manufacturing enterprises in Guangdong Province, China. Data were collected on hearing protection knowledge and attitudes, HPD wearing comfort and behavior, and work-related factors through a questionnaire. Using structural equation modeling (SEM), we tested the association among the study variables. RESULTS: Among the total workers, 69.47% wore HPD continuously, and the attitudes of hearing protection (26.17 ± 2.958) and total HPD wearing comfort (60.13 ± 8.924) were satisfactory, while hearing protection knowledge (3.54 ± 1.552) was not enough. SEM revealed that hearing protection knowledge had direct effects on attitudes (ß = 0.333, p < 0.01) and HPD wearing behavior (ß = 0.239, p < 0.01), and the direct effect of total HPD wearing comfort on behavior was ß = 0.157 (p < 0.01). The direct effect also existed between work shifts and behavior (ß=-0.107, p < 0.05). Indirect relationships mainly existed between other work-related factors, hearing protection attitudes, and HPD wearing behavior through knowledge. Meanwhile, work operation had a direct and negative effect on attitudes (ß=-0.146, p < 0.05), and it can also indirectly and positively affect attitudes through knowledge (ß = 0.08, p < 0.05). CONCLUSION: The behavior of wearing HPD was influenced by hearing protection knowledge, comfort in wearing HPD, and work-related factors. The results showed that to improve the compliance of noise-exposed workers wearing HPD continuously when exposed to noise, the HPD wearing comfort and work-related factors must be taken into consideration. In addition, we evaluated HPD wearing comfort in physical and functional dimensions, and this study initially verified the availability of the questionnaire scale of HPD wearing comfort.
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Perda Auditiva Provocada por Ruído , Ruído Ocupacional , Humanos , Perda Auditiva Provocada por Ruído/prevenção & controle , Estudos Transversais , Análise de Classes Latentes , Ruído Ocupacional/efeitos adversos , Ruído Ocupacional/prevenção & controle , Dispositivos de Proteção das Orelhas , Audição , Inquéritos e Questionários , ChinaRESUMO
OBJECTIVE: We aimed to describe the trends and influence factors in the prevalence, awareness, treatment, and control of hypertension among US Adults from 1999 to 2018. METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning ten survey cycles (n = 53,496). Prevalence, awareness, treatment, and control of hypertension were calculated using survey weights. Joinpoint regression and survey-weighted generalized linear models were used to analyze trends and influence factors, respectively. RESULTS: The estimated prevalence of hypertension increased significantly from 33.53% to 40.58% (AAPC = 0.896, P = 0.002) during 1999-2018 with dropping rate of newly diagnosed hypertension from 8.62% to 4.82% before 2014 (APC = -4.075, P = 0.001), and then rose to 7.51% in 2018 (APC = 12.302, P = 0.126). Despite modest improvements or stability in the awareness, treatment, and control since 1999, the latter two remained inadequate in 2018 at 59.52% and 51.71%. There was an uptrend in the use of angiotensin-converting enzyme inhibitors (from 24.02% to 45.71%) and angiotensin receptor blockers (from 20.22% to 38.38%), and downtrend in ß-blocker (from 12.71% to 4.21%). Men were at higher risk of incidence, un-awareness, un-treatment, and un-control for hypertension. Lower income and education were associated with susceptibility to hypertension, while being married was favorable for treatment and control. Optimal health reduced the incidence of hypertension, and increased the awareness and treatment. CONCLUSION: Although the rate of newly diagnosed hypertension has declined slightly since 2010 in the US, the prevalence of hypertension is increasing, and treatment and control rates remain inadequate. To manage hypertension effectively, we need to focus on screening and prevention for high-risk populations, while advocating for optimal health to improve the burden of hypertension.
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Hipertensão , Masculino , Adulto , Humanos , Inquéritos Nutricionais , Prevalência , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , Fatores de Risco , Modelos Lineares , Conhecimentos, Atitudes e Prática em Saúde , Conscientização , Anti-Hipertensivos/uso terapêuticoRESUMO
Cardiotoxicity linked to doxorubicin (DOX) is primarily caused by inflammation, oxidative stress, and apoptosis. The role of tubeimoside I (TBM) in DOX-induced cardiotoxicity remains ambiguous, despite growing evidence that it could reduce inflammation, oxidative stress, and apoptosis in various diseases. This study was designed to investigate the role of TBM in DOX-induced cardiotoxicity and uncover the underlying mechanisms. H9c2 cell line and C57BL/6 mice were used to construct an in vitro and in vivo model of DOX-induced myocardial injury, respectively. We observed that DOX treatment provoked inflammation, oxidative stress, and cardiomyocyte apoptosis, which were significantly alleviated by TBM administration. Mechanistically, TBM attenuated DOX-induced downregulation of sirtuin 3 (SIRT3), and SIRT3 inhibition abrogated the beneficial effects of TBM both in vitro and in vivo. In conclusion, TBM eased inflammation, oxidative stress, and apoptosis in DOX-induced cardiotoxicity by increasing the expression of SIRT3, suggesting that it holds great promise for treating DOX-induced cardiac injury.
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Traumatismos Cardíacos , Sirtuína 3 , Camundongos , Animais , Cardiotoxicidade/metabolismo , Sirtuína 3/metabolismo , Camundongos Endogâmicos C57BL , Doxorrubicina/efeitos adversos , Estresse Oxidativo , Traumatismos Cardíacos/metabolismo , Apoptose , Inflamação/metabolismo , Miócitos Cardíacos/metabolismoRESUMO
Ginsenoside Rh2 (GRh2) is a monomer isolated from red ginseng that has extensive pharmacological effects. However, whether GRh2 has a protective effect on ischaemia/reperfusion (I/R) in the myocardium has yet to be elucidated. The present study aimed to identify the anti-inflammatory and antioxidant effects of GRh2 on I/R in the myocardium and its underlying mechanism. A rat model of myocardial I/R injury was constructed by ligating the left anterior descending coronary artery, which was subsequently treated with GRh2. A total of 40 male Sprague-Dawley rats were divided into the following four groups: The sham group, the I/R group, the I/R+GRh2 (10 mg/kg) group and the I/R+GRh2 (20 mg/kg) group. Neonatal rat cardiomyocytes were also used to evaluate the protective effect of GRh2 on hypoxia/reoxygenation (H/R)-induced myocardial injury in vitro. The GRh2 pre-treatment reduced the I/R- or H/R-induced release of myocardial enzymes and the production of IL-1ß, IL-18 and TNF-α. GRh2 reduced the area of myocardial infarction and the histological changes in the myocardium and improved cardiac functions. In addition, GRh2 reduced the expression levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein, caspase-1, malondialdehyde and reactive oxygen species and increased the expression levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase and superoxide dismutase. In conclusion, the present study confirmed that GRh2 could reduce oxidative stress and inflammation in cardiomyocytes after reperfusion, and its mechanism of action may be related to its regulation of the Nrf2/HO-1/NLRP3 signalling pathway.
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BACKGROUND: Malignant ventricular arrhythmia (VA) is a major contributor to sudden cardiac death (SCD) in patients with pulmonary arterial hypertension (PAH)-induced right heart failure (RHF). Recently, dapagliflozin (DAPA), a sodium/glucose cotransporter-2 inhibitor (SGLT2i), has been found to exhibit cardioprotective effects in patients with left ventricular systolic dysfunction. In this study, we examined the effects of DAPA on VA vulnerability in a rat model of PAH-induced RHF. METHODS: Rats randomly received monocrotaline (MCT, 60 mg/kg) or vehicle via a single intraperitoneal injection. A day later, MCT-injected rats were randomly treated with placebo, low-dose DAPA (1 mg/kg/day), or high-dose (3 mg/kg/day) DAPA orally for 35 days. Echocardiographic analysis, haemodynamic experiments, and histological assessments were subsequently performed to confirm the presence of PAH-induced RHF. Right ventricle (RV) expression of calcium (Ca2+) handling proteins were detected via Western blotting. RV expression of connexin 43 (Cx43) was determined via immunohistochemical staining. An optical mapping study was performed to assess the electrophysiological characteristics in isolated hearts. Cellular Ca2+ imaging from RV cardiomyocytes (RVCMs) was recorded using Fura-2 AM or Fluo-4 AM. RESULTS: High-dose DAPA treatment attenuated RV structural remodelling, improved RV function, alleviated Cx43 remodelling, increased the conduction velocity, restored the expression of key Ca2+ handling proteins, increased the threshold for Ca2+ and action potential duration (APD) alternans, decreased susceptibility to spatially discordant APD alternans and spontaneous Ca2+ events, promoted cellular Ca2+ handling, and reduced VA vulnerability in PAH-induced RHF rats. Low-dose DAPA treatment also showed antiarrhythmic effects in hearts with PAH-induced RHF, although with a lower level of efficacy. CONCLUSION: DAPA administration reduced VA vulnerability in rats with PAH-induced RHF by improving RVCM Ca2+ handling.
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Insuficiência Cardíaca , Hipertensão Arterial Pulmonar , Disfunção Ventricular Direita , Animais , Arritmias Cardíacas , Compostos Benzidrílicos , Cálcio/metabolismo , Conexina 43/metabolismo , Modelos Animais de Doenças , Fura-2 , Glucose , Glucosídeos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Monocrotalina/toxicidade , Hipertensão Arterial Pulmonar/induzido quimicamente , Hipertensão Arterial Pulmonar/complicações , Hipertensão Arterial Pulmonar/tratamento farmacológico , Ratos , Sódio , Disfunção Ventricular Direita/tratamento farmacológico , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/prevenção & controle , Remodelação VentricularRESUMO
Objective: Studies on extracorporeal membrane oxygenation (ECMO) with and without an intra-aortic balloon pump (IABP) for cardiogenic shock (CS) have been published, but there have been no meta-analyses that compare the efficacy of these two cardiac support methods. This meta-analysis evaluated the outcomes of these two different treatment measures. Methods: The PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials databases were searched until March 2022. Studies that were related to ECMO with or without IABP in patients with CS were screened. Quality assessments were evaluated with the methodological index for nonrandomized studies (MINORS). The primary outcome was in-hospital survival, while the secondary outcomes included duration of ECMO, duration of ICU stay, infection/sepsis, and bleeding. Revman 5.3 and STATA software were used for this meta-analysis. Results: In total, nine manuscripts with 2,573 patients were included in the systematic review. CS patients who received ECMO in combination with IABP had significantly improved in-hospital survival compared with ECMO alone (OR = 1.58, 95% CI = 1.26-1.98, P < 0.0001). However, there were no significant differences in the duration of ECMO (MD = 0.36, 95% CI = -0.12-0.84, P = 0.14), duration of ICU stay (MD = -1.95, 95% CI = -4.05-0.15, P = 0.07), incidence of infection/sepsis (OR = 1.0, 95% CI = 0.58-1.72, P = 1.0), or bleeding (OR = 1.28, 95% CI = 0.48-3.45, P = 0.62) between the two groups of patients with CS. Conclusion: ECMO combined with IABP can improve in-hospital survival more effectively than ECMO alone in patients with CS.
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To evaluate the effects and safety of sacubitril/valsartan in patients with acute myocardial infarction (AMI), a total of four databases, including PubMed, Cochrane Library, Embase and Web of Science, and the ClinicalTrials.gov website were searched. Using a combination of medical subject headings and entry terms, the final search was performed in July 2021. A manual search of cross-references from the original articles was also conducted. The meta-analysis was subsequently performed with Revman 5.3 software and a total of four studies comprising 586 patients were included. The results disclosed a significant reduction in major adverse cardiovascular and cerebrovascular events (MACCEs) [odds ratio (OR), 0.47; 95% confidence interval (CI), 0.30-0.73; P=0.0007], readmission (OR, 0.45; 95% CI, 0.29-0.71; P=0.0006), incidence of acute heart failure (AHF) (OR, 0.45; 95% CI, 0.28-0.71; P=0.0007) and N-terminal pro B-type natriuretic peptide [standardized mean difference (SMD), -0.88; 95% CI, -1.55-(-0.21); P=0.01] in the sacubitril/valsartan group compared with that in the control group, and a random effects model was used to pool these data. No significant differences were identified in the incidence of hypotension (OR, 2.91; 95% CI, 0.55-15.51; P=0.21), adverse events (OR, 2.19; 95% CI, 0.42-11.37; P=0.35), left ventricular ejection fraction (mean difference, 1.96; 95% CI, -0.84-4.76; P=0.17) or soluble suppression of tumorigenesis-2 (SMD, -0.45; 95% CI, -1.62-0.71; P=0.45) according to the random effects model. In conclusion, the present meta-analysis revealed that sacubitril/valsartan was able to effectively reduce the incidence of MACCEs, readmission and AHF in patients with AMI after revascularization without any obvious adverse events.
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Subsequently to the publication of the above article, the authors have realized that the immunohistochemical staining of CD31 in the 'AdNC group' portrayed in Fig. 7 on p. 1539 was published with an image that had been incorrectly captured from the 'Saline' group. This inadvertent error arose as a consequence of miscommunication between a pair of the authors on the paper when capturing the images. The authors have reexamined their original data and identified the correct data for the AdNC group in Fig. 7. The corrected version of Fig. 7, showing the correct CD31 staining data for the AdNC group, is shown below. Note that this error did not affect the major conclusions reported in the paper. All the authors have agreed to this corrigendum, and apologize to the Editor of International Journal of Molecular Medicine and to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 45: 15341542, 2020; DOI: 10.3892/ijmm.2020.4533].
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Background: Regulatory T (Treg) cells are a class of anti-inflammatory lymphocyte subpopulations with a potential protective effect against atherosclerosis, whereas T helper 17 (Th17) cells have been reported to possess proatherogenic activity. It was believed that disturbed circulating Treg/Th17 balance was associated with the onset and progression of atherosclerosis. This study is designed to probe the regulative action of serum Nod-like receptor protein 3 (NLRP3) on the Treg/Th17 balance in patients with atherosclerosis. Methods: Fifty-two patients with coronary atherosclerosis and stenosis degrees of more than 50% were assigned to the coronary artery disease (CAD) group, and an equal number of people without coronary atherosclerosis were assigned to the control group (assessed by coronary angiography). Peripheral blood mononuclear cells (PBMCs) from two group patients were extracted and cultivated. The calculation of the Treg/Th17 ratio and quantitative analysis of the Treg and Th17 cell frequencies were performed through flow cytometry. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was executed for the quantitative mRNA detection of the fork head-winged helix transcription factor (Foxp3) and the retinoic acid-related orphan nuclear receptor C (RORC) in PBMCs. Enzyme-linked immunosorbent assays were applied to measure the serum level of NLRP3, interleukin (IL)-10, IL-1 ß , IL-17A, IL-23, and transforming growth factor (TGF)- ß 1. Additionally, the connection between serum Treg/Th17 ratio and NLRP3 levels was analyzed using the Pearson correlation coefficient. Results: The baseline parameters, including sex, age, or blood biochemical indices had no difference in both groups (p > 0.05). The CAD group showed higher Th17 cell frequency, lower Treg cell frequency, and a lower Treg/Th17 ratio when compared to the control (p < 0.05). Consistent with the variation in the T-cell subset ratio, in patients with atherosclerosis, the Th17-cell-related transcription factor RORC showed a markedly higher mRNA level (p < 0.05), conversely, the mRNA expression of the Treg cell-related transcription factor Foxp3 was notably reduced (p < 0.05). Similarly, the serum levels of NLRP3, IL-17A, IL-1, and IL-23 were significantly enhanced in CAD group but IL-10 and TGF- ß 1 were reduced (p < 0.05). Additionally, a negative correlation was found between NLRP3 and the Treg/Th17 ratio (r = -0.69, p < 0.001). Conclusions: Due to the potential impact on the serum Treg/Th17 ratio, NLRP3 may act as an aggravator in the onset and progression of atherosclerotic disease.
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ABSTRACT: Although inflammation plays an important role in myocardial ischemia/reperfusion injury (MI/RI), an anti-inflammatory treatment with a single target has little clinical efficacy because of the multifactorial disorders involved in MI/RI. MicroRNAs (miR-24) can achieve multitarget regulation in several diseases, suggesting that this factor may have ideal effects on alleviation of MI/RI. In the present study, bioinformatics method was used to screen potential therapeutic targets of miR-24 associated with MI/RI. Three days before ischemia/reperfusion surgery, rats in the ischemia/reperfusion, miR-24, and adenovirus-negative control groups were injected with saline, miR-24, and adenovirus-negative control (0.1 mL of 5 × 109 PFU/mL), respectively. Myocardial enzymes, myocardial infarct size, cardiac function, and the possible molecular mechanism were subsequently analyzed. In contrast to the level of S100A8, the level of miR-24 in myocardial tissue was significantly reduced after 30 minutes of ischemia followed by reperfusion for 2 hours. Overexpression of miR-24 reduced the myocardial infarction area and improved the heart function of rats 3 days after MI/RI. Moreover, miR-24 inhibited infiltration of inflammatory cells in the peri-infarction area and decreased creatine kinase myocardial band and lactate dehydrogenase release. Interestingly, miR-24 upregulation reduced S100A8 expression, followed by inhibition of toll-like receptor 4/MyD-88/nuclear factor-k-gene binding signaling activation. In conclusion, miR-24 can alleviate MI/RI via inactivation of the S100A8/toll-like receptor 4/MyD-88/nuclear factor-k-gene binding signaling pathway.
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Calgranulina A/metabolismo , MicroRNAs/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Calgranulina A/genética , Modelos Animais de Doenças , Masculino , MicroRNAs/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Ratos Sprague-Dawley , Transdução de Sinais , Função Ventricular EsquerdaRESUMO
Objective: The diagnostic performance of soluble suppression of tumorigenicity (sST2) in heart failure (HF) had been investigated in multiple studies, but the results were inconsistent. This meta-analysis evaluated the diagnostic value of sST2 in HF. Methods: Pubmed, Web of Science, Embase, and Cochrane Library databases were searched until March 2021. Cohort studies or case-control studies relevant to the diagnostic value of sST2 in HF were screened, and true positive (TP), false positive (FP), false negative (FN), and true negative (TN) data were extracted for calculating sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). The quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS), the threshold effect was determined by calculating Spearman correlation coefficients and summary receiver operating characteristic (SROC) curve patterns, the heterogeneity was evaluated using the I 2 statistic and the Galbraith radial plot, and sensitivity analysis was also performed. Deeks' test was used to assess publication bias. Results: A total of 11 studies from 10 articles were included in this meta-analysis. The Spearman correlation coefficient was 0.114, p = 0.739, and the SROC curve did not show a "shoulder-arm" shape, which suggests that there was no threshold effect, but study heterogeneity existed because of non-threshold effects. The combined sensitivity was 0.72 [95% confidence interval (CI): 0.65-0.78], specificity was 0.65 (95% CI: 0.45-0.81), PLR was 1.75 (95% CI: 1.33-2.31), NLR was 0.48 (95% CI: 0.37-0.63), DOR was 3.63 (95% CI: 2.29-5.74), and AUC was 0.75. The Deeks' test suggested no significant publication bias in the included studies (P = 0.94). Conclusion: sST has some diagnostic value in HF, but this should be further evaluated in additional studies with rigorous design and high homogeneity.
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Fluvastatin, a traditional fat-decreasing drug, is widely used for curing cardiovascular disease. Previous reports demonstrated that fluvastatin pretreatment protected against myocardial ischemia/reperfusion (I/R) by inhibiting TLR4 signaling pathway and/or reducing proinflammatory cytokines. However, whether fluvastatin has a cardioprotective effect against apoptosis and autophagy remains unknown. This study aims to evaluate whether the cardioprotective role of fluvastatin in I/R is mediated by high-mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4) pathway via anti-apoptotic and anti-autophagic functions. Sprague-Dawley rats were anesthetized, artificially ventilated and subjected to 30 min of coronary occlusion, followed by 4 h of reperfusion. The animals were randomized into four groups: (i) Sham operation; (ii) I/R; (iii) I/R + low-dosage fluvastatin (10 mg/kg); and (iv) I/R + high-dosage fluvastatin (20 mg/kg). After reperfusion, the hemodynamic parameters, myocardial infarct size, structural alteration of myocardium, apoptosis index, pro-inflammatory cytokine production, Beclin-1, Light chain 3 (LC3), HMGB1, TLR4 and Nuclear factor kappa B (NF-κB) protein levels were measured and recorded. It was found that fluvastatin preconditioning improved left ventricular dysfunction, reduced HMGB1/TLR4/NF-κB expressions, and inhibited cardiomyocyte apoptosis, autophagy, and inflammation reaction. Moreover, treatment with fluvastatin ameliorated myocardial injury by reducing infarct size, causing less damage to cardiac structure, downregulating autophagy-related protein expression and releasing pro-inflammation mediators. Our findings indicate that fluvastatin exerts beneficial effects on cardiac ischemic damage, which may be associated with its anti-autophagic and anti-apoptotic functions via inhibition of HMGB1/TLR4-related pathway during I/R injury.
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Apoptose/fisiologia , Autofagia/fisiologia , Fluvastatina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cardiotônicos/metabolismo , Cardiotônicos/farmacologia , China , Fluvastatina/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Masculino , Infarto do Miocárdio/metabolismo , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Although miR-327 had a protective effect on cardiomyocytes as described previously, the potential mechanism still needs further exploration. The aim of this study was to investigate the role and mechanism of miR-327 on oxidative stress in myocardial ischemia/reperfusion injury (MI/RI) process. Oxidative stress and cardiomyocytes injury were detected in rat model of MI/RI, hypoxia/reoxygenation (H/R), and tert-butyl hydroperoxide (TBHP) model of H9c2 cells. In vitro, downregulation of miR-327 inhibited both H/R- and TBHP-induced oxidative stress, and suppressed apoptosis. Meanwhile, fibroblast growth factor 10(FGF10) was enhanced by miR-327 knocked down, followed by the activation of p-PI3K and p-Akt, and the translocation of Nrf2. However, miR-327 overexpression performed with opposite effects. Consistent with the results in vitro, downregulation of miR-327 attenuated reactive oxygen species (ROS) generation as well as intrinsic apoptosis, and alleviated I/R injury. In conclusion, inhibition of miR-327 improved antioxidative ability and myocardial cell survival via regulating the FGF10/Akt/Nrf2 pathway.
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Myocardial ischemia/reperfusion injury (MIRI) may cause myocardial stunning, reperfusion arrhythmia, noreflow phenomenon and lethal reperfusion injury, which has a significant effect on the prognosis of patients undergoing thrombolytic agent therapy and percutaneous coronary intervention. Increasing evidence suggests that apoptosis, innate inflammation, oxidative stress, calcium overload and autophagy are involved in the pathogenesis of MIRI. Recent advancements in RNA sequencing technologies and genomewide analyses led to the finding of small noncoding RNAs (ncRNAs). ncRNAs modulate cellular processes such as signal transduction, transcription, chromatin remodeling and posttranscriptional modification. The effects of ncRNAs on cellular biology is more considerable than initially expected, and thus ncRNAs have gained increasing attention and focus in modern medical research. There are several types of ncRNAs, such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), which have been shown to regulate gene expression at the transcription, posttranscription and epigenetic levels. Dysregulation of ncRNAs, including miRNAs, lncRNAs and circRNAs, may participate in the molecular mechanisms of MIRI. The present review summarizes the characteristics and biological roles of miRNAs, lncRNAs and circRNAs, with particular emphasis on their role in MIRI, which show the novel complexity of ischemic hearts and may offer valuable insights into the pathogenesis of MIRI.