Left atrial function index predicts poor outcomes in acute myocardial infarction patients treated with percutaneous coronary intervention.

Background and aims: The left atrial function index (LAFI) is an index that combines the left atrial emptying fraction, adjusted left atrial volume and stroke volume. The prognostic value of LAFI in acute myocardial infarction (AMI) patients treated with percutaneous coronary intervention (PCI) is unknown. This study aims to determine whether LAFI predicts prognosis in AMI patients treated with PCI. Methods: Patients with newly diagnosed AMI who were treated with PCI at Hunan Provincial People's Hospital from March 2020 to October 2021 were prospectively enrolled. All patients underwent transthoracic echocardiography (TTE) at baseline and follow-up. The endpoint events included rehospitalization due to unstable angina, nonfatal myocardial infarction, rehospitalization due to heart failure and cardiovascular death. Results: A total of 368 patients with AMI (92 women; mean age, 61.45 ± 11.91 years) were studied with a median follow-up of 14 ± 6.58 months. Sixty-nine patients had endpoint events. Patients who presented with events had a significantly lower LAFI than patients without events (34.25 ± 12.86 vs. 48.38 ± 19.42, P < 0.0001). Multivariate Cox analysis demonstrated that LAFI (HR = 0.97 [95% CI: 0.95; 0.99]; P = 0.012) and the Killip classification (HR = 1.51 [95% CI: 1.03; 2.22]; P = 0.034) were independently predictive of endpoint events. Kaplan-Meier survival curves showed that patients with LAFI ≤ 40.17 cm/ml/m2 had higher events than patients with LAFI > 40.17 cm/ml/m2 (HR = 8.53 [95% CI: 4.74; 15.35]; P < 0.0001). Conclusion: LAFI is a strong and independent predictor of adverse events and can be used for risk stratification in patients with AMI treated with PCI.

Effects of Dietary Inclusion of Asiaticoside on Growth Performance, Lipid Metabolism, and Gut Microbiota in Yellow-Feathered Chickens.

Excessive abdominal fat deposition in chickens is a major concern in the poultry industry. Nutritional interventions are a potential solution, but current options are limited. Asiaticoside (Asi), a herbal extract, has shown positive effects in animals, but its impact on poultry lipid metabolism is still unknown. In this study, the effects of dietary Asi on yellow-feathered chicken lipid metabolism and its potential mechanisms were investigated. A total of 120 chickens were randomly divided into three groups, with five replicates per group and 8 chickens per replicate. The chickens were fed a basal diet supplemented with 0, 0.01, or 0.05% Asi for 6 wk. The results showed that Asi down-regulated lipogenic gene expression and up-regulated lipid-breakdown-related genes in both the liver and fat tissues of the chickens, which resulted in a half reduction in abdominal fat while not affecting meat yield. Mechanistically, the hepatic and adipose PI3K/AKT pathway may be involved in Asi-induced fat loss in chickens as revealed by computer-aided reverse drug target prediction and gene expression analysis. Moreover, Asi ingestion also significantly modified the cecal microbiota of the chickens, resulting in a reduced Firmicutes to Bacteroidetes ratio and decreased abundance of bacteria positively correlated with abdominal fat deposition such as Ruminococcus, while increasing the abundance of bacteria inversely correlated with abdominal fat deposition such as Lactobacillus, Bacteroides, and Blautia. Collectively, these data suggest that Asi could ameliorate the abdominal fat deposition in yellow-feathered chickens, probably through modulating the PI3K/AKT pathway and gut microbiota function.

Effects of dietary supplementation of Anoectochilus roxburghii extract (ARE) on growth performance, abdominal fat deposition, meat quality, and gut microbiota in broilers.

The broiler industry frequently encounters 2 common problems: excessive deposition of abdominal fat and poor quality of meat. However, there are limited nutritional manipulation strategies to address these issues. While Anoectochilus roxburghii (Wall.) Lindl., a traditional Chinese herb, has been shown to have multiple beneficial effects in humans, its potential roles in broiler chickens remain unexplored. In this study, the effects of dietary supplementation with Anoectochilus roxburghii extract (ARE) on growth performance, abdominal fat deposition, meat quality, blood indices, and gut microbiota were investigated in yellow-feather broiler chickens. A total of 90 twenty-one-day-old yellow-feather broilers were randomly divided into 3 treatments, and each treatment included 5 replicates with 6 birds per replicate. Birds were fed a basal diet supplemented with 0, 0.15, or 0.30% ARE for 6 wk. The results showed that the inclusion of ARE in the diet did not have any significant effect on meat yield (P > 0.05). However, it did lead to a reduction in abdominal fat deposition and an improvement in meat quality (P < 0.05). Mechanistically, the addition of ARE inhibited lipid biosynthesis and enhanced lipid breakdown in both the liver and adipose tissue of the broilers. Furthermore, ARE supplementation increased the antioxidase activities in the muscle and serum of the broilers (P < 0.05). In addition, the supplementation of ARE optimized the diversity and composition of the cecal microbiota, particularly by lowering the ratio of Firmicutes to Bacteroidetes (P < 0.05). Moreover, the abundance of some bacteria that were positively correlated with abdominal fat deposition was reduced by ARE, and vice versa (P < 0.05). Collectively, the results suggest that ARE is a promising candidate as a feed additive for reducing abdominal fat deposition and improving meat quality in the broiler industry.

Left atrial function index predicts poor outcome in STEMI patients treated with percutaneous coronary intervention.

The prognostic value of the left atrial function index (LAFI) in acute ST segment elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention (PCI) is unknown. This study sought to determine whether the LAFI predicts prognosis in STEMI patients treated with PCI. Patients with newly diagnosed STEMI who were treated with PCI in Hunan Provincial People's Hospital from March 2020 to October 2020 were prospectively enrolled. All patients underwent transthoracic echocardiography at baseline and follow-up. The endpoint events included rehospitalization due to unstable angina, nonfatal myocardial infarction, rehospitalization due to heart failure and cardiovascular death. A total of 156 STEMI patients treated with PCI were studied with a median follow-up of 14 months. Forty-eight patients had endpoint events. The LAFI had the highest area under the receiver operating characteristic curve (AUC) predicting the endpoint events, with an AUC of 0.90 (95% CI 0.84-0.94). Multivariate Cox analysis demonstrated that only the LAFI (HR: 0.91, 95% CI 0.87-0.96, P < 0.0001) was independently predictive of endpoint events. Kaplan‒Meier survival curves showed that patients with an LAFI ≤ 42.25 cm/cc/m2 had more events than patients with an LAFI > 42.25 cm/cc/m2 (HR: 19.15, 95% CI 8.90-41.21, P < 0.001). The LAFI is a strong and independent predictor of events in STEMI patients treated with PCI.

5-Methoxyflavone ameliorates non-alcoholic fatty liver disease through targeting the cytochrome P450 1A1.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease that is closely related to obesity and metabolic disorders. 5-methoxyflavone (5-MF) is a flavonoid with DNA polymerase-ß inhibitory properties. In this study, we explored the effects of 5-MF on NAFLD and its potential mechanisms using oleic acid/palmitic acid-treated HepG2 cells and high-fat diet-fed C57BL/6J mice. Our results showed that 5-MF not only alleviated fat deposition and hepatic steatosis, but also improved oxidative damage. In addition, 5-MF has the effect of alleviating disorders of glucose metabolism and enhancing energy expenditure in HFD-induced obese mice. Mechanistically, reverse screening methods and molecular docking analysis were used in combination, and revealed that cytochrome P450 1A1 (CYP1A1) is the target for 5-MF. Further experiments showed that 5-MF ameliorated triglycerides deposition by inhibiting the enzyme activity and protein expression of CYP1A1. In conclusion, 5-MF provides a novel strategy for the prevention and treatment of high-fat-induced NAFLD.

Reducing Healthcare Employees' Burnout through Ethical Leadership: The Role of Altruism and Motivation.

Globally, employee burnout (EBO) is a black swan in healthcare management. Previous organizational management literature shows that EBO was often misunderstood by assuming it as a personal issue. However, the new definition by the World Health Organization (WHO) clearly indicates that EBO is an occupational phenomenon that places responsibility on organizations to manage it. Although recent evidence suggests ethical leadership (ELP) style may be important to mitigate EBO, shockingly, such relationships were not tested in healthcare systems, especially in low- and middle-income countries. Filling this knowledge gap in the existing body of knowledge, this study aimed to investigate the ELP-EBO relationship. To explain the underlying mechanism of how ELP reduces EBO, this study included two psychological factors as a mediator and a moderator: altruism (AL) and intrinsic motivation (IM). The data were obtained from hospital employees via a self-administered questionnaire (n = 289, paper-pencil method). A hypothetical framework was designed and tested for empirical validation through structural equation modeling (SEM). Empirical evidence confirmed that ELP reduces the risk of burnout among hospital employees, and AL mediates this relationship. The results also confirmed the conditional indirect role of IM in the above proposed mediated relationship. This study's outcomes can help hospital administration deal with EBO's epidemic in an ELP framework. Other, different implications have also been discussed in detail.

Discovery of New Inhibitors of eEF2K from Traditional Chinese Medicine Based on In Silico Screening and In Vitro Experimental Validation.

Eukaryotic elongation factor 2 kinase (eEF2K) is a highly conserved α kinase and is increasingly considered as an attractive therapeutic target for cancer as well as other diseases. However, so far, no selective and potent inhibitors of eEF2K have been identified. In this study, pharmacophore screening, homology modeling, and molecular docking methods were adopted to screen novel inhibitor hits of eEF2K from the traditional Chinese medicine database (TCMD), and then cytotoxicity assay and western blotting were performed to verify the validity of the screen. Resultantly, after two steps of screening, a total of 1077 chemicals were obtained as inhibitor hits for eEF2K from all 23,034 compounds in TCMD. Then, to verify the validity, the top 10 purchasable chemicals were further analyzed. Afterward, Oleuropein and Rhoifolin, two reported antitumor chemicals, were found to have low cytotoxicity but potent inhibitory effects on eEF2K activity. Finally, molecular dynamics simulation, pharmacokinetic and toxicological analyses were conducted to evaluate the property and potential of Oleuropein and Rhoifolin to be drugs. Together, by integrating in silico screening and in vitro biochemical studies, Oleuropein and Rhoifolin were revealed as novel eEF2K inhibitors, which will shed new lights for eEF2K-targeting drug development and anticancer therapy.

Effects of Dietary Inclusion of ß-Hydroxy-ß-Methylbutyrate on Growth Performance, Fat Deposition, Bile Acid Metabolism, and Gut Microbiota Function in High-Fat and High-Cholesterol Diet-Challenged Layer Chickens.

Excessive lipid deposition in layer chickens due to inappropriate feeding adversely affects egg production; however, nutritional manipulation methods to deal with this issue are still limited. ß-hydroxy-ß-methylbutyrate (HMB), a metabolite of L-leucine, was recently reported as a lipid-lowering nutrient in mice and pigs, although its role in layers had not been investigated. Here, we employed high-fat and high-cholesterol diet (HFHCD)-challenged growing layers as an obese model to explore HMB function in the regulation of lipid metabolism and the potential mechanisms involved. We found that dietary supplementation with (0.05% or 0.10%) HMB significantly reduced HFHCD-induced bodyweight growth in layers, mainly due to reduction in abdominal fat deposition. Mechanistically, HMB supplementation enhanced hepatic bile acid synthesis from cholesterol through elevating expression of Cyp7a1, a gene coding a key enzyme in bile acid synthesis. Furthermore, 16S rRNA gene sequencing revealed that HMB supplementation remodeled the diversity and composition of the layers' cecal microbiota, and the abundance of Bacteroidetes at the phylum level were especially affected. Correlation analysis further indicated a strong negative association between Bacteroidetes abundance and lipid metabolism-related parameters. Taken together, these data suggest that dietary HMB supplementation could improve abdominal fat deposition in layers, probably through modulating hepatic bile acid synthesis and gut microbiota function.

Association Between Circulating Cell-Free DNA Level at Admission and the Risk of Heart Failure Incidence in Acute Myocardial Infarction Patients.

Plasma cell-free DNA (cfDNA) was elevated in patients with acute myocardial infarction (AMI) or heart failure (HF). However, whether cfDNA could serve as a predictor for risk of HF after AMI remains unknown. In this study, we conducted a pilot prospective cohort study in which 98 AMI patients were enrolled from a single center to assess the association between cfDNA levels at admission and risk of HF in an AMI population. Patients with cfDNA above the median level (14.39 ng/mL) showed higher low-density lipoprotein cholesterol, cardiac troponin I (cTnI), and soluble suppression of tumorigenicity 2 (sST2) levels compared with patients below the median. cfDNA was positively correlated with cTnI (r = 0.377, p < 0.001) and sST2 (r = 0.443, p < 0.001). Within a median follow-up of about 345 days, 46 patients (52.6%) developed HF. Multivariate Cox analysis showed that a higher cfDNA (above the cutoff value: 9.227 ng/mL) was an effective risk predictor (C-index = 0.74, 95% confidence interval [CI]: 0.733-0.748) for HF incidence after AMI (adjusted hazard ratio [HR]: 2.805; 95% CI: 1.087-7.242; p = 0.033). Moreover, a linear association was observed between cfDNA and risk of HF incidence adjusted for by age, gender, and history of chronic kidney disease (p for linear trend = 0.044). Taken together, the cfDNA levels at admission are associated with the incidence of HF in AMI patients. A positive correlation between cfDNA and the fibrotic factor sST2 was proved, but the underlying mechanisms require further study.

Maternal High-Fructose Intake Activates Myogenic Program in Fetal Brown Fat and Predisposes Offspring to Diet-Induced Metabolic Dysfunctions in Adulthood.

Excess dietary fructose intake is a major public health concern due to its deleterious effect to cause various metabolic and cardiovascular diseases. However, little is known about the effects of high-fructose consumption during pregnancy on offspring metabolic health in adulthood. Here, we show that maternal consumption of 20% (w/v) fructose water during pregnancy does not alter the metabolic balance of offspring with a chow diet, but predisposes them to obesity, fatty liver, and insulin resistance when challenged by a high-fat diet. Mechanistically, diet-induced brown fat reprogramming and global energy expenditure in offspring of fructose-fed dams are impaired. RNA-seq analysis of the fetal brown fat tissue reveals that the myogenic pathway is predominantly upregulated in the fructose-treated group. Meanwhile, circulating fructose level is found to be significantly elevated in both fructose-fed dams and their fetuses. Importantly fructose gavage also acutely activates the myogenic program in mice brown fat. Together, our data suggest that maternal high-fructose intake impairs fetal brown fat development, resultantly attenuates diet-induced thermogenesis and causes metabolic disorders in adult offspring probably through inducing myogenic signature in brown fat at the fetal stage.

An Inclusive Leadership Framework to Foster Employee Creativity in the Healthcare Sector: The Role of Psychological Safety and Polychronicity.

Creativity at the level of employees is of utmost importance for every sector of an economy, with no exception to a healthcare system. The reason why employee creativity is important lies in the fact that employees have profound knowledge of their job and thus can serve as a source of meaningful innovation in an organization. Research shows that employee creativity is largely dependent on leadership. Corporate leaders significantly influence subordinates' behavior. However, with the economic development, globalization, and changing business environment, a traditional authoritative leadership style can no longer be effective in understanding employees' psychological needs to foster their creative behavior. In this regard, the role of inclusive leadership as an effective organizational management strategy was recently discussed in literature at different levels. It was also stated that an inclusive leader could foster employee creativity. However, such relationships in healthcare systems of developing economies have largely remained under-explored previously. We explored employee creativity in a healthcare context of a developing economy in an inclusive leadership framework to bridge such knowledge gaps. We also investigated the mediating roles of psychological safety and polychronicity in the above-stated relationship. We collected the data from hospital employees through a questionnaire (paper-pencil method). A hypothetical model was developed, which was tested through structural equation modeling in AMOS. Based upon the statistical outcomes, we found that an inclusive leadership style in a hospital can significantly foster employee creativity, whereas psychological safety and polychronicity mediate this relationship. This study offers different theoretical and practical insights, especially to a healthcare system. An important finding was that an inclusive leader can motivate the followers to be more creative. This finding is significant for a hospital because creative employees provide a hospital with a solid competitive base.

Dapagliflozin, sildenafil and their combination in monocrotaline-induced pulmonary arterial hypertension.

BACKGROUND: Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), can reduce cardiovascular events and mortality in patients with heart failure. A number of mechanisms have been proposed to explain the beneficial effects of SGLT2 inhibitors. The purpose of this study was to determine whether dapagliflozin can improve pulmonary vascular remodelling and the efficacy of dapagliflozin as an add-on therapy to sildenafil in rats with pulmonary arterial hypertension (PAH). METHODS: A monocrotaline (MCT)-induced PAH rat model was used in our study. MCT-injected rats were randomly divided into four groups and treated for 3 weeks with daily per os treatment with vehicle, dapagliflozin (1 mg/kg/day), sildenafil (25 mg/kg/day), or a combination of dapagliflozin (1 mg/kg/day) and sildenafil (25 mg/kg/day). Haemodynamic measurements, histological analysis, enzyme-linked immunosorbent assay and western blotting analysis were employed to detect the changes in PAH rats after treatments. RESULTS: Dapagliflozin significantly attenuated MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) in PAH rats. Dapagliflozin effectively decreased the thickening of pulmonary artery media and decreased the muscularization of pulmonary arterioles in PAH rats. Moreover, dapagliflozin attenuated nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in lung tissues and the levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in plasma. However, dapagliflozin as an add-on therapy to sildenafil in rats with PAH did not show a more pronounced beneficial effect on right ventricular systolic pressure and pulmonary vascular remodelling in MCT rats than sildenafil alone. CONCLUSIONS: Dapagliflozin reduces right ventricular systolic pressure and pulmonary vascular remodelling in a rat model of PAH. However, combination therapy with dapagliflozin and sildenafil was not more effective than monotherapy with sildenafil in PAH rats.

Employee Voice: A Mechanism to Harness Employees' Potential for Sustainable Success.

Listening to employees' concerns reduces their dissatisfaction, but moreover, for an organization to achieve sustainable success, employees must raise their creative voice and give their input in decision-making without the fear of rejection in a psychologically safe environment. Ethical leaders facilitate such a participative style of management. A bureaucratic culture, as is generally encountered in Pakistan's work settings, poses real challenges to those who dare to speak up, therefore the importance of ethical leadership, leader-member exchange (LMX), and psychological safety cannot be neglected as coping mechanisms to sustain the employee voice for mutual gains. To investigate ethical leadership's mediating mechanisms and boundary conditions on voice behavior, we examined a moderated mediation model with the leader-member exchange as a moderator and psychological safety as a mediator. Grounded in social exchange theory (SET), the current study uniquely posits and tests that employees feel psychologically safe in the presence of an ethical leader with whom they have high-quality social exchanges. Data were collected from 281 employees from the public corporations and private enterprises of the petroleum sector of Karachi. Results of the analysis, through SPSS and AMOS, revealed that psychological safety mediated the relationship of ethical leadership and voice behavior, while the indirect effect of ethical leadership on voice behavior (via psychological safety) is stronger for those employees who enjoy high-quality exchanges with ethical leaders. LMX was also found to moderate the relationship between ethical leadership and voice behavior. Contributions, recommendations, and limitations of the current study and further research areas are also discussed. The study offers practical insight on the mechanism of ethical leadership on employee voice behavior and recommends leaders to develop social exchanges to improve voice behavior for sustainable success.

Relationship between Green Leaders' Emotional Intelligence and Employees' Green Behavior: A PLS-SEM Approach.

The green leadership (GL) concept has significantly gained popularity over the last decade. Consequently, more research has been conducted on this emerging leadership concept, emphasizing leadership styles that promote the green environment so that sustainable goals can be achieved. In the present research, leaders' emotional intelligence (EI) is positioned as a mediating variable between GL and employees' green organizational citizenship behavior (GOCB). The data of this research comprised managerial and non-managerial staff from the manufacturing and service industries. A PLS-SEM was used to evaluate the relationship between the various factors among 422 employees. The empirical findings indicated that GL and GOCB had a favorable and robust relationship. The results of the study also suggested that a leader's EI mediates the influence of green leadership on their employees' green organizational citizenship behavior. Green leadership is essential in creating sustainable environmental behaviors among employees. It can strengthen leaders' EI, which successively helps them to garner positivity and foster an environment of mutual harmony and cooperation in the workplace to support pro-environmental policies. Overall, our study contributes to and advances previous studies and shows that green leadership plays a critical role in influencing a leader's own EI which, in turn, predicts the green OCB of their employees in the workplace.

The Relationship between Corporate Social Responsibility on Social Media and Brand Advocacy Behavior of Customers in the Banking Context.

This research study aims to investigate the relationship between corporate social responsibility (CSR)-related communication on social media and brand advocacy behavior of retail banking customers in a developing country. This study also proposes a dual mediating mechanism of customer engagement and customer-company identification in the above-proposed relationship. The data were collected from retail banking customers with the help of a self-administered questionnaire (n = 356). To test the hypothesized relationships, a theoretical model was developed in this study. For hypothesis testing, we used the structural equation modeling (SEM) technique in AMOS software. The empirical analysis results confirmed our theoretical assumption that the manifestation of CSR-related communication on social media by a bank significantly influenced the advocacy behavior of retail banking customers. Our study also confirmed the mediating function of customer engagement and customer-company identification. The findings of this study offer different implications for the banking sector. For example, our study highlights the critical role of CSR-related communication on social media for meaningful customer-brand relationships by promoting the advocacy behavior of customers.

Translatomics Probes Into the Role of Lycopene on Improving Hepatic Steatosis Induced by High-Fat Diet.

Liver is an important organ for fat metabolism. Excessive intake of a high-fat/energy diet is a major cause of hepatic steatosis and its complications such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Supplementation with lycopene, a natural compound, is effective in lowering triglyceride levels in the liver, although the underlying mechanism at the translational level is unclear. In this study, mice were fed a high-fat diet (HFD) to induce hepatic steatosis and treated with or without lycopene. Translation omics and transcriptome sequencing were performed on the liver to explore the regulatory mechanism of lycopene in liver steatosis induced by HFD, and identify differentially expressed genes (DEGs). We identified 1,358 DEGs at the translational level. Through transcriptomics and translatomics joint analysis, we narrowed the range of functional genes to 112 DEGs and found that lycopene may affect lipid metabolism by regulating the expression of LPIN1 at the transcriptional and translational levels. This study provides a powerful tool for translatome and transcriptome integration and a new strategy for the screening of candidate genes.

Human epididymis protein 4: a novel predictor of ischemic cardiomyopathy.

BACKGROUND: The prognostic value of human epididymis protein 4 (HE4) in patients with ischemic cardiomyopathy (ICM) is unknown. METHODS: A total of 103 patients with ICM were prospectively enrolled in this study from Hunan Provincial People's Hospital between February 2019 and June 2019. All patients were tested for HE4 levels at baseline and follow-up. Endpoints of the study included cardiovascular death and heart failure-related hospitalization. RESULTS: A total of 96 patients with ICM were included for analysis. After a mean follow-up period of 263 (153-313) days, cardiovascular events were observed in 45 patients. Serum HE4 levels in patients with events were significantly higher than those in patients without events [188.70 (113.35-326.82) pmol/L versus 92.90 (61.50-123.20) pmol/L, P < 0.001]. Multivariate Cox regression analysis revealed that HE4 [χ2: 9.602, hazard ratio (HR): 1.003, 95% confidence interval (CI): 1.001-1.005, P = 0.002] and age [χ2: 4.55, HR: 1.044, 95% CI: 1.003-1.085, P = 0.033] were independent predictors of events. After adjusting for age and sex, the risk of events in patients with HE4 > 100.2 pmol/L was higher than that in patients with HE4 ≤ 100.2 pmol/L [HR: 3.372, 95% CI: 1.409-8.065, P < 0.001]. CONCLUSION: HE4 is an independent predictor of cardiovascular death and heart failure-related rehospitalization in patients with ICM.

MiR-200a-3p Aggravates DOX-Induced Cardiotoxicity by Targeting PEG3 Through SIRT1/NF-κB Signal Pathway.

Doxorubicin (DOX) is a widely used cytotoxic drug whose application is limited by its severe side effects. Little was known regarding how to offset its side effects. Therefore this study aims to explore the role of miR-200a-3p in DOX-induced cardiotoxicity and its possible mechanism. DOX-induced myocardial injury rat models were established, which were then injected with miR-200a-3p inhibitor (miR-200a-3p suppression) to observe the effects of miR-200a-3p on cell proliferation, and apoptosis. Heart function and weights of rat models were also measured. Cardiomyocytes were induced by DOX, in which PEG3 knockdown or corresponding plasmids were transfected to assess the possible effect of PEG3 on cell activity. Dual luciferase reporter assay was applied to verify the binding of PEG3 with miR-200a-3p. Elevated levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and left ventricular end-diastolic pressure (LVEDP), as well as suppressed left ventricular systolic pressure (LVSP) and ± dp/dt max were showed in myocardial injury rat models. DOX induced myocardial injury and increased miR-200a-3p expression levels. miR-200a-3p inhibitor could partially attenuate DOX-induced cardiotoxicity in rat models, while PEG3 could regulate myocardial injury in DOX-treated cell models. miR-200a-3p, by targeting PEG3 through SIRT1/NF-κB signal pathway, regulated cell proliferation, inflammation and apoptosis of myocardiocytes. The results in current study demonstrated that miR-200a-3p regulates cell proliferation and apoptosis of cardiomyocytes by targeting PEG3 through SIRT1/NF-κB signal pathway. This result may provide a potential clue for the treatment of DOX-induced cardiotoxicity.

miR-520d suppresses rapid pacing-induced apoptosis of atrial myocytes through mediation of ADAM10.

MicroRNAs (miRNAs) play a key role in various pathological processes like atrial fibrillation (AF). However, the mechanisms remain unclear. Herein, this study was undertaken to probe the roles of ADAM10 and its targeting miR-520d in rapid pacing-induced apoptosis in atrial myocytes. In this study, the atrial myocytes grew adherently with irregular morphology. Immunofluorescence showed that more than 90% of atrial myocytes were α-sarcomeric actin (α-SCA) positive, indicating that the primary cells were positive for α-SCA staining and atrial myocytes were successfully isolated. The pacing atrial myocyte model was established after rapid pacing stimulation and we found the rapid pacing stimulation caused elevated ADAM10 and suppressed miR-520d. CCK-8 assay was applied for evaluation of cell viability, TUNEL staining for assessment of cell apoptosis and dual-luciferase reporter gene assay for verification of the targeting relationship between miR-520d and ADAM10. Overexpression of miR-520d or silencing of ADAM10 could enhance cell viability and reduce cell apoptosis in the rapid pacing-induced atrial myocytes. ADAM10 was a target gene of miR-520d. MiR-520d negatively targeted ADAM10, thereby promoting cell viability and inhibiting apoptosis in rapid pacing atrial myocyte model. In summary, miR-520d enhances atrial myocyte viability and inhibits cell apoptosis in rapid pacing-induced AF mouse model through negative mediation of ADAM10.

Long non-coding RNA KCNQ1OT1/microRNA-204-5p/LGALS3 axis regulates myocardial ischemia/reperfusion injury in mice.

Myocardial ischemia/reperfusion (IR) injury is one of the most prevalent cardiovascular diseases, known for its high mortality and morbidity worldwide. Based on pre-existing evidence, LGALS3 has been found to be closely associated with cardiac diseases. Hence, the objective of our study is to explore the potential function of KCNQ1OT1/microRNA-204-5p (miR-204-5p)/ LGALS3 axis on myocardial IR injury and the underlying mechanism. A myocardial IR injury mouse model was established in vivo and an in vitro cardiomyocyte model was induced by hypoxia/Reoxygenation exposure. Next, gain- and loss-of-function experiments were employed in order to measure the viability and apoptosis of cardiomyocytes and the area of ischemic infarct by CCK-8, TUNEL staining and Evans blue/TTC double staining. LGALS3 was found to be highly expressed in myocardial IR injury. The downregulation of LGALS3 resulted in the alleviation of myocardial IR injury in mouse models. In addition, KCNQ1OT1 could promote the LGALS3 expression by binding to miR-204-5p, which led to aggravated myocardial IR injury. In conclusion, KCNQ1OT1 binds to miR-204-5p to exacerbate myocardial IR injury in mice through the up-regulation of LGALS3, providing a novel insight for myocardial IR injury treatment.