The mechanism of cardiovascular diseases (CVDs) is complex and threatens human health. Cardiomyocyte death is an important participant in the pathophysiological basis of CVDs. Ferroptosis is a new type of iron-dependent programmed cell death caused by excessive accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS) and abnormal iron metabolism. Ferroptosis differs from other known cell death pathways, such as apoptosis, necrosis, necroptosis, autophagy and pyroptosis. Several compounds have been shown to induce or inhibit ferroptosis by regulating related key factors or signalling pathways. Recent studies have confirmed that ferroptosis is associated with the development of diverse CVDs and may be a potential therapeutic drug target for CVDs. In this review, we summarize the characteristics and related mechanisms of ferroptosis and focus on its role in CVDs, with the goal of inspiring novel treatment strategies.

Individuals in any country are badly impacted both economically and physically whenever an epidemic of infectious illnesses breaks out. A novel coronavirus strain was responsible for the outbreak of the coronavirus sickness in 2019. Corona Virus Disease 2019 (COVID-19) is the name that the World Health Organization (WHO) officially gave to the pneumonia that was caused by the novel coronavirus on February 11, 2020. The use of models that are informed by machine learning is currently a major focus of study in the field of improved forecasting. By displaying annual trends, forecasting models can be of use in performing impact assessments of potential outcomes. In this paper, proposed forecast models consisting of time series models such as long short-term memory (LSTM), bidirectional long short-term memory (Bi-LSTM), generalized regression unit (GRU), and dense-LSTM have been evaluated for time series prediction of confirmed cases, deaths, and recoveries in 12 major countries that have been affected by COVID-19. Tensorflow1.0 was used for programming. Indices known as mean absolute error (MAE), root means square error (RMSE), Median Absolute Error (MEDAE) and r2 score are utilized in the process of evaluating the performance of models. We presented various ways to time-series forecasting by making use of LSTM models (LSTM, BiLSTM), and we compared these proposed methods to other machine learning models to evaluate the performance of the models. Our study suggests that LSTM based models are among the most advanced models to forecast time series data.

Mitochondrial dysfunction is involved in the pathogenesis of various cardiovascular disorders. Although mitochondrial dynamics, including changes in mitochondrial fission and fusion, have been implicated in the development of cardiac hypertrophy, the underlying molecular mechanisms remain mostly unknown. Here, we show that NFATc3, miR-153-3p, and mitofusion-1 (Mfn1) constitute a signaling axis that mediates mitochondrial fragmentation and cardiomyocyte hypertrophy.

BACKGROUND: Cardiac hypertrophy and its associated remodeling are among the leading causes of heart failure. Lysine crotonylation is a recently discovered posttranslational modification whose role in cardiac hypertrophy remains largely unknown. NAE1 (NEDD8 [neural precursor cell expressed developmentally downregulated protein 8]-activating enzyme E1 regulatory subunit) is mainly involved in the neddylation modification of protein targets. However, the function of crotonylated NAE1 has not been defined. This study aims to elucidate the effects and mechanisms of NAE1 crotonylation on cardiac hypertrophy. METHODS: Crotonylation levels were detected in both human and mouse subjects with cardiac hypertrophy through immunoprecipitation and Western blot assays. Tandem mass tag (TMT)-labeled quantitative lysine crotonylome analysis was performed to identify the crotonylated proteins in a mouse cardiac hypertrophic model induced by transverse aortic constriction. We generated NAE1 knock-in mice carrying a crotonylation-defective K238R (lysine to arginine mutation at site 238) mutation (NAE1 K238R) and NAE1 knock-in mice expressing a crotonylation-mimicking K238Q (lysine to glutamine mutation at site 238) mutation (NAE1 K238Q) to assess the functional role of crotonylation of NAE1 at K238 in pathological cardiac hypertrophy. Furthermore, we combined coimmunoprecipitation, mass spectrometry, and dot blot analysis that was followed by multiple molecular biological methodologies to identify the target GSN (gelsolin) and corresponding molecular events contributing to the function of NAE1 K238 (lysine residue at site 238) crotonylation. RESULTS: The crotonylation level of NAE1 was increased in mice and patients with cardiac hypertrophy. Quantitative crotonylomics analysis revealed that K238 was the main crotonylation site of NAE1. Loss of K238 crotonylation in NAE1 K238R knock-in mice attenuated cardiac hypertrophy and restored the heart function, while hypercrotonylation mimic in NAE1 K238Q knock-in mice significantly enhanced transverse aortic constriction–induced pathological hypertrophic response, leading to impaired cardiac structure and function. The recombinant adenoviral vector carrying NAE1 K238R mutant attenuated, while the K238Q mutant aggravated Ang II (angiotensin II)–induced hypertrophy. Mechanistically, we identified GSN as a direct target of NAE1. K238 crotonylation of NAE1 promoted GSN neddylation and, thus, enhanced its protein stability and expression. NAE1 crotonylation–dependent increase of GSN promoted actin-severing activity, which resulted in adverse cytoskeletal remodeling and progression of pathological hypertrophy. CONCLUSIONS: Our findings provide new insights into the previously unrecognized role of crotonylation on nonhistone proteins during cardiac hypertrophy. We found that K238 crotonylation of NAE1 plays an essential role in mediating cardiac hypertrophy through GSN neddylation, which provides potential novel therapeutic targets for pathological hypertrophy and cardiac remodeling.

PIWI‐interacting RNAs (piRNAs) are recently discovered small non‐coding RNAs consisting of 24‐35 nucleotides, usually including a characteristic 5‐terminal uridine and an adenosine at position 10. PIWI proteins can specifically bind to the unique structure of the 3′ end of piRNAs. In the past, it was thought that piRNAs existed only in the reproductive system, but recently, it was reported that piRNAs are also expressed in several other human tissues with tissue specificity. Growing evidence shows that piRNAs and PIWI proteins are abnormally expressed in various diseases, including cancers, neurodegenerative diseases and ageing, and may be potential biomarkers and therapeutic targets. This review aims to discuss the current research status regarding piRNA biogenetic processes, functions, mechanisms and emerging roles in various diseases.

Reduction oxidation (REDOX) reaction is crucial in life activities, and its dynamic balance is regulated by ROS. Reactive oxygen species (ROS) is associated with a variety of metabolic diseases involving in multiple cellular signalling in pathologic and physiological signal transduction. ROS are the by-products of numerous enzymatic reactions in various cell compartments, including the cytoplasm, cell membrane, endoplasmic reticulum (ER), mitochondria, and peroxisome. ROS signalling is not only involved in normal physiological processes but also causes metabolic dysfunction and maladaptive responses to inflammatory signals, which depends on the cell type or tissue environment. Excess oxidants are able to alter the normal structure and function of DNA, lipids, and proteins, leading to mutations or oxidative damage. Therefore, excessive oxidative stress is usually regarded as the cause of various pathological conditions, such as cancer, neurodegeneration, cardiovascular diseases (CVDs), diabetes, and kidney diseases. Currently, it has been possible to detect diabetes and other cardiac diseases by detecting derivatives accompanied by oxidative stress in vivo as biomarkers, but there is no effective method to treat these diseases. In consequence, it is essential for us to seek new therapy targeting these diseases through understanding the role of ROS signalling in regulating metabolic activity, inflammatory activation, and cardiac diseases related to metabolic dysfunction. In this review, we summarize the current literature on REDOX and its role in the regulation of cardiac metabolism and inflammation, focusing on ROS, local REDOX signalling pathways, and other mechanisms.