Although the treatment of myocardial infarction (MI) has improved considerably, it is still a worldwide disease with high morbidity and high mortality. Whilst there is still a long way to go for discovering ideal treatments, therapeutic strategies committed to cardioprotection and cardiac repair following cardiac ischemia are emerging. Evidence of pathological characteristics in MI illustrates cell signaling pathways that participate in the survival, proliferation, apoptosis, autophagy of cardiomyocytes, endothelial cells, fibroblasts, monocytes, and stem cells. These signaling pathways include the key players in inflammation response, e.g., NLRP3/caspase-1 and TLR4/MyD88/NF-κB; the crucial mediators in oxidative stress and apoptosis, for instance, Notch, Hippo/YAP, RhoA/ROCK, Nrf2/HO-1, and Sonic hedgehog; the controller of myocardial fibrosis such as TGF-β/SMADs and Wnt/β-catenin; and the main regulator of angiogenesis, PI3K/Akt, MAPK, JAK/STAT, Sonic hedgehog, etc. Since signaling pathways play an important role in administering the process of MI, aiming at targeting these aberrant signaling pathways and improving the pathological manifestations in MI is indispensable and promising. Hence, drug therapy, gene therapy, protein therapy, cell therapy, and exosome therapy have been emerging and are known as novel therapies. In this review, we summarize the therapeutic strategies for MI by regulating these associated pathways, which contribute to inhibiting cardiomyocytes death, attenuating inflammation, enhancing angiogenesis, etc. so as to repair and re-functionalize damaged hearts. 

https://www.nature.com/articles/s41392-022-00925-z.pdf

Signaling pathways and targeted therapy for myocardial infarction

DNA, a genetic material, has been employed in different scientific directions for various biological applications as driven by DNA nanotechnology in the past decades, including tissue regeneration, disease prevention, inflammation inhibition, bioimaging, biosensing, diagnosis, antitumor drug delivery, and therapeutics. With the rapid progress in DNA nanotechnology, multitudinous DNA nanomaterials have been designed with different shape and size based on the classic Watson-Crick base-pairing for molecular self-assembly. Some DNA materials could functionally change cell biological behaviors, such as cell migration, cell proliferation, cell differentiation, autophagy, and anti-inflammatory effects. Some single-stranded DNAs (ssDNAs) or RNAs with secondary structures via self-pairing, named aptamer, possess the ability of targeting, which are selected by systematic evolution of ligands by exponential enrichment (SELEX) and applied for tumor targeted diagnosis and treatment. Some DNA nanomaterials with three-dimensional (3D) nanostructures and stable structures are investigated as drug carrier systems to delivery multiple antitumor medicine or gene therapeutic agents. While the functional DNA nanostructures have promoted the development of the DNA nanotechnology with innovative designs and preparation strategies, and also proved with great potential in the biological and medical use, there is still a long way to go for the eventual application of DNA materials in real life. Here in this review, we conducted a comprehensive survey of the structural development history of various DNA nanomaterials, introduced the principles of different DNA nanomaterials, summarized their biological applications in different fields, and discussed the current challenges and further directions that could help to achieve their applications in the future.

The biological applications of DNA nanomaterials: current challenges and future directions

One of the novel interesting topics in the study of cardiovascular disease is the role of the oxidation system, since inflammation and oxidative stress are known to lead to cardiovascular diseases, their progression and complications. During decades of research, many complex interactions between agents of oxidative stress, oxidation, and antioxidant systems have been elucidated, and numerous important pathophysiological links to na number of disorders and diseases have been established. This review article will present the most relevant knowledge linking oxidative stress to vascular dysfunction and disease. The review will focus on the role of oxidative stress in endotheleial dysfunction, atherosclerosis, and other pathogenetic processes and mechanisms that contribute to the development of ischemic heart disease.

/pdf/oxidative-stress-in-ischemic-heart-disease-28o15edzn2.pdf

Oxidative Stress in Ischemic Heart Disease.

The heart as a target for deltamethrin toxicity: Inhibition of Nrf2/HO-1 pathway induces oxidative stress and results in inflammation and apoptosis.

The heme oxygenase (HO) enzyme system catabolizes heme to carbon monoxide (CO), ferrous iron, and biliverdin-IXα (BV), which is reduced to bilirubin-IXα (BR) by biliverdin reductase (BVR). HO activity is represented by two distinct isozymes, the inducible form, HO-1, and a constitutive form, HO-2, encoded by distinct genes (HMOX1, HMOX2, respectively). HO-1 responds to transcriptional activation in response to a wide variety of chemical and physical stimuli, including its natural substrate heme, oxidants, and phytochemical antioxidants. The expression of HO-1 is regulated by NF-E2-related factor-2 and counter-regulated by Bach-1, in a heme-sensitive manner. Additionally, HMOX1 promoter polymorphisms have been associated with human disease. The induction of HO-1 can confer protection in inflammatory conditions through removal of heme, a pro-oxidant and potential catalyst of lipid peroxidation, whereas iron released from HO activity may trigger ferritin synthesis or ferroptosis. The production of heme-derived reaction products (i.e., BV, BR) may contribute to HO-dependent cytoprotection via antioxidant and immunomodulatory effects. Additionally, BVR and BR have newly recognized roles in lipid regulation. CO may alter mitochondrial function leading to modulation of downstream signaling pathways that culminate in anti-apoptotic, anti-inflammatory, anti-proliferative and immunomodulatory effects. This review will present evidence for beneficial effects of HO-1 and its reaction products in human diseases, including cardiovascular disease (CVD), metabolic conditions, including diabetes and obesity, as well as acute and chronic diseases of the liver, kidney, or lung. Strategies targeting the HO-1 pathway, including genetic or chemical modulation of HO-1 expression, or application of BR, CO gas, or CO donor compounds show therapeutic potential in inflammatory conditions, including organ ischemia/reperfusion injury. Evidence from human studies indicate that HO-1 expression may represent a biomarker of oxidative stress in various clinical conditions, while increases in serum BR levels have been correlated inversely to risk of CVD and metabolic disease. Ongoing human clinical trials investigate the potential of CO as a therapeutic in human disease.

/pdf/heme-oxygenase-1-an-anti-inflammatory-effector-in-1x3nefr5.pdf

Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders

Cardiovascular disease, which can lead to angina and shortness of breath, remains one of the most serious threats to human health. Owing to its imperceptible symptoms, it is difficult to determine the pathogenesis and treatment methods for cardiovascular disease. Nuclear factor erythropoietin-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) is a protein found in all cells of the human body. It is activated, transferred to the nucleus, and bound to DNA by antioxidant response elements (AREs). As a regulator of the antioxidant system, it upregulates the expression of HO-1 to reduce oxidative stress. Nrf2/HO-1 also has the ability to modulate calcium levels to prevent ferroptosis, pyroptosis, autophagy, programmed cell necrosis, alkaliptosis, and clockophagy. In view of the importance of Nrf2/HO-1 in the regulation of homeostasis, this review summarizes current research on the relationship between cardiovascular disease and Nrf2/HO-1. Normal cardiovascular diseases, such as viral myocarditis and myocardial ischemia-reperfusion injury, have been treated with Nrf2/HO-1. Rheumatic heart disease, cardiac tumors, arteriosclerosis, arrhythmia, hypertensive heart disease, and myocardial infarction have also been treated during experiments. Research has demonstrated the clinical application of Nrf2/HO-1 in pediatric cardiovascular disease; further clinical trials will help elucidate the potential of the Nrf2/HO-1 signaling axis.

/pdf/the-nrf-2-ho-1-signaling-axis-a-ray-of-hope-in-2g937p5d0b.pdf

The Nrf-2/HO-1 Signaling Axis: A Ray of Hope in Cardiovascular Diseases.

In December 2019, pneumonia of unknown cause broke out, and currently more than 150 countries around the world have been affected. Globally, as of 5: 46 pm CET, 6 November 2020, the World Health Organization (WHO) had reported 48 534 508 confirmed cases of COVID-19, including 1 231 017 deaths. The novel coronavirus disease (COVID-19) outbreak, caused by the SARS-CoV-2 virus, is the most important medical challenge in decades. Previous research mainly focused on the exploration of lung changes. However, with development of the disease and deepening research, more and more patients showed cardiovascular diseases, even in those without respiratory symptoms, and some researchers have found that underlying cardiovascular diseases increase the risk of infection. Although the related mechanism is not thoroughly studied, based on existing research, we speculate that the interaction between the virus and its receptor, inflammatory factors, various forms of the stress response, hypoxic environment, and drug administration could all induce the development of cardiac adverse events. Interventions to control these pathogenic factors may effectively reduce the occurrence of cardiovascular complications. This review summarizes the latest research on the relationship between COVID-19 and its associated cardiovascular complications, and we also explore possible mechanisms and treatments.

Impact of Cardiovascular Diseases on COVID-19: A Systematic Review.

Tumor microenvironment (TME) is of great importance to regulate the initiation and advance of cancer. The immune infiltration patterns of TME have been considered to impact the prognosis and immunotherapy sensitivity in Head and Neck squamous cell carcinoma (HNSCC). Whereas, specific molecular targets and cell components involved in the HNSCC tumor microenvironment remain a twilight zone.Immune scores of TCGA-HNSCC patients were calculated via ESTIMATE algorithm, followed by weighted gene co-expression network analysis (WGCNA) to filter immune infiltration-related gene modules. Univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression were applied to construct the prognostic model. The predictive capacity was validated by meta-analysis including external dataset GSE65858, GSE41613 and GSE686. Model candidate genes were verified at mRNA and protein levels using public database and independent specimens of immunohistochemistry. Immunotherapy-treated cohort GSE159067, TIDE and CIBERSORT were used to evaluate the features of immunotherapy responsiveness and immune infiltration in HNSCC.Immune microenvironment was significantly associated with the prognosis of HNSCC patients. Total 277 immune infiltration-related genes were filtered by WGCNA and involved in various immune processes. Cox regression identified nine prognostic immune infiltration-related genes (MORF4L2, CTSL1, TBC1D2, C5orf15, LIPA, WIPF1, CXCL13, TMEM173, ISG20) to build a risk score. Most candidate genes were highly expressed in HNSCC tissues at mRNA and protein levels. Survival meta-analysis illustrated high prognostic accuracy of the model in the discovery cohort and validation cohort. Higher proportion of progression-free outcomes, lower TIDE scores and higher expression levels of immune checkpoint genes indicated enhanced immunotherapy responsiveness in low-risk patients. Decreased memory B cells, CD8+ T cells, follicular helper T cells, regulatory T cells, and increased activated dendritic cells and activated mast cells were identified as crucial immune cells in the TME of high-risk patients.The immune infiltration-related gene model was well-qualified and provided novel biomarkers for the prognosis of HNSCC. 

/pdf/a-meta-validated-immune-infiltration-related-gene-model-3rbuhzrw.pdf

Hanyu Lei

Papers

The Nrf-2/HO-1 Signaling Axis: A Ray of Hope in Cardiovascular Diseases.

Impact of Cardiovascular Diseases on COVID-19: A Systematic Review.

A meta-validated immune infiltration-related gene model predicts prognosis and immunotherapy sensitivity in HNSCC