Tissue repair strategies: What we have learned from COVID-19 in the application of MSCs therapy.

Coronavirus disease 2019 (COVID-19) infection evokes severe proinflammatory storm and pulmonary infection with the number of confirmed cases (more than 200 million) and mortality (5 million) continue to surge globally. A number of vaccines (e.g., Moderna, Pfizer, Johnson/Janssen and AstraZeneca vaccines) have been developed over the past two years to restrain the rapid spread of COVID-19. However, without much of effective drug therapies, COVID-19 continues to cause multiple irreversible organ injuries and is drawing intensive attention for cell therapy in the management of organ damage in this devastating COVID-19 pandemic. For example, mesenchymal stem cells (MSCs) have exhibited promising results in COVID-19 patients. Preclinical and clinical findings have favored the utility of stem cells in the management of COVID-19-induced adverse outcomes via inhibition of cytokine storm and hyperinflammatory syndrome with coinstantaneous tissue regeneration capacity. In this review, we will discuss the existing data with regards to application of stem cells for COVID-19.

Association between obstructive sleep apnea and cardiovascular diseases.

Obstructive sleep apnea (OSA) is a common respiratory disorder characterized by partial obstruction of upper respiratory tract and repetitive cessation of breathing during sleep. The etiology behind OSA is associated with the occurrence of intermittent hypoxemia, recurrent arousals and intrathoracic pressure swings. These contributing factors may turn on various signaling mechanisms including elevated sympathetic tone, oxidative stress, inflammation, endothelial dysfunction, cardiovascular variability, abnormal coagulation and metabolic defect ( e.g., insulin resistance, leptin resistance and altered hepatic metabolism). Given its close tie with major cardiovascular risk factors, OSA is commonly linked to the pathogenesis of a wide array of cardiovascular diseases (CVDs) including hypertension, heart failure, arrhythmias, coronary artery disease, stroke, cerebrovascular disease and pulmonary hypertension (PH). The current standard treatment for OSA using adequate nasal continuous positive airway pressure (CPAP) confers a significant reduction in cardiovascular morbidity. Nonetheless, despite the availability of effective therapy, patients with CVDs are still deemed highly vulnerable to OSA and related adverse clinical outcomes. A better understanding of the etiology of OSA along with early diagnosis should be essential for this undertreated disorder in the clinical setting.

Health influence of SARS-CoV-2 (COVID-19) on cancer: a review.

The novel coronavirus, namely, SARS-CoV-2 (COVID-19), broke out two years ago and has caused major global health issues. Adequate treatment options are still lacking for the management of COVID-19 viral infections. Many patients afflicted with COVID-19 may range from asymptomatic to severe symptomatic, triggering poor clinical outcomes, morbidity, and mortality. Cancer is one of the leading causes of death worldwide. It is pertinent to re-examine cancer prevalence during the COVID-19 pandemic to prevent mortality and complications. Understanding the impact of SARS-CoV-2 on cancer is key to appropriate healthcare measures for the treatment and prevention of this vulnerable population. Data was acquired from PubMed using key search terms. Additional databases were utilized, such as the Centers for Disease Prevention and Control, American Cancer Society (ACS), and National Cancer Institute (NCI). Cancer patients are more prone to SARS-CoV-2 infection and exhibit poor health outcomes, possibly due to a chronic immunosuppressive state and anticancer therapies. Male sex, older age, and active cancer disease or previous cancer are risk factors for COVID-19 infection, leading to possible severe complications, including morbidity or mortality. The speculated mechanism for potentially higher mortality or COVID-19 complications is through reduced immune system function and inflammatory processes through cancer disease, anticancer therapy, and active COVID-19 infection. This review includes prostate, breast, ovarian, hematologic, lung, colorectal, esophageal, bladder, pancreatic, cervical, and head and neck cancers. This review should help better maintain the health of cancer patients and direct clinicians for COVID-19 prevention to improve the overall health outcomes.

The E3 ubiquitin ligase MARCH2 protects against myocardial ischemia-reperfusion injury through inhibiting pyroptosis via negative regulation of PGAM5/MAVS/NLRP3 axis.

Inflammasome activation and pyroptotic cell death are known to contribute to the pathogenesis of cardiovascular diseases, such as myocardial ischemia-reperfusion (I/R) injury, although the underlying regulatory mechanisms remain poorly understood. Here we report that expression levels of the E3 ubiquitin ligase membrane-associated RING finger protein 2 (MARCH2) were elevated in ischemic human hearts or mouse hearts upon I/R injury. Genetic ablation of MARCH2 aggravated myocardial infarction and cardiac dysfunction upon myocardial I/R injury. Single-cell RNA-seq analysis suggested that loss of MARCH2 prompted activation of NLRP3 inflammasome in cardiomyocytes. Mechanistically, phosphoglycerate mutase 5 (PGAM5) was found to act as a novel regulator of MAVS-NLRP3 signaling by forming liquid-liquid phase separation condensates with MAVS and fostering the recruitment of NLRP3. MARCH2 directly interacts with PGAM5 to promote its K48-linked polyubiquitination and proteasomal degradation, resulting in reduced PGAM5-MAVS co-condensation, and consequently inhibition of NLRP3 inflammasome activation and cardiomyocyte pyroptosis. AAV-based re-introduction of MARCH2 significantly ameliorated I/R-induced mouse heart dysfunction. Altogether, our findings reveal a novel mechanism where MARCH2-mediated ubiquitination negatively regulates the PGAM5/MAVS/NLRP3 axis to protect against cardiomyocyte pyroptosis and myocardial I/R injury.

Clinical cardiovascular emergencies and the cellular basis of COVID-19 vaccination: from dream to reality?

OBJECTIVES: SARS-CoV-2 is responsible for the global COVID-19 pandemic, with little prevention or treatment options. More than 600 million mortalities have been documented from SARS-CoV-2 infection, with the majority of fatalities occurring among elderly patients (aged >65 years). A number of vaccines have been developed in an effort to restrain the rapid spread of SARS-CoV-2. Considering the widespread administration of these vaccines, substantial side or undesired effects in multiple organ systems have emerged, necessitating essential critical care. Herein, we tabulate the adverse cardiovascular responses resulting from COVID-19 vaccines. DESIGN OR METHODS: We searched PubMed for articles published through April, 2022, with the terms "SARS-CoV-2", "COVID-19", "cardiovascular", "SARS-CoV-2 vaccines", "COVID-19 vaccines", "myocarditis", "pericarditis", "thrombosis", "thrombocytopenia", "vaccine-induced thrombotic thrombocytopenia", "acute coronary syndrome", "myocardial infarction", "hypertension", "arrythmia", "postural orthostatic tachycardia syndrome", "Takotsubo cardiomyopathy", "cardiac arrest" and "death". We mainly selected publications from the past 3 years, but did not exclude widely referenced and highly regarded older publications. Besides, we searched the reference lists of articles identified by above search method and chose those we considered relevant. RESULTS: COVID-19 vaccines evoke rare but fatal thrombotic events, whereas messenger RNA\055based vaccines appear to be associated with risks of pericarditis/myocarditis, with the latter being more predominant in young adults following the second dose. Reports of other cardiovascular responses, including hypertension, arrhythmia, acute coronary syndrome, and cardiac arrest, have also been indicated. CONCLUSION: The undesired cardiovascular complications remain infrequent, giveng the large number of vaccinations inoculated to general population. And lower mortality takes precedence over the undesired cardiovascular complications.

Cell death regulation by MAMs: from molecular mechanisms to therapeutic implications in cardiovascular diseases.

The endoplasmic reticulum (ER) and mitochondria are interconnected intracellular organelles with vital roles in the regulation of cell signaling and function. While the ER participates in a number of biological processes including lipid biosynthesis, Ca2+ storage and protein folding and processing, mitochondria are highly dynamic organelles governing ATP synthesis, free radical production, innate immunity and apoptosis. Interplay between the ER and mitochondria plays a crucial role in regulating energy metabolism and cell fate control under stress. The mitochondria-associated membranes (MAMs) denote physical contact sites between ER and mitochondria that mediate bidirectional communications between the two organelles. Although Ca2+ transport from ER to mitochondria is vital for mitochondrial homeostasis and energy metabolism, unrestrained Ca2+ transfer may result in mitochondrial Ca2+ overload, mitochondrial damage and cell death. Here we summarize the roles of MAMs in cell physiology and its impact in pathological conditions with a focus on cardiovascular disease. The possibility of manipulating ER-mitochondria contacts as potential therapeutic approaches is also discussed.