Extracellular vesicles (EVs) hold great promise as therapeutic modalities due to their endogenous characteristics, however, further bioengineering refinement is required to address clinical and commercial limitations. Clinical applications of EV-based therapeutics are being trialed in immunomodulation, tissue regeneration and recovery, and as delivery vectors for combination therapies. Native/biological EVs possess diverse endogenous properties that offer stability and facilitate crossing of biological barriers for delivery of molecular cargo to cells, acting as a form of intercellular communication to regulate function and phenotype. Moreover, EVs are important components of paracrine signaling in stem/progenitor cell-based therapies, are employed as standalone therapies, and can be used as a drug delivery system. Despite remarkable utility of native/biological EVs, they can be improved using bio/engineering approaches to further therapeutic potential. EVs can be engineered to harbor specific pharmaceutical content, enhance their stability, and modify surface epitopes for improved tropism and targeting to cells and tissues in vivo. Limitations currently challenging the full realization of their therapeutic utility include scalability and standardization of generation, molecular characterization for design and regulation, therapeutic potency assessment, and targeted delivery. The fields' utilization of advanced technologies (imaging, quantitative analyses, multi-omics, labeling/live-cell reporters), and utility of biocompatible natural sources for producing EVs (plants, bacteria, milk) will play an important role in overcoming these limitations. Advancements in EV engineering methodologies and design will facilitate the development of EV-based therapeutics, revolutionizing the current pharmaceutical landscape.

/pdf/development-of-extracellular-vesicle-therapeutics-challenges-12mnb7vmn3.pdf

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities.

The COVID-19 outbreak and the sudden lockdown of society in March 2020 had a large impact on people's daily life and gave rise to concerns for the mental health in the general population. The aim of the study was to examine post-traumatic stress reactions related to the COVID-19 pandemic, the prevalence of symptom-defined post-traumatic stress disorder (PTSD), and factors associated with post-traumatic stress in the Norwegian population during the early stages of the COVID-19 outbreak. A survey was administered via social media channels, to which a sample of 4527 adults (≥18 years) responded. Symptom-defined PTSD was measured with the PTSD Checklist for the DSM-5. The items were specifically linked to the COVID-19 pandemic. We used the DSM-5 diagnostic guidelines to categorize participants as fulfilling the PTSD symptom criteria or not. Associations with PTSD were examined with single and multiple logistic regression analyses. The prevalence of symptom-defined PTSD was 12.5% for men and 19.5% for women. PTSD was associated with lower age, female gender, lack of social support, and a range of pandemic-related variables such as economic concerns, expecting economic loss, having been in quarantine or isolation, being at high risk for complications from COVID-19 infection, and having concern for family and close friends. In conclusion, post-traumatic stress reactions appear to be common in the Norwegian population in the early stages of the COVID-19 outbreak. Concerns about finances, health, and family and friends seem to matter.

https://www.mdpi.com/1660-4601/17/24/9210/pdf

Post-Traumatic Stress Disorder and Associated Factors during the Early Stage of the COVID-19 Pandemic in Norway.

Extracellular vesicles (EVs), including exosomes and microvesicles, are lipid bilayer particles naturally released from the cell. While exosomes are formed as intraluminal vesicles (ILVs) of the multivesicular endosomes (MVEs) and released to extracellular space upon MVE-plasma membrane fusion, microvesicles are generated through direct outward budding of the plasma membrane. Exosomes and microvesicles have same membrane orientation, different yet overlapping sizes; their cargo contents are selectively packed and dependent on the source cell type and functional state. Both exosomes and microvesicles can transfer bioactive RNAs, proteins, lipids, and metabolites from donor to recipient cells and influence the biological properties of the latter. Over the last decade, their potential roles as effective inter-tissue communicators in cardiovascular physiology and pathology have been increasingly appreciated. In addition, EVs are attractive sources of biomarkers for the diagnosis and prognosis of diseases, because they acquire their complex cargoes through cellular processes intimately linked to disease pathogenesis. Furthermore, EVs obtained from various stem/progenitor cell populations have been tested as cell-free therapy in various preclinical models of cardiovascular diseases and demonstrate unequivocally encouraging benefits. Here we summarize the findings from recent research on the biological functions of EVs in the ischemic heart disease and heart failure, and their potential as novel diagnostic biomarkers and therapeutic opportunities. 

Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications

Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications.

Creative Commons CC BY: This article is distributed under the terms of the Creative Commons Attribution

https://journals.sagepub.com/doi/pdf/10.1177/20563051211033821

Loneliness and Its Association With Social Media Use During the COVID-19 Outbreak

Myocardial infarction (MI) remains the most common cause of death worldwide. Many MI survivors will suffer from recurrent heart failure (HF), which has been recognized as a determinant of adverse prognosis. Despite the success of improved early survival after MI by primary percutaneous coronary intervention, HF after MI is becoming the major driver of late morbidity, mortality, and healthcare costs. The development of regenerative medicine has brought hope to MI treatment in the past decade. Mesenchymal stem cell (MSC)-derived exosomes have been established as an essential part of stem cell paracrine factors for heart regeneration. However, its regenerative power is hampered by low delivery efficiency to the heart. We designed, fabricated, and tested a minimally invasive exosome spray (EXOS) based on MSC exosomes and biomaterials. In a mouse model of acute myocardial infarction, EXOS improved cardiac function and reduced fibrosis, and promoted endogenous angiomyogenesis in the post-injury heart. We further tested the feasibility and safety of EXOS in a pig model. Our results indicate that EXOS is a promising strategy to deliver therapeutic exosomes for heart repair.

A Minimally Invasive Exosome Spray Repairs Heart after Myocardial Infarction.

The association between body mass index (BMI) and mortality of patients with percutaneous coronary intervention (PCI) is still controversial. We hope to explore whether the 'obesity paradox' really exists through this dose-response meta-analysis. PubMed, Embase and Cochrane databases were systematically searched for eligible studies up to April 2020. The random-effects restricted cubic spline models were used to evaluate the potential non-linear relationship between BMI and all-cause mortality of patients undergoing PCI. Fifteen studies were identified and included total 138 592 participants. The pooled hazard ratio of all-cause mortality was 0.60 (95% confidence interval: 0.45-0.82) when compared the highest category (mean = 33.32 kg m-2 ) of BMI with the lowest category (mean = 18.89 kg m-2 ). A non-linear U-shaped dose-response curve between BMI and the risk of all-cause mortality was found, with higher mortality rate at BMI lower than 27 kg m-2 and higher than 32 kg m-2 . The 'obesity paradox' does exist after PCI. The association between BMI and the risk of all-cause mortality for patients undergoing PCI is U shaped, with a nadir of risk at a BMI of 27 to 32 kg m-2 and the highest risk at patients with underweight. The relationship between other prognostic indicators and BMI is worthy of further research.

Body mass index and all-cause mortality in patients with percutaneous coronary intervention: A dose-response meta-analysis of obesity paradox.

Mental health and psychological impact of COVID-19: Potential high-risk factors among different groups.

The potential role of inflammation reaction in COVID-19 related posttraumatic stress disorder

http://www.heartrhythmjournal.com/article/S1547527123015229/pdf

Lijie Mi

Papers

A Minimally Invasive Exosome Spray Repairs Heart after Myocardial Infarction.

Body mass index and all-cause mortality in patients with percutaneous coronary intervention: A dose-response meta-analysis of obesity paradox.

Mental health and psychological impact of COVID-19: Potential high-risk factors among different groups.

The potential role of inflammation reaction in COVID-19 related posttraumatic stress disorder

Po-04-201 a case of pvc occurring right bundle branch block and pr interval prolonged during ethanol ablation via the coronary venous system