Aging and diabetes drive the COVID-19 forwards; unveiling nature and existing therapies for the treatment.

Human SARS Coronavirus-2 (SARS-CoV-2) has infected more than 170 million people worldwide and resulted in more than 3.5 million deaths so far. The infection causes Coronavirus disease (COVID-19) in people of all age groups, notably diabetic and old age people, at a higher risk of infectivity and fatality. Around 35% of the patients who have died of the disease were diabetic. The infection is associated with weakening immune response, chronic inflammation, and potential direct pancreatic impairment. There seems to be a three-way association of the SARS-CoV-2 infection with diabetes and aging. The COVID-19 infection causes metabolism complications, which may induce diabetes and accelerate aging in healthy individuals. How does diabetes elevate the likelihood of the infection is not clearly understood. we summarize mechanisms of accelerated aging in COVID-19 and diabetes, and the possible correlation of these three diseases. Various drug candidates under different stages of pre-clinical or clinical developments give us hope for the development of COVID-19 therapeutics, but there is no approved drug so far to treat this disease. Here, we explored the potential of anti-diabetic and anti-aging natural compounds for the COVID-19 treatment. We have also reviewed different therapeutic strategies with plant-based natural products that may be used to cure patients infected with SARS-CoV-2 and post-infection syndrome.

Role of BRAFV600E in the first preclinical model of multifocal infiltrating myopericytoma development and microenvironment.

Myopericytoma (MPC) is a rare tumor with perivascular proliferation of pluripotent stem-cell-like pericytes. Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and diagnostic biomarkers of MPC are poorly understood. We discovered that 15% of benign MPCs (thyroid, skin; 3 of 20 samples) harbored BRAF(WT/V600E); 33.3% (1 of 3 samples) of BRAF(WT/V600E)-MPCs were multifocal/infiltrative/recurrent. Patient-MPC and primary MPC cells harbored BRAF(WT/V600E), were clonal and expressed pericytic-differentiation biomarkers crucial for its microenvironment. BRAF(WT/V600E)-positive thyroid MPC primary cells triggered in vitro (8.8-fold increase) and in vivo (3.6-fold increase) angiogenesis. Anti-BRAF(V600E) therapy with vemurafenib disrupted angiogenic and metabolic properties (~3-fold decrease) with down-regulation (~2.2-fold decrease) of some extracellular-matrix (ECM) factors and ECM-associated long non-coding RNA (LincRNA) expression, with no effects in BRAF(WT)-pericytes. Vemurafenib also inhibited (~3-fold decrease) cell viability in vitro and in BRAF(WT/V600E)-positive thyroid MPC patient-derived xenograft (PDX) mice (n = 5 mice per group). We established the first BRAF(WT/V600E)-dependent thyroid MPC cell culture. Our findings identify BRAF(WT/V600E) as a novel genetic aberration in MPC pathogenesis and MPC-associated biomarkers and imply that anti-BRAF(V600E) agents may be useful adjuvant therapy in BRAF(WT/V600E)-MPC patients. Patients with BRAF(WT/V600E)-MPC should be closely followed because of the risk for multifocality/recurrence.