COVID-19 Is an Endothelial Disease: Implications of Nitric Oxide.

Endothelial cells are a clinically important infection site for COVID-19, both as a mechanism for disease pathogenesis and as a therapeutic target. People with dysfunctional endothelium, defined by nitric oxide deficiency, appear to have a more severe disease course. As such, nitric oxide has therapeutic potential to mitigate COVID-19 severity. Inhaled nitric oxide appears to improve outcomes, although this strategy neglects systemic endothelium. Meanwhile, early studies have documented that endothelial protective medications, such as the administration of statins and ACE-inhibitors, are associated with less severe disease and reduced mortality. Importantly, these medications augment endothelial sources of nitric oxide, which may explain this effect.

Associastion of In-hospital Use of Statins, Aspirin, and Renin-Angiotensin-Aldosterone Inhibitors with Mortality and ICU Admission Due to COVID-19.

The exaggerated host response to Sars-CoV-2 plays an important role in COVID-19 pathology but provides a therapeutic opportunity until definitive virus targeted therapies and vaccines become available. Given a central role of endothelial dysfunction and systemic inflammation, repurposing ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, and aspirin has been of interest. In this retrospective, single-center study, we evaluated the primary outcomes of mortality and ICU admission in 587 hospitalized patients with documented COVID-19 with or without ACEIs, ARBs, statins, and aspirin. Atorvastatin was associated with reduced mortality, which persisted after adjusting for age, lockdown status, and other medications (OR: 0.18. 95% CI: 0.06-0.49, P = 0.001). ACEIs were also associated with reduced mortality in the crude model (OR: 0.20, CI: 0.06-0.66, P = 0.008), as ACEIs and ARBs were combined as a single group (OR: 0.35, CI: 0.16-0.75, P = 0.007), although ARBs alone did not reach statistical significance. There was no association between any medications and risk of ICU admission. Aspirin only achieved a significant association of reduced mortality in a subgroup of patients with diabetes in the crude model (OR: 0.17, CI: 0.04-0.80, P = 0.02). The reduced mortality observed with atorvastatin is consistent with other literature, and consideration should be given to atorvastatin as a COVID-19 treatment. While there was suggested benefit of ACEIs and ARBs in the present study, other studies are varied and further studies are warranted to recommend employing these medications as a treatment strategy. Nevertheless, this study combined with others continues to give credibility that ACEIs and ARBs are safe to continue in the setting of COVID-19.

Exosomal Long Noncoding RNAs: Insights into Emerging Diagnostic and Therapeutic Applications in Lung Cancer.

Lung cancer is the most common cause of cancer-related deaths worldwide. Annually, millions of people die from lung cancer because of late detection and ineffective therapies. Recently, exosomes have been introduced as new therapeutic players with the potential to improve upon current diagnostic and treatment options. Exosomes are small membranous vesicles produced during endosomal merging. This allows for cell packaging of nucleic acids, proteins, and lipids and transfer to adjacent or distant cells. While exosomes are a part of normal intercellular signaling, they also allow malignant cells to transfer oncogenic material leading to tumor spread and metastasis. Exosomes are an interesting field of discovery for biomarkers and therapeutic targets. Among exosomal materials, lncRNAs have priority; lncRNAs are a class of noncoding RNAs longer than 200 base pairs. In the case of cancer, primary interest regards their oncogene and tumor suppressor functions. In this review, the advantages of exosomal lncRNAs as biomarkers and therapeutic targets will be discussed in addition to reviewing studies of their application in lung cancer.

Regional muscle and whole-body composition factors related to mobility in older individuals: a review.

PURPOSE: To describe previously reported locomotor muscle and whole-body composition factors related to mobility in older individuals. METHODS: A narrative review of the literature, including a combination of search terms related to muscle and whole-body composition factors and to mobility in older individuals, was carried out. Statistical measures of association and risk were consolidated to summarize the common effects between studies. RESULTS: Fifty-three studies were reviewed. Muscle and whole-body factors accounted for a substantial amount of the variability in walking speed, with coefficients of determination ranging from 0.30 to 0.47. Muscle power consistently accounted for a greater percentage of the variance in mobility than did strength. Risks associated with high fat mass presented a minimum odds ratio (OR) of 0.70 and a maximum OR of 4.07, while the minimum and maximum ORs associated with low lean mass were 0.87 and 2.30 respectively. Whole-body and regional fat deposits accounted for significant amounts of the variance in mobility. CONCLUSION: Muscle power accounts for a greater amount of the variance in the level of mobility in older individuals than does muscle strength. Whole-body fat accounts for a greater amount of the variance in level of mobility than does whole-body lean tissue. Fat stored within muscle also appears to increase the risk of a mobility limitation in older individuals.