Highlights In this meta-analysis of 24 studies with 12882 confirmed COVID-19 patients, we assessed the association of comorbid liver disease, acute liver injury, and elevated liver enzymes with outcomes in COVID-19 hospitalized patients. Overall prevalence of pre-existing chronic liver disease and COVID-19-associated acute liver injury were 2.6% and 26.5%, respectively and elevated AST and ALT were 41.1% and 29.1%, respectively. In our study, COVID-19-associated acute liver injury was having 1.7 folds higher risk of poor outcomes. Elevated AST and ALT were also independently associated with higher odds of poor outcomes. These findings may help in early triage, close monitoring of the occurrence of liver injury, and careful use of drugs which can cause liver toxicity in COVID-19 patients.

Our data suggest that after MI, rBM-MSCs secrete paracrine factors in response to TNF-α and hypoxia that work together to manipulate the microenvironment and decrease inflammation. In addition, these signaling factors trigger angiogenic and migratory effects at the site of the infarct to promote myocardial healing and improve the cardiac function.

BRIL/IFITM5 is a membrane protein present almost exclusively in osteoblasts, which is believed to adopt a type III (N-out/C-out) topology. Mutations in IFITM5 cause OI type V, but the characteristics of the mutant protein and the mechanism involved are still unknown. The purpose of the current study was to re-assess the topology, localization, and biochemical properties of BRIL and compare it to the OI type V mutant in MC3T3 osteoblasts. Immunofluorescence labeling was performed with antibodies directed against BRIL N-or C-terminus. In intact cells, BRIL labeling was conspicuously detected at the plasma membrane only with the anti-C antibody. Detection of BRIL N-terminus was only possible after cell permeabilization, revealing both plasma membrane and Golgi labeling. Trypsinization of live cells expressing BRIL only cleaved off the C-terminus, confirming that it is a type II protein and that its Nterminus is intracellular. A truncated form of BRIL lacking the last 18 residues did not appear to affect localization, whereas mutation of a single leucine to arginine within the transmembrane segment abolished plasma membrane targeting. BRIL is first targeted to the endoplasmic reticulum as the entry point to the secretory pathway and rapidly traffics to the Golgi via a COPII-dependent pathway. BRIL was found to be palmitoylated and two conserved cysteine residues (C52 and C53) were critical for targeting to the plasma membrane. The OI type V mutant BRIL, having a five residue extension (MALEP) at its N-terminus, presented with exactly the same topological and biochemical characteristics as wild type BRIL. In contrast, the S42 > L mutant BRIL was trapped intracellularly in the Golgi. BRIL proteins and transcripts were equally detected in bone from a patient with OI type V, suggesting that the cause of the disease is a gain of function mediated by a faulty intracellular activity of the mutant BRIL.

Our current results suggest that hPD-MSCs could represent a viable and effective alternative to hBM-MSCs for translational studies in cardiocellular repair.