Metformin prevents osteoblast-like potential and calcification in lung cancer A549 cells.

In spite of recent advances made in understanding its progression, cancer is still a leading cause of death across the nations. Molecular pathophysiology of these cancer cells largely differs depending on cancer types and even within the same tumor. Pathological mineralization/calcification is seen in various tissues including breast, prostate, and lung cancer. Osteoblast-like cells derived after trans-differentiation of mesenchymal cells usually drive calcium deposition in various tissues. This study aims to explore the presence of osteoblast-like potential in lung cancer cells and its prevention. ALP assay, ALP staining, nodule formation, RT-PCR, RT-qPCR, and western blot analysis experiments were carried out in lung cancer A549 cells to achieve said objective. Expressions of various osteoblast markers (e.g., ALP, OPN, RUNX2, and Osterix) along with osteoinducer genes (BMP-2 and BMP-4) were observed in A549 cells. Moreover, ALP activity and ability leading to nodule formation revealed the presence of osteoblast-like potential in lung cancer cells. Here, BMP-2 treatment increased expressions of osteoblast transcription factors such as RUNX2 and Osterix, enhanced ALP activity, and augmented calcification in this cell line. It was also observed that antidiabetic metformin inhibited BMP-2 mediated increase in osteoblast-like potential and calcification in these cancer cells. The current study noted that metformin blocked BMP-2 mediated increase in epithelial to mesenchymal transition (EMT) in A549 cells. The above findings for the first time unravel that A549 cells possess osteoblast-like potential which drives lung cancer calcification. Metformin might prevent BMP-2 induced osteoblast-like phenotype of the lung cancer cells with concomitant inhibition of EMT to inhibit lung cancer tissue calcification.

A Retrospective Analysis of Clinical Manifestations, Management and Outcome of Acute Respiratory Distress Syndrome Associated with Coronavirus Disease-2019 Infection in Children.

Background: Acute respiratory distress syndrome (ARDS) associated with COVID-19 in children is not well described in the literature, so this study was designed to assess the severity, clinical course, different treatment measures, and outcome of this group of patients. Patients and methods: This descriptive study was performed by retrospective chart review of children admitted in pediatric intensive care unit (PICU) in the age-group of 1 month to 12 years over the period of 6 months (July-December 2020) in a tertiary care pediatric COVID facility in eastern India. Severity of ARDS, ventilator settings, oxygenation and laboratory parameters, and outcomes were documented. Predictors associated with severe ARDS were evaluated. Results: Among 128 laboratory-confirmed pediatric COVID-19 cases admitted in PICU, 18 (14%) developed ARDS, 6 (33.3%) had severe ARDS, and 3 (16.6%) succumbed to death. Outcome was measured by median hospital stay [20 days (IQR 19, 21)], PICU stay [13 days (IQR 10, 16)], and 28-day ventilator-free days [14 days (IQR 13, 22)]. Half (n = 9) of our study cohort had different comorbidities and congenital heart disease being the most common (4, 22.2%). Median positive end-expiratory pressure requirement was 10 cm H2O (9, 11) for invasively ventilated children (n = 13, 72.2%) along with peak inspiratory pressure of 24 cm H2O (20, 29) and mean airway pressure of 17 cm H2O (14, 20). Median oxygenation index was 13.3 (10.5, 18.6). Nine (69.2%) out of 13 intubated children had undergone prone ventilation. C-reactive protein (CRP) and D-dimer levels were significantly high in children with severe ARDS alongside pSOFA and lung USG score. Conclusion: Incidence of ARDS in pediatric COVID-19 though less but is not rare. Elevated CRP, D-dimer values, and high lung USG scores were associated with severe ARDS. Those who died had significant comorbidity. How to cite this article: Sarkar M, Das B, Mahapatra MK, Roychowdhoury S, Das S, Konar MC. A Retrospective Analysis of Clinical Manifestations, Management and Outcome of Acute Respiratory Distress Syndrome Associated with Coronavirus Disease-2019 Infection in Children. Indian J Crit Care Med 2022;26(3):331-338.