Correlation between serum ferritin level and liver function tests in thalassemic patients receiving multiple blood transfusions

Background:Multiple blood transfusions are the mainstay of thalassemic patients in order to combat the severe anemia. These frequent blood transfusions result in the excessive iron deposition, leading to multiple injuries to a variety of organs in the body. In response to these injuries, the levels of various enzymes are disturbed. The whole phenomena usually involve the interrelation of one parameter with some other. The present study aimed to estimate the levels of serum ferritin and hepatic enzymes and to find out any possible correlation between them in thalassemic patients receiving multiple blood transfusions.  Methods:A total number of 90 thalassemic patients of both sexes ranging from 10-15 years, receiving multiple blood transfusions were included in the present study. Blood samples from all the patients were withdrawn and analyzed for the values of serum ferritin, hemoglobin and hepatic enzymes (serum alanine transaminase, serum aspartate transaminase, serum alkaline phosphatase). Pearson correlation coefficient was applied to observe correlation between serum ferritin level and hepatic enzymes. A P value of ≤0.05 was considered statistically significant.Results:The overall values of serum ferritin, and hepatic enzymes (serum Alanine Transaminase, serum Aspartate Transaminase, serum Alkaline Phosphatase) were remarkably increased than their normal values. However, hemoglobin level was considerably decreased in thalassemic patients. A weak positive insignificant correlation was observed between serum ferritin with hepatic enzymes and hemoglobin in thalassemic patients.Conclusion:Multiple blood transfusions cause iron overload in the body, which in turn, lead to increased serum ferritin levels in thalassemic patients. High levels of hepatic enzymes are somewhat correlated to serum ferritin concentration. However, the exact reason of elevated levels is still unclear. Further detailed studies should be conducted in order to identify the exact mechanism behind this and to search for the promising correlations of various parameters in thalassemic patients receiving multiple blood transfusions.

A cGAS-dependent response links DNA damage and senescence in alveolar epithelial cells:A potential drug target in IPF

Alveolar epithelial cell (AEC) senescence is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Mitochondrial dysfunction including release of mitochondrial DNA (mtDNA) is a feature of senescence, which led us to investigate the role of the DNA-sensing GMP-AMP synthase (cGAS) in IPF, with a focus on AEC senescence. cGAS expression in fibrotic tissue from lungs of IPF patients was detected within cells immunoreactive for epithelial cell adhesion molecule (EpCAM) and p21, epithelial and senescence markers respectively. Submerged primary cultures of AECs isolated from lung tissue of IPF patients (IPF-AECs, n=5) exhibited higher baseline senescence than AECs from control donors (Ctrl-AECs, n=5-7), as assessed by increased nuclear histone 2AXγ phosphorylation, p21 mRNA and expression of senescence-associated secretory phenotype (SASP) cytokines. Pharmacological cGAS inhibition using RU.521 diminished IPF-AEC senescence in culture and attenuated induction of Ctrl-AEC senescence following etoposide-induced DNA damage. Short interfering RNA (siRNA) knockdown of cGAS also attenuated etoposide-induced senescence of the AEC line, A549. Higher levels of mtDNA were detected in the cytosol and culture supernatants of primary IPF- and etoposide-treated Ctrl-AECs when compared to Ctrl-AECs at baseline. Furthermore, ectopic mtDNA augmented cGAS-dependent senescence of Ctrl-AECs, whereas DNAse I treatment diminished IPF-AEC senescence. This study provides evidence that a self-DNA driven, cGAS-dependent response augments AEC senescence, identifying cGAS as a potential therapeutic target for IPF

A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications