Rare association of celiac disease with congenital heart disease

Celiac disease (CD) is an autoimmune enteropathy caused by exposure to dietary gluten in genetically predisposed individuals. CD is a multisystem disease involving gastrointestinal, hepatobiliary, nervous, hematologic, and cardiovascular systems. Few associations of congenital heart disease have been reported with CD. We report a case of an 8-year-old female, who was presented to the hospital with severe anemia and undernutrition. She had severe pallor, clubbing, hepatomegaly, and a Grade Ш systolic ejection murmur. Echocardiography revealed a large ostium secundum type of atrial septal defect and patent ductus arteriosus. The increased levels of serum IgA anti-tissue transglutaminase (anti-TTG) antibody have arisen suspicion of CD, which was confirmed after the histopathological study of the duodenal biopsy. We are reporting this case to highlight the rare association of the CD with congenital heart disease

Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell Line by Decreasing Half-Life of mRNA

One of the most frequent genetic aberrations in acute myeloid leukemia (AML) is chromosomal translocation between AML1/RUNX1 on chromosome 21 and ETO gene on chromosome 8 resulting in the expression of chimeric oncogene AML1-ETO. Although patients with t(8;21) translocation have good prognosis, 5-year survival is observed only in 50% of the cases. AML1-ETO translocation is usually accompanied by overexpression of mutant C-Kit, a tyrosine kinase, which contributes to uncontrolled proliferation of premature blood cells leading to relapse and poor prognosis. We illustrate the potential use of esculetin on leukemic cell line, Kasumi-1, bearing t(8;21) translocation and mutated C-Kit gene. Esculetin decreases the expression of AML1-ETO at both protein and transcript level within 24 hours of treatment. Half-life of AML1-ETO mRNA was reduced from 7 hours to 1.5 hours. Similarly half-life of C-Kit mRNA was reduced to 2 hours from 5 hours in esculetin treated cells. Esculetin also perturbed the expression of ectopically expressed AML1-ETO in U937 cells. The decreased expression of AML1-ETO chimeric gene was associated with increased expression of LAT1 and RUNX3 genes, targets of AML1. We envisage that discovery of a drug candidate which could target both these mutated genes would be a considerable breakthrough for future application

Biased eviction of variant histone H3 nucleosomes triggers biofilm growth in Candida albicans

ABSTRACT Candida albicans is an opportunistic human pathogen that colonizes the gastrointestinal and genitourinary tracts of healthy individuals. C. albicans yeast cells can switch to filamentous forms. On biotic and abiotic surfaces, the planktonic free-floating yeast cells often form biofilms, a multi-drug-resistant three-dimensional community of yeast and filamentous cells. While alterations in gene expression patterns during planktonic to biofilm growth transitions in C. albicans have been studied, the underlying molecular mechanisms largely remain unexplored. Previously, we identified a histone H3 variant (H3VCTG), which acts as a negative regulator of biofilm growth in C. albicans. In the current study, we performed genome-wide profiling of H3VCTG nucleosomes in C. albicans planktonic cells and found them to be enriched at promoter regions. In planktonic cells, H3VCTG-enriched regions are mostly devoid of histone H3 post-translational modifications that allow active transcription, thus strengthening the role of H3VCTG as a negative regulator of biofilm formation. By combining genome-wide transcriptional alterations, nucleosome positioning (MNase-seq), and DNA accessibility (ATAC-seq) assays, we show a significant reduction in the total number of nucleosomes in biofilm cells as compared to planktonic cells indicating a more open chromatin state during biofilm growth. Finally, we propose that H3VCTG-nucleosome eviction at promoters of biofilm-relevant genes in biofilm-grown cells contributes to achieve the open chromatin state by facilitating easy promoter access of master regulators (activators and repressors) for modulation of gene expression observed during growth phase transitions. IMPORTANCE Candida albicans lives as a commensal in most healthy humans but can cause superficial skin infections to life-threatening systemic infections. C. albicans also forms biofilms on biotic and abiotic surfaces. Biofilm cells are difficult to treat and highly resistant to antifungals. A specific set of genes is differentially regulated in biofilm cells as compared to free-floating planktonic cells of C. albicans. In this study, we addressed how a variant histone H3VCTG, a previously identified negative regulator of biofilm formation, modulates gene expression changes. By providing compelling evidence, we show that biased eviction of H3VCTG nucleosomes at the promoters of biofilm-relevant genes facilitates the accessibility of both transcription activators and repressors to modulate gene expression. Our study is a comprehensive investigation of genome-wide nucleosome occupancy in both planktonic and biofilm states, which reveals transition to an open chromatin landscape during biofilm mode of growth in C. albicans, a medically relevant pathogen

Demographic Pattern and Hospitalization Outcomes of Depression among 2.1 Million Americans with Four Major Cancers in the United States

Objective: To compare the prevalence of depression in the four most common cancers in the US and evaluate differences in demographics and hospital outcomes. Methods: This was a cross-sectional study using the Nationwide Inpatient Sample (2010⁻2014). We selected patients who had received ICD-9 codes of breast, lung, prostate, and colorectal cancers and major depressive disorder (MDD). Pearson’s chi-square test and independent sample t-test were used for categorical and continuous data, respectively. Results: MDD prevalence rate was highest in lung cancer (11.5%), followed by breast (10.3%), colorectal (8.1%), and prostate cancer (4.9%). Within colorectal and lung cancer groups, patients with MDD were significantly older (>80 years, p < 0.001) than non-MDD patients. Breast, lung, and colorectal cancer showed a higher proportion of female and Caucasian in the MDD group. Severe morbidity was seen in a greater proportion of the MDD group in all cancer types. The mean inpatient stay and cost were higher in the MDD compared to non-MDD group. Conclusion: Particular attention should be given to elderly, female, and to lung cancer patients with depression. Further studies of each cancer type are needed to expand our understanding of the different risk factors for depression as a higher proportion of patients had severe morbidity