Biology subjects

Munir, R.

Publications and source records attributed to Munir, R..

4 recordsLinked to original sources

bioRxiv2020

Revisiting the Association between Human Leukocyte Antigen and End-Stage Renal Disease

Multiple works have studied possible associations between human leukocyte antigen (HLA) alleles and end stage renal disease (ESRD) showing, however, contradictory and inconsistent results. Here, we revisit the association between ESRD and HLA antigens, comparing HLA polymorphism (at HLA-A, -B, -C, -DRB1, -DQB1 and DQA1 loci) in ESRD patients (n=497) and controls (n=672). Our data identified several HLA alleles that displayed a significant positive or negative association with ESRD. We also determined whether heterozygosity or homozygosity of the ESRD-associated HLA alleles at different loci could modify the prevalence of the disease. Few HLA allele combinations displayed significant associations with ESRD among which HLA-A*3-HLA-A*26 combination showed the highest strength of association (OR= 4.488, P[≤] 0.05) with ESRD. Interestingly, the age of ESRD onset was not affected by HLA allele combinations at different loci. We also performed an extensive literature analysis to determine whether the association of HLA to ESRD can be similar across different ethnic groups. Our analysis showed at least for certain alleles, HLA-A*11, HLA-DRB1*11, and HLA-DRB1*4, a significant association of HLA to ESRD in different ethnic groups. The findings of our study will help in determining possible protective or susceptible roles of various HLA alleles in ESRD.

molecular biology↗

bioRxiv2019

Abundance, fatty acid composition and saturation index of neutral lipids are significantly different between isogenic primary and metastatic colon cancer cell lines

Lipid droplets, the dynamic organelles that store triglycerides (TG) and cholesterol esters (CE), are highly accumulated in colon cancer cells. This work studies the TG and CE subspecies profile in colon carcinoma cells lines, SW480 derived from primary tumor, and SW620 derived from a metastasis of the same tumor. It was previously reported that the total TG and CE content is dramatically higher in SW620 cells; however, TG and CE subspecies profile has not been investigated in detail. The presented work confirms that total TG and CE content is significantly higher in SW620 cells. Moreover, the FA-composition of TGs is significantly altered in SW620 cells, with significant decrease in the abundance of saturated triglycerides. This resulted in significantly decreased TG saturation index in SW620 cells. The saturation index of CEs was also significantly decreased in SW620 cells. The saturation indices of some other major lipid classes were either similar or only moderately different between SW480 and SW620 cells. We also compared the expression of metabolic genes that may regulate these changes in the lipidomic profiles.

cancer biology↗

bioRxiv2018

Modulation of ADARs mRNA expression in congenital heart defect patients

Adenosine (A) to inosine (I) RNA editing, is a hydrolytic deamination reaction catalyzed by adenosine deaminase (ADAR) acting on RNA enzymes. RNA editing is a molecular process that involves the post-transcriptional modification of RNA transcripts. Interestingly, few studies have been carried out to determine the role of RNA editing in vascular disease. The current study found that in blood samples positive for congenital heart disease (CHD) ADAR1 and ADAR2 expression change at RNA level was opposite to each other. That is, an increase of ADAR1 mRNA was noticed in human CHD cases, whereas ADAR2 mRNA was vastly down-regulated. The increase in ADAR1 may be explained by the stress induced by CHD. The dramatic decrease in ADAR2 in CHD cases was unexpected and prompted further investigation into its effects on the heart. Therefore we performed expression analysis on a microarray data encompassing ischemic and non-Ischemic cardiomyopathy patient myocardial tissues. A strong down-regulation of ADAR2 was observed in both ischemic and especially non-ischemic cases. However, ADAR1 showed a mild increase in the case of non-ischemic myocardial tissues. To further explore the role of ADAR2 with respect to heart physiology. We selected a protein coding gene filamin B (FLNB). FLNB is known to play an important role in heart development. Although there were no observable changes in its expression, the editing levels of FLNB dropped dramatically in ADAR2-/- mice. We also performed miRNA profiling from ADAR2 -/- mice heart tissue revealed a decrease in expression of miRNAs. It is established that aberrant expression of these miRNAs is often associated with cardiac defects. This study proposes that sufficient amounts of ADAR2 might play a vital role in preventing cardiovascular defects.

molecular biology↗

bioRxiv2018

Patterns of recurrence after curative-intent surgery for pancreas cancer reinforce the importance of locoregional control and adjuvant chemotherapy.

IntroductionThe pattern of recurrence after surgical excision of pancreas cancer may guide alternative pre-operative strategies to either detect occult disease or need for chemotherapy. This study investigated patterns of recurrence after pancreatic surgery.\n\nMethodsRecurrence patterns were described in a series of resected pancreas cancers over a 2-year period and recurrence risk expressed as odds ratio (OR) with 95% confidence interval (C.I.). Survival was displayed by Kaplan-Meier curves.\n\nResultsOf 107 pancreas resections, 69 (65%) had pancreatic cancer. R0 resection was achieved in 21 of 69 (30.4%). Analysis was based on 66 patients who survived 30 days after surgery with median follow up 21 months. Recurrence developed in 41 (62.1%) patients with median time to first recurrence of 13.3 months (interquartile range 6.9, 20.8 months). Recurrence site was most frequently locoregional (n=28, 42%), followed by liver (n=23, 35%), lymph nodes (n=21, 32%), and lungs (n=13, 19%). In patients with recurrence, 9 of 41 had single site recurrence; the remaining 32 patients had more than one site of recurrence. Locoregional recurrence was associated with R+ resection (53% vs 25% for R+ vs R0, respectively; OR 3.5, 95% C.I. 1.1-11.2; P=0.034). Venous invasion was associated with overall recurrence risk (OR 3.3, 95% C.I. 1.1-9.4; P=0.025). In multivariable analysis, R-stage and adjuvant chemotherapy predicted longer survival.\n\nDiscussionThe predominant locoregional recurrence pattern, multiple sites of recurrence and a high R+ resection rate reflect the difficulty in achieving initial local disease control.

pathology↗