http://reposit.library.du.ac.bd:8080/xmlui/xmlui/handle/123456789/49 Tue, 07 Apr 2026 09:09:05 GMT 2026-04-07T09:09:05Z http://reposit.library.du.ac.bd:8080/xmlui/xmlui/handle/123456789/4723 Molecular Basis of the Pelvi-Ureteric Junction Obstruction in Children with Hydronephrosis SHADRUL ALAM, MOHAMMED ABSTRACT: Background: Pelvi-Ureteric Junction Obstruction (PUJO) represents a significant cause of congenital hydronephrosis that can lead to progressive renal damage if untreated. While the condition is well-characterized clinically, its molecular pathogenesis remains poorly understood. This study aimed to identify key genetic alterations in PUJO through comprehensive transcriptomic analysis. Methods: We conducted a prospective study from January 2016 to December 2023 involving 9 pediatric patients (18 tissue samples) undergoing Anderson-Hynes pyeloplasty. Paired samples were collected from stenotic PUJ segments and adjacent normal ureteral tissue. RNA sequencing was performed followed by bioinformatic analysis to identify differentially expressed genes (DEGs) and pathway enrichment. Clinical parameters including demographics, presentation, and postoperative outcomes were systematically recorded. Results: The cohort showed male predominance (3.5:1 ratio) with mean age 40.22±32.61 months and left-sided predominance (77.8%). Key clinical presentations included abdominal distension (55.6%) and urinary tract infections (33.3%). Postoperative complications occurred in 22.2% cases. Transcriptomic analysis revealed 590 significant DEGs (292 upregulated, 298 downregulated), with notable enrichment in neuroactive ligand-receptor interactions (141 genes) and olfactory transduction pathways (50 genes). Chromosomal analysis identified 29 enriched regions, particularly on chromosomes 19, 17, and 9. Key dysregulated genes included KRT8 (upregulated) and SEMA3F (downregulated), implicating defects in smooth muscle differentiation and ureteral development. Conclusion: This first Bangladeshi transcriptomic study of PUJO identifies distinct molecular signatures involving neural signaling, ion transport, and developmental pathways. The findings provide novel insights into PUJO pathogenesis and potential biomarkers for early diagnosis. These results establish a foundation for developing targeted therapies to prevent renal damage in affected children. This thesis is submitted for the degree of Doctor of Philosophy. Wed, 05 Nov 2025 00:00:00 GMT http://reposit.library.du.ac.bd:8080/xmlui/xmlui/handle/123456789/4723 2025-11-05T00:00:00Z http://reposit.library.du.ac.bd:8080/xmlui/xmlui/handle/123456789/4684 Impacts of pathogenic mutations and XmnI polymorphism on the severity of haemoglobin E β-thalassaemia patients in Bangladesh Aziz, Md. Abdul Background: Haemoglobin E β-thalassaemia is a common blood disorder in South Asia, especially Bangladesh. The disorder can range from mild and asymptomatic anemia to life-threatening anemia. Patients with asymptomatic anemia do not require blood transfusions in their lifetime. Mild Hb E beta thalassaemia patients require occasional blood transfusions. However, patients with life-threatening anemia need frequent blood transfusions. The presence of XmnI polymorphism with specific mutation led to a delay of blood transfusions, higher haemoglobin levels, better response to hydroxyurea treatment, and milder phenotypic presentation among Hb E β thalassaemia patients. Aims: The aim of this study is to examine how the HBB gene mutations and the XmnI polymorphism affect the severity and transfusion needs of haemoglobin E β thalassaemia patients. Methodology: In this study, a total of 360 Hb E β-thalassaemia patients were included. The seven common HBB mutations in Bangladesh were detected by amplification refractory mutation system (ARMS) method, and rare/novel mutations were detected by Sanger sequencing. Moreover, XmnI (PdmI) restriction site was detected by XmnI (PdmI) restriction enzyme digestion. Results: Among the subjects in this research, 62.5% (n=225) were regular transfusion dependent, 22.8% (n=82) were occasionally transfusion-dependent, 8.1% (n=29) were one-time transfusion patients, and 6.7% (n=24) were transfusion-independent patients. This study identified a total of thirteen pathogenic mutations among the 360 Hb E β thalassaemia patients. The most common mutation was IVS 1-5 (G>C), accounting for 57.8% (n=208) of cases, followed by Fr 41/42(-CTTT) 12.2% (n=44), codon 30 (G>C) 8.3% (n=30), Fr 8/9 (+G) 7.5% (n=27), codon 16 (-C) 3.9% (n=14), and codon 15 (G>A) 2.8% (n=10). The study also identified six rare mutations, including -90(C>T) 3.1% (n=11), IVS-I-130(G>A) 3.1% (n=11), IVS II-654 (C>T) 0.6% (n=2), and -30 (T>C) 0.3% (n=1), codon 14/15 (+G) 0.3% (n=1) and -29 (A>G) 0.3% (n=1). Of these, -29 (A>G) had not been reported previously in Bangladesh. Page | v This study found that those with codon 16 (-C) mutation required regular transfusions, while those with codon 30 (G>C) mutations had the least transfusion dependency (6.7%). Patients with codon 30 (G>C) mutations had the highest response to hydroxyurea therapy (76.7% (n=23)) (p=0.051), while patients with Codon 16 (-C) mutations had the lowest response (0% (n=14)) (p=0.057). Codon 16 (-C) mutation was associated with the least HbF (mean ± SD= 24.8±7.7%), while codon 30 (G>C) mutation was associated with the highest HbF (mean ± SD= 41.9±16.10%). Regarding XmnI polymorphism, Codon 16 (-C) mutation was associated with the highest wild type (-/-) (n=11) genotype (p=0.153), while codon 30 (G>C) mutation was associated with the highest homozygous mutated (+/+) (n=11) and the least wild type (-/-) (n=4) of XmnI polymorphism genotype (p=0.157). Conclusion: The outcomes of this study will be useful for developing treatment strategies involving HU therapy and for managing Hb E β-thalassemia patients in Bagladesh. This thesis is submitted for the degree of Doctor of Philosophy. Mon, 07 Jul 2025 00:00:00 GMT http://reposit.library.du.ac.bd:8080/xmlui/xmlui/handle/123456789/4684 2025-07-07T00:00:00Z http://reposit.library.du.ac.bd:8080/xmlui/xmlui/handle/123456789/4107 Expression and regulation of efflux transporters in chemoresistant breast, colon and ovarian cancer cells in Bangladeshi patients Deb Nath, Sudipta Chemotherapy is a cornerstone in cancer treatment, but multidrug resistance (MDR) poses a substantial challenge. Hyperactivity of efflux pumps is one of the vital reasons to confer MDR. P-GP, MRP1 and ABCG2- these key ABC efflux pumps collectively transport a spectrum of chemotherapeutic drugs out of cells. HIF1A, a master regulator, is also associated with cancer biology, influencing cellular invasion, angiogenesis and metabolism. HuR regulates the expression of various carcinogenic molecules by mRNA trafficking, stabilization and enhancement of protein translation as well. Thereby this study addresses a crucial research gap in Bangladeshi population by inspecting the expression patterns of P-GP, MRP1 and ABCG2 in chemoresistant breast, colorectal and ovarian tissues. This study also aimed to delve into the mechanisms of drug resistance, focusing on HIF1A and HuR driven overexpression of ABC transporters, thus leading to chemoresistance. In this prospective study, 57 (chemoresistant) and 57 (paired control) tissue samples from Bangladeshi cancer patients were processed for immunofluorescence staining. The data showed the consistent co-expression of P-GP, MRP1 and ABCG2 across all cases, suggesting a potential synergistic function of transporter proteins in chemoresistance. The observations from this study also revealed that HIF1A and HuR overexpress in chemoresistant tissues, suggesting their pivotal role in chemoresistance mechanisms across malignancies and potential as therapeutic targets in Bangladeshi population. This study also suggests a direct regulation of P-GP, MRP1 and ABCG2 transcription by HIF1A that binds to the 'CGTG' sequence in the promoter regions. Besides, HuR might facilitate posttranscriptional mRNA stabilization by interacting with AU-rich elements (AREs) in the 3'UTR regions of the ABC transporters. Inhibition of these interactions of HIF1A and HuR appears as a promising approach to reverse chemoresistance. Thus, this study offers constructive insights for designing more efficient treatment strategies. This thesis is submitted for the degree of Master of Philosophy. Sun, 20 Apr 2025 00:00:00 GMT http://reposit.library.du.ac.bd:8080/xmlui/xmlui/handle/123456789/4107 2025-04-20T00:00:00Z http://reposit.library.du.ac.bd:8080/xmlui/xmlui/handle/123456789/3591 Metabolomics Profiling for Amino Acidopathies of Infants in Hospital Based Settings in Bangladesh and Development of Easy-to-Use Kit for Disease Diagnosis and Monitoring Hossain, Md. Shawkat This study aimed to address the challenges associated with identifying inborn errors of metabolism (IEM) in resource-constrained environments, focusing on amino acid and galactose metabolism disorders in the Bangladeshi infant population. Liquid Chromatography Mass Spectrometry (LC-MS) is a robust diagnostic tool but faces limitations due to cost, complexity, and accessibility. Therefore alternative approaches, including enzyme assays, genetic testing, and metabolite profiling, were explored for effective IEM detection. In pursuit of an affordable diagnostic solution, a low-cost kit was developed for early detection and intervention of amino acid and galactose-related disorders. A validated HPLC-based method was established for accurate quantification of amino acids. The method exhibited strong linearity (R2 = 0.9999) and high accuracy (99.10% average recovery), establishing its suitability for amino acid analysis. Precision was confirmed through repeatability and intermediate precision tests, with low RSD values (0.30% to 1.53% and 0.23% to 0.66%, respectively). Amino acid cutoff ranges were determined for the Bangladeshi population using the validated HPLC method. Noteworthy variations in amino acid counts were observed in positive samples, emphasizing the importance of accurate cutoff values. A lateral flow paper-based diagnostic kit was designed for phenylalanine detection, offering a cost-effective means for phenylketonuria (PKU) monitoring. The kit demonstrated a minimum detection limit of 2 mg/dL, catering to PKU therapy needs. The study also concentrated on Galactosemia as a model disorder, underlining the necessity of early intervention. Molecular analysis of the GALT gene unveiled specific mutations in the Bangladeshi population, contributing to Galactosemia's molecular diversity. Evaluation of silent mutations' impact on splicing shed light on potential gene expression and protein function alterations, influencing Galactosemia outcomes. An easy-to-use lateral flow diagnostic kit for Galactosemia was developed, showing specificity for galactose and delivering rapid results within 5 minutes. Stability assessment revealed promising results at 2-8°C storage over a year, with signal degradation at higher temperatures, emphasizing proper storage conditions. The study highlights the potential of the HPLC method for amino acid detection, paving the way for accessible and cost-effective amino acidopathy detection facilities. The Galactosemia kit, with further refinement, holds promise for broader use. Insights into alternate GALT gene splicing patterns provide avenues for therapeutic exploration. Future research should fine-tune kits and establish precise phenylalanine and galactose cutoff ranges for the Bangladeshi population, contributing to improved IEM management. A DESSERTATION SUBMITTED TO THE UNIVERSITY OF DHAKA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN GENETIC ENGINEERING AND BIOTECHNOLOGY. Sun, 09 Feb 2025 00:00:00 GMT http://reposit.library.du.ac.bd:8080/xmlui/xmlui/handle/123456789/3591 2025-02-09T00:00:00Z