551 research outputs found
UMSL Bulletin 2023-2024
The 2023-2024 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1088/thumbnail.jp
UMSL Bulletin 2022-2023
The 2022-2023 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1087/thumbnail.jp
Analytical validation of innovative magneto-inertial outcomes: a controlled environment study.
peer reviewe
Gut-brain interactions affecting metabolic health and central appetite regulation in diabetes, obesity and aging
The central aim of this thesis was to study the effects of gut microbiota on host energy metabolism and central regulation of appetite. We specifically studied the interaction between gut microbiota-derived short-chain fatty acids (SCFAs), postprandial glucose metabolism and central regulation of appetite. In addition, we studied probable determinants that affect this interaction, specifically: host genetics, bariatric surgery, dietary intake and hypoglycemic medication.First, we studied the involvement of microbiota-derived short-chain fatty acids in glucose tolerance. In an observational study we found an association of intestinal availability of SCFAs acetate and butyrate with postprandial insulin and glucose responses. Hereafter, we performed a clinical trial, administering acetate intravenously at a constant rate and studied the effects on glucose tolerance and central regulation of appetite. The acetate intervention did not have a significant effect on these outcome measures, suggesting the association between increased gastrointestinal SCFAs and metabolic health, as observed in the observational study, is not paralleled when inducing acute plasma elevations.Second, we looked at other determinants affecting gut-brain interactions in metabolic health and central appetite signaling. Therefore, we studied the relation between the microbiota and central appetite regulation in identical twin pairs discordant for BMI. Second, we studied the relation between microbial composition and post-surgery gastrointestinal symptoms upon bariatric surgery. Third, we report the effects of increased protein intake on host microbiota composition and central regulation of appetite. Finally, we explored the effects of combination therapy with GLP-1 agonist exenatide and SGLT2 inhibitor dapagliflozin on brain responses to food stimuli
Interrogating the interconnected biological networks in liver diseases reveals the core components of a perturbed homeostatic system.
This thesis explores the interplay between genetics, environment, and immunological regulation in metabolic associated fatty liver disease (MAFLD), metabolic steatohepatitis (MeSH), and hepatocellular carcinoma (HCC), focusing on liver response to dietary exposome and bone marrow hematopoietic stem and progenitor cells (HSPCs) activity. Using weighted gene co-expression network analysis (WGCNA), we assessed mRNA expression in murine models and human datasets, identifying conserved metabolic and immunological programs and discrepancies in immune responses. The heightened immune response in certain mouse models, reflective of bone marrow HSPCs response, is found protective and consistent with human data, emphasizing the crucial role of immune system-tumorigenesis interplay.
Investigating regulatory factors, we spotlight bile acids’ significance. Maintaining a robust immune response is linked to reduced liver tumor burden, with HSPC dietary response as a potential regulatory factor. While cholesterol homeostasis disruptions alone don’t stimulate HSPCs, when combined with disrupted bile acid homeostasis, they significantly impact HSPCs. Rescuing bile acid synthesis dampens HSPC activity, underscoring bile acids' regulatory role.
Our findings provide valuable insights into the intricate regulatory networks governing liver disease, presenting potential new avenues for research, including exploring bile acid metabolism’s direct regulation of bone marrow HSPCs, assessing the long-term impact of HSPC stimulation, and investigating liver cholesterol homeostasis’s effect on immunotherapy response. This research suggests exploration of minimal therapeutics targeting sensitive targets and context-driven interpretation in animal model extrapolation. Overall, our experimental approach shows potential in aiding the development of effective treatments for liver diseases, paving the way for future studies in this field
Effective Utilization of Molecular Genetic Screening of Patients with Sickle Cell Disease and Beta Thalassemia Major in Saudi Arabia
Hereditary blood diseases are prevalent in the Kingdom of Saudi Arabia. The majority of these blood disorders are sickle cell disease and β-thalassemia with variants located on the beta globin gene (HBB). Aim: To determine the profile of novel or previously reported causative mutations in more than 150 transfusion dependent individuals using TaqMan genotyping and next-generation DNA sequencing. In addition, I explored the genomic variation in a family with transfusion dependency but without a definitive genetic diagnosis related to HBB. I also attempted to detect unknown genetic variations in functionally related genes and applied in-silico analysis of the detected variants to propose candidate genes that may contribute to the severe etiology of thalassemia within a family. Methods: To identify HBB variants, I conducted Taqman genotyping tests using SCD, c.92+5G>C, c.92+1G>A, c.93-21G>A, c.27dupG, and c.118C>T as the most frequently identified HBB variants within the Saudi population. After that, targeted next generation sequencing was performed on samples with either negative or only heterozygous results for these variants. The use of different molecular techniques including MLPA alpha thalassemia, whole exome sequencing, cytoscan HD array, and whole genome sequencing was undertaken on samples that needed further investigation. Implementation of different data filtering approaches and several in-silico techniques were utilized to investigate the detected variants. Results: After Taqman genotyping of the 154 DNA samples, 100 samples were either homozygous or compound heterozygous for the most frequently known HBB variants. The rest of these samples were sequenced using targeted NGS and 20 different common and rare HBB variants were identified. Three out of the 154 samples did not have any apparent HBB mutation and further investigation was applied using additional molecular techniques. This led to the identification of two gene candidates, SMC5 and TALDO1, with possible novel associations in increasing the severity of clinical manifestation in transfusion-dependent patients with heterozygous pathogenic variant of beta thalassemia. Conclusion: Beta thalassemia is a heterogenous disease with a wide range of clinical severity and the steps towards identification of the underlying genetic cause of the phenotype is different from case to case and may require a combination of several molecular techniques. Therefore, the interaction of illness-causing variations with the rest of an individual's genome is crucial to gaining a complete understanding of the condition. Excellent detection rates in less time may be achieved with a specialized filtering technique and strategy, making this an option for primary laboratory workflow
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