Medical Biochemistry Commons^™

Gut Pathophysiology In Mouse Models Of Social Behavior Deficits, Kyla Scott

Undergraduate Honors Theses

Autism spectrum disorders (ASD) encompass neurodevelopment disorders characterized by atypical patterns of development that impact multiple areas of functioning beginning in early childhood. The etiology of ASD is unknown and there are currently no preventative treatment options. Gastrointestinal symptoms are commonly associated comorbidities. The microbiota-gut-brain axis is a multidirectional communication chain that connects the central and enteric nervous system that relates brain function to peripheral intestinal functions. Changes within this axis have been postulated in ASD. For example, the “leaky gut theory” proposes that chronic inflammation is linked to alterations in the bacterial profiles of the gut microbiome and subsequent …

Small Extracellular Vesicles Modulated By Αvβ3 Integrin Induce Neuroendocrine Differentiation In Recipient Cancer Cells, Fabio Quaglia, Shiv Ram Krishn, George G. Daaboul, Srawasti Sarker, Raffaella Pippad, Josep Domingo-Domenech, Gaurav Kumar, Paolo Fortina, Peter Mccuee, William K. Kelly, Himisha Beltran, Qin Liu, Lucia R. Languinoa

Department of Biochemistry and Molecular Biology Faculty Papers

The ability of small extracellular vesicles (sEVs) to reprogram cancer cells is well established. However, the specific sEV components able to mediate aberrant effects in cancer cells have not been characterized. Integrins are major players in mediating sEV functions. We have previously reported that the αVβ3 integrin is detected in sEVs of prostate cancer (PαVβ3rCa) cells and transferred into recipient cells. Here, we investigate whether sEVs from -expressing cells affect tumour growth differently than sEVs from control cells that do not express αVβ3. We compared the ability of sEVs to stimulate tumour growth, using sEVs isolated from PrCa C4-2B cells …

The Determination Of Phosphorylation Of Nato3 By Pka, Miranda M. Regenold

Masters Theses

One of the leading regulators of neuronal cell differentiation in the CNS is the family of basic helix–loop–helix (bHLH) transcription factors. One of these proteins, Nato3, is associated with the formation of dopaminergic neurons. Transcription factors can be regulated by kinase activity, and in order to detect the associated change of phosphorylation of Nato3, we have generated Nato3 with specific epitope tags that allow for the detection and isolation of the Nato3 protein. Through subcloning techniques and a successful transformation of the Nato3 gene with the sequences of the 3X-Flag epitope and the Myc epitope into the pcDNA3.0 vector, we …

Alternative Polyadenylation Modulates Expression Of Pro-Fibrotic Proteins And Contributes To Lung Fibrosis, Junsuk Ko

Dissertations and Theses (Open Access)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease which affects about 5 to 8 million individuals in the world. Despite the high prevalence, there is currently no cure for IPF, and the cause of this disease is still unclear. Our laboratory and collaborators have shown that nudix hydrolase 21 (NUDT21, which is also known as cleavage factor 25, CFIm25) is a key regulator of alternative polyadenylation (APA). NUDT21 depletion causes 3’UTR shortening via APA leading to enhanced mRNA stability and protein translation. This NUDT21 reduction promotes tumor growth in glioblastoma by enhancing expression of oncogenes. Cancer and IPF share …

Lectin Properties Of Synthetically Produced Glucuronate, Alginate, And Related Boronates, Vanessa Angel

Honors Theses

In the nineteenth century, researchers discovered that some proteins had the ability to agglutinate red blood cells (Goldstein, 1980). These proteins were found mainly in the seeds of leguminous plants and were named phytohemagglutinins or hemagglutinins. Particular hemagglutinins were able to agglutinate red blood cells (RBCs) of a specific blood type. Now a days, these proteins are more widely known as Lectins. Lectins are proteinaceous macromolecules of nonimmune origin, capable of interacting with carbohydrates to form complexes (Goldstein, 1980). Lectins sources derive mainly from leguminous plants, animals, fruiting bodies of fungi, and bacteria. This research focuses on identifying the lectin …

Potential Role Of The Large Protein Titin In The Development Of Heart Failure, Mary M. Prickett

Senior Theses

I will be exploring the impact of the large protein Titin on heart failure with a preserved ejection fraction (HFpEF). It was hypothesized that myocardial Titin plays a significant role in the progression of HFpEF through isoform, N2BA and N2B, changes. It was hypothesized that an increase in the quantity of N2B Titin, less compliant, and a decrease in N2BA Titin, more compliant, will be observed as HF progresses, contributing to an increase in passive stiffness involved in heart contraction. I will cover a detailed report on the role of Titin in HFpEF and propose research methods to explore further.

Method And System For Identification Of Metabolites Using Mass Spectra, Hunter N. B. Moseley, William J. Carreer, Joshua Mitchell, Robert M. Flight

Molecular and Cellular Biochemistry Faculty Patents

A method and system is provided for mass spectrometry for identification of a specific elemental formula for an unknown compound which includes but is not limited to a metabolite. The method includes calculating a natural abundance probability (NAP) of a given isotopologue for isotopes of non-labelling elements of an unknown compound. Molecular fragments for a subset of isotopes identified using the NAP are created and sorted into a requisite cache data structure to be subsequently searched. Peaks from raw spectrum data from mass spectrometry for an unknown compound. Sample-specific peaks of the unknown com- pound from various spectral artifacts in …

Prostate Field Cancerization And Exosomes: Association Between Cd9, Early Growth Response 1 And Fatty Acid Synthase, Farideh Amirrad, Philip A. Pytak, Neda Sadeghiani-Pelar, Julie P. T. Nguyen, Emily L. Cauble, Anna C. Jones

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Intracapsular and well‑defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre‑malignancy. Such alterations in histologically normal tumor‑adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR‑1) and the lipogenic enzyme fatty acid synthase …

Development And Characterization Of A Wee1 Kinase Degrader, Zhengnian Li, Benika J Pinch, Calla M Olson, Katherine A Donovan, Radosław P Nowak, Caitlin E Mills, David A Scott, Zainab M Doctor, Nicholas A Eleuteri, Mirra Chung, Peter K Sorger, Eric S Fischer, Nathanael S Gray

Faculty, Staff and Students Publications

The G1/S cell cycle checkpoint is frequently dysregulated in cancer, leaving cancer cells reliant on a functional G2/M checkpoint to prevent excessive DNA damage. Wee1 regulates the G2/M checkpoint by phosphorylating CDK1 at Tyr15 to prevent mitotic entry. Previous drug development efforts targeting Wee1 resulted in the clinical-grade inhibitor, AZD1775. However, AZD1775 is burdened by dose-limiting adverse events, and has off-target PLK1 activity. In an attempt to overcome these limitations, we developed Wee1 degraders by conjugating AZD1775 to the cereblon (CRBN)-binding ligand, pomalidomide. The resulting lead compound, ZNL-02-096, degrades Wee1 while sparing PLK1, induces G2/M accumulation at 10-fold lower doses …

Identification Of The Kaposi's Sarcoma-Associated Herpesvirus (Kshv) Surface Glycoprotein Targets Of Human Kshv-Specific Neutralizing Antibody Responses, Yasaman Mortazavi

School of Biological Sciences: Dissertations, Theses, and Student Research

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the etiological agent of Kaposi’s sarcoma (KS), and is also associated with two B cell malignancies, primary effusion lymphoma and multicentric Castleman's disease. The distribution of KSHV varies globally with high prevalence in some areas of sub-Saharan Africa (SSA), where seroprevalence can be as high as 80%. It is estimated that nearly 44,000 new cases of KS emerge annually globally, with the highest incidents occurring in Africa, where KSHV is endemic. Currently, there is no prophylactic vaccine against KSHV, and efforts to develop prophylactic vaccines have been limited. …

Targeting Potential Drivers Of Covid-19: Neutrophil Extracellular Traps., Bj Barnes, Jm Adrover, A Baxter-Stoltzfus, A Borczuk, J Cools-Lartigue, Jm Crawford, J Daßler-Plenker, P Guerci, A Weber, M Egeblad, +13 Additional Authors

Journal Articles

No abstract provided.

Dysfunctional Mitochondrial Biogenesis: A Potential Underlying Cause For Metabolic Diseases, Caroline Ann Hunter

Theses, Dissertations and Capstones

Mitochondria are essential organelles that play crucial roles in many aspects of cellular homeostasis. More importantly, the mitochondria are home to the majority of the metabolic pathways within the cell and are responsible for producing most of the cell’s useable energy in the form of adenine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). In mammals, the majority of OXPHOS complex subunits are encoded by nuclear deoxyribonucleic acid (DNA); however, 13 core subunits essential for the function of OXPHOS complexes I, III, IV, and V are encoded in the mitochondrial (mt) DNA (mtDNA) and are synthesized within the mitochondria by its own …

Differentiating Peripherally-Located Small Cell Lung Cancer From Non-Small Cell Lung Cancer Using A Ct Radiomic Approach, Bihong T. Chen, Zikuan Chen, Ningrong Ye, Isa Mambetsariev, Jeremy Fricke, Ebenezer Daniel, George Wang, Chi Wah Wong, Russell C. Rockne, Rivka R. Colen, Mohd W. Nasser, Surinder K. Batra, Andrei I. Holodny, Sagus Sampath, Ravi Salgia

Journal Articles: Biochemistry & Molecular Biology

Lung cancer can be classified into two main categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which are different in treatment strategy and survival probability. The lung CT images of SCLC and NSCLC are similar such that their subtle differences are hardly visually discernible by the human eye through conventional imaging evaluation. We hypothesize that SCLC/NSCLC differentiation could be achieved via computerized image feature analysis and classification in feature space, as termed a radiomic model. The purpose of this study was to use CT radiomics to differentiate SCLC from NSCLC adenocarcinoma. Patients with primary lung cancer, …

G6pd Activity, Oxidative Stress, And Alu Methylation In Hbv-Related Hepatocellular Carcinoma, Watcharapong Jugnam-Ang

Chulalongkorn University Theses and Dissertations (Chula ETD)

Hepatocellular carcinoma (HCC) is the third leading caused cancer death in worldwide. The effective diagnosis markers are needed because of the late diagnosis and low survival time. G6PD is the rate-limiting enzyme in pentose phosphate pathway (PPP) that elevated in several cancers including HCC. Alu element is a common repetitive sequence in human genome, that its methylation alteration has been reported in cancers. In this study, we aimed to investigate the level of blood G6PD activity, the expression of G6PD in HCC liver tissues, the level of Alu methylation in PBMCs and clinicopathological parameters of HCC patients. Blood G6PD activity …

Precision Medicine And Actionable Alterations In Lung Cancer: A Single Institution Experience, Isa Mambetsariev, Yingyu Wang, Chen Chen, Sorena Nadaf, Rebecca Pharaon, Jeremy Fricke, Idoroenyi Amanam, Arya Amini, Andrea Bild, Peiguo Chu, Loretta Erhunmwunsee, Jae Kim, Janet Munu, Raju Pillai, Dan Raz, Sagus Sampath, Lalit Vora, Fang Qiu, Lynette M. Smith, Surinder K. Batra, Erminia Massarelli, Marianna Koczywas, Karen Reckamp, Ravi Salgia

Journal Articles: Biochemistry & Molecular Biology

OBJECTIVES: Oncology has become more reliant on new testing methods and a greater use of electronic medical records, which provide a plethora of information available to physicians and researchers. However, to take advantage of vital clinical and research data for precision medicine, we must initially make an effort to create an infrastructure for the collection, storage, and utilization of this information with uniquely designed disease-specific registries that could support the collection of a large number of patients.

MATERIALS AND METHODS: In this study, we perform an in-depth analysis of a series of lung adenocarcinoma patients (n = 415) with genomic …

Micrornas Orchestrate Pathophysiology Of Breast Cancer Brain Metastasis: Advances In Therapy, Ranjana K. Kanchan, Jawed A. Siddiqui, Sidharth Mahapatra, Surinder K. Batra, Mohd W. Nasser

Journal Articles: Biochemistry & Molecular Biology

Brain metastasis (BM) predominantly occurs in triple-negative (TN) and epidermal growth factor 2 (HER2)-positive breast cancer (BC) patients, and currently, there is an unmet need for the treatment of these patients. BM is a complex process that is regulated by the formation of a metastatic niche. A better understanding of the brain metastatic processes and the crosstalk between cancer cells and brain microenvironment is essential for designing a novel therapeutic approach. In this context, the aberrant expression of miRNA has been shown to be associated with BM. These non-coding RNAs/miRNAs regulate metastasis through modulating the formation of a metastatic niche …

Determining The Role Of Satellite Cells During Skeletal Muscle Adaptation, Davis A. Englund

Theses and Dissertations--Rehabilitation Sciences

Physical inactivity, advancing age, limb immobilization, degenerative diseases and various systemic diseases (many cancers, sepsis, HIV, COPD, kidney disease) all lead to skeletal muscle wasting. The loss of muscle mass is of major clinical importance because it leads to an increased risk for morbidity, disability, and the loss of independence; collectively contributing to a substantive increase in healthcare utilization and cost. The prevalence of cachexia (disease-induced muscle wasting) can reach as high as 80% in certain patient populations and the average cost per hospital stay is $4,641 more than in non-cachectic patients. Direct healthcare costs attributable to sarcopenia were estimated …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

Evaluation Of The Diagnostic Accuracy And Utility Of A New Dengue Rapid Diagnostic Test In Malaysia, Zhuo Lin Chong

Student Works (2020-2029)

Dengue is an emerging arboviral disease endemic to many tropical countries including Malaysia. Due to its unspecific symptoms, dengue diagnosis can only be confirmed through diagnostic tests. Existing laboratory-based dengue diagnostics like enzyme linked immunosorbent assay (ELISA) is accurate in detecting dengue non-structural protein-1 (NS1), and anti-dengue immunoglobulin M (IgM) and G (IgG); but is also more complicated and time-consuming. Commercially available dengue rapid immunochromatographic test (RIT) is efficient but less sensitive. A new dengue rapid diagnostic rest (RDT) using biosensors may be both efficient and accurate in diagnosing acute dengue. This study evaluated this new dengue NS1-based RDT and …

Pneumovirus Infections: Understanding Rsv And Hmpv Entry, Replication, And Spread, Jonathan T. Kinder

Theses and Dissertations--Molecular and Cellular Biochemistry

Pneumoviruses including human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are significant causes of respiratory tract infections globally. Children, elderly, and immunocompromised patients are at the greatest risk for developing severe infections, which can have devastating outcomes. Although these viruses are ubiquitous with significant impacts on human health, there are no antivirals or vaccines available. The only FDA approved therapy is a monoclonal antibody for RSV, given prophylactically during the infectious season, and this treatment is only available for high risk infants. The work presented in this thesis aims to increase our understanding of how these viruses enter, replicate, and …

The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz

Faculty, Staff and Students Publications

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling …

Mechanistic And Functional Shades Of Mucins And Associated Glycans In Colon Cancer, Ramesh Pothuraju, Shiv Ram Krishn, Shailendra K. Gautam, Priya Pai, Koelina Ganguly, Sanjib Chaudhary, Satyanarayana Rachagani, Sukhwinder Kaur, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucus serves as the chief protective barrier against pathogenic and mechanical insults in respiratory, gastrointestinal, and urogenital tracts. Altered mucin expression, the major component of mucus, in conjunction with differential glycosylation has been strongly associated with both benign and malignant pathologies of colon. Mucins and their associated glycans arbitrate their impact sterically as well as mechanically by altering molecular and microbial spectrum during pathogenesis. Mucin expression in normal and pathological conditions is regulated by nonspecific (dietary factors and gut microbiota) and specific (epigenetic and transcriptional) modulators. Further, recent studies highlight the impact of altering mucin glycome (cancer-associated carbohydrate antigens including …

Molecular Implications Of Muc5ac-Cd44 Axis In Colorectal Cancer Progression And Chemoresistance, Ramesh Pothuraju, Satyanarayana Rachagani, Shiv Ram Krishn, Sanjib Chaudhary, Rama Krishna Nimmakayala, Jawed A. Siddiqui, Koelina Ganguly, Imayavaramban Lakshmanan, Jesse L. Cox, Kavita Mallya, Sukhwinder Kaur, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Differential expression of mucins has been associated with several cancers including colorectal cancer (CRC). In normal physiological conditions, secretory mucin MUC5AC is not expressed in the colonic mucosa, whereas its aberrant expression is observed during development of colon cancer and its precursor lesions. To date, the molecular mechanism of MUC5AC in CRC progression and drug resistance remains obscure.

METHODS: MUC5AC expression was determined in colon tissue microarray by immunohistochemistry. A RNA interference and CRISPR/Cas9-mediated system was used to knockdown/knockout the MUC5AC in CRC cell lines to delineate its role in CRC tumorigenesis using in vitro functional assays and in …

Educational Needs Of Newly Diagnosed Cancer Patients In Learning About Cancer: A Qualitative Study In The Malaysian Urban Setting, Munisamy Murallitharan

Student Works (2020-2029)

Patients with chronic diseases such as cancer are able to have better outcomes if they understand about all aspects of the disease, develop the correct attitude to manage themselves and their disease better; and engage in preventive practices that can help them prevent worsening of disease or recurrence. Patient education is an intervention that has proven to be effective in different settings for this. However in the Malaysian cancer setting, the educational needs of patients are poorly understood. The aim of this study was to explore and understand the educational needs of newly diagnosed cancer patients in learning about cancer …

Telomere Shortening And Cellular Senescence Induced By Oxalate And Nephrolithiasis Urine In Hk-2 Cells, Kamonchanok Chuenwisad

Chulalongkorn University Theses and Dissertations (Chula ETD)

Kidney stone disease is a common urologic problem worldwide, especially in the tropics such as Thailand. It is known as a multifactorial condition, and aging increases the risk of stone development. The major type of stones is calcium oxalate (CaOx), and its formation is driven by increased urinary oxalate excretion and calcium oxalate monohydrate (COM) crystallization. Both oxalate and COM are known to induce reactive oxygen species (ROS) production and cause oxidative stress. Furthermore, patients with CaOx stone have increased extent of oxidative stress. In this study, we investigated the induction of cellular senescence and telomere shortening through oxidative stress …

Circulating-Tumor Dna And Cancer-Induced Gene Expression As Novel Liquid Biomarkers Of Liver Cancers, Pattapon Kunadirek

Chulalongkorn University Theses and Dissertations (Chula ETD)

Liver cancer is one of the most cancer-related mortality with high incidence worldwide. Hepatocellular carcinoma (HCC) is the most common liver cancer type. Currently, Liquid biopsy is known as a non-invasive biomarker tool that specifically represents tumor appearance, leading to improved patient outcomes. Therefore, the novel biomarkers of liquid biopsy in Thai HCC patients are still unexplored and needed for precision medicine. The main aims of this study were First, to explore genetic profiles from liquid biopsies of circulating cell-free DNA (cfDNA) and peripheral blood mononuclear cells (PBMCs) using next-generation sequencing (NGS) and identify novel biomarkers for HCC from these …

การแสดงออกของยีนและคุณลักษณะของเซลล์ต้นกำเนิดมะเร็งในประชากรเซลล์ไลน์ U87mg Glioblastoma, รุ่งนภา บุตรศรี

Chulalongkorn University Theses and Dissertations (Chula ETD)

มะเร็งสมองชนิดกลัยโอบลาสโตมา (Glioblastoma หรือ GBM) เป็นมะเร็งสมองชนิดที่พบมากที่สุด มีความรุนแรงและมีอัตราการเสียชีวิตสูง ทำให้คนไข้โดยเฉลี่ยเสียชีวิตภายในหนึ่งปี นอกจากนี้เซลล์ GBM ยังมีความหลากหลายทางสัณฐาน ดังนั้นผู้วิจัยจึงเล็งเห็นความสำคัญของเซลล์ต้นกำเนิดมะเร็งที่เป็นประชากรที่มีความสำคัญในแง่ของการตอบสนองต่อการรักษาและการกลับมาเป็นซ้ำของโรคมะเร็ง การที่จะสามารถพัฒนาการรักษาที่มีความจำเพาะในการกำจัดเซลล์ต้นกำเนิดมะเร็งนี้ จะต้องมีกระบวนการในการระบุเซลล์ต้นกำเนิดมะเร็ง (identification) ที่มีความจำเพาะและแม่นยำ ผู้วิจัยจึงต้องการค้นคว้าในเชิงลึกเพื่อหาการแสดงออกของยีนและโปรตีนที่เกี่ยวข้องกับความเป็นเซลล์ต้นกำเนิดมะเร็ง โดยทำการแยกประชากรเซลล์ U87MG ออกเป็น 3 กลุ่ม ได้แก่ ประชากรเซลล์รวม ประชากรเซลล์ใหญ่ และประชากรเซลล์เล็กออกจากกัน โดยใช้ความแตกต่างของขนาดเซลล์ ด้วยเทคนิค Fluorescence-activated cell sorting (FACS) จากนั้นนำประชากรดังกล่าวมาเลี้ยงแยกกัน โดยทำการศึกษาประชากรทั้งหมด ประชากรขนาดใหญ่และประชากรขนาดเล็ก แล้วศึกษาความเป็นเซลล์ต้นกำเนิดในระดับอาร์เอ็นเอด้วยเทคนิค Real-Time PCR โดยมุ่งเน้นไปที่การศึกษา (1) pluripotency markers/ transcription factor ได้แก่ OCT4, SOX2, NANOG และ c-MYC (2) cancer stem cell signalling ได้แก่ mTOR pathway โดยเน้นไปที่ mTORC2 และ LIN28/let-7 pathway และ (3) cellular phenotypes ได้แก่ วัฏจักรของเซลล์ (cell cycle) การแบ่งตัวของเซลล์ (cell proliferation) และการเคลื่อนที่ของเซลล์ (cell migration) งานวิจัยนี้เป็นรายงานแรกที่ศึกษาความเป็นเซลล์ต้นกำเนิดมะเร็ง GBM ใน U87MG โดยการแยกเซลล์ออกเป็นประชากรเซลล์ใหญ่และประชากรเซลล์เล็กด้วย FACS โดยพบว่าเซลล์ U87MG มีการแสดงออกของยีนที่บ่งชี้ความเป็นเซลล์ต้นกำเนิด ได้แก่ OCT4, SOX2, LIN28B,c-MYC, ZWINT, TYMS และ RCF4 ยีนที่เกี่ยวข้องกับ GBM ที่ทำการศึกษาการแสดงออก ได้แก่ SPARCL1, GDF15, LAMA1, …

Obese Zucker Rats As A Reverse Translational Model Of Human Left Ventricular Hypertrophy, Mackenzie Shelby Newman

Graduate Theses, Dissertations, and Problem Reports (ETD)

Heart failure is a lifelong disability that for over half of those affected leads to mortality within five years after initial diagnosis. Left ventricular hypertrophy (LVH) is one of the most reliable independent predictors of heart failure. Pathological LVH is irreversible, but early diagnosis is often missed due to its asymptomatic nature. Obese Zucker rats (OZR), which develop obesity due to dysfunctional leptin signaling, naturally exhibit a LVH that mimics the obese human condition. Animal models are necessary because human donor tissue is scarce. The central hypothesis is that genes and proteins that are differentially expressed during development of LVH, …

The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun

Center for Translational Medicine Faculty Papers

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo.Wefound that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found …

Gasdermins In Apoptosis: New Players In An Old Game., Corey Rogers, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

Apoptosis is a form of programmed cell death (PCD) that plays critical physiological roles in removing superfluous or dangerous cell populations that are unneeded or threatening to the health of the host organism. Although the molecular pathways leading to activation of the apoptotic program have been extensively studied and characterized starting in the 1970s, new evidence suggests that members of the gasdermin superfamily are novel pore-forming proteins that augment apoptosis by permeabilizing the mitochondria and participate in the final stages of the apoptotic program by inducing secondary necrosis/pyroptosis. These findings may explain outstanding questions in the field such as why …