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Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Elucidating Molecular Function Of Mithramycin And Analogues For The Treatment Of Ews-Ets Expressing Cancers, Reiya Hayden

Theses and Dissertations--Pharmacy

Introduction: Chromosomal translocations are common in cancer. In many cancers such as prostate cancer, leukemia and Ewing sarcoma, chromosomal translocations are the main driver of malignancy. Ewing sarcoma is a cancer diagnosed mostly in children and adolescents that has very grim outcomes for patients with metastasis and recurrent disease. Malignancy in Ewing sarcoma is due to EWS-FLI1, an aberrant transcription factor that is the result of a chromosomal translocation. EWS-FLI1 is the main driver of oncogenesis in Ewing sarcoma and has been the target of many drugs developed to treat the disease. Mithramycin (MTM) was identified as a potent inhibitor …

Functional Impact Of Angiotensinogen Specific Domains On Angiotensin Ii-Mediated Functions, Chia-Hua Wu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Angiotensinogen (AGT) is the only substrate for all angiotensin peptides in the renin angiotensin system (RAS). Cleavage of AGT by renin is a rate-limiting step of angiotensin peptides productions in the RAS and regulates angiotensin peptides-associated pathophysiological functions. Only ten N-terminal residues are cleaved by renin and the functions of remaining part of AGT protein, which is called des(angiotensin I)AGT, remain unclear. Despite of pivotal roles of AGT in the RAS, studies related to how AGT is metabolized and how des(angiotensin I)AGT regulates AGT functions or AngII-mediated functions are limited.

Renin cleavage of AGT shows species specificity. It has been …

Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer

Theses and Dissertations--Physiology

Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …

Physiological Effects On Scientist Astronaut Candidates: Hypobaric Training Assessment, Pedro Llanos, Diego Garcia

Publications

This paper is addressed to expanding our understanding of the effects of hypoxia training on our bodies to better model its dynamics and leverage some of its implications and effects on human health. Hypoxia training is a recommended practice for military and civilian pilots that allow them to recognize their early hypoxia signs and symptoms, and Scientist Astronaut Candidates (SACs) who underwent hypobaric hypoxia (HH) exposure as part of a training activity for prospective suborbital flight applications. This observational-analytical study describes physiologic responses and symptoms experienced by a SAC group before, during and after HH exposure and proposes a model …

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 …

The Effect Of Hibiscus.Sabdariffa. L On Blood Pressure And Arterial Stiffness In Humans, Basirat Tolulope Shittu

Dissertations, Master's Theses and Master's Reports

Cardiovascular diseases (CVD) are the foremost cause of death worldwide. The main risk factor for CVD is uncontrolled hypertension (HTN). The prescription of only anti-hypertensive regimens in the management of HTN is becoming more challenging due to the high cost and adverse effects linked to the persistent usage of the drugs. Eighteen participants completed the study by consuming 2g of Hibiscus sabdariffa or oolong tea twice daily for six weeks. We lost an additional twelve participants in the study due to the COVID-19 pandemic. Central arterial stiffness was analyzed as cfPWV using applanation tonometry technique. The HS tea intervention (n=11) …

Circadian Clock And Lipid Metabolism Disruption In Fatty Liver Disease, Jennifer Valcin

All ETDs from UAB

Hepatic Steatosis, characterized by the accumulation of triglyceride (TG) in the liver is the first stage of Alcoholic Liver Disease (ALD) and Nonalcoholic Fatty Liver Disease (NAFLD). Many metabolic pathways, including lipid metabolism, are regulated by the molecular circadian clock. Importantly, alcohol consumption and obesity induce circadian clock disruption, a risk factor for many diseases, including liver disease. In our first study, we investigated the combined effect of clock disruption and alcohol feeding on liver pathology, and diurnal rhythms in the liver molecular clock and lipid metabolism. Male liver-specific Bmal1 knockout (LKO) mice and control littermates were fed a control …

Dna Methylation: A Mechanism For Sustained Alteration Of Kir4.1 Expression Following Central Nervous System Insult, Jessica Boni

All ETDs from UAB

Astrocytes are the most numerous cells in the brain and play a critical role in maintaining homeostatic extracellular potassium ([K+]e). Maintaining low [K+]e is essential for many cellular functions including maintenance of intensely negative resting membrane potentials in the central nervous system. This process is mediated, in part, by a glial-specific, inwardly rectifying potassium channel, Kir4.1. Underscoring the role of Kir4.1 in CNS functioning, genetic mutations in Kcnj10, the gene which encodes Kir4.1, causes seizures, ataxia and developmental disability in humans. Notably, loss of Kir4.1 protein and mRNA are consistently observed after CNS injury, and in a number of neurological …

Generation Of Induced Pluripotent Stem Cells From Blood Cell Of Glucose-6-Phosphate Dehydrogenase (G6pd) Deficiency, Malinee Tongbaen

Chulalongkorn University Theses and Dissertations (Chula ETD)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic enzyme disorder that affects more than 400 million people worldwide. Insufficient of G6PD enzyme or defect in enzyme activity can cause acute hemolysis after exposure to oxidative stress. The disease model used for pathogenesis study underlying oxidative damage or drug screening in G6PD deficient patients is still needed. In vitro generation of human-induced pluripotent stem cells (iPSCs) afford the potential source of the disease model in medical research. This study aimed to generate the iPSCs derived from G6PD deficient-subjects for used as a specific-disease model. The G6PD-derived iPSCs were generated from …

Rna Sequencing Of Human Peripheral Nerve In Response To Injury: Distinctive Analysis Of The Nerve Repair Pathways., Andrew S. Welleford, Jorge E. Quintero, Nader El Seblani, Eric Blalock, Sumedha Gunewardena, Steven M. Shapiro, Sean M. Riordan, Peter Huettl, Zain Guduru, John A. Stanford, Craig G. Van Horne, Greg A. Gerhardt

Manuscripts, Articles, Book Chapters and Other Papers

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson's disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another …

Copper/N-Acetylcysteine Coated Iron Oxide Nanoparticles Synthesis, Characterization, And Antimicrobial Activities, Danya Belnour

Electronic Theses and Dissertations, 2020-2023

In recent years, there is a growing interest in developing metal based antimicrobial nanomaterials suitable for agricultural and biomedical applications. For centuries, Copper (Cu) biocide has been used for protecting a wide variety of crops from devastating bacterial and fungal diseases. However, prolonged and aggressive use of Cu led to the development of resistance and accumulation in soil. The latter has been linked to aquatic toxicity due to soil Cu leaching. Furthermore, copper build up in soil causes phytotoxicity and reduces uptake of micronutrient Zn through the root system. In biomedical field, Cu has been historically used as an antimicrobial …

การศึกษาตามขวางเปรียบเทียบความชุกของผู้ติดเชื้อวัณโรคระยะแฝง ในนิสิตแพทย์ชั้นปรีคลินิก และนิสิตแพทย์ชั้นคลินิกโดยวิธี ควอนติเฟอรอนทีบีโกลพลัส และการทดสอบวัณโรคทางผิวหนัง, นันทนา จำปา

Chulalongkorn University Theses and Dissertations (Chula ETD)

ที่มา นิสิตแพทย์เป็นกลุ่มประชากรที่มีความเสี่ยงสูงที่จะติดเชื้อวัณโรคจากผู้ป่วยในโรงพยาบาลและกลายเป็นวัณโรคชนิดมีอาการที่สามารถแพร่กระจายได้โดยเฉพาะในโรงพยาบาลของประเทศที่มีความชุกของผู้ติดเชื้อวัณโรคสูง วัตถุประสงค์ เพื่อที่จะหาความชุกของนิสิตแพทย์ที่ติดเชื้อวัณโรคระยะแฝงเปรียบเทียบกันระหว่างนิสิตแพทย์ชั้นปีที่ 4 ที่เพิ่งผ่านการเรียนการสอนในชั้นปรีคลินิกและนิสิตแพทย์ชั้นปีที่ 6 ที่ผ่านการสัมผัสผู้ป่วยในโรงพยาบาลมาแล้วอย่างน้อย 2 ปี โดยการใช้วิธีการตรวจ QuantiFERON-TB Gold Plus (QFT-Plus) และการทดสอบวัณโรคทางผิวหนัง (Tuberculin Skin Test) วิธีการวิจัย เป็นการศึกษาแบบตัดขวางในอาสาสมัครนิสิตแพทย์ชั้นปีที่ 4 และนิสิตแพทย์ชั้นปีที่ 6 ที่กำลังศึกษาอยู่ในคณะแพทยศาสตร์จุฬาลงกรณ์มหาวิทยาลัย โดยนิสิตที่สมัครใจเข้าร่วมการศึกษาจะได้รับการตรวจ QFT-Plus จากการเก็บตัวอย่างเลือด และบางส่วนของนิสิตที่เขาร่วมการศึกษาจะได้รับการทดสอบ TST หลังจากการเจาะเลือด โดยก่อนหน้าเข้าเก็บตัวอย่างนิสิตแพทย์อาสาสมัครจะต้องทำแบบสอบถามเกี่ยวกับความเสี่ยงในการได้รับเชื้อวัณโรค ผลการศึกษา มีนิสิตสนใจเข้าการศึกษาทั้งหมด 158 คน โดยความชุกของผู้ติดเชื้อวัณโรคระยะแฝงโดยวิธี QFT-Plus รวมทั้งหมดมี 10 คน คิดเป็นร้อยละ 6.3 โดยแบ่งเป็นความชุกในนิสิตแพทย์ชั้นปีที่ 6 คิดเป็นร้อยละ 9.4 และความชุกของนิสิตแพทย์ชั้นปีที่ 4 ร้อยละ 2.7 โดยไม่พบความสัมพันธ์กับเสี่ยงของการติดเชื้อวัณโรคกับปัจจัยอื่นที่เกี่ยวข้องอย่างมีนัยยะสำคัญทางสถิติเมื่อทำการวิเคราะห์แบบพหุตัวแปร โดยในการศึกษานี้นิสิตส่วนมาก ร้อยละ 88 ให้ประวัติว่าเคยได้รับวัคซีน BCG ตั้งแต่เด็ก นอกจากนั้นในรายที่ให้ผลบวกจากการทดสอบ QFT-Plus และ TST ไมีมีนิสิตที่มีผลภาพรังสีปอดที่ผิดปกติ โดยจากนิสิตที่เข้าการศึกษาทั้งหมด 158 ราายมีนิสิตจำนวน 41 ราย คิดเป็นร้อยละ 25.9 สมัครใจรับการทดสอบ TST โดยพบว่าหากใช้จุดตัดของ TST ตามมาตรฐานที่ตั้งแต่ 10 มิลลิเมตรขึ้นไป พบว่ามี 6 รายให้ผลบวกสอดคล้องกับ QFT-Plus และมี 4 รายที่ TST ให้ผลลบ ไม่สอดคล้องกับ QFT-Plus เมื่อคิดค่าความสอดคล้องกันระหว่างการทดสอบทั้ง 2 พบว่ามีความสอดคล้องกันในระดับปานกลาง สรุป การตรวจคัดกรองผู้ป่วยที่ติดเชื้อวัณโรคในบุคลากรใหม่ที่เข้ามาทำงานในโรงพยาบาลโดยเฉพาะนิสิตแพทย์มีความสำคัญในการช่วยลดการแพร่กระจายอุบัติการของการเกิดวัณโรคติดต่อภายในโรงพยาบาล ในการศึกษานี้พบว่าในนิสิตแพทย์ปี 6 มีค่าความชุกของผู้ป่วยวัณโรคแฝง สูงกว่านิสิตแพทย์ชั้นปี 4 ดังนั้นประชากรกลุ่มนิสิตนี้จึงมีความเสี่ยงสูงที่จะได้รับบเชื้อวัณโรคจากการฝึกปฏิบัติงานในโรงพยาบาล แม้ว่าจากการศึกษานี้มีจำนวนผนิสิตที่เข้าร่วมปริมาณไม่มากจนสามารถแสดงให้เห็นถึงความเสี่ยงของชั้นปี …

Genomic-Based Identification Of Environmental And Clinical Listeria Monocytogenes Strains Associated With An Abortion Outbreak In Beef Heifers, Katherine J. Whitman, James L. Bono, Michael L. Clawson, John D. Loy, Joseph M. Bosilevac, Terrance M. Arthur, Jeff D. Ondrak

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: In a beef cattle facility an outbreak of abortions occurred over a 36-day period and included samples from two aborted (non-viable) fetuses and 21 post-abortion clinical cases. There are numerous etiologies, including clinical listeriosis. At the species level, Listeria monocytogenes is ubiquitous in cattle production environments, including soil, feed, and occasionally water sources, and is a common enteric resident of cattle and other mammals. There are four genetically distinct lineages of L. monocytogenes (I-IV), with most lineage III and IV isolates obtained from ruminants. Definitive diagnosis of L. monocytogenes as a causative agent in disease outbreaks relies upon case …

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 Antiviral Activity Of Lichen Metabolites Against Dengue Virus, Naphat Loeanurit

Chulalongkorn University Theses and Dissertations (Chula ETD)

Dengue fever is one of the mosquito-borne infectious diseases globally. Currently, no specific treatment was established. Depsidones and depsides are one of the most common lichen secondary metabolites produced for the organism’s survival in extreme environments. These compounds have been reported as antivirals against the other virus in Flaviviridae family, hepatitis C virus. In this study, depsidones and depsides were explored for anti-dengue efficacy and cellular toxicity. One depsidone, VK-0014, and two depsides, TT-031 and TT-032, exhibited an anti-DENV2 with effective concentration (EC50) of 17.42 ± 3.21, 2.43 ± 0.19, and 0.91 ± 0.15 µM, respectively. Cytotoxicity concentration (CC50) in …

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 …

Analyzing The Effects Of Opioids On Cortical Pore Networks In Rabbit Tibiae And Femora, Kassidy Wilson

Williams Honors College, Honors Research Projects

The following project was approved by the Institutional Animal Care and Use Committee (IACUC) (Protocol number #18-11-12 ARC). This study was completed as a subset of Dr. Andronowski's overarching lab project. Femora and tibiae were procured from New Zealand White rabbits to study the prolonged effects of opioid use in bone remodeling. This specific project analyzed the effects of opioids on the pore networks and the pore orientation.

Modulation Of Epileptogenesis: A Paradigm For The Integration Of Enzyme-Based Microelectrode Arrays And Optogenetics, Corwin R. Butler, Jeffery A. Boychuk, Francois Pomerleau, Ramona Alcala, Peter Huettl, Yi Ai, Johan Jakobsson, Sidney W. Whiteheart, Greg A. Gerhardt, Bret N. Smith, John T. Slevin

Physiology Faculty Publications

BACKGROUND: Genesis of acquired epilepsy includes transformations spanning genetic-to- network-level modifications, disrupting the regional excitatory/inhibitory balance. Methodology concurrently tracking changes at multiple levels is lacking. Here, viral vectors are used to differentially express two opsin proteins in neuronal populations within dentate gyrus (DG) of hippocampus. When activated, these opsins induced excitatory or inhibitory neural output that differentially affected neural networks and epileptogenesis. In vivo measures included behavioral observation coupled to real-time measures of regional glutamate flux using ceramic-based amperometric microelectrode arrays (MEAs).

RESULTS: Using MEA technology, phasic increases of extracellular glutamate were recorded immediately upon application of blue light/488 nm …

Melanopsin-Expressing Retinal Ganglion Cells In Control Vs. Glaucomatous Retinas, Edward Hamad

Williams Honors College, Honors Research Projects

Glaucoma is a common cause of vision loss worldwide and has a large scope of symptoms, ranging from pupillary reflex defects to sleep disorders. These issues can be explained partially by a recently found subtype of retinal ganglion cells that express melanopsin, denoted melanopsin-expressing retinal ganglion cells or mRGCs for short. These cells function primarily as photoreceptors in the non-image forming pathway, but can receive input from rods and cones. Since mRGCs play a role in the pupillary reflex and regulation of the sleep-wake cycle, I investigated if glaucoma leads to the degeneration of these cells in a mouse model …

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, …

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 …

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 …

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 …

Monitoring Pathological Gene Expression And Studying Endogenous Epigenetic Architecture By Crispr/Cas9-Based Tool Development Using Alpha-Synuclein As A Model, Levi Adams

Electronic Theses and Dissertations, 2020-2023

Until recently, complete understanding of the endogenous activity of pathologically relevant genes was out of reach and research was confined to in situ work, plasmid-based constructs and artificial model systems. The development and expansion of the CRISPR/Cas9 genome editing technique has enabled us to explore the molecular underpinnings of gene activation using the cell's own endogenous regulatory environment. In this work, we report on the development of a novel tool to monitor the endogenous activity of a causative gene in Parkinson's disease, a-synuclein. We use CRISPR/Cas9 to insert a highly sensitive engineered luciferase at the C-terminal of a-synuclein and assessed …

Data-Driven Identification Of Chemopreventive Agents For Breast Cancer, Deni̇z Can Güven, Cemal Orhan, Kazi̇m Şahi̇n, Fatih Mehmet Uçkun

Turkish Journal of Medical Sciences

Preclinical animal models of breast cancer provide the opportunity to identify chemopreventive drugs with single-agent activity as well as effective multi-modality regimens for primary as well as secondary prevention in high-risk persons. Our group has used the 7,12-dimethylbenz(a)anthracene (DMBA) mouse model of carcinogen-induced breast cancer to explore the clinical potential of two tyrosine kinase inhibitors and a nucleoside analog as chemopreventive agents. All three agents exhibited promising preclinical activity both as monotherapy and as components of combination therapy with the standard chemotherapy drug paclitaxel. The tumors developing despite chemoprevention were not only small and grew slowly, but they also displayed …

The Efficacy Of The 3-Dimensional Vibe-Caipirinha-Dixon Technique In The Evaluation Of Pancreatic Steatosis, Ural Koç, Gökhan Ocakoğlu, Oktay Algin

Turkish Journal of Medical Sciences

Background/aim: CAIPIRINHA is a new technique in abdominal imaging. Pancreatic steatosis (PS) is a subject of increasing scientific interest. The aim of this study was to investigate the efficacy of the isotropic 3D-VIBE- CAIPIRINHA -DIXON technique on a new generation 3-tesla MR unit in the evaluation of PS.Materials and methods: In this retrospective study, the imaging findings of 49 patients with PS and 41 control subjects were examined. The pancreas-to-spleen ratio (PSR), pancreas-to-muscle ratio (PMR), and pancreatic signal intensity index (PSII) were defined as 3 new parameters and these indexes were calculated from the in-phase/out of phase 3D-VIBE- CAIPIRINHA-DIXON images. …

Posterior Fossa Horns; A New Calvarial Finding Of Mucopolysaccharidoses With Well-Known Cranial Mri Features, Çağri Damar, Betül Emi̇ne Deri̇nkuyu, Muazzez Asburçe Bi̇ke Olgaç Kiliçkaya, Mehmet Öztürk, Çi̇ğdem Öztunali, Ayşe Gül Alimli, Öznur Leman Boyunaga, Murat Uçar, Fati̇h Süheyl Ezgü, Leyla Tümer, Alp Özgün Börcek, Ahmet Siğirci

Turkish Journal of Medical Sciences

Background/aim: Mucopolysaccharidoses (MPS) are a group of hereditary metabolic diseases. The aim of this study was to share the previously unreported calvarial finding of internal hypertrophy of the occipitomastoid sutures (IHOMS) together with some other well- known cranial MRI findings in this patient series. Materials and methods: A retrospective evaluation was conducted of 80 cranial MRIs of patients who had been diagnosed and followed up with MPS from 2008 to 2019 in our center. Of these patients, 11 had Hurler, 14 had Hunter, 24 had Sanfilippo, 15 had Morquio, 14 had Maroteaux-Lamy, and 2 had Sly disease. The cranial MRIs …

Comparison Of The Efficacy Between Bilateral Proximal Tubal Occlusion And Total Salpingectomy On Ovarian Reserve And The Cholinergic System: An Experimental Study, Remzi̇ Atilgan, Şehmus Pala, Tuncay Kuloğlu, Cengi̇z Şanli, Şeyda Yavuzkir, Zehra Sema Özkan

Turkish Journal of Medical Sciences

Background and aim: To compare the effects of bilateral proximal tubal occlusion and bilateral total salpingectomy on ovarian reserve and the cholinergic system via rat experiment. Materials and methods: Twenty-one adult female rats were randomly divided into the following three groups: G1 (n = 7), sham group; G2 (n = 7), bilateral total salpingectomy group; and G3 (n = 7), bilateral proximal tubal occlusion group. Four weeks later, the abdomen of the rats was opened. The right ovarian tissues were stored in 10% formaldehyde, whereas the left ovarian tissues were stored at ?80 °C in aluminum foil. Serum samples were …