Medical Biochemistry Commons^™

Role Of Thymidine Phosphorylase In Type 2 Diabetes-Associated High-Risk Of Thrombosis, Adam Belcher

Theses, Dissertations and Capstones

Cardiovascular diseases (CVDs), such as ischemic heart disease and stroke, are the leading causes of death globally that disproportionally affects patients with type 2 diabetes mellitus (T2DM) at a 2-4-fold rate compared to non-diabetic patients. These CVDs result from a blood clot, also known as a thrombus, formed in arteries that can block blood flow resulting in tissue damage and death. Antiplatelet drugs, such as aspirin and clopidogrel, used to prevent thrombosis have been found to be less effective in diabetics and increase the risk of hemorrhagic events. The T2DM epidemic has made it imperative to find therapies that decrease …

Treatments For The Mitigation Of Immunotherapy-Related Neurotoxicities In Patients With Non-Small Cell Lung Cancer, Gautam Chiang

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Lung cancer is the most common cancer type worldwide, with one of the highest mortality rates across all cancer types. Cancer immunotherapeutics such as immune checkpoint inhibitors (ICIs) have improved cancer treatment by promoting the body’s natural immune response to tumor development while avoiding toxic effects associated with traditional cytotoxic chemotherapy. However, immunotherapies have been associated with unique toxic effects similar to autoimmune disorders known as immune-related adverse events (irAEs). 4.2% of immunotherapy-treated cancer patients reportedly developed neurological irAEs. In this review, different immunotherapies were studied, including ICIs and mechanism-specific novel therapies, in order to determine a combination therapy to …

Mir-212-3p Functions As A Tumor Suppressor Gene In Group 3 Medulloblastoma Via Targeting Nuclear Factor I/B (Nfib), Naveenkumar Perumal, Ranjana K. Kanchan, David Doss, Noah Bastola, Pranita Atri, Ramakanth C. Venkata, Ishwor Thapa, Raghupathy Vengoji, Shailendra K. Maurya, David Klinkebiel, Geoffrey A. Talmon, Mohd W. Nasser, Surinder K. Batra, Sidharth Mahapatra

Journal Articles: Biochemistry & Molecular Biology

Haploinsufficiency of chromosome 17p and c-Myc amplification distinguish group 3 medulloblastomas which are associated with early metastasis, rapid recurrence, and swift mortality. Tumor suppressor genes on this locus have not been adequately characterized. We elucidated the role of miR-212-3p in the pathophysiology of group 3 tumors. First, we learned that miR-212-3p undergoes epigenetic silencing by histone modifications in group 3 tumors. Restoring its expression reduced cancer cell proliferation, migration, colony formation, and wound healing in vitro and attenuated tumor burden and improved survival in vivo. MiR-212-3p also triggered c-Myc destabilization and degradation, leading to elevated apoptosis. We then isolated an …

Differential Gene Expression-Based Connectivity Mapping Identified Novel Drug Candidate And Improved Temozolomide Efficacy For Glioblastoma, Raghupathy Vengoji, Pranita Atri, Muzafar A. Macha, Parthasarathy Seshacharyulu, Naveenkumar Perumal, Kavita Mallya, Yutong Liu, Lynette M. Smith, Satyanarayana Rachagani, Sidharth Mahapatra, Moorthy P. Ponnusamy, Maneesh Jain, Surinder K. Batra, Nicole Shonka

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Glioblastoma (GBM) has a devastating median survival of only one year. Treatment includes resection, radiation therapy, and temozolomide (TMZ); however, the latter increased median survival by only 2.5 months in the pivotal study. A desperate need remains to find an effective treatment.

METHODS: We used the Connectivity Map (CMap) bioinformatic tool to identify candidates for repurposing based on GBM's specific genetic profile. CMap identified histone deacetylase (HDAC) inhibitors as top candidates. In addition, Gene Expression Profiling Interactive Analysis (GEPIA) identified HDAC1 and HDAC2 as the most upregulated and HDAC11 as the most downregulated HDACs. We selected PCI-24781/abexinostat due to …

Growth In A Biofilm Sensitizes Cutibacterium Acnes To Nanosecond Pulsed Electric Fields, Asia Poudel, Adenrele Oludiran, Esin B. Sözer, Maura Casciola, Erin B. Purcell, Claudia Muratori

Bioelectrics Publications

The Gram-positive anaerobic bacterium Cutibacterium acnes (C. acnes) is a commensal of the human skin, but also an opportunistic pathogen that contributes to the pathophysiology of the skin disease acne vulgaris. C. acnes can form biofilms; cells in biofilms are more resilient to antimicrobial stresses. Acne therapeutic options such as topical or systemic antimicrobial treatments often show incomplete responses. In this study we measured the efficacy of nanosecond pulsed electric fields (nsPEF), a new promising cell and tissue ablation technology, to inactivate C. acnes. Our results show that all tested nsPEF doses (250 to 2000 pulses, 280 ns pulses, …

Epigenetic Regulation Of Reactive Oxygen Species-Induced Tumor Progression In Hepatocellular Carcinoma, Suchittra Phoyen

Chulalongkorn University Theses and Dissertations (Chula ETD)

Oxidative stress is a consequence of an imbalance of antioxidants and reactive species. The most common form of reactive species is derived from oxygen, called reactive oxygen species (ROS). ROS involve in pathogenesis of several diseases including cancers. Cancer genesis and progression are contributed through both genetic and epigenetic mechanisms. Histone modification, a post-translational modification at histone tails, is one of the epigenetic mechanisms known to participate in carcinogenesis and tumor progression. Although the ROS-induced histone modification alteration has been demonstrated in some cancers, the change in histone methylation and gene expression by ROS in hepatocellular carcinoma (HCC) is scarcely …

Contribution Of The Human Microbiome And Proteus Mirabilis To Onset And Progression Of Rheumatoid Arthritis: Potential For Targeted Therapy, Jessica Kerpez, Marc Kesselman, Michelle Demory Beckler

Internet Journal of Allied Health Sciences and Practice

The human microbiome has been shown to play a role in the regulation of human health, behavior, and disease. Data suggests that microorganisms that co-evolved within humans have an enhanced ability to prevent the development of a large spectrum of immune-related disorders but may also lead to the onset of conditions when homeostasis is disrupted. In many conditions, a link between dysbiosis (microbial imbalance or microbiome upset) has been identified and associated with immune conditions such as rheumatoid arthritis (RA). This review provides insight into how an individual’s unique microbiome, combined with a genetic predisposition and environmental factors may lead …

The Current Landscape Of Antibody-Based Therapies In Solid Malignancies, Ashu Shah, Sanchita Rauth, Abhijit Aithal, Sukhwinder Kaur, Koelina Ganguly, Catherine Orzechowski, Grish C. Varshney, Maneesh Jain, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Over the past three decades, monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy. Still, this benefit remains restricted to a small proportion of patients due to moderate response rates and resistance emergence. The field has started to embrace better mAb-based formats with advancements in molecular and protein engineering technologies. The development of a therapeutic mAb with long-lasting clinical impact demands a prodigious understanding of target antigen, effective mechanism of action, gene engineering technologies, complex interplay between tumor and host immune system, and biomarkers for prediction of clinical response. This review discusses the various approaches used by mAbs for …

Repurposing Niclosamide For Targeting Pancreatic Cancer By Inhibiting Hh/Gli Non-Canonical Axis Of Gsk3Β, Jyoti B. Kaushal, Rakesh Bhatia, Ranjana K. Kanchan, Pratima Raut, Surya Mallapragada, Quan P. Ly, Surinder K. Batra, Satyanarayana Rachagani

Journal Articles: Biochemistry & Molecular Biology

Niclosamide (Nic), an FDA-approved anthelmintic drug, is reported to have anti-cancer efficacy and is being assessed in clinical trials for various solid tumors. Based on its ability to target multiple signaling pathways, in the present study, we evaluated the therapeutic efficacy of Nic on pancreatic cancer (PC) in vitro. We observed an anti-cancerous effect of this drug as shown by the G0/G1 phase cell cycle arrest, inhibition of PC cell viability, colony formation, and migration. Our results revealed the involvement of mitochondrial stress and mTORC1-dependent autophagy as the predominant players of Nic-induced PC cell death. Significant reduction of Nic-induced reactive …

Emerging Role Of Mir-345 And Its Effective Delivery As A Potential Therapeutic Candidate In Pancreatic Cancer And Other Cancers, Nagabhishek Sirpu Natesh, Brianna M. White, Maia M. C. White, Metin Uz, Rakhee Rathnam Kalari Kandy, Surinder K. Batra, Surya K. Mallapragada, Satyanarayana Rachagani

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, poor prognosis, and palliative treatments, due to the rapid upregulation of alternative compensatory pathways and desmoplastic reaction. miRNAs, small non-coding RNAs, have been recently identified as key players regulating cancer pathogenesis. Dysregulated miRNAs are associated with molecular pathways involved in tumor development, metastasis, and chemoresistance in PDAC, as well as other cancers. Targeted treatment strategies that alter miRNA levels in cancers have promising potential as therapeutic interventions. miRNA-345 (miR-345) plays a critical role in tumor suppression and is differentially expressed in various cancers, including pancreatic cancer (PC). The underlying …

Dynamic Phenotypic Switching And Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy, Arin Nam, Atish Mohanty, Supriyo Bhattacharya, Sourabh Kotnala, Srisairam Achuthan, Kishore Hari, Saumya Srivastava, Linlin Guo, Anusha Nathan, Rishov Chatterjee, Maneesh Jain, Mohd W. Nasser, Surinder K. Batra, Govindan Rangarajan, Erminia Massarelli, Herbert Levine, Mohit Kumar Jolly, Prakash Kulkarni, Ravi Salgia

Journal Articles: Biochemistry & Molecular Biology

Drug resistance, a major challenge in cancer therapy, is typically attributed to mutations and genetic heterogeneity. Emerging evidence suggests that dynamic cellular interactions and group behavior also contribute to drug resistance. However, the underlying mechanisms remain poorly understood. Here, we present a new mathematical approach with game theoretical underpinnings that we developed to model real-time growth data of non-small cell lung cancer (NSCLC) cells and discern patterns in response to treatment with cisplatin. We show that the cisplatin-sensitive and cisplatin-tolerant NSCLC cells, when co-cultured in the absence or presence of the drug, display dynamic group behavior strategies. Tolerant cells exhibit …

The Role Of Vascular Endothelial Growth Factor In Leukemia Trafficking, Shaw Powell

Theses and Dissertations--Medical Sciences

Vascular endothelial growth factor (VEGF) is a signaling protein involved in inducing and regulating endothelial cell proliferation and function (Duffy et al 2000). VEGF is also involved in cancer progression, as it induces vascular permeability and promotes angiogenesis to tumor laden areas, giving cancer cells critical oxygen and nutrients (Hoeppner et al.,2012. Studies indicate VEGF prevents lymphoblast apoptosis, which may contribute to leukemia formation and enable the proliferation of leukemic cells (Duffy et al 2000). Ongoing research seeks to further examine VEGF in leukemia, using a rag2:GFP-Myc expressing transgenic zebrafish as the animal model of T-cell Acute Lymphoblastic Leukemia (T-ALL). …

Carnosic Acid Differentially Modulates The Nrf2- Antioxidant Response In Male And Female Mice Following Experimental Traumatic Brain Injury, Jacob A. Dunkerson

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Each year, an estimated 2.8 million Americans are diagnosed with a TBI due to falling, motor vehicle collisions, gun violence, and sports related concussions. Although inflicted by a single event, the post-traumatic effects of TBI often develop into a life-long disease. Survivors often experience cognitive decline, memory loss, emotional instability, changes in personality, and physical disabilities. A single TBI, and more-so repetitive TBI's, place an individual at a greater risk of developing chronic neurological disorders, such as dementia or Alzheimer’s disease, earlier in life. …

Notch Signaling Regulates Perivascular Adipose Tissue (Pvat) Function During Diet-Induced Obesity, C Yang, A Harrington, L Ryzhova, L Liaw

Costas T. Lambrew Research Retreat 2021

Objectives:

-To test the hypothesis that canonical Notch signaling influence vascular function by regulating PVAT-derived vascular relaxation factors.

-To determine how overexpression of Notch signaling or loss of the key Notch signaling component influence PVAT function.

Characterization Of Cucurbitacin-Inspired Estrone Analogues As Novel Inhibitors Of Human Atp- Binding Cassette Proteins (Abcb1 And Abcc1), Jennifer Kyeremateng

Electronic Theses and Dissertations

ATP-binding cassette (ABC) transporters are a large class of integral membrane proteins that contribute to key physiological functions in all organisms by utilizing ATP binding and hydrolysis to transport diverse substrates across membrane barriers. P-glycoprotein (P-gp/ ABCB1) and Multidrug Resistance protein 1 (MRP1/ABCC1) are widely reported ABC transporters associated with multidrug resistance in cancer. Multidrug resistance (MDR) mediated by P-gp and MRP1 is responsible for treatment failures of many metastatic cancers as a result of reduced accumulation, bioavailability and diminished potency of anticancer drugs. Currently, known P-gp and MRP1 inhibitors are limited due to toxicity, lack of selectivity and low …

A Biochemical Characterization Of The Fusion Proteins From Enveloped Rna Viruses, Chelsea T. Barrett

Theses and Dissertations--Molecular and Cellular Biochemistry

Enveloped viruses must bind target cells and then fuse the viral membrane with a cell membrane to enter a host cell. These viruses use one or more surface glycoproteins to carry out these critical functions. The surface glycoprotein that carries out the fusion function, termed a fusion protein, is divided into three classes based on structural similarities. Some of the most studied human viral pathogens, such as human immunodeficiency virus (HIV), Ebola virus, influenza, measles, and the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), possess class I fusion proteins. Following synthesis, class I fusion proteins associate as non-covalently …

Entry And Early Infection Of Non-Segmented Negative Sense Rna Viruses, Jean Mawuena Branttie

Theses and Dissertations--Molecular and Cellular Biochemistry

Paramyxoviruses, pneumoviruses, and other non-segmented negative sense (NNS) RNA viruses have historically been of public health concern. Although their genomes are typically small (up to 19kbs) they are able to inflict large-scale detrimental pathologies on host cells. Human metapneumovirus (HMPV) is a widespread pathogen and is a NNS RNA virus. HMPV results respiratory tract infections and is particularly dangerous for preterm infants, the elderly, and immunocompromised individuals. Other viruses within the NNS RNA virus order include the deadly Ebola, Hendra, and Nipah viruses (EBOV, HeV, and NiV), as well as the re-emerging measles virus (MeV). Despite their public impact, there …

Pre-Clinical Advancements In Biomarkers, Tools, And Therapeutics For A Metabolic Neurodegenerative Disease, Zoë Simmons

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the storage form of glucose and a highly important substrate for cellular metabolism. Characterization of the enzymes and mechanisms of glycogen metabolism began over 70 years ago and over the last 20 years, a previously unknown protein called laforin has emerged as an important contributor to glycogen metabolism homeostasis. Multiple labs demonstrated that laforin is a glycogen phosphatase and mutations in the gene encoding laforin cause the formation of aberrant glycogen-like aggregates called Lafora bodies (LBs). LBs are cytoplasmic, water-insoluble aggregates that drive neurodegeneration and early death in Lafora disease (LD) patients. The direct relationship between mutated laforin, …

Monopolar Gene Electrotransfer Enhances Plasmid Dna Delivery To Skin, Anna Bulysheva, Loree Heller, Michael Francis, Frency Varghese, Carly Boye, Richard Heller

Electrical & Computer Engineering Faculty Publications

A novel monopolar electroporation system and methodologies were developed for in vivo electroporation intended for potential clinical applications such as gene therapy. We hypothesized that an asymmetric anode/cathode electrode applicator geometry could produce favorable electric fields for electroporation, without the typical drawback associated with traditional needle and parallel plate geometries. Three monopolar electrode applicator prototypes were built and tested for gene delivery of reporter genes to the skin in a guinea pig model. Gene expression was evaluated in terms of kinetics over time and expression distribution within the treatment site. Different pulsing parameters, including pulse amplitude, pulse duration, and pulse …

Protein-Functionalized Poly(Ethylene Glycol) Hydrogels As Scaffolds For Monolayer Organoid Culture, Reid L Wilson, Ganesh Swaminathan, Khalil Ettayebi, Carolyn Bomidi, Xi-Lei Zeng, Sarah E Blutt, Mary K Estes, K Jane Grande-Allen

Faculty, Staff and Students Publications

Stem cell-derived, organotypic in vitro models, known as organoids, have emerged as superior alternatives to traditional cell culture models due to their unparalleled ability to recreate complex physiological and pathophysiological processes. For this reason, they are attractive targets of tissue-engineering efforts, as constructs that include organoid technology would be expected to better simulate the many functions of the desired tissue or organ. While the 3D spheroidal architecture that is the default architecture of most organoid models may be preferred for some applications, 2D monolayer arrangements remain the preferred organization for many applications in tissue engineering. Therefore, in this work, we …

Open Problems In Extracellular Rna Data Analysis: Insights From An Ercc Online Workshop, Roger P Alexander, Robert R Kitchen, Juan Pablo Tosar, Matthew Roth, Pieter Mestdagh, Klaas E A Max, Joel Rozowsky, Karolina Elżbieta Kaczor-Urbanowicz, Justin Chang, Leonora Balaj, Bojan Losic, Eric L Van Nostrand, Emily Laplante, Bogdan Mateescu, Brian S White, Rongshan Yu, Aleksander Milosavljevic, Gustavo Stolovitzky, Ryan M Spengler

Faculty, Staff and Students Publications

We now know RNA can survive the harsh environment of biofluids when encapsulated in vesicles or by associating with lipoproteins or RNA binding proteins. These extracellular RNA (exRNA) play a role in intercellular signaling, serve as biomarkers of disease, and form the basis of new strategies for disease treatment. The Extracellular RNA Communication Consortium (ERCC) hosted a two-day online workshop (April 19–20, 2021) on the unique challenges of exRNA data analysis. The goal was to foster an open dialog about best practices and discuss open problems in the field, focusing initially on small exRNA sequencing data. Video recordings of workshop …

Evaluation Of Somatic Mutations In Solid Metastatic Pan-Cancer Patients, Moom R. Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Angel R. Baroz, Joseph Chao, Chen Chen, Mohd W. Nasser, Ramakanth C. Venkata, Maneesh Jain, Lynette M. Smith, Susan E. Yost, Karen L. Reckamp, Raju Pillai, Leonidas Arvanitis, Michelle Afkhami, Edward W. Wang, Vincent Chung, Mihaela Cristea, Marwan Fakih, Marianna Koczywas, Erminia Massarelli, Joanne Mortimer, Yuan Yuan, Surinder K. Batra, Sumanta Pal, Ravi Salgia

Journal Articles: Biochemistry & Molecular Biology

Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx^® panel. The most prevalent genes with somatic mutations were TP53, KRAS, APC, and LRP1B. In this analysis, these genes had mutation frequencies higher than in publicly available datasets. We identified that the somatic mutations were seven mutually exclusive gene pairs and an additional fifty-two co-occurring gene pairs. Mutations …

Disruption Of Fdps/Rac1 Axis Radiosensitizes Pancreatic Ductal Adenocarcinoma By Attenuating Dna Damage Response And Immunosuppressive Signalling, Parthasarathy Seshacharyulu, Sushanta Halder, Rama Krishna Nimmakayala, Satyanarayana Rachagani, Sanjib Chaudhary, Pranita Atri, Ramakanth C. Venkata, Michel M. Ouellette, Joseph Carmicheal, Shailendra K. Gautam, Raghupathy Vengoji, Shuo Wang, Sicong Li, Lynette M. Smith, Geoffrey A. Talmon, Kelsey Klute, Quan P. Ly, Bradley N. Reames, Jean L. Grem, Lyudmyla Berim, James C. Padussis, Sukhwinder Kaur, Sushil Kumar, Moorthy P. Ponnusamy, Maneesh Jain, Chi Lin, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Radiation therapy (RT) has a suboptimal effect in patients with pancreatic ductal adenocarcinoma (PDAC) due to intrinsic and acquired radioresistance (RR). Comprehensive bioinformatics and microarray analysis revealed that cholesterol biosynthesis (CBS) is involved in the RR of PDAC. We now tested the inhibition of the CBS pathway enzyme, farnesyl diphosphate synthase (FDPS), by zoledronic acid (Zol) to enhance radiation and activate immune cells.

METHODS: We investigated the role of FDPS in PDAC RR using the following methods: in vitro cell-based assay, immunohistochemistry, immunofluorescence, immunoblot, cell-based cholesterol assay, RNA sequencing, tumouroids (KPC-murine and PDAC patient-derived), orthotopic models, and PDAC patient's …

การตรวจสอบการกลายพันธุ์บริเวณ Basal Core Promoter ในผู้ป่วยที่ติดเชื้อไวรัสตับอักเสบบี ด้วยเทคนิคปฏิกิริยาลูกโซ่พอลิเมอเรสแบบดรอปเลทดิจิตอล, ชวิศ พลพงษ์

Chulalongkorn University Theses and Dissertations (Chula ETD)

การกลายพันธุ์บริเวณ Basal core promoter (BCP) ตำแหน่ง A1762T/G1764A ของไวรัสตับอักเสบบี มีความสัมพันธ์กับการดำเนินโรคไวรัสตับอักเสบบีแบบเรื้อรัง(chronic hepatitis B; CHB) อย่างไรก็ตามส่วนใหญ่เป็นการศึกษาด้วย Sanger sequencing ที่ให้ผลเชิงคุณภาพ แต่การศึกษาด้วยเทคนิคอื่นเช่นเทคนิค droplet digital PCR(ddPCR) ที่สามารถบ่งบอกปริมาณร้อยละการกลายพันธุ์ (mutation percentage) ได้ยังคงมีจำกัด การศึกษานี้จึงมีจุดประสงค์เพื่อพัฒนาวิธีการตรวจสอบการกลายพันธุ์บริเวณ BCP โดยใช้ ddPCR เปรียบเทียบกับ Sanger sequencing และ Real- Time PCR และหาความสัมพันธ์ของ mutation percentage กับปัจจัยทางไวรัสและคลินิก ในผู้ป่วย CHB จำนวน 185 คน ผลการศึกษาพบว่าจากจำนวนผู้ป่วยทั้งหมดมีผู้ป่วย 78 รายที่นำมาศึกษาเปรียบเทียบกันได้ทั้ง 3 วิธี โดยพบว่า ddPCR สามารถตรวจพบการกลายพันธุ์ได้มากกว่าSanger sequence(84.6%vs.43.6%,P<0.001) และReal-time PCR(84.6%vs. 60.3%,P<0.001) และพบการกลายพันธุ์ได้(limit of detection(LOD)ตั้งแต่ร้อยละ0.25 การศึกษาด้วย ddPCR พบว่าผู้ป่วย HBeAg-positive มีร้อยละการกลายพันธุ์ต่ำกว่าผู้ป่วย HBeAg-negative (31.36±33.56vs.46.86±27.88 ,P<0.001) นอกจากนี้ยังพบความสัมพันธ์เชิงลบกับระดับ HBcrAg ในเลือดของผู้ป่วย HBeAg-positive(r=-0.286,P=0.070) และพบว่าผู้ป่วยกลุ่ม wild type มีระดับของ HBcrAg สูงสุด และพบระดับ HBcrAg ลดลงเมื่อมีการกลายพันธุ์เพิ่มขึ้น ส่วนในผู้ป่วย HBeAg-negative พบว่าการกลายพันธุ์มีความสัมพันธ์เชิงบวกกับ HBcrAg(r=0.273,P=0.008) ผลการศึกษาสรุปได้ว่า ddPCR เป็นเทคนิคที่มีประสิทธิภาพและมีความไวในการตรวจสอบการกลายพันธุ์บริเวณ BCP ได้ดีที่สุด นอกจากนี้ยังพบความสัมพันธ์กับระดับของ HBcrAg ในเลือดซึ่งเป็นตัวบ่งชี้ใหม่ที่ใช้ในทางคลินิก ดังนั้นเทคนิค ddPCR จึงอาจจะสามารถเป็นวิธีทางเลือกหนึ่งในการตรวจสอบการกลายพันธุ์ของไวรัสตับอักเสบบีได้

บทบาทของ Advanced Glycation End Products และภาวะเครียดออกซิเดชันในโรคกระดูกสันหลังส่วนเอวเสื่อม, มนัสนันท์ จิตรจำนงค์

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคกระดูกสันหลังส่วนเอวเสื่อมเป็นโรคที่เกิดจากการเสื่อมสภาพของหมอนรองกระดูกสันหลัง พบได้บ่อยในผู้สูงอายุ ปัจจัยหนึ่งที่เป็นสาเหตุร่วมทำให้เกิดการเสื่อมคือภาวะเครียดออกซิเดชัน การสะสมของสารอนุมูลอิสระ และ advanced glycation end products (AGEs) ซึ่งอาจมีบทบาทสำคัญต่อการเกิดและการดำเนินโรค วัตถุประสงค์ของการศึกษานี้เพื่อศึกษาบทบาทของ AGEs, receptor for AGEs (RAGE) ตัวชี้วัดภาวะเครียดออกซิเดชัน สารต้านอนุมูลอิสระ และความยาวเทโลเมียร์ในเลือดของผู้ป่วยโรคกระดูกสันหลังส่วนเอวเสื่อม การศึกษานี้แบ่งกลุ่มตัวอย่างเป็นสองกลุ่ม กลุ่มคนปกติที่มีสุขภาพดีและกลุ่มผู้ป่วยโรคกระดูกสันหลังส่วนเอวเสื่อม กลุ่มละ 75 ราย ซึ่งใช้ภาพถ่ายคลื่นแม่เหล็กไฟฟ้า (Magnetic Resonance Imaging, MRI) เพื่อแบ่งกลุ่มผู้ป่วยโรคกระดูกสันหลังส่วนเอวเสื่อมตามระดับความรุนแรงของโรค โดยทำการเก็บตัวอย่างเลือดจากอาสาสมัครทั้งสองกลุ่มเพื่อตรวจวัดระดับ AGEs, RAGE, 8-hydroxy-2'-deoxyguanosine (8-OHdG), protein carbonyl, malondialdehyde (MDA), nitrite ในพลาสมา การแสดงออกของยีน inducible nitric oxide synthase (iNOS) ในเลือด ระดับ total antioxidant capacity (TAC), ferric reducing antioxidant power (FRAP) ในพลาสมา ค่า catalase activity ค่า superoxide dismutase (SOD) activity ค่า glutathione peroxidase (GPx) activity และความยาวเทโลเมียร์ในเลือด จากการศึกษาพบว่าระดับ AGEs, RAGE, 8-OHdG, protein carbonyl, MDA, nitrite ในพลาสมา การแสดงออกของยีน iNOS ในเลือดของกลุ่มผู้ป่วยโรคกระดูกสันหลังส่วนเอวเสื่อมมีค่าสูงกว่ากลุ่มควบคุมอย่างมีนัยสำคัญทางสถิติ (P < 0.001, P < 0.001, P = 0.001, P = 0.01, P = 0.02, P < 0.001, P < 0.001 ตามลำดับ) และค่า GPx activity ในเลือดของกลุ่มผู้ป่วยโรคกระดูกสันหลังส่วนเอวเสื่อมมีค่าต่ำกว่ากลุ่มควบคุมอย่างมีนัยสำคัญทางสถิติ (P = 0.04) สำหรับระดับ TAC, FRAP ค่า catalase activity ค่า SOD activity และความยาวเทโลเมียร์ในเลือดพบว่าไม่มีความแตกต่างกันระหว่างกลุ่มผู้ป่วยโรคกระดูกสันหลังส่วนเอวเสื่อมและกลุ่มควบคุม นอกจากนี้ยังพบว่าระดับ protein carbonyl และ nitrite ในพลาสมามีความสัมพันธ์กับระดับความรุนแรงของโรคที่เพิ่มขึ้นจากภาพถ่ายคลื่นแม่เหล็กไฟฟ้า การศึกษานี้สรุปได้ว่าระดับ protein carbonyl และ nitrite ในพลาสมาอาจนำมาประยุกต์ใช้เป็นตัวชี้วัดในการพยากรณ์ระดับความรุนแรงของโรคกระดูกสันหลังส่วนเอวเสื่อมได้

Development Of Novel Point-Of-Care-Testing For Oxalate Detection In Urine Based On Oxalate-Binding Ligands, Naruerat Joybumrung

Chulalongkorn University Theses and Dissertations (Chula ETD)

Kidney stone disease is the third most common urinary tract disease worldwide that is more prevalent in the tropics. In Thailand, the highest stone prevalence up to 17% is reported in the Northeast. The disease is highly recurrent with a recurrence rate of about 50% within 5-10 years. The most common type of kidney stones is calcium oxalate (CaOx), and an increased urinary oxalate excretion is an important risk factor. Most of kidney stone patients have a hyperoxaluria condition (urinary oxalate >40 mg/day or >0.46 mmol/day). Therefore, urinary oxalate measurement has been widely used for estimating the risk of CaOx …

Integrative Transcriptomic Analysis And Validation Of Non-Coding Rna In Liver Cancers, Varunya Virushkul

Chulalongkorn University Theses and Dissertations (Chula ETD)

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) are the most common and cause cancer-related deaths. Due to the lack of sensitivity and specificity of conventional markers, such as AFP, CA19-9 and CEA. Thus, this study aimed to identify miRNAs as a diagnostic biomarker for HCC and iCCA. First, in discovery set, RNA sequencing and small RNA sequencing data of 992 HCC and adjacent tissues and 116 iCCA and adjacent tissues were downloaded from the GEO database. After that, the lncRNA-miRNA-mRNA network was constructed and analyzed for the differential expression of lncRNA (DElncRNA), miRNA (DEmiRNA), and mRNA (DEmRNA). Then, the significant …

Goblet Cell Carcinoma Of The Appendix: A Case Report On Goblet Cell Carcinoid, Sheliza Kabani, Aubtin Saedi, Austin Lehr, Lina O'Brien

HCA Healthcare Journal of Medicine

Goblet cell carcinoid of the appendix is a rare neoplasm with histological features of both neuroendocrine and adenocarcinomas. The combination of its aggressive behavior, infrequent occurrence, and variable clinical presentation convolutes the management of this tumor. We report the case of a 75-year-old female presenting with acute appendicitis. A laparoscopic appendectomy was performed. The pathology report showed goblet cell carcinoid at the base of the appendix with involvement of the proximal surgical margins. At her postoperative visit, the patient’s pathology report and options for management were reviewed, and the patient agreed to proceed with a right hemicolectomy 8-10 weeks after …

Purification And Use Of Trna For Enzymatic Post-Translational Addition Of Amino Acids To Proteins., Irem Avcilar-Kucukgoze, Howard Gamper, Ya-Ming Hou, Anna Kashina

Department of Biochemistry and Molecular Biology Faculty Papers

Post-translational addition of amino acids to proteins by enzymes using aminoacyl-tRNA is an emerging regulatory mechanism. Examples include Arg transfer in eukaryotes, Leu/Phe transfer in bacteria, and tRNA-synthetase-mediated addition of amino acids to Lys side chains. Here, we present a method of purification and use of tRNA for such reactions, focusing on tRNA^Arg and its use for arginylation. This method can also be used for other tRNA-mediated reactions. For complete details on the use and execution of this protocol, please refer to Avcilar-Kucukgoze et al. (2020).

Impact Of Endangered Animal Protection Rights, Policies, And Practices On Zoonotic Disease Spread, Daniella Fedak-Lengel

Honors Projects

Building on field research in Costa Rica and Belize, this honors project analyzes environmental and endangered animal protection policies, rights, and practices in Central America and the Caribbean, and assesses the impact of veterinary science and biological research and practice, particularly conservation biology, on animal welfare concerns. Informed by the recent surge in awareness regarding zoonoses and zoonotic disease transmission, prevention and control, resulting from the current global pandemic of SARS-CoV-2, the project assesses the need for new and innovative types of collaboration, particularly involving conservation biologists, environmental scientists, public health experts, law and policy makers, and global trade and …