Medical Biochemistry Commons^™

Spdef Modulates Transcriptional Output To Regulate Multiple Pathways: Immune And Inflammatory Pathways As Potential Hubs Targeted By Spdef In Rcc 7/T Cells, A Line Of Prostate Cancer Cells Of African American Origin, Mousa Vatanmakanian, Sweaty Koul, Hari Koul

School of Graduate Studies Faculty Publications

DiscoverBMB, March 25 - 28, 2023, Seattle, WA

Basal Expression Of Nuclear Transcription Factor, Nr4a1, Is Lower In Triple Negative Breast Cancer Compared To Other Breast Cancer Subsets, Manu Khosla, Hassan Yousefi, Celeste Wagner, Arian Lahiji, Suresh Alahari

School of Graduate Studies Faculty Publications

DiscoverBMB, March 25 - 28, 2023, Seattle, WA

Facile Green Synthesis Of Cinnamomum Tamala Extract Capped Silver Nanoparticles And Its Biological Applications, Sajina Narath, S. Sharath Shankar, Saranya Kothaplamoottil Sivan, Bini George, T. Dennis Thomas, Sankarannair Sabarinath, Sajithkumar K. Jayaprakash, Stanisław Wacławek, Vinod V.T. Padil

Department of Medicine Faculty Papers

The plant mediated biogenic synthesis of nanoparticles is of magnificent concern due to its eco-benign and single pot nature. Here, Cinnamomum tamala (C. tamala) aqueous leaf extract was utilised for the silver nanoparticles’ (Ag NPs) synthesis. The phytoconstituents in the leaf extract were analysed by standard methods. These metabolites, especially carbohydrate polymers reduce Ag ions to Ag NPs accompanied by a reddish-brown coloration of the reaction mixture. The visual observation of intense brown colour is the first indication of the formation of Ag NPs. Various spectro-analytical techniques further characterise the Ag NPs. The green synthesised spherical Ag NPs were crystalline …

Lkb1 Signaling And Patient Survival Outcomes In Hepatocellular Carcinoma, Khoa Nguyen, Katherine Hebert, Emily Mcconnell, Nicole Cullen, Thomas Cheng, Susanna Awoyode, Elizabeth Martin, Weina Chen, Tong Wu, Suresh K. Alahari, Reza Izadpanah, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow

School of Medicine Faculty Publications

The liver is a major organ that is involved in essential biological functions such as digestion, nutrient storage, and detoxification. Furthermore, it is one of the most metabolically active organs with active roles in regulating carbohydrate, protein, and lipid metabolism. Hepatocellular carcinoma is a cancer of the liver that is associated in settings of chronic inflammation such as viral hepatitis, repeated toxin exposure, and fatty liver disease. Furthermore, liver cancer is the most common cause of death associated with cirrhosis and is the 3rd leading cause of global cancer deaths. LKB1 signaling has been demonstrated to play a role in …

Successful Heart-Liver Transplant Using Dual-Organ Normothermic Perfusion In A Patient With Fontan Failure, Anton Kozyryev, Daniel Lemen, Jessica Dunn, Steven E Rokita

Faculty, Staff and Student Publications

Iodotyrosine deiodinase (IYD) is unusual in its reliance on flavin to promote reductive dehalogenation of halotyrosines under aerobic conditions. Applications of this activity can be envisioned for bioremediation, but expansion of its specificity requires an understanding of the mechanistic steps that limit the rate of turnover. Key processes capable of controlling steady-state turnover have now been evaluated and described in this study. While proton transfer is necessary for converting the electron-rich substrate into an electrophilic intermediate suitable for reduction, kinetic solvent deuterium isotope effects suggest that this process does not contribute to the overall efficiency of catalysis under neutral conditions. …

The Non-Coding Rna Journal Club: Highlights On Recent Papers—12, Patrick K.T. Shiu, Mirolyuba Ilieva, Anja Holm, Shizuka Uchida, Johanna K. Distefano, Agnieszka Bronisz, Ling Yang, Yoh Asahi, Ajay Goel, Liuqing Yang, Ashok Nuthanakanti, Alexander Serganov, Suresh K. Alahari, Chunru Lin, Barbara Pardini, Alessio Naccarati, Jing Jin, Beshoy Armanios, Xiao Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, André P. Gerber, He Lin, Simon J. Conn, Doha Magdy Mostafa Sleem

School of Graduate Studies Faculty Publications

No abstract provided.

Circulating Plasma Exosomal Proteins Of Either Shiv-Infected Rhesus Macaque Or Hiv-Infected Patient Indicates A Link To Neuropathogenesis, Partha K. Chandra, Stephen E. Braun, Sudipa Maity, Jorge A. Castorena-Gonzalez, Hogyoung Kim, Jeffrey G. Shaffer, Sinisa Cikic, Ibolya Rutkai, Jia Fan, Jessie J. Guidry, David K. Worthylake, Chenzhong Li, Asim B. Abdel-Mageed, David W. Busija

School of Medicine Faculty Publications

Despite the suppression of human immunodeficiency virus (HIV) replication by combined antiretroviral therapy (cART), 50–60% of HIV-infected patients suffer from HIV-associated neurocognitive disorders (HAND). Studies are uncovering the role of extracellular vesicles (EVs), especially exosomes, in the central nervous system (CNS) due to HIV infection. We investigated links among circulating plasma exosomal (crExo) proteins and neuropathogenesis in simian/human immunodeficiency virus (SHIV)-infected rhesus macaques (RM) and HIV-infected and cART treated patients (Patient-Exo). Isolated EVs from SHIV-infected (SHIV-Exo) and uninfected (CTL-Exo) RM were predominantly exosomes (particle size < 150 nm). Proteomic analysis quantified 5654 proteins, of which 236 proteins (~4%) were significantly, differentially expressed (DE) between SHIV-/CTL-Exo. Interestingly, different CNS cell specific markers were abundantly expressed in crExo. Proteins involved in latent viral reactivation, neuroinflammation, neuropathology-associated interactive as well as signaling molecules were expressed at significantly higher levels in SHIV-Exo than CTL-Exo. However, proteins involved in mitochondrial biogenesis, ATP production, autophagy, endocytosis, exocytosis, and cytoskeleton organization were significantly less expressed in SHIV-Exo than CTL-Exo. Interestingly, proteins involved in oxidative stress, mitochondrial biogenesis, ATP production, and autophagy were significantly downregulated in primary human brain microvascular endothelial cells exposed with HIV+/cART+ Patient-Exo. We showed that Patient-Exo significantly increased blood–brain barrier permeability, possibly due to loss of platelet endothelial cell adhesion molecule-1 protein and actin cytoskeleton structure. Our novel findings suggest that circulating exosomal proteins expressed CNS cell markers—possibly associated with viral reactivation and neuropathogenesis—that may elucidate the etiology of HAND.

Myo1e Overexpression In Lung Adenocarcinoma Is Associated With Increased Risk Of Mortality, Ignacio Jusue-Torres, Richies Tiv, Julio C. Ricarte-Filho, Apurva Mallisetty, Leglys Contreras-Vargas, Maria Jose Godoy-Calderon, Karam Khaddour, Kathleen Kennedy, Klara Valyi-Nagy, Odile David, Martha Menchaca, Anastasia Kottorou, Angelos Koutras, Foteinos Dimitrakopoulos, Khaled M. Abdelhady, Malek Massad, Israel Rubinstein, Lawrence Feldman, John Stewart, Takeshi Shimamura, Ludmila Danilova, Alicia Hulbert

School of Medicine Faculty Publications

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. …

Mechanosensitive Membrane Proteins: Usual And Unusual Suspects In Mediating Mechanotransduction, Miriam B Goodman, Elizabeth S Haswell, Valeria Vásquez

Faculty, Staff and Student Publications

This Viewpoint, which accompanies a Special Issue focusing on membrane mechanosensors, discusses unifying and unique features of both established and emerging mechanosensitive (MS) membrane proteins, their distribution across protein families and phyla, and current and future challenges in the study of these important proteins and their partners. MS membrane proteins are essential for tissue development, cellular motion, osmotic homeostasis, and sensing external and self-generated mechanical cues like those responsible for touch and proprioception. Though researchers' attention and this Viewpoint focus on a few famous ion channels that are considered the usual suspects as MS mechanosensors, we also discuss some of …

Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei

Markey Cancer Center Faculty Publications

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation–reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the …

Harnessing Transcriptionally Driven Chromosomal Instability Adaptation To Target Therapy-Refractory Lethal Prostate Cancer., Brittiny Dhital, Sandra Santasusagna, Perumalraja Kirthika, Michael Xu, Peiyao Li, Marc Carceles-Cordon, Rajesh K. Soni, Zhuoning Li, Ronald C. Hendrickson, Matthew J. Schiewer, William K. Kelly, Cora N. Sternberg, Jun Luo, Amaia Lujambio, Carlos Cordon-Cardo, Monica Alvarez-Fernandez, Marcos Malumbres, Haojie Huang, Adam Ertel, Josep Domingo-Domenech, Veronica Rodriguez-Bravo

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Metastatic prostate cancer (PCa) inevitably acquires resistance to standard therapy preceding lethality. Here, we unveil a chromosomal instability (CIN) tolerance mechanism as a therapeutic vulnerability of therapy-refractory lethal PCa. Through genomic and transcriptomic analysis of patient datasets, we find that castration and chemotherapy-resistant tumors display the highest CIN and mitotic kinase levels. Functional genomics screening coupled with quantitative phosphoproteomics identify MASTL kinase as a survival vulnerability specific of chemotherapy-resistant PCa cells. Mechanistically, MASTL upregulation is driven by transcriptional rewiring mechanisms involving the non-canonical transcription factors androgen receptor splice variant 7 and E2F7 in a circuitry that restrains deleterious CIN and …

A Complete Methyl-Lysine Binding Aromatic Cage Constructed By Two Domains Of Phf2, John R Horton, Jujun Zhou, Qin Chen, Xing Zhang, Mark T Bedford, Xiaodong Cheng

Faculty, Staff and Student Publications

The N-terminal half of PHF2 harbors both a plant homeodomain (PHD) and a Jumonji domain. The PHD recognizes both histone H3 trimethylated at lysine 4 and methylated nonhistone proteins including vaccinia-related kinase 1 (VRK1). The Jumonji domain erases the repressive dimethylation mark from histone H3 lysine 9 (H3K9me2) at select promoters. The N-terminal amino acid sequences of H3 (AR2TK4) and VRK1 (PR2VK4) bear an arginine at position 2 and lysine at position 4. Here, we show that the PHF2 N-terminal half binds to H3 and VRK1 peptides containing K4me3, with dissociation constants (KD values) of 160 nM and 42 nM, …

Differential Transcriptional Alterations In Detoxification Genes In Parkinson’S Disease In Egypt, Nourhan Shebl

Theses and Dissertations

PD is the most common motor neurodegenerative disease worldwide. The underlying cause of PD is still unknow, owingthis to the complexity of the disease. Often, genetics and environmental factors are collaborating in the initiation of the disease. Despite the diversity of its genetical and environmental profiles, the Egyptian population is one of the mostunderrepresented population in terms of PD research. In this study, we investigated PD through various perspectives tohighlight the complexity of the disease in Egypt, taking into consideration the diversity of the Egyptian population. We recruited PD patients and reference controls from 4 governorates: Cairo, Giza, Alexandria, and …

Semi-Quantitative Detection Of Pseudouridine Modifications And Type I/Ii I/Ii Hypermodifications In Human Mrnas Using Direct Long-Read Sequencing, Sepideh Tavakoli, Mohammad Nabizadeh, Amr Makhamreh, Howard Gamper, Caroline A Mccormick, Neda K Rezapour, Ya-Ming Hou, Meni Wanunu, Sara H Rouhanifard

Department of Biochemistry and Molecular Biology Faculty Papers

Here, we develop and apply a semi-quantitative method for the high-confidence identification of pseudouridylated sites on mammalian mRNAs via direct long-read nanopore sequencing. A comparative analysis of a modification-free transcriptome reveals that the depth of coverage and specific k-mer sequences are critical parameters for accurate basecalling. By adjusting these parameters for high-confidence U-to-C basecalling errors, we identify many known sites of pseudouridylation and uncover previously unreported uridine-modified sites, many of which fall in k-mers that are known targets of pseudouridine synthases. Identified sites are validated using 1000-mer synthetic RNA controls bearing a single pseudouridine in the center position, demonstrating systematic …

Sgc-Camkk2-1: A Chemical Probe For Camkk2, Carrow Wells, Yi Liang, Thomas L Pulliam, Chenchu Lin, Dominik Awad, Benjamin Eduful, Sean O'Byrne, Mohammad Anwar Hossain, Carolina Moura Costa Catta-Preta, Priscila Zonzini Ramos, Opher Gileadi, Carina Gileadi, Rafael M Couñago, Brittany Stork, Christopher G Langendorf, Kevin Nay, Jonathan S Oakhill, Debarati Mukherjee, Luigi Racioppi, Anthony R Means, Brian York, Donald P Mcdonnell, John W Scott, Daniel E Frigo, David H Drewry

Faculty, Staff and Student Publications

The serine/threonine protein kinase calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) plays critical roles in a range of biological processes. Despite its importance, only a handful of inhibitors of CAMKK2 have been disclosed. Having a selective small molecule tool to interrogate this kinase will help demonstrate that CAMKK2 inhibition can be therapeutically beneficial. Herein, we disclose SGC-CAMKK2-1, a selective chemical probe that targets CAMKK2.

Disruption Of The Interaction Between Mutationally Activated Gαq And Gβγ Attenuates Aberrant Signaling, Jenna L Aumiller, Philip B Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G protein stimulation via G protein-coupled receptors promotes downstream proliferative signaling. Mutations can occur in Gα proteins which prevent GTP hydrolysis; this allows the G proteins to signal independently of G protein-coupled receptors and can result in various cancers, such as uveal melanoma (UM). Most UM cases harbor Q209L, Q209P, or R183C mutations in Gαq/11 proteins, rendering the proteins constitutively active (CA). Although it is generally thought that active, GTP-bound Gα subunits are dissociated from and signal independently of Gβγ, accumulating evidence indicates that some CA Gα mutants, such as Gαq/11, retain binding to Gβγ, and this interaction is …

Differentiating Pc12 Cells To Evaluate Neurite Densities Through Live-Cell Imaging, Jordyn Karliner, Diane E Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Although PC12 cells are a valuable tool in neuroscience research, previously published PC12 cell differentiation techniques fail to consider the variability in differentiation rates between different PC12 cell strains and clonal variants. Here, we present a comprehensive protocol to differentiate PC12 cells into equivalent neurite densities through live-cell imaging for morphological, immunocytochemical, and biochemical analyses. We detail steps on optimized substrate coating, plating techniques, culture media, validation steps, and quantification techniques.

Quantifying Metal Interactions With The Antimicrobial Peptide Calcitermin, Maria G. Aviles-Sandoval, Michael Stevenson

Featured Student Work

Antimicrobial Peptides (AMPs) are novel therapeutic agents that play important roles in the innate immune system with its ability to kill gram-positive and gram-negative bacteria. Antibiotics are losing their efficacy, thus requiring a larger dose of medicine for treatment resulting in the increase of antibiotic resistance. AMPs are an attractive approach for exploration due to their broad-spectrum activity and ease of synthesis. Furthermore, fewer bacteria have developed resistance to AMPs. Several AMPs have demonstrated increased antimicrobial activity with metal ions, like Zn(II) and Cu(II) binding to the peptide. In this study, we performed the purification of Calcitermin through high-performance liquid …

Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Composed of sphingosine and a fatty acid, ceramides are lipid molecules that serve as key metabolic signaling molecules of a sphingolipid pathway. While it acts as a precursor of complex sphingolipids, inducing ceramide generation can cause cell stress leading to subsequent cell death via apoptosis, necrosis, and even mitophagy. With regards to cell death specifically, a novel form of regulated cell death, ferroptosis, has recently been recognized of necrotic nature. Its unique morphological features and distinct properties have been observed over the last several decades; however, the molecular features were not identifiable as pure evidence of cell death, until recently …

Molecular Signaling Network And Therapeutic Developments In Breast Cancer Brain Metastasis, Mercilena Benjamin, Pushkar Malakar, Rohit Anthony Sinha, Mohd Wasim Nasser, Surinder K. Batra, Jawed A. Siddiqui, Bandana Chakravarti

Journal Articles: Biochemistry & Molecular Biology

Breast cancer (BC) is one of the most frequently diagnosed cancers in women worldwide. It has surpassed lung cancer as the leading cause of cancer-related death. Breast cancer brain metastasis (BCBM) is becoming a major clinical concern that is commonly associated with ER-ve and HER2+ve subtypes of BC patients. Metastatic lesions in the brain originate when the cancer cells detach from a primary breast tumor and establish metastatic lesions and infiltrate near and distant organs via systemic blood circulation by traversing the BBB. The colonization of BC cells in the brain involves a complex interplay in the tumor microenvironment (TME), …

Development Of Raman Spectroscopy-Integrated Calcium Oxalate Crystallization Index (Rcoci) Test And Its Clinical Validation For Diagnosing Calcium Oxalate Urolithiasis, Kamonchat Boonkam

Chulalongkorn University Theses and Dissertations (Chula ETD)

Urinary stone disease is mostly formed in the kidney and is highly recurrent. The most common type of urinary stones is calcium oxalate (CaOx). The development of urinary screening tests for estimating risk of CaOx stone formation is still challenging. Recently, we developed a urinary test, called indole-reacted calcium oxalate crystallization index (iCOCI) test, that provided a high diagnostic accuracy for CaOx urolithiasis. However, the iCOCI test is time-consuming and highly acidic chemicals are required for quantifying amount of CaOx. In this study, we proposed to develop a new method, called Raman spectroscopy-integrated calcium oxalate crystallization index (rCOCI) test, that …

Crispr-Cas12a-Based Detection And Differentiation Of Mycobacterium Spp., Peeraphan Compiro

Chulalongkorn University Theses and Dissertations (Chula ETD)

Mycobacterium species cause several vital human diseases, including tuberculosis (TB) and non-tuberculous mycobacterial (NTM) infections. TB is a chronic infectious disease caused by the Mycobacterium tuberculosis complex (MTBC). Additionally, non-tuberculous mycobacteria infections are caused by major NTM species, including Mycobacterium abscessus, Mycobacterium avium, Mycobacterium fortuitum, Mycobacterium kansasii, Mycobacterium gordonae, and Mycobacterium intracelulare, are medically necessary. Both groups of infections can lead to outbreaks in immunocompromised individuals and AIDS patients. It is crucial to differentiate between these two groups of mycobacterial infections, as they require distinct treatment approaches. However, initial diagnosis poses limitations in terms of time and diagnostic tools. Therefore, …

Role Of The Ormdls In Keratinocytes, Souad Hatmi

Theses and Dissertations

The epidermis, the outermost layer of the skin, serves as a vital barrier protecting the body from environmental stressors, pathogens, and dehydration. Keratinocytes, the predominant cell type in the epidermis, play a central role in maintaining skin integrity and barrier function. In normal human skin, keratinocytes move from the basal layer to the stratum corneum, the top layer of the epidermis. In their travel, keratinocytes undergo a process of terminal differentiation, loss their ability to proliferate, secrete sphingolipids into the extracellular space, and gradually loss their nucleus and organelles. Sphingolipids, particularly ceramides, are key components of the intercellular lipid lamellae …

Microrna-1 Attenuates The Growth And Metastasis Of Small Cell Lung Cancer Through Cxcr4/Foxm1/Rrm2 Axis, Parvez Khan, Jawed A. Siddiqui, Prakash Kshirsagar Dr., Ramakanth Chirravuri Venkata, Shailendra K. Maurya, Tamara Mirzapoiazova, Naveenkumar Perumal, Sanjib Chaudhary, Ranjana K. Kanchan, Mahek Fatima, Md Arafat Khan, Asad Ur Rehman, Imayavaramban Lakshmanan, Sidharth Mahapatra, Geoffrey A. Talmon, Prakash Kulkarni, Apar Kishor Ganti, Maneesh Jain, Ravi Salgia, Surinder K. Batra, Mohd W. Nasser

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype that is associated with high recurrence and poor prognosis. Due to lack of potential drug targets, SCLC patients have few therapeutic options. MicroRNAs (miRNAs) provide an interesting repertoire of therapeutic molecules; however, the identification of miRNAs regulating SCLC growth and metastasis and their precise regulatory mechanisms are not well understood.

METHODS: To identify novel miRNAs regulating SCLC, we performed miRNA-sequencing from donor/patient serum samples and analyzed the bulk RNA-sequencing data from the tumors of SCLC patients. Further, we developed a nanotechnology-based, highly sensitive method to detect microRNA-1 (miR-1, …

Roles Unveiled For Membrane-Associated Mucins At The Ocular Surface Using A Muc4 Knockout Mouse Model, Rafael Martinez-Carrasco, Satyanarayan Rachagani, Surinder K. Batra, Pablo Argüeso, M Elizabeth Fini

Journal Articles: Biochemistry & Molecular Biology

Membrane-associated mucins (MAMs) are proposed to play critical roles at the ocular surface; however, in vivo evidence has been lacking. Here we investigate these roles by phenotyping of a Muc4 KO mouse. Histochemical analysis for expression of the beta-galactosidase transgene replacing Muc4 revealed a spiraling ribbon pattern across the corneal epithelium, consistent with centripetal cell migration from the limbus. Depletion of Muc4 compromised transcellular barrier function, as evidenced by an increase in rose bengal staining. In addition, the corneal surface was less smooth, consistent with disruption of tear film stability. While surface cells presented with well-developed microprojections, an increase in …

ความหลากหลายทางพันธุกรรมของโรคไขมันพอกตับที่สัมพันธ์กับการติดเชื้อเอชไอวีและโรคมะเร็งตับ, กมลชนก มูลลิสาร

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคไขมันพอกตับเป็นหนึ่งในสาเหตุหลักของโรคตับอักเสบเรื้อรังที่สามารถดำเนินโรคไปสู่โรคมะเร็งตับได้ ความชุกของโรคไขมันพอกตับในประเทศไทยพบประมาณร้อยละ 20-30 สาเหตุของการเกิดไขมันพอกตับที่พบบ่อยได้แก่โรคอ้วน เบาหวาน กลุ่มโรคเมตาบอลิกและปัจจัยทางพันธุกรรม การศึกษาที่ผ่านมาพบว่ามียีนหลายตำแหน่งที่มีบทบาทเกี่ยวข้องกับกลไกการเกิดโรค ที่สำคัญได้แก่ PNPLA3, TM6SF2 และ HSD17B13 งานวิจัยนี้มีจุดประสงค์เพื่อหาความสัมพันธ์ของความหลากหลายทางพันธุกรรมของยีนดังกล่าวกับการเกิดโรคไขมันพอกตับในคนไทย โดยศึกษาจีโนไทป์ของทั้งสามยีนด้วยเทคนิค TaqMan Real-time PCR จากตัวอย่างเลือด 900 ตัวอย่างของ 4 กลุ่มได้แก่ กลุ่มควบคุมที่มีสุขภาพดี ผู้ป่วยโรคไขมันพอกตับที่มีและไม่มีการติดเชื้อเอชไอวี และกลุ่มผู้ป่วยมะเร็งตับ ผลการศึกษาพบว่าจีโนไทป์ GG ของยีน PNPLA3 rs738409 เป็นปัจจัยเสี่ยงของการเกิดโรคไขมันพอกตับในทุกกลุ่มที่ศึกษาเมื่อเปรียบเทียบกับกลุ่มควบคุม ดังนี้ กลุ่มผู้ป่วยที่ไม่มีการติดเชื้อเอชไอวี [odds ratio (OR)=6.52, 95% confidence interval (CI) 2.64-16.08, P<0.001] กลุ่มผู้ป่วยที่มีการติดเชื้อเอชไอวี(OR=2.76, 95% CI 1.09-7.00, P=0.03) และกลุ่มผู้ป่วยมะเร็งตับ (OR=9.96, 95% CI 4.06-24.44, P<0.001) อย่างไรก็ตามไม่ พบความสัมพันธ์ของยีน TM6SF2 rs58542926 และ HSD17B13 rs6834314 กับการเกิดโรคของ กลุ่มตัวอย่างต่างๆ จากการวิเคราะห์หาปัจจัยเสี่ยงอิสระด้วยสมการถดถอยพบว่า ค่าดัชนีมวลกาย ที่สูง โรคเบาหวาน ระดับเอนไซม์ALT ที่สูงและการไม่ติดเชื้อเอชไอวีเป็นปัจจัยเสี่ยงในการทำให้ เกิดความรุนแรงในการสะสมไขมันในตับ โดยสรุปผลการวิจัยนี้พบว่าความหลากหลายทาง พันธุกรรมของ PNPLA3 มีความสัมพันธ์กับการเกิดโรคไขมันพอกตับและเพิ่มความเสี่ยงต่อการเกิด โรคมะเร็งตับในประชากรไทย แต่ไม่พบความสัมพันธ์ดังกล่าวสำหรับยีน TM6SF2 และ HSD17B13

การมีส่วนร่วมของปัจจัยทางพันธุกรรมต่อการสร้างซีซีซีดีเอ็นเอของไวรัสตับอักเสบบี, กัลยกร สิงห์สังข์

Chulalongkorn University Theses and Dissertations (Chula ETD)

การติดเชื้อไวรัสตับอักเสบบี (hepatitis B virus infection; HBV) เป็นปัญหาทางด้านสาธารณสุขที่สำคัญทั่วโลก เนื่องจากผู้ติดเชื้อไวรัสตับอักเสบบีสามารถพัฒนาความรุนแรงไปเป็นโรคตับแข็ง (cirrhosis) และมะเร็งตับ (hepatocellular carcinoma: HCC) ซึ่งนำไปสู่การเสียชีวิตได้ในที่สุด ถึงแม้ว่าในปัจจุบันโรคติดเชื้อไวรัสตับอักเสบบีสามารถรักษาได้ด้วยยาต้านไวรัส อย่างไรก็ตามยังไม่สามารถรักษาให้หายขาดได้ เนื่องจากการคงอยู่ของ covalently closed circular DNA (cccDNA) ซึ่งเป็น DNA สายคู่แบบวงปิดคล้ายโครโมโซมขนาดเล็กภายในนิวเคลียสของเซลล์ตับ ขบวนการสร้าง cccDNA จำเป็นต้องอาศัยการทำงานของปัจจัยทางพันธุกรรมของเซลล์เจ้าบ้าน (host factors) หลายชนิด โดยเฉพาะอย่างยิ่ง DNA damage binding protein 2 (DDB2) และ DNA polymerase δ (DNA pol δ) อย่างไรก็ตามการศึกษายังไม่พบการศึกษาการแสดงออกของ host factors ดังกล่าวต่อการสร้าง cccDNA ในเซลล์ตับของผู้ป่วยโรคไวรัสตับอักเสบบี โดยเฉพาะไวรัสตับอักเสบบีแบบแอบแฝง (occult HBV infection หรือ OBI) รวมทั้งยังไม่มีวิธีมาตรฐานในการตรวจวัดระดับของ cccDNA ในเซลล์ตับ ดังนั้นการศึกษานี้จึงมีวัตถุประสงค์ในการศึกษาความสัมพันธ์ของระดับของ cccDNA และ host factors ในเซลล์ตับของผู้ป่วยมะเร็งตับที่เกิดจากจากติดเชื้อไวรัสตับอักเสบบี (HBV-related HCC) และไวรัสตับอักเสบบีแบบแอบแฝง (occult HBV (OBI)-related HCC) ด้วยการทำdroplet digital PCR (ddPCR) และ Western blot ตามลำดับ จากเนื้อเยื่อบริเวณ non-tumor หรือ adjacent tissues ผลการศึกษาระดับการแสดงออกของ intrahepatic HBV DNA และ cccDNA ในเซลล์ตับ ของผู้ป่วย พบว่าผู้ป่วยกลุ่ม HBV-related HCC มีการแสดงออกของ intrahepatic HBV …

Development Of Sensors For Bacteria And Wound Environment Monitoring, Pannawich Thirabowonkitphithan

Chulalongkorn University Theses and Dissertations (Chula ETD)

Diabetes mellitus (DM) is a leading cause of death and reduces life expectancy. Complications from diabetes have wreaked havoc not only on patients' quality of life, but also on the global burdens of public health and socioeconomic development. The most frequent complication among patients with diabetes mellitus is diabetic wounds, particularly diabetic foot ulcers because of the damage to sensory nerves and blood vessel issues brought on by elevated blood glucose levels. As a result, chronic wounds eventually develop and are prone to infection. In this study, several novel analytical devices for the detection of wound infections and the wound …

Mycobacterium Spp. Identification By Nanopore Technology, Samitanan Sunantawanit

Chulalongkorn University Theses and Dissertations (Chula ETD)

Tuberculosis is caused by infection with Mycobacterium tuberculosis (MTB). Although TB and non-tuberculous mycobacteria (NTM) infection exhibit similar symptoms, their treatments differ significantly. NTM strains need a specific drug regimen and some NTM strains are resistant to anti-TB drugs. Hence, mycobacterial identification is crucial. At present, the culture-based technique is the gold standard in mycobacterium detection, but it is time-consuming (3-6 weeks). Here, this study aimed to develop mycobacterial amplicon-based nanopore sequencing (Myco-ANS) assay for the differentiation of eight reference strains of mycobacteria, as well as to assess the diagnostic accuracy of Myco-ANS compared with reference line probe assay for …

Hif-1 Activation And Inflammatory Responses To Hypoxia, Shazreen Shaharuddin, Nik Mohd Afizan Nik Abd Rahman, Mas Jaffri Masarudin, Mohammedarfat N Alamassi

International Journal of Aviation, Aeronautics, and Aerospace

Acute hypoxia is a significant physiological danger during high-altitude flying and military aircraft missions. The human brain requires a constant supply of oxygen to function properly, and is susceptible to settings with low availability of air oxygen. Hypoxia can influence inflammatory signalling, and both central and systemic responses can activate HIF pathway genes. HIFs are critical molecules that regulate inflammation andhypoxia, ensuring appropriate cell function and survival. Hypoxia is the condition in which insufficient oxygen reaches the body's tissues. It can be caused by a decrease in partial oxygen pressure (PO2) in the environment, problems with breathing and/or oxygen transport, …