Medical Biochemistry Commons^™

Evidence For Paracrine Protective Role Of Exogenous Αa-Crystallin In Retinal Ganglion Cells, Madhu Nath, Zachary B Sluzala, Ashutosh S Phadte, Yang Shan, Angela M Myers, Patrice E Fort

Department of Biochemistry and Molecular Biology Faculty Papers

Expression and secretion of neurotrophic factors have long been known as a key mechanism of neuroglial interaction in the central nervous system. In addition, several other intrinsic neuroprotective pathways have been described, including those involving small heat shock proteins such as α-crystallins. While initially considered as a purely intracellular mechanism, both αA-crystallins and αB-crystallins have been recently reported to be secreted by glial cells. While an anti-apoptotic effect of such secreted αA-crystallin has been suggested, its regulation and protective potential remain unclear. We recently identified residue threonine 148 (T148) and its phosphorylation as a critical regulator of αA-crystallin intrinsic neuroprotective …

Viral Ejection Proteins: Mosaically Conserved, Conformational Gymnasts, Nicholas A. Swanson, Chun-Feng Hou, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Bacterial viruses (or bacteriophages) have developed formidable ways to deliver their genetic information inside bacteria, overcoming the complexity of the bacterial-cell envelope. In short-tailed phages of the Podoviridae superfamily, genome ejection is mediated by a set of mysterious internal virion proteins, also called ejection or pilot proteins, which are required for infectivity. The ejection proteins are challenging to study due to their plastic structures and transient assembly and have remained less characterized than classical components such as the phage coat protein or terminase subunit. However, a spate of recent cryo-EM structures has elucidated key features underscoring these proteins’ assembly and …

Positive Selection And Enhancer Evolution Shaped Lifespan And Body Mass In Great Apes, Daniela Tejada-Martinez, Roberto A Avelar, Inês Lopes, Bruce Zhang, Guy Novoa, João Pedro De Magalhães, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body …

Liquid-Liquid Phase Separation Of Tdp-43 And Fus In Physiology And Pathology Of Neurodegenerative Diseases, Jenny L Carey, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Liquid-liquid phase separation of RNA-binding proteins mediates the formation of numerous membraneless organelles with essential cellular function. However, aberrant phase transition of these proteins leads to the formation of insoluble protein aggregates, which are pathological hallmarks of neurodegenerative diseases including ALS and FTD. TDP-43 and FUS are two such RNA-binding proteins that mislocalize and aggregate in patients of ALS and FTD. They have similar domain structures that provide multivalent interactions driving their phase separation in vitro and in the cellular environment. In this article, we review the factors that mediate and regulate phase separation of TDP-43 and FUS. We also …

Synthesis, Characterization And Physicochemical Properties Of Biogenic Silver Nanoparticle-Encapsulated Chitosan Bionanocomposites, Sreelekha Ediyilyam, Mahesh M Lalitha, Bini George, Sarojini Sharath Shankar, Stanisław Wacławek, Miroslav Černík, Vinod Vellora Thekkae Padil

Department of Medicine Faculty Papers

Green bionanocomposites have garnered considerable attention and applications in the pharmaceutical and packaging industries because of their intrinsic features, such as biocompatibility and biodegradability. The work presents a novel approach towards the combined effect of glycerol, tween 80 and silver nanoparticles (AgNPs) on the physicochemical properties of lyophilized chitosan (CH) scaffolds produced via a green synthesis method.The produced bionanocomposites were characterized with the help of Fourier transform infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM). The swelling behavior, water vapor transmission rate, moisture retention capability, degradation in Hanks solution, biodegradability in soil, mechanical strength and electrochemical performance of the composites …

Interplay Between An Atp-Binding Cassette F Protein And The Ribosome From Mycobacterium Tuberculosis, Zhicheng Cui, Xiaojun Li, Joonyoung Shin, Howard Gamper, Ya-Ming Hou, James C Sacchettini, Junjie Zhang

Department of Biochemistry and Molecular Biology Faculty Papers

EttA, energy-dependent translational throttle A, is a ribosomal factor that gates ribosome entry into the translation elongation cycle. A detailed understanding of its mechanism of action is limited due to the lack of high-resolution structures along its ATPase cycle. Here we present the cryo-electron microscopy (cryo-EM) structures of EttA from Mycobacterium tuberculosis (Mtb), referred to as MtbEttA, in complex with the Mtb 70S ribosome initiation complex (70SIC) at the pre-hydrolysis (ADPNP) and transition (ADP-VO4) states, and the crystal structure of MtbEttA alone in the post-hydrolysis (ADP) state. We observe that MtbEttA binds the E-site of the Mtb 70SIC, remodeling the …

Ultrasound 96 Probe Device Protocol For Cancer Cell Treatment, Aisling Field, Brijesh K. Tiwari, James F. Curtin, Julie R M Mondala, Janith Wanigasekara

Articles

Ultrasound is a sound wave with frequencies ranging between 20 kHz and 20 MHz. Ultrasound is able to temporarily and repeatedly open the BBB safely and enhance chemotherapeutic delivery without adverse effects. This novel technique in drug delivery benefits from the powerful ability of ultrasound to produce cavitation activity. Cavitation is the generation and activity of gas-filled bubbles in a medium exposed to ultrasound. As the pressure wave passes through the media, gas bubbles expand at low pressure and contract at high pressure. This leads to oscillation which produces a circulating fluid flow known as microstreaming around the bubble with …

Channelopathy-Causing Mutations In The S45A/S45B And Ha/Hb Helices Of KCa2.3 And KCa3.1 Channels Alter Their Apparent Ca2+ Sensitivity, Razan Orfali, Young-Woo Nam, Hai Minh Nguyen, Mohammad Asikur Rahman, Grace Yang, Meng Cui, Heike Wulff, Miao Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca²⁺-activated potassium (K_Ca2.x and K_Ca3.1, also called SK and IK) channels are activated exclusively by a Ca²⁺-calmodulin gating mechanism. Wild-type K_Ca2.3 channels have a Ca²⁺ EC₅₀ value of ∼0.3 μM, while the apparent Ca²⁺ sensitivity of wild-type K_Ca3.1 channels is ∼0.27 μM. Heterozygous genetic mutations of K_Ca2.3 channels have been associated with Zimmermann-Laband syndrome and idiopathic noncirrhotic portal hypertension, while K_Ca3.1 channel mutations were reported in hereditary xerocytosis patients. K_Ca2.3_S436C and K_Ca2.3_V450L channels with …

Liquid Biopsy: A Step Closer To Transform Diagnosis, Prognosis And Future Of Cancer Treatments, Saife N. Lone, Sabah Nisar, Tariq Masoodi, Mayank Singh, Arshi Rizwan, Sheema Hashem, Wael El-Rifai, Davide Bedognetti, Surinder K. Batra, Mohammad Haris, Ajaz A. Bhat, Muzafar A. Macha

Journal Articles: Biochemistry & Molecular Biology

Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly …

Development Of An Hipsc-Cortical Neuron Long-Term Potentiation Model And Its Application To Alzheimer's Disease Modeling And Drug Evaluation, Kaveena Autar

Electronic Theses and Dissertations, 2020-2023

Alzheimer's disease (AD) is commonly characterized by a loss of cognitive function due to the deterioration of neuronal synapses from the presence of senile amyloid beta-42 (Aß42) plaques. Evaluating cognitive deficits caused by Aß42 using human cortical neurons poses a challenge due to sourcing difficulties, and the use of animal models to assess drug efficacy creates biological hurdles from lack of species translatability. Recent advances in induced-pluripotent stem cell technology have enabled the development of mature, human-based cortical neuron models. The development of an hiPSC-cortical neuron differentiation protocol facilitates the exploration of disease onset and functional analysis from a patient-derived …

Plasmonic Sensor Based Detection Of Dopamine, Sang Lee

Electronic Theses and Dissertations, 2020-2023

With a rapidly ageing population, neurological diseases are becoming increasingly relevant in the design of public health policies and strategies in western societies. In the last decades, biochemical research has consistently shown the critical role that neurotransmitters and their associated metabolites play as biomarkers in tracking and diagnosis of different brain disorders and cancers. In particular, dopamine, an organic electrochemical neurotransmitter, has been shown to be paramount for the proper functioning of the neural system. Dopamine's dysfunction, has been shown to underlie the pathogenesis in several neurological disorders such as Parkinson's disease, depression, chronic schizophrenia and psychosis. Unfortunately, currently available …

Treatment Of Hypothyroidism: Desiccated Thyroid Extract, Aimee Fong

Capstone Showcase

The treatment of hypothyroidism with Levothyroxine (T4) has been well studied and FDA approved. However, many patients continue to have signs and symptoms of hypothyroidism while on Levothyroxine treatment despite reaching appropriate thyroid levels. An additional thyroid treatment known as desiccated thyroid extract (DTE) is made from dried pig thyroid glands and is advertised as a “natural” alternative to Levothyroxine. Despite lack of FDA approval and studies surrounding DTE, clinicians have prescribed DTE to patients, many of whom reported relief of their symptoms. The following poster highlights the approach to the treatment of hypothyroidism with Levothyroxine and DTE and outlines …

Ubiquitous Aberration In Cholesterol Metabolism Across Pancreatic Ductal Adenocarcinoma, Venugopal Gunda, Thiago C. Genaro-Mattos, Jyoti B. Kaushal, Ramakanth C. Venkata, Gopalakrishnan Natarajan, Kavita Mallya, Paul M. Grandgenett, Karoly Mirnics, Surinder K. Batra, Zeljka Korade, Satyanarayana Rachagani

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding metabolic genes across the clinical specimens and preclinical PC models. Cholesterol is one of the critical metabolites supporting PC, synthesized or acquired by PC cells. Nevertheless, the significance of the de novo cholesterol synthesis pathway has been controversial in PC, indicating the need to reassess this pathway in PC. We utilized preclinical models and clinical specimens of PC patients and cell lines and utilized mass spectrometry-based sterol analysis. Further, we also performed in silico analysis to corroborate the significance …

Depletion Of Transmembrane Mucin 4 (Muc4) Alters Intestinal Homeostasis In A Genetically Engineered Mouse Model Of Colorectal Cancer, Ramesh Pothuraju, Priya Pai, Sanjib Chaudhary, Jawed A. Siddiqui, Jesse L. Cox, Sukhwinder Kaur, Satyanarayana Rachagani, Hemant K. Roy, Michael Bouvet, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucins are components of the mucus layer overlying the intestinal epithelial cells, which maintains physiological homeostasis. Altered mucin expression is associated with disease progression. Expression of MUC4 decreases in colorectal cancer (CRC); however, its functional role and implications in the intestinal pathology in CRC are not studied well. Therefore, we generated a genetically engineered Muc4 knockout (Muc4^-/-) CRC mouse model by crossing with Muc4^-/- and Apc^flox/flox mice in the presence of colon-specific inducible Cre. We observed that deficiency of Muc4 results in an increased number of macroscopic tumors in the colon and rectal region and leads …

Liquid Biopsies To Occult Brain Metastasis, Asad Ur Rehman, Parvez Khan, Shailendra K. Maurya, Jawed A. Siddiqui, Juan A. Santamaria-Barria, Surinder K. Batra, Mohd W. Nasser

Journal Articles: Biochemistry & Molecular Biology

Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the …

Gdf15 Promotes Prostate Cancer Bone Metastasis And Colonization Through Osteoblastic Ccl2 And Rankl Activation, Jawed A. Siddiqui, Parthasarathy Seshacharyulu, Sakthivel Muniyan, Ramesh Pothuraju, Parvez Khan, Raghupathy Vengoji, Sanjib Chaudhary, Shailendra K. Maurya, Subodh M. Lele, Maneesh Jain, K Datta, Mohd W. Nasser, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Bone metastases occur in patients with advanced-stage prostate cancer (PCa). The cell-cell interaction between PCa and the bone microenvironment forms a vicious cycle that modulates the bone microenvironment, increases bone deformities, and drives tumor growth in the bone. However, the molecular mechanisms of PCa-mediated modulation of the bone microenvironment are complex and remain poorly defined. Here, we evaluated growth differentiation factor-15 (GDF15) function using in vivo preclinical PCa-bone metastasis mouse models and an in vitro bone cell coculture system. Our results suggest that PCa-secreted GDF15 promotes bone metastases and induces bone microarchitectural alterations in a preclinical xenograft model. Mechanistic studies …

The Gsk3 Kinase And Lztr1 Protein Regulate The Stability Of Ras Family Proteins And The Proliferation Of Pancreatic Cancer Cells, Chitra Palanivel, Neha Chaudhary, Parthasarathy Seshacharyulu, Jesse L. Cox, Ying Yan, Surinder K. Batra, Michel M. Ouellette

Journal Articles: Biochemistry & Molecular Biology

Ras family proteins are membrane-bound GTPases that control proliferation, survival, and motility. Many forms of cancers are driven by the acquisition of somatic mutations in a RAS gene. In pancreatic cancer (PC), more than 90% of tumors carry an activating mutation in KRAS. Mutations in components of the Ras signaling pathway can also be the cause of RASopathies, a group of developmental disorders. In a subset of RASopathies, the causal mutations are in the LZTR1 protein, a substrate adaptor for E3 ubiquitin ligases that promote the degradation of Ras proteins. Here, we show that the function of LZTR1 is regulated …

Tumor Microenvironment Enriches The Stemness Features: The Architectural Event Of Therapy Resistance And Metastasis, Palanisamy Nallasamy, Rama Krishna Nimmakayala, Seema Parte, Abhirup C. Are, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

Cancer divergence has many facets other than being considered a genetic term. It is a tremendous challenge to understand the metastasis and therapy response in cancer biology; however, it postulates the opportunity to explore the possible mechanism in the surrounding tumor environment. Most deadly solid malignancies are distinctly characterized by their tumor microenvironment (TME). TME consists of stromal components such as immune, inflammatory, endothelial, adipocytes, and fibroblast cells. Cancer stem cells (CSCs) or cancer stem-like cells are a small sub-set of the population within cancer cells believed to be a responsible player in the self-renewal, metastasis, and therapy response of …

Defining Patient Cohorts For Guiding Clinical Trials And Treatment In Lafora Disease: A Model For The Rare Disease Community, Katherine Janae Donohue

Theses and Dissertations--Molecular and Cellular Biochemistry

In the US, approximately 8000 rare diseases have been identified. Combined, rare diseases impact more than 30 million people in the U.S. alone, with 75% of those being children. However, research, funding, and therapeutic development for the rare disease community remains challenging because of the incredible diversity – not only between diseases, but often even within a single disease.

LD is an ultra-rare childhood dementia and epilepsy caused by mutations in one of two driver genes: EPM2A, which encodes for the glycogen phosphatase laforin, and EPM2B/NHLRC1, which encodes the E3 ubiquitin ligase malin. Children with LD …

Role Of Mtorc2 In The Regulation Of Glycolytic Metabolism In Glioblastoma Through Pkcδ Phosphorylation, Chatchapon Chuenjit

Chulalongkorn University Theses and Dissertations (Chula ETD)

Glioblastoma (GBM) is the most common and highly aggressive primary cancer within the central nervous system (CNS). The mTORC2 is a primary regulator of glycolytic reprogramming in highly malignant cells through both Akt-dependent and AKT-independent pathways. However, the mechanism that cancer glycolysis through AKT-independent pathways remains largely unexplored. This study aimed to investigate the mechanism of mTORC2/ PKCδ signaling-regulated glycolysis of GBM cells by AKT-independent mechanisms. We examined the impact of various pharmacological inhibitors on the suppression of mTORC1, mTORC2, AKT, and PKCδ signaling. Our results revealed that the phosphorylation of PKCδ at residue serine 664 was diminished by AZD8055, …

ผลของการบริโภคฟักข้าวต่อระดับไตรเมทิลามีนเอ็นออกไซด์ในเลือดและการเกิดโรคหัวใจในหนูไตวายเรื้อรัง, ภานุมาศ เข้มแข็ง

Chulalongkorn University Theses and Dissertations (Chula ETD)

บทนํา: ไตรเมทิลามีน (Trimethylamine) เป็นสารที่สร้างจากแบคทีเรียในลําไส้และเป็นสารตั้งต้นในการสร้าง Trimethylamine N-oxide (TMAO) ซึ่งทําให้เกิดโรคหัวใจและหลอดเลือดโดยเฉพาะในวิธีการทดลอง: หนูแรทเพศผู้สายพันธุ์วิสตาร์จํานวนกลุ่มละ 9 ตัว แบ่งออกเป็น 6 กลุ่ม ได้แก่ กลุ่มควบคุม (Control) กลุ่มไตเรื้อรัง (chronic kidney disease) กลุ่มสารทดสอบฟักข้าว (Gac) กลุ่มสารทดสอบไลโคปีนและเบต้าแคโรทีน (STD) กลุ่มสารทดสอบฟักข้าวร่วมกับแบคทีเรีย B. longum และ L. salivarius (Synbiotic) และกลุ่มสารโปรไบโอติกควบคุม L. Casei (Lactobacillus Casei) โดยหนูกลุ่มทดสอบจะถูกเหนี่ยวนําให้เป็นไตวาเรื้อรังโดย Cisplatinและทุกกลุ่มได้รับอาหารเสริม choline เป็นระยะเวลา 15 สัปดาห์ ผลการทดลอง: พบว่าหนูกลุ่ม Synbiotic มีระดับ serum TMAO ลดลงอย่างมีนัยสําคัญทางสถิติ (P<0.05)เมื่อเปรียบเทียบกับกลุ่ม CKD รวมถึงยังพบการลดลงของเชื้อในกลุ่ม Proteobacteria ในลําไส้และลดการแสดงออกของเอนไซม์ Trimethylamine-(TMA) lyase ซึ่งจําเป็นต่อการสร้าง TMA อย่างมีนัยสําคัญทางสถิติ(P<0.05) นอกจากนี้ยังพบว่าการเสริม Synbiotics ยังกระตุ้นการแสดงออกของ Zonula occludens type 1 (ZO-1) ซึ่งเป็น tight junction gene ที่บริเวณลําไส้ใหญ่ (Colon) อย่างมีนัยสําคัญ ในขณะที่การให้สารสกัดฟักข้าวเพียงอย่างเดียว หรือการให้โปรไบโอติกควบคุมไม่พบความเปลี่ยนแปลงเมื่อเปรียบเทียบกับกลุ่ม CKD สรุปผล: การเสริม Synbiotic ซึ่งประกอบด้วยสารสกัดฟักข้าว และโปรไบโอติกชนิด B. longum และ L.salivarius ที่มีประสิทธิภาพในการลดการรั่วที่ผนังลําไส้ ช่วยลดเชื้อ Proteobacteria ในลําไส้หนู CKD ลดการแสดงออกของ TMA lyase enzyme เพิ่มการแสดงออกของ tight junction gene ZO-1 และสามารถลดระดับ serum TMAO ได้อย่างมีนัยสําคัญ หรือ การเสริม Synbiotic ซึ่งประกอบด้วยสารสกัดฟักข้าว และโปรไบโอติกชนิด B. longum และ L. salivarius สารถลดระดับ serum TMAO ในหนูโรคไตเรื้อรังได้อย่างมีนัยสําคัญมีความเป็นไปได้ในการพัฒนาเป็นผลิตภัณฑ์ช่วยลดความเสี่ยงต่อการเกิดภาวะแทรกซ้อนทางหัวใจและหลอดเลือดในผู้ป่วยโรคไตเรื้อรังต่อไต

ผลกระทบของการปลูกถ่ายจุลินทรีย์ในลำไส้ของผู้ป่วยโรคนิ่วไตต่อการเกิดโรคนิ่วแคลเซียมออกซาเลตในทางเดินปัสสาวะของหนู, สิทธิพงษ์ หุ่นไทย

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคนิ่วไตพบมากในคนไทยโดยเฉพาะผู้ที่อาศัยในเขตภาคตะวันออกเฉียงเหนือและภาคเหนือ มีปัจจัยเสี่ยงคือ ภาวะซิเตรทในปัสสาวะต่ำ แคลเซียมและออกซาเลตในปัสสาวะสูง โดยพบมากในผู้ที่มีอายุ 40 ปีขึ้นไป จากการศึกษาก่อนหน้าพบความแตกต่างของประชากรจุลินทรีย์ในลำไส้ของผู้ป่วยโรคนิ่วไตจากคนสุขภาพดี จึงเชื่อว่าความแตกต่างของจุลินทรีย์ลำไส้ส่งผลให้เกิดความเสี่ยงของการเกิดโรคนิ่วไต เพื่อศึกษาความผิดปกตินี้ ผู้วิจัยจึงศึกษาความแตกต่างของจุลินทรีย์ในลำไส้เปรียบเทียบระหว่างอาสาสมัครคนปกติและผู้ป่วยโรคนิ่วไต พบว่าจุลินทรีย์ phylum Bacteroidata ในอุจจาระของผู้ป่วยโรคนิ่วไตสูงกว่าคนสุขภาพดี และพบ genus Bifidobacterium ต่ำกว่าคนสุขภาพดี จากนั้นนำจุลินทรีย์จากอุจจาระของอาสาสมัครทั้งสองกลุ่ม ปลูกถ่ายลงในหนู Wistar เป็นเวลา 4 สัปดาห์ พบว่า หนูกลุ่มที่ได้รับจุลินทรีย์จากกลุ่มผู้ป่วยโรคนิ่วไตมีปริมาณออกซาเลตในปัสสาวะมีแนวโน้มสูงขึ้น ปริมาณแมกนีเซียมในปัสสาวะลดลง รวมทั้ง pH ในปัสสาวะเป็นด่างมากขึ้น และพบดัชนีความเสี่ยงต่อการเกิดนิ่ว (Tiselius’s supersaturation index) เพิ่มสูงขึ้น นอกจากนี้ ยังพบ จุลินทรีย์ genus Muribaculaceae สูงขึ้นในหนูที่ได้รับการปลูกถ่ายเชื้อจุลินทรีย์จากผู้ป่วยโรคนิ่วไต และ genus Roseburia มีจำนวนลดลง รวมถึงการแสดงออกของ tight junction (Zonula occluden-1 หรือ ZO-1) ที่ลดลง และพบการแสดงออกของ oxalate transporter มีแนวโน้มสูงขึ้น สรุปได้ว่าหนูที่ได้รับเชื้อจุลินทรีย์ในอุจจาระจากผู้ป่วยโรคนิ่วไตมีความเสี่ยงต่อการเกิดโรคนิ่วสูงขึ้น โดยมีกลไกจากการแสดงออกของโปรตีน ZO-1 ลดลง และเพิ่ม oxalate transporter ที่ลำไส้ ทำให้ร่างกายได้รับออกซาเลตจากอาหารในลำไส้เพิ่มขึ้น และขับออกทางปัสสาวะเพิ่มขึ้น เป็นหลักฐานยืนยันว่าความผิดปกติของสมดุลเชื้อจุลินทรีย์ในลำไส้เพิ่มความเสี่ยงต่อการเกิดโรคนิ่วไต

Exploring Roles Of Mir-885-5p In Hepatocellular Carcinoma, Archittapon Nokkeaw

Chulalongkorn University Theses and Dissertations (Chula ETD)

Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, exerts a significant burden on Southeast Asian countries and stands as the third leading cause of cancer-related mortality worldwide. Despite this alarming impact, effective treatments for HCC are lacking, resulting in low survival rates and high recurrence rates. Therefore, a comprehensive understanding of the disease's underlying mechanisms is crucial for the development of novel and potent therapies. Recently, it has been recognized that microRNAs (miRNAs) play a vital role in tumorigenesis, including HCC. Our bioinformatic analysis has highlighted hsa-miR-885-5p as a potential candidate miRNA due to its downregulation in HCC …

Exploring Roles Of Mir-372-3p In Proliferation Of Hepatocellular Carcinoma Cells, Pannathon Thamjamrassri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC has a replicative immortality and sustained proliferation rate. In addition, cell cycle-related protein regulating proliferation in cancer are often found dysregulated, allowing cancer cells to proceed their proliferation uncontrollably. Recently, a small non-coding RNA, microRNA (miRNA), was found to play an important role in numerous biological functions. Specific miRNA may ameliorate or promote cancer progression through different target mRNA. MiR-372-3p has been explored in various cancers such as colon cancer, colorectal cancer, and glioma. However, its functions have been rarely studied in HCC, especially in the aspect …

Classification Of Bacteria And Fungi In Peritoneal Dialysis Fluids Of Patients With Chronic Kidney Disease Based On Metagenomic Analysis, Suthida Visedthorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Chronic kidney disease (CKD) is a long-term condition where sustained damage of the renal parenchyma leads to the chronic deterioration of renal function that may gradually progress to end-stage kidney disease (ESKD). Peritoneal dialysis (PD) is a type of ESKD treatment that is beneficial to improve a patient's quality of life. However, PD-associated peritonitis is a major complication that contributes cause of death, and the detection of the pathogen provided a high culture-negative rate. This study aims to apply metagenomic approaches for identifying the bacteria and fungi in peritoneal dialysis effluent (PDE) of CKD patients based on the full-length 16S …

Effects Of Chitosan Oligosaccharide And Probiotics On Chronic Kidney Disease Rats, Weerapat Anegkamol

Chulalongkorn University Theses and Dissertations (Chula ETD)

Chronic kidney disease (CKD) patients suffer from the accumulation of toxic substances in their blood due to the loss of kidney function, which results in hyperphosphatemia. This condition contributes to hyperparathyroidism, leading to the development of chronic kidney disease-related mineral bone disorder (CKD-MBD). Additionally, CKD patients experience changes in their gut microbiota, disrupting epithelial tight junctions and allowing excessive absorption of dietary phosphate. In this study, we aimed to investigate the effects of various oligosaccharides and probiotics on the gut microbiota, intestinal barrier, hyperphosphatemia, and hyperparathyroidism in CKD rats. We isolated Lactobacillus and Bifidobacterium strains from healthy participants and tested …

Detection Of Egfr Mutations In Lung Cancer Based On Oxford Nanopore Sequencing Technology, Patinya Akkhasutthikun

Chulalongkorn University Theses and Dissertations (Chula ETD)

Epidermal growth factor receptor (EGFR) mutation is an important and highly prevalent oncogene driver in patients with non-small cell lung cancer (NSCLC) in East Asia. The detection of EGFR mutations is a standard biomarker testing that routinely performed in patients with advanced lung cancer for the selection of targeted therapy. Here, we aimed to develop a portable and cost-effective new technique for detecting EGFR 19Del, T790M and L858R mutations based on blocker displacement amplification (BDA) combined with Oxford Nanopore Technologies (ONT). The method optimization was performed using wild-type and mutant EGFR allele generated from lung cancer cell lines. The assay …

Roles Of Mtor Complex 2 In Canonical Wnt Signaling In Glioblastoma., Tankun Banlue

Chulalongkorn University Theses and Dissertations (Chula ETD)

Glioblastoma (GBM) is the most common type of primary brain tumor in adults, comprising 75% of cases. The failure of GBM treatments is closely related to a subset of cells known as glioblastoma stem cells (GSCs), which possess stemness characteristics. While the Wnt signaling pathway plays a crucial role in regulating stem cell homeostasis, the interplay between this pathway and the mTORC2 signaling pathway in GBM remains unclear. Thus, this research aimed to investigate the collaborative regulation of stemness-related mechanisms by mTORC2 and canonical Wnt signaling pathways in glioblastoma using 3D spheroid culture. The study found that inhibiting mTORC2 resulted …