Digital Commons Network^™

Epigenetic Regulation Of Cancer Testis Antigens In Hepatocellular Carcinoma, Rinrada Klankajorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Hepatocellular carcinoma (HCC) represents one of the most common causes of cancer-related death worldwide, with few available treatment options. Cancer-testis antigens (CTAs), notably from the MAGE gene family, have opened new possibilities for improving immunotherapy in HCC due to their tumor-specific expression and high immunogenicity. However, the mechanisms regulating MAGE gene expression are largely unknown. This study explored mechanisms controlling the expression of MAGE-A3 and MAGE-C2. We utilized HCC organoid cultures derived from patient HCC tissues known to represent cancer epigenetic status more accurately than cell lines to study the MAGE gene family expression patterns and promoter methylation patterns. Our …

Periodontal Regeneration Related To Periodontitis Treated By Garden Cress And Ozone Therapy. (Randomized Clinical &Experimental Study), Zienab S. Farid, Doaa Adel Habba, Gihan Adel Balbola, Noura Mohammed Bakr

Journal of Medicine in Scientific Research

Objective: In this article, garden cress and ozone were evaluated for their potential therapeutic properties of PDL and resorption of alveolar bone in the periodontal tissues based on rats' experimental periodontitis and to assess the clinical effectiveness of local application of garden cress and ozone for treatment and management of periodontitis patients using scaling and root planing. Methodology: Thirty mature Wistar male albino rats. Three groups of rats were formed; periodontitis without treatment, periodontitis with garden cress, and periodontitis plus ozone therapy. The present study also included thirty periodontitis Patients were randomly allocated to one of three groups of ten …

The Rage Gene Crucial Function In The Etiology And Consequences Of Type I Diabetes, Amal A. Mohamed, Mohamed O. Mahmoud, Gamil M. Abdallah, Nada S. Ali, Mona Abdelmotaleb Abdelfatah Hussein, Ibrahim T. Ibrahim

Journal of Medicine in Scientific Research

Type I Diabetes, among the ten greatest causes of mortality worldwide, is estimated to afflict 642 million individuals by 2040. It is an auto-immune illness brought on by an association of environmental and genetic variables. that cause T lymphocytes to destroy insulin-producing β-cells. Its prevalence continues to rise by 3-4% annually worldwide, enhancing the risk of mortality. So, the idea of diabetic kidney disease (DKD) is widely established, and systemic treatment is essential. RAGEs are linked to inflammatory disorders that exist in a variety of TID-related cells; especially T cells. Variations in circulating RAGE concentrations have been linked to a …

The Role Of Renal Resistive Index (Rri) As Early Non Invasive Predictor Of Renal Dysfunction And Relation To Estimated Gfr In Nafld Patients, Atteyat Aboelmaged Semeya, Hala Abd-Elhameed Tabl, Naglaa F. Al-Mihy

Journal of Medicine in Scientific Research

Background: Non-alcoholic fatty liver (NAFLD) is the diagnosis of fatty infiltration of the liver (steatosis) in the absence of other reasons, done through histology or imaging, with or without fibrosis or inflammation. We sought to ascertain the function of RRI as early non-invasive predictor of renal dysfunction and the relationship between eGFR and RRI in patients with NAFLD.

Methods: This cross-sectional research comprised 250 patients and controls gathered from outpatient clinic of the Hepatogasteroenterology Department, Benha teaching Hospitals. They were split into three groups: group 1 consisted of 100 NASH patients, fibrosis-free or with a history of the condition; group …

Oral Collagen Supplementation In 2nd Degree Burn And Chronic Pressure Ulcers, Wesam Ibrahem Homouda, Helmy Ahmed Soliman, Esayed Hussien Elmokadem

Journal of Medicine in Scientific Research

Background: Healing of wounds requires adequate intake of protein, iron, Vitamin-C and zinc. In case of deficiency in the dietary intake, supplements may be prescribed. Collagen-peptide supplements can enhance skin hydration, elasticity, and reduce wrinkles. Burns, caused by various agents, severely damage skin layers. Pressure ulcers occur when prolonged pressure on the skin leads to tissue ischaemia, disrupting nutrition and oxygen supply, resulting in tissue necrosis. Systematic reviews show that oral collagen, either intact or hydrolyzed, effectively improves skin health.

Objectives: This article aim to evaluate the effect of oral collagen intake as a healing promoting supplementation in management of …

Understanding The Effects Of Hormone Treatments On The Transgender Singer: A Pedagogical Study And Voice Studio Guide, Erin M. Hannon

Theses and Dissertations--Music

Transitioning from one gender to another can be an arduous and emotionally charged experience, accompanied by many physical and mental transformations. The journey of self-discovery and vocal explorations is both unique and deeply personal. Modifications that emerge in an individual's vocal characteristics have a profound influence on their capacity to communicate and express themselves.

Transgender vocal students and professional singers must navigate the delicate balance between their vocal and gender identities while considering the possible risks of Gender Affirming Hormone Therapy. Though these therapies may significantly alter one's appearance and overall well-being, they are also capable of causing notable declines …

Association Of Genetic Polymorphisms With Clinical Characteristics And Survival Of Hepatocellular Carcinoma Patients With Or Without Metabolic Dysfunction-Associated Steatotic Liver Disease (Masld), Theint Cho Zin Aung

Chulalongkorn University Theses and Dissertations (Chula ETD)

The influence of single-nucleotide polymorphisms (SNPs) on hepatocellular carcinoma (HCC) in terms of etiological factors remains to be explored. This study evaluated the distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs6834314 and overall survival of HCC patients with metabolic dysfunction-associated steatotic liver disease (MASLD-HCC) and viral-related HCC (VIRAL-HCC). In this study, 564 patients with HCC were included: 254 with MASLD-HCC and 310 with VIRAL-HCC. The SNPs were determined by real-time PCR using TaqMan assays. Results: The mean ages of patients with MASLD-HCC and VIRAL-HCC were 68.4 vs. 60.9 years (p < 0.001), with a significant difference between groups. The prevalence of PNPLA3 genotype GG in MASLD-HCC was significantly higher in MASLD-HCC than in VIRAL-HCC (24.0 % vs. 15.5%; OR = 1.86; 95% CI = 1.14–3.05; p = 0.009). Similarly, the prevalence of TM6SF2 genotype TT in MASLD-HCC and VIRAL-HCC was 7.1% vs. 2.6% (OR = 3.39; 95% CI = 1.36–9.21; p = 0.003), while HSD17B13 genotype GG in the corresponding groups was 7.1% vs. 12.6% (OR = 0.53; 95 % CI = 0.27–1.01; p = 0.039). The overall median survival of MASLD-HCC was significantly shorter than the VIRAL-HCC group (42 vs. 66 months; p = 0.035). In Cox regression hazard analysis, HSD17B13 GG genotype was significantly associated with a lower mortality rate in MASLD-HCC (HR = 0.38 ; 95% CI = 0.18–0.81; p = 0.011). In contrast, PNPLA3 and TM6SF2 were not associated with overall survival in patients with MASLD-HCC or VIRAL-HCC. Conclusions: These data demonstrated that the prevalence of the studied SNPs significantly differed between MASLD-HCC and VIRAL-HCC. The HSD176B13 GG genotype was also associated with a survival benefit in Thai patients with MASLD-HCC.

Crosstalk Between Cytokines And The Diverse Pattern Of Tumor Immune Microenvironment (Time) In Egfr Mutant Advanced Stage Non-Small Cell Lung Cancer Receiving Egfr Tyrosine Kinase Inhibitor, Sorawich Kuendee

Chulalongkorn University Theses and Dissertations (Chula ETD)

Introduction: Although EGFR-TKI therapy significantly improves outcomes in patients with EGFR-mutant advanced NSCLC, inter-individual variability in treatment response remains a major challenge. One potential contributing factor is the tumor immune microenvironment (TIME), which plays a critical role in tumor behavior and may influence therapeutic efficacy. However, the relationship between baseline cytokine profiles and TIME features in this patient population remains unclear. Methods: Prospective observational study involving patients with advanced EGFR-mutant NSCLC receiving first-line EGFR-TKI therapy. Baseline cytokine levels were measured using the Bio-Plex Pro™ Human 27-Plex Cytokine Assay. Immunohistochemistry was used to evaluate CD8⁺ TILs and PD-L1 expression. The primary …

Roles Of Mtor Complex 2 Signaling In The Sphingolipid Production Of Brain Cancer Cell Lines, Nuanwan Songcharoen

Chulalongkorn University Theses and Dissertations (Chula ETD)

Gliomas, which include low- and high-grade types, represent a particularly aggressive form of primary brain tumor, especially glioblastoma (GBM). Metabolic reprogramming in lipid metabolism supports cell proliferation; alterations in the sphingolipid pathway, elevated glucosylceramide (GlcCer) levels through glucosylceramide synthase (GCS), promote the production of glycosphingolipids, which serve as building blocks for cancer cells. Furthermore, mTORC2, which is a kinase protein, contributes to lipid metabolism. Thus, the study aims to investigate the roles of mTORC2 signaling in lipid metabolism through lipid accumulation, which was reduced with AZD8055 treatment as the mTORC2 inhibitor. Additionally, p-AKT (S473), which is downstream of mTORC2, was …

Clinical Study Of Combined Arthroscopic Drilling And Platelet Rich Plasma Injection In Knee Osteochondral Lesions In Middle-Aged Patients, Mohamed Salah Labib Mohamed, Mohamed Abd Elmoneam Gafar

Journal of Medicine in Scientific Research

Background: Osteochondral lesions commonly occur in the knee joints and causes detrimental effects on the quality of life. Arthroscopic drilling is the treatment option for mild to moderate lesions. However, it is debatable whether regenerated cartilage from arthroscopic drilling surgery is durable. It is speculated that induction of chondrocyte differentiation from subchondral mesenchymal stem cells is facilitated by platelet-rich plasma (PRP), which is a rich source of diverse growth factors.

Aim of work: To evaluate the procedures of combined arthroscopic drilling and PRP injection intra-articularly for mild to moderate knee osteochondral lesions management.

Patients and Methods: This randomized prospective study …

Synthetic Neuroactive Steroids Targeting Gaba-A Receptors As A Potential Therapy For Contraceptive-Associated Mood Disorders, Alexandria A. Davis

Scripps Senior Theses

4-10% of women who use hormonal oral contraceptives (HOCs) discontinue use after experiencing symptoms of anxiety, irritability, and depression in the first 3 months of administration. Previous studies have acknowledged a relationship between HOCs and emotional dysregulation but have not identified mechanisms by which HOCs have this effect. As a result, effective treatment options for HOC-induced mood disorders are lacking. Current theories implicate combined-HOCs, particularly those containing ethinyl estradiol and levonorgestrel (EE-LNG), in reducing neuroactive steroid levels. Specifically, HOC users show decreases in allopregnanolone, a positive allosteric modulator associated with neuronal inhibition and emotional regulation. The objective of this study …

Psychotropic Polypharmacy On Heart Rate Of Daphnia Magna, Gwendolynne Miller, Brian Bagatto

Williams Honors College, Honors Research Projects

The prevalence of patients being prescribed multiple medications concurrently is significantly rising, and so is the importance of investigating any interactions between medications. One common example—sertraline and clomipramine have been used together to treat obsessive compulsive disorder. Clomipramine, however, is known to cause tachyarrhythmias in some patients. The present study set out to investigate the role of this drug combination on the heart rate of a simple animal model, Daphnia magna, or the water flea. The water flea was exposed to saline, sertraline, clomipramine, or sertraline plus clomipramine, and heart rate was measured subsequently. It was found that the …

Protein-Centric Omics Analysis Reveals Circulating Complements Linked To Non-Viral Liver Diseases As Potential Therapeutic Targets, Yingzhou Shi, Hang Dong, Shiwei Sun, Xiaoqin Wu, Jiansong Fang, Jianbo Zhao, Junming Han, Zongyue Li, Huixiao Wu, Luna Liu, Wanhong Wu, Yang Tian, Guandou Yuan, Xiude Fan, Chao Xu

Faculty, Staff and Student Publications

BACKGROUND/AIMS: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.

METHODS: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.

RESULTS: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018-1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk …

Prioritizing Clinically Significant Lung Cancer Somatic Mutations For Targeted Therapy Through Efficient Ngs Data Filtering System, Jinlian Wang, Hui Li, Hongfang Liu

Faculty, Staff and Student Publications

In the realm of lung cancer treatment, where genetic heterogeneity presents formidable challenges, precision oncology demands an exacting approach to identify and hierarchically sort clinically significant somatic mutations. Current Next-Generation Sequencing (NGS) data filtering pipelines, while utilizing various external databases for mutation screening, often fall short in comprehensive integration and flexibility needed to keep pace with the evolving landscape of clinical data. Our study introduces a sophisticated NGS data filtering system, which not only aggregates but effectively synergizes diverse data sources, encompassing genetic variants, gene functions, clinical evidence, and an extensive body of literature. This system is distinguished by a …

Developing Medical Genetics In A Low-Income Country: Unveiling The Journey Of The Pakistani Society Of Medical Genetics And Genomics (Psmg), Aisha Furqan, Syed A Ahmed, Rizwan Naeem, Myla Ashfaq

Faculty, Staff and Student Publications

No abstract provided.

Mouse Models Of Chronic Lymphocytic Leukemia And Richter Transformation: What We Have Learnt And What We Are Missing, Maria Teresa Sabrina Bertilaccio, Shih-Shih Chen

Faculty, Staff and Student Publications

Although the chronic lymphocytic leukemia (CLL) treatment landscape has changed dramatically, unmet clinical needs are emerging, as CLL in many patients does not respond, becomes resistant to treatment, relapses during treatment, or transforms into Richter. In the majority of cases, transformation evolves the original leukemia clone into a diffuse large B-cell lymphoma (DLBCL). Richter transformation (RT) represents a dreadful clinical challenge with limited therapeutic opportunities and scarce preclinical tools. CLL cells are well known to highly depend on survival signals provided by the tumor microenvironment (TME). These signals enhance the frequency of immunosuppressive cells with protumor function, including regulatory CD4

A Relay Velocity Model Infers Cell-Dependent Rna Velocity, Shengyu Li, Pengzhi Zhang, Weiqing Chen, Lingqun Ye, Kristopher W Brannan, Nhat-Tu Le, Jun-Ichi Abe, John P Cooke, Guangyu Wang

Faculty, Staff and Student Publications

RNA velocity provides an approach for inferring cellular state transitions from single-cell RNA sequencing (scRNA-seq) data. Conventional RNA velocity models infer universal kinetics from all cells in an scRNA-seq experiment, resulting in unpredictable performance in experiments with multi-stage and/or multi-lineage transition of cell states where the assumption of the same kinetic rates for all cells no longer holds. Here we present cellDancer, a scalable deep neural network that locally infers velocity for each cell from its neighbors and then relays a series of local velocities to provide single-cell resolution inference of velocity kinetics. In the simulation benchmark, cellDancer shows robust …

Fc Gamma Receptors Promote Antibody-Induced Lilrb4 Internalization And Immune Regulation Of Monocytic Aml, Joshua W Morse, Xun Gui, Mi Deng, Ryan Huang, Xiaohua Ye, Peng Zhao, Xuejun Fan, Wei Xiong, Chengcheng Zhang, Ningyan Zhang, Zhiqiang An

Faculty, Staff and Student Publications

The immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4) is found specifically on the cell surface of acute monocytic leukemia (monocytic AML), an aggressive and common subtype of AML. We have developed a humanized monoclonal IgG1 LILRB4-blocking antibody (h128-3), which improved immune regulation but reduced cell surface expression of LILRB4 in monocytic AML models by 40–60%. Interestingly, most of this effect was neutralized by mutation of the Fc region of the antibody (h128-3/N297A), which prevents interaction with Fc gamma receptors (FcγRs). This suggested that there is FcγR-dependent antigenic modulation underlying h128-3’s effects, a mechanism known to alter the function of antibodies …

Approaches To Estimate Bidirectional Causal Effects Using Mendelian Randomization With Application To Body Mass Index And Fasting Glucose, Jinhao Zou, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Mendelian randomization (MR) is an epidemiological framework using genetic variants as instrumental variables (IVs) to examine the causal effect of exposures on outcomes. Statistical methods based on unidirectional MR (UMR) are widely used to estimate the causal effects of exposures on outcomes in observational studies. To estimate the bidirectional causal effects between two phenotypes, investigators have naively applied UMR methods separately in each direction. However, bidirectional causal effects between two phenotypes create a feedback loop that biases the estimation when UMR methods are naively applied. To overcome this limitation, we proposed two novel approaches to estimate bidirectional causal effects using …

Secondhand Tobacco Smoke Exposure In Homes And Vehicles In Youth: Disparities Among Racial, And Sexual And Gender Minorities, Rajesh Talluri, Sahil S Shete, Surendra S Shastri, Sanjay Shete

Faculty, Staff and Student Publications

BACKGROUND: Secondhand smoke exposure (SHSe) among youth is a serious public health concern, leading to an increased risk of conditions such as asthma and respiratory infections. However, there is little research on SHSe among vulnerable populations, such as racial and sexual minorities. Understanding the factors associated with youth SHSe in homes and vehicles is crucial to developing better protective policies.

METHODS: This study utilized 2020 data from the National Youth Tobacco Survey, a representative sample of middle- and high-school students in the US. The primary outcomes were youth SHSe at home and while riding in a vehicle. Multinomial regression models …

Immune-Related Adverse Event In The Emergency Department: Methodology Of The Immune-Related Emergency Disposition Index (Iredi), Cielito C Reyes-Gibby, Jeffrey M Caterino, Christopher J Coyne, Demetrios N Kyriacou, Aiham Qdaisat, Jennifer Mcquade, Dwight H Owen, Jason J Bischof, Sanjay Shete, Sai-Ching Jim Yeung

Faculty, Staff and Student Publications

For many cancer patients, immune checkpoint inhibitors (ICIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICIs can be debilitating and can quickly become severe or even be fatal. Often, irAEs will precipitate visits to the emergency department (ED). Therefore, early recognition and the decision to admit, observe, or discharge these patients from the ED can be key to a cancer patient's morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe, or discharge) within 2-6 h from their patient's ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the …

A Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Diseasea Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Disease, Ofir Sade, Daphna Fischel, Noa Barak-Broner, Shir Halevi, Irit Gottfried, Dana Bar-On, Stefan Sachs, Anat Mirelman, Avner Thaler, Aviv Gour, Meir Kestenbaum, Mali Gana Weisz, Saar Anis, Claudio Soto, Melanie Shanie Roitman, Shimon Shahar, Kathrin Doppler, Markus Sauer, Nir Giladi, Nirit Lev, Roy N Alcalay, Sharon Hassin-Baer, Uri Ashery

Faculty, Staff and Student Publications

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson’s disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, …

Sotorasib With Panitumumab In Chemotherapy-Refractory Kras G12c-Mutated Colorectal Cancer: A Phase 1b Trial, Yasutoshi Kuboki, Marwan Fakih, John Strickler, Rona Yaeger, Toshiki Masuishi, Edward J Kim, Christine M Bestvina, Scott Kopetz, Gerald S Falchook, Corey Langer, John Krauss, Sonam Puri, Panli Cardona, Emily Chan, Tracy Varrieur, Lata Mukundan, Abraham Anderson, Qui Tran, David S Hong

Faculty, Staff and Student Publications

The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, and panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, was hypothesized to overcome treatment-induced resistance. This phase 1b substudy of the CodeBreaK 101 master protocol evaluated sotorasib plus panitumumab in patients with chemotherapy-refractory KRAS

A Phase 2, Multicenter, Open-Label Study Of Anti-Lag-3 Ieramilimab In Combination With Anti-Pd-1 Spartalizumab In Patients With Advanced Solid Malignancies, Chia-Chi Lin, Elena Garralda, Patrick Schöffski, David S Hong, Lillian L Siu, Miguel Martin, Michela Maur, Rina Hui, Ross A Soo, Joanne Chiu, Tian Zhang, Brigette Ma, Chrisann Kyi, Daniel Sw Tan, Philippe A Cassier, John Sarantopoulos, Andrew Weickhardt, Richard D Carvajal, Jennifer Spratlin, Taito Esaki, Fréderic Rolland, Wallace Akerley, Barbara Deschler-Baier, Lawrence Rispoli, Tanay S Samant, Niladri Roy Chowdhury, Daniel Gusenleitner, Eunice L Kwak, Vasileios Askoxylakis, Filippo De Braud

Faculty, Staff and Student Publications

Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated). Patients received ieramilimab (400 mg) followed by spartalizumab (300 mg) every 3 weeks. The primary endpoint was objective response rate (ORR), along …

Candidate Circulating Microrna Biomarkers In Dogs With Chronic Pancreatitis, Susan K Armstrong, Robert W Hunter, Wilna Oosthyuzen, Maciej Parys, Adam G Gow, Silke Salavati Schmitz, James W Dear, Richard J Mellanby

Faculty, Staff and Student Publications

BACKGROUND: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis.

HYPOTHESIS: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers.

ANIMALS: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17).

METHODS: A retrospective case-control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, …

From Transcriptomics To Digital Twins Of Organ Function, Jens Hansen, Abhinav R Jain, Philip Nenov, Peter N Robinson, Ravi Iyengar

Faculty, Staff and Student Publications

Cell level functions underlie tissue and organ physiology. Gene expression patterns offer extensive views of the pathways and processes within and between cells. Single cell transcriptomics provides detailed information on gene expression within cells, cell types, subtypes and their relative proportions in organs. Functional pathways can be scalably connected to physiological functions at the cell and organ levels. Integrating experimentally obtained gene expression patterns with prior knowledge of pathway interactions enables identification of networks underlying whole cell functions such as growth, contractility, and secretion. These pathways can be computationally modeled using differential equations to simulate cell and organ physiological dynamics …

Phospholipid Metabolic Adaptation Promotes Survival Of Idh2 Mutant Acute Myeloid Leukemia Cells, Tatsuya Morishima, Koichi Takahashi, Desmond Wai Loon Chin, Yuxin Wang, Kenji Tokunaga, Yuichiro Arima, Masao Matsuoka, Toshio Suda, Hitoshi Takizawa

Faculty, Staff and Student Publications

Genetic mutations in the isocitrate dehydrogenase (IDH) gene that result in a pathological enzymatic activity to produce oncometabolite have been detected in acute myeloid leukemia (AML) patients. While specific inhibitors that target mutant IDH enzymes and normalize intracellular oncometabolite level have been developed, refractoriness and resistance has been reported. Since acquisition of pathological enzymatic activity is accompanied by the abrogation of the crucial WT IDH enzymatic activity in IDH mutant cells, aberrant metabolism in IDH mutant cells can potentially persist even after the normalization of intracellular oncometabolite level. Comparisons of isogenic AML cell lines with and without IDH2 gene mutations …

New Triazinephosphonate Dopants For Nafion Proton Exchange Membranes (Pem), Fátima C Teixeira, António P S Teixeira, C M Rangel

Faculty, Staff and Student Publications

A new paradigm for energy is underway demanding decarbonized energy systems. Some of them rely on emerging electrochemical devices, crucial in hydrogen technologies, including fuel cells, CO2 and water electrolysers, whose applications and performances depend on key components such as their separators/ion-exchange membranes. The most studied and already commercialized Nafion membrane shows great chemical stability, but its water content limits its high proton conduction to a limited range of operating temperatures. Here, we report the synthesis of a new series of triazinephosphonate derivatives and their use as dopants in the preparation of new modified Nafion membranes. The triazinephosphonate derivatives were …

Targeting The Renin-Angiotensin System (Ras) For Neuropsychiatric Disorders, Aline Silva De Miranda, Danielle S Macedo, Natalia P Rocha, Antonio L Teixeira

Faculty, Staff and Student Publications

BACKGROUND: Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer's disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic …

G-Quadruplex Dna And Rna In Cellular Senescence, Rocio Diaz Escarcega, Paul Marshall, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Normal cells divide, are damaged, and are repaired across their lifetime. As cells age, they enter cellular senescence, characterized by a permanent state of cell-cycle arrest triggered by various stressors. The molecular mechanisms that regulate senescent phenotypes have been actively investigated over the last several decades; however, one area that has been neglected is how G-quadruplex (G4) DNA and RNA (G4-DNA and G4-RNA) mediate senescence. These non-canonical four-stranded DNA and RNA structures regulate most normative DNA and RNA-dependent processes, such as transcription, replication, and translation, as well as pathogenic mechanisms, including genomic instability and abnormal stress granule function. This review …