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Glutamate Optimization As A Treatment For Depression: A Clinical Guideline, Luisa Angeles Collins Villares Jan 2024

Glutamate Optimization As A Treatment For Depression: A Clinical Guideline, Luisa Angeles Collins Villares

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Based on the use of drugs to treat hypertension and tuberculosis for depression, the monoamine hypothesis led to the development of antidepressants in 1952. Serotonin was recognized as a deficiency associated with depression in 1967. As a fine-tuning orchestration of neurotransmitters and neuromodulators, the glutamate system became known using Spravato in 2019 and Auvelity in 2022. In this pilot study, mental health experts rated the importance of 24 science-based recommendations to optimize glutamatergic therapy in depression for a proposed guideline on a Likert scale from zero to four. The results were analyzed using a non-parametric predictive modeling method called Chi-Square …


Enlarged Perivascular Spaces Are A Clinically Relevant Neuroimaging Biomarker Of Cerebral Small Vessel Disease, Timothy Justin Libecap Jan 2024

Enlarged Perivascular Spaces Are A Clinically Relevant Neuroimaging Biomarker Of Cerebral Small Vessel Disease, Timothy Justin Libecap

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) represents the intersection between cerebrovascular disease and cognitive decline. Cerebral small vessel disease (cSVD) is an important risk factor that may precede the onset of VCID by years. cSVD is characterized by in-vivo neuroimaging biomarkers including enlarged perivascular spaces (ePVS). PVS are the site of interchange between interstitial fluid (ISF) and cerebrospinal fluid (CSF) which is believed to play a role in the removal of brain waste. Reduced clearance may lead to enlargement of the PVS and subsequent accumulation of toxic solutes characteristic of neurodegeneration. Given the presence of ePVS in brain …


Repolarizing Tumor-Associated Macrophages In Ovarian Cancer: A Novel Immunotherapeutic Approach, David Schweer Jan 2024

Repolarizing Tumor-Associated Macrophages In Ovarian Cancer: A Novel Immunotherapeutic Approach, David Schweer

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer, recognized for its high lethality and resistance to conventional immunotherapies, mandates innovative strategies to confront its intricate challenges. The tumor microenvironment (TME), orchestrated by tumor-associated macrophages (TAMs), assumes a pivotal role in disease progression, rendering TAMs an appealing therapeutic target. This study endeavors to explore the prospect of repolarizing TAMs from a protumor M2 phenotype to an antitumor M1 state, employing M1 macrophage-derived vesicles (MEVs) as a groundbreaking immunotherapeutic approach.

The primary objective is to investigate the capacity of M1 MEVs to repolarize M2 macrophages in vitro towards an anti-tumor M1-like phenotype. By inducing human macrophages to adopt …


Autonomic Modulation Of Cardiac Function In Hypertrophic Cardiomyopathy, Jenna Rose Disser Jan 2024

Autonomic Modulation Of Cardiac Function In Hypertrophic Cardiomyopathy, Jenna Rose Disser

Dissertations, Master's Theses and Master's Reports

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disorder. HCM is characterized by cardiac hypertrophy, fibrosis, and an increased risk of fatal arrhythmias and sudden cardiac death. Previous studies in humans with HCM have demonstrated increased cardiac norepinephrine spillover and reduced beta-1 receptor (β1R) expression in the left ventricle (LV). We have previously demonstrated that cardiac sympathetic tone is elevated in an alpha-tropomyosin mutant mouse model of HCM. We hypothesized that HCM mice would demonstrate reduced β1R expression in the LV and attenuated heart rate (HR) and dP/dt max responses to ramped infusion of the β1R agonist, dobutamine. …


Suprachoroidal Space Injection Technique Expert Panel Guidance, Charles C. Wykoff, Robert L. Avery, Mark R. Barakat, David S. Boyer, David M. Brown, Alexander J. Brucker, Emmett T. Cunningham Jr., Jeffrey S. Heier, Nancy M. Holekamp, Peter K. Kaiser, Arshad M. Khanani, Judy E. Kim, Hakan Demirci, Carl D. Regillo, Glenn C. Yiu, Thomas A. Ciulla Jan 2024

Suprachoroidal Space Injection Technique Expert Panel Guidance, Charles C. Wykoff, Robert L. Avery, Mark R. Barakat, David S. Boyer, David M. Brown, Alexander J. Brucker, Emmett T. Cunningham Jr., Jeffrey S. Heier, Nancy M. Holekamp, Peter K. Kaiser, Arshad M. Khanani, Judy E. Kim, Hakan Demirci, Carl D. Regillo, Glenn C. Yiu, Thomas A. Ciulla

Wills Eye Hospital Papers

Purpose:

To develop professional guidelines for best practices for suprachoroidal space (SCS) injection, an innovative technique for retinal therapeutic delivery, based on current published evidence and clinical experience.

Methods:

A panel of expert ophthalmologists reviewed current published evidence and clinical experience during a live working group meeting to define points of consensus and key clinical considerations to inform the development of guidelines for in-office SCS injection.

Results:

Core consensus guidelines for in-office SCS injection were reached and reported by the expert panel. Current clinical evidence and physician experience supported SCS injection as a safe and effective method for delivering retinal …


A Comparison Of Concurrent Training And Moderate Intensity Continuous Training In Patients With Coronary Artery Disease, Amanda Alfaro-Chaverri, John Quindry, Charles Dumke, Brian Loyd Jan 2024

A Comparison Of Concurrent Training And Moderate Intensity Continuous Training In Patients With Coronary Artery Disease, Amanda Alfaro-Chaverri, John Quindry, Charles Dumke, Brian Loyd

Graduate Student Theses, Dissertations, & Professional Papers

Moderate intensity continuous training (MICT) is the most studied method in cardiac rehabilitation (CR) for patients with coronary artery disease (CAD). Traditionally, resistance training has been utilized as a secondary role in CR. Recent interest in the topic suggests that MICT and resistance training should be applied collectively, an approach termed concurrent training (CT). The collective understanding of the potential of CT in CR patients is currently lacking.

Purpose: The aim of this professional paper is to analyze scientific evidence regarding the efficacy and safety of CT versus MICT. The analysis will focus on five primary measurements: exercise capacity, cardiovascular …


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 Jan 2024

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 …


Feasible Diet And Circadian Interventions Reduce In Vivo Progression Of Flt3-Itd-Positive Acute Myeloid Leukemia, Megan Rodriguez, Baharan Fekry, Brianna Murphy, Mary Figueroa, Tiewei Cheng, Margaret Raber, Lisa Wartenberg, Donna Bell, Lisa Triche, Karla Crawford, Huaxian Ma, Kendra Allton, Ruwaida Ahmed, Jaime Tran, Christine Ranieri, Marina Konopleva, Michelle Barton, Cesar Nunez, Kristin Eckel-Mahan, Joya Chandra Jan 2024

Feasible Diet And Circadian Interventions Reduce In Vivo Progression Of Flt3-Itd-Positive Acute Myeloid Leukemia, Megan Rodriguez, Baharan Fekry, Brianna Murphy, Mary Figueroa, Tiewei Cheng, Margaret Raber, Lisa Wartenberg, Donna Bell, Lisa Triche, Karla Crawford, Huaxian Ma, Kendra Allton, Ruwaida Ahmed, Jaime Tran, Christine Ranieri, Marina Konopleva, Michelle Barton, Cesar Nunez, Kristin Eckel-Mahan, Joya Chandra

Faculty, Staff and Student Publications

BACKGROUND: Acute myeloid leukemia (AML) with an internal tandem duplication in the fms-like tyrosine kinase receptor 3 gene (FLT3-ITD) is associated with poor survival, and few studies have examined the impact of modifiable behaviors, such as nutrient quality and timing, in this subset of acute leukemia.

METHODS: The influence of diet composition (low-sucrose and/or low-fat diets) and timing of diet were tested in tandem with anthracycline treatment in orthotopic xenograft mouse models. A pilot clinical study to test receptivity of pediatric leukemia patients to macronutrient matched foods was conducted. A role for the circadian protein, BMAL1 (brain and muscle ARNT-like …


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 Jan 2024

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.


Human Equilibrative Nucleoside Transporter 1: Novel Biomarker And Prognostic Indicator For Patients With Gemcitabine-Treated Pancreatic Cancer, Jianchun Xiao, Fangyu Zhao, Wenhao Luo, Gang Yang, Yicheng Wang, Jiangdong Qiu, Yueze Liu, Lei You, Lianfang Zheng, Taiping Zhang Jan 2024

Human Equilibrative Nucleoside Transporter 1: Novel Biomarker And Prognostic Indicator For Patients With Gemcitabine-Treated Pancreatic Cancer, Jianchun Xiao, Fangyu Zhao, Wenhao Luo, Gang Yang, Yicheng Wang, Jiangdong Qiu, Yueze Liu, Lei You, Lianfang Zheng, Taiping Zhang

Faculty, Staff and Student Publications

AIM: This article aimed to find appropriate pancreatic cancer (PC) patients to treat with Gemcitabine with better survival outcomes by detecting hENT1 levels.

METHODS: We collected surgical pathological tissues from PC patients who received radical surgery in our hospital from September 2004 to December 2014. A total of 375 PC tissues and paired adjacent nontumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of the 4 TMAs was examined by HE staining. We performed immunohistochemistry analysis to evaluate hENT1 expression in the TMAs. Moreover, we detected hENT1 expression level and proved the role of hENT1 …


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 Jan 2024

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


Neuromuscular Polytrauma Pain Is Resolved By Macrophage Cox-2 Nanoimmunomodulation, Ibdanelo Cortez, Caitlyn M Gaffney, Riddhi Vichare, Caitlin V Crelli, Lu Liu, Eric Lee, Jules Edralin, James M Nichols, Hoang Vu Pham, Syed Mehdi, Jelena M Janjic, Andrew J Shepherd Jan 2024

Neuromuscular Polytrauma Pain Is Resolved By Macrophage Cox-2 Nanoimmunomodulation, Ibdanelo Cortez, Caitlyn M Gaffney, Riddhi Vichare, Caitlin V Crelli, Lu Liu, Eric Lee, Jules Edralin, James M Nichols, Hoang Vu Pham, Syed Mehdi, Jelena M Janjic, Andrew J Shepherd

Faculty, Staff and Student Publications

Soft tissue injuries often involve muscle and peripheral nerves and are qualitatively distinct from single-tissue injuries. Prior research suggests that damaged innervation compromises wound healing. To test this in a traumatic injury context, we developed a novel mouse model of nerve and lower limb polytrauma, which features greater pain hypersensitivity and more sustained macrophage infiltration than either injury in isolation. We also show that macrophages are crucial mediators of pain hypersensitivity in this model by delivering macrophage-targeted nanoemulsions laden with the cyclooxygenase-2 (COX-2) inhibitor celecoxib. This treatment was more effective in males than females, and more effective when delivered 3 …


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 Jan 2024

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, …


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 Jan 2024

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 …


Targeting The Renin-Angiotensin System (Ras) For Neuropsychiatric Disorders, Aline Silva De Miranda, Danielle S Macedo, Natalia P Rocha, Antonio L Teixeira Jan 2024

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 Jan 2024

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 …


Clic1-Mediated Autophagy Confers Resistance To Ddp In Gastric Cancer, Zhen-Liang Nong, Kun Zhao, Ye Wang, Zhu Yu, Cong-Jun Wang, Jun-Qiang Chen Jan 2024

Clic1-Mediated Autophagy Confers Resistance To Ddp In Gastric Cancer, Zhen-Liang Nong, Kun Zhao, Ye Wang, Zhu Yu, Cong-Jun Wang, Jun-Qiang Chen

Faculty, Staff and Student Publications

Gastric cancer has been a constant concern to researchers as one of the most common malignant tumors worldwide. The treatment options for gastric cancer include surgery, chemotherapy and traditional Chinese medicine. Chemotherapy is an effective treatment for patients with advanced gastric cancer. Cisplatin (DDP) has been approved as a critical chemotherapy drug to treat various kinds of solid tumors. Although DDP is an effective chemotherapeutic agent, many patients develop drug resistance during treatment, which has become a severe problem in clinical chemotherapy. This study aims to investigate the mechanism of DDP resistance in gastric cancer. The results show that intracellular …


A Novel Assessment Of Whole-Mount Gleason Grading In Prostate Cancer To Identify Candidates For Radical Prostatectomy: A Machine Learning-Based Multiomics Study, Jing Ning, Clemens P Spielvogel, David Haberl, Karolina Trachtova, Stefan Stoiber, Sazan Rasul, Vojtech Bystry, Gabriel Wasinger, Pascal Baltzer, Elisabeth Gurnhofer, Gerald Timelthaler, Michaela Schlederer, Laszlo Papp, Helga Schachner, Thomas Helbich, Markus Hartenbach, Bernhard Grubmüller, Shahrokh F Shariat, Marcus Hacker, Alexander Haug, Lukas Kenner Jan 2024

A Novel Assessment Of Whole-Mount Gleason Grading In Prostate Cancer To Identify Candidates For Radical Prostatectomy: A Machine Learning-Based Multiomics Study, Jing Ning, Clemens P Spielvogel, David Haberl, Karolina Trachtova, Stefan Stoiber, Sazan Rasul, Vojtech Bystry, Gabriel Wasinger, Pascal Baltzer, Elisabeth Gurnhofer, Gerald Timelthaler, Michaela Schlederer, Laszlo Papp, Helga Schachner, Thomas Helbich, Markus Hartenbach, Bernhard Grubmüller, Shahrokh F Shariat, Marcus Hacker, Alexander Haug, Lukas Kenner

Faculty, Staff and Student Publications

Purpose: This study aims to assess whole-mount Gleason grading (GG) in prostate cancer (PCa) accurately using a multiomics machine learning (ML) model and to compare its performance with biopsy-proven GG (bxGG) assessment.

Materials and Methods: A total of 146 patients with PCa recruited in a pilot study of a prospective clinical trial (NCT02659527) were retrospectively included in the side study, all of whom underwent 68Ga-PSMA-11 integrated positron emission tomography (PET) / magnetic resonance (MR) before radical prostatectomy (RP) between May 2014 and April 2020. To establish a multiomics ML model, we quantified PET radiomics features, pathway-level genomics …


Toxicity In The Era Of Immune Checkpoint Inhibitor Therapy, Synat Keam, Naimah Turner, Fernanda G Kugeratski, Rene Rico, Jocelynn Colunga-Minutti, Rayansh Poojary, Sayan Alekseev, Anisha B Patel, Yuanteng Jeff Li, Ajay Sheshadri, Monica E Loghin, Karin Woodman, Ashley E Aaroe, Sarah Hamidi, Priyanka Chandrasekhar Iyer, Nicolas L Palaskas, Yinghong Wang, Roza Nurieva Jan 2024

Toxicity In The Era Of Immune Checkpoint Inhibitor Therapy, Synat Keam, Naimah Turner, Fernanda G Kugeratski, Rene Rico, Jocelynn Colunga-Minutti, Rayansh Poojary, Sayan Alekseev, Anisha B Patel, Yuanteng Jeff Li, Ajay Sheshadri, Monica E Loghin, Karin Woodman, Ashley E Aaroe, Sarah Hamidi, Priyanka Chandrasekhar Iyer, Nicolas L Palaskas, Yinghong Wang, Roza Nurieva

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory immune checkpoint molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success and have become the standard of care for many cancers, they are often accompanied by off-target inflammation that can occur in any organ system. These immune related adverse events (irAEs) often require steroid use and/or cessation of ICI therapy, which can both lead to cancer progression. Although irAEs are common, the detailed molecular and immune mechanisms underlying their development are still elusive. To further our understanding …


A Pthrp Gradient Drives Mandibular Condylar Chondrogenesis Via Runx2, C Tsutsumi-Arai, Y Arai, A Tran, M Salinas, Y Nakai, S Orikasa, W Ono, N Ono Jan 2024

A Pthrp Gradient Drives Mandibular Condylar Chondrogenesis Via Runx2, C Tsutsumi-Arai, Y Arai, A Tran, M Salinas, Y Nakai, S Orikasa, W Ono, N Ono

Faculty, Staff and Student Publications

The mandibular condylar cartilage (MCC) is an essential component of the temporomandibular joint, which orchestrates the vertical growth of the mandibular ramus through endochondral ossification with distinctive modes of cell differentiation. Parathyroid hormone–related protein (PTHrP) is a master regulator of chondrogenesis; in the long bone epiphyseal growth plate, PTHrP expressed by resting zone chondrocytes promotes chondrocyte proliferation in the adjacent layer. However, how PTHrP regulates chondrogenesis in the MCC remains largely unclear. In this study, we used a Pthrp-mCherry knock-in reporter strain to map the localization of PTHrP+ cells in the MCC and define the function of PTHrP in the …


Independent Regulation Of Piezo1 Activity By Principal And Intercalated Cells Of The Collecting Duct, Kyrylo Pyrshev, Anna Atamanchuk-Stavniichuk, Mariya Kordysh, Oleg Zaika, Viktor N Tomilin, Oleh Pochynyuk Jan 2024

Independent Regulation Of Piezo1 Activity By Principal And Intercalated Cells Of The Collecting Duct, Kyrylo Pyrshev, Anna Atamanchuk-Stavniichuk, Mariya Kordysh, Oleg Zaika, Viktor N Tomilin, Oleh Pochynyuk

Faculty, Staff and Student Publications

The renal collecting duct is continuously exposed to a wide spectrum of fluid flow rates and osmotic gradients. Expression of a mechanoactivated Piezo1 channel is the most prominent in the collecting duct. However, the status and regulation of Piezo1 in functionally distinct principal and intercalated cells (PCs and ICs) of the collecting duct remain to be determined. We used pharmacological Piezo1 activation to quantify Piezo1-mediated [Ca2+]i influx and single-channel activity separately in PCs and ICs of freshly isolated collecting ducts with fluorescence imaging and electrophysiological tools. We also employed a variety of systemic treatments to examine their consequences on Piezo1 …


Rare Genomic Copy Number Variants Implicate New Candidate Genes For Bicuspid Aortic Valve, Steven G Carlisle, Hasan Albasha, Hector I Michelena, Anna Sabate-Rotes, Lisa Bianco, Julie De Backer, Laura Muiño Mosquera, Anji T Yetman, Malenka M Bissell, Maria Grazia Andreassi, Ilenia Foffa, Dawn S Hui, Anthony Caffarelli, Yuli Y Kim, Dongchuan Guo, Rodolfo Citro, Margot De Marco, Justin T Tretter, Kim L Mcbride, Dianna M Milewicz, Simon C Body, Siddharth K Prakash, Ebav Investigators, Bavcon Investigators Jan 2024

Rare Genomic Copy Number Variants Implicate New Candidate Genes For Bicuspid Aortic Valve, Steven G Carlisle, Hasan Albasha, Hector I Michelena, Anna Sabate-Rotes, Lisa Bianco, Julie De Backer, Laura Muiño Mosquera, Anji T Yetman, Malenka M Bissell, Maria Grazia Andreassi, Ilenia Foffa, Dawn S Hui, Anthony Caffarelli, Yuli Y Kim, Dongchuan Guo, Rodolfo Citro, Margot De Marco, Justin T Tretter, Kim L Mcbride, Dianna M Milewicz, Simon C Body, Siddharth K Prakash, Ebav Investigators, Bavcon Investigators

Faculty, Staff and Student Publications

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control …


The Immunobiology Of Myelodysplastic Neoplasms: A Mini-Review, Shruthi Kannan, Rolando A Vedia, Jeffrey J Molldrem Jan 2024

The Immunobiology Of Myelodysplastic Neoplasms: A Mini-Review, Shruthi Kannan, Rolando A Vedia, Jeffrey J Molldrem

Faculty, Staff and Student Publications

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing …


Nasal Bots Carry Relevant Titers Of Cwd Prions In Naturally Infected White-Tailed Deer, Paulina Soto, Francisca Bravo-Risi, Carlos Kramm, Nazaret Gamez, Rebeca Benavente, Denise L Bonilla, J Hunter Reed, Mitch Lockwood, Terry R Spraker, Tracy Nichols, Rodrigo Morales Jan 2024

Nasal Bots Carry Relevant Titers Of Cwd Prions In Naturally Infected White-Tailed Deer, Paulina Soto, Francisca Bravo-Risi, Carlos Kramm, Nazaret Gamez, Rebeca Benavente, Denise L Bonilla, J Hunter Reed, Mitch Lockwood, Terry R Spraker, Tracy Nichols, Rodrigo Morales

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting farmed and free-ranging cervids. CWD is rapidly expanding across North America and its mechanisms of transmission are not completely understood. Considering that cervids are commonly afflicted by nasal bot flies, we tested the potential of these parasites to transmit CWD. Parasites collected from naturally infected white-tailed deer were evaluated for their prion content using the protein misfolding cyclic amplification (PMCA) technology and bioassays. Here, we describe PMCA seeding activity in nasal bot larvae collected from naturally infected, nonclinical deer. These parasites efficiently infect CWD-susceptible mice in ways suggestive of high infectivity …


Novel Spirocyclic Dimer, Spid3, Targets Chronic Lymphocytic Leukemia Survival Pathways With Potent Preclinical Effects, Alexandria Eiken, Audrey L. Smith, Sydney A. Skupa, Elizabeth Schmitz, Sandeep Rana, Sarbjit Singh, Siddhartha Kumar, Jayapal Reddy Mallareddy, Aguirre A. De Cubas, Akshay Krishna, Achyuth Kalluchi, M. Jordan Rowley, Christopher R. D'Angelo, Matthew A. Lunning, Gregory Bociek, Julie M. Vose, Amarnath Natarajan, Dalia El-Gamal Jan 2024

Novel Spirocyclic Dimer, Spid3, Targets Chronic Lymphocytic Leukemia Survival Pathways With Potent Preclinical Effects, Alexandria Eiken, Audrey L. Smith, Sydney A. Skupa, Elizabeth Schmitz, Sandeep Rana, Sarbjit Singh, Siddhartha Kumar, Jayapal Reddy Mallareddy, Aguirre A. De Cubas, Akshay Krishna, Achyuth Kalluchi, M. Jordan Rowley, Christopher R. D'Angelo, Matthew A. Lunning, Gregory Bociek, Julie M. Vose, Amarnath Natarajan, Dalia El-Gamal

Journal Articles: Oncology and Hematology

Chronic lymphocytic leukemia (CLL) cell survival and growth is fueled by the induction of B-cell receptor (BCR) signaling within the tumor microenvironment (TME) driving activation of NFκB signaling and the unfolded protein response (UPR). Malignant cells have higher basal levels of UPR posing a unique therapeutic window to combat CLL cell growth using pharmacologic agents that induce accumulation of misfolded proteins. Frontline CLL therapeutics that directly target BCR signaling such as Bruton tyrosine kinase (BTK) inhibitors (e.g., ibrutinib) have enhanced patient survival. However, resistance mechanisms wherein tumor cells bypass BTK inhibition through acquired BTK mutations, and/or activation of alternative survival …


Myc Overexpression In Natural Killer Cell Lymphoma: Prognostic And Therapeutic Implications, Chengfeng Bi, Yuhua Huang, Roshia Ali, Fang Wang, Xia Yang, Alyssa Bouska, Lu Xu, Xinbao Hao, Matthew A. Lunning, Wing C. Chan, Javeed Iqbal, Dennis D. Weisenburger, Julie M. Vose, Kai Fu Jan 2024

Myc Overexpression In Natural Killer Cell Lymphoma: Prognostic And Therapeutic Implications, Chengfeng Bi, Yuhua Huang, Roshia Ali, Fang Wang, Xia Yang, Alyssa Bouska, Lu Xu, Xinbao Hao, Matthew A. Lunning, Wing C. Chan, Javeed Iqbal, Dennis D. Weisenburger, Julie M. Vose, Kai Fu

Journal Articles: Oncology and Hematology

The current clinical management of extranodal natural killer (NK)/T-cell lymphoma (ENKTL) primarily depends on conventional chemotherapy and radiotherapy, underscoring the need for innovative therapeutic strategies. This study explores the clinical significance and therapeutic implication of c-MYC (MYC) in ENKTL. Initially, we identified MYC protein overexpression in approximately 75% of cases within a large cohort of 111 patients. MYC overexpression was strongly correlated with lymphoma cell proliferation and poor clinical outcomes. Intriguingly, integrating MYC expression into the prognostic index of NK cells lymphoma with Epstein-Barr virus (PINK-E) prognostic model significantly enhanced its predictive power. Subsequently, we implemented MYC knockdown in NK …


Sunitinib Induced Gomerular Thrombotic Microangiopathy, Aisha Khan Jan 2024

Sunitinib Induced Gomerular Thrombotic Microangiopathy, Aisha Khan

Gulf Coast Division GME Research Symposium 2024

No abstract provided.


Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht Jan 2024

Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht

Saha Cardiovascular Research Center Faculty Publications

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model.

Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice …


Novel Engineering Approaches For Orthopedic Injury Treatment And Infection Diagnosis, Cynthia Co Jan 2024

Novel Engineering Approaches For Orthopedic Injury Treatment And Infection Diagnosis, Cynthia Co

Bioengineering Dissertations - Archive

Bioengineering has made significant contributions to the treatment of orthopedic injury through interdisciplinary approaches. Central to these advancements are many orthopedic implants, including anchors and joint replacements, which have been designed to restore mobility. Despite their functional efficacy, these products have limited lifespan and are associated with many complications, such as implant-associated infection. The success of implant design and function, both in the short and long term, is paramount for enhancing patient outcomes and overall well-being. Therefore, my thesis work is dedicated to addressing these critical challenges, aiming to maximize their treatment effect while minimizing the implant-associated complications.

Long-term patient …


Mesoporous Silica Administration As A New Strategy In The Management Of Warfarin Toxicity: An In-Vitro And In-Vivo Study, Fatemeh Farjadian, Fatemeh Parsi, Reza Heidari, Khatereh Zarkesh, Hamid Reza Mohammadi, Soliman Mohammadi-Samani, Lobat Tayebi Jan 2024

Mesoporous Silica Administration As A New Strategy In The Management Of Warfarin Toxicity: An In-Vitro And In-Vivo Study, Fatemeh Farjadian, Fatemeh Parsi, Reza Heidari, Khatereh Zarkesh, Hamid Reza Mohammadi, Soliman Mohammadi-Samani, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Purpose: Warfarin is one of the most widely used anticoagulants that functions by inhibiting vitamin K epoxide reductase. Warfarin overdose, whether intentional or unintentional, can cause life-threatening bleeding. Here, we present a novel warfarin adsorbent based on mesoporous silica that could serve as an antidote to warfarin toxicity.

Method: Amino-functionalized mesoporous silica (MS-NH₂) was synthesized based on the cocondensation method through a soft template technique followed by template removal. The prepared structure and functional group were studied by Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) checked the morphology. The …