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Emerging Regenerative Medicine And Tissue Engineering Strategies For Parkinson's Disease., James P Harris, Justin C Burrell, Laura A Struzyna, H Isaac Chen, Mijail D Serruya, John A Wolf, John E Duda, D Kacy Cullen Jan 2020

Emerging Regenerative Medicine And Tissue Engineering Strategies For Parkinson's Disease., James P Harris, Justin C Burrell, Laura A Struzyna, H Isaac Chen, Mijail D Serruya, John A Wolf, John E Duda, D Kacy Cullen

Department of Neurology Faculty Papers

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease, affecting 1-2% of people over 65. The classic motor symptoms of PD result from selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in a loss of their long axonal projections to the striatum. Current treatment strategies such as dopamine replacement and deep brain stimulation (DBS) can only minimize the symptoms of nigrostriatal degeneration, not directly replace the lost pathway. Regenerative medicine-based solutions are being aggressively pursued with the goal of restoring dopamine levels in the striatum, with several emerging techniques attempting to reconstruct the …


Conditions For Combining Gene Therapy With Bone Marrow Transplantation In Murine Krabbe Disease., Mohammad Rafi, Paola Luzi, David A Wenger Jan 2020

Conditions For Combining Gene Therapy With Bone Marrow Transplantation In Murine Krabbe Disease., Mohammad Rafi, Paola Luzi, David A Wenger

Department of Neurology Faculty Papers

No abstract provided.


Melanopsin-Expressing Retinal Ganglion Cells In Control Vs. Glaucomatous Retinas, Edward Hamad Jan 2020

Melanopsin-Expressing Retinal Ganglion Cells In Control Vs. Glaucomatous Retinas, Edward Hamad

Williams Honors College, Honors Research Projects

Glaucoma is a common cause of vision loss worldwide and has a large scope of symptoms, ranging from pupillary reflex defects to sleep disorders. These issues can be explained partially by a recently found subtype of retinal ganglion cells that express melanopsin, denoted melanopsin-expressing retinal ganglion cells or mRGCs for short. These cells function primarily as photoreceptors in the non-image forming pathway, but can receive input from rods and cones. Since mRGCs play a role in the pupillary reflex and regulation of the sleep-wake cycle, I investigated if glaucoma leads to the degeneration of these cells in a mouse model …


Diabetes Risk Status And Physical Activity In Pregnant Women: U.S. Brfss 2011, 2013, 2015, 2017, Bethany Rand Jan 2020

Diabetes Risk Status And Physical Activity In Pregnant Women: U.S. Brfss 2011, 2013, 2015, 2017, Bethany Rand

UNF Graduate Theses and Dissertations

Objective: We sought to examine differences in aerobic activity (AA) and muscle-strengthening activity (MSA) by diabetes risk status (DRS) among pregnant women in the United States.

Background: Pregnant women without complications are advised to engage in physical activity (PA) to mitigate adverse outcomes. Differences may exist among pregnant women of diverging diabetes status in meeting national PA recommendations.

Methods: The sample (n=9,597) included pregnant women ages 18-44, who participated in 2011, 2013, 2015, and 2017 Behavioral Risk Factor Surveillance System. Levels of DRS were: no diabetes (ND), high risk for diabetes (HRD) due to self-reported gestational diabetes or …


Lsd1 Promotes Bladder Cancer Progression By Upregulating Lef1 And Enhancing Emt., Qiubo Xie, Tang Tang, Jian Pang, Jing Xu, Xingxia Yang, Linang Wang, Yiqiang Huang, Zhuowei Huang, Gaolei Liu, Dali Tong, Yao Zhang, Luofu Wang, Dianzheng Zhang, Weihua Lan, Qiuli Liu, Jun Jiang Jan 2020

Lsd1 Promotes Bladder Cancer Progression By Upregulating Lef1 And Enhancing Emt., Qiubo Xie, Tang Tang, Jian Pang, Jing Xu, Xingxia Yang, Linang Wang, Yiqiang Huang, Zhuowei Huang, Gaolei Liu, Dali Tong, Yao Zhang, Luofu Wang, Dianzheng Zhang, Weihua Lan, Qiuli Liu, Jun Jiang

PCOM Scholarly Works

Epithelial-to-mesenchymal transition (EMT) is one of the important underlying molecular mechanisms for most types of cancers including bladder cancer. The precise underlying molecular mechanism in EMT-mediated bladder cancer progression is far from completed. LSD1, a histone lysine-specific demethylase, is known to promote cancer cell proliferation, metastasis, and chemoresistance. We found in this study that LSD1 is highly upregulated in bladder cancer specimens, especially those underwent chemotherapy, and the elevated levels of LSD1 are highly associated with bladder cancer grades, metastasis status, and prognosis. Inhibiting or knockdown LSD1 repressed not only EMT process but also cancer progression. Mechanistically, LSD1 complexes with …


The Vhl/Hif Axis In The Development And Treatment Of Pheochromocytoma/Paraganglioma, Song Peng, Jun Zhang, Xintao Tan, Yiqiang Huang, Jing Xu, Natalie Silk, Dianzheng Zhang, Qiuli Liu, Jun Jiang Jan 2020

The Vhl/Hif Axis In The Development And Treatment Of Pheochromocytoma/Paraganglioma, Song Peng, Jun Zhang, Xintao Tan, Yiqiang Huang, Jing Xu, Natalie Silk, Dianzheng Zhang, Qiuli Liu, Jun Jiang

PCOM Scholarly Works

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells in the adrenal medulla (PCCs) or extra-adrenal sympathetic or parasympathetic paraganglia (PGLs). About 40% of PPGLs result from germline mutations and therefore they are highly inheritable. Although dysfunction of any one of a panel of more than 20 genes can lead to PPGLs, mutations in genes involved in the VHL/HIF axis including


Nr2e3 Is A Genetic Modifier That Rescues Retinal Degeneration And Promotes Homeostasis In Multiple Models Of Retinitis Pigmentosa, Sujun Li, Shyamtanu Datta, Emily Brabbit, Zoe Love, Victoria Woytowicz, Kyle Flattery, Jessica Capri, Katie Yao, Siqi Wu, Michael Imboden, Arun Upadhyay, Rasappa Arumugham, Wallace B. Thoreson, Margaret M Deangelis, Neena B. Haider Jan 2020

Nr2e3 Is A Genetic Modifier That Rescues Retinal Degeneration And Promotes Homeostasis In Multiple Models Of Retinitis Pigmentosa, Sujun Li, Shyamtanu Datta, Emily Brabbit, Zoe Love, Victoria Woytowicz, Kyle Flattery, Jessica Capri, Katie Yao, Siqi Wu, Michael Imboden, Arun Upadhyay, Rasappa Arumugham, Wallace B. Thoreson, Margaret M Deangelis, Neena B. Haider

Journal Articles: Ophthalmology

Recent advances in viral vector engineering, as well as an increased understanding of the cellular and molecular mechanism of retinal diseases, have led to the development of novel gene therapy approaches. Furthermore, ease of accessibility and ocular immune privilege makes the retina an ideal target for gene therapies. In this study, the nuclear hormone receptor gene Nr2e3 was evaluated for efficacy as broad-spectrum therapy to attenuate early to intermediate stages of retinal degeneration in five unique mouse models of retinitis pigmentosa (RP). RP is a group of heterogenic inherited retinal diseases associated with over 150 gene mutations, affecting over 1.5 …


A High Docosahexaenoic Acid Diet Alters The Lung Inflammatory Response To Acute Dust Exposure, Edward C. Dominguez, Art J. Heires, Jacqueline A. Pavlik, Tricia D. Larsen, Stephanie Guardado, Joseph H. Sisson, Michelle L. Baack, Debra J. Romberger, Tara M. Nordgren Jan 2020

A High Docosahexaenoic Acid Diet Alters The Lung Inflammatory Response To Acute Dust Exposure, Edward C. Dominguez, Art J. Heires, Jacqueline A. Pavlik, Tricia D. Larsen, Stephanie Guardado, Joseph H. Sisson, Michelle L. Baack, Debra J. Romberger, Tara M. Nordgren

Journal Articles: Internal Medicine

Agricultural workers are at risk for the development of acute and chronic lung diseases due to their exposure to organic agricultural dusts. A diet intervention using the omega-3 fatty acid docosahexaenoic acid (DHA) has been shown to be an effective therapeutic approach for alleviating a dust-induced inflammatory response. We thus hypothesized a high-DHA diet would alter the dust-induced inflammatory response through the increased production of specialized pro-resolving mediators (SPMs). Mice were pre-treated with a DHA-rich diet 4 weeks before being intranasally challenged with a single dose of an extract made from dust collected from a concentrated swine feeding operation (HDE). …


Myd88 Regulates A Prolonged Adaptation Response To Environmental Dust Exposure-Induced Lung Disease, Amber N. Johnson, Jack R. Harkema, Amy J. Nelson, John D. Dickinson, Julianna Kalil, Michael J. Duryee, Geoffrey M. Thiele, Balawant Kumar, Amar B. Singh, Rohit Gaurav, Sarah C. Glover, Ying Tang, Debra J. Romberger, Tammy Kielian, Jill A. Poole Jan 2020

Myd88 Regulates A Prolonged Adaptation Response To Environmental Dust Exposure-Induced Lung Disease, Amber N. Johnson, Jack R. Harkema, Amy J. Nelson, John D. Dickinson, Julianna Kalil, Michael J. Duryee, Geoffrey M. Thiele, Balawant Kumar, Amar B. Singh, Rohit Gaurav, Sarah C. Glover, Ying Tang, Debra J. Romberger, Tammy Kielian, Jill A. Poole

Journal Articles: Internal Medicine

BACKGROUND: Environmental organic dust exposures enriched in Toll-like receptor (TLR) agonists can reduce allergic asthma development but are associated with occupational asthma and chronic bronchitis. The TLR adaptor protein myeloid differentiation factor88 (MyD88) is fundamental in regulating acute inflammatory responses to organic dust extract (ODE), yet its role in repetitive exposures is unknown and could inform future strategies.

METHODS: Wild-type (WT) and MyD88 knockout (KO) mice were exposed intranasally to ODE or saline daily for 3 weeks (repetitive exposure). Repetitively exposed animals were also subsequently rested with no treatments for 4 weeks followed by single rechallenge with saline/ODE.

RESULTS: Repetitive …


Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik Jan 2020

Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik

Journal Articles: Eppley Institute

In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to …


Tlr2 And Caspase-1 Signaling Are Critical For Bacterial Containment But Not Clearance During Craniotomy-Associated Biofilm Infection, Amy L. Aldrich, Cortney E. Heim, Wen Shi, Rachel W. Fallet, Bin Duan, Tammy Kielian Jan 2020

Tlr2 And Caspase-1 Signaling Are Critical For Bacterial Containment But Not Clearance During Craniotomy-Associated Biofilm Infection, Amy L. Aldrich, Cortney E. Heim, Wen Shi, Rachel W. Fallet, Bin Duan, Tammy Kielian

Journal Articles: Pathology and Microbiology

BACKGROUND: A craniotomy is required to access the brain for tumor resection or epilepsy treatment, and despite precautionary measures, infectious complications occur at a frequency of 1-3%. Approximately half of craniotomy infections are caused by Staphylococcus aureus (S. aureus) that forms a biofilm on the bone flap, which is recalcitrant to antibiotics. Our prior work in a mouse model of S. aureus craniotomy infection revealed a critical role for myeloid differentiation factor 88 (MyD88) in bacterial containment and pro-inflammatory mediator production. Since numerous receptors utilize MyD88 as a signaling adaptor, the current study examined the importance of Toll-like receptor 2 …


Search Strategies For “A Comprehensive Analysis Of Mutations In Cutaneous Squamous Cell Carcinoma Reveals Novel Genes And Mutations Associated With Patient-Specific Characteristics And Metastasis”, Marissa Lobl, Dillon Clarey, Cynthia M. Schmidt, Christopher Wichman, Ashley Wysong Jan 2020

Search Strategies For “A Comprehensive Analysis Of Mutations In Cutaneous Squamous Cell Carcinoma Reveals Novel Genes And Mutations Associated With Patient-Specific Characteristics And Metastasis”, Marissa Lobl, Dillon Clarey, Cynthia M. Schmidt, Christopher Wichman, Ashley Wysong

Search Strategies: Leon S. McGoogan Health Sciences Library

No abstract provided.


Hypogonadism, Type-2 Diabetes Mellitus, And Bone Health: A Narrative Review, Vittoria Russo, Rui Chen, Reina Armamento-Villareal Jan 2020

Hypogonadism, Type-2 Diabetes Mellitus, And Bone Health: A Narrative Review, Vittoria Russo, Rui Chen, Reina Armamento-Villareal

Faculty, Staff and Students Publications

One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could …


Sirt3 Promotes Lipophagy And Chaperon-Mediated Autophagy To Protect Hepatocytes Against Lipotoxicity, Tian Zhang, Jingxin Liu, Shengnan Shen, Qiang Tong, Xiaojun Ma, Ligen Lin Jan 2020

Sirt3 Promotes Lipophagy And Chaperon-Mediated Autophagy To Protect Hepatocytes Against Lipotoxicity, Tian Zhang, Jingxin Liu, Shengnan Shen, Qiang Tong, Xiaojun Ma, Ligen Lin

Faculty, Staff and Students Publications

Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs) breakdown, to initiate lipolysis via either cytosolic lipases or macroautophagy. SIRT3, a mitochondrial NAD+-dependent deacetylase, regulates the acetylation status and activity of many substrates involving in energy metabolism. However, the role of SIRT3 in regulating lipophagy is controversial. The current study showed that SIRT3 expression was decreased and the macroautophagy flux was blocked in the primary hepatocytes from high-fat diet fed mice and P/O (palmitic acid and oleic acid mixture) treated AML12 mouse hepatocytes, compared with the corresponding controls. …


Functional Neuroimaging In Psychiatry-Aiding In Diagnosis And Guiding Treatment. What The American Psychiatric Association Does Not Know., Theodore A Henderson, Muriel J Van Lierop, Mary Mclean, John Michael Uszler, John F Thornton, Yin-Hui Siow, Dan G Pavel, Joe Cardaci, Phil Cohen Jan 2020

Functional Neuroimaging In Psychiatry-Aiding In Diagnosis And Guiding Treatment. What The American Psychiatric Association Does Not Know., Theodore A Henderson, Muriel J Van Lierop, Mary Mclean, John Michael Uszler, John F Thornton, Yin-Hui Siow, Dan G Pavel, Joe Cardaci, Phil Cohen

Articles, Abstracts, and Reports

While early efforts in psychiatry were focused on uncovering the neurobiological basis of psychiatric symptoms, they made little progress due to limited ability to observe the living brain. Today, we know a great deal about the workings of the brain; yet, none of this neurobiological awareness has translated into the practice of psychiatry. The categorical system which dominates psychiatric diagnosis and thinking fails to match up to the real world of genetics, sophisticated psychological testing, and neuroimaging. Nevertheless, the American Psychiatric Association (APA) recently published a position paper stating that neuroimaging provided no benefit to the diagnosis and treatment of …


Investigating The Effects Of Brainstem Neuronal Adaptation On Cardiovascular Homeostasis., James H Park, Jonathan Gorky, Babatunde Ogunnaike, Rajanikanth Vadigepalli, James S Schwaber Jan 2020

Investigating The Effects Of Brainstem Neuronal Adaptation On Cardiovascular Homeostasis., James H Park, Jonathan Gorky, Babatunde Ogunnaike, Rajanikanth Vadigepalli, James S Schwaber

Articles, Abstracts, and Reports

Central coordination of cardiovascular function is accomplished, in part, by the baroreceptor reflex, a multi-input multi-output physiological control system that regulates the activity of the parasympathetic and sympathetic nervous systems via interactions among multiple brainstem nuclei. Recent single-cell analyses within the brain revealed that individual neurons within and across brain nuclei exhibit distinct transcriptional states contributing to neuronal function. Such transcriptional heterogeneity complicates the task of understanding how neurons within and across brain nuclei organize and function to process multiple inputs and coordinate cardiovascular functions within the larger context of the baroreceptor reflex. However, prior analysis of brainstem neurons revealed …


Current Advancements In The Management Of Spinal Cord Injury: A Comprehensive Review Of Literature., Manan Shah, Catherine Peterson, Emre Yilmaz, Dia Radi Halalmeh, Marc Moisi Jan 2020

Current Advancements In The Management Of Spinal Cord Injury: A Comprehensive Review Of Literature., Manan Shah, Catherine Peterson, Emre Yilmaz, Dia Radi Halalmeh, Marc Moisi

Articles, Abstracts, and Reports

Background: Spinal cord injury (SCI) carries debilitating lifelong consequences and, therefore, requires careful review of different treatment strategies.

Methods: An extensive review of the English literature (PubMed 1990 and 2019) was performed regarding recent advances in the treatment of SCI; this included 46 articles written over 28 years.

Results: Results of this search were divided into five major modalities; neuroprotective and neuroregenerative pharmaceuticals, neuromodulation, stem cell-based therapies, and various external prosthetic devices. Lately, therapeutic strategies were mainly focused on two major areas: neuroregeneration and neuroprotection.

Conclusion: Despite recent advancements, more clinical trials on a larger scale and further research are …


Targeting Homologous Recombination Addicted Tumors: Challenges And Opportunities, Talia Golan, Jonathan Brody, Md Jan 2020

Targeting Homologous Recombination Addicted Tumors: Challenges And Opportunities, Talia Golan, Jonathan Brody, Md

Kimmel Cancer Center Faculty Papers

Recent advances in next generation sequencing (NGS) and molecular subtyping of tumors have opened the door to clinically available targeted therapies. Although the treatment of many solid tumors still rely on a steady regimen of non-targeted chemotherapeutic agents, it is becoming increasingly more apparent that certain tumors with defects in DNA damage repair (DDR) genes may be exquisitely sensitive to DNA damaging agents or therapies targeting key elements of this pathway such PARP1, ATR, or ATM. Still, for tumors with DDR defects the challenges are multi-fold including: (I) identifying these tumors in patients in time for a window of opportunity …


The Evolving Pharmacotherapeutic Landscape For The Treatment Of Sickle Cell Disease., Samir K Ballas Jan 2020

The Evolving Pharmacotherapeutic Landscape For The Treatment Of Sickle Cell Disease., Samir K Ballas

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) is an extremely heterogeneous disease that has been associated with global morbidity and early mortality. More effective and inexpensive therapies are needed. During the last five years, the landscape of the pharmacotherapy of SCD has changed dramatically. Currently, 54 drugs have been used or under consideration to use for the treatment of SCD. These fall into 3 categories: the first category includes the four drugs (Hydroxyurea, L-Glutamine, Crizanlizumab tmca and Voxelotor) that have been approved by the United States Food and Drug Administration (FDA) based on successful clinical trials. The second category includes 22 drugs that …


Myo/Nog Cells Are Nonprofessional Phagocytes, Jacquelyn Gerhart, Lindsay Gugerty, Paul Lecker, Fathma Abdalla, Mark Martin, Olivia Gerhart, Colby Gerhart, Karanveer Johal, Jake Bernstein, John Spikes, Keith Mathers, Arturo Bravo Nuevo, Mindy George-Weinstein Jan 2020

Myo/Nog Cells Are Nonprofessional Phagocytes, Jacquelyn Gerhart, Lindsay Gugerty, Paul Lecker, Fathma Abdalla, Mark Martin, Olivia Gerhart, Colby Gerhart, Karanveer Johal, Jake Bernstein, John Spikes, Keith Mathers, Arturo Bravo Nuevo, Mindy George-Weinstein

PCOM Scholarly Works

Myo/Nog cells were discovered in the chick embryo epiblast. Their expression of MyoD reflects a commitment to the skeletal muscle lineage and capacity to differentiate into myofibroblasts. Release of Noggin by Myo/Nog cells is essential for normal morphogenesis. Myo/Nog cells rapidly respond to wounding in the skin and eyes. In this report, we present evidence suggesting that Myo/Nog cells phagocytose tattoo ink in tissue sections of human skin and engulf cell corpses in cultures of anterior human lens tissue and magnetic beads injected into the anterior chamber of mice in vivo. Myo/Nog cells are distinct from macrophages in the skin …


The Impact Of The Fda Warning On Post-Tonsillectomy Opioid Prescribing In Publicly And Privately Insured Children, Dianna J. Soelberg Jan 2020

The Impact Of The Fda Warning On Post-Tonsillectomy Opioid Prescribing In Publicly And Privately Insured Children, Dianna J. Soelberg

Theses and Dissertations

Due to reports of significant adverse events, the U.S. FDA placed a Boxed Warning on the opioid codeine in February 2013 – contraindicating its use in pediatric patients undergoing tonsillectomy and/or adenoidectomy. Studies conducted in privately insured children showed a reduction in codeine prescribing and a slight increase in alterative opioid prescribing following the FDA warning, yet the extent to which the FDA warning impacted prescribing in publicly insured children is unknown. Using a quasi-experimental interrupted time series design, this study evaluated codeine and alternative opioid prescribing before and after the FDA warning in both publicly and privately insured children …


Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation, Ria C. Fyffe-Freil Jan 2020

Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation, Ria C. Fyffe-Freil

Theses and Dissertations

Of the over 108,000 American awaiting a life-saving organ transplant today, over 12,000 (11%) of those need a new liver (OPTN, 2020). Last year, only 35% of patients on the waiting list for an organ were transplanted. Improving the quality of marginal organs by preventing or reversing preservation injury could vastly increase the number of transplants performed. Washout of circulating blood during liver procurement with cold University of Wisconsin solution flushes out any endogenous pro-survival signaling molecules. We investigated lysophospholipid (LPL) surface receptors (G-protein coupled receptors for lysophosphatidic acid (LPA) and sphingosine- 1-phosphate (S1P)) and their role in protecting hepatocytes …


Characterizing Glycosaminoglycan And Glycosaminoglycan-Oligo Interactions With Cancer Stem Cells And Their Regulators, Rahaman Navaz Gangji Jan 2020

Characterizing Glycosaminoglycan And Glycosaminoglycan-Oligo Interactions With Cancer Stem Cells And Their Regulators, Rahaman Navaz Gangji

Theses and Dissertations

Tumor metastasis and recurrence account for more than 90% of cancer-associated deaths and are thought to occur due to a small subpopulation of neoplastic cells known as cancer stem cells (CSCs). Because CSCs are resistant to conventional chemotherapy, there is a critical need to develop CSC-targeting agents. Microenvironmental components, especially glycosaminoglycans (GAGs), play a key role in regulating CSC phenotype. GAGs such as heparan sulfate (HS) interact with hundreds of proteins and influence a variety of biological processes including tumor proliferation, angiogenesis, metastasis and stem cell biology.

Recently, the Desai and Patel laboratories have demonstrated that a hexasaccharide form of …


Identification Of Genetic And Antigenic Variation And Evolution Pattern Among Influenza A And B Viruses In Thailand, Nungruthai Suntronwong Jan 2020

Identification Of Genetic And Antigenic Variation And Evolution Pattern Among Influenza A And B Viruses In Thailand, Nungruthai Suntronwong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Seasonal influenza viruses commonly cause respiratory disease and have a considerable impact on public health threats which annually estimates 3 to 5 million cases of severe illness worldwide. The triggering of the seasonal influenza epidemic results from a complex interplay between viral, host and external factors such as climate. Although vaccination is an effective tool for influenza prevention and its complications, the composition of vaccine strain has been changed every year due to influenza constantly evolving. Here, we aim to examine the association between influenza activity and local climate factors, host immunity, genetic and antigenic variation and evolution pattern among …


Isolation And Characterization Of Α-Gal-Containing Extracellular Vesicles (Evs) From Three Major Genotypes Of Trypanosoma Cruzi: Potential Biomarkers Of Chagas Disease, Nasim Karimi Hosseini Jan 2020

Isolation And Characterization Of Α-Gal-Containing Extracellular Vesicles (Evs) From Three Major Genotypes Of Trypanosoma Cruzi: Potential Biomarkers Of Chagas Disease, Nasim Karimi Hosseini

Open Access Theses & Dissertations

Chagas disease (ChD) is a neglected tropical disease (NTD) caused by the protozoan parasite, Trypanosoma cruzi. It is transmitted by the insect-vector triatomine (popular known as kissing bug), blood transfusion, organ transplantation, congenitally, and contaminated foods and juices. T. cruzi has evolved several strategies to invade the host cells, including the release extracellular vesicles (EVs), which assist pathogen survival and its replication within the host. T. cruzi is covered with highly glycosylated surface molecules such as glycoproteins and glycolipids, which are shown to be involved in the interaction with host immune cells. These molecules are highly immunogenic and reactive with …


Targeting Epha2 In Hepatocellular Carcinoma: Uncovering Its Therapeutic Potential And Beyond, Hao Wang Jan 2020

Targeting Epha2 In Hepatocellular Carcinoma: Uncovering Its Therapeutic Potential And Beyond, Hao Wang

Dissertations

Hepatocellular Carcinoma (HCC) remains one of the deadliest malignancies worldwide. One major obstacle to treatment is a lack of effective molecular-targeted therapies. Here, we identify EphA2 receptor tyrosine kinase as a clinically relevant target for HCC. EphA2 expression and signaling is enriched in human HCC and associates with poor prognosis. Loss of EphA2 suppressed the initiation and growth of HCC in vitro and in vivo. Furthermore, CRISPR/CAS9 mediated EphA2 inhibition significantly delayed tumor development in a genetically-engineered murine model of HCC. Mechanistically, we discovered that targeting EphA2 simultaneously suppresses both JAK1/STAT3 and AKT signaling, two separate oncogenic pathways in HCC. …


Extracellular Mitochondria Released From Traumatized Brains Induced Platelet Procoagulant Activity, Zilong Zhao, Yuan Zhou, Tristan Hilton, Fanjian Li, Cha Han, Li Liu, Hengjie Yuan, Ying Li, Xin Xu, Xiaoping Wu, Fangyi Zhang, Perumal Thiagarajan, Andrew Cap, Fu-Dong Shi, Jianning Zhang, Jing-Fei Dong Jan 2020

Extracellular Mitochondria Released From Traumatized Brains Induced Platelet Procoagulant Activity, Zilong Zhao, Yuan Zhou, Tristan Hilton, Fanjian Li, Cha Han, Li Liu, Hengjie Yuan, Ying Li, Xin Xu, Xiaoping Wu, Fangyi Zhang, Perumal Thiagarajan, Andrew Cap, Fu-Dong Shi, Jianning Zhang, Jing-Fei Dong

Faculty, Staff and Students Publications

Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant. In testing this hypothesis experimentally, we found that the extracellular mitochondria purified from brain trauma mice and those released from brains subjected to freeze-thaw injury remained metabolically active and produced reactive …


Spironolactone In Pulmonary Arterial Hypertension: Results Of A Cross-Over Study, Zeenat Safdar, Adaani Frost, Arya Basant, Anita Deswal, E O'Brian Smith, Mark Entman Jan 2020

Spironolactone In Pulmonary Arterial Hypertension: Results Of A Cross-Over Study, Zeenat Safdar, Adaani Frost, Arya Basant, Anita Deswal, E O'Brian Smith, Mark Entman

Faculty, Staff and Students Publications

The renin–angiotensin–aldosterone system is implicated in the pathophysiology of pulmonary arterial hypertension. We undertook this study to determine the effects of spironolactone, a mineralocorticoid receptor blocker, on collagen metabolism in pulmonary arterial hypertension patients. After obtaining institutional review board approval and informed consent, 42 pulmonary arterial hypertension patients were prospectively enrolled and 35 patients completed the 16-week randomized double-blinded crossover clinical trial. Subjects received 50 mg spironolactone or placebo and at the end of week 8, treatment arm was switched. Circulating levels of collagen biomarkers, brain natriuretic peptide, and aldosterone levels were measured, and six-minute walk distance, liver function tests, …


Black Women And Body Image: Implications Of The Racialized Beauty Aesthetic, Rachel L. Boutte Jan 2020

Black Women And Body Image: Implications Of The Racialized Beauty Aesthetic, Rachel L. Boutte

Theses and Dissertations

Black women have the highest prevalence of overweight and obesity relative to any other demographic group in the United States, however current weight management interventions appear least effective for them. Although several hypotheses have been proposed to explain these outcomes, few studies have collected data to evaluate how well they fit the lived experiences of Black women. In particular, the potential roles of body image and body dissatisfaction in the development and maintenance of overweight and obesity in Black women are not well understood. Extant literature largely reports that Black women are inoculated from body dissatisfaction due to cultural factors, …


Proprotein Convertase Subtilisin/Kexin Type-9 (Pcsk-9) Inhibitors Induced Liver Injury - A Retrospective Analysis., Yousuf Zafar, Yasar Sattar, Waqas Ullah, Sohaib Roomi, Mamoon-Ur- Rashid, Muhammad Shayan Khan, Laura Schmidt Jan 2020

Proprotein Convertase Subtilisin/Kexin Type-9 (Pcsk-9) Inhibitors Induced Liver Injury - A Retrospective Analysis., Yousuf Zafar, Yasar Sattar, Waqas Ullah, Sohaib Roomi, Mamoon-Ur- Rashid, Muhammad Shayan Khan, Laura Schmidt

Abington Jefferson Health Papers

Background: Proprotein convertase subtilisin/Kexin type 9 (PCSK-9) inhibitors induced liver dysfunction in patients with or without previous liver injury, and this is not well discussed in the previous literature.

Methods: A total sample of 202 patients were retrospectively reviewed at the University of Missouri, Kansas City, from the year 2015 to 2018 based on predefined selection criteria. Inclusion criteria involved patients with dyslipidemia, with or without PCSK-9 inhibitors, liver function tests and lipid profile at baseline and at a mean of 6-month follow-up. The variables, including age, gender, and confounding factors like other medications (statin, oral antidiabetic, and antihypertensive) induced, …