Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma,
2022
Jacksonville State University
Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter
Theses
Ewing sarcoma (ES) is an aggressive pediatric bone cancer with low five-year survival rates, particularly with recurrent disease because ES often becomes resistant to chemotherapy in these recurrences. Cannabidiol (CBD) has been identified as a potentially promising therapeutic for patients with ES. In other cancer types, CBD has demonstrated effects on two major proteins that contribute to chemotherapy resistance. The first, Poly (ADP-ribose) Polymerase I (PARP1), is a DNA damage repair enzyme that is overexpressed in recurrent ES. Though chemotherapy induces DNA damage in these cancer cells, the high levels of PARP1 facilitate repair of the DNA, allowing the mutated …
Artificial Gravity Partially Protects Space-Induced Neurological Deficits In Drosophila Melanogaster,
2022
Embry-Riddle Aeronautical University
Artificial Gravity Partially Protects Space-Induced Neurological Deficits In Drosophila Melanogaster, Amber M. Paul, Siddhita D. Mhatre, Janani Iyer, Juli Petereit, Roberta M. Dolling-Boreham
Publications
Spaceflight poses risks to the central nervous system (CNS), and understanding neurological responses is important for future missions. We report CNS changes in Drosophila aboard the International Space Station in response to spaceflight microgravity (SFmg) and artificially simulated Earth gravity (SF1g) via inflight centrifugation as a countermeasure. While inflight behavioral analyses of SFmg exhibit increased activity, postflight analysis displays significant climbing defects, highlighting the sensitivity of behavior to altered gravity. Multiomics analysis shows alterations in metabolic, oxidative stress and synaptic transmission pathways in both SFmg and SF1g; however, neurological changes immediately postflight, including neuronal loss, glial cell count alterations, oxidative …
Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation,
2022
Wright State University
Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation, Morgan M. Highlander, Sherif M. Elbasiouny
Neuroscience, Cell Biology & Physiology Faculty Publications
Spinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. …
Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids,
2022
Wright State University - Main Campus
Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids, J. Ashot Kozak
Neuroscience, Cell Biology & Physiology Faculty Publications
No abstract provided.
Unreliable Automated Complete Blood Count Results: Causes, Recognition, And Resolution,
2022
Thomas Jefferson University
Unreliable Automated Complete Blood Count Results: Causes, Recognition, And Resolution, Gene Gulati, Guldeep Uppal, Jerald Z. Gong
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Automated hematology analyzers generate accurate complete blood counts (CBC) results on nearly all specimens. However, every laboratory encounters, at times, some specimens that yield no or inaccurate result(s) for one or more CBC parameters even when the analyzer is functioning properly and the manufacturer's instructions are followed to the letter. Inaccurate results, which may adversely affect patient care, are clinically unreliable and require the attention of laboratory professionals. Laboratory professionals must recognize unreliable results, determine the possible cause(s), and be acquainted with the ways to obtain reliable results on such specimens. We present a concise overview of the known causes …
Role Of Decorin At The Fetal-Maternal Interface,
2022
The University of Western Ontario
Role Of Decorin At The Fetal-Maternal Interface, Chidambra D. Halari
Electronic Thesis and Dissertation Repository
The human placenta is an invasive tumor-like structure, this invasion being physiological. A subset of placental trophoblast called extra-villous trophoblast invades the uterine decidua and remodels uterine arteries into low-resistance, high-flow tubes to permit adequate flow of maternal blood to nourish the fetus. A poor extra-villous trophoblast invasion and uterine arterial remodeling can lead to fetal growth restriction and a serious pregnancy-associated maternal disease preeclampsia. Decorin, a leucine-rich proteoglycan produced by uterine decidual cells restrains multiple trophoblast functions: self-renewal and differentiation of trophoblast stem cells, migration, invasion, proliferation and endovascular differentiation. Additionally, decidual overproduction of decorin was associated with preeclampsia, …
Hashimoto’S Thyroiditis Minimizes Lymph Node Metastasis In Braf Mutant Papillary Thyroid Carcinomas,
2022
LSU Health Sciences Center - New Orleans
Hashimoto’S Thyroiditis Minimizes Lymph Node Metastasis In Braf Mutant Papillary Thyroid Carcinomas, Peter P. Issa, Mahmoud Omar, Yusef Buti, Chad P. Issa, Bert Chabot, Christopher J. Carnabatu, Ruhul Munshi, Mohammad Hussein, Mohamed Aboueisha, Mohamed Shama, Ralph L. Corsetti, Eman Toraih, Emad Kandil
School of Medicine Faculty Publications
Hashimoto’s thyroiditis (HT) (autoimmune thyroiditis) is a clinicopathological entity associated with chronic lymphocytic infiltration resulting in hypothyroidism. HT is a double-edged sword that increases the risk of papillary thyroid cancer (PTC), yet it serves as a protective factor for PTC progression. BRAF mutation in PTCs is associated with rapid cell growth, aggressive tumor characteristics, and higher mortality rates. Here, we aimed to analyze the influence of HT in patients with PTCs and its effect on lymph node metastasis (LNM) in BRAF mutant tumors. Adults diagnosed with PTC between 2008 and January 2021 were retrospectively included. A total of 427 patients, …
Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models,
2022
Western University
Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak
Undergraduate Student Research Internships Conference
Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas3, an excessive and/or prolonged immune response1, the activation and proliferation of fibrosis-inducing progenitor cells4, and a pro-fibrotic extra-cellular microenvironment5. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …
Constructing An In Vitro 3d Model Of The Human Placenta,
2022
Western University
Constructing An In Vitro 3d Model Of The Human Placenta, Michael Zheng
Undergraduate Student Research Internships Conference
The placenta is critical for nurturing fetal growth and development, with dysregulated placentation associated with adverse pregnancy outcomes. The main fetal and maternal placental components consist of trophoblasts and modified endometrial stromal cells known as decidual cells, respectively. Since investigating in vivo placentas in humans through non-invasive methods is challenging, comprehensive in vitro placental models are needed for in-depth studies. However, in vitro 3D placental models that adequately represent and combine fetal and maternal components have been lacking. In this study, we achieved valuable progress in developing an in vitro 3D placental model inclusive of fetal and maternal constituents. We …
Mistranslating Trnas Alter The Heat Shock Activation By Hsf1,
2022
Western University
Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib
Undergraduate Student Research Internships Conference
Translation, or the production of protein from an mRNA blueprint, is among the most fundamental processes to life as we know it. tRNAs are essential to accurate translation, as they decode the codons of mRNA and recruit corresponding amino acids. Variant tRNAs with anticodon mutations can decrease translational fidelity by recruiting the incorrect amino acid, an aberrant process known as mistranslation. When proteins are produced with incorrect amino acid sequences, they may misfold. The heat shock response functions to alleviate cellular stress caused by misfolded proteins, either by refolding or targeting misfolded proteins for degradation. Hsf1 acts as a transcriptional …
Latency Trend Analysis As A Guide To Screening Malignancy Survivors For Second Primary Thyroid Cancer,
2022
Tulane University School of Medicine
Latency Trend Analysis As A Guide To Screening Malignancy Survivors For Second Primary Thyroid Cancer, Mohammad Hussein, Lauren Mueller, Peter P. Issa, Muhib Haidari, Lily Trinh, Eman Toraih, Emad Kandil
School of Medicine Faculty Publications
Primary cancer survivors have a higher risk of developing second primary thyroid cancer (SPTC). Patients with SPTC who survived primary malignancies, diagnosed from 1975 to 2016, were identified from the Surveillance, Epidemiology, and End Results (SEER) database (SEER 18 Registry). A total of 33,551 cancer cases were enrolled in the final analysis. Individuals with a primary malignancy were at a significant 90% increased risk of developing SPTC (SIR = 1.90, 95%CI = 1.86–1.93, p < 0.05) compared to the general population. More than half (54.7%) of SPTC diagnoses were made in the first three years after primary cancer diagnosis, and the most aggressive presentations of SPTC occurred within the first year following malignancy. A latency trend analysis identified persistent high risk for development of SPTC after diagnosis of lymphoma, leukemia, soft tissue tumors, kidney, breast, and uterine cancer; elevated 10-year risk for most cancers such as salivary gland, melanoma, stomach, lung, colon, ovarian, pancreas, prostate, and bladder; and high 5-year risk after cancers such as larynx, oral, orbit, bone, small intestine, and liver. Our latency period model identifying risk according to each type of primary cancer may aid clinicians in identifying at-risk patients to be screened for thyroid cancer and guide them in developing a surveillance plan according to the latency period attributed to a patient’s primary cancer.
Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length,
2022
Chapman University
Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length, Young-Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Laren-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang
Pharmacy Faculty Articles and Research
Small-conductance Ca2+-activated potassium (KCa2.x) channels are gated exclusively by intracellular Ca2+. The activation of KCa2.3 channels induces hyperpolarization, which augments Ca2+ signaling in endothelial cells. Cilia are specialized Ca2+ signaling compartments. Here, we identified compound 4 that potentiates human KCa2.3 channels selectively. The subtype selectivity of compound 4 for human KCa2.3 over rat KCa2.2a channels relies on an isoleucine residue in the HA/HB helices. Positive modulation of KCa2.3 channels by compound 4 increased flow-induced Ca2+ signaling and cilia length, while negative …
Dual Mechanisms Implemented By Lin-28 For Positive Regulation Of Hbl-1 Are Necessary For Proper Development Of Distinct Tissues In Caenorhabditis Elegans,
2022
Rowan University
Dual Mechanisms Implemented By Lin-28 For Positive Regulation Of Hbl-1 Are Necessary For Proper Development Of Distinct Tissues In Caenorhabditis Elegans, Madeleine Minutillo
Graduate School of Biomedical Sciences Theses and Dissertations
In Caenorhabditis elegans, the heterochronic pathway is comprised of a hierarchy of genes that control the proper timing of developmental events. hbl-1 (Hunchback Like-1) encodes an Ikaros family zinc-finger transcription factor that promotes the L2 stage cell fate events of the hypodermis. The downregulation ofhbl-1 is a crucial step for the transition from the L2 to the L3 stage. There are two known processes through which negative regulation of hbl-1 occurs: suppression of hbl-1 expression by 3 let-7 miRNAs through the hbl-1 3’UTR and inhibition of HBL-1 activity by LIN-46. The mechanisms by which hbl-1 is positively regulated have not …
Glucose Uptake By Glut1 In Photoreceptors Is Essential For Outer Segment Renewal And Rod Photoreceptor Survival,
2022
Thomas Jefferson University
Glucose Uptake By Glut1 In Photoreceptors Is Essential For Outer Segment Renewal And Rod Photoreceptor Survival, Lauren L. Daniele, John Y.S. Han, Ivy S Samuels, Ravikiran Komirisetty, Nikhil Mehta, Jessica L Mccord, Minzhong Yu, Yekai Wang, Kathleen Boesze-Battaglia, Brent A Bell, Jianhai Du, Neal S Peachey, Nancy J. Philp
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or …
Patient With Multiple Genetically Distinct Thyroid Nodules Including Papillary Thyroid Carcinoma Harboring Novel Ywhag-Braf Fusion,
2022
Thomas Jefferson University
Patient With Multiple Genetically Distinct Thyroid Nodules Including Papillary Thyroid Carcinoma Harboring Novel Ywhag-Braf Fusion, Ruihe Lin, Zi-Xuan Wang, Elizabeth Cottrill, Nitika Badjatia, Stacey Gargano
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Next-generation sequencing (NGS) analysis of thyroid samples aids in risk stratification of cytologically indeterminate nodules and contributes to our understanding of molecular mechanisms in thyroid neoplasia. Several genes, including BRAF, RAS, and EIF1AX, are known to play a role in thyroid tumorigenesis. Here we report a case of papillary thyroid carcinoma (PTC) in which a single lesion harbored a novel YWHAG-BRAF fusion and EIF1AX mutation and displayed mixed morphological findings. The patient is a 74-year-old female with multiple incidentally discovered thyroid nodules, two of which were sampled by ultrasound-guided fine needle aspiration (FNA). Cytologic diagnosis for both nodules was suspicious …
Altered Genome-Wide Hippocampal Gene Expression Profiles Following Early Life Lead Exposure And Their Potential For Reversal By Environmental Enrichment,
2022
Thomas Jefferson University
Altered Genome-Wide Hippocampal Gene Expression Profiles Following Early Life Lead Exposure And Their Potential For Reversal By Environmental Enrichment, Garima Singh, V Singh, T Kim, A Ertel, W Fu, J S Schneider
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Early life lead (Pb) exposure is detrimental to neurobehavioral development. The quality of the environment can modify negative influences from Pb exposure, impacting the developmental trajectory following Pb exposure. Little is known about the molecular underpinnings in the brain of the interaction between Pb and the quality of the environment. We examined relationships between early life Pb exposure and living in an enriched versus a non-enriched postnatal environment on genome-wide transcription profiles in hippocampus CA1. RNA-seq identified differences in the transcriptome of enriched vs. non-enriched Pb-exposed animals. Most of the gene expression changes associated with Pb exposure were reversed by …
A Conserved Mechanism For Hormesis In Molecular Systems,
2022
Rowan University
A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …
The Role Of Microglia In Neuroinflammation Of The Spinal Cord After Peripheral Nerve Injury,
2022
Wright State University
The Role Of Microglia In Neuroinflammation Of The Spinal Cord After Peripheral Nerve Injury, Tana S. Pottorf, Travis M. Rotterman, William M. Mccallum, Zoë A. Haley-Johnson, Francisco J. Alvarez
Neuroscience, Cell Biology & Physiology Faculty Publications
Peripheral nerve injuries induce a pronounced immune reaction within the spinal cord, largely governed by microglia activation in both the dorsal and ventral horns. The mechanisms of activation and response of microglia are diverse depending on the location within the spinal cord, type, severity, and proximity of injury, as well as the age and species of the organism. Thanks to recent advancements in neuro-immune research techniques, such as single-cell transcriptomics, novel genetic mouse models, and live imaging, a vast amount of literature has come to light regarding the mechanisms of microglial activation and alluding to the function …
A Mathematical Model Of Glut1 Modulation In Rods And Rpe And Its Differential Impact In Cell Metabolism,
2022
Arizona State University
A Mathematical Model Of Glut1 Modulation In Rods And Rpe And Its Differential Impact In Cell Metabolism, Andrea Aparicio, Erika T Camacho, Nancy J. Philp, Stephen A Wirkus
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
We present a mathematical model of key glucose metabolic pathways in two cells of the human retina: the rods and the retinal pigmented epithelium (RPE). Computational simulations of glucose transporter 1 (GLUT1) inhibition in the model accurately reproduce experimental data from conditional knockout mice and reveal that modification of GLUT1 expression levels of both cells differentially impacts their metabolism. We hypothesize that, under glucose scarcity, the RPE’s energy producing pathways are altered in order to preserve its functionality, impacting the photoreceptors’ outer segment renewal. On the other hand, when glucose is limited in the rods, aerobic glycolysis is preserved, which …
Ros And Mirna Dysregulation In Ovarian Cancer Development, Angiogenesis And Therapeutic Resistance,
2022
Thomas Jefferson University
Ros And Mirna Dysregulation In Ovarian Cancer Development, Angiogenesis And Therapeutic Resistance, David C Stieg, Yifang Wang, Ling-Zhi Liu, Bing-Hua Jiang
Kimmel Cancer Center Faculty Papers
The diverse repertoires of cellular mechanisms that progress certain cancer types are being uncovered by recent research and leading to more effective treatment options. Ovarian cancer (OC) is among the most difficult cancers to treat. OC has limited treatment options, especially for patients diagnosed with late-stage OC. The dysregulation of miRNAs in OC plays a significant role in tumorigenesis through the alteration of a multitude of molecular processes. The development of OC can also be due to the utilization of endogenously derived reactive oxygen species (ROS) by activating signaling pathways such as PI3K/AKT and MAPK. Both miRNAs and ROS are …
