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Articles 31 - 47 of 47
Full-Text Articles in Medical Biochemistry
Helical Remodeling Augments 5-Lipoxygenase Activity In The Synthesis Of Proinflammatory Mediators, Eden M. Gallegos, Tanner D. Reed, Forge A. Mathes, Nelson V. Guevara, David B. Neau, Wei Huang, Marcia E. Newcomer, Nathaniel C. Gilbert
Helical Remodeling Augments 5-Lipoxygenase Activity In The Synthesis Of Proinflammatory Mediators, Eden M. Gallegos, Tanner D. Reed, Forge A. Mathes, Nelson V. Guevara, David B. Neau, Wei Huang, Marcia E. Newcomer, Nathaniel C. Gilbert
School of Medicine Faculty Publications
The synthesis of proinflammatory leukotrienes implicated in asthma, allergic rhinitis, and atherosclerosis is initiated by the enzyme 5-lipoxygenase (5-LOX). The crystal structure of human Stable-5-LOX revealed a conformation where the catalytic iron was inaccessible to bulk solvent as two aromatic residues on a conserved helix-α2 (Hα2) plugged the substrate access portal. Whether 5-LOX can also adopt a more open conformation has not been resolved. Here, we present a new conformation of 5-LOX where Hα2 adopts an elongated conformation equivalent to that described in other animal lipoxygenase structures. Our observation of the sigmoidal kinetic behavior of 5-LOX, which is indicative of …
An Rtn4/Nogo-A-Interacting Micropeptide Modulates Synaptic Plasticity With Age, S. Kragness, Z. Clark, A. Mullin, J. Guidry, L. R. Earls
An Rtn4/Nogo-A-Interacting Micropeptide Modulates Synaptic Plasticity With Age, S. Kragness, Z. Clark, A. Mullin, J. Guidry, L. R. Earls
School of Medicine Faculty Publications
Micropeptides, encoded from small open reading frames of 300 nucleotides or less, are hidden throughout mammalian genomes, though few functional studies of micropeptides in the brain are published. Here, we describe a micropeptide known as the Plasticity–Associated Neural Transcript Short (Pants), located in the 22q11.2 region of the human genome, the microdeletion of which conveys a high risk for schizophrenia. Our data show that Pants is upregulated in early adulthood in the mossy fiber circuit of the hippocampus, where it exerts a powerful negative effect on long-term potentiation (LTP). Further, we find that Pants is secreted from neurons, where it …
Nr4a Family Genes: A Review Of Comprehensive Prognostic And Gene Expression Profile Analysis In Breast Cancer, Hassan Yousefi, Jordyn Fong, Suresh K. Alahari
Nr4a Family Genes: A Review Of Comprehensive Prognostic And Gene Expression Profile Analysis In Breast Cancer, Hassan Yousefi, Jordyn Fong, Suresh K. Alahari
School of Medicine Faculty Publications
This report analyzes nuclear receptor (NR) subfamily 4A’s potential role in treating those diagnosed with breast cancer. Here we reviewed the current literature on NR4 family members. We also examined the relative gene expression of the NR4A receptor subfamily in the basal, HER2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B subtypes using data from tumor samples in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). These data showed a positive link between NR4A1-NR4A3 expression and increased overall survival and relapse-free survival in breast cancer patients. In addition, we observed …
Association Of Serum Magnesium With Blood Pressure In Patients With Hypertensive Crises: A Retrospective Cross-Sectional Study, Ifeanyichukwu O. Onor, Lashira M. Hill, Modupe M. Famodimu, Mallory R. Coleman, Carolkim H. Huynh, Robbie A. Beyl, Casey J. Payne, Emily K. Johnston, John I. Okogbaa, Christopher J. Gillard, Daniel F. Sarpong, Amne Borghol, Samuel C. Okpechi, Ifeyinwa Norbert, Shane E. Sanne, Shane G. Guillory
Association Of Serum Magnesium With Blood Pressure In Patients With Hypertensive Crises: A Retrospective Cross-Sectional Study, Ifeanyichukwu O. Onor, Lashira M. Hill, Modupe M. Famodimu, Mallory R. Coleman, Carolkim H. Huynh, Robbie A. Beyl, Casey J. Payne, Emily K. Johnston, John I. Okogbaa, Christopher J. Gillard, Daniel F. Sarpong, Amne Borghol, Samuel C. Okpechi, Ifeyinwa Norbert, Shane E. Sanne, Shane G. Guillory
School of Graduate Studies Faculty Publications
The role of magnesium in blood pressure has been studied among hypertensive patients; however, there is a dearth of studies exploring the role of magnesium in hypertensive crises. The primary objective of this study was to evaluate the relationship between serum magnesium and blood pressure in patients with hypertensive crises. This was a singlecenter, retrospective, chart review, cross-sectional study of patients with hypertensive crises. Patients were included if they were eighteen years of age or older, with an international classification disease ninth revision (ICD-9) code of 401.9 (hypertensive crises: emergency or urgency) and a documented magnesium level on their electronic …
Trojan Horses And Tunneling Nanotubes Enable Α-Synuclein Pathology To Spread In Parkinson Disease, Santhanasabapathy Rajasekaran, Stephan N. Witt
Trojan Horses And Tunneling Nanotubes Enable Α-Synuclein Pathology To Spread In Parkinson Disease, Santhanasabapathy Rajasekaran, Stephan N. Witt
School of Graduate Studies Faculty Publications
No abstract provided.
The Roles Of Tumor-Derived Exosomes In Altered Differentiation, Maturation And Function Of Dendritic Cells, Reza Hosseini, Leila Asef-Kabiri, Hassan Yousefi, Hamzeh Sarvnaz, Majid Salehi, Mohammad Esmaeil Akbari, Nahid Eskandari
The Roles Of Tumor-Derived Exosomes In Altered Differentiation, Maturation And Function Of Dendritic Cells, Reza Hosseini, Leila Asef-Kabiri, Hassan Yousefi, Hamzeh Sarvnaz, Majid Salehi, Mohammad Esmaeil Akbari, Nahid Eskandari
School of Graduate Studies Faculty Publications
Tumor-derived exosomes (TDEs) have been shown to impede anti-tumor immune responses via their immunosuppressive cargo. Since dendritic cells (DCs) are the key mediators of priming and maintenance of T cell-mediated responses; thus it is logical that the exosomes released by tumor cells can exert a dominant influence on DCs biology. This paper intends to provide a mechanistic insight into the TDEs-mediated DCs abnormalities in the tumor context. More importantly, we discuss extensively how tumor exosomes induce subversion of DCs differentiation, maturation and function in separate sections. We also briefly describe the importance of TDEs at therapeutic level to help guide …
Evaluation Of Liver Kinase B1 Downstream Signaling Expression In Various Breast Cancers And Relapse Free Survival After Systemic Chemotherapy Treatment, Khoa Nguyen, Andrew Rivera, Madlin Alzoubi, Henri Wathieu, Shengli Dong, Hassan Yousefi, Margarite Matossian, Suresh Alahari, David Drewry, Matthew Burow, Bridgette Collins-Burow
Evaluation Of Liver Kinase B1 Downstream Signaling Expression In Various Breast Cancers And Relapse Free Survival After Systemic Chemotherapy Treatment, Khoa Nguyen, Andrew Rivera, Madlin Alzoubi, Henri Wathieu, Shengli Dong, Hassan Yousefi, Margarite Matossian, Suresh Alahari, David Drewry, Matthew Burow, Bridgette Collins-Burow
School of Medicine Faculty Publications
LKB1-signaling has prominent roles in cancer development and metastasis. This report evaluates LKB1-signaling pathway gene expression associations with patient survival in overall breast cancer, specific subtypes, as well as pre- and post-chemotherapy. Subtypes analyzed were based on intrinsic molecular subtyping and traditional biomarker classifications. Intrinsic molecular subtypes included were Luminal-A, Luminal-B, HER2-enriched, and Basal-like. The biomarker subtypes assessed were Estrogen-Receptor Positive (ER+) and Negative (ER-), Wild-Type TP53 (WT-TP53) & Mutant-TP53, and Triple-Negative Breast Cancer (TNBC). Additionally, comparisons were made between these subtypes and breast cancer overall, and analyses between LKB1 signaling to patient survival before and after chemotherapy were made. …
Global Sex Disparity Of Covid-19: A Descriptive Review Of Sex Hormones And Consideration For The Potential Therapeutic Use Of Hormone Replacement Therapy In Older Adults, Samuel C. Okpechi, Jordyn T. Fong, Shawn S. Gill, Jarrod C. Harman, Tina H. Nguyen, Queendaleen Chukwurah, Ifeanyichukwu O. Onor, Suresh K. Alahari
Global Sex Disparity Of Covid-19: A Descriptive Review Of Sex Hormones And Consideration For The Potential Therapeutic Use Of Hormone Replacement Therapy In Older Adults, Samuel C. Okpechi, Jordyn T. Fong, Shawn S. Gill, Jarrod C. Harman, Tina H. Nguyen, Queendaleen Chukwurah, Ifeanyichukwu O. Onor, Suresh K. Alahari
School of Graduate Studies Faculty Publications
The 2019-2020 SARS-related coronavirus-2 (SARS-CoV-2) pandemic has brought unprecedented challenges to healthcare sectors around the world. As of November 2020, there have been over 64 million confirmed cases and approaching 2 million deaths globally. Despite the large number of positive cases, there are very limited established standards of care and therapeutic options available. To date, there is still no Food and Drug Administration (FDA) approved vaccine for COVID-19, although there are several options in various clinical trial stages. Herein, we have performed a global review evaluating the roles of age and sex on COVID-19 hospitalizations, ICU admissions, deaths in hospitals, …
Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan
Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan
School of Medicine Faculty Publications
Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined …
Characterization Of The 5′-Flanking Region Of The Human And Mouse Chac1 Genes, Yuki Nomura, Charity F. Sylvester, Lisa O. Nguyen, Mahmoud Kandeel, Yoko Hirata, Imran N. Mungrue, Kentaro Oh-Hashi
Characterization Of The 5′-Flanking Region Of The Human And Mouse Chac1 Genes, Yuki Nomura, Charity F. Sylvester, Lisa O. Nguyen, Mahmoud Kandeel, Yoko Hirata, Imran N. Mungrue, Kentaro Oh-Hashi
School of Medicine Faculty Publications
The Unfolded Protein Response pathway is a conserved signaling mechanism having important roles in cellular physiology and is perturbed accompanying disease. We previously identified the novel UPR target gene CHAC1, a direct target of ATF4, downstream of PERK-EIF2A and activated by the UPR pathway. CHAC1 enzyme directs catalysis of γ-linked glutamate bonds within specific molecular targets. CHAC1 is the first enzyme characterized that can catalyze intracellular glutathione degradation in eukaryotes, having implications for regulation of oxidative stress. DDIT3 (CHOP) is a terminal UPR transcription factor, regulated by ATF4 and an output promoting cell death signaling. Herein we examine the relationship …
Chemically Modified Variants Of Fenofibrate With Antiglioblastoma Potential, J Stalinska, E Zimolag, N. A. Pianovich, A Zapata, A Lassak, M Rak, M Dean, D Ucar-Bilyeu, D Wyczechowska, F Culicchia, L Marrero, Luis Del Valle, J Sarkaria, F Peruzzi, B. S. Jursic, K. Reiss
Chemically Modified Variants Of Fenofibrate With Antiglioblastoma Potential, J Stalinska, E Zimolag, N. A. Pianovich, A Zapata, A Lassak, M Rak, M Dean, D Ucar-Bilyeu, D Wyczechowska, F Culicchia, L Marrero, Luis Del Valle, J Sarkaria, F Peruzzi, B. S. Jursic, K. Reiss
School of Medicine Faculty Publications
Anticancer effects of a common lipid-lowering drug, fenofibrate, have been described in the literature for a quite some time; however, fenofibrate has not been used as a direct anticancer therapy. We have previously reported that fenofibrate in its unprocessed form (ester) accumulates in the mitochondria, inhibits mitochondrial respiration, and triggers a severe energy deficit and extensive glioblastoma cell death. However, fenofibrate does not cross the blood brain barrier and is quickly processed by blood and tissue esterases to form the PPARα agonist fenofibric acid, which is practically ineffective effective in triggering cancer cell death. To address these issues, we have …
Glia-To-Neuron Transfer Of Mirnas Via Extracellular Vesicles: A New Mechanism Underlying Inflammation-Induced Synaptic Alterations, Ilaria Prada, Martina Gabrielli, Elena Turola, Alessia Iorio, Giulia D'Arrigo, Roberta Parolisi, Mariacristina De Luca, Marco Pacifici, Mattia Bastoni, Marta Lombardi, Giuseppe Legname, Dan Cojoc, Annalisa Buffo, Roberto Furlan, Francesca Peruzzi, Claudia Verderio
Glia-To-Neuron Transfer Of Mirnas Via Extracellular Vesicles: A New Mechanism Underlying Inflammation-Induced Synaptic Alterations, Ilaria Prada, Martina Gabrielli, Elena Turola, Alessia Iorio, Giulia D'Arrigo, Roberta Parolisi, Mariacristina De Luca, Marco Pacifici, Mattia Bastoni, Marta Lombardi, Giuseppe Legname, Dan Cojoc, Annalisa Buffo, Roberto Furlan, Francesca Peruzzi, Claudia Verderio
School of Medicine Faculty Publications
Recent evidence indicates synaptic dysfunction as an early mechanism affected in neuroinflammatory diseases, such as multiple sclerosis, which are characterized by chronic microglia activation. However, the mode(s) of action of reactive microglia in causing synaptic defects are not fully understood. In this study, we show that inflammatory microglia produce extracellular vesicles (EVs) which are enriched in a set of miRNAs that regulate the expression of key synaptic proteins. Among them, miR-146a-5p, a microglia-specific miRNA not present in hippocampal neurons, controls the expression of presynaptic synaptotagmin1 (Syt1) and postsynaptic neuroligin1 (Nlg1), an adhesion protein which play a crucial role in dendritic …
A Mirna Signature For Cognitive Deficits And Alcohol Use Disorder In Persons Living With Hiv/Aids, Dorota Wyczechowska, Hui-Yi Lin, Andrea Laplante, Duane Jeansonne, Adam Lassak, Christopher H. Parsons, Patricia E. Molina, Francesca Peruzzi
A Mirna Signature For Cognitive Deficits And Alcohol Use Disorder In Persons Living With Hiv/Aids, Dorota Wyczechowska, Hui-Yi Lin, Andrea Laplante, Duane Jeansonne, Adam Lassak, Christopher H. Parsons, Patricia E. Molina, Francesca Peruzzi
School of Medicine Faculty Publications
HIV-associated neurocognitive disorders (HAND) affects more than half of persons living with HIV-1/AIDS (PLWHA). Identification of biomarkers representing the cognitive status of PLWHA is a critical step for implementation of successful cognitive, behavioral and pharmacological strategies to prevent onset and progression of HAND. However, the presence of co-morbidity factors in PLWHA, the most common being substance abuse, can prevent the identification of such biomarkers. We have optimized a protocol to profile plasma miRNAs using quantitative RT-qPCR and found a miRNA signature with very good discriminatory ability to distinguish PLWHA with cognitive impairment from those without cognitive impairment. Here, we have …
Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi
Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi
School of Medicine Faculty Publications
The HIV-1 transactivator protein Tat is implicated in the neuronal damage that contributes to neurocognitive impairment affecting people living with HIV/AIDS. Aberrant splicing of TAU exon 10 results in tauopathies characterized by alterations in the proportion of TAU isoforms containing three (3R) or four (4R) microtubule-binding repeats. The splicing factor SC35/SRSF2 binds to nuclear RNA and facilitates the incorporation of exon 10 in the TAU molecule. Here, we utilized clinical samples, an animal model, and neuronal cell cultures and found that Tat promotes TAU 3R up-regulation through increased levels of phosphorylated SC35, which is retained in nuclear speckles. This mechanism …
Anti-Tumoral Effects Of Mir-3189-3p In Glioblastoma, Duane Jeansonne, Mariacristina Deluca, Luis Marrero, Adam Lassak, Marco Pacifici, Dorota Wyczechowska, Anna Wilk, Krzysztof Reiss, Francesca Peruzzi
Anti-Tumoral Effects Of Mir-3189-3p In Glioblastoma, Duane Jeansonne, Mariacristina Deluca, Luis Marrero, Adam Lassak, Marco Pacifici, Dorota Wyczechowska, Anna Wilk, Krzysztof Reiss, Francesca Peruzzi
School of Medicine Faculty Publications
Glioblastoma is one of the most aggressive brain tumors. We have previously found up-regulation of growth differentiation factor 15 (GDF15) in glioblastoma cells treated with the anticancer agent fenofibrate. Sequence analysis of GDF15 revealed the presence of a microRNA, miR-3189, in the single intron. We then asked whether miR-3189 was expressed in clinical samples and whether it was functional in glioblastoma cells. We found that expression of miR-3189-3p was down-regulated in astrocytoma and glioblastoma clinical samples compared with control brain tissue. In vitro, the functionality of miR-3189-3p was tested by RNA-binding protein immunoprecipitation, and miR-3189-3p coimmunoprecipitated with Argonaute 2 together …
Role Of Host Micrornas In Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis, Zhiqiang Qin, Francesca Peruzzi, Krzysztof Reiss, Lu Dai
Role Of Host Micrornas In Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis, Zhiqiang Qin, Francesca Peruzzi, Krzysztof Reiss, Lu Dai
School of Medicine Faculty Publications
MicroRNAs (miRNAs) are small non-coding RNA species that can bind to both untranslated and coding regions of target mRNAs, causing their degradation or post-transcriptional modification. Currently, over 2500 miRNAs have been identified in the human genome. Burgeoning evidence suggests that dysregulation of human miRNAs can play a role in the pathogenesis of a variety of diseases, including cancer. In contrast, only a small subset of human miRNAs has been functionally validated in the pathogenesis of oncogenic viruses, in particular, Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is the etiologic agent of several human cancers, such as primary effusion lymphoma (PEL) and Kaposi's …
Differential Effects Of Micrornas On Glioblastoma Growth And Migration, Duane Jeansonne, Marco Pacifici, Adam Lassak, Krzysztof Reiss, Giuseppe Russo, Jovanny Zabaleta, Francesca Peruzzi
Differential Effects Of Micrornas On Glioblastoma Growth And Migration, Duane Jeansonne, Marco Pacifici, Adam Lassak, Krzysztof Reiss, Giuseppe Russo, Jovanny Zabaleta, Francesca Peruzzi
School of Medicine Faculty Publications
Glioblastoma multiforme is characterized by rapid proliferation, aggressive metastatic potential, and resistance to radio- and chemotherapy. The matricellular protein CYR61 regulates cellular proliferation and migration and is highly expressed in Glioblastomas. MicroRNAs are 22-nucleotides long RNAs that regulate gene expression post-transcriptionally. Here, we utilized the LN229 glioblastoma cell line and found that CYR61 is a target of miR-136, miR-155, and miR-634. Over-expression of miR-136 and miR-634 miRNAs negatively affected proliferation, but not migration, while expression of miR-155 reduced migration but did not affect the proliferation of LN229 cells. Investigation of the molecular mechanisms affected by expression of miR-634 revealed an …