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Articles 1 - 30 of 71
Full-Text Articles in Medicine and Health Sciences
Hyperkalemia: Pharmacotherapies And Clinical Considerations, Evan S. Sinnathamby, Kelly T. Banh, William T. Barham, Tyler D. Hernandez, Audrey J. De Witt, Danielle M. Wenger, Vincent G. Klapper, David Mcgregor, Antonella Paladini, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi
Hyperkalemia: Pharmacotherapies And Clinical Considerations, Evan S. Sinnathamby, Kelly T. Banh, William T. Barham, Tyler D. Hernandez, Audrey J. De Witt, Danielle M. Wenger, Vincent G. Klapper, David Mcgregor, Antonella Paladini, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi
School of Medicine Faculty Publications
Hyperkalemia has been defined as a condition where a serum potassium level is > 5.5 mmol/l. It is associated with fatal dysrhythmias and muscular dysfunction. Certain medical conditions, such as chronic kidney disease (CKD), diabetes mellitus, and others, can lead to hyperkalemia. Many of the signs of hyperkalemia are nonspecific. A history and physical examination can be beneficial in the diagnosis of the condition. In this regard, certain characteristic electrocardiogram findings are associated with hyperkalemia along with laboratory potassium levels. In acute and potentially lethal conditions, hyperkalemia treatments include glucose and insulin, bicarbonate, calcium gluconate, beta-2 agonists, hyperventilation, and dialysis. There …
Nonhormonal Pharmacotherapies For The Treatment Of Postmenopausal Vasomotor Symptoms, Taylor Witten, Julia Staszkiewicz, Logan Gold, Mallory A. Granier, Rachel J. Klapper, Gabriel Lavespere, Bradley Dorius, Varsha Allampalli, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi
Nonhormonal Pharmacotherapies For The Treatment Of Postmenopausal Vasomotor Symptoms, Taylor Witten, Julia Staszkiewicz, Logan Gold, Mallory A. Granier, Rachel J. Klapper, Gabriel Lavespere, Bradley Dorius, Varsha Allampalli, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi
School of Medicine Faculty Publications
An average of 60-80% of all menopausal women experience bothersome vasomotor symptoms (VMSs), such as flushing and sweating, within the first seven years of onset. However, despite increasing prevalence, these hot flashes remain hard to treat and have a negative effect on the quality of life. Though hormone replacement therapy is commonly utilized as a standard treatment for VMSs, this therapy is not recommended for all women. Specifically, the oral form of hormone replacement therapy is associated with several contraindications, including a history of thromboembolic disease, migraine headache with aura, liver failure, heart disease, and hormone-dependent cancers. For women with …
Regulation Of Tissue Factor Activity By Interaction With The First Pdz Domain Of Magi1, Mohammad A. Mohammad, Sophie Featherby, Camille Ettelaie
Regulation Of Tissue Factor Activity By Interaction With The First Pdz Domain Of Magi1, Mohammad A. Mohammad, Sophie Featherby, Camille Ettelaie
School of Medicine Faculty Publications
Background; Tissue factor (TF) activity is stringently regulated through processes termed encryption. Post-translational modification of TF and its interactions with various protein and lipid moieties allows for a multi-step de-encryption of TF and procoagulant activation. Membrane-associated guanylate kinase-with inverted configuration (MAGI) proteins are known to regulate the localisation and activity of a number of proteins including cell-surface receptors. Methods; The interaction of TF with MAGI1 protein was examined as a means of regulating TF activity. MDA-MB-231 cell line was used which express TF and MAGI1, and respond well to protease activated receptor (PAR)2 activation. Proximity ligation assay (PLA), co-immunoprecipitation and …
Stevens-Johnson Syndrome From Combined Allopurinol And Angiotensin-Converting Enzyme Inhibitors: A Narrative Review, Isabella M. Fabian, Kirsten Maddox, Cameron Robicheaux, Rahib K. Islam, Ahmed Anwar, Bradley Dorius, Christopher L. Robinson, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye
Stevens-Johnson Syndrome From Combined Allopurinol And Angiotensin-Converting Enzyme Inhibitors: A Narrative Review, Isabella M. Fabian, Kirsten Maddox, Cameron Robicheaux, Rahib K. Islam, Ahmed Anwar, Bradley Dorius, Christopher L. Robinson, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye
School of Medicine Faculty Publications
Stevens-Johnson syndrome (SJS) is a severe and potentially debilitating skin reaction frequently related to medication use. Allopurinol and angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for prevalent health conditions worldwide, and their interaction associated with SJS warrants further investigation. A comprehensive literature search was performed to investigate cases as studies related to SJS occurring in patients with concomitant use of allopurinol and ACE inhibitors. We identified case reports and studies detailing hypersensitivity reactions, including SJS, attributed to a combination of allopurinol and ACE inhibitors. Despite the drug-drug interactions or lack thereof seen in patient populations, there is no definitive …
Folate Deficiency Modifies The Risk Of Cin3+ Associated With Dna Methylation Levels: A Nested Case–Control Study From The Ascus-Col Trial, María C. Agudelo, Samuel Agudelo, Attila Lorincz, Arianis Tatiana Ramírez, Kelly Melisa Castañeda, Isabel Garcés-Palacio, Arnold H. Zea, Chandrika Piyathilake, Gloria Ines Sanchez
Folate Deficiency Modifies The Risk Of Cin3+ Associated With Dna Methylation Levels: A Nested Case–Control Study From The Ascus-Col Trial, María C. Agudelo, Samuel Agudelo, Attila Lorincz, Arianis Tatiana Ramírez, Kelly Melisa Castañeda, Isabel Garcés-Palacio, Arnold H. Zea, Chandrika Piyathilake, Gloria Ines Sanchez
School of Medicine Faculty Publications
Purpose: To our knowledge, there are very few studies evaluating if the levels of folate modify the risk of cervical intraepithelial neoplasia grade 2 and higher (CIN2+ and CIN3+) associated with the levels of HPV genome methylation, two cofactors related to single carbon metabolism and independently associated with cervical cancer in previous studies. We conducted a case–control study nested in a three-arm randomized clinical pragmatic trial (ASCUS-COL trial) to evaluate the risk of CIN3+ associated with methylation levels according to serum folate concentrations. Methods: Cases (n = 155) were women with histologically confirmed CIN2+ (113 CIN2, 38 CIN3, and 4 …
Myod-Skp2 Axis Boosts Tumorigenesis In Fusion Negative Rhabdomyosarcoma By Preventing Differentiation Through P57kip2 Targeting, Silvia Pomella, Matteo Cassandri, Lucrezia D’Archivio, Antonella Porrazzo, Cristina Cossetti, Doris Phelps, Clara Perrone, Michele Pezzella, Antonella Cardinale, Marco Wachtel, Sara Aloisi, David Milewski, Marta Colletti, Prethish Sreenivas, Zoë S. Walters, Giovanni Barillari, Angela Di Giannatale, Giuseppe Maria Milano, Cristiano De Stefanis, Rita Alaggio, Sonia Rodriguez-Rodriguez, Nadia Carlesso, Christopher R. Vakoc, Enrico Velardi, Beat W. Schafer, Ernesto Guccione, Susanne A. Gatz, Lucio Miele
Myod-Skp2 Axis Boosts Tumorigenesis In Fusion Negative Rhabdomyosarcoma By Preventing Differentiation Through P57kip2 Targeting, Silvia Pomella, Matteo Cassandri, Lucrezia D’Archivio, Antonella Porrazzo, Cristina Cossetti, Doris Phelps, Clara Perrone, Michele Pezzella, Antonella Cardinale, Marco Wachtel, Sara Aloisi, David Milewski, Marta Colletti, Prethish Sreenivas, Zoë S. Walters, Giovanni Barillari, Angela Di Giannatale, Giuseppe Maria Milano, Cristiano De Stefanis, Rita Alaggio, Sonia Rodriguez-Rodriguez, Nadia Carlesso, Christopher R. Vakoc, Enrico Velardi, Beat W. Schafer, Ernesto Guccione, Susanne A. Gatz, Lucio Miele
School of Medicine Faculty Publications
Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer. SKP2 in FN-RMS promotes cell cycle progression and prevents differentiation by directly targeting p27Kip1 and p57Kip2, respectively. SKP2 depletion unlocks a partly MYOD-dependent myogenic transcriptional program and strongly affects stemness and tumorigenic …
First-Generation Cephalosporins For Treatment Of Acute Hematogenous Osteomyelitis In Children: A Study Of Efficacy And Adverse Effects, Lisa Hiskey, Hiba Saifuddin, Emily R. Levy, Roland Hentz, Nipunie S. Rajapakse, Laura M. Dinnes, Elizabeth H. Ristagno
First-Generation Cephalosporins For Treatment Of Acute Hematogenous Osteomyelitis In Children: A Study Of Efficacy And Adverse Effects, Lisa Hiskey, Hiba Saifuddin, Emily R. Levy, Roland Hentz, Nipunie S. Rajapakse, Laura M. Dinnes, Elizabeth H. Ristagno
School of Medicine Faculty Publications
BACKGROUND: Acute hematogenous osteomyelitis (AHO) is a relatively infrequent but significant infection in pediatric patients. As is the most common cause of AHO, intravenous and oral first-generation cephalosporins are common therapies. Cephalexin is a commonly prescribed oral therapy for pediatric AHO, although it requires frequent dosing that may affect adherence. Cefadroxil is a comparable oral first-generation cephalosporin with a more desirable dosing schedule. METHODS: We reviewed pediatric patients admitted to Mayo Clinic between March 2002 and September 2020 for management of AHO who received treatment with a first-generation cephalosporin. We reviewed timing of oral therapy transition, therapy-associated adverse effects, and …
Elovanoid-N34 Modulates Txnrd1 Key In Protection Against Oxidative Stress-Related Diseases, Jorgelina M. Calandria, Surjyadipta Bhattacharjee, Sayantani Kala-Bhattacharjee, Pranab K. Mukherjee, Yuehan Feng, Jakob Vowinckel, Tobias Treiber, Nicolas G. Bazan
Elovanoid-N34 Modulates Txnrd1 Key In Protection Against Oxidative Stress-Related Diseases, Jorgelina M. Calandria, Surjyadipta Bhattacharjee, Sayantani Kala-Bhattacharjee, Pranab K. Mukherjee, Yuehan Feng, Jakob Vowinckel, Tobias Treiber, Nicolas G. Bazan
School of Graduate Studies Faculty Publications
The thioredoxin (TXN) system is an NADPH + H+/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases. Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival. Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34. TXNRD1 silencing confirmed that the ELV-N34 target was isoform 2 or 3. This …
Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle
Association Of Chlamydia Trachomatis Burden With The Vaginal Microbiota, Bacterial Vaginosis, And Metronidazole Treatment, Caleb M. Ardizzone, Christopher M. Taylor, Evelyn Toh, Rebecca A. Lillis, Jacob H. Elnaggar, John W. Lammons, Patricia Dehon Mott, Emily L. Duffy, Li Shen, Alison J. Quayle
School of Graduate Studies Faculty Publications
Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming …
Incidence Of Rapidly Progressive Osteoarthritis Following Intra-Articular Hip Corticosteroid Injection: A Systematic Review And Meta-Analysis, Franco M. Sabatini, Anna Cohen-Rosenblum, Travis B. Eason, Charles P. Hannon, Samuel D. Mounce, Chad A. Krueger, F Winston Gwathmey, Stephen T. Duncan, David C. Landy
Incidence Of Rapidly Progressive Osteoarthritis Following Intra-Articular Hip Corticosteroid Injection: A Systematic Review And Meta-Analysis, Franco M. Sabatini, Anna Cohen-Rosenblum, Travis B. Eason, Charles P. Hannon, Samuel D. Mounce, Chad A. Krueger, F Winston Gwathmey, Stephen T. Duncan, David C. Landy
School of Medicine Faculty Publications
BACKGROUND: The American Academy of Orthopedic Surgery recommends intra-articular corticosteroid injections (CSIs) for managing hip osteoarthritis (OA) based on short-term, prospective studies. Recent retrospective studies have raised concerns that CSIs may lead to rapidly progressive OA (RPOA). We sought to systematically review the literature of CSIs for hip OA to estimate the incidence of RPOA. METHODS: MEDLINE, Embase, and Cochrane Library were searched to identify original research of hip OA patients receiving CSIs. Overall, 27 articles involving 5831 patients published from 1988 to 2022 were included. Study design, patient characteristics, CSI details, follow-up, and cases of RPOA were recorded. Studies …
The Evolving Role Of Vericiguat In Patients With Chronic Heart Failure, Ross M. Dies, Corrie N. Jackson, Chelsi J. Flanagan, Evan S. Sinnathamby, Noah J. Spillers, Pooja Potharaju, Naina Singh, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye
The Evolving Role Of Vericiguat In Patients With Chronic Heart Failure, Ross M. Dies, Corrie N. Jackson, Chelsi J. Flanagan, Evan S. Sinnathamby, Noah J. Spillers, Pooja Potharaju, Naina Singh, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye
School of Medicine Faculty Publications
Heart failure (HF) is a chronic and progressive clinical disorder characterized by an inability to pump sufficient blood to meet metabolic demands. It poses a substantial global healthcare burden, leading to high morbidity, mortality, and economic impact. Current treatments for HF include lifestyle modifications, guideline-directed medical therapies (GDMT), and device interventions, but the need for novel therapeutic approaches remains significant. The introduction of vericiguat, a soluble guanylate cyclase stimulator, has shown promise in improving outcomes for heart failure patients. Vericiguat addresses the underlying pathophysiological mechanisms of heart failure by augmenting the cyclic guanosine monophosphate (cGMP) pathway, leading to enhanced cardiac …
Prefrontal Cortex Glutamatergic Adaptations In A Mouse Model Of Alcohol Use Disorder, Mahum T. Siddiqi, Dhruba Podder, Amanda R. Pahng, Alexandria C. Athanason, Tali Nadav, Chelsea Cates-Gatto, Max Kreifeldt, Candice Contet, Amanda J. Roberts, Scott Edwards, Marisa Roberto, Florence P. Varodayan
Prefrontal Cortex Glutamatergic Adaptations In A Mouse Model Of Alcohol Use Disorder, Mahum T. Siddiqi, Dhruba Podder, Amanda R. Pahng, Alexandria C. Athanason, Tali Nadav, Chelsea Cates-Gatto, Max Kreifeldt, Candice Contet, Amanda J. Roberts, Scott Edwards, Marisa Roberto, Florence P. Varodayan
School of Graduate Studies Faculty Publications
Alcohol use disorder (AUD) produces cognitive deficits, indicating a shift in prefrontal cortex (PFC) function. PFC glutamate neurotransmission is mostly mediated by α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid-type ionotropic receptors (AMPARs); however preclinical studies have mostly focused on other receptor subtypes. Here we examined the impact of early withdrawal from chronic ethanol on AMPAR function in the mouse medial PFC (mPFC). Dependent male C57BL/6J mice were generated using the chronic intermittent ethanol vapor-two bottle choice (CIE-2BC) paradigm. Non-dependent mice had access to water and ethanol bottles but did not receive ethanol vapor. Naïve mice had no ethanol exposure. We used patch-clamp electrophysiology to measure …
Effectiveness Of A Bivalent Mrna Vaccine Dose Against Symptomatic Sars-Cov-2 Infection Among U.S. Healthcare Personnel, September 2022–May 2023, Ian D. Plumb, Melissa Briggs Hagen, Ryan Wiegand, Ghinwa Dumyati, Christopher Myers, Karisa K. Harland, Anusha Krishnadasan, Jade James Gist, Glen Abedi, Katherine E. Fleming-Dutra, Nora Chea, Jane E. Lee, Melissa Kellogg, Alexandra Edmundson, Amber Britton, Lucy E. Wilson, Sara A. Lovett, Valerie Ocampo, Tiffanie M. Markus, Howard A. Smithline, Peter C. Hou, Lilly C. Lee, William Mower, Fernand Rwamwejo, Mark T. Steele, Stephen C. Lim, Walter A. Schrading, Brian Chinnock
Effectiveness Of A Bivalent Mrna Vaccine Dose Against Symptomatic Sars-Cov-2 Infection Among U.S. Healthcare Personnel, September 2022–May 2023, Ian D. Plumb, Melissa Briggs Hagen, Ryan Wiegand, Ghinwa Dumyati, Christopher Myers, Karisa K. Harland, Anusha Krishnadasan, Jade James Gist, Glen Abedi, Katherine E. Fleming-Dutra, Nora Chea, Jane E. Lee, Melissa Kellogg, Alexandra Edmundson, Amber Britton, Lucy E. Wilson, Sara A. Lovett, Valerie Ocampo, Tiffanie M. Markus, Howard A. Smithline, Peter C. Hou, Lilly C. Lee, William Mower, Fernand Rwamwejo, Mark T. Steele, Stephen C. Lim, Walter A. Schrading, Brian Chinnock
School of Medicine Faculty Publications
Background: Bivalent mRNA vaccines were recommended since September 2022. However, coverage with a recent vaccine dose has been limited, and there are few robust estimates of bivalent VE against symptomatic SARS-CoV-2 infection (COVID-19). We estimated VE of a bivalent mRNA vaccine dose against COVID-19 among eligible U.S. healthcare personnel who had previously received monovalent mRNA vaccine doses. Methods: We conducted a case-control study in 22 U.S. states, and enrolled healthcare personnel with COVID-19 (case-participants) or without COVID-19 (control-participants) during September 2022–May 2023. Participants were considered eligible for a bivalent mRNA dose if they had received 2–4 monovalent (ancestral-strain) mRNA vaccine …
Ca2+-Regulated Expression Of High Affinity Methylaminoisobutryic Acid Transport In Hippocampal Neurons Inhibited By Riluzole And Novel Neuroprotective Aminothiazoles, Jeffrey D. Erickson, Thomas Kyllo, Heike Wulff
Ca2+-Regulated Expression Of High Affinity Methylaminoisobutryic Acid Transport In Hippocampal Neurons Inhibited By Riluzole And Novel Neuroprotective Aminothiazoles, Jeffrey D. Erickson, Thomas Kyllo, Heike Wulff
School of Medicine Faculty Publications
High affinity methylaminoisobutyric acid(MeAIB)/glutamine(Gln) transport activity regulated by neuronal firing occurs at the plasma membrane in mature rat hippocampal neuron-enriched cultures. Spontaneous Ca2+-regulated transport activity was similarly inhibited by riluzole, a benzothiazole anticonvulsant agent, and by novel naphthalenyl substituted aminothiazole derivatives such as SKA-378. Here, we report that spontaneous transport activity is stimulated by 4-aminopyridine (4-AP) and that phorbol-myristate acetate (PMA) increases high K+ stimulated transport activity that is inhibited by staurosporine. 4-AP-stimulated spontaneous and PMA-stimulated high K+-induced transport is not present at 7 days in vitro (DIV) and is maximal by DIV∼21. The relative affinity for MeAIB is similar …
Protein S Antibody As An Adjunct Therapy For Hemophilia B, Hope P. Wilson, Aliyah Pierre, Ashley L. Paysse, Narender Kumar, Brian C. Cooley, Pratyadipta Rudra, Adrianne W. Dorsey, Diana Polania-Villanueva, Sabyasachi Chatterjee, Maissaa Janbain, Maria C. Velez, Rinku Majumder
Protein S Antibody As An Adjunct Therapy For Hemophilia B, Hope P. Wilson, Aliyah Pierre, Ashley L. Paysse, Narender Kumar, Brian C. Cooley, Pratyadipta Rudra, Adrianne W. Dorsey, Diana Polania-Villanueva, Sabyasachi Chatterjee, Maissaa Janbain, Maria C. Velez, Rinku Majumder
School of Medicine Faculty Publications
ABSTRACT: Hemophilia B (HB) is caused by an inherited deficiency of plasma coagulation factor IX (FIX). Approximately 60% of pediatric patients with HB possess a severe form of FIX deficiency (< 1% FIX activity). Treatment typically requires replacement therapy through the administration of FIX. However, exogenous FIX has a limited functional half-life, and the natural anticoagulant protein S (PS) inhibits activated FIX (FIXa). PS ultimately limits thrombin formation, which limits plasma coagulation. This regulation of FIXa activity by PS led us to test whether inhibiting PS would extend the functional half-life of FIX and thereby prolong FIX-based HB therapy. We assayed clotting times and thrombin generation to measure the efficacy of a PS antibody for increasing FIX activity in commercially obtained plasma and plasma from pediatric patients with HB. We included 11 pediatric patients who lacked additional comorbidities and coagulopathies. In vivo, we assessed thrombus formation in HB mice in the presence of the FIXa ± PS antibody. We found an accelerated rate of clotting in the presence of PS antibody. Similarly, the peak thrombin formed was significantly greater in the presence of the PS antibody, even in plasma from patients with severe HB. Furthermore, HB mice injected with PS antibody and FIX had a 4.5-fold higher accumulation of fibrin at the thrombus induction site compared with mice injected with FIX alone. Our findings imply that a PS antibody would be a valuable adjunct to increase the effectiveness of FIX replacement therapy in pediatric patients who have mild, moderate, and severe HB.
Integrated Inflammatory Signaling Landscape Response After Delivering Elovanoid Free-Fatty-Acid Precursors Leading To Experimental Stroke Neuroprotection, Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung Ha Hong, Nicolas G. Bazan
Integrated Inflammatory Signaling Landscape Response After Delivering Elovanoid Free-Fatty-Acid Precursors Leading To Experimental Stroke Neuroprotection, Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung Ha Hong, Nicolas G. Bazan
School of Graduate Studies Faculty Publications
Despite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood–brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6. Gene expression revealed increased anti-inflammatory and pro-homeostatic genes and decreases in expression of pro-inflammatory genes in …
Her3 Functions As An Effective Therapeutic Target In Triple Negative Breast Cancer To Potentiate The Antitumor Activity Of Gefitinib And Paclitaxel, Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D. Thor, Bolin Liu
Her3 Functions As An Effective Therapeutic Target In Triple Negative Breast Cancer To Potentiate The Antitumor Activity Of Gefitinib And Paclitaxel, Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D. Thor, Bolin Liu
School of Medicine Faculty Publications
Background: Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease. Methods: Immunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. …
Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan
Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan
School of Medicine Faculty Publications
Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, …
Topiramate (Topamax): Evolving Role In Weight Reduction Management: A Narrative Review, Irza Wajid, Alexis Vega, Katherine Thornhill, Jack Jenkins, Chandler Merriman, Debbie Chandler, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye
Topiramate (Topamax): Evolving Role In Weight Reduction Management: A Narrative Review, Irza Wajid, Alexis Vega, Katherine Thornhill, Jack Jenkins, Chandler Merriman, Debbie Chandler, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye
School of Medicine Faculty Publications
Obesity has emerged as a widespread disease with epidemic proportions, necessitating effective management to enhance the overall health outcomes of patients. Medical intervention for weight loss becomes necessary when diet and exercise prove ineffective, and topiramate emerges as a potential treatment option for this global problem. Currently approved as an anti-epileptic and migraine prophylaxis medication, topiramate is frequently utilized as adjunctive therapy for patients with mood and eating disorders, as well as for alcohol use disorders. Its multifaceted mechanisms of action contribute to reducing neuronal excitation and enhancing neuronal inhibition. Given its variety of mechanisms, topiramate shows several off-label outcomes, …
Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec
Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec
School of Medicine Faculty Publications
Background: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. …
Minoxidil Weakens Newly Synthesized Collagen In Fibrotic Synoviocytes From Osteoarthritis Patients, Stefan Sarkovich, Peter P. Issa, Andrew Longanecker, Davis Martin, Kaitlyn Redondo, Patrick Mcternan, Jennifer Simkin, Luis Marrero
Minoxidil Weakens Newly Synthesized Collagen In Fibrotic Synoviocytes From Osteoarthritis Patients, Stefan Sarkovich, Peter P. Issa, Andrew Longanecker, Davis Martin, Kaitlyn Redondo, Patrick Mcternan, Jennifer Simkin, Luis Marrero
School of Medicine Faculty Publications
Purpose: Synovial fibrosis (SFb) formation and turnover attributable to knee osteoarthritis (KOA) can impart painful stiffness and persist following arthroplasty. To supplement joint conditioning aimed at maximizing peri-operative function, we evaluated the antifibrotic effect of Minoxidil (MXD) on formation of pyridinoline (Pyd) cross-links catalyzed by Plod2-encoded lysyl hydroxylase (LH)2b that strengthen newly synthesized type-I collagen (COL1) in fibroblastic synovial cells (FSCs) from KOA patients. MXD was predicted to decrease Pyd without significant alterations to Col1a1 transcription by FSCs stimulated with transforming growth factor (TGF)β1. Methods: Synovium from 10 KOA patients grouped by SFb severity was preserved for picrosirius and LH2b …
Comparing Antimicrobial Resistant Genes And Phenotypes Across Multiple Sequencing Platforms And Assays For Enterobacterales Clinical Isolates, Rebecca Rose, David J. Nolan, Deborah Ashcraft, Amy K. Feehan, Leonor Velez-Climent, Christopher Huston, Benjamin Lain, Simon Rosenthal, Lucio Miele, Gary B. Fogel, George Pankey, Julia Garcia-Diaz, Susanna L. Lamers
Comparing Antimicrobial Resistant Genes And Phenotypes Across Multiple Sequencing Platforms And Assays For Enterobacterales Clinical Isolates, Rebecca Rose, David J. Nolan, Deborah Ashcraft, Amy K. Feehan, Leonor Velez-Climent, Christopher Huston, Benjamin Lain, Simon Rosenthal, Lucio Miele, Gary B. Fogel, George Pankey, Julia Garcia-Diaz, Susanna L. Lamers
School of Medicine Faculty Publications
Introduction: Whole genome sequencing (WGS) of bacterial isolates can be used to identify antimicrobial resistance (AMR) genes. Previous studies have shown that genotype-based AMR has variable accuracy for predicting carbapenem resistance in carbapenem-resistant Enterobacterales (CRE); however, the majority of these studies used short-read platforms (e.g. Illumina) to generate sequence data. In this study, our objective was to determine whether Oxford Nanopore Technologies (ONT) long-read WGS would improve detection of carbapenem AMR genes with respect to short-read only WGS for nine clinical CRE samples. We measured the minimum inhibitory breakpoint (MIC) using two phenotype assays (MicroScan and ETEST) for six antibiotics, …
Unlocking The Potential Of Kinase Targets In Cancer: Insights From Canceromicsnet, An Ai-Driven Approach To Drug Response Prediction In Cancer, Manali Singha, Limeng Pu, Gopal Srivastava, Xialong Ni, Brent A. Stanfield, Ifeanyi K. Uche, Paul J.F. Rider, Konstantin G. Kousoulas, J. Ramanujam, Michal Brylinski
Unlocking The Potential Of Kinase Targets In Cancer: Insights From Canceromicsnet, An Ai-Driven Approach To Drug Response Prediction In Cancer, Manali Singha, Limeng Pu, Gopal Srivastava, Xialong Ni, Brent A. Stanfield, Ifeanyi K. Uche, Paul J.F. Rider, Konstantin G. Kousoulas, J. Ramanujam, Michal Brylinski
School of Medicine Faculty Publications
Deregulated protein kinases are crucial in promoting cancer cell proliferation and driving malignant cell signaling. Although these kinases are essential targets for cancer therapy due to their involvement in cell development and proliferation, only a small part of the human kinome has been targeted by drugs. A comprehensive scoring system is needed to evaluate and prioritize clinically relevant kinases. We recently developed CancerOmicsNet, an artificial intelligence model employing graph-based algorithms to predict the cancer cell response to treatment with kinase inhibitors. The performance of this approach has been evaluated in large-scale benchmarking calculations, followed by the experimental validation of selected …
Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu
Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu
School of Medicine Faculty Publications
Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …
Effect Of Biological Variation In Hba1c And Blood Glucose On The Diagnosis Of Prediabetes, James M. Hempe, Shengping Yang, Daniel S. Hsia
Effect Of Biological Variation In Hba1c And Blood Glucose On The Diagnosis Of Prediabetes, James M. Hempe, Shengping Yang, Daniel S. Hsia
School of Medicine Faculty Publications
Introduction: People with a low or high haemoglobin glycation index (HGI) have lower or higher HbA1c than other people with the same FPG. This study compared the prevalence of prediabetes based on FPG, 2hOGTT and HbA1c in people with low, moderate or high HGI. Methods: Prediabetes was diagnosed based on ADA cutpoints in 10,488 NHANES participants without self-reported diabetes. HGI was calculated as the difference between a participant's observed HbA1c and a predicted HbA1c where predicted HbA1c = 0.024 FPG + 3.1. Participants were divided into low (HGI < −0.15%), moderate (HGI −0.15% to +0.15%) and high (HGI > +0.15%) HGI subgroups. Results: The prevalence of prediabetes was 42.4% based on …
Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari
Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari
School of Graduate Studies Faculty Publications
Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased …
High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin
High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin
School of Graduate Studies Faculty Publications
Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …
Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart
Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart
School of Graduate Studies Faculty Publications
Pattern-recognition receptors (PRRs) are critical to recognizing endogenous and exogenous threats to mount a protective proinflammatory innate immune response. PRRs may be located on the outer cell membrane, cytosol, and nucleus. The cGAS/STING signaling pathway is a cytosolic PRR system. Notably, cGAS is also present in the nucleus. The cGAS-mediated recognition of cytosolic dsDNA and its cleavage into cGAMP activates STING. Furthermore, STING activation through its downstream signaling triggers different interferon-stimulating genes (ISGs), initiating the release of type 1 interferons (IFNs) and NF-κB-mediated release of proinflammatory cytokines and molecules. Activating cGAS/STING generates type 1 IFN, which may prevent cellular transformation …
Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. West, Charles Wood, Peter C. Angeletti
Yes-Associated Protein-1 Overexpression In Ocular Surface Squamous Neoplasia; A Potential Diagnostic Marker And Therapeutic Target, Peter Julius, Stepfanie N. Siyumbwa, Fred Maate, Phyllis Moonga, Guobin Kang, Trevor Kaile, John T. West, Charles Wood, Peter C. Angeletti
School of Graduate Studies Faculty Publications
Yes-associated protein-1 (YAP-1) is a Hippo system transcription factor, which serves as an oncogene in squamous cell carcinoma, and several solid tumors when the Hippo pathway is dysregulated. Yet, the activity of YAP-1 in ocular surface squamous neoplasia (OSSN) has not been determined. Here, we investigate the relationship between YAP-1 overexpression and OSSN. Using a cross-sectional study design, we recruited 227 OSSN patients from the University Teaching Hospitals in Lusaka, Zambia. Immunohistochemistry was used to assess YAP-1 protein overexpression in tumor tissue relative to surrounding benign squamous epithelium. OSSN patient samples (preinvasive, n = 62, 27% and invasive, n = …
Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun
Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun
School of Medicine Faculty Publications
Background: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …