Open Access. Powered by Scholars. Published by Universities.®

Chemicals and Drugs Commons™

Open Access. Powered by Scholars. Published by Universities.®

Diseases

Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 511 - 540 of 1225

Full-Text Articles in Chemicals and Drugs

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 Aug 2023

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, …

Go to article

The Noloco Strategy For Essential Hypertension, F. Matthew Mihelic Md Aug 2023

The Noloco Strategy For Essential Hypertension, F. Matthew Mihelic Md

Faculty Publications

Ninety-nine percent of all “essential” hypertension can be controlled by using the NoLoCo strategy, without causing any significant side-effects and without an increase in insulin resistance. NoLoCo stands for Norvasc (amlodipine), Lozol (indapamide), and Cozaar (losartan), but the medicines are considered and used in reverse order.

Go to article

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 Aug 2023

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 …

Go to article

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman Aug 2023

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Go to article

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 Aug 2023

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 …

Go to article

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 Aug 2023

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 …

Go to article

Probing Conformational Landscapes Of Binding And Allostery In The Sars-Cov-2 Omicron Variant Complexes Using Microsecond Atomistic Simulations And Perturbation-Based Profiling Approaches: Hidden Role Of Omicron Mutations As Modulators Of Allosteric Signaling And Epistatic Relationships, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao Aug 2023

Probing Conformational Landscapes Of Binding And Allostery In The Sars-Cov-2 Omicron Variant Complexes Using Microsecond Atomistic Simulations And Perturbation-Based Profiling Approaches: Hidden Role Of Omicron Mutations As Modulators Of Allosteric Signaling And Epistatic Relationships, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we systematically examine the conformational dynamics, binding and allosteric communications in the Omicron BA.1, BA.2, BA.3 and BA.4/BA.5 spike protein complexes with the ACE2 host receptor using molecular dynamics simulations and perturbation-based network profiling approaches. Microsecond atomistic simulations provided a detailed characterization of the conformational landscapes and revealed the increased thermodynamic stabilization of the BA.2 variant which can be contrasted with the BA.4/BA.5 variants inducing a significant mobility of the complexes. Using the dynamics-based mutational scanning of spike residues, we identified structural stability and binding affinity hotspots in the Omicron complexes. Perturbation response scanning and network-based mutational …

Go to article

Effect Of Biological Variation In Hba1c And Blood Glucose On The Diagnosis Of Prediabetes, James M. Hempe, Shengping Yang, Daniel S. Hsia Jul 2023

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 …

Go to article

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 Jul 2023

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 …

Go to article

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 Jul 2023

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 …

Go to article

Cancer Cell-Specific Cgas/Sting Signaling Pathway In The Era Of Advancing Cancer Cell Biology, Vijay Kumar, Caitlin Bauer, John H. Stewart Jul 2023

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 …

Go to article

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 Jul 2023

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 = …

Go to article

Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich Jul 2023

Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a …

Go to article

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 Jul 2023

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 …

Go to article

Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart Jun 2023

Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …

Go to article

Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder Jun 2023

Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder

School of Graduate Studies Faculty Publications

Through a process termed clot retraction, platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from Cudrania trucuspidata, Arctium lappa, …

Go to article

Persistent Increase In Serum Ferritin Levels Despite Converting To Permanent Vascular Access In Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study, Ali Mirza Onder, Md Abu Yusuf Ansari, Fang Deng, Matthew M. Grinsell, Larry Patterson, Jennifer Jetton, Sahar Fathallah-Shaykh, Daniel Ranch, Diego Aviles, Lawrence Copelovitch, Eileen Ellis, Vimal Chadha, Ayah Elmaghrabi, Jen-Jar Lin, Lavjay Butani, Maha Haddad, Olivera Marsenic, Paul Brakeman, Raymond Quigley, H Stella Shin, Rouba Garro, Rupesh Raina, Craig B. Langman Jun 2023

Persistent Increase In Serum Ferritin Levels Despite Converting To Permanent Vascular Access In Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study, Ali Mirza Onder, Md Abu Yusuf Ansari, Fang Deng, Matthew M. Grinsell, Larry Patterson, Jennifer Jetton, Sahar Fathallah-Shaykh, Daniel Ranch, Diego Aviles, Lawrence Copelovitch, Eileen Ellis, Vimal Chadha, Ayah Elmaghrabi, Jen-Jar Lin, Lavjay Butani, Maha Haddad, Olivera Marsenic, Paul Brakeman, Raymond Quigley, H Stella Shin, Rouba Garro, Rupesh Raina, Craig B. Langman

School of Medicine Faculty Publications

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (p = 0.035), being from a center that enrolled >10 cases (p = …

Go to article

KCa2 And KCa3.1 Channels In The Airways: A New Therapeutic Target, Razan Orfali, Ali Alfaiz, Mohammad Asikur Rahman, Liz Lau, Young-Woo Nam, Miao Zhang Jun 2023

KCa2 And KCa3.1 Channels In The Airways: A New Therapeutic Target, Razan Orfali, Ali Alfaiz, Mohammad Asikur Rahman, Liz Lau, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

K+ channels are involved in many critical functions in lung physiology. Recently, the family of Ca2+-activated K+ channels (KCa) has received more attention, and a massive amount of effort has been devoted to developing selective medications targeting these channels. Within the family of KCa channels, three small-conductance Ca2+-activated K+ (KCa2) channel subtypes, together with the intermediate-conductance KCa3.1 channel, are voltage-independent K+ channels, and they mediate Ca2+-induced membrane hyperpolarization. Many KCa2 channel members are involved in crucial roles in physiological and pathological …

Go to article

Mirnas Signature As Potential Biomarkers For Cervical Precancerous Lesions In Human Papillomavirus Positive Women, Martha I. González-Ramírez, Yurley T. Cardona, María C. Agudelo, Carolina López, Juan J. Florez-Acosta, Samuel Agudelo-Gamboa, Jone Garai, Li Li, Carlos A. Orozco-Castaño, Jovanny Zabaleta, Gloria I. Sánchez Jun 2023

Mirnas Signature As Potential Biomarkers For Cervical Precancerous Lesions In Human Papillomavirus Positive Women, Martha I. González-Ramírez, Yurley T. Cardona, María C. Agudelo, Carolina López, Juan J. Florez-Acosta, Samuel Agudelo-Gamboa, Jone Garai, Li Li, Carlos A. Orozco-Castaño, Jovanny Zabaleta, Gloria I. Sánchez

School of Medicine Faculty Publications

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by …

Go to article

7-Ketocholesterol Promotes Retinal Pigment Epithelium Senescence And Fibrosis Of Choroidal Neovascularization Via Iqgap1 Phosphorylation-Dependent Signaling, Haibo Wang, Aniket Ramshekar, Thaonhi Cung, Chris Wallace-Carrete, Chandler Zaugg, Jasmine Nguyen, Gregory J. Stoddard, M. Elizabeth Hartnett Jun 2023

7-Ketocholesterol Promotes Retinal Pigment Epithelium Senescence And Fibrosis Of Choroidal Neovascularization Via Iqgap1 Phosphorylation-Dependent Signaling, Haibo Wang, Aniket Ramshekar, Thaonhi Cung, Chris Wallace-Carrete, Chandler Zaugg, Jasmine Nguyen, Gregory J. Stoddard, M. Elizabeth Hartnett

School of Medicine Faculty Publications

Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of endothelial-mesenchymal transition. To address the hypothesis that 7KC causes mesenchymal transition of retinal pigment epithelial cells (RPE), we exposed human primary RPE (hRPE) to 7KC or a control. 7KC-treated hRPE did not manifest increased mesenchymal markers, but instead maintained RPE-specific proteins and exhibited signs of senescence with increased serine phosphorylation of histone H3, serine/threonine phosphorylation of mammalian target of rapamycin (p-mTOR), p16 and p21, β-galactosidase labeling, and reduced LaminB1, suggesting senescence. The cells …

Go to article

An Aerobic Exercise Intervention To Improve Metabolic Health Among People Living With Hiv With At-Risk Alcohol Use: The Alive-Ex Research Study Protocol, Liz Simon, Stefany D. Primeaux, Danielle E. Levitt, Brianna Bourgeois, Neil M. Johannsen, Adrianna Peters, Jameel Ahmed, Richard H. Marshall, Alexandra H. Fairchild, Tekeda F. Ferguson, Patricia E. Molina Jun 2023

An Aerobic Exercise Intervention To Improve Metabolic Health Among People Living With Hiv With At-Risk Alcohol Use: The Alive-Ex Research Study Protocol, Liz Simon, Stefany D. Primeaux, Danielle E. Levitt, Brianna Bourgeois, Neil M. Johannsen, Adrianna Peters, Jameel Ahmed, Richard H. Marshall, Alexandra H. Fairchild, Tekeda F. Ferguson, Patricia E. Molina

School of Medicine Faculty Publications

Background: Effective antiretroviral therapy (ART) in people living with HIV (PLWH) has improved life expectancy and increased risk of age-associated cardiometabolic comorbidities. At-risk alcohol use is more frequent among PLWH and increases the risk of health challenges. PLWH with at-risk alcohol use are more likely to meet criteria for prediabetes/diabetes and this is associated with impaired whole-body glucose-insulin dynamics. Methods: The Alcohol & Metabolic Comorbidities in PLWH: Evidence Driven Interventions Study (ALIVE-Ex Study, NCT03299205) is a longitudinal, prospective, interventional study to determine the effects of an aerobic exercise protocol on improving dysglycemia among PLWH with at-risk alcohol use. The intervention …

Go to article

Comparison Of Medical Management Versus Parathyroidectomy In Patients With Mild Primary Hyperparathyroidism: A Meta-Analysis., Katherine A. Cironi, Peter P. Issa, Aaron L. Albuck, Christina Mccarthy, Leely Rezvani, Mohammad Hussein, Xinyi Luo, Mohamed Shama, Eman Toraih, Emad Kandil Jun 2023

Comparison Of Medical Management Versus Parathyroidectomy In Patients With Mild Primary Hyperparathyroidism: A Meta-Analysis., Katherine A. Cironi, Peter P. Issa, Aaron L. Albuck, Christina Mccarthy, Leely Rezvani, Mohammad Hussein, Xinyi Luo, Mohamed Shama, Eman Toraih, Emad Kandil

School of Medicine Faculty Publications

Background: Parathyroidectomy is the definitive cure for patients with primary hyperparathyroidism (pHPT) and has an annual prevalence of 0.2–1% in the United States. Some patients with mild disease are medically managed effectively using calcium-lowering medications and drugs against complications such as osteoporosis; however, many maintain a persistently high calcium level that negatively impacts their skeletal, renal, and psychogenic systems over the long term. This meta-analysis aims to compare the outcomes of medical management versus parathyroidectomy in patients with mild pHPT. Study Design: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines …

Go to article

Genome Editing For Cystic Fibrosis, Guoshun Wang Jun 2023

Genome Editing For Cystic Fibrosis, Guoshun Wang

School of Medicine Faculty Publications

Cystic fibrosis (CF) is a monogenic recessive genetic disorder caused by mutations in the CF Transmembrane-conductance Regulator gene (CFTR). Remarkable progress in basic research has led to the discovery of highly effective CFTR modulators. Now ~90% of CF patients are treatable. However, these modulator therapies are not curative and do not cover the full spectrum of CFTR mutations. Thus, there is a continued need to develop a complete and durable therapy that can treat all CF patients once and for all. As CF is a genetic disease, the ultimate therapy would be in-situ repair of the genetic lesions in the …

Go to article

Death After Marijuana Use In A 27-Year-Old Male: A Case Report, Samantha M. Lavertue*, Sadie Signorella*, Rohail Baig, Amarah Emerson, John Joyce, Roland Zhang Jun 2023

Death After Marijuana Use In A 27-Year-Old Male: A Case Report, Samantha M. Lavertue*, Sadie Signorella*, Rohail Baig, Amarah Emerson, John Joyce, Roland Zhang

Advances in Clinical Medical Research and Healthcare Delivery

The dangers of marijuana use are well documented across most body systems. We report a 27-year-old male who ingested marijuana and then experienced an ST-elevation myocardial infarction, subsequent cerebrovascular accident, and death within the span of a week. Toxicology reports were positive for THC only, echocardiography revealed diffuse hypokinesis with an ejection fraction estimated at 15-20%, and troponins peaked at greater than 270,000 pg/mL. Due to decreased Glasgow Coma Score and hemodynamic instability, the patient was not taken for cardiac catheterization, but was subsequently sedated, intubated, and placed on pressor support in the ICU. Initial brain imaging was negative for …

Go to article

Microrna (Mirna) Complexity In Alzheimer’S Disease (Ad), Walter J. Lukiw May 2023

Microrna (Mirna) Complexity In Alzheimer’S Disease (Ad), Walter J. Lukiw

School of Medicine Faculty Publications

AD is a complex, progressive, age-related neurodegenerative disorder representing the most common cause of senile dementia and neurological dysfunction in our elderly domestic population. The widely observed heterogeneity of AD is a reflection of the complexity of the AD process itself and the altered molecular-genetic mechanisms operating in the diseased human brain and CNS. One of the key players in this complex regulation of gene expression in human pathological neurobiology are microRNAs (miRNAs) that, through their actions, shape the transcriptome of brain cells that normally associate with very high rates of genetic activity, gene transcription and messenger RNA (mRNA) generation. …

Go to article

Dextromethorphan/Quinidine For The Pseudobulbar Affect In Neurological Disorders And Injuries: Systematic Review And Meta-Analysis, Magnolia Livingston May 2023

Dextromethorphan/Quinidine For The Pseudobulbar Affect In Neurological Disorders And Injuries: Systematic Review And Meta-Analysis, Magnolia Livingston

Honors Theses

AVP-923, commonly known as Nuedexta or Zenvia, is a drug that has recently been suggested as a potential treatment for Pseudobulbar Affect in patients affected by different neurological disorders and injuries. Studies have been done to examine the effectiveness of AVP-923 on PBA, but the results of these studies don’t seem to be comparable. The goal of this meta-analysis is to assess the efficacy and safety of AVP-923. 781 individuals from six trials were included in the analysis. The analysis's findings revealed that AVP-923 considerably lowered the Center for Neurological Study Lability Scale (CNS-LS) scores and the frequency and severity …

Go to article

Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta May 2023

Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, structural stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and …

Go to article

Study Of The Potential Toxicity Of Adrenaline To Neurons, Using The Sh-Sy5y Human Cellular Model, Vera Marisa Costa, João Paulo Capela, Maria Lourdes Bastos, Fernando Remião, Kurt James Varner, José Alberto Duarte, Félix Carvalho May 2023

Study Of The Potential Toxicity Of Adrenaline To Neurons, Using The Sh-Sy5y Human Cellular Model, Vera Marisa Costa, João Paulo Capela, Maria Lourdes Bastos, Fernando Remião, Kurt James Varner, José Alberto Duarte, Félix Carvalho

School of Graduate Studies Faculty Publications

Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration-and time-dependent in both assays, since the lowest concentration …

Go to article

Oxidative Stress And Micrornas In Endothelial Cells Under Metabolic Disorders, Morgan Minjares, Wendy Wu, Jie-Mei Wang May 2023

Oxidative Stress And Micrornas In Endothelial Cells Under Metabolic Disorders, Morgan Minjares, Wendy Wu, Jie-Mei Wang

Pharmaceutical Sciences Faculty Publications

Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced …

Go to article

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield May 2023

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Go to article

First Prev Next Last