Medicine and Health Sciences Commons^™

Natural Phaeosphaeride A Derivatives Overcome Drug Resistance Of Tumor Cells And Modulate Signaling Pathways, Victoria Abzianidze, Natalia Moiseeva, Diana Suponina, Sofya Zakharenkova, Nadezhda Rogovskaya, Lidia Laletina, Alvin A. Holder, Denis Krivorotov, Alexander Bogachenkov, Alexander Garabadzhiu, Anton Ukolov, Vyacheslav Kosorukov

Chemistry & Biochemistry Faculty Publications

n the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds …

Pkcε Activation Restores Loss Of Pkcε, Manganese Superoxide Dismutase, Vascular Endothelial Growth Factor, And Microvessels In Aged And Alzheimer's Disease Hippocampus, Guetchyn Millien, Huaixing Wang, Zongxiu Zhang, Dan L Alkon, Jarin Hongpaisan

Center for Translational Medicine Faculty Papers

Vascular endothelial dysfunction and capillary loss are currently considered to be a primary phenotype of normal human aging and Alzheimer's disease (AD). Activation of protein kinase C (PKCε) improves several molecular, cellular, physiological, and behavioral endpoints, yet it is not known whether a loss of PKCε activity occurs in the microvascular endothelium in aged and AD hippocampi, whether this loss contributes to microvascular change, or whether activation of PKCε protects against microvascular damage, an early change that induces age-associated memory defect and AD. We investigated the effect of the PKCε activation on microvascular loss in the hippocampus, important for memory …

Escherichia Coli Alanyl-Trna Synthetase Maintains Proofreading Activity And Translational Accuracy Under Oxidative Stress, Arundhati Kavoor, Paul Kelly, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability. Recent studies showed that environmental challenges such as exposure to reactive oxygen species can also alter aaRS synthetic and proofreading functions, prompting us to investigate if oxidation might positively or negatively affect AlaRS activity. We found that while oxidation leads to modification of several residues in Escherichia coli AlaRS, unlike …

The Impact Of Aging On The Lung Alveolar Environment, Predetermining Susceptibility To Respiratory Infections, Jordi B. Torrelles, Blanca I. Restrepo, Yidong Bai, Corinna Ross, Larry S. Schlesinger, Joanne Turner

School of Medicine Publications and Presentations

Respiratory infections are one of the top causes of death in the elderly population, displaying susceptibility factors with increasing age that are potentially amenable to interventions. We posit that with increasing age there are predictable tissue-specific changes that prevent the immune system from working effectively in the lung. This mini-review highlights recent evidence for altered local tissue environment factors as we age focusing on increased tissue oxidative stress with associated immune cell changes, likely driven by the byproducts of age-associated inflammatory disease. Potential intervention points are presented.

Antioxidative Properties Of Phenolic Compounds And Their Effect On Oxidative Stress Induced By Severe Physical Exercise, Joanna Kruk, Basil Aboul-Enein, Ewa Duchnik, Mariola Marchlewicz

Health & Wellness Department Faculty Publications and Research

Extensive research has found strongly increased generation of reactive oxygen species, free radicals, and reactive nitrogen species during acute physical exercise that can lead to oxidative stress (OS) and impair muscle function. Polyphenols (PCs), the most abundant antioxidants in the human diet, are of increasing interest to athletes as antioxidants. Current literature suggests that antioxidants supplementation can effectively modulate these processes. This overview summarizes the actual knowledge of chemical and biomechanical properties of PCs and their impact as supplements on acute exercise-induced OS, inflammation control, and exercise performance. Evidence maintains that PC supplements have high potency to positively impact redox …

Synthesis, In Silico And Pharmacological Evaluation Of New Thiazolidine-4-Carboxylic Acid Derivatives Against Ethanol-Induced Neurodegeneration And Memory Impairment, Shagufta Naz, Lina Tariq Al Kury, Humaira Nadeem, Fawad Ali Shah, Rehan Zafar Paracha, Muhammad Imran, Shupeng Li, Aman Ullah

All Works

Introduction: Several studies revealed that alcohol utilization impairs memory in adults; however, the underlying mechanism is still unclear. The production of inflammatory markers and reactive oxygen species (ROS) plays a major role in neurodegeneration, which leads to memory impairment. Therefore, targeting neuroinflammation and oxidative distress could be a useful strategy for abrogating the hallmarks of ethanol-induced neurodegeneration. Moreover, several studies have demonstrated multiple biological activities of thiazolidine derivatives including neuroprotection. Methods: In the current study, we synthesized ten (10) new thiazolidine-4-carboxylic acid derivatives (P1-P10), characterized their synthetic properties using proton nuclear magnetic resonance (1 H-NMR) and carbon-13 NMR, and further …

Benzimidazole Derivatives As New Potential Nlrp3 Inflammasome Inhibitors That Provide Neuroprotection In A Rodent Model Of Neurodegeneration And Memory Impairment, Aman Ullah, Lina Tariq Al Kury, Yusuf S. Althobaiti, Tahir Ali, Fawad Ali Shah

All Works

Objective: The study investigated the effect of newly synthesized benzimidazole derivatives against ethanol-induced neurodegenera-tion. According to evidence, ethanol consumption may cause a severe insult to the central nervous system (CNS), resulting in mental retardation, neuronal degeneration, and oxidative stress. Targeting neuroinflammation and oxidative stress may be a useful strategy for preventing ethanol-induced neurodegeneration. Methodology: Firstly, the newly synthesized compounds were subjected to molecular simulation and docking in order to predict ligand binding status. Later, for in vivo observations, adult male Sprague Dawley rats were used for studying behavioral and oxidative stress markers. ELIZA kits were used to analyse tumour necrosis …

Early Gestational Profiling Of Oxidative Stress And Angiogenic Growth Mediators As Predictive, Preventive And Personalised (3p) Medical Approach To Identify Suboptimal Health Pregnant Mothers Likely To Develop Preeclampsia, Enoch O. Anto, David A. Coall, Otchere Addai-Mensah, Yaw Amo Wiafe, William K. B. A. Owiredu, Christian Obirikorang, Max E. Annani-Akollor, Eric Adua, Augustine Tawiah, Emmanuel Acheampong, Evans Adu Asamoah, Xueqing Wang, Stephen Opoku, Derick Kyei Boakye, Haifeng Hou, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Pregnant women, particularly in developing countries are facing a huge burden of preeclampsia (PE) leading to high morbidity and mortality rates. This is due to delayed diagnosis and unrecognised early targeted preventive measures. Adapting innovative solutions via shifting from delayed to early diagnosis of PE in the context of predictive diagnosis, targeted prevention and personalisation of medical care (PPPM/3 PM) is essential. The subjective assessment of suboptimal health status (SHS) and objective biomarkers of oxidative stress (OS) and angiogenic growth mediators (AGMs) could be used as new PPPM approach for PE; however, these factors have only been studied in isolation …

Oxidative Stress Induced By Reactive Oxygen Species (Ros) And Nadph Oxidase 4 (Nox4) In The Pathogenesis Of The Fibrotic Process In Systemic Sclerosis: A Promising Therapeutic Target, Sonsoles Piera-Velazquez, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

Numerous clinical and research investigations conducted during the last two decades have implicated excessive oxidative stress caused by high levels of reactive oxygen species (ROS) in the development of the severe and frequently progressive fibrotic process in Systemic Sclerosis (SSc). The role of excessive oxidative stress in SSc pathogenesis has been supported by the demonstration of increased levels of numerous biomarkers, indicative of cellular and molecular oxidative damage in serum, plasma, and other biological fluids from SSc patients, and by the demonstration of elevated production of ROS by various cell types involved in the SSc fibrotic process. However, the precise …

Mitochondrial Targeted Antioxidants, Mitoquinone And Skq1, Not Vitamin C, Mitigate Doxorubicin-Induced Damage In H9c2 Myoblast: Pretreatment Vs. Co-Treatment, Brian Sacks, Halil Onal, Rose Martorana, Amogh Sehgal, Amanda Harvey, Catherine Wastella, Hafsa Ahmad, Erin Ross, Adona Pjetergjoka, Sachin Prasad, Robert J. Barsotti, Lindon H. Young, Qian Chen

PCOM Scholarly Papers

BACKGROUND: Preconditioning of the heart ameliorates doxorubicin (Dox)-induced cardiotoxicity. We tested whether pretreating cardiomyocytes by mitochondrial-targeted antioxidants, mitoquinone (MitoQ) or SKQ1, would provide better protection against Dox than co-treatment.

METHODS: We investigated the dose-response relationship of MitoQ, SKQ1, and vitamin C on Dox-induced damage on H9c2 cardiomyoblasts when drugs were given concurrently with Dox (e.g., co-treatment) or 24 h prior to Dox (e.g., pretreatment). Moreover, their effects on intracellular and mitochondrial oxidative stress were evaluated by 2,7-dichlorofluorescin diacetate and MitoSOX, respectively.

RESULTS: Dox (0.5-50 μM, n = 6) dose-dependently reduced cell viability. By contrast, co-treatment of MitoQ (0.05-10 μM, n …

Exercise-Induced Oxidative Stress And Melatonin Supplementation: Current Evidence, Joanna Kruk, Basil Hassan Aboul-Enein, Ewa Duchnik

Health & Wellness Department Faculty Publications and Research

Melatonin possesses the indoleamine structure and exerts antioxidant and anti-inflammatory actions and other physiological properties. Physical exercise can influence secretion of melatonin. Melatonin is used as a natural supplement among athletes to regulate sleep cycles and protect muscles against oxidative damage. Despite decades of research, there is still a lack of a comprehensive and critical review on melatonin supplementation and physical activity relationship. The aim of this literature review is to examine the antioxidant, anti-inflammatory and other biological functions played by melatonin with reference to the effect of physical exercise on melatonin secretion and the effect of this compound supplementation …

Insights Into The Mechanisms Of Brain Endothelial Erythrophagocytosis, Jiahong Sun, Prema Vyas, Samar Mann, Annlia Paganini-Hill, Ane C. F. Nunes, Wei Ling Lau, David H. Cribbs, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 …

Streptococcus Mutans Lacking Sufcdsub Is Viable, But Displays Major Defects In Growth, Stress Tolerance Responses And Biofilm Formation, Kassapa Ellepola, Xiaochang Huang, Ryan P. Riley, Jacob P. Bitoun, Zezhang Tom Wen

School of Dentistry Faculty Publications

Streptococcus mutans appears to possess a sole iron-sulfur (Fe-S) cluster biosynthesis system encoded by the sufCDSUB cluster. This study was designed to examine the role of sufCDSUB in S. mutans physiology. Allelic exchange mutants deficient of the whole sufCDSUB cluster and in individual genes were constructed. Compared to the wild-type, UA159, the sufCDSUB-deficient mutant, Δsuf::kanr, had a significantly reduced growth rate, especially in medium with the absence of isoleucine, leucine or glutamate/glutamine, amino acids that require Fe-S clusters for biosynthesis and when grown with medium adjusted to pH 6.0 and under oxidative and nitrosative stress conditions. Relative to UA159, Δsuf::kanr …

Potential Role Of Vitamin C As An Antioxidant On Bisphenol(Bpa) Induced Oxidative Stress In Wistar Rats, Rekha Kini

Faculty work

No abstract provided.

Developmental Ethanol Exposure Causes Central Nervous System Dysfunction And May Slow The Aging Process In A Drosophila Model Of Fetal Alcohol Spectrum Disorder, Khaoula Belhorma, Nahed Darwish, Elizabeth Benn-Hirsch, Annalisa Duenas, Hillary Gates, Navneet Sanghera, Jodie Wu, Rachael L. French

Faculty Research, Scholarly, and Creative Activity

Alcohol is a known teratogen, and developmental exposure to ethanol results in fetal alcohol spectrum disorder (FASD). Children born with FASD can exhibit a range of symptoms including low birth weight, microcephaly, and neurobehavioral problems. Treatment of patients with FASD is estimated to cost 4 billion dollars per year in the United States alone, and 2 million dollars per affected individual's lifetime. We have established Drosophila melanogaster as a model organism for the study of FASD. Here we report that mutations in Dementin (Dmtn), the Drosophila ortholog of the Alzheimer's disease-associated protein TMCC2, convey sensitivity to developmental ethanol exposure, …

Emerging Targets For The Diagnosis Of Parkinson's Disease: Examination Of Systemic Biomarkers., Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Parkinson's disease (PD) is a highly prevalent and irreversible neurodegenerative disorder that is typically diagnosed in an advanced stage. Currently, there are no approved biomarkers that reliably identify PD patients before they have undergone extensive neuronal damage, eliminating the opportunity for future disease-modifying therapies to intervene in disease progression. This unmet need for diagnostic and therapeutic biomarkers has fueled PD research for decades, but these efforts have not yet yielded actionable results. Recently, studies exploring mechanisms underlying PD progression have offered insights into multisystemic contributions to pathology, challenging the classic perspective of PD as a disease isolated to the brain. …

Chronic Inflammation In Chronic Kidney Disease Progression: Role Of Nrf2., Peter Stenvinkel, Glenn M. Chertow, Prasad Devarajan, Adeera Levin, Sharon P. Andreoli, Sripal Bangalore, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

Despite recent advances in the management of chronic kidney disease (CKD), morbidity and mortality rates in these patients remain high. Although pressure-mediated injury is a well-recognized mechanism of disease progression in CKD, emerging data indicate that an intermediate phenotype involving chronic inflammation, oxidative stress, hypoxia, senescence, and mitochondrial dysfunction plays a key role in the etiology, progression, and pathophysiology of CKD. A variety of factors promote chronic inflammation in CKD, including oxidative stress and the adoption of a proinflammatory phenotype by resident kidney cells. Regulation of proinflammatory and anti-inflammatory factors through NF-κB- and nuclear factor, erythroid 2 like 2 (Nrf2)-mediated …

Potential Roles Of Endoplasmic Reticulum Stress And Cellular Proteins Implicated In Diabesity, Sagir Mustapha, Mustapha Mohammed, Ahmad Khusairi Azemi, Ismaeel Yunusa, Aishatu Shehu, Lukman Mustapha, Yusuf Wada, Mubarak Hussaini Ahmad, Wan Amir Wan Ahmad, Aida Hanum Ghulam Rasool, Siti Safiah Mokhtar

Faculty Publications

The role of the endoplasmic reticulum (ER) has evolved from protein synthesis, processing, and other secretory pathways to forming a foundation for lipid biosynthesis and other metabolic functions. Maintaining ER homeostasis is essential for normal cellular function and survival. An imbalance in the ER implied stressful conditions such as metabolic distress, which activates a protective process called unfolded protein response (UPR). This response is activated through some canonical branches of ER stress, i.e., the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6). Therefore, chronic hyperglycemia, hyperinsulinemia, increased proinflammatory …

The Interconnectivity Of Parkinson's Disease And Type Two Diabetes Mellitus, Erica Olfson

Honors Scholars Collaborative Projects

This thesis is about the biochemical connection between Parkinson's disease and Type II Diabetes Mellitus.

Diabetes And Cancer: Metabolic Association, Therapeutic Challenges, And The Role Of Natural Products, Wamidh H. Talib, Asma Ismail Mahmod, Sara Feras Abuarab, Eliza Hasen, Amer A. Munaim, Shatha Khaled Haif, Amani Marwan Ayyash, Samar Khater, Intisar Hadi Al-Yasari, Lina T. Al Kury

All Works

Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible for approximately 9.6 million deaths. Globally, about one in six deaths are caused by cancer. A strong correlation was found between diabetes mellitus and carcinogenesis with the most evident correlation was with type 2 diabetes mellitus (T2DM). Research has proven that elevated blood glucose levels take part in cell proliferation and cancer cell progression. However, limited studies were conducted to evaluate the efficiency of conventional therapies in diabetic cancer patients. In this review, the correlation between cancer and diabetes will be discussed and the …

Interplay Between Oxidative Stress, Sirt1, Reproductive And Metabolic Functions, Faiza Alam, Hareem Syed, Sofia Amjad, Mukhtiar Baig, Taseer Ahmed Khan, Rehana Rehman

Department of Biological & Biomedical Sciences

Silent information Regulators (SIRT1) gene stimulates antioxidants' expression, repairs cells damaged by oxidative stress (OS), and prevents the cells' dysfunction. In particular, the role of different Sirtuins, particularly SIRT1 in reproduction, has been widely studied over the past decade. Decreased SIRT 1 causes mitochondrial dysfunction by increasing Reactive Oxygen Species (ROS), lipid peroxidation, and DNA damage in both male and female gametes (Sperms and Oocytes), leading to infertility. In the female reproductive system, SIRT1 regulates proliferation and apoptosis in granulosa cells (GCs), and its down-regulation is associated with a reduced ovarian reserve. SIRT1 also modulates the stress response to OS …

Chronic Voluntary Alcohol Drinking Causes Anxiety-Like Behavior, Thiamine Deficiency, And Brain Damage Of Female Crossed High Alcohol Preferring Mice, Hong Xu, Hui Li, Dexiang Liu, Wen Wen, Mei Xu, Jacqueline A. Frank, Jing Chen, Haining Zhu, Nicholas J. Grahame, Jia Luo

Molecular and Cellular Biochemistry Faculty Publications

The central nervous system is vulnerable to chronic alcohol abuse, and alcohol dependence is a chronically relapsing disorder which causes a variety of physical and mental disorders. Appropriate animal models are important for investigating the underlying cellular and molecular mechanisms. The crossed High Alcohol Preferring mice prefer alcohol to water when given free access. In the present study, we used female cHAP mice as a model of chronic voluntary drinking to evaluate the effects of alcohol on neurobehavioral and neuropathological changes. The female cHAP mice had free-choice access to 10% ethanol and water, while control mice had access to water …

Rap1a Overlaps The Age/Rage Signaling Cascade To Alter Expression Of Α‐Sma, P‐Nf‐Κb, And P‐Pkc‐Ζ In Cardiac Fibroblasts Isolated From Type 2 Diabetic Mice, Stephanie D. Burr, James A. Stewart

Faculty and Student Publications

Cardiovascular disease, specifically heart failure, is a common complication for individu-als with type 2 diabetes mellitus. Heart failure can arise with stiffening of the left ventricle, which can be caused by “active” cardiac fibroblasts (i.e., myofibroblasts) remodeling the extracellular matrix (ECM). Differentiation of fibroblasts to myofibroblasts has been demonstrated to be an outcome of AGE/RAGE signaling. Hyperglycemia causes advanced glycated end products (AGEs) to accu-mulate within the body, and this process is greatly accelerated under chronic diabetic conditions. AGEs can bind and activate their receptor (RAGE) to trigger multiple downstream outcomes, such as altering ECM remodeling, inflammation, and oxidative stress. …

Cardiac Inflammation, Oxidative Stress, Nrf2 Expression, And Coagulation Events In Mice With Experimental Chronic Kidney Disease, Abderrahim Nemmar, Suhail Al-Salam, Sumaya Beegam, Nur Elena Zaaba, Javed Yasin, Naserddine Hamadi, Badreldin H. Ali

All Works

Chronic kidney disease (CKD) is known to be associated with cardiovascular dysfunction. Dietary adenine intake in mice is also known to induce CKD. However, in this experimental model, the mechanisms underlying the cardiotoxicity and coagulation disturbances are not fully understood. Here, we evaluated cardiac inflammation, oxidative stress, DNA damage, and coagulation events in mice with adenine (0.2% w/w in feed for 4 weeks)-induced CKD. Control mice were fed with normal chow for the same duration. Adenine increased water intake, urine output, relative kidney weight, the plasma concentrations of urea and creatinine, and the urinary concentrations of kidney injury molecule-1 and …

Myeloperoxidase: A Versatile Mediator Of Endothelial Dysfunction And Therapeutic Target During Cardiovascular Disease, Sophie L. Maiocchi, Jacqueline Ku, Thuan Thai, Enoch Chan, Martin D. Rees, Shane R. Thomas

Education Papers and Journal Articles

Myeloperoxidase (MPO) is a prominent mammalian heme peroxidase and a fundamental component of the innate immune response against microbial pathogens. In recent times, MPO has received considerable attention as a key oxidative enzyme capable of impairing the bioactivity of nitric oxide (NO) and promoting endothelial dysfunction; a clinically relevant event that manifests throughout the development of inflammatory cardiovascular disease. Increasing evidence indicates that during cardiovascular disease, MPO is released intravascularly by activated leukocytes resulting in its transport and sequestration within the vascular endothelium. At this site, MPO catalyzes various oxidative reactions that are capable of promoting vascular inflammation and impairing …

Involvement Of Tgfβ Signaling Pathway In Oxidative Stress And Diabetic Retinopathy, Reanna Rodriguez, Kristine L. Lowe, Megan Keniry, Andrew Tsin

School of Medicine Publications and Presentations

Diabetic Retinopathy (DR) is a leading cause of blindness in the U.S. However, not much is known of underlying molecular mechanism and how oxidative stress contributes to its development. In the present study, we investigated the involvement of TGFβ signaling pathway on the effect of oxidative stress on VEGF secretion and viability of retinal cells. VEGF is the hallmark that exacerbates DR progression in prolonged diabetes. Some major concerns that have arisen are the underlying effects of antioxidants in elevating VEGF secretion in diabetes. In this study, we evaluated how hypoxia (or low oxygen) impacts viability and VEGF secretion using …

Exercise Improves Endothelial Function Associated With Alleviated Inflammation And Oxidative Stress Of Perivascular Adipose Tissue In Type 2 Diabetic Mice, Jinju Wang, Venkata Polaki, Shuzhen Chen, Ji Chen Bihl, Pasquale Pagliaro

Pharmacology and Toxicology Faculty Publications

Perivascular adipose tissue (PVAT), a type of adipose tissue that surrounds the blood vessels, has been considered an active component of the blood vessel walls and involved in vascular homeostasis. Recent evidence shows that increased inflammation and oxidative stress in PVAT contribute to endothelial dysfunction in type 2 diabetes (T2D). Exercise is an important nonpharmacological approach for vascular diseases. However, there is limited information regarding whether the beneficial effects of exercise on vascular function is related to the PVAT status. In this study, we investigated whether exercise can decrease oxidative stress and inflammation of PVAT and promote the improvement of …

The Effect Of Dietary Nitrate And Vitamin C On Endothelial Function, Oxidative Stress And Blood Lipids In Untreated Hypercholesterolemic Subjects: A Randomized Double-Blind Crossover Study, Reem Basaqr, Michealia Skleres, Rani Jayswal, D. Travis Thomas

Athletic Training and Clinical Nutrition Faculty Publications

BACKGROUND: Vitamin C may enhance nitric oxide (NO) production through stepwise reduction of dietary nitrate (NO₃) to nitrite (NO₂) to NO. The combined effect of vitamin C and NO₃ supplementation is relatively unexplored in untreated hypercholesterolemia.

AIMS: We aimed to examine whether co-administration of vitamin C and nitrate for 4-weeks would improve endothelial function (primary outcome), plasma NO metabolites, oxidative stress, and blood lipids (secondary outcomes).

METHODS: Subjects 50–70 years of age with low density lipoprotein (LDL) > 130 mg/dL and RHI ≤ 2 were enrolled in this randomized double-blind crossover study. Subjects were assigned to …

Neuronal Calcium Imaging, Excitability, And Plasticity Changes In The Aldh2-/- Mouse Model Of Sporadic Alzheimer's Disease, Adam O. Ghoweri, Peter Gagolewicz, Hilaree N. Frazier, John C. Gant, R. David Andrew, Brian M. Bennett, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Dysregulated signaling in neurons and astrocytes participates in pathophysiological alterations seen in the Alzheimer's disease brain, including increases in amyloid-β, hyperphosphorylated tau, inflammation, calcium dysregulation, and oxidative stress. These are often noted prior to the development of behavioral, cognitive, and non-cognitive deficits. However, the extent to which these pathological changes function together or independently is unclear.

OBJECTIVE: Little is known about the temporal relationship between calcium dysregulation and oxidative stress, as some reports suggest that dysregulated calcium promotes increased formation of reactive oxygen species, while others support the opposite. Prior work has quantified several key outcome measures associated with …

Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and …