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Inflammation

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A Population-Based Study Of Children Suggests Blunted Morning Cortisol Rhythms Are Associated With Alterations Of The Systemic Inflammatory State, Runia Roy, Utkarsh J. Dang, Kim M. Huffman, Tchilabalo Alayi, Yetrib Hathout, Kanneboyina Nagaraju, Paul S. Visich, Eric P. Hoffman Jan 2024

A Population-Based Study Of Children Suggests Blunted Morning Cortisol Rhythms Are Associated With Alterations Of The Systemic Inflammatory State, Runia Roy, Utkarsh J. Dang, Kim M. Huffman, Tchilabalo Alayi, Yetrib Hathout, Kanneboyina Nagaraju, Paul S. Visich, Eric P. Hoffman

Pharmacy Faculty Scholarship

Background: In children, digital media, lifestyle, and the COVID pandemic have impacted sunlight exposure, exercise, and diet patterns - cues that entrain the circadian clock. We hypothesized that low morning cortisol reflects a weak circadian clock, impacting the pro-inflammatory state. The primary objective was to test relationships between diurnal cortisol fluctuations and the inflammatory state in children as a means of providing indirect support for this hypothesis. Methods: The Cardiovascular Health Intervention Program (CHIP) was a population-based cross-sectional and longitudinal study of circadian health in public elementary school children in Southern Maine, USA (recruitment period 2012–2017). Participants were 689 students …


Role Of Inflammatory And Growth Factors In Diabetes Mellitus, Sayed Mohammed Firdous, Sourav Pal Jan 2024

Role Of Inflammatory And Growth Factors In Diabetes Mellitus, Sayed Mohammed Firdous, Sourav Pal

Palestinian Medical and Pharmaceutical Journal

In diabetes mellitus, both inflammatory and growth factors play significant roles in the development and progression of the disease and its associated complications. Diabetics frequently show signs of chronic, low-grade inflammation. Insulin resistance and beta-cell dysfunction are exacerbated by the high levels of pro-inflammatory cytokines prevalent in diabetes, such as TNF-α and IL-6. High levels of the inflammatory marker C-reactive protein are linked to insulin resistance and an increased risk of cardiovascular disease. An upsurge in in diabetes is caused by NF-κB activation. Complications and pathological processes in diabetes may be exacerbated by a dysregulation of growth factors. The angiogenesis-related …


Identifying Unexpected Inflammation Resulting From Drug-Drug Interactions, Keegan Jolly Jan 2023

Identifying Unexpected Inflammation Resulting From Drug-Drug Interactions, Keegan Jolly

All Master's Theses

Adverse drug events result in nearly 1.3 million emergency room visits per year in the United States of America. As much as 30% of these adverse events are a result of drug-drug interactions (DDI’s). There is a gap in knowledge concerning these DDI outcomes especially when it comes to inflammation. Inflammation is linked to a variety of chronic health conditions and non-infectious diseases such as cancer. Purpose: The goal of this study was to examine how many active drug ingredients from FDA’s Adverse Event Reporting System (FAERS), when combined (in groups of two or more), elicit an inflammatory response …


Tlr4/Nfκb-Mediated Anti-Inflammatory And Antioxidative Effect Of Hexanic And Ethanolic Extracts Of Curcuma Longa L. In Buffalo Mammary Epithelial Cells, Insha Amin, Shahzada Mudasir Rashid, Sheikh Shubeena, Ishraq Hussain Dec 2022

Tlr4/Nfκb-Mediated Anti-Inflammatory And Antioxidative Effect Of Hexanic And Ethanolic Extracts Of Curcuma Longa L. In Buffalo Mammary Epithelial Cells, Insha Amin, Shahzada Mudasir Rashid, Sheikh Shubeena, Ishraq Hussain

Faculty and Student Publications

Mastitis is the commonest disease of bovines imposing a great economic setback and a drastic public health concern worldwide. Antibiotic resistance is the preliminary con of excessive antibiotics use for disease treatment. Studies validate an alarming increase in the antibiotic resistance of both humans and animals. For ages, medicinal plants have been used to treat a number of ailments in humans and animals, including mastitis. Curcuma longa, or turmeric, is the prerequisite in Indian cooking and has been used in traditional medicine for its magical properties. The rhizome of C. longa possesses significant anti-inflammatory, antibacterial, antifungal, and antioxidative properties. In …


Rosmarinic Acid Prevents Cisplatin-Induced Liver And Kidney Injury By Inhibiting Inflammatory Responses And Enhancing Total Antioxidant Capacity, Thereby Activating The Nrf2 Signaling Pathway, Yifei Xiang, Min Ji, Liqin Wu, Li Lv Nov 2022

Rosmarinic Acid Prevents Cisplatin-Induced Liver And Kidney Injury By Inhibiting Inflammatory Responses And Enhancing Total Antioxidant Capacity, Thereby Activating The Nrf2 Signaling Pathway, Yifei Xiang, Min Ji, Liqin Wu, Li Lv

Faculty and Student Publications

Drug-induced liver and kidney damage is an emergent clinical issue that should be addressed. Rosmarinic acid (RA) has obvious anti-inflammatory and antioxidant effects, so we evaluated the anti-inflammatory and antioxidant effects of RA pretreatment on serum and liver and kidney tissues of cisplatin (CP)-treated mice and explored the possible mechanisms. The results showed that RA pretreatment effectively downregulated the serum, liver, and kidney levels of ALT, AST, BUN, and CRE and the inflammatory factors IL-1β, IL-6, and TNF-α, and simultaneously enhanced the total antioxidant capacity of the liver and kidney. RA pretreatment significantly reduced the levels of MPO, MDA, and …


Serpin-Derived Novel Peptide For The Treatment Against Hiv-Induced Inflammation In The Central Nervous System, Yemmy Soler Jun 2022

Serpin-Derived Novel Peptide For The Treatment Against Hiv-Induced Inflammation In The Central Nervous System, Yemmy Soler

FIU Electronic Theses and Dissertations

In the brain, HIV predominantly infects microglia/macrophages and astrocytes to a lesser extent. These cells form virus reservoirs with low levels of infection that are very hard to eradicate. Even though the use of cART increases survival rate in HIV patients, the virus persists as a chronic condition. cART is not able to effectively cross the BBB, control HIV replication, or attenuate inflammation in brain reservoirs. Therefore, the virus still causes neuronal dysfunction, pain-related pathology, and ultimately HAND. In this study, we decided to test the hypothesis that a serpin-derived small peptide, SP16, can serve as an anti-viral, anti-inflammatory, pro-survival, …


Ameliorative Effects Of Minor Cannabinoids Over Hiv-1 Tat-Mediated Visceral Pain, Charlie Worth Apr 2022

Ameliorative Effects Of Minor Cannabinoids Over Hiv-1 Tat-Mediated Visceral Pain, Charlie Worth

Honors Theses

As the total number of people living with HIV continues to rise across the world, an effective HIV treatment is still sought after. While modern-day advanced therapies exist for mitigating much of the negative effects of HIV, the virus remains evasive and problematic in the central nervous system. Thus, even with treatment, many people living with HIV continue to suffer from a plethora of symptoms. However, a large proportion of HIV-positive patients claim to feel a reduction in those persevering symptoms after cannabis usage. This anecdotal evidence has sparked interest in the efficacy of cannabis constituents for HIV therapy. This …


10-Minute Ebd: Preferred Analgesia For Orthodontic Tooth Movement: Acetaminophen Or Nsaids?, Ryan N. Mcgovern Apr 2022

10-Minute Ebd: Preferred Analgesia For Orthodontic Tooth Movement: Acetaminophen Or Nsaids?, Ryan N. Mcgovern

The Journal of the Michigan Dental Association

This 10-Minute EBD column explores the choice between acetaminophen and NSAIDs for managing pain during orthodontic tooth movement. The author presents a scenario involving a patient's discomfort after archwire adjustment and delves into the impact of tooth movement on the periodontium. The PICO question focuses on the effectiveness of NSAIDs and acetaminophen in controlling discomfort without impeding tooth movement. The literature search reveals varying recommendations on analgesics, with some studies favoring acetaminophen. The evidence suggests that acetaminophen and short-term celecoxib are suitable choices for orthodontic analgesia. However, caution is advised in extrapolating findings from animal studies to human conditions.


Biomarkers Of Inflammation And Oxidative Stress In The Prediction And Management Of Acute Coronary Syndrome, Udaya Ralapanawa, Sivakanesan R Jan 2022

Biomarkers Of Inflammation And Oxidative Stress In The Prediction And Management Of Acute Coronary Syndrome, Udaya Ralapanawa, Sivakanesan R

Health Sciences

The assessment of patients presenting with chest pain or symptoms indicative of cardiac ischemia remains a diagnostic challenge. Many types of research have focused on the search for ideal biological markers for the rapid detection of cardiac cell injuries. Markers of inflammation and oxidative stress are the way forward. At present, the biomarker most widely used for diagnosing acute coronary syndrome is cardiac troponin though it has some limitations. Apart from cardiac troponin, several other biomarkers, especially inflammation and oxidative stress markers in acute coronary syndrome, have been investigated. However, most of them still require validation in further studies. As …


Effects Of Annexin A5 On Endothelial Inflammation Induced By Lipopolysaccharide-Activated Platelets And Extracellular Vesicles, Brent Jeffrey Tschirhart Dec 2021

Effects Of Annexin A5 On Endothelial Inflammation Induced By Lipopolysaccharide-Activated Platelets And Extracellular Vesicles, Brent Jeffrey Tschirhart

Electronic Thesis and Dissertation Repository

Sepsis is a dysregulated immune response to infection and the leading cause of mortality globally, accounting for 11 million deaths in 2017. To date, no therapeutics are available to treat the underlying septic response. Previous research from our laboratory has shown that annexin A5 (Anx5) treatment increased survival by 40% in mice with endotoxemia, a model of sepsis. During sepsis, activated platelets release membrane fragments called extracellular vesicles (EVs) with externalization of phosphatidylserine to which annexin A5 binds with a high affinity. We hypothesized that annexin A5 will block the pro-inflammatory response induced by activated platelets and EVs in vascular …


Arrhythmogenic Hearts In Pkd2 Mutant Mice Are Characterized By Cardiac Fibrosis, Systolic, And Diastolic Dysfunctions, Farideh Amirrad, Rajasekharreddy Pala, Kiumars Shamloo, Brian S. Muntean, Surya M. Nauli Nov 2021

Arrhythmogenic Hearts In Pkd2 Mutant Mice Are Characterized By Cardiac Fibrosis, Systolic, And Diastolic Dysfunctions, Farideh Amirrad, Rajasekharreddy Pala, Kiumars Shamloo, Brian S. Muntean, Surya M. Nauli

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (PKD) is a hereditary disorder affecting multiple organs, including the heart. PKD has been associated with many cardiac abnormalities including the arrhythmogenic remodeling in clinical evaluations. In our current study, we hypothesized that Pkd2 gene mutation results in structural and functional defects in the myocardium. The structural and functional changes of Pkd2 mutant hearts were analyzed in the myocardial-specific Pkd2 knockout (KO) mouse. We further assessed a potential role of TGF-b1 signaling in the pathology of Pkd2-KO hearts. Hearts from age-matched 6-month-old MyH6Pkd2wt/wt (control or wild-type) and MyH6 …


Variations In Er Stress And Unfolded Protein Response Predict Disease Susceptibility, Youwen Zhang Oct 2021

Variations In Er Stress And Unfolded Protein Response Predict Disease Susceptibility, Youwen Zhang

Theses and Dissertations

Numerous studies linked endoplasmic reticulum (ER) stress and unfolded protein response (UPR) to physiological responses to stress and various human pathologies, including metabolic disorders. Although variability in stress responses among individuals has been widely recognized, how such variations in the UPR affect susceptibility to diseases remains unknown. Using outbred deer mice as a model, we explored the consequences of the differential propensity to UPR at the transcriptomic, cellular, and organismic level.

Initially, we analyzed the correlation between several UPR-related genes in primary fibroblasts, at the whole transcriptome level, after ER stress induction. The analysis of correlated transcripts revealed that their …


Neuron-Derived Extracellular Vesicles Modulate Microglia Activation And Function, Hui Peng, Brock T. Harvey, Christopher I. Richards, Kimberly Nixon Sep 2021

Neuron-Derived Extracellular Vesicles Modulate Microglia Activation And Function, Hui Peng, Brock T. Harvey, Christopher I. Richards, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Microglia act as the immune cells of the central nervous system (CNS). They play an important role in maintaining brain homeostasis but also in mediating neuroimmune responses to insult. The interactions between neurons and microglia represent a key process for neuroimmune regulation and subsequent effects on CNS integrity. However, the molecular mechanisms of neuron-glia communication in regulating microglia function are not fully understood. One recently described means of this intercellular communication is via nano-sized extracellular vesicles (EVs) that transfer a large diversity of molecules between neurons and microglia, such as proteins, lipids, and nucleic acids. To determine the effects of …


Identification Of Human Kinin-Forming Enzyme Inhibitors From Medicinal Herbs, Hassan Madkhali, Amer Tarawneh, Zulfiqar Ali, Hoang V. Le Jul 2021

Identification Of Human Kinin-Forming Enzyme Inhibitors From Medicinal Herbs, Hassan Madkhali, Amer Tarawneh, Zulfiqar Ali, Hoang V. Le

Faculty and Student Publications

The goal of this study was to assess the pharmacological effects of black tea (Camellia sinensis var. assamica) water extract on human kinin-forming enzymes in vitro. Tea is a highly consumed beverage in the world. Factor XII (FXII, Hageman factor)-independent-and-dependent activation of prekallikrein to kallikrein leads to the liberation of bradykinin (BK) from high-molecular-weight kininogen (HK). The excessive BK production causes vascular endothelial and nonvascular smooth muscle cell permeability, leading to angioedema. The prevalence of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema appears to be through BK. Both histamine and BK are potent inflammatory mediators. However, the treatments for histamine-mediated angioedema are …


Evidence That Maackia Amurensis Seed Lectin (Masl) Exerts Pleiotropic Actions On Oral Squamous Cells With Potential To Inhibit Sars-Cov-2 Infection And Covid-19 Disease Progression, Stephanie A. Sheehan, Kelly L. Hamilton, Edward P. Retzbach, Premalatha Balachandran Jun 2021

Evidence That Maackia Amurensis Seed Lectin (Masl) Exerts Pleiotropic Actions On Oral Squamous Cells With Potential To Inhibit Sars-Cov-2 Infection And Covid-19 Disease Progression, Stephanie A. Sheehan, Kelly L. Hamilton, Edward P. Retzbach, Premalatha Balachandran

Faculty and Student Publications

COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 125 million confirmed COVID-19 cases that have caused over 27 million deaths worldwide as of March 2021. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface “spike” protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia …


Repurposing Drugs To Treat Heart And Brain Illness, Maranda S. Cantrell, Alejandro Soto-Avellaneda, Jackson D. Wall, Aaron D. Ajeti, Brad E. Morrison, Lisa R. Warner, Owen M. Mcdougal Jun 2021

Repurposing Drugs To Treat Heart And Brain Illness, Maranda S. Cantrell, Alejandro Soto-Avellaneda, Jackson D. Wall, Aaron D. Ajeti, Brad E. Morrison, Lisa R. Warner, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

Drug development is a complicated, slow and expensive process with high failure rates. One strategy to mitigate these factors is to recycle existing drugs with viable safety profiles and have gained Food and Drug Administration approval following extensive clinical trials. Cardiovascular and neurodegenerative diseases are difficult to treat, and there exist few effective therapeutics, necessitating the development of new, more efficacious drugs. Recent scientific studies have led to a mechanistic understanding of heart and brain disease progression, which has led researchers to assess myriad drugs for their potential as pharmacological treatments for these ailments. The focus of this review is …


Apigenin And Structurally Related Flavonoids Allosterically Potentiate The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Waheed Shabbir, Keun-Hang Susan Yang, Bassem Sadek, Murat Oz May 2021

Apigenin And Structurally Related Flavonoids Allosterically Potentiate The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Waheed Shabbir, Keun-Hang Susan Yang, Bassem Sadek, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Phytochemicals, such as monoterpenes, polyphenols, curcuminoids, and flavonoids, are known to have anti-inflammatory, antioxidant, neuroprotective, and procognitive effects. In this study, the effects of several polyhydroxy flavonoids, as derivatives of differently substituted 5,7-dihydroxy-4H-chromen-4-one including apigenin, genistein, luteolin, kaempferol, quercetin, gossypetin, and phloretin with different lipophilicities (cLogP), as well as topological polar surface area (TPSA), were tested for induction of Ca2+ transients by α7 human nicotinic acetylcholine (α7 nACh) receptors expressed in SH-EP1 cells. Apigenin (10 μM) caused a significant potentiation of ACh (30 μM)-induced Ca2+ transients, but did not affect Ca2+ transients induced by high K+ …


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 Mar 2021

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. …


Anti-Inflammatory Effects Of Α7-Nicotinic Ach Receptors Are Exerted Through Interactions With Adenylyl Cyclase-6, Simeng Zhu, Shiqian Huang, Guofang Xia, Jin Wu, Yan Shen, Ying Wang, Rennolds S. Ostrom, Ailian Du, Chengxing Shen, Congfeng Xu Feb 2021

Anti-Inflammatory Effects Of Α7-Nicotinic Ach Receptors Are Exerted Through Interactions With Adenylyl Cyclase-6, Simeng Zhu, Shiqian Huang, Guofang Xia, Jin Wu, Yan Shen, Ying Wang, Rennolds S. Ostrom, Ailian Du, Chengxing Shen, Congfeng Xu

Pharmacy Faculty Articles and Research

Background and purpose

Alpha 7 nicotinic acetylcholine receptors (CHRNA7) suppress inflammation through diverse pathways in immune cells, so is potentially involved in a number of inflammatory diseases. However, the detailed mechanisms underlying CHRNA7’s anti‐inflammatory effects remain elusive.

Experimental approach

The anti‐inflammatory effects of CHRNA7 agonists in both murine macrophages (RAW 264.7) and bone marrow‐derived macrophages (BMDM) stimulated with LPS were examined. The role of adenylyl cyclase 6 (AC6) in Toll‐like Receptor 4 (TLR4) degradation was explored via overexpression and knockdown. A mouse model of chronic obstructive pulmonary disease was used to confirm key findings.

Results

Anti‐inflammatory effects of CHRNA7 were …


Immunomodulatory Effects Of Azithromycin Revisited: Potential Applications To Covid-19, Vincent J. Venditto, Dalia Haydar, Ahmed K. Abdel-Latif, John C. Gensel, Michael I. Anstead, Michelle G. Pitts, Jarrod W. Creameans, Timothy J. Kopper, Chi Peng, David J. Feola Feb 2021

Immunomodulatory Effects Of Azithromycin Revisited: Potential Applications To Covid-19, Vincent J. Venditto, Dalia Haydar, Ahmed K. Abdel-Latif, John C. Gensel, Michael I. Anstead, Michelle G. Pitts, Jarrod W. Creameans, Timothy J. Kopper, Chi Peng, David J. Feola

Pharmaceutical Sciences Faculty Publications

The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support the premise of targeting the immune response. However, because suppressing immune mechanisms could also impact the clearance of the virus in the early stages of infection, therapeutic success is likely to depend on …


Understanding The Variable Drivers Of Toxicity For The Broad Class Of Carbon Nanotubes And Nanofibers From U.S. Facilities, Kelly E. Fraser Jan 2021

Understanding The Variable Drivers Of Toxicity For The Broad Class Of Carbon Nanotubes And Nanofibers From U.S. Facilities, Kelly E. Fraser

Graduate Theses, Dissertations, and Problem Reports

Pulmonary exposure to carbon nanotubes or nanofibers (CNT/F) is known to induce inflammation, toxicity, or tumorigenesis, and is a concern in the occupational setting. U. S. facility employees are at risk of inhalation exposure of multi-walled carbon nanotubes and carbon nanofibers during primary and secondary manufacturing. To date, only one MWCNT, Mitsui-7 has been classified as possibly carcinogenic to humans (Group 2B), while all other materials were subsequently categorized as unclassifiable (Group 3). This class of material has recently been listed as a high priority to the International Agency for Research on Cancer due to this significant knowledge gap. Furthermore, …


Are We Missing The Target? Are We Aiming Too Low? What Are The Aerobic Exercise Prescriptions And Their Effects On Markers Of Cardiovascular Health And Systemic Inflammation In Patients With Knee Osteoarthritis? A Systematic Review And Meta-Analysis, Jenna M. Schulz, Trevor B. Birmingham, Hayden F. Atkinson, Emilie Woehrle, Codie A. Primeau, Michael J. Lukacs, Baraa K. Al-Khazraji, Michaela C.M. Khan, Bryn O. Zomar, Robert J. Petrella, Frank Beier, C. Thomas Appleton, J. Kevin Shoemaker, Dianne M. Bryant Jul 2020

Are We Missing The Target? Are We Aiming Too Low? What Are The Aerobic Exercise Prescriptions And Their Effects On Markers Of Cardiovascular Health And Systemic Inflammation In Patients With Knee Osteoarthritis? A Systematic Review And Meta-Analysis, Jenna M. Schulz, Trevor B. Birmingham, Hayden F. Atkinson, Emilie Woehrle, Codie A. Primeau, Michael J. Lukacs, Baraa K. Al-Khazraji, Michaela C.M. Khan, Bryn O. Zomar, Robert J. Petrella, Frank Beier, C. Thomas Appleton, J. Kevin Shoemaker, Dianne M. Bryant

Physiology and Pharmacology Publications

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Objectives We systemically reviewed published studies that evaluated aerobic exercise interventions in patients with knee osteoarthritis (OA) to: (1) report the frequency, intensity, type and time (FITT) of exercise prescriptions and (2) quantify the changes in markers of cardiovascular health and systemic inflammation. Data sources PubMed, CINAHL, Scopus; inception to January 2019. Eligibility criteria Randomised clinical trials (RCT), cohort studies, case series. Design We summarised exercise prescriptions for all studies and calculated effect sizes with 95% CIs for between-group (RCTs that compared exercise and …


Inflammation Profiling Of Critically Ill Coronavirus Disease 2019 Patients., Douglas D Fraser, Gediminas Cepinskas, Marat Slessarev, Claudio Martin, Mark Daley, Michael R Miller, David B O'Gorman, Sean E Gill, Eric K Patterson, Claudia C Dos Santos Jun 2020

Inflammation Profiling Of Critically Ill Coronavirus Disease 2019 Patients., Douglas D Fraser, Gediminas Cepinskas, Marat Slessarev, Claudio Martin, Mark Daley, Michael R Miller, David B O'Gorman, Sean E Gill, Eric K Patterson, Claudia C Dos Santos

Physiology and Pharmacology Publications

Objectives: Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019.

Design: Daily blood inflammation profiling with immunoassays.

Setting: Tertiary care ICU and academic laboratory.

Subjects: All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus …


Recombinant Human Proteoglycan-4 Mediates Interleukin-6 Response In Both Human And Mouse Endothelial Cells Induced Into A Sepsis Phenotype, Holly A. Richendrfer, Mitchell M. Levy, Khaled A. Elsaid, Tannin A. Schmidt, Ling Zhang, Ralph Cabezas, Gregory D. Jay Jun 2020

Recombinant Human Proteoglycan-4 Mediates Interleukin-6 Response In Both Human And Mouse Endothelial Cells Induced Into A Sepsis Phenotype, Holly A. Richendrfer, Mitchell M. Levy, Khaled A. Elsaid, Tannin A. Schmidt, Ling Zhang, Ralph Cabezas, Gregory D. Jay

Pharmacy Faculty Articles and Research

Objectives:

Sepsis is a leading cause of death in the United States. Putative targets to prevent systemic inflammatory response syndrome include antagonism of toll-like receptors 2 and 4 and CD44 receptors in vascular endothelial cells. Proteoglycan-4 is a mucinous glycoprotein that interacts with CD44 and toll-like receptor 4 resulting in a blockade of the NOD-like receptor pyrin domain-containing-3 pathway. We hypothesized that endothelial cells induced into a sepsis phenotype would have less interleukin-6 expression after recombinant human proteoglycan 4 treatment in vitro.

Design:

Enzyme-linked immunosorbent assay and reverse transcriptase-quantitative polymerase chain reaction to measure interleukin-6 protein and gene expression.

Setting: …


Commentary: Phytocannabinoids As Therapeutic Agents To Combat Chronic Gingival Disease., Nick Narek Ohanian May 2020

Commentary: Phytocannabinoids As Therapeutic Agents To Combat Chronic Gingival Disease., Nick Narek Ohanian

Pacific Journal of Health

The therapeutic potential of cannabis has been harnessed for thousands of years yet the United States Food and Drug Administration (FDA) has still not approved cannabis as a safe or effective drug. The FDA has, however, approved the manufacturing of pharmaceutical drugs, which contain a “synthetic version of a substance that is present in the marijuana” and other compounds that mimic its action. A search of the US National Library of Medicine and National Institute of Health for keywords “CBD” and “Periodontitis” together yields only 2 publications. Although the current State and Federal regulations on the use of cannabis for …


Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann May 2020

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …


Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt May 2020

Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt

Honors Theses

Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ9-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired …


Gm-1111 Preserves Phagocytic Function Of Macrophages Exposed To Prolonged Hyperoxia Via Interruption Of Hmgb1-Mediated Signaling, Leanne Daley Jan 2020

Gm-1111 Preserves Phagocytic Function Of Macrophages Exposed To Prolonged Hyperoxia Via Interruption Of Hmgb1-Mediated Signaling, Leanne Daley

Theses and Dissertations

Supraphysiological levels of oxygen (i.e. hyperoxia) are used to treat patients with respiratory distress. Prolonged exposure to hyperoxia can impair alveolar macrophage functions and increase susceptibility to ventilator-associated pneumonia (VAP). Hyperoxia-induced alveolar macrophage dysfunction is, in part, mediated by high airway levels of the pro-inflammatory mediator, high mobility group box-1 (HMGB1). An early generation glycosaminoglycan (GAG), 2-O, 3-O desulfated heparin (ODSH), attenuates hyperoxia-compromised innate immunity by preventing the binding of HMGB1 with receptors that activate pro-inflammatory pathways. In this study, we investigated whether the next generation GAG, GM-1111, can attenuate hyperoxia-compromised macrophage function. GM-1111 (100μM) prevented hyperoxia-induced (95% O2 for …


Anticholinergic Burden And Risk Of Cognitive Impairment In Older Adults, Syeda Hashimi Jan 2020

Anticholinergic Burden And Risk Of Cognitive Impairment In Older Adults, Syeda Hashimi

Theses and Dissertations

Studies reveal that 10-27% of older adults chronically use anticholinergic medications. Increased cumulative anticholinergic burden scores are associated with increased risks of dementia. The mechanisms by which anticholinergic drugs negatively impact cognition remain elusive. However, researchers speculate that the drug’s impairment of cholinergic neurons promotes neuroinflammation.

We hypothesize that drugs with anticholinergic properties will induce inflammation in the brain. MCP1 and IL 6 are chemokines that contribute to neuroinflammation. We investigated the influence of diphenhydramine (Benadryl) on the production of MCP1 and IL-6 in Normal Human Astrocytes and Paroxetine on the production of MCP1 in Normal Human Astrocytes and Normal …


Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg Jan 2019

Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg

Graduate Theses, Dissertations, and Problem Reports

Nanoparticles, which measure 100 nm in at least one dimension, have surged in development, production, and use for a wide range of applications. However, the rapid pace of development for these emerging materials with unclear/unknown toxicity profiles makes it difficult to adequately assess health risk associated with exposure. One critical obstacle which limits scientific research to fill these critical knowledge gaps is the lack of accurate and predictive models for nanotoxicology studies, particularly those which involve occupationally relevant exposure scenarios (pulmonary exposure to low dose of particles in the circulating air). Typically, animal models are used to assess potential systemic …