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Biodistribution Comparison Of Fentanyl And Morphine Following Acute And Repeated Expsoure, Rosamond M. Goodson 2024 Virginia Commonwealth University

Biodistribution Comparison Of Fentanyl And Morphine Following Acute And Repeated Expsoure, Rosamond M. Goodson

Theses and Dissertations

The ongoing opioid crisis constitutes a dire public health threat that has resulted in staggering loss of life. In 2021, opioids were implicated in over 75% of the approximately 107,000 deaths attributed to drug overdose (CDC), and synthetic opioids such as fentanyl and its analogues are key drivers of the surge in opioid fatalities in recent years. Although fentanyl is a μ opioid receptor agonist, it has several distinct attributes compared to other drugs in this category, such as morphine. These include enhanced lipophilicity, heightened potency to induce respiratory depression, more rapid entry into the central nervous system, reduced sensitivity …


Therapeutic Intervention Of Neuroinflammation In Alzheimer Disease By Inhibition Of Classical Complement Pathway Using Anti-C1r Loaded Exosomes, Terjahna Richards 2024 Saint John's University, Jamaica New York

Therapeutic Intervention Of Neuroinflammation In Alzheimer Disease By Inhibition Of Classical Complement Pathway Using Anti-C1r Loaded Exosomes, Terjahna Richards

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disease associated with memory decline and cognitive impairment. It is a growing global health and socioeconomic concern, affecting more than 50 million people worldwide. Current therapeutics focus solely on symptomatic management instead of preventative or curative strategies. This is mainly a result of the complexity of the pathophysiological mechanism and the poor understanding of the disease progression. Recently, studies have focused on bridging knowledge gaps giving rise to substantial evidence on the vital role of neuroinflammation in the progression of AD. Neuroinflammation has been shown to be a precursor to apparent amyloid plaque accumulation …


Hjp 272, An Endothelin Receptor Antagonist, And Its Role In Cancer Cell Migration And Invasion, Nabeela Fatima Baig 2024 Saint John's University, Jamaica New York

Hjp 272, An Endothelin Receptor Antagonist, And Its Role In Cancer Cell Migration And Invasion, Nabeela Fatima Baig

Theses and Dissertations

Endothelins are a family of versatile peptides composed of 21 amino acids with three isoforms: ET-1, ET-2, and ET-3. As the most abundant of the three isoforms, ET-1 is involved in various biological processes, such as regulation of vascular tone, humoral homeostasis, and neural crest development. However, focus is now being directed towards investigating the functions of the Endothelin axis in the progression of different tumor types including ovarian, prostate, breast, lungs etc. HJP 272 is a novel ETAR antagonist and while our group has previously researched its effects on lung inflammation and preterm birth, this study marks the first …


Characterizing The Role Of Epigenetic Regulator Menin In Pediatric Neuroblastoma Growth Using Pre-Clinical Models, Rameswari Chilamakuri 2024 Saint John's University, Jamaica New York

Characterizing The Role Of Epigenetic Regulator Menin In Pediatric Neuroblastoma Growth Using Pre-Clinical Models, Rameswari Chilamakuri

Theses and Dissertations

Epigenetic regulators such as Menin and MLL1 drive cancer progression, metastasis, and relapse. MLL1 forms a COMPASS complex with its binding partners, including Menin, to function as an epigenetic enzyme H3K4 methyltransferase. H3K4 methyltransferases are known to promote cancer stem cells' (CSCs) self-renewal capacity and metastasis. CSCs are one of the major causes of tumor relapse and metastasis conditions, ultimately leading to poor overall patient survival. Neuroblastoma (NB) is an extracranial solid tumor that accounts for 8-10% of all pediatric cancers, and approximately 50% of patients display metastasis at the time of diagnosis. In this study, we hypothesized and used …


Opioid System's Potential Involvement In Ketamine's Cognitive And Antidepressant-Like Effects In Rats, Fan Zhang 2024 Virginia Commonwealth University

Opioid System's Potential Involvement In Ketamine's Cognitive And Antidepressant-Like Effects In Rats, Fan Zhang

Theses and Dissertations

Depression stands as one of the most pervasive mental health challenges worldwide, including the United States. Conventional antidepressants typically display a delayed onset of therapeutic action (4-8 weeks) and lack efficacy in a substantial portion of patients (over 40% of depressed patients are treatment-resistant). The dissociative anesthetic ketamine, which is a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, has emerged as a promising novel treatment due to its rapid and prolonged antidepressant effects, and it is especially beneficial for treatment-resistant depression. Nevertheless, the precise neurochemical mechanisms underlying ketamine’s antidepressant properties remain elusive, hampering the development of safer and more efficacious treatments. The present …


Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson 2024 University of Kentucky

Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neuro- behavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical ex- periences in individuals …


Impacts Of Xylazine On Fentanyl Demand, Body Weight, And Acute Withdrawal In Rats: A Comparison To Lofexidine, Safiyah M. Sadek, Shailesh N. Khatri, Zachary A. Kipp, Kelly E. Dunn, Joshua S. Beckmann, William W. Stoops, Terry D. Hinds, Jr., Cassandra D. Gipson 2024 University of Kentucky

Impacts Of Xylazine On Fentanyl Demand, Body Weight, And Acute Withdrawal In Rats: A Comparison To Lofexidine, Safiyah M. Sadek, Shailesh N. Khatri, Zachary A. Kipp, Kelly E. Dunn, Joshua S. Beckmann, William W. Stoops, Terry D. Hinds, Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl’s behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is …


Oxycodone Withdrawal Is Associated With Increased Cocaine Self-Administration And Aberrant Accumbens Glutamate Plasticity In Rats, Shailesh N. Khatri, Hanaa Ulangkaya, Erin E. Maher, Safiyah M. Sadek, Mei Hong, Andrea M. Woodcox, William W. Stoops, Cassandra D. Gipson 2024 Univeristy of Kentucky

Oxycodone Withdrawal Is Associated With Increased Cocaine Self-Administration And Aberrant Accumbens Glutamate Plasticity In Rats, Shailesh N. Khatri, Hanaa Ulangkaya, Erin E. Maher, Safiyah M. Sadek, Mei Hong, Andrea M. Woodcox, William W. Stoops, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Individuals with opioid use disorder (OUD) frequently use other substances, including cocaine. Opioid with- drawal is associated with increased likelihood of cocaine use, which may represent an attempt to ameliorate opioid withdrawal effects. Clinically, 30% of co-using individuals take opioids and cocaine exclusively in a sequential manner. Preclinical studies evaluating mechanisms of drug use typically study drugs in isolation. However, polysubstance use is a highly prevalent clinical issue and thus, we established a novel preclinical model of sequential oxycodone and cocaine self-administration (SA) whereby rats acquired oxycodone and cocaine SA in an A-B-A-B design. Somatic signs of withdrawal were evaluated …


Myokine Probdnf-P75ntr Signaling In Skeletal Muscle Injury And Sterile Inflammation, Katherine Aby 2024 University of South Dakota

Myokine Probdnf-P75ntr Signaling In Skeletal Muscle Injury And Sterile Inflammation, Katherine Aby

Dissertations and Theses

Originally discovered in the brain, brain-derived neurotrophic factor (BDNF) has been shown to be expressed and released from skeletal muscle as a myokine. However, the function of myokine BDNF is not fully understood. Of interest to this study is the function of the BDNF precursor proBDNF in skeletal muscle. We first show that skeletal muscle expresses unique BDNF splice variants compared to the brain, and at the protein level, skeletal muscle expresses significantly more proBDNF than mature BDNF under basal conditions. Consistent with this, expression of major protein convertases in skeletal muscle were significantly lower. The role of myokine proBDNF …


Photoluminescence Switching In Quantum Dots Connected With Fluorinated And Hydrogenated Photochromic Molecules, Ephraiem S. Sarabamoun, Jonathan M. Bietsch, Pramod Aryal, Amelia G. Reid, Maurice Curran, Grayson Johnson, Esther H. R. Tsai, Charles W. Machan, Guijun Wang, Joshua J. Choi 2024 University of Virginia

Photoluminescence Switching In Quantum Dots Connected With Fluorinated And Hydrogenated Photochromic Molecules, Ephraiem S. Sarabamoun, Jonathan M. Bietsch, Pramod Aryal, Amelia G. Reid, Maurice Curran, Grayson Johnson, Esther H. R. Tsai, Charles W. Machan, Guijun Wang, Joshua J. Choi

Chemistry & Biochemistry Faculty Publications

We investigate switching of photoluminescence (PL) from PbS quantum dots (QDs) crosslinked with two different types of photochromic diarylethene molecules, 4,4'-(1-cyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (1H) and 4,4'-(1-perfluorocyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (2F). Our results show that the QDs crosslinked with the hydrogenated molecule (1H) exhibit a greater amount of switching in photoluminescence intensity compared to QDs crosslinked with the fluorinated molecule (2F). With a combination of differential pulse voltammetry and density functional theory, we attribute the different amount of PL switching to the different energy levels between 1H and 2F molecules which result in different potential barrier …


Examining The Effects Of Artemisia Annua On Neuro2a Cells, Wesley Lim 2024 University of Central Florida

Examining The Effects Of Artemisia Annua On Neuro2a Cells, Wesley Lim

Honors Undergraduate Theses

Artemisia annua L. is a well-known medicinal herb used in Traditional Chinese Medicine for many centuries and contains artemisinin, which exhibits antimalarial properties [1] and is a potential treatment for SARS-CoV-2 [2]. However, the neurological effect of A. annua and its compounds are poorly understood. We hypothesize that A. annua extracts and artemisinin will provide protection against oxidative stress in mouse neuronal Neuro2A cells. Superoxide dismutase 1 (SOD1) is an anti-oxidant enzyme that protects against oxidative damage [3]. Growth Arrest and DNA Damage-inducible 45 alpha (Gadd45a) is involved in DNA repair and is a common biomarker for DNA damage[4]. SOD1 …


Corrigendum To "Ssr-Based Molecular Diagnosis For Taiwan Tea Cultivars And Its Application In Identifying Cultivar Composition Of The Processed Tea", 2023 Taiwan Food and Drug Administration

Corrigendum To "Ssr-Based Molecular Diagnosis For Taiwan Tea Cultivars And Its Application In Identifying Cultivar Composition Of The Processed Tea"

Journal of Food and Drug Analysis

No abstract provided.


Acknowledgment Of Reviewers, 2023 Taiwan Food and Drug Administration

Acknowledgment Of Reviewers

Journal of Food and Drug Analysis

No abstract provided.


Application Of The Us Food And Drug Administration’S Sentinel Routine Querying Tools To The Taiwan Sentinel Data Model-Formatted National Health Insurance Research Database, Fang-Ju Lin, Ling-Ya Huang, Chi-Chuan Wang, Sengwee Toh 2023 Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan

Application Of The Us Food And Drug Administration’S Sentinel Routine Querying Tools To The Taiwan Sentinel Data Model-Formatted National Health Insurance Research Database, Fang-Ju Lin, Ling-Ya Huang, Chi-Chuan Wang, Sengwee Toh

Journal of Food and Drug Analysis

The U.S. Food and Drug Administration’s Sentinel System is a leading distributed data network for drug safety surveillance in the world. The National Health Insurance Research Database (NHIRD) in Taiwan was converted into the Taiwan Sentinel Data Model (TSDM) based on the Sentinel Common Data Model (SCDM) version 6.0.2. The goal of this study was to investigate the feasibility of applying the same study designs, analytic choices, and analytic tools as used by the U.S. Sentinel System to examine the same drug-outcome associations in the TSDM-formatted NHIRD. Four known drug-outcome associations previously examined by the U.S. Sentinel System were selected …


Isolation Of Glp-1 Enhancing Indolizidine Alkaloids From Boehmeria Formosana, Ching-Yi Lu, Zheng-Ying Huang, Meng-Chin Chen, Hui-Kang Liu, Shoei-Sheng Lee, Chia-Chuan Chang 2023 School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan, R.O.C.

Isolation Of Glp-1 Enhancing Indolizidine Alkaloids From Boehmeria Formosana, Ching-Yi Lu, Zheng-Ying Huang, Meng-Chin Chen, Hui-Kang Liu, Shoei-Sheng Lee, Chia-Chuan Chang

Journal of Food and Drug Analysis

Boehmeria formosana, with its related species, demonstrates anti-glycemic effect, inhibition of HBV production, anti-cancer activities, etc. Some indolizidine alkaloids from the same genus are bioactive but sensitive to light. To overcome this problem and obtain more phenanthroindolizidine alkaloids, isolation was performed in darkness, yielding 10 new indolizidine alkaloids and 17 known compounds. Among them, seven enhanced glucagon-like receptor 1 (GLP-1) activity at 50 mM, especially 14 and 6 (3.5- and 2.3-fold than the negative control). This procedure yielded bioactive indolizidine alkaloids with novel structures.


An Integrated Strategy To Evaluate Active Substances Of Astragali Radix-Carthami Flos Combination On The Treatment Of Cerebral Ischemia Reperfusion Injury Based On Tqsm Polypharmacokinetics And Pharmacodynamics, Qiang Zeng, Chang Li, Shouchao Xu, Yu He 2023 School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, PR China

An Integrated Strategy To Evaluate Active Substances Of Astragali Radix-Carthami Flos Combination On The Treatment Of Cerebral Ischemia Reperfusion Injury Based On Tqsm Polypharmacokinetics And Pharmacodynamics, Qiang Zeng, Chang Li, Shouchao Xu, Yu He

Journal of Food and Drug Analysis

As a classic herb pair, Astragali Radix-Carthami Flos (AR-CF) has revealed good biological activity in the treatment of cerebral ischemia/reperfusion injury (CI/RI), which remained to be further clarified together with the underlying efficacy related compounds for material basis. In this study, the nine formulations were obtained by L9(34) orthogonal array design of four active fractions (saponin and flavonoid extracted from AR, safflower yellow and safflower red extracted from CF). The concentrations of eleven components and the levels of four biochemical indicators in rat plasma were continuously detected after intragastric administration of nine formulations, respectively. The collected …


Cryptocaryone Induces Apoptosis In Human Hepatocellular Carcinoma Cells By Inhibiting Aerobic Glycolysis Through Akt And C-Src Signaling Pathways, Chen-Lin Yu, Yu-Wei Lai, Jih-Jung Chen, Jie-Jen Lee, Tsung-Hsien Chou, Chen-Chen Huang, Shih-Chia Liu, Guang-Wei Chen, Chung‐Hsin Tsai, Shih-Wei Wang 2023 Institute of Biomedical Science, MacKay Medical College, New Taipei City, Taiwan

Cryptocaryone Induces Apoptosis In Human Hepatocellular Carcinoma Cells By Inhibiting Aerobic Glycolysis Through Akt And C-Src Signaling Pathways, Chen-Lin Yu, Yu-Wei Lai, Jih-Jung Chen, Jie-Jen Lee, Tsung-Hsien Chou, Chen-Chen Huang, Shih-Chia Liu, Guang-Wei Chen, Chung‐Hsin Tsai, Shih-Wei Wang

Journal of Food and Drug Analysis

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with the second highest mortality rate in all cancer. Energy reprogramming is one of the hallmarks of cancer, and emerging evidence showed that targeting glycolysis is a promising strategy for HCC treatment. Cryptocaryone has been shown to display promising anti-cancer activity against numerous types of cancer. Previous study also indicated that cryptocaryone induces cytotoxicity by inhibiting glucose transport in cancer cells, but the detailed mechanism still needs to be elucidated. Therefore, this study aimed to investigate the relationship between the anti-cancer effect and glycolytic metabolism of cryptocaryone in human …


Dehulled Adlay (Coix Lachryma-Jobi L.) Ameliorates Hepatic Gluconeogenesis And Steatosis In Streptozotocin/High-Fat Diet-Induced Diabetic Rats, Shing-Hwa Liu, Wan-Hsin Wu, Huei-Ping Tzeng, Wenchang Chiang, Meng-Tsan Chiang 2023 Institute of Toxicology, National Taiwan University, Taipei, Taiwan

Dehulled Adlay (Coix Lachryma-Jobi L.) Ameliorates Hepatic Gluconeogenesis And Steatosis In Streptozotocin/High-Fat Diet-Induced Diabetic Rats, Shing-Hwa Liu, Wan-Hsin Wu, Huei-Ping Tzeng, Wenchang Chiang, Meng-Tsan Chiang

Journal of Food and Drug Analysis

Adlay (Coix lachryma-jobi L.) is a traditional Chinese herbal medicine with various biological activities. We investigated the anti-diabetic effects of different parts of adlay seeds, including polished adlay (PA), adlay bran (AB) and dehulled adlay (DA) in a streptozotocin (STZ)/high fat diet (HFD) diabetic rat model (DM). DM rats supplemented with or without PA (43%), AB (3%), or DA (46%) diet for 8 weeks. The plasma glucose and insulin levels and the insulin resistance index (HOMA-IR) were increased in DM group; among the three adlay diets, DA has the best effects attenuating all of these alterations in DM …


Biological And Clinical Significance Of The Age-Rage Axis In The Aggressiveness And Prognosis Of Prostate Cancer, Shih-Hong Khoo, Pei-Ru Wu, Kun-Tu Yeh, Shih-Lan Hsu, Chi-Hao Wu 2023 School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan

Biological And Clinical Significance Of The Age-Rage Axis In The Aggressiveness And Prognosis Of Prostate Cancer, Shih-Hong Khoo, Pei-Ru Wu, Kun-Tu Yeh, Shih-Lan Hsu, Chi-Hao Wu

Journal of Food and Drug Analysis

Dietary factors and chronic hyperglycemia are linked to the formation of advanced glycation end products (AGEs) and prostate cancer (PCa) risk. The activation of the receptor for AGEs (RAGE) acts as a bridge between various RAGE ligands and certain malignancies. This study showed that the interaction of AGEs and RAGE promoted PCa cell proliferation, invasion, and autophagy-mediated survival in response to chemotherapeutic agents. RAGE-overexpressed PCa cells underwent epithelial-mesenchymal transition and showed increased cancer stem cell-like properties. In mouse xenograft models, RAGE-overexpressed cells showed more substantial tumorigenic capacity than parental cells, whereas RAGE knockdown decreased tumorigenicity. The clinical data validated a …


Steamed Daylily Flower (Hemerocallis Fulva L.) Protected Cardiac And Hepatic Cells Against Ethanol Induced Apoptotic And Oxidative Damage, Sheng-Lei Yan, Wen-Tzu Wu, Mei-Chin Mong, Mei-Chin Yin 2023 Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua County, Taiwan

Steamed Daylily Flower (Hemerocallis Fulva L.) Protected Cardiac And Hepatic Cells Against Ethanol Induced Apoptotic And Oxidative Damage, Sheng-Lei Yan, Wen-Tzu Wu, Mei-Chin Mong, Mei-Chin Yin

Journal of Food and Drug Analysis

Our previous study examined the phytochemical composition and bio-activities of raw daylily flower (Hemerocallis fulva L.). However, this plant food is usually served via heat process such as cooking in a soup. This study aimed to investigate the phytochemical profile and biofunctions of steamed daylily flower (SDF). The content of total phenolic acids, total flavonoids, total carotenoids, total anthocyanins and total triterpenoids in SDF aqueous extract was assessed. Normal cardiac and hepatic cells, H9c2 and L-02 cells, were used to evaluate the protective effects of SDF against ethanol. SDF concentrations of 0.25%, 0.5%, and 1% were applied to treat …


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