Medicinal Chemistry and Pharmaceutics Commons^™

Efficacy Of Mcl-1 Inhibitors In Multiple Myeloma Cells Resistant To Bortezomib, Emily Nelson, Omar S. Al-Odat, Sabrina M. Paparo, Daniel A. Guirguis, Gabriella Yao, Manoj Pandey, Subash Jonnalagadda, Tulin Budak-Alpdogan

Rowan-Virtua Research Day

Multiple myeloma (MM) is a type of cancer that affects plasma B cells. Patients with MM often experience frequent relapses and can develop resistance to drugs. As a medical researcher, it is important to understand the role of Mcl-1 in preventing intrinsic apoptosis and drug resistance. Mcl-1 belongs to the anti-apoptotic subgroup of Bcl-2 family proteins and plays a crucial role in these processes. Mcl-1 plays a crucial role in driving disease progression and contributing to drug resistance in MM. It has been observed that there is an increased expression of Mcl-1 in 52% of patients with MM during diagnosis, …

Intra-Accumbens Microinfusion Of The Dopamine D3 Receptor Partial Agonist (±)Vk4-40 Does Not Affect Basal Locomotion In Mice, Yeonwoo Sim, Nicole M. Hinds, Amy Hauck Newman, Daniel F. Manvich

Rowan-Virtua Research Day

The opioid epidemic remains a pressing public health crisis, prompting the search for alternative pharmacotherapies for Opioid Use Disorder (OUD). This study explores the potential of the dopamine D3 receptor (D3R) partial agonist, (±)VK4-40, as a novel treatment option. We investigated the impact of intra-nucleus accumbens (NAc) microinfusion of VK4-40 on basal locomotion in mice. Results indicate that VK4-40 did not significantly alter basal locomotion, suggesting that its therapeutic effects may not be mediated through disruptions in generalized motor function. Future research will focus on elucidating the neuropharmacological mechanisms underlying VK4-40's therapeutic actions and exploring its effects on psychostimulant-induced hyperlocomotion. …

The Revolutionary St. Louis Insane Asylum, Julia Talbert

Undergraduate Research Symposium

Even with its grand structure on Arsenal Street towering over the city below, few residents of St. Louis and surrounding areas are aware of the grand history or even existence of the St. Louis Insane Asylum. The building is over 150 years old and was a place of hope, failure, strife, and empathy. The asylum had a large impact on St. Louis and provided revolutionary outlooks, unique perspectives, and curious therapies.

An Acute Herb-Drug Interaction Of Magnoliae Officinalis Cortex With Methotrexate Via Inhibiting Multidrug Resistance-Associated Protein 2, Chung-Ping Yu, Pei-Ying Li, Szu-Yu Chen, Shiuan-Pey Lin, Ying-Chen Chen, Lu-Ching Ho, Yow-Wen Hsieh, Yu-Chi Hou

Journal of Food and Drug Analysis

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX …

An Auxiliary Strategy Of Partial Least Squares Regression In Pharmacokinetic/Pharmacodynamic Studies: A Case Of Application Of Guhong Injection In Myocardial Ischemia/Reperfusion Rats, Hai-Yang Chen, Chang Li, Chong-Yu Shao, Yu-Jia Wu, Hai-Tong Wan, Yu He

Journal of Food and Drug Analysis

Guhong injection (GHI) has been applied in the therapy of cardio-cerebrovascular disease in clinic, but there is no report about the pharmacokinetic/pharmacodynamic (PK/PD) research on GHI treating myocardial ischemia/reperfusion (MI/R) injury in rats. In this study, eight compounds of GHI in plasma, including N-acetyl-L-glutamine (NAG), chlorogenic acid (CGA), hydroxysafflor yellow A (HSYA), p-coumaric acid (pCA), rutin, hyperoside, kaempferol-3-O-rutinoside, and kaempferol-3-O-glucoside, were quantified by LC-MS/MS. We discovered that the values of t_1/2β, k₁₂, V₂, and CL₂ were larger than those of t_1/2α, k₂₁, V₁, and …

Ionizable Copolymer Functionalized Magnetic Nanocomposite As An Adsorbent For Boosting The Extraction Selectivity Of Aristolochic Acids, Qi-Yue Xie, Yang Chen, Chang-Jun Li, Jia-Bin Zhang, Xiu-Jun Cao, Jun Lu

Journal of Food and Drug Analysis

Aristolochic acid nephropathy (AAN) has drawn increasing public attention. Organic anion transporters (OATs) are considered to be responsible for mediating nephrotoxicity of aristolochic acids (AAs), as AAs are typical OAT1 substrates that exhibit anionic properties and contain one hydrophobic domain. Inspired by the OAT1 three-dimensional structure or substrate/protein interactions involved in transport, we designed a magnetic polymeric hybrid, mimicking the effect of basic and aromatic residues of OAT1, for efficient enriching aristolochic acid I (AA I) and aristolochic acid II (AA II) in Traditional Chinese patent medicines (TCPM). N, N-dimethylaminopropyl acrylamide (DMAPAm) was used as a cationic monomer and copolymerized …

Effect Of Indian Gooseberry Extract On Improving Methylglyoxal-Associated Leptin Resistance In Peripheral Tissues Of High-Fat Diet-Fed Rats, Sheng-Yi Chen, Yue-Ning Huang, Jer-An Lin, Gow-Chin Yen

Journal of Food and Drug Analysis

Increased leptin resistance and methylglyoxal (MG) levels are observed in obese patients. However, whether MG deposits contribute to leptin resistance, oxidative stress, and inflammation in peripheral tissues remains unclear. In addition, the edible fruit of Indian gooseberry (Phyllanthus emblica L.) contains abundant bioactive components such asvitamin C, β-glucogallin (β-glu), gallic acid (GA), and ellagic acid (EA). Water extract of Indian gooseberry fruit (WEIG) and GA has been shown to improve cognitive decline by suppressing brain MG-induced insulin resistance in rats administered a high-fat diet (HFD). Accordingly, this study investigated the functions of WEIG and GA in inhibiting MG-induced leptin …

Pomelo (Citrus Grandis (L.) Osbeck) Sponge Layers As A Potential Source Of Soluble Dietary Fiber: Evaluation Of Its Physicochemical, Structural And Functional Properties, Xiaowei Chen, Jiajia Chen, Jian Peng, Yuanshan Yu, Jijun Wu, Jing Wen, Zhiying Kang, Yanhui Wang, Yujuan Xu, Lu Li

Journal of Food and Drug Analysis

Pomelo sponge layer (PSL) had been considered as a potential source of soluble dietary fiber (SDF), while they were mostly disposed of as waste. To promote high-value utilization of pomelo wastes, this study extracted SDF from PSL of six varieties of pomelo, and their physicochemical, structural and functional properties were investigated. Results indicated that all PSL-SDFs showed good physicochemical and functional properties. Among them, PSL-SDF from grapefruit (GRSDF) showed better water holding capacity and swelling capacity, whereas Shatian pomelo PSL-SDF and Guanxi pomelo PSL-SDF had the highest thermal stability and oil holding capacity, respectively. Furthermore, compared with other PSL-SDFs, GRSDF …

Trans-2-Nonadecyl-4-(Hydroxymethyl)-1,3-Dioxolane (Tnhd) Purified From Freshwater Clams Markedly Alleviates Dimethylnitrosamine-Induced Hepatic Fibrosis, Ya-Ru Kuo, Chen-Yu Tsai, Wei-Sheng Lin, Chi-I Chang, Ching-Shu Lai, Min-Hsiung Pan

Journal of Food and Drug Analysis

Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression …

Human Mitragynine And 7-Hydroxymitragynine Pharmacokinetics After Single And Multiple Daily Doses Of Oral Encapsulated Dried Kratom Leaf Powder, Marilyn A. Huestis, Martin A. Brett, John Bothmer, Ramsey Atallah

Institute of Emerging Health Professions Faculty Papers

Kratom leaves, consumed by millions worldwide as tea or ground leaf powder, contain multiple alkaloids, with mitragynine being the most abundant and responsible for most effects. Mitragynine is a partial µ-opioid receptor agonist and competitive antagonist at κ- and δ-opioid receptors; however, unlike morphine, it does not activate the β-arrestin-2 respiratory depression pathway. Due to few human mitragynine data, the largest randomized, between-subject, double-blind, placebo-controlled, dose-escalation study of 500–4000 mg dried kratom leaf powder (6.65–53.2 mg mitragynine) was conducted. LC-MS/MS mitragynine and 7-hydroxymitragynine plasma concentrations were obtained after single and 15 daily doses. Mitragynine and 7-hydroxymitragynine C_max increased dose …

Metabolic Stability And Metabolite Identification Of N-Ethyl Pentedrone Using Rat, Mouse And Human Liver Microsomes, Alexandre Barcia Godoi, Natalícia De Jesus Antunes, Kelly Francisco Cunha, Aline Franco Martins, Marilyn A. Huestis, Jose Luiz Costa

Institute of Emerging Health Professions Faculty Papers

New Psychoactive Substances (NPSs) are defined as a group of substances produced from molecular modifications of traditional drugs. These molecules represent a public health problem since information about their metabolites and toxicity is poorly understood. N-ethyl pentedrone (NEP) is an NPS that was identified in the illicit market for the first time in the mid-2010s, with four intoxication cases later described in the literature. This study aims to evaluate the metabolic stability of NEP as well as to identify its metabolites using three liver microsomes models. To investigate metabolic stability, NEP was incubated with rat (RLM), mouse (MLM) and human …

The Biobehavioral Effects Of Embryonic Exposure To Neural Inflammation And Oxidative Stress In Zebrafish, Dalton J. Anderson

Honors College Theses

The purpose of this research is to improve understanding of the neurodevelopmental effects of embryonic exposure to elevated inflammation and oxidative stress induced by the antipyretic drug acetaminophen (APAP). Our study was the first to examine the interactive effects of APAP and inflammation in zebrafish embryos and how the treatments affect brain development and larval behavior. Experimental groups of zebrafish larvae were exposed to lipopolysaccharide (LPS) to induce inflammation, APAP, or LPS + APAP and larval behavior was analyzed using Ethovision automated behavioral tracking software. We also measured changes in whole-brain Glycogen Synthase Kinase 3 Beta (GSK3B) and GSK3B phosphorylation, …

Melittin: A Natural Component Of Honeybee Venom As A Potential Anti-Cancer Therapy, Niamh Donnellan, Anne M. Friel

SURE Journal: Science Undergraduate Research Experience Journal

Cancer is a major cause of death worldwide and while chemotherapy is the main approach there are many negative associations in current treatment procedures. These include lack of selectivity, side effects and drug resistance. The hallmarks of cancer are a fundamental concept which aids the development of new means to treat human cancers through the understanding of the acquisition of these hallmarks from cells.

Melittin is a major peptide component of bee venom which has shown to be efficacious as an anticancer agent in preclinical and animal models. Melittin has many biological functions including pore formation in the phospholipid bilayer …

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

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

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

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

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

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

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 …