Pharmacology Commons^™

Elucidation Of Molecular Mechanisms Underlying Novel Multi-Targeted Therapy Strategies For, Qianqian Hu

USF Tampa Graduate Theses and Dissertations

EML4-ALK fusion non-small cell lung cancer (NSCLC) represents a distinct subset of lung cancers that possesses unique molecular and clinical features, paving the way for targeted therapeutic interventions. Despite the promise of ALK-directed therapies, challenges such as metastasis at the time of diagnosis and treatment resistance persist, necessitating deeper research into the underlying mechanisms and potential solutions. In the context of these challenges, our study embarked on two specific objectives. The first goal, elucidated in Chapter 2, revolved around brain metastasis, an event critically facilitated by cell migration. Here, we assessed the anti-migratory activities of several clinical ALK inhibitors in …

Enteroendocrine Cell Regulation Of The Gut-Brain Axis, Joshua Barton, Annie Londregan, Tyler Alexander, Ariana Entezari, Manuel Covarrubias, Scott Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Enteroendocrine cells (EECs) are an essential interface between the gut and brain that communicate signals about nutrients, pain, and even information from our microbiome. EECs are hormone-producing cells expressed throughout the gastrointestinal epithelium and have been leveraged by pharmaceuticals like semaglutide (Ozempic, Wegovy), terzepatide (Mounjaro), and retatrutide (Phase 2) for diabetes and weight control, and linaclotide (Linzess) to treat irritable bowel syndrome (IBS) and visceral pain. This review focuses on role of intestinal EECs to communicate signals from the gut lumen to the brain. Canonically, EECs communicate information about the intestinal environment through a variety of hormones, dividing EECs into …

Assessing The Potentiation Of The (Alpha4)3(Beta2)2 Nicotinic Acetylcholine Receptor By Analogs Of The Allosteric Agonist Cmpi, Josue Gaona, Marcos Bermudez, Wilder Felix, Amaya Rolling, Ganesh Thakur, Ayman K. Hamouda

School of Medicine Student Publications and Presentations

The (α4)3(β2)2 nicotinic acetylcholine receptor (nAChR) is the major heteromeric nAChR isoform expressed in the cortex and is believed to play a role in memory, cognition, and neuronal survival during aging. As such, selective potentiators of the (α4)3(β2)2 nAChR have potential therapeutic benefits in conditions associated with decline in the output of nAChR in the brain. In previous work, we have studied the pharmacology of the allosteric agonist CMPI (3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)- 1H-pyrazol-4-yl) isoxazole) at the (α4)3(β2)2 nAChR and identified its binding site at the α4:α4 subunit extracellular interface. As part of our ongoing efforts to define structural features that confer CMPI …

Synthetic Contraceptive Hormones Occlude The Ability Of Nicotine To Reduce Ethanol Consumption In Ovary-Intact Female Rats, Erin E. Maher, Ashley M. White, Ashley Craig, Shailesh N. Khatri, Percell T. Kendrick Jr., Mary E. Matocha, Emma O. Bondy, Nikhil Pallem, Grace W. Breakfield, Madison Botkins, Olivia Sweatt, William C. Griffin, Brent A. Kaplan, Jessica Jane Weafer, Joshua S. Beckmann, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Rates of tobacco and alcohol use in women are rising, and women are more vulnerable than men to escalating tobacco and alcohol use. Many women use hormonal birth control, with the oral contraceptive pill being the most prevalent. Oral contraceptives contain both a progestin (synthetic progesterone) and a synthetic estrogen (ethinyl estradiol; EE) and are contraindicated for women over 35 years who smoke. Despite this, no studies have examined how synthetic contraceptive hormones impact this pattern of polysubstance use in females. To address this critical gap in the field, we treated ovary-intact female rats with either sesame oil (vehicle), the …

Neuroendocrine Regulation Of Chemokine Receptor-Mediated Leukocyte Migration Via Heteromeric G Protein-Coupled Receptor Complexes, Garrett Enten

USF Tampa Graduate Theses and Dissertations

Neuroendocrine regulation of the innate immune system is a well-documentedphenomenon. The underlying mechanisms, however, are not well understood. Here we show that at least 20 members of the human chemokine receptor (CR) family heteromerize with one or more members of the α1-adrenergic receptor (AR) family and that all CRs, apart from CXCR1, heteromerize with arginine vasopressin receptor 1A (AVPR1A) in recombinant systems. These heteromeric complexes are detectable in human monocytes and the monocytic leukemia cell line THP-1. Though currently technical limitations prevent the direct visualization of endogenously expressed higher-order hetero-oligomeric receptor complexes, we provide evidence through functional analysis and proximity-based …

Antidiabetic Potential Of Vitex Mombassae Fruits Extract In Streptozotocin-Nicotinamide Induced Diabetic Wistar Rat Model, Mussa B. Mbegeze, Joan J.E. Munissi, Flora Stephano, Ramadhani S.O. Nondo, Stephen S. Nyandoro

Tanzania Journal of Science

Besides changes in life styles and improper dietary patterns, the rapidly increasing burden of diabetes mellitus type 2 is correlated with antidiabetic agents currently in clinical use, which are costly, less effective, and present undesirable side effects. Natural products from plants are promising alternative sources for developing more effective and cost friendly antidiabetic agents. This study therefore investigated the antidiabetic potential of Vitex mombassae fruits extract (VMFE) in streptozotocin-nicotinamide induced diabetic Wistar rat model. Oral acute toxicity test was conducted in male Wistar rat using up and down method by following OECD Guideline 423 (2002). No clinical signs of toxicity …

Anticancer Potential Of The Leaf Extracts From The Selected Croton Species, Peter V. Fayyu, Joan J.E. Munissi, Stephen S. Nyandoro, Flora Stephano

Tanzania Journal of Science

The reported investigations were aimed at establishing anticancer potential of the leaf extracts from Croton dictyophlebodes (CDE), C. kilwae (CKE) and C. longipedicellatus ssp austrotanzanicus (CLE). In vitro cytotoxicity assays of the extracts were performed against human laryngeal cancer cell line (HEp-2) and human breast cancer cell line (MCF-7), while in vivo toxicological studies were done using Swiss albino mice (Mus musculus) following the Organization for Economic Cooperation and Development guideline number 423 of 2001. Results for in vitro assays revealed that CDE and CLE induced cytotoxicity to MCF-7 and HEp-2 cell lines at EC50 values of 86 and 63 …

Ethnobotanical Survey On The Knowledge And Use Of Medicinal Plants For Malaria Management Among University Students, Felista W. Mwingira, Deokary J. Matiya, Neema G. Mogha

Tanzania Journal of Science

Malaria remains a public health problem in Tanzania, escalated by the emergence of both parasite and vector resistance. Plant-based traditional medicines have been widely utilized as alternatives to malaria management. However, proper documentation is minimal, especially among the younger generation. This study assessed the knowledge of medicinal plants for malaria management among 532 Dar es Salaam University College of Education students. Overall, twenty-four plant species, most belonging to the family Asteraceae, were identified with Azaradichta indica being the most dominant species. These results reveal a substantial knowledge of medicinal plants for malaria management among university students.

Piperine Encourages Apoptosis In Human Cervical Adenocarcinoma Cells Through Ros Generation, Dna Fragmentation, Caspase-3 Activation And Cell Cycle Arrest, Asif Jafri, Juhi Rais, Sudhir Kumar, Md Arshad

Research Symposium

Background: Cancer is one of the most common destructive diseases and the second leading cause of death in humans. Among cancer, cervical cancer is the second most common malignancy among women globally. Thus, there is a continuous need to search for chemotherapeutic chemicals or naturally occurring drugs to resolve this global health problem. Piperine (1-piperoylpeperdine) is present in the fruits of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). It possesses several pharmacological properties and in the present study we have evaluated its anti-cancer potential on human cervical adenocarcinoma (HeLa) cells.

Methods: The anti-proliferative effect …

Adipocyte-Derived Pxr Signaling Is Dispensable For Diet-Induced Obesity And Metabolic Disorders In Mices, Fang Wang, Jinwei Liu, Rebecca Hernandez, Se-Hyung Park, Ying-Jing Lai, Shuxia Wang, Bruce Blumberg, Changcheng Zhou

UK CARES Faculty Publications

Pregnane X receptor (PXR) is a xenobiotic receptor that can be activated by numerous chemicals including endogenous hormones, dietary steroids, pharmaceutical agents, and environmental chemicals. PXR has been established to function as a xenobiotic sensor to coordinately regulate xenobiotic metabolism by regulating the expression of many enzymes and transporters required for xenobiotic metabolism. Recent studies have implicated a potentially important role for PXR in obesity and metabolic disease beyond xenobiotic metabolism, but how PXR action in different tissues or cell types contributes to obesity and metabolic disorders remains elusive. To investigate the role of adipocyte PXR in obesity, we generated …

New Insights On The Differential Interaction Of Sulfiredoxin With Members Of The Peroxiredoxin Family Revealed By Protein-Protein Docking And Experimental Studies, Murli Mishra, Hong Jiang, Qiou Wei

Markey Cancer Center Faculty Publications

Sulfiredoxin (Srx) is the enzyme that restores the peroxidase activity of peroxiredoxins (Prxs) through catalyzing the reduction of hyperoxidized Prxs back to their active forms. This process involves protein-protein interaction in an enzyme-substrate binding manner. The integrity of the Srx-Prx axis contributes to the pathogenesis of various oxidative stress related human disorders including cancer, inflammation, cardiovascular and neurological diseases. The purpose of this study is to understand the structural and molecular biology of the Srx-Prx interaction, which may be of significance for prediction of target site for the novel drug-discovery. Homology modeling and protein-protein docking approaches were applied to examine …

Jinhua Qinggan Granule Uhplc-Q-Extractive-Orbitrap-Ms Assay: Putative Identification Of 45 Potential Anti-Covid-19 Constituents, Confidential Addition, And Pharmacopoeia Quality-Markers Recommendation, Jingyuan Zeng, Xican Li, Rongxin Cai, Chunhou Li, Shaoman Chen

Journal of Food and Drug Analysis

The study combined UHPLC-Q-Orbitrap-MS analysis with authentic standards, to create a novel strategy for isomers recognition and putative identification. Through the strategy, anti-Covid-19 Jinhua Qinggan Granule was found to comprise 28 isomers and 45 potential anti-Covid-19 constituents. The detection of three constituents (Danshensu, cryptotanshin, and tanshinone IIA) suggests Danshen as confidential additive. Based on this, 6 constituents are recommended as quality-marker candidates, including chlorogenic acid, acteoside, peimisine, baicalein, licoricesaponin H2, and tanshinone IIA. Obviously, the study can not only help the public to really understand the Granule's formula and chemistry, but also facilitate its Pharmacopoeia collection in future.

Autophagy-Urea Cycle Pathway Is Essential For The Statin-Mediated Nitric Oxide Bioavailability In Endothelial Cells, Wen-Hua Chen, Bei-Chia Guo, Chia-Hui Chen, Man-Chen Hsu, Chih-Hsien Wang, Tzong-Shyuan Lee

Journal of Food and Drug Analysis

Statins induce nitric oxide (NO) bioavailability by activating endothelial nitric oxide synthase via kinase- and calciumdependent pathways in endothelial cells (ECs). However, their effect on the metabolism of L-arginine, the precursor for NO biosynthesis, and regulatory mechanism have not yet been investigated. In this study, we investigated the role of the autophagy–urea cycle-L-arginine pathway in simvastatin-mediated NO bioavailability in ECs. Griess's assay was used to determine the NO bioavailability. Protein expression was assessed using Western blot analysis. Further, immunocytochemistry was performed to observe autophagosome formation, while conventional assay kits were used to quantify the levels of different intermediate substrates of …

Identification For Metabolism Profiles And Pharmacokinetic Studies Of Tradition Chinese Prescription Ji-Ming-San And Its Major Metabolites In Rats By Uhplc-Q-Tof-Ms/Ms And Uhplc-Ms/Ms, Cheng-Yang Hsieh, Ching-Chiung Wang, Lemmuel L. Tayo, Po-Wei Tsai, Chia-Jung Lee

Journal of Food and Drug Analysis

Ji-Ming-Shan (JMS) is a traditional prescription use for patients with rheumatism, tendons swelling, athlete's foot, diuresis and even gout. This study developed a rapid and sensitive method for the analysis of JMS chemical components in the Traditional Chinese medicine (TCM) prescription and in the serum samples of rats which were administered with the herbal extract. Two mass spectrometric approaches were used namely Ultra-performance liquid chromatographyquadrupole time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) method for the major metabolites of the JMS extract while Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for the detection of the JMS metabolites in the sera of rats. It was …

Cordycepin Inhibits Erk Pathway To Suppress Fgf9-Induced Tumorigenesis With Ma-10 Mouse Leydig Tumor Cells, Li-Ching Chen, Chin-Ying Chen, Yi-Ping Lee, Bu-Miin Huang

Journal of Food and Drug Analysis

Fibroblast growth factor 9 (FGF9) is a member of FGF family, and abnormal expression of FGF9 can promote tumorigenesis. Cordycepin, a major bioactive component in fungus Cordyceps sinensis, could suppress various tumors. We have shown that cordycepin could inhibit FGF9-induced testicular tumor growth in vitro and in vivo with MA-10 mouse Leydig tumor cells. In the present study, the mechanisms related to apoptosis and autophagy were determined. Results show that cordycepin significantly suppressed cell viability and colony formation with correlatedly morphological change related to cell death in FGF9-treated MA-10 cells. Flow cytometry and western blotting results further demonstrate that …

An Integrative Approach For Compressive Quality Control Of Respireaidtm, A Traditional Chinese Medicine Formula Against Sars-Cov-2, Kun-Teng Wang, Chia-Jung Lee, Ming-Chung Lee, Chao-Yu Chen, Yun-Chen Tsai, Wu-Chang Chuang

Journal of Food and Drug Analysis

RespireAid™ (NRICM101) is an effective anti-SARS-CoV-2 traditional Chinese medicine formula and has been licensed as a drug or dietary supplement in Taiwan, Luxembourg, Australia, Singapore, Cambodia, Philippines, and Canada. In this study, we provided integrated quality control strategy to analyze the ingredient of RespireAid™. In addition, the lot-to-lot efficacy stabilities were also evaluated. We found that RespireAid™ comprised of monosaccharides and disaccharides (34.0%), maltodextrin (23.5%), inorganic elements and ash (12.2%), oligosaccharides and polysaccharides (11.4%), principal components (4.4%), moisture (4.0%), amino acids (3.5%), b-Cyclodextrin (0.25%), menthol (0.25%), and nucleotides (0.14%), while the remainder was unidentified (6.36%). This is the first time …

Attenuation Of Diabetes-Mediated Muscle Atrophy In Rats By Fish Oil Enriched Omega-3 Polyunsaturated Fatty Acids Supplementation, Shing-Hwa Liu, Wei-Hsuan Lin, Huei-Ping Tzeng, Meng-Tsan Chiang

Journal of Food and Drug Analysis

Diabetes is associated with an increased risk of muscle wasting/atrophy, which adversely affects quality of life. We hypothesized that long term supplementation of fish oil may have protective effects against sarcopenia or muscle atrophy in streptozotocin (STZ) and high-fat (HF) diet-induced diabetic rat model. Wistar rats at age of 7 weeks were injected with saline or STZ to induce hyperglycemia. After one week, they were fed on a normal control diet or HF diet with/without supplementation of fish oil for 18 weeks. Feeding diabetic rats with a fish oil-enriched diet alleviated body weight loss and the impaired glucose tolerance using …

Ssr-Based Molecular Diagnosis For Taiwan Tea Cultivars And Its Application In Identifying Cultivar Composition Of The Processed Tea, Chih-Yi Hu, Hsien-Tung Tsai, Chui-Feng Chiu, Tsung-Chen Su, Nguyen Hoang Khoi Le, Shu-Dan Yeh

Journal of Food and Drug Analysis

Taiwan specialty teas are produced with distinct manufacturing processes from specific cultivars of tea plants in Camellia. Due to the widespread transplantation of Taiwan tea cultivars and active international trading of tea materials, an accurate and reliable method to identify tea cultivars at the border is vital to protect the image of premium Taiwan specialty teas. In this study, we introduced the Taiwan Tea Variety Identification (TTVID) kit, a capillary electrophoresis-based multiplex PCR assay consisting of 12 simple sequence repeat (SSR) markers. A database composing these 12 SSR loci genotypes in 144 cultivars was established for marker assessment and …

Determination And Evaluation Of Epa And Dha Ethyl Esters In Fish Oils Using The Tmah Transesterification Method, Pai-Wen Wu, Ching-Hsuan Tsai, Ching-Yu Hsu, Shu-Han Chang, Ya-Min Kao, Su-Hsiang Tseng, Der-Yuan Wang

Journal of Food and Drug Analysis

A simple and dependable technique, known as THAM method, has been developed to detect and measure ethyl eicosapentaenoate (EE-EPA) and ethyl docosahexaenoate (EE-DHA) in encapsulated fish oils. This technique involves using tetramethylammonium hydroxide (TMAH) as a catalyst, followed by analysis using gas chromatography equipped with a flame ionization detector. Recoveries of EE-EPA and EE-DHA spiked between 5 mg/g and 20 mg/g were found to be between 90.8% and 95.2%, with coefficients of variation ranging from 0.2% to 2.5%, demonstrating the accuracy and precision of the technique. Additionally, its limitation of quantitation of EE-EPA and EE-DHA in fish oil samples was …

Cannabis Sativa L.: A Comprehensive Review On Legislation, Decriminalization, Phytochemistry, Antimicrobial Activity, And Safety, Mohammed Dalli, Salah-Eddine Azizi, Ali Azghar, Abderrazak Saddari, Elmostapha Benaissa, Yassine Ben Lahlou, Mostafa Elouennass, Adil Maleb

Journal of Food and Drug Analysis

Throughout history, medicinal and aromatic plants have been used extensively to cure a variety of ailments. This article provides a comprehensive overview of Cannabis sativa, specifically focusing on its legislative status, decriminalization, phytochemistry, antimicrobial activity, and safety. The study begins by briefly outlining the plant's history, including its cultivation, harvesting, and storage methods. The review analyzes extensively the antimicrobial properties of Cannabis sativaand its derivatives, specifically examining their reported antiviral, antibacterial, antifungal, and antiparasitic capabilities, which have been documented in databases such as Scopus, ScienceDirect, PubMed, and Web of Science. The paper also discusses trends in studies about the …