Chemicals and Drugs Commons^™

Cardiovascular Effects Of Excess Growth Hormone: How Real Is The Threat?, Frederick Berro Rivera, Marianne Katharina Taliño, Marie Francesca Ansay, Gerard Francis Mangubat, Mer Lorraine Mahilum, Rajiv Hans Menghrajani, Siena Placino, Sung Whoy Cha, John Paul Aparece, Marc Gregory Yu, Michael Lawrenz Co, Edgar Lerma, Krishnaswami Vijayaraghavan, Peter A. Mccullough

Division of Cardiology Faculty Papers

Patients with acromegaly carry a high risk of developing cardiovascular diseases (CVD). In fact, CVD is the leading cause of mortality among this group of patients. The most frequent cardiovascular complications are heart failure (HF), valvular disease, hypertension, arrhythmias, and coronary artery disease (CAD). The pathophysiology centers on the family of growth hormone (GH). These hormones are involved in normal cardiac development and function; however, excess of insulin-like growth factor-1 (IGF-1), the principally active hormone, can also cause negative effects on the cardiovascular system. HF in acromegaly usually presents with biventricular enlargement and diastolic dysfunction and is strongly associated with …

Amphiphilic Cell-Penetrating Peptides Containing Arginine And Hydrophobic Residues As Protein Delivery Agents, Jonathan Moreno, Khalid Zoghebi, David Salehi, Lois Kim, Sorour Khayyatnejad Shoushtari, Rakesh K. Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The entry of proteins through the cell membrane is challenging, thus limiting their use as potential therapeutics. Seven cell-penetrating peptides, designed in our laboratory, were evaluated for the delivery of proteins. Fmoc solid-phase peptide synthesis was utilized for the synthesis of seven cyclic or hybrid cyclic–linear amphiphilic peptides composed of hydrophobic (tryptophan (W) or 3,3-diphenylalanine (Dip) and positively-charged arginine (R) residues, such as [WR]4, [WR]9, [WWRR]4, [WWRR]5, [(RW)5K](RW)5, [R5K]W7, and [DipR]5. Confocal microscopy was used to screen the peptides as a protein delivery system of model cargo proteins, green and red fluorescein proteins (GFP and RFP). Based on the confocal …

Circulating Plasma Exosomal Proteins Of Either Shiv-Infected Rhesus Macaque Or Hiv-Infected Patient Indicates A Link To Neuropathogenesis, Partha K. Chandra, Stephen E. Braun, Sudipa Maity, Jorge A. Castorena-Gonzalez, Hogyoung Kim, Jeffrey G. Shaffer, Sinisa Cikic, Ibolya Rutkai, Jia Fan, Jessie J. Guidry, David K. Worthylake, Chenzhong Li, Asim B. Abdel-Mageed, David W. Busija

School of Medicine Faculty Publications

Despite the suppression of human immunodeficiency virus (HIV) replication by combined antiretroviral therapy (cART), 50–60% of HIV-infected patients suffer from HIV-associated neurocognitive disorders (HAND). Studies are uncovering the role of extracellular vesicles (EVs), especially exosomes, in the central nervous system (CNS) due to HIV infection. We investigated links among circulating plasma exosomal (crExo) proteins and neuropathogenesis in simian/human immunodeficiency virus (SHIV)-infected rhesus macaques (RM) and HIV-infected and cART treated patients (Patient-Exo). Isolated EVs from SHIV-infected (SHIV-Exo) and uninfected (CTL-Exo) RM were predominantly exosomes (particle size < 150 nm). Proteomic analysis quantified 5654 proteins, of which 236 proteins (~4%) were significantly, differentially expressed (DE) between SHIV-/CTL-Exo. Interestingly, different CNS cell specific markers were abundantly expressed in crExo. Proteins involved in latent viral reactivation, neuroinflammation, neuropathology-associated interactive as well as signaling molecules were expressed at significantly higher levels in SHIV-Exo than CTL-Exo. However, proteins involved in mitochondrial biogenesis, ATP production, autophagy, endocytosis, exocytosis, and cytoskeleton organization were significantly less expressed in SHIV-Exo than CTL-Exo. Interestingly, proteins involved in oxidative stress, mitochondrial biogenesis, ATP production, and autophagy were significantly downregulated in primary human brain microvascular endothelial cells exposed with HIV+/cART+ Patient-Exo. We showed that Patient-Exo significantly increased blood–brain barrier permeability, possibly due to loss of platelet endothelial cell adhesion molecule-1 protein and actin cytoskeleton structure. Our novel findings suggest that circulating exosomal proteins expressed CNS cell markers—possibly associated with viral reactivation and neuropathogenesis—that may elucidate the etiology of HAND.

Deciphering The N-Glycomic And Collagen Proteomic Molecular Signatures Towards Breast Cancer Control And Prevention, Denys Rujchanarong

MUSC Theses and Dissertations

Breast cancer is the most diagnosed cancer among women worldwide and the incidence rates are rising annually. The rates of metastatic breast cancer are projected to increase by 54.3% from 2015 to 2030. Breast stroma plays a significant role in breast cancer risk and progression yet remains poorly understood. In breast stroma, regulation of post-translational modifications (PMTs) is representative of the health state of the local microenvironment. Two abundant PTMs in the extracellular matrix include hydroxylation of prolines (HYP) and N-glycosylation in collagen and non-collagen proteins, respectively. Here, mass spectrometry imaging (MSI) was used to investigate the spatial N-glycomic and …

Preclinical Perspectives On The Mechanisms Underlying The Therapeutic Actions Of Psilocybin In Psychiatric Disorders, Andreas B. Wulff, Charles D. Nichols, Scott M. Thompson

School of Medicine Faculty Publications

Psychedelic compounds have shown extraordinary potential in treating a wide range of neuropsychiatric disorders. Psilocybin, for example, has now been shown in several clinical trials to induce a rapid (within days) and persistent (3–12 months) improvement in human treatment-resistant depression and other neuropsychiatric conditions. Here we review the preclinical models and experimental approaches that have been used to study the neurobiological actions of psychedelic drugs. We further summarize the insights these studies have provided into the possible mechanisms underlying the induction of their therapeutic actions, including the receptors to which psychedelics bind and the second messenger signaling cascades that they …

Induction Of Antimicrobial Protein S100a15 Expression By Oral Microbial Pathogens Is Toll-Like Receptors-Dependent Activation Of C-Jun-N-Terminal Kinase (Jnk), P38, And Nf-Κb Pathways, Denis Selimovic, Naji Kharouf, Florence Carrouel, Sofie Yasmin Hassan, Thomas W. Flanagan, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

The antimicrobial protein S100A15 belongs to the S100 family, which is differentially expressed in a variety of normal and pathological tissues. Although the function of S100A15 protein has been discussed in several studies, its induction and regulation in oral mucosa, so far, are largely unknown. In this study, we demonstrate that S100A15 is induced by the stimulation of oral mucosa with gram− or gram+ bacterial pathogens, as well as with the purified membrane components, namely lipopolysaccharides (LPS) and lipoteichoic acid (LTA). The stimulation of the human gingival fibroblast (GF) and the human mouth epidermal carcinoma (KB) cell lines with either …

Past, Present, And A Glance Into The Future Of Multiple Myeloma Treatment., Weam Othman Elbezanti, Kishore B Challagundla, Subash C. Jonnalagadda, Tulin Budak-Alpdogan, Manoj K Pandey

College of Science & Mathematics Departmental Research

Multiple myeloma (MM) is a challenging hematological cancer which typically grows in bone marrow. MM accounts for 10% of hematological malignancies and 1.8% of cancers. The recent treatment strategies have significantly improved progression-free survival for MM patients in the last decade; however, a relapse for most MM patients is inevitable. In this review we discuss current treatment, important pathways for proliferation, survival, immune suppression, and resistance that could be targeted for future treatments.

A New, Extremely Sensitive, Turn-Off Optical Sensor Utilizing Schiff Base For Fast Detection Of Cu(Ii), Lotfi M Aroua, Reham Ali, Abuzar E A E Albadri, Sabri Messaoudi, Fahad M Alminderej, Sayed M Saleh

Faculty, Staff and Student Publications

Throughout this research, a unique optical sensor for detecting one of the most dangerous heavy metal ions, Cu(II), was designed and developed. The (4-mercaptophenyl) iminomethylphenyl naphthalenyl carbamate (MNC) sensor probe was effectively prepared. The Schiff base of the sensor shows a "turn-off" state with excellent sensitivity to Cu(II) ions. This innovative fluorescent chemosensor possesses distinctive optical features with a substantial Stocks shift (about 114 nm). In addition, MNC has remarkable selectivity for Cu(II) relative to other cations. Density functional theory (DFT) and the time-dependent DFT (TDDFT) theoretical calculations were performed to examine Cu(II) chelation structures and associated electronic properties in …

Reasons For Ineligibility For Clinical Trials Of Patients With Medication-Resistant Epilepsy, Wesley T. Kerr, Hai Chen, Mariana Figuera Losada, Christopher Cheng, Tiffany Liu, Jaqueline French

School of Medicine Faculty Publications

Selection criteria for clinical trials for medication-resistant epilepsy are used to limit variability and to ensure safety. However, it has become more challenging to recruit subjects for trials. This study investigated the impact of each inclusion and exclusion criterion on medication-resistant epilepsy clinical trial recruitment at a large academic epilepsy center. We retrospectively identified all patients with medication-resistant focal or generalized onset epilepsy who attended an outpatient clinic over a consecutive 3-month period. We assessed each patient's eligibility for trials with commonly required inclusion and exclusion criteria to evaluate the proportion of eligible patients and the most common reasons for …

Addressing A Lack Of Education Surrounding Fentanyl Use And Recovery, Nicole Sala, Luciana Gonzalez, Caroline Dorvilien, Teo Keilwitz, Maddy Terhune, Portia Forson

Nursing Leadership in Community Engagement Projects

Nursing Leadership Executive Summary: Addressing a Lack of Education Surrounding Fentanyl Use and Recovery

Our project focused on assisting a nonprofit organization who exists to serve the most vulnerable of families in the Seattle area. They offer a number of programs including a mobile outreach team that seeks to bring resources to families, a program for families which provides the opportunity for new mothers to bond with their newborn, and another program which assists families with medically fragile children to find healthcare resources, and more. Our team was made up of six students from the Lydia Green Nursing Program at …

Sfd Indications And Technique: When And How To Use Sdf To Manage Caries Lesions, Margherita Fontana Dds, Phd

The Journal of the Michigan Dental Association

The aim of this article is to review indications for 38% SDF and the appropriate technique for use. Evidence-based recommendations by the American Dental Association and umbrella reviews of systematic reviews are summarized to provide indications for SDF use in primary and permanent teeth, including sound surfaces and those with non-cavitated and cavitated caries lesions. High-quality evidence supports that SDF is an effective treatment alternative for managing active cavitated coronal and root caries lesions and preventing root caries lesions. Dentists can help by incorporating SDF as an option into their caries prevention and management armamentarium and by helping to train …

Quantitative Phosphoproteomic Analysis Reveals Unique Camp Signaling Pools Emanating From Ac2 And Ac6 In Human Airway Smooth Muscle Cells, Isabella Cattani-Cavalieri, Yue Li, Jordyn Margolis, Amy S. Bogard, Moom R. Roosan, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Human airway smooth muscle (HASM) is the primary target of ßAR agonists used to control airway hypercontractility in asthma and chronic obstructive pulmonary disease (COPD). ßAR agonists induce the production of cAMP by adenylyl cyclases (ACs), activate PKA and cause bronchodilation. Several other G-protein coupled receptors (GPCR) expressed in human airway smooth muscle cells transduce extracellular signals through cAMP but these receptors elicit different cellular responses. Some G-protein coupled receptors couple to distinct adenylyl cyclases isoforms with different localization, partly explaining this compartmentation, but little is known about the downstream networks that result. We used quantitative phosphoproteomics to define the …

Burning Mouth Disorder And Parkinson's Disease: A Scoping Review Of The Literature, O. Guru, Ramesh Balasubramaniam, Gary D. Klasser

School of Dentistry Faculty Publications

Background: Burning mouth disorder (BMD) is a complex medical condition characterized by a burning sensation in the mouth of fluctuating intensity. BMD is considered a diagnosis of exclusion, as oral burning can occur secondary to local or systemic conditions. Parkinson's disease (PD) is one such condition. Objective: To provide a scoping review of the literature by assessing all articles written in English that investigated the relationship between BMD and PD. Materials and Methods: Various databases (PubMed, Ovid, Web of Science, Science Direct and Scopus) and a search platform (EBSCOhost) were searched following similar investigative approaches. Duplicates were removed and reference …

A Modern Multimodal Pain Protocol Eliminates The Need For Opioids For Most Patients Following Total Knee Arthroplasty: Results From A Retrospective Comparative Cohort Study, Leland Van Deventer, Amy Bronstone, Claudia Leonardi, Matthew Bennett, Peter Yager, Vinod Dasa

School of Medicine Faculty Publications

Purpose: Modern multimodal analgesia has been shown to significantly reduce opioid use following total knee arthroplasty (TKA). This study was conducted to determine if changing TKA discharge opioid prescriptions from automatic to upon request resulted in more opioid free recoveries without compromising pain control. Methods: Between December 2019 and August 2021, an orthopedic surgeon performed 144 primary unilateral TKAs; patients received the same multimodal analgesia protocol except for postoperative opioid prescribing. The first consecutively-treated cohort automatically received an opioid prescription following discharge (automatic group) and the second cohort received opioid prescriptions only upon request (upon request group). Opioid prescription data …

Rationale And Design Of The Restore Trial: A Multicenter, Randomized, Double-Blinded, Parallel-Group, Placebo-Controlled Trial To Evaluate The Effect Of Shenfu Injection On Myocardial Injury In Stemi Patients After Primary Pci, Xiao Wang, Ruifeng Guo, Yingying Guo, Qian Guo, Yan Yan, Wei Gong, Wen Zheng, Hui Wang, Lei Xu, Hui Ai, Bin Que, Xiaoyan Yan, Xin-Liang Ma, Shaoping Nie

Department of Emergency Medicine Faculty Papers

BACKGROUND: The mortality following ST-segment elevation myocardial infarction (STEMI) remains substantial in the reperfusion era. Shenfu injection, as a traditional Chinese herbal formula, can alleviate ischemia-reperfusion injury through multiple pharmacologic effects. However, no robust data are available regarding the role of Shenfu injection in reducing infarct size for patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).

METHODS/DESIGN: This RESTORE trial is a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (NCT04493840). A total of 326 eligible patients with first-time anterior STEMI undergoing PPCI within 12 h of symptom onset will be enrolled from 10 centers in mainland China. Patients are randomized …

Vitamin C Contributes To Epigenetic Regulation Of Genes Related To Diabetic Retinopathy In Retinal Endothelial Cells, Elizabeth L. Turner, Jonathon Reynolds, Walker Kay, Marianne Becnel, Matthew Conway, Alexander Kim, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

The Effects Of Vitamin B1 Analog, Benfotiamine, On The Prevention Of Non-Small Cell Lung Cancer, Emely Fernandez, Hannah Christensen, Kota A. Ramana

Annual Research Symposium

No abstract provided.

Carvacrol Regulates Endotoxin -Induced Arachidonic Acid Metabolism., Aliea M. Jalali, Spencer Norton

Annual Research Symposium

Plant-derived essential oil prevents endotoxin-induced inflammatory response

The Role Of The Kcc2 In Substance Use And Abuse: A Systematic Review [Protocol], Alfred Amendolara, Steven Salazar, Chad Thompson, Hyrum Wright, Andrew Payne

Annual Research Symposium

This poster presents the protocol for an ongoing systematic review investigating the role of potassium chloride co-transporter 2 (KCC2) in substance use, abuse, and addiction.

Practice Of Building Biomedical Innovation Highland In The United States And Its Enlightenment To China, Xiaoling Ma

Bulletin of Chinese Academy of Sciences (Chinese Version)

The modern pharmaceutical industry began with the large-scale production of chemical drugs. With the radical innovation of basic sciences, such as life science, biomedicine has become the focus of the pharmaceutical industry, with broad prospects. Since World War II, the U.S. government, enterprises and scientific community have cultivated the biomedical industry and scientific foundation, created an environment for innovation, established an effective life science innovation system, and gradually become the innovation highland of biomedicine in the world. Building a biomedical innovation highland is an important part of China to become the world science center. China can learn from U.S. experience …