Medicinal and Pharmaceutical Chemistry Commons^™

An Injectable In Situ Forming Collagen/Alginate/Caso4 Composite Hydrogel For Tissue Engineering Applications: Optimization, Characterization And In Vitro Assessments, Samar A. Salim, Samar A. Salim

Nanotechnology Research Centre

In situ injectable hydrogels are effectively employed to fill irregular cavitary bone defects with initiating bone growth in targeted areas. Herein, an injectable composited hydrogel composed of collagen and alginate cross-linked in situ using different concentrations of calcium sulfate (0.15, 0.3 and 0.6%, wt./v) was synthesized. Recently, CaSO4 is frequently supported as a bone graft material for bone regeneration, owing to its biocompatibility and osteoconductive properties. Moreover, hydroxyapatite (Hap) after salinization-step by (3-Aminopropyl) triethoxysilane (APTES) was incorporated for further enhancing the osteoconductive property of injected hydrogels. All fabricated hydrogels were characterized by SEM, FTIR and XRD analyses. While physiochemical characteristics …

Modulation Of Hippocampal Protein Expression By A Brain Penetrant Biologic Tnf-Α Inhibitor In The 3xtg Alzheimer’S Disease Mice, Nataraj Jagadeesan, G. Chuli Roules, Devaraj V. Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer’s disease (AD) if these macromolecules can cross the blood–brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD).

Methods

Eight-month-old female 3xTg-AD mice were injected intraperitoneally with …

A Novel Micropeptide, Slitharin, Exerts Cardioprotective Effects In Myocardial Infarction, Ahmed G. E. Ibrahim, Alessandra Ciullo, Shukuro Yamaguchi, Chang Li, Travis Antes, Xaviar Jones, Liang Li, Ramachandran Murali, Innokentiy Maslennikov, Niveda Sundararaman, Daniel Soetkamp, Eugenio Cingolani, Jennifer Van Eyk, Eduardo Marbán

Pharmacy Faculty Articles and Research

Purpose: Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery of a novel micropeptide, dubbed slitharin (Slt), in conditioned media from Cardiosphere-derived cells (CDCs), a therapeutic cardiac stromal cell type.

Experimental design: We performed mass spectrometry of peptide-enriched fractions from the conditioned media of CDCs and a therapeutically inert cell type (human dermal fibrobasts). We then evaluated the therapeutic capacity of the candidate peptide using an in vitro model of cardiomyocyte injury and a rat model of myocardial infarction.

Results: We identified a novel 24-amino acid micropeptide …

Six-Month Report Assessing The Feasibility And Effectiveness Of Amniotic Membrane Injections In Patients With Short, Anterior, Urethral Strictures, Nicholas Pryde, Jack Vernocke, Aron Liaw, Michael Sessine, Nivedita Dhar

Medical Student Research Symposium

Introduction: Urethral stricture treatment has high recurrence rates and adjunct injectable agents have been explored. Amniotic membranes (AM) promote apoptosis of pro-inflammatory cells, prevent differentiation of pro-fibrotic cells, and decrease scar formation. These tissues generated interest in reconstructive urethral surgery. Thus, we performed urethral dilation combined with micronized AM injection in urethral scar tissue for treatment of urethral stricture.

Materials and Methods: Adult males with strictures ≤12Fr in diameter and ≤2 cm in length, International Prostate Symptom Score (IPSS) ≥11 and maximum flowrate <15 ml/s. Reconstituted 100mg micronized AM was injected at the time of urethral dilation. Primary study end point was anatomical success (≥14Fr by cystoscopy) at 6 months. Secondary end points were questionnaires, flow rate, and post void residual. Outcomes assessed at baseline, 5 days, 14 days, 3 months, and 6 months post-injection. Safety was analyzed.

Results: Ten men, mean age of 52 ± 15 years, were included. There were 7 patients with …

Repurposing Of Us-Fda-Approved Drugs As Negative Modulators Of Ubiquitin Specific Protease-7 (Usp7), Seema Zadi, Sumaira Javaid, Atia-Tul-Wahab, Humaira Zafar, Muhammad Awais, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target. In this study, a drug repurposing approach was used to identify new hits against the USP7 enzyme. It is one of the most strategic approaches to find new uses for drugs in a cost- and time-effective way. Nuclear Magnetic Resonance-based screening of 172 drugs identified 11 compounds that bind to the catalytic domain of …

Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly …

De Novo Drug Design Using Transformer-Based Machine Translation And Reinforcement Learning Of An Adaptive Monte Carlo Tree Search, Dony Ang, Cyril Rakovski, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researchers to explore innovative methods that harness the power of deep learning and reinforcement learning techniques. Here, we introduce a novel drug design approach called drugAI that leverages the Encoder–Decoder Transformer architecture in tandem with Reinforcement Learning via a Monte Carlo Tree Search (RL-MCTS) to expedite the process of drug discovery while ensuring the production of valid small molecules with drug-like characteristics and strong binding affinities towards …

Ai Renaissance: Pharmaceuticals And Diagnostic Medicine, Ty J. Feeney, Michael S. Sinha

All Faculty Scholarship

The explosive growth of Artificial Intelligence (AI) in the modern era has led to significant advancements in the world of medicine. In drug discovery, AI technology is used to classify proteins as drug targets or non-targets for specific diseases, more accurately interpret and describe pharmacology in a quantitative fashion, and predict protein structures based on only a protein sequence for input. AI methods are used in drug development to generate predictive models for drug screening purposes, refine and modify candidate structures of drugs to optimize compounds, and predict a drug’s physiochemical properties, bioactivity, and toxicity. For medical devices, the advancement …