Recent publications
- Structural Insights into the Nonmutagenicity of 2-Haloacetophenone March 27, 2025A wide variety of endogenous and exogenous alkylating agents covalently modify DNA to produce N7-alkyl-2'-deoxyguanosine (N7-alkylG) adducts as major DNA lesions. The mutagenic potentials of many N7-alkylG adducts with an intercalatable moiety remain poorly understood. We have discovered that the antiriot agent 2-chloroacetophenone readily reacts with dG to produce N7-acetophenone-dG adducts, implicating the genotoxic properties […]Hunmin Jung
- Molecular Insight into Lipid Nanoparticle Assembly from NMR Spectroscopy and Molecular Dynamics Simulation March 26, 2025Lipid nanoparticles (LNPs) have emerged as the premier drug delivery system for oligonucleotide vaccines and therapeutics in recent years. Despite their prosperous advancement in research and clinical applications, there is a significant lack of mechanistic understanding of the assembly of lipid particles at the molecular level. In our study, we utilized a combination of solution […]Mingyue Li
- Impact on efficacy of target reduction of two FDA-approved ASO drugs by intracellular glucose levels in <em>in vitro</em> cell models March 19, 2025Antisense oligonucleotides (ASOs) have emerged as a new therapeutic modality for the treatment of both rare and common human diseases. A significant proportion of the patient population that may benefit from ASO therapy may also have common diseases, such as diabetes mellitus. The potential influence of prevalent diseases on the effectiveness of ASO drugs in […]Le Tra Giang Nguyen
- Protocol Development for CRISPR/Cas9 Knockout of the Anti-inflammatory Protein TNIP1 in HaCaT Keratinocytes March 19, 2025Gene editing in cultured cells, including the intent of sequence disruption to achieve a functional knockout of the targeted gene, has been greatly facilitated with the advent of Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) technology. Primary cell strains and immortalized cell lines from diverse tissue types have been successfully targeted both […]Liam E Carman
- Investigation of structural and dynamic properties of the Butyrophilin BTN3A1/BTN2A1 cytoplasmic complex by <sup>19</sup>F solution NMR March 13, 2025Butyrophilin 3A1 (BTN3A1) is an integral membrane protein capable of detecting phosphoantigens, like (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP), through its internal B30.2 domain. Detection of phosphoantigens leads to interactions with butyrophilin 2A1 and the subsequent activation of γδ-T cells. Though crystallography and functional assays have been crucial for determining vital residues of the BTN3A1/HMBPP/BTN2A1 complex, the mechanism […]Khiem Nguyen
- PVR exposure influences the activation, adhesion, and protein expression of human CD8+ T cells, including the CD96-mediated transfer of PVR March 12, 2025Poliovirus receptor (PVR) ligands have gained attention as immunotherapy targets, yet their regulation remains unclear. Here, we examine the impact of PVR exposure on primary human CD8+ T cells. We used flow cytometry and Western blot analysis to quantify expression of PVR and its ligands in naïve and effector T cells and used adhesion assays […]Xueting Huang
- Role of HNF4A-AS1/HNRNPC-mediated HNF4A ubiquitination protection against ritonavir-induced hepatotoxicity March 4, 2025Ritonavir (RTV) is an important drug for anti-human immunodeficiency virus treatment and is mainly metabolized by cytochrome P450 (CYP) 3A4. Clinically, the most common side effect of RTV treatment is hepatoxicity. We previously showed that the long noncoding RNA hepatocyte nuclear factor 4 alpha (HNF4A) antisense 1 (HNF4A-AS1) negatively regulated CYP3A4 expression and participated in […]Xiaofei Wang
- Impact of agglomeration on in vitro performance of long-acting injectable suspensions February 26, 2025Long-acting injectable (LAI) suspensions are controlled drug delivery systems that provide sustained drug release over durations ranging from one to six months. Although it is recognized that the particle agglomeration behavior could play a critical role on product clinical performance, factors that can affect this behavior have not yet been fully understood. This study explores […]Nilesh Malavia
- Advanced Manufacturing, Modeling And Analytical Tools In Injectable Products February 26, 2025Although great progress has been made in the effectiveness and availability of medicines, there is still more work to do assuring greater access and continuing to advance disease treatments. Recent advances in both the types of treatments that can be developed and the technology to produce, characterize, collect relevant data from, and deliver medicines to […]Howard Stamato
- Synthesis and evaluation of triazole-containing aryl/acyloxy prodrugs of a BTN3A1 ligand February 7, 2025The most effective natural ligand for the butyrophilins is (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate. However, due to its susceptibility to plasma hydrolysis and its high charge that limits passive diffusion across cell membranes, its potential as a drug is limited. Our efforts to identify compounds that stimulate γδ T cell proliferation have been focused on phosphonates to gain […]Umed Singh
- Optimization of Carrier-Based Dry Powder Inhaler Performance: A Review January 25, 2025Dry powder inhalers (DPI's) are becoming increasingly popular due to growing interest in pulmonary drug delivery and their performance is the net result of a series of processes carried out during the formulation development and manufacturing process such as excipient selection, blending, milling, filling, and spray drying. To reach the small airways of the deep […]Tanu Mehta
- Critical Analysis of Cytoplasmic Progression of Inflammatory Signaling Suggests Potential Pharmacologic Targets for Wound Healing and Fibrotic Disorders January 8, 2025Successful skin wound healing is dependent on an interplay between epidermal keratinocytes and dermal fibroblasts as they react to local extracellular factors (DAMPs, PAMPs, cytokines, etc.) surveyed from that environment by numerous membrane receptors (e.g., TLRs, cytokine receptors, etc.). In turn, those receptors are the start of a cytoplasmic signaling pathway where balance is key […]Michael L Samulevich
- Janus LAAM-loaded electrospun fibrous buccal films for treating opioid use disorder January 3, 2025The opioid crisis has claimed approximately one million lives in the United States since 1999, underscoring a significant public health concern. This surge in opioid use disorder (OUD) fatalities necessitates improved therapeutic options. Current OUD therapies often require daily clinical visits, leading to poor patient compliance and high costs to the health systems. Levo-alpha-acetylmethadol (LAAM) […]Hadi Sudarjat
- Discovery of small molecules against porcine reproductive and respiratory syndrome virus replication by targeting NendoU activity January 2, 2025Porcine reproductive and respiratory syndrome (PRRS) remains a major threat to animal health and causes substantial economic losses worldwide. The nonstructural protein 11 (NSP11) of the causative agent, PRRS virus (PRRSV), contains a highly conserved nidoviral uridylate-specific endoribonuclease (NendoU) domain essential for viral replication and immune evasion. Targeting NSP11 offers a novel approach to antiviral […]Jiaqi Zhu
- Long-acting injectable in situ forming implants: Impact of polymer attributes and API December 28, 2024Poly(DL-lactide-co-glycolide) (PLGA) and N-methyl-2-pyrrolidone (NMP)-based in situ forming implants are liquid formulations that solidify through phase separation following injection into the body. Drug is dissolved or suspended in the final formulation liquid prior to injection. Depending on the polymers used, the depots formed can deliver drug over different periods of time. Accordingly, it is important […]Xiaoyi Wang
- Exploring Imaging Applications of a Red-Emitting π-Acceptor (π-A) Pyrene-Benzothiazolium Dye December 27, 2024Bright biocompatible fluorescent imaging dyes with red to near-infrared (NIR) emissions are ideal candidates for fluorescence microscopy applications. Pyrene-benzothiazolium hemicyanine dyes are a new class of lysosome-specific probes reported on recently. In this work, we conduct a detailed implementation study for a pyrene-benzothiazolium derivative, BTP, to explore its potential imaging applications in fluorescence microscopy. The […]Chathura S Abeywickrama
- The 2024 Nobel Prize in Physiology or Medicine: microRNA Takes Center Stage December 27, 2024The Non-coding Journal Editorial Board Members would like to congratulate Victor Ambros and Gary Ruvkun, who were jointly awarded the 2024 Nobel Prize in Physiology or Medicine for their groundbreaking discovery of microRNAs and the role of microRNAs in post-transcriptional gene regulation, uncovering a previously unknown layer of gene control in eukaryotes [...].George A Calin
- Investigating the crosstalk between <em>ABCC4</em> and <em>ABCC5</em> in 3T3-L1 adipocyte differentiation December 24, 2024CONCLUSION: These results highlight the complex interplay between ABCC4 and ABCC5 transporters in adipocyte function and suggest their individual contributions toward obesity and related disorders.Ankit P Laddha
- Tumor specific delivery and radiation-enhanced tumor penetration of mesoporous silica nanoparticles for effective radionuclide therapy of ovarian peritoneal metastasis December 11, 2024Advanced ovarian cancer with peritoneal metastasis is challenging to treat. Limited tumor delivery and penetration of the therapeutics to deep tumor regions are significant barriers to effective treatment. The rising radiopharmaceuticals offer hopes for patients through targeted delivery. However, site specific delivery avoiding off target effect remain critical and challenging. We have developed radioactive ^(166)Holmium […]Derek Hargrove
- Evolution of antisense oligonucleotides: navigating nucleic acid chemistry and delivery challenges December 9, 2024INTRODUCTION: Antisense oligonucleotide (ASO) was established as a viable therapeutic option for genetic disorders. ASOs can target RNAs implicated in various diseases, including upregulated mRNA and pre-mRNA undergoing abnormal alternative splicing events. Therapeutic applications of ASOs have been proven with the Food and Drug Administration approval of several drugs in recent years. Earlier enzymatic stability […]Ruchi Ruchi