111 papers
Pharmacology and toxicology explore how substances interact with living systems, ranging from the development of life-saving medicines to understanding the dangers of chemical exposure. This field sits at the critical intersection of chemistry and biology, asking essential questions about how drugs work, how the body processes them, and what happens when things go wrong. It is a dynamic area where researchers constantly strive to improve patient safety while discovering new therapeutic possibilities.
At Gist.Science, we bridge the gap between complex research and public understanding by curating the latest preprints from bioRxiv in this vital category. Our team processes every new submission from bioRxiv as it appears, transforming dense scientific data into both plain-language overviews and detailed technical summaries. This ensures that whether you are a specialist or a curious reader, you can grasp the significance of these emerging findings without getting lost in jargon.
Below are the most recent pharmacology and toxicology papers from bioRxiv, each accompanied by our expert analysis to help you navigate the latest scientific breakthroughs.
This study demonstrates that the stereochemical identity of lipid nanoparticles, particularly the cis isomer of the ionizable lipid cKK-E12, significantly enhances protein expression by modulating internal lipid organization and structural phases, thereby revealing a critical yet overlooked determinant of RNA delivery efficacy.
This study utilizes deep mutational scanning and computational methods to demonstrate that the CFTR corrector VX-121 generally enhances the expression of rare CF variants more effectively than VX-445, particularly for MSD1 mutations, while also revealing a specific variant (Y1032C) with reduced responsiveness and confirming that VX-121 avoids a key off-target interaction associated with VX-445.
This study demonstrates that in genetically diverse rats, higher severity of addiction-like behaviors, particularly escalated oxycodone intake and motivation, predicts more intense and prolonged withdrawal-induced mechanical allodynia, suggesting that pain sensitivity during abstinence serves as a robust marker of addiction severity.
Simpatico is an open-source, ultra-fast virtual screening tool that leverages atomic-level embeddings and nearest-neighbor retrieval to achieve state-of-the-art accuracy in predicting protein-ligand binding, significantly outperforming both traditional docking and existing embedding-based methods in speed and precision without requiring 3D pose estimation.
This study demonstrates that a human immune system tumor-bearing mouse model treated with nivolumab and ipilimumab reproducibly recapitulates human ICI-induced nephrotoxicity, revealing that renal injury is driven by CD4+ T-cell enrichment and specific immune protein shifts rather than traditional biomarkers, thereby validating this platform for mechanistic investigation and therapeutic testing.
This study employs an integrative computational framework combining network pharmacology, machine learning, and ODE kinetic modeling to demonstrate that co-exposure to PFOS and PFOA drives prostate cancer progression by disrupting the androgen receptor axis, activating the PI3K-AKT pathway, and remodeling the tumor microenvironment into an immunosuppressive state, while identifying a synergistic drug combination of enzalutamide and Alpelisib as a potential therapeutic intervention.
Despite promising results in C. elegans models, this study demonstrates that 4-phenylbutyrate and AI-identified analogs fail to rescue locomotion deficits or reduce seizure activity in STXBP1-deficient zebrafish, arguing against their repurposing for treating STXBP1-related disorders.
This study demonstrates that acute inflammation, induced by either lipopolysaccharides or restraint stress, suppresses methamphetamine-induced behavioral sensitization in mice through distinct COX-2 and TNF-α pathways, respectively, offering new insights into how mild inflammation may alleviate positive symptoms of schizophrenia.
Using a computational model of human ventricular cardiomyocytes, this study demonstrates that a 45% reduction in female IKs conductance significantly amplifies the action potential prolongation caused by IKr blockade compared to males, providing a quantitative ionic basis for the higher susceptibility of women to drug-induced Torsades de Pointes.
This study demonstrates that synthetic lipid nanoparticles activate the TRPA1 ion channel through a novel, non-canonical mechanism involving stochastic interactions with the plasma membrane that trigger both TRPA1-dependent and independent calcium signaling pathways, with potential implications for cancer and nasal vaccine development.