bioRxiv Subject Collection: Pharmacology And Toxicology
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This feed contains articles for bioRxiv Subject Collection "Pharmacology And Toxicology"
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Increases in serum corticosterone level and diuresis induced by the selective kappa opioid receptor (KOR) agonist U50,488H are unaffected by KOR phosphorylation
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https://www.biorxiv.org/content/10.64898/2026.07.10.737784v1?rss=1
2026-07-16doi:10.64898/2026.07.10.737784Cold Spring Harbor Laboratory2026-07-16
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Multi-Modal Toxicological Evaluation of NiO nanoparticles and ionic nickel in a Human Lung-Cardiac Co-Culture System
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https://www.biorxiv.org/content/10.64898/2026.07.10.737738v1?rss=1
2026-07-16doi:10.64898/2026.07.10.737738Cold Spring Harbor Laboratory2026-07-16
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From exact gradients to exact standard errors: third-order sensitivity equations for the FOCE and FOCEI population likelihood
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https://www.biorxiv.org/content/10.64898/2026.07.09.737434v1?rss=1
2026-07-15doi:10.64898/2026.07.09.737434Cold Spring Harbor Laboratory2026-07-15
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Effect of Immunosuppressive Drugs on Glucose-Stimulated Insulin Secretion: Concentration-Response Studies in Dynamic Perifusion Assays
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https://www.biorxiv.org/content/10.64898/2026.07.09.737557v1?rss=1
2026-07-15doi:10.64898/2026.07.09.737557Cold Spring Harbor Laboratory2026-07-15
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Allosteric modulation of β1 integrin through the hybrid domain reverses articular cartilage injury and functional impairment in a murine model of inflammatory arthritis
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https://www.biorxiv.org/content/10.64898/2026.07.09.737517v1?rss=1
2026-07-15doi:10.64898/2026.07.09.737517Cold Spring Harbor Laboratory2026-07-15
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Comprehensive dissection of GPCR signaling using a NanoBiT-based platform
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https://www.biorxiv.org/content/10.64898/2026.07.09.737439v1?rss=1
2026-07-14doi:10.64898/2026.07.09.737439Cold Spring Harbor Laboratory2026-07-14
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AlfaDAX-Derived ActRIIA/B Antibody with Semaglutide Enhances Fat Loss and Improves Weight-Loss Quality in DIO Mice
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https://www.biorxiv.org/content/10.64898/2026.07.09.737400v1?rss=1
2026-07-13doi:10.64898/2026.07.09.737400Cold Spring Harbor Laboratory2026-07-13
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In vitro EAS-mediated activity of Alternaria toxins
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https://www.biorxiv.org/content/10.64898/2026.07.09.737498v1?rss=1
2026-07-13doi:10.64898/2026.07.09.737498Cold Spring Harbor Laboratory2026-07-13
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Hazard characterization of Alternaria toxins - filling data gaps on in vitro genotoxicity.
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https://www.biorxiv.org/content/10.64898/2026.07.08.737172v1?rss=1
2026-07-13doi:10.64898/2026.07.08.737172Cold Spring Harbor Laboratory2026-07-13
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Netrin-1 inhibition does not attenuate cancer-induced bone pain in three translational models
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https://www.biorxiv.org/content/10.64898/2026.07.10.733710v1?rss=1
2026-07-13doi:10.64898/2026.07.10.733710Cold Spring Harbor Laboratory2026-07-13
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The D2-mdx mouse as a preclinical model for Duchenne muscular dystrophy: a natural history study across two independent sites
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https://www.biorxiv.org/content/10.64898/2026.07.08.737223v1?rss=1
2026-07-12doi:10.64898/2026.07.08.737223Cold Spring Harbor Laboratory2026-07-12
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Cytotoxicity of Pelargonic Acid and Its Commercial Formulation Roundup NL (Glyphosate-Free Roundup)
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https://www.biorxiv.org/content/10.64898/2026.07.07.736979v1?rss=1
2026-07-11doi:10.64898/2026.07.07.736979Cold Spring Harbor Laboratory2026-07-11
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Voclosporin Preserves Mitochondrial Function Compared With Cyclosporine A in Perfused Human Proximal Tubule Microphysiological Systems
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https://www.biorxiv.org/content/10.64898/2026.07.07.737071v1?rss=1
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org.highwire.dtl.DTLVardef@11f473aorg.highwire.dtl.DTLVardef@7d5136org.highwire.dtl.DTLVardef@15ebfddorg.highwire.dtl.DTLVardef@186618a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG BackgroundCalcineurin inhibitors (CNIs) are indispensable for transplantation immunosuppression, yet cyclosporine A (CsA) produces renal toxicity. Voclosporin (VCS), a CsA analog, is proposed to be less nephrotoxic, but mechanisms remain unclear.
MethodsPrimary human proximal tubule epithelial cells (PTECs) were exposed to CsA or VCS in 2D monolayers and perfused 3D kidney microphysiological system (MPS). Viability was assessed in 2D cultures by MTS, mitochondrial membrane potential ({Delta}{Psi}m) by TMRM flow cytometry, and soluble injury and inflammatory biomarkers in MPS effluents by ELISA and MSD multiplex assays. RNA sequencing of 3D-cultured PTECs was used to identify differentially expressed genes and pathways.
ResultsIn 2D PTECs, neither drug reduced viability. In 3D MPS effluents, KIM-1 did not distinguish CsA from VCS, whereas the MSD biomarker panel showed larger aggregate deviation with CsA. Confocal tomography showed CsA-associated mitochondrial fragmentation, whereas VCS preserved reticular mitochondrial architecture. TMRM flow cytometry showed a treatment-dependent difference in TMRM-positive cells, with VCS yielding the highest TMRM-positive fraction and exceeding CsA, supporting preservation of {Delta}{Psi}m relative to CsA. RNA-seq identified 1188 CsA-specific and 185 VCS-specific differentially expressed genes, with 304 shared. Pathway analysis indicated CsA enrichment of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, p21-associated G2/M checkpoint arrest, and transcriptional signatures consistent with ferroptosis priming, while VCS mainly induced ER chaperone and ER-associated degradation gene programs without activating canonical UPR sensors and showed limited cell-cycle suppression.
ConclusionsA physiologically relevant 3D kidney MPS revealed sublethal tubular stress from CsA that is masked in 2D culture, including mitochondrial depolarization, proteostatic stress, and ferroptosis priming. At matched exposure, VCS preserved mitochondrial function and proteostasis while eliciting a narrower, adaptive ER quality control response. These data support VCS as a nephron-sparing immunosuppressant and 3D MPS as a mechanism-based platform for evaluating renal safety of drugs and nominating early sub-lethal tubular injury biomarkers.
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Modulation of NF-κB signaling by Alternaria mycotoxins: in vitro and in silico insights into molecular mechanisms of immunosuppression in THP-1 monocytes
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https://www.biorxiv.org/content/10.64898/2026.07.06.736814v1?rss=1
2026-07-09doi:10.64898/2026.07.06.736814Cold Spring Harbor Laboratory2026-07-09
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Mechanistic characterization of tenuazonic acid-induced cellular stress responses in human esophageal KYSE-510 cells
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https://www.biorxiv.org/content/10.64898/2026.07.06.736731v1?rss=1
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DSPE-PEG does not retain targeting antibodies on LNP surfaces in vivo; a higher molecular weight anchor is required
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https://www.biorxiv.org/content/10.64898/2026.07.02.736109v1?rss=1
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Environmentally relevant depleted uranium exposure damages mitochondria, decreases cytosolic reductive capacity, and increases global DNA damage accumulation through a ROS-independent mechanism involving slingshot protein phosphatase 1b enrichment.
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https://www.biorxiv.org/content/10.64898/2026.07.02.736169v1?rss=1
2026-07-08doi:10.64898/2026.07.02.736169Cold Spring Harbor Laboratory2026-07-08
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Ocimum gratissimum essential oil nanoemulsions as a safe topical nanoplatform for antibacterial and wound-healing activities
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https://www.biorxiv.org/content/10.64898/2026.07.01.735794v1?rss=1
2026-07-07doi:10.64898/2026.07.01.735794Cold Spring Harbor Laboratory2026-07-07
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Green-synthesized silver nanoparticles enhance Guibourtia tessmannii antithromboinflammatory therapeutic potential
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https://www.biorxiv.org/content/10.64898/2026.07.03.736249v1?rss=1
2026-07-06doi:10.64898/2026.07.03.736249Cold Spring Harbor Laboratory2026-07-06
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Suprachoroidal Delivery of Anti-Angiogenic Peptide Microparticles Enables Sustained Activity with Favorable Ocular Safety
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https://www.biorxiv.org/content/10.64898/2026.06.30.735614v1?rss=1
2026-07-05doi:10.64898/2026.06.30.735614Cold Spring Harbor Laboratory2026-07-05
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Novel apoptosis signal-regulating kinase 1 (ASK1) inhibitor SRT-015: Potential therapeutic for multiple liver diseases
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https://www.biorxiv.org/content/10.64898/2026.06.30.735673v1?rss=1
2026-07-05doi:10.64898/2026.06.30.735673Cold Spring Harbor Laboratory2026-07-05
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β-alanine betaine and nAChRs in Ascaris
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https://www.biorxiv.org/content/10.64898/2026.06.30.735465v1?rss=1
2026-07-03doi:10.64898/2026.06.30.735465Cold Spring Harbor Laboratory2026-07-03
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Adenosine A2B Receptor Activation: A Novel Therapeutic Strategy for Accelerating Liver Recovery After Acetaminophen Overdose
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https://www.biorxiv.org/content/10.64898/2026.06.29.735109v1?rss=1
2026-07-03doi:10.64898/2026.06.29.735109Cold Spring Harbor Laboratory2026-07-03
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Evaluation of Retinal Safety of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors
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https://www.biorxiv.org/content/10.64898/2026.06.29.735161v1?rss=1
2026-07-02doi:10.64898/2026.06.29.735161Cold Spring Harbor Laboratory2026-07-02
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The effects of estrogen exposure on survival, growth, and fecundity of Daphnia magna
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https://www.biorxiv.org/content/10.64898/2026.06.27.734946v1?rss=1
2026-07-02doi:10.64898/2026.06.27.734946Cold Spring Harbor Laboratory2026-07-02
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Computational Design of Two Novel BRAF V600E Inhibitors: Exploiting Sulfoximine Bioisosterism and Chiral Constraints to Evade Paradoxical Activation
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https://www.biorxiv.org/content/10.64898/2026.06.25.734343v1?rss=1
2026-06-30doi:10.64898/2026.06.25.734343Cold Spring Harbor Laboratory2026-06-30
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Proteomic profiling of xenobiotic and nutrient transporters in human placenta of different gestational ages
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https://www.biorxiv.org/content/10.64898/2026.06.25.730994v1?rss=1
2026-06-30doi:10.64898/2026.06.25.730994Cold Spring Harbor Laboratory2026-06-30
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Basal Internalization and Subcellular Localization of XCR1
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https://www.biorxiv.org/content/10.64898/2026.06.25.734240v1?rss=1
2026-06-30doi:10.64898/2026.06.25.734240Cold Spring Harbor Laboratory2026-06-30
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Synapse-based bispecific immune cell engager model predicts invariance in synapse behavior across different effector-to-tumor cell ratios
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https://www.biorxiv.org/content/10.64898/2026.06.24.733437v1?rss=1
2026-06-29doi:10.64898/2026.06.24.733437Cold Spring Harbor Laboratory2026-06-29
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Enhanced TRPV1 activation through TLR-4 and PKA signaling in Dorsal Root Ganglia Neurons
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https://www.biorxiv.org/content/10.64898/2026.06.24.734307v1?rss=1
2026-06-29doi:10.64898/2026.06.24.734307Cold Spring Harbor Laboratory2026-06-29