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An Immunocytochemistry Method to Investigate the Translationally Active HIV Reservoir.
Int J Mol Sci
January 2025
MRL, Merck & Co., Inc., Rahway, NJ 07065, USA.
Despite the success of combination antiretroviral therapy (cART) to suppress HIV replication, HIV persists in a long-lived reservoir that can give rise to rebounding viremia upon cART cessation. The translationally active reservoir consists of HIV-infected cells that continue to produce viral proteins even in the presence of cART. These active reservoir cells are implicated in the resultant viremia upon cART cessation and likely contribute to chronic immune activation in people living with HIV (PLWH) on cART.
View Article and Find Full Text PDFHERV-W Env Induces Neuron Pyroptosis via the NLRP3-CASP1-GSDMD Pathway in Recent-Onset Schizophrenia.
Int J Mol Sci
January 2025
State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
HERVs (Human endogenous retroviruses) are remnants of ancient exogenous retroviruses that have integrated into the human genome, particularly in germ-line cells. Among these, the envelope protein gene (Human endogenous retroviruses W family envelope protein), located on chromosome 7 and primarily expressed in the human placenta, has been closely linked to various neuropsychiatric disorders, including schizophrenia, as well as autoimmune diseases and cancer. Recent studies have highlighted the abnormal expression of cytokines as a key factor in the pathophysiology of schizophrenia.
View Article and Find Full Text PDFPre-Clinical Rationale for Amcenestrant Combinations in HER2+/ER+ Breast Cancer.
Int J Mol Sci
January 2025
Cancer Biotherapeutics Research Group, Life Sciences Institute, School of Biotechnology, Dublin City University, Dublin 9, D09 NR58 Dublin, Ireland.
HER2-positive/oestrogen receptor-positive (HER2+/ER+) represents a unique breast cancer subtype. The use of individual HER2- or ER-targeting agents can lead to the acquisition of therapeutic resistance due to compensatory receptor crosstalk. New drug combinations targeting HER2 and ER could improve outcomes for patients with HER2+/ER+ breast cancer.
View Article and Find Full Text PDFMechanistic insights into Wnt-β-catenin pathway activation and signal transduction.
Nat Rev Mol Cell Biol
January 2025
Donnelly Centre for Cellular and Biomolecular Research and Department of Biochemistry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
In multicellular organisms, Wnt proteins govern stem and progenitor cell renewal and differentiation to regulate embryonic development, adult tissue homeostasis and tissue regeneration. Defects in canonical Wnt signalling, which is transduced intracellularly by β-catenin, have been associated with developmental disorders, degenerative diseases and cancers. Although a simple model describing Wnt-β-catenin signalling is widely used to introduce this pathway and has largely remained unchanged over the past 30 years, in this Review we discuss recent studies that have provided important new insights into the mechanisms of Wnt production, receptor activation and intracellular signalling that advance our understanding of the molecular mechanisms that underlie this important cell-cell communication system.
View Article and Find Full Text PDFEnhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo.
Vaccines (Basel)
January 2025
Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China.
Background: Inefficient cellular uptake is a significant limitation to the efficacy of DNA vaccines. In this study, we introduce S-Cr9T, a stearyl-modified cell-penetrating peptide (CPP) designed to enhance DNA vaccine delivery by forming stable complexes with plasmid DNA, thereby protecting it from degradation and promoting efficient intracellular uptake.
Methods And Results: In vitro studies showed that S-Cr9T significantly improved plasmid stability and transfection efficiency, with optimal performance at an N/P ratio of 0.
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