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Acidic pH can attenuate immune killing through inactivation of perforin.
EMBO Rep
January 2025
Killer Cell Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Cytotoxic lymphocytes are crucial to our immune system, primarily eliminating virus-infected or cancerous cells via perforin/granzyme killing. Perforin forms transmembrane pores in the plasma membrane, allowing granzymes to enter the target cell cytosol and trigger apoptosis. The prowess of cytotoxic lymphocytes to efficiently eradicate target cells has been widely harnessed in immunotherapies against haematological cancers.
View Article and Find Full Text PDFIdentifying Protein-Nucleotide Binding Residues via Grouped Multi-task Learning and Pre-trained Protein Language Models.
J Chem Inf Model
January 2025
School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
The accurate identification of protein-nucleotide binding residues is crucial for protein function annotation and drug discovery. Numerous computational methods have been proposed to predict these binding residues, achieving remarkable performance. However, due to the limited availability and high variability of nucleotides, predicting binding residues for diverse nucleotides remains a significant challenge.
View Article and Find Full Text PDFACNO hydrogel enhances diabetic wound healing by modulating the Bcl-2/Bax/Caspase-3/PARP pathway.
Int Immunopharmacol
January 2025
College of Pharmacy, Zunyi Medical University, Zunyi 563006, China; Key Lab of the Basic Pharmacology of the Ministry of Education & Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China. Electronic address:
Centella asiatica (L.) Urban, one of the authentic medicinal materials from Guizhou Province in China, has been traditionally applied for the treatment of contusions and fractures, as well as for promoting wound healing. Preliminary research suggests that asiaticoside-nitric oxide hydrogel (ACNO) exhibits the potential to enhance the healing of diabetic wounds (DWs); however, the underlying molecular mechanisms require further elucidation.
View Article and Find Full Text PDFHarnessing the Sulfur-for-Oxygen Shift: A Magic Bullet for Dynamic Photophysical and Anticancer Activities of Indole-Barbituric Acid Construct.
ChemMedChem
January 2025
IIT Roorkee: Indian Institute of Technology Roorkee, Chemistry, Department of Chemistry, 247667, Roorkee, INDIA.
The development of small molecule-based drugs emerged as a cornerstone of modern drug discovery. Structural activity relationship (SAR) studies in medicinal chemistry are crucial for lead optimization, where a subtle change in the substituent can significantly alter its binding affinity with the biological target. Herein, a highly efficient single-atom substitution (SAS) approach has been developed, where sulfur for oxygen strategy is utilized as a powerful molecular editing technique to identify N-vinyl Indole-thiobarbituric acid (6a) as a novel small molecule-based scaffold with tunable photophysical and antiproliferative activities.
View Article and Find Full Text PDFBiomarkers.
Alzheimers Dement
December 2024
Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Background: Oxidative stress, which refers to an imbalance between the production of reactive oxygen/nitrogen species (ROS/RNS) and the body's antioxidant defense mechanisms, is implicated in the pathogenesis of various chronic diseases by promoting cellular damage, inflammation, and dysfunction. Numerous methods have been reported for detecting ROS/RNS in vitro and in vivo; however, detecting methods for the secondary products of the ROS/RNS reactions, particularly quasi-stable oxidized products, have been much less explored.
Method: In this report, we discovered that acetylacetone, a core moiety of curcumins, is a new scaffold for generating chemiluminescence in the presence of oxidants.
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