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EGFR-targeting RNase A-cetuximab antibody-drug conjugate induces ROS-mediated apoptosis to overcome drug resistance in KRAS mutant cancer cells.
Sci Rep
January 2025
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Antibody-drug conjugates (ADCs) are an emerging strategy in cancer therapy, enhancing precision and efficacy by linking targeted antibodies to potent cytotoxic agents. This study introduces a novel ADC that combines ribonuclease A (RNase A) with cetuximab (Cet), an anti-EGFR monoclonal antibody, through a polyethylene glycol (PEG) linker (RN-PEG-Cet), aimed to induce apoptosis in KRAS mutant colorectal cancer (CRC) via a ROS-mediated pathway. RN-PEG-Cet was successfully synthesized and characterized for its physicochemical properties, retaining full enzymatic activity in RNA degradation and high binding affinity to EGFR.
View Article and Find Full Text PDFNano-LC with New Hydrophobic Monolith Based on 9-Antracenylmethyl Methacrylate for Biomolecule Separation.
Int J Mol Sci
December 2024
Department of Chemistry, College of Science, Taif University, Taif P.O. Box 11099, Saudi Arabia.
In this study, new monolithic poly(9-anthracenylmethyl methacrylate-co-trimethylolpropane trimethacrylate (TRIM) columns, referred as ANM monoliths were prepared, for the first time, and were used for the separation media for biomolecules and proteomics analysis by nano-liquid chromatography (nano-LC). Monolithic columns were prepared by in situ polymerization of 9-anthracenylmethyl methacrylate (ANM) and trimethylolpropane trimethacrylate (TRIM) in a fused silica capillary column of 100 µm ID. Polymerization solution was optimized in relation to monomer and porogenic solvent.
View Article and Find Full Text PDFSpontaneous base flipping helps drive Nsp15's preferences in double stranded RNA substrates.
Nat Commun
January 2025
Molecular and Cellular Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Coronaviruses evade detection by the host immune system with the help of the endoribonuclease Nsp15, which regulates levels of viral double stranded RNA by cleaving 3' of uridine (U). While prior structural data shows that to cleave double stranded RNA, Nsp15's target U must be flipped out of the helix, it is not yet understood whether Nsp15 initiates flipping or captures spontaneously flipped bases. We address this gap by designing fluorinated double stranded RNA substrates that allow us to directly relate a U's sequence context to both its tendency to spontaneously flip and its susceptibility to cleavage by Nsp15.
View Article and Find Full Text PDFTrehalose Ameliorates Nonalcoholic Fatty Liver Disease by Regulating IRE1α-TFEB Signaling Pathway.
J Agric Food Chem
January 2025
Department of Clinical Nutrition and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu 610041, P. R. China.
Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic lipid deposition, is one of the most prevalent chronic metabolic disorders globally, and its pharmaceutical treatments are still limited. Excessive lipid accumulation triggers endoplasmic reticulum (ER) stress and autophagy flux dysfunction, which are important mechanisms for NAFLD. Trehalose (Tre), a natural disaccharide, has been identified to reduce hepatic steatosis and glucose intolerance.
View Article and Find Full Text PDFDNA target binding-induced pre-crRNA processing in type II and V CRISPR-Cas systems.
Nucleic Acids Res
December 2024
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, No. 4221, Xiang'an South Road, Xiamen 361102, China.
Article Synopsis
- Precursor CRISPR RNA (pre-crRNA) processing involves the removal of segments from both repeat and spacer sequences, which is essential for maturation of crRNA.
- The study reveals that specific type II and V Cas proteins, like Cas12a and Cas9, can cleave pre-crRNA spacers when bound to DNA targets, showcasing different activation mechanisms.
- The researchers also developed a straightforward, highly sensitive, and specific one-step DNA detection method utilizing the newly discovered cleavage activity of pre-crRNA spacers.
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