Engineering RAFT Polymers to the Protein-capped Gold Nanoclusters for Developing Fluorescent Polymeric Nanoconjugates.

The synthesis of fluorescent hybrid nanomaterials engineered via the chain-end modification of reversible addition-fragmentation chain-transfer (RAFT) polymers on the surface of bovine serum albumin (BSA) protein-stabilized gold nanoclusters (AuNCs@BSA) is described. Based on the "grafting-to" approach the core-shell structured nanoconjugates AuNCs@BSA/polymer are generated via effective ligation of hydrophilic, and stimuli-responsive polymers. Such nanomaterials are characterized via various microscopic and spectroscopic studies and exhibit their size as ≈5 nm and emission peak at ≈650 nm.

Dysregulated cellular redox status during hyperammonemia causes mitochondrial dysfunction and senescence by inhibiting sirtuin-mediated deacetylation.

Perturbed metabolism of ammonia, an endogenous cytotoxin, causes mitochondrial dysfunction, reduced NAD /NADH (redox) ratio, and postmitotic senescence. Sirtuins are NAD -dependent deacetylases that delay senescence. In multiomics analyses, NAD metabolism and sirtuin pathways are enriched during hyperammonemia.

Shared and unique phosphoproteomics responses in skeletal muscle from exercise models and in hyperammonemic myotubes.

Skeletal muscle generation of ammonia, an endogenous cytotoxin, is increased during exercise. Perturbations in ammonia metabolism consistently occur in chronic diseases, and may blunt beneficial skeletal muscle molecular responses and protein homeostasis with exercise. Phosphorylation of skeletal muscle proteins mediates cellular signaling responses to hyperammonemia and exercise.

Metabolic reprogramming during hyperammonemia targets mitochondrial function and postmitotic senescence.

Ammonia is a cytotoxic metabolite with pleiotropic molecular and metabolic effects, including senescence induction. During dysregulated ammonia metabolism, which occurs in chronic diseases, skeletal muscle becomes a major organ for nonhepatocyte ammonia uptake. Muscle ammonia disposal occurs in mitochondria via cataplerosis of critical intermediary metabolite α-ketoglutarate, a senescence-ameliorating molecule.

Small peptide inhibitor from the sequence of RUNX3 disrupts PAK1-RUNX3 interaction and abrogates its phosphorylation-dependent oncogenic function.

P21 Activated Kinase 1 (PAK1) is an oncogenic serine/threonine kinase known to play a significant role in the regulation of cytoskeleton and cell morphology. Runt-related transcription factor 3 (RUNX3) was initially known for its tumor suppressor function, but recent studies have reported the oncogenic role of RUNX3 in various cancers. Previous findings from our laboratory provided evidence that Threonine 209 phosphorylation of RUNX3 acts as a molecular switch in dictating the tissue-specific dualistic functions of RUNX3 for the first time.

Systems Biology Analyses Show Hyperactivation of Transforming Growth Factor-β and JNK Signaling Pathways in Esophageal Cancer.

Background & Aims: Esophageal adenocarcinoma (EAC) is resistant to standard chemoradiation treatments, and few targeted therapies are available. We used large-scale tissue profiling and pharmacogenetic analyses to identify deregulated signaling pathways in EAC tissues that might be targeted to slow tumor growth or progression.

Methods: We collected 397 biopsy specimens from patients with EAC and nonmalignant Barrett's esophagus (BE), with or without dysplasia.