Acetohydroxamic acid 250mg capsules

Ketone bodies generated in hepatocytes in the adult liver are used for nonhepatic tissues as an energy source. However, ketolysis is reactivated in hepatocellular carcinoma (HCC) cells with largely unelucidated mechanisms. Here, we demonstrate that 3-oxoacid CoA-transferase 1 (OXCT1), a rate-limiting enzyme in ketolysis, interacts with SUCLA2 upon IGF1 stimulation in HCC cells. This interaction results from ERK2-mediated SUCLA2 S124 phosphorylation and subsequent PIN1-mediated cis-trans isomerization of SUCLA2. OXCT1-associated SUCLA2 generates succinyl-CoA, which not only serves as a substrate for OXCT1 but also directly succinylates OXCT1 at K421 and activates OXCT1. SUCLA2-regulated OXCT1 activation substantially enhances ketolysis, HCC cell proliferation, and tumor growth in mice. Notably, treatment with acetohydroxamic acid, an OXCT1 inhibitor used clinically for urinary infection, inhibits liver tumor growth in mice and significantly enhances lenvatinib therapy. Our findings highlight the role of SUCLA2-coupled regulation of OXCT1 succinylation in ketolysis and unveil an unprecedented strategy for treating HCC by interrupting ketolysis.

Abstract licence: CC BY

Helicobacter pylori, a Gram-negative bacterium, exhibits unique adaptations to thrive in an acidic gastric environment. Urease enzyme present in the bacteria converts urea to ammonia and carbon dioxide, making the surrounding acidic environment of the bacteria neutral. This adaptation helps the bacteria to survive and travel further to gastric epithelial cells, where it attaches to mucin and damages the tissues, leading to gastritis, peptic ulcer, and ultimately, cancer. Physicians typically prescribe first-, second-, and third-line antibiotic therapies to eliminate the bacterium, but these treatments frequently fail to achieve complete eradication. This failure, driven by factors such as the coccoid form, high bacterial load, and biofilm formation, contributes to the growing problem of antibiotic resistance. Targeting urease activity presents a promising strategy to reduce the H. pylori pathogenicity and enhance its susceptibility to antibiotics. Inhibiting urease enzyme activity would be an option to make the bacteria less pathogenic and more prone to antibiotic treatment. Including the urease inhibitors as an adjuvant with the current antibiotic treatment regimen would effectively eradicate the bacteria. This comprehensive review discusses the structural characteristics of the urease enzyme and its role in pathogenesis and the available urease inhibitors along with their pharmacophoric features. An elaborative pharmacophore-based screening and docking study on scaffolds such as chlorogenic acid, catechol, and hydroxamic acid to discover a potent urease inhibitor is a future scope identified in this review.

Abstract licence: CC BY

BackgroundMedicinal mushrooms are sources of natural substances with diverse biological functions. The study evaluated the biological activity of Phellinus hartigii (Allesch. & Schnabl) Pat. and optimized extraction conditions to the maximize its bioactive potential.MethodsExtraction was performed using a Soxhlet apparatus under varying conditions: temperatures (30, 50, and 70 °C), durations (1, 5.5, and 10 h), and ethanol/water ratios (0%, 50%, and 100%). Total antioxidant status (TAS) was analyzed across 17 experiments, and the optimal conditions were identified using response surface methodology (RSM). Extracts from optimal conditions were further analyzed for antioxidant capacity (Rel assay kits, DPPH, FRAP), anticholinesterase activity (acetyl- and butyrylcholinesterase inhibition), antiproliferative activity (A549 lung cancer cell line), total phenolic content (Folin-Ciocalteu method), and phenolic compound profile (LC-MS/MS).ResultsOptimal extraction conditions were determined to be 48.22 ˚C, 9.04 h, and an ethanol/water ratio of 52.22%. The extract exhibited significant antiproliferative effects against the A549 lung cancer cells, with activity increasing in a concentration-dependent manner. The inhibition values (IC50) of acetylcholinesterase and butyrylcholinesterase were 21.29 ± 0.41 and 35.51 ± 0.53 μg/mL, respectively. The TPC (total phenolic content) value of the optimized extract was determined as 88.21 ± 1.50 mg/g, FRAP value as 137.81 ± 1.72 mg/g, DPPH value as 106.07 ± 2.44 mg/g, TOS (total oxidant status) value as 9.27 ± 0.06 µmol/L, TAS value as 4.98 ± 0.03 mmol/L and OSI (oxidative stress index) value as 0.19 ± 0.002. LC-MS/MS analysis identified nine phenolic compounds, with gallic acid and catechin hydrate as the most abundant.ConclusionsThe extract of P. hartigii obtained under optimal conditions demonstrated substantial antioxidant, anticholinesterase, and antiproliferative activities, highlighting its therapeutic potential.

Abstract licence: CC BY-NC-ND