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The Diverse Binding Modes Explain the Nanomolar Levels of Inhibitory Activities Against 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase from Exhibited by Reverse Hydroxamate Analogs of Fosmidomycin with Varying -Substituents.
Molecules
December 2024
School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
It is established that reverse hydroxamate analogs of fosmidomycin inhibit the growth of by inhibiting 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate pathway, which is absent in humans. Recent biochemical studies have demonstrated that novel reverse fosmidomycin analogs with phenylalkyl substituents at the hydroxamate nitrogen exhibit inhibitory activities against DXR at the nanomolar level. Moreover, crystallographic analyses have revealed that the phenyl moiety of the -phenylpropyl substituent is accommodated in a previously unidentified subpocket within the active site of DXR.
View Article and Find Full Text PDFHepatocellular Carcinoma Cells in Humans Exhibit Resistance to Suberoylanilide Hydroxamic Acid (SAHA) Owing to the Diminished Level of Hsa-miR-125a-5p.
Chem Biol Drug Des
January 2025
Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Hepatocellular carcinoma (HCC) presents an escalating public health challenge globally. However, drug resistance has emerged as a major impediment to successful HCC treatment, limiting the efficacy of curative interventions. Despite numerous investigations into the diverse impacts of hsa-miR-125a-5p on tumor growth across different cancer types, its specific involvement in chemotherapy resistance in HCC remains elusive.
View Article and Find Full Text PDFImproving sulforaphane content in broccoli sprouts by applying Se: transcriptome profiling and coexpression network analysis provide insights into the mechanistic response.
Physiol Plant
January 2025
College of Horticulture, Hunan Agricultural University, Changsha, China.
Sulforaphane (SF) is a sulfur (S)-containing isothiocyanate found in cruciferous vegetables and is known for its potent anticancer properties. Broccoli sprouts, in particular, are considered safe and healthy dietary choices due to their high SF content and other beneficial biological activities, such as enhanced metabolite ingestion. The application of selenium (Se) is an excellent approach to enhance the abundance of SF.
View Article and Find Full Text PDFSigma-1 Receptor as a Novel Therapeutic Target in Diabetic Kidney Disease.
Int J Mol Sci
December 2024
MTA-SE Lendület "Momentum" Diabetes Research Group, 1083 Budapest, Hungary.
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease. Current treatments for DKD do not halt renal injury progression, highlighting an urgent need for therapies targeting key disease mechanisms. Our previous studies demonstrated that activating the Sigma-1 receptor (S1R) with fluvoxamine (FLU) protects against acute kidney injury by inhibiting inflammation and ameliorating the effect of hypoxia.
View Article and Find Full Text PDFThe Chicken Promoter and Its Regulation by MYC and HIF1A.
Genes (Basel)
November 2024
Jiangsu Province Key Laboratory of Animal Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
Background: Histone deacetylase 4 () is a member of the class II histone deacetylase family, whose members play a crucial role in various biological processes. An in-depth investigation of the transcriptional characteristics of chicken can provide fundamental insights into its function.
Methods: We examined expression in chicken embryonic stem cells (ESC) and spermatogonial stem cells (SSC) and cloned a 444 bp fragment from upstream of the chicken transcription start site.
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