Hexaribouridylic acid, prepared by digestion of poly(U) with cobra venom endonuclease, and trinucleotide AUG synthesized chemically by triester approach were joined by RNA-ligase to yield a nonaribonucleotide AUGU6 bearing the initiation codon at its 5'-terminus. 2',3'-O-(4-[N-(2-chloro(or hydroxy) ethyl-N-Methylamino])- benzylidene residues were introduced at the 3'-terminus of oligonucleotide AUGU6 and its benzylidene derivatives AUGU6CHRCl or AUGU6CHROH were obtained. The mRNA analogs synthesized were tested for their template activity in the formation of 70S initiation complex. AUGU6, AUGU6CHRC1 and AUGU6CHROH were shown to stimulate factor-dependent binding of fMet-tRNA to ribosomes. The effect of benzylidene fragment on the template activity of AUGU6CHROH in the course of translation process was studied. It was shown that AUGU6CHROH stimulates synthesis of di- and tripeptides with the same efficiency as AUGU6.
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Stem Cell Res Ther
January 2025
Department of Medicine, Veterans Affairs Medical Center, Washington, DC, USA.
Introduction: Effects of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) was examined on peripheral blood derived CD34 + Hematopoetic Stem Cells (HSCs) as a cellular CVD biomarker. Both Dapa (a sodium-glucose co-transporter 2 or SGLT2, receptor inhibitor) and Saxagliptin (a Di-peptydl-peptidase-4 or DPP4 enzyme inhibitor) are commonly used type 2 diabetes mellitus or T2DM medications, however the benefit of using the combination has not been evaluated for cardio-renal risk assessment, in a real-life practice setting, compared to a placebo.
Hypothesis: We hypothesized that Dapa will improve the outcomes when compared to placebo and the Combo maybe even more beneficial.
Structure
January 2025
Department of Hepatobiliary Surgery, Innovative Institute of Tumor Immunity and Medicine (ITIM), Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address:
NSUN6 preferentially catalyzes the methylation of cytosine nucleotides in mRNA substrates, which enhances transcription. Dysregulation of NSUN6 catalysis drives the oncogenesis of certain cancers. In this study, we determined the crystal structure of human NSUN6 in complex with its S-adenosyl-L-methionine analog and a bound NECT-2 3'-UTR RNA substrate at 2.
View Article and Find Full Text PDFMed Oncol
January 2025
School of Basic Medicine, Gannan Medical University, Ganzhou, 341000, Jiangxi, China.
Osteosarcoma (OS) is the most commonly diagnosed primary malignant bone tumor in children and adolescents. Despite significant advancements in therapeutic strategies against OS over the past few decades, the prognosis for this disease remains poor, largely due to its high invasiveness and challenges associated with its treatment. N6-methyladenosine (m6A) modification is one of the most abundant epigenetic modifications of RNAs, and many studies have highlighted its crucial role in OS.
View Article and Find Full Text PDFBiotechnol Prog
January 2025
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India.
Type 2 diabetes mellitus (T2DM) and obesity are critical global health issues with rising incidence rates. Glucagon-like peptide-1 (GLP-1) analogues have emerged as effective treatments due to their ability to regulate blood glucose levels and gastric emptying through central nervous signals involving hypothalamic receptors, such as leptin. To address the short plasma half-life of native GLP-1, a C-16 fatty acid was conjugated to lysine in the GLP-1 analogue sequence to enhance its longevity.
View Article and Find Full Text PDFClin Exp Metastasis
January 2025
Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, No.88, Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Background: In recent years, the emphasis has shifted to understanding the role of N1-methyladenosine (m1A) in tumor progression as little is known about its regulatory effect on mRNA and its role in the metastasis of colorectal cancer (CRC).
Methods: We performed methylated RNA immunoprecipitation sequencing of tumor tissues and tumor-adjacent normal tissues from three patients with CRC to determine the m1A profile of mRNA in CRC. The expression of diaphanous-related formin 3 (DIAPH3) and its correlation with clinicopathological characteristics of CRC were evaluated using immunohistochemistry and online datasets.
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