Biochemical and biophysical research communications最新文献

New phosphate-modified nucleic acid derivatives are of great significance in basic research and biomedical applications. We have recently developed a new class of phosphoramide benzoazole oligonucleotides (PABAOs). In this work, th properties of N-benzoxazole oligodeoxyribonucleotides have been thoroughly examined. We have demonstrated the convenient automated solid-phase synthesis of oligomers with a different number of modifications (up to six) at various positions. Optical properties, thermal stability, structure, and dynamics of PABAO/DNA complexes have been investigated. The N-benzoxazole-modified phosphate group is uncharged at neutral pH and has a pKa value of 8.52. Structural analysis performed by the CD spectroscopy and MD simulation indicate B-form of PABAO/DNA duplexes. The thermal stability of PABAO/DNA complexes bearing N-benzoxazole is reduced by 2.5-6.2° per modification compared to native duplexes at standard and near physiological buffer conditions. The performed study underlines a great potential of phosphoramide benzoazole oligonucleotides for basic research, applied sciences, and biotechnology.

Mitochondrial dysfunction contributes to septic acute kidney injury (S-AKI), making mitochondrial protection a potential therapeutic strategy. This study investigates the effects of S14G-humanin (HNG) in S-AKI, utilizing 4D-label-free and parallel reaction monitoring (PRM) techniques for proteomic analysis. An S-AKI model was created in male C57BL/6 mice using lipopolysaccharide (LPS) injection, followed by HNG administration. After 24 h, kidney tissues were analyzed for histology, biochemistry, mitochondrial function, and proteomics. HNG treatment improved renal function, reduced tubular injury, and decreased pro-inflammatory cytokines and oxidative stress markers. Proteomic analysis identified 5900 proteins, with 5111 quantifiable. HNG altered the expression of 132 proteins, with 18 selected for PRM validation. Ten of these proteins were linked to key pathways, including fatty acid degradation and PPAR signaling. This study is the first to show HNG's protective effects in S-AKI, providing insights into its mechanisms through advanced proteomic techniques.

Human genes have numerous copy number variations (CNVs) and single-nucleotide polymorphisms (SNPs) that control most of the body's core functions. On average, 12-16 % of human genes have CNVs, and a single gene can have a few hundred to several thousand SNPs. Numerous genome-wide association studies (GWAS) have shown that CNVs and SNPs can coexist in certain genomic regions, amplifying their effects on gene expression and regulation and disease susceptibility. Researchers initially categorized CNVs and SNPs into two types: homozygous and heterozygous. However, copy numbers were soon found to have a much wider range, underscoring their significance in certain diseases and microbial interactions. Because of the significant impact of CNVs and SNPs, research groups worldwide have eagerly sought effective methods for detecting both simultaneously. Despite yielding some minor results, these simultaneous counting methods have failed to meet expectations, leaving researchers to measure CNVs and SNPs separately. To overcome these limitations, we developed a novel approach by combining primers designed using the STexS method with matching probes used in the STexS II method. This method successfully detected both CNVs and SNPs in CYP2A6 and CYP2A7 using a single quantitative polymerase chain reaction. Once properly adjusted based on the three core principles, this new method markedly improved the time, cost-effectiveness, and overall accuracy of determining an individual's genetic status. Further testing of 100 human genomic DNA samples enabled calculations of the overall frequency of the [T] and [G] alleles of the CYP2A6 -48T > G SNP within an East Asian population yielded results that were highly congruent with those in a National Institutes of Health (NIH) database. This novel method will redefine genetic profiling and provide a means to successfully predict genetic characteristics and enhance personalized medicine by pinpointing appropriate individualized treatments.