Nucleosides, Nucleotides & Nucleic Acids最新文献

The short-amplicon sequencing of hypervariable regions of 16S rRNA gene is the widely used method for bacterial identification and microbiota profiling. Bacteria possess multiple copies of 16S rRNA gene and may contain single nucleotide variations (SNPs) or amplicon sequence variants (ASVs). The ASVs based determination of microbial taxa can be better representation over operational taxonomic units (OTUs). Illumina based NGS platforms are mostly used to define the ASVs whereas Ion-torrent platform is commonly used for diagnostic purposes. We aimed to identify bacterial isolates having ASVs and infer the copy numbers of16S rRNA gene using short read sequencing performed on the Ion Gene Studio S5 NGS platform. The V2-V3 regions of 16S rRNA gene were amplified from the bacterial isolates and subjected to NGS. Further, the sequences produced by NGS were compared with those generated from Sanger sequencing. The bacterial isolates were identified and characterize during ASVs. The copy number of the 16S rRNA gene was established in Gram-negative isolates. Assigning bacterial taxa based on ASVs would provide a more accurate representation of the variant data.

Epigenetic modifications play a crucial role in various diseases, including cancer. Targeting chromatin modulators to normalize these epigenetic markers is a promising avenue for overcoming cancer drug resistance and improving treatment efficacy. Histone chaperones, implicated in cancer due to their imperfect compensatory mechanisms, represent potential targets for epidrugs. To identify these targets, we performed enrichment and network analyses of histone chaperone interactions, both among themselves and with other proteins. This approach provided insights into structure-function relationships. The selective binding of histone chaperones to canonical histones highlights their potential as epidrugs targets. Network analysis of common histone chaperones identified key hub proteins: HSP90AB1, RBBP4, NPM1, DAXX, and SET. These hub proteins, particularly RBBP4, which formed the largest protein cluster was found associated with oncogenesis, suggesting RBBP4 as prime candidates for therapeutic intervention. Druggability prediction of these hub protein pockets further identified RBBP4 as the most promising target, with Ritonavir emerging as a potential epidrugs. These findings provide a crucial foundation for future epidrugs discovery targeting cancer.

Objective: Using DNA microarray technology, we compared the differences in mRNA expression profiles between human hypertrophic scars (HTS) and normal skin tissues. Analyzing the differential genes in bioinformatics, to explore the pathogenesis of HTS at the molecular level, and to provide new targets for clinical treatment of HTS.

Methods: Three HTS samples and their adjacent normal skin samples were collected. The extraction of total RNA was performed for cDNA microarray analysis. The screening of differentially expressed genes was carried out by using Genespring 10.0 software, and cluster analysis was performed between HTS and normal skin groups within the group, and Gene Ontology (GO) and biological pathway analysis were performed for differentially expressed genes by using DAVID Bioinformatics Resources 6.7.

Results: In the 3 HTS samples, 3832 mRNAs overlapped in 3 HTS samples with more than 2-fold changes, 1920 mRNAs with more than 2-fold up-regulation, 1912 mRNAs with more than 2-fold down-regulation, 18 mRNAs with more than 5-fold up-regulation, and 29 mRNAs with more than 5-fold down-regulation. The results of the GO analysis showed that CDKN1C, CDKN2A, CTNNA3, COL6A3, HOXB4 and other differentially expressed genes are closely related to biological processes such as cell cycle, cell proliferation, and cell adhesion. The kegg pathway enrichment analysis showed that TGF-β1, CDKN1C, CDKN2A, CDC14A, ITGB6, EGF and other differentially expressed genes are mainly involved in the formation of adhesion plaques, β transforming factor signaling pathways, cell cycle signaling pathways, P53 signaling pathways, and tumor-related signaling pathways.

Conclusion: The mRNA expression profile of human HTS samples showed significant changes compared to normal skin samples. TGF-β1, SMAD2, SMAD7, BAX, IGF2, COL1A1, COL1A2, MMPs, CDC14A, ITGB6, EGF, CDKN1C, CDKN2A, CTNNA3, HOXA3 and other related genes involved in biological processes, molecular functions, signaling pathways may be closely related to the occurrence and development of hypertrophic scars.

This study introduces a new and simple method for the synthesis of a series of 3-(benzo[d]thiazol-2-yl)-5-phenylisoxazole derivatives 3(a-f), and examines its potential interactions with DNA. The synthesis includes the reaction of 2-aminobenzenethiol (1) with a variety of substituted 5-phenylisoxazole-3-carbaldehydes 2(a-f) in the presence of a cost-effective and reusable nanocatalyst, Calcium-Zincate (CaZnO₂). The CaZnO₂ catalyst showed a consistent and long-lasting catalytic activity over several reaction cycles and retained its unique heterogeneous properties. The resulting compounds were characterized in detail using various spectroscopic and analytical techniques in order to confirm their structures. In addition, the interaction of these synthesized compounds with calf thymus-DNA (CT-DNA) using absorption spectroscopy and viscosity measurements was assessed. In silico docking studies were performed to predict their binding affinity with human DNA (PDB ID: 1G3X). The compounds were further analyzed using the Density Functional Theory (DFT) with the B3LYP functional and the 6-31 G(d) basis set in chloroform, with the results aligning closely with the experimental findings. Furthermore, the compounds ability to cleave PUC19 DNA was assessed, along with their photoinduced nuclease activity under UV-visible light, confirmed by photo-induced cleavage assays.

The relationship between TMEM132D and depressive symptoms in community populations has not been investigated. Therefore, we explored the association between TMEM132D gene polymorphism and depressive symptoms based on data from a community sample of older adults in Qingdao. A total of 863 older adults were included in this study to examine the relationship between 12 SNPs and depressive symptoms. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Logistic regression analysis was used to analyze the relationship between SNPs and depressive symptoms based on five genetic models. Finally, linkage disequilibrium analysis was performed, and haplotype domains were constructed. We discovered a statistically significant difference between groups with and without depressive symptoms in the genotype and allele frequencies of rs2292723. In addition, multivariate logistic regression showed that rs2292723 and rs2170820 were positively associated with depressive symptoms, and rs61944776 was negatively associated with depressive symptoms. Finally, we found that the haplotype "CTC" of rs2292723, rs492759, and rs61944776 was significantly associated with depressive symptoms by haplotype analysis. Our study suggested that TMEM132D was associated with depressive symptoms, which supplemented the role of the TMEM132D gene in psychiatric disorders.

Lipids and glucose are important components of energy metabolism closely linked to each other. Glucose regulates cholesterol uptake via regulating the expression of different membrane transport proteins including NPC1L1, SR-B1 and ATP-binding cassette (ABC) transporters. Here, we explored further the mechanism underlying glucose-mediated regulation of cholesterol absorption and secretion. Caco-2 cells were cultivated in glucose-repletion versus glucose-depletion conditions. Quantitative real-time PCR and western blot were performed to assess mRNA and protein levels of different transporters. The amount of 25-NBD cholesterol uptake and the activity of P-gp (ABCB1) protein were measured by direct fluorometry and Rhodamine 123 efflux assay, respectively. Glucose-depleted Caco-2 cells showed lower NPC1L1 expression accompanied by reduced cholesterol uptake when compared to glucose-repleted cells. This effect was associated with an increase in the apical secretion of cholesterol compared with the basal secretion. In addition, glucose depletion upregulated both the expression level and activity of ABCB1, an apical pole transporter. However, the expression levels of ABCG5/G8, an apical sterol dimer transporter as well as ABCA1, a basal cholesterol transporter, were unchanged. The knockdown of ABCB1 in Caco-2 cells increased the intracellular accumulation of cholesterol. Glucose depletion reduces cholesterol accumulation in intestinal cells upon inducing its apical removal via ABCB1-dependent mechanism.

Objectives: Coronavirus disease 2019 (COVID-19) is the most influential public health emergency worldwide. Controlling viral infection with people's health and reducing the impact on people's freedom is difficult at present. The precise control of COVID-19 in a city may be a suitable solution.

Methods: An anonymous cross-sectional survey was conducted among Hangzhou people between 1 January and 28 February 2022. We organized the classification, incidence rate and mortality of COVID-19. And we introduced the discovery process of Omicron, health code of four colors, the epidemiological investigation and the policies of government in Hangzhou. This paper discusses various measures taken against Omicron in Hangzhou, China, which are effective methods to deal with such public health emergencies.

Conclusions: Hangzhou quickly controlled the epidemic through precise control. As of February 1, Hangzhou had 115 confirmed cases with total population is 12.204 million. The rate of severe and death is 0%. Hangzhou's new model of precise control provides an important reference for the global city's response to COVID-19 and the reduction in losses caused by COVID-19. The COVID-19 Omicron variant outbreak indicates that people will still face unpredictable health risks in the future. Precise control is one of the best ways to effectively manage an epidemic, minimize its severity, and reduce losses in all aspects.

Colon cancer ranks among the prevalent malignancies globally, and its proclivity for metastasis significantly contributes to the adverse prognostic outcomes observed in patients. The epithelial-mesenchymal transition (EMT) represents a critical biological process through which tumor cells gain migratory and invasive capabilities. Nilotinib is a selective inhibitor of tyrosine kinases, commonly utilized in the treatment of chronic myeloid leukemia. Prior investigations have demonstrated that the Nilotinib derivative, N-12, exhibits significant antitumor properties. The objective of this study is to elucidate the inhibitory effects of N-12 on the progression of EMT in colon cancer cells. So, the human colon cancer cell line HCT116 and SW480 were selected for experimentation. Initially, assessments of cell proliferation, migration and invasion were conducted utilizing MTT, colony formation, Edu and Transwell assays. Subsequently, the chick embryo chorioallantoic membrane model was employed to evaluate tumor size and its impact on angiogenesis in vivo. Thereafter, HCT116 cells treated with N-12 underwent RNA sequencing for analysis. Finally, the expression levels of EMT markers in colon cancer cells were determined by Western blot analysis. The results showed that N-12 significantly curtails the proliferation, migration, and invasion of colon cancer cells, and concurrently impedes tumor growth in vivo by influencing angiogenesis within the chick embryo chorioallantoic membrane. Furthermore, RNA sequencing and Western blot analyses have elucidated that the antitumor efficacy of N-12 is attributable to the inhibition of the EMT signaling pathway. These results underscore the therapeutic potential of N-12 in the management of colon cancer and delineate its mechanism of action.

The MBL2 gene encodes the mannose-binding lectin protein (MBL), which is secreted by the liver. Several variants of MBL2 have been found to be associated with altered serum levels and susceptibility to various chronic diseases. Defects in MBL protein polymerization that result in functional impairments and/or low serum levels may influence genetic susceptibility to type 2 diabetes (T2D) and its complications. Therefore, the present case-control study was conducted to assess the potential association of six MBL2 gene variants and haplotypes with susceptibility to T2D and its complications in Morocco. The MBL2 gene was genotyped by PCR-sequencing for the promoting, non-coding, and coding regions in 435 individuals. Our findings revealed a significant association between the heterozygous CG and homozygous recessive GG genotypes of the variant at position -221 C > G in the MBL2 gene promoter with an increased risk of T2D. Similarly, for +4 C > T in the non-coding region, statistical analysis indicates a strong association with T2D risk, particularly with the heterozygous CT and homozygous recessive TT genotypes. The LYQC haplotype is also found to be associated with T2D risk. Furthermore, the heterozygous CT genotype, and recessive T allele of the variant at position +4 C > T, and heterozygous GA genotype of codon Gly54Asp of the MBL2 gene, are associated with protection against hypertension in T2D patients. However, no association was observed between MBL2 variants and dyslipidemia in T2D patients. The study concludes that -221 C > G and +4 C > T variants of the MBL2 gene significantly contribute to T2D susceptibility in Morocco.

Mitochondrial dysfunction in failing hearts has been described as a driving force for energy deprivation and cardiomyocyte energy supply-demand imbalance. Isoproterenol (ISO), the β1/β2-adrenergic receptor agonist that leads to myocardial stress and mitochondrial damage, is extensively used for in vitro and in vivo studies to test the efficacy of therapeutic strategies in heart failure (HF). This study evaluated the cell morphology, nucleotide concentrations, and mitochondrial function of ISO-treated cardiomyocytes stimulated with the activators of mitochondrial biogenesis and nucleotide precursors. H9c2 rat cardiomyocyte line cells were treated with ISO in the presence of mitochondrial biogenesis stimuli quercetin (Que), rosiglitazone (Ros), S-Nitroso-N-acetyl-DL-penicillamin (SNAP), and NAD⁺ precursor, nicotinamide riboside (NR). The intracellular concentrations of nucleotides were analyzed using high-performance liquid chromato-graphy, and the Seahorse metabolic flux analyzer determined the mitochondrial function. ISO decreased intracellular ATP concentration in H9c2 cells as compared to control. The treatment with SNAP increased ATP concentration compared to ISO-only treated cells, while Que, Ros, and NR had no effect. NR treatment led to the elevation of intracellular NAD⁺ concentration, while the treatment with SNAP, Ros, and NR stimulated the mitochondrial respiration in ISO-pretreated H9c2 cells. In conclusion, mitochondrial biogenesis activators consistently improved cardiomyocyte mitochondrial function, but only selected molecules helped to improve ATP or NAD⁺ concentrations. This information may help to optimize treatment to ameliorate energy imbalance in failing cardiomyocytes.