Nucleosides, Nucleotides & Nucleic Acids最新文献

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.

In the early stages, chronic kidney disease (CKD) can be asymptomatic, marking diagnosis difficult. This study aimed to investigate the diagnostic role and potential regulatory mechanisms of nucleolar protein 14 (NOP14) -antisense RNA 1 (AS1) in patients with CKD. Herein, 68 patients with CKD, 65 patients with CKD undergoing peridialysis, and 80 healthy adults were included. The real-time reverse transcription-quantitative polymerase chain reaction was performed to assess NOP14-AS1 levels, and its diagnostic value was evaluated using receiver operating characteristic curves. Additionally, cell proliferation and apoptosis were assessed by Cell Counting Kit-8 assay. and flow cytometry, respectively. Oxidative stress levels were determined using superoxide dismutase and malondialdehyde MDA kits, and the dual-luciferase reporter assay was performed to determine the relationship between NOP14-AS1 and microRNA-326 (miR-326) target binding. Lastly, the potential mechanism underlying miR-326 target gene regulation in CKD progression were explored utilizing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Notably, patients with CKD exhibited decreasedNOP14-AS1 levels and upregulated miR-326 levels. NOP14-AS1 and miR-326 exhibited combined effects on cell proliferation, apoptosis, inflammatory factors, and oxidative stress levels. Furthermore, the target genes of miR-326 showed enrichment in CKD-associated rat sarcoma and phosphoinositide 3-kinase protein kinase B pathways. Altogether, the findings of this study show the potential of NOP14-AS1 as a diagnostic marker in CKD. Overall, NOP14-AS1 regulates the miR-326 expression, which, in turn, regulates various miR-326 target gene-associated signaling pathways, thereby affecting the occurrence and development of CKD.

This article presents a new and facile method for the synthesis of Schiff base compounds with a benzimidazole group using a low-cost and reusable calcium aluminate nanophosphorus catalyst (CaAl₂O₄). This approach avoids harmful solvents and reactants, supporting a more environmentally friendly synthesis process. The catalyst maintained its activity and heterogeneity over four cycles with minimal loss of efficiency. The synthesis process was straightforward and eliminated the need for column chromatography. The Schiff base ligand (HL=(E)-N-((6-(thiophen-2-yl)pyridin-2-yl)methylene)-1H-benzo[d]imidazol-2-amine)) was synthesized by the reaction of 6-(thiophen-2-yl)pyridine-2-carbaldehyde with 1H-benzimidazole-2-amine. Subsequently, metal(II) complexes of Co(II), Ni(II), and Cu(II) were prepared using this ligand. Structural analysis of both the ligand and its metal complexes was carried out using various physicochemical and spectroscopic methods. Ni(II) and Co(II) complexes were found to adopt an octahedral geometry, while the Cu(II) complex exhibited a square-planar structure. Binding studies with calf thymus DNA (CT-DNA) at pH 7.2 were performed using UV-visible spectroscopy, viscosity measurements, and thermal denaturation studies and showed that the metal complexes intercalate into the DNA and produced a distinct binding pattern. Molecular docking simulations with AutoDock Vina provided insights into the interaction of these complexes with the B-DNA dodecamer. Furthermore, the ligand and its metal complexes showed UV-visible photonuclease activity against pUC19 DNA. Agarose gel electrophoresis showed that the metal complexes exhibit photoinduced nuclease activity, confirming their ability to cleave DNA upon exposure to light.

Objective: Type 2 Diabetes Mellitus (T2DM) can lead to long-term vascular complications such as diabetic peripheral neuropathy (DPN). This study aimed to investigate the role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) and angiotensin II type 1 receptor (AT1R) A1166C variants in the predisposition to T2DM in the Turkish population and their association with DPN.

Methods: The study included 90 T2DM patients (42 with DPN) and 50 healthy individuals. ACE I/D and ATIR A1166C gene regions were analyzed for the variant. Both the general genotype distribution of these variants and the observed genotype ratios were examined separately.

Results: In the T2DM group, the proportion of individuals with the AA genotype of the AT1R A1166C variant was lower than in the control group, and the proportion of individuals with the AC genotype was higher. There was no significant difference in the genotype distribution between the groups for the ACE I/D variant. There was no significant difference in the genotype distribution of the ACE I/D and ATIR A1166C variants in patients with and without DPN.

Conclusion: In the Turkish population, no significant difference was observed in the overall genotype distribution of ACE I/D and AT1R A1166C variants between T2DM patients and healthy individuals, whereas the AC genotype of the AT1R A1166C variant was more frequent in T2DM patients, and the AA genotype was less frequent. For both variants, no significant difference was observed in the genotype distribution between T2DM patients with and without DPN.

The field of biomedical science has witnessed another milestone with the advent of RNA-based therapeutics. This review explores three major RNA molecules, namely: messenger RNA (mRNA), RNA interference technology (RNAi), and Antisense Oligonucleotide (ASO), and analyses U.S. Food and Drug Administration drugs from 14 RNA-based pharmaceutical companies in terms of targeted genes, diseases and types, clinical trials and status, the mode of delivery, and the year of production. Many of such drugs are clinically approved or pending approval by the U.S. Food and Drug Administration (FDA) alongside other leading drugs agencies. Regarding diseases, this article emphasizes cancer therapy, genetic diseases, viral infections, and two categories of drug delivery systems include viral vectors and nanoparticles. Despite the tremendous progress made, key issues associated with these delivery systems are stability, off-target activities of RNA payloads, efficiency in cellular uptake, and the innovative need for engineering techniques for modifications. This review emphasizes the transformative potential of RNA therapeutics and the role of innovative technologies in addressing clinical needs, paving the way for a new era in precision medicine.

Contamination of sodium ions in oligonucleotides often causes issues in mass spectrometric analysis. This study investigated the efficiency of the combination of ammonium acetate and alcohol in desalting oligonucleotides. It was found that oligonucleotide samples containing up to 4 M NaCl can be effectively desalted through precipitation with ethanol or isopropanol in the presence of 1 or 5 M ammonium acetate. The level of sodium ions was reduced by 2-3 orders of magnitude as determined by atomic emission spectroscopy. The desalted samples were successfully analyzed by direct-infusion electrospray ionization mass spectrometry.

Breast cancer is the most common malignancy that affects women. MicroRNAs (miRNAs) play an essential role in cancer therapy and regulate many biological processes such as cisplatin resistance. The study's objective was to determine whether miR-182 dysregulation was the cause of cisplatin resistance in TNBC cell line MDA-MB-231. To determine the expression of miR-182, PCR was performed with primers specific to miR-182, and agarose gel electrophoresis was performed. To reduce the expression of miR-182 in MDA-MB-231 cells, anti-miR-182 oligonucleotides were used. RT-qPCR was used to confirm knockdown. The knockdown and control groups were treated with cisplatin at the same time. Propidium iodide (PI) and Annexin V staining were performed for apoptosis assay. Flow cytometric analysis was used to investigate the effect of miR-182 knockdown on cell cycle arrest. In comparison to untreated control MDA-MB-231 cells with MDA-MB-231 cells treated with anti-miR-182, there was a significant increase in the cisplatin-induced early apoptosis phase (p = 0.023). Also, inhibition of miR-182 significantly increased the cell cycle arrest at the G2/M phase in MDA-MB-231 cells (p = 0.031). Our results revealed that miR-182 inhibition may play a role in the overcoming of cisplatin resistance by inducing apoptosis and, cell cycle arrest in TNBC.

In this study, Taguchi optimization method was applied to determine the optimum operating conditions for batch adsorption of Cr(VI) from aqueous solution. Initial pH of solution, adsorbent dose, initial hexavalent chromium concentration, contact time and adsorbent type were selected as the variables, and the removal efficiency of Cr(VI) was chosen for the designated response. L₁₈(3⁵) orthogonal array, signal-to-noise (S/N) ratio and analysis of variance statistical procedures were applied to identify the effect of each operating parameter on the removal of Cr(VI) from aqueous solution. The signal-to-noise (S/N) ratio results showed that the optimal combination for Cr(VI) removal was at pH 1.0, adsorbent dose of 3.6 g.L^-1, Cr(VI) concentration of 30 mg.L^-1, contact time of 95 min and olive leaves as adsorbent type. A removal of 95.09% was obtained at these optimum conditions. The analysis of variance of the data revealed that initial pH of solution was the most dominant parameter affecting Cr(VI) removal efficiency, followed by adsorbent type, adsorbent dose, contact time and initial metal concentration. Under optimal conditions, adsorption kinetic of Cr(VI) was studied and modeled using the pseudo first-order, pseudo-second-order and intraparticle diffusion models. It was found that the pseudo-second-order model fitted the adsorption data most with the highest determination coefficient (R² = 0.996). Freundlich isotherm model, with regression coefficient R² of 0.953, fit well with the equilibrium isotherm data. The Langmuir maximum adsorption capacity was found to be 62.5 mg.g^-1. The experimental values of ΔH°, ΔG° and ΔS° revealed that the adsorption process was spontaneous and endothermic.

MicroRNA-134 (miRNA134) has emerged as a critical regulator in the pathogenesis of epilepsy, particularly in intractable cases resistant to conventional therapies. This review explores the multifaceted roles of miRNA134 in epileptogenesis, focusing on its influence on dendritic spine morphology and synaptic plasticity. Through its interactions with proteins such as LIM kinase 1 (LIMK1), Pumilio 2 (PUM2), and Tubby-like protein 1 (TULP1), miRNA134 modulates various molecular pathways implicated in epilepsy development. Preclinical studies have shown pro-mising results in targeting miRNA134 for mitigating seizure activity, highlighting its potential as a therapeutic target. Furthermore, miRNA134 holds promise as a biomarker for epilepsy diagnosis and prognosis, offering opportunities for personalized treatment approaches. However, further research is warranted to elucidate the precise mechanisms underlying miRNA134's effects and to translate these findings into clinical applications.

Background: Multimerin 1 (MMRN1) is a factor V binding protein, which can support platelet adhesion and thrombus formation. In recent years, the role of MMRN1 in cancer has begun to attract attention. But systematic studies in this area are lacking. Therefore, we used bioinformatics methods to analyze MMRN1 in tumors to reveal the possible role of MMRN1.

Methods: Using the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database, we obtained relevant data for analyzing MMRN1. Using Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA), TCGA, GeneMANIA, and cBioPortal, we explored the potential role of MMRN1 in different types of tumors. Tumor Immune System Interactions and Drug Bank (TISIDB) and Sangerbox were used to analyze the correlation between MMRN1 and tumor immunity. Gene set cancer analysis (GSCA) and UALCAN were used to analyze the methylation of MMRN1. GSCA was also used to analyze the drug sensitivity of MMRN1.

Results: MMRN1 is down-regulated in most cancer types and is closely related to the prognosis of cancer patients. Interestingly, in most tumors, MMRN1 is positively correlated with immune -related genes. In addition, we observed different levels of methylation and mutations in different types of tumors. Drug sensitivity analysis found that MMRN1 was negatively correlated with several drugs, including GW-2580 and TL-1-85, suggesting that it can be used to develop potential anticancer therapies.

Conclusion: Our analysis demonstrated a significant relationship between MMRN1 and prognosis, tumor immunity, and drug sensitivity of several tumors. As a rising star in cancer, it needs further research.