Nucleosides, Nucleotides & Nucleic Acids最新文献

Understanding the interaction of therapeutic drugs with DNA is crucial for designing highly selective DNA-targeted medicines that could overcome the current therapeutic limitations. In this endeavour, the DNA binding behaviour of arbutin (ATN) was explored using multi-spectroscopic, electrochemical and computational studies. The UV-Vis spectral studies authenticated the complexation of ATN with CT-DNA and exposed ATN as a moderately strong DNA binder with a binding constant of 8.029 × 10³ M^-1. The findings of fluorescence spectral studies not only revealed the spontaneous ground state complex formation between ATN and CT-DNA, but also emphasised the role of hydrogen bonding and Van der Waals interactions in stabilising the ATN/CT-DNA complex. Since the competitive dye displacement assay strongly excluded the plausibility of classical intercalation and conventional groove binding mode of ATN, viscosity studies provided clues regarding the external binding mode of ATN. The appreciable enhancement resulted in the fluorescence emission of the ATN/CT-DNA complex upon increasing NaCl concentration, which certified ATN as an external binder. The CD spectral results exposed the ATN-induced moderate conformational alterations in CT-DNA. Remarkably, the voltammetric titration results labelled the glucopyranoside moiety of ATN as a DNA binding unit with a formation constant of 2.57 × 10⁴ M^-1 rather than the hydroquinone moiety of ATN. Molecular docking and metadynamics simulation outcomes served as pictorial evidence of experimental results. They revealed the predominant contribution of hydrogen bonding interactions in stabilising ATN/DNA complexation.

The main objective of this study is to detect the variants in patients who were diagnosed with familial Mediterranean fever (FMF) according to Tel-Hashomer diagnostic criteria and investigated the relationship between genotype-phenotype and the gene expression levels of the Mediterranean fever (MEFV) gene. Variant screening was achieved by automated sanger sequencing, and expression levels of the MEFV gene were analyzed by quantitative real time polymerase chain reaction (RT-PCR). A total of 46 patients with MEFV gene pathogenic variants and 8 control individuals without any variants were enrolled in the study. The most commonly encountered variants in heterozygote genotype were M694V (n = 4), E148Q (n = 3), and M680I (n = 2); in compound heterozygote genotype were M694V/R202Q (n = 4), and R202Q/E148Q (n = 3); in complex heterozygote genotype were R202Q/M694V/M680I (n = 4) and R202Q/M694V/V726A (n = 3); in homozygote genotype were M680I/M680I (n = 7) and M694V/M694V (n = 4). The gene expression levels of the patients with homozygous variants were found to be significantly lower than the healthy control group and patients with heterozygous variants. In patients with M694V homozygous variants, where clinical manifestations are severe, a remarkable decrease in the gene expression of the MEFV gene was observed. It was detected that there was a relationship between the genotype and gene expression level and that the level of gene expression and clinical symptoms were inversely correlated in patients with FMF.

Background: Esophageal cancer (EC) is among the deadliest malignancies in humans, with various miRNAs shown to regulate its progression by targeting distinct genes. miR-508-5p was identified as being linked to the malignant behavior of various tumors. Nevertheless, the precise role and mechanism of miR-508-5p in esophageal cancer (EC) remain ambiguous.

Objective: This investigation focuses on the role and mechanism of the miR-508-5p/TSGA10 axis in the progression of EC.

Methods: The expression of miR-508-5p and TSGA10 in EC cell lines was evaluated using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Cell transfection techniques were used to knock down miR-508-5p and observe its effects on cell proliferation, migration, invasion, and apoptosis. A dual-luciferase reporter gene assay was conducted to verify the targeting relationship of miR-508-5p with TSGA10. Co-culture studies were undertaken to examine the regulatory effect of the miR-508-5p/TSGA10 axis on the polarization state of tumor-associated macrophages (TAMs) and the malignant behavior of EC cells.

Results: The expression of miR-508-5p was significantly elevated in EC cells. Knocking down miR-508-5p curbed cell proliferation, migration, and invasion while promoting apoptosis. TSGA10 was validated as a primary target gene of miR-508-5p. miR-508-5p knockdown could inhibit the M2 polarization of TAMs by upregulating TSGA10, thereby suppressing the tumorigenic behavior of EC cells.

Conclusion: miR-508-5p promotes the M2 polarization of TAMs and enhances the malignant behavior of EC cells by inhibiting TSGA10.

Bacteriophage-based gene delivery systems are emerging as a promising alternative to traditional viral and non-viral vectors for targeted gene therapy in breast cancer. Their unique structural adaptability, low immunogenicity, and cost-effective production make them ideal candidates for precision medicine applications. Unlike conventional gene delivery platforms, bioengineered bacteriophages can be functionalized with tumor-specific ligands, modified for PEGylation to enhance circulation stability, and integrated with CRISPR/Cas9 gene-editing systems for precise genomic modifications. Additionally, bacteriophage vectors can be utilized in combination therapy, amplifying the effectiveness of chemotherapy and immunotherapy in breast cancer treatment. This mini-review discusses the bioengineering strategies used to enhance bacteriophage-based gene delivery, including surface modifications for tumor targeting, ligand-receptor binding for cellular uptake, and controlled genetic cargo release. We further examine in vitro and in vivo studies that demonstrate the potential of bacteriophage vectors in tumor suppression, gene expression efficiency, and immunomodulation. Furthermore, we explore the challenges and future directions of integrating bacteriophage-mediated gene therapy into clinical applications, addressing key issues such as systemic circulation half-life, off-target effects, and immune system interactions.

LncRNAs serve as crucial regulators in the survival and proliferation of tumors. This study is dedicated to exploring the functional significance of lncRNA PGM5-AS1 in breast cancer (BRCA). First, the expression level of PGM5-AS1 in BRCA patients and its diagnostic ability for BRCA were analyzed by RT-qPCR and Receiver Operating Characteristic curve. Subsequently, LnCAR database was used to preliminarily explore the relationship between PGM5-AS1 and prognosis. Moreover, we investigated the effects PGM5-AS1 on proliferation, apoptosis, and migration of BRCA cells by MTT assay, flow cytometry, and Transwell assay. More importantly, the regulation effect of PGM5-AS1 on the downstream target miR-182-5p was verified by dual luciferase reporting experiment, and the role of miR-182-5p was further explored in vitro experiments. PGM5-AS1 is significantly decreased in both BRCA patients and BRCA cell lines. In the diagnosis of BRCA, the sensitivity and specificity of PGM5-AS1 were 81.5% and 78.5%. Furthermore, lower levels of PGM5-AS1 are associated with a poor prognosis for affected patients. In vitro studies demonstrate that the upregulation of PGM5-AS1 confers a protective effect against BRCA, markedly inhibiting the viability and migratory capacity of tumor cells. More importantly, overexpression of PGM5-AS1 inhibited the high expression of miR-182-5p in tumor cells. In fact, inhibition of miR-182-5p is detrimental to the proliferation and migration of BRCA cells in vitro. lncRNA PGM5-AS1 has potential as a diagnostic marker for BRCA and acts as an inhibitor in BRCA. It inhibits tumor proliferation and metastasis by targeting miR-182-5p.

Objective: This study aimed to explore the diagnostic and prognostic value of miR-378c in hepatocellular carcinoma (HCC) patients.

Methods: This study included 97 HCC patients, 84 cirrhosis patients and 80 healthy volunteers. Serum miR-378c of all subjects and HCC cell lines was detected by qRT-PCR, and ROC curves were plotted to assess the clinical diagnostic value of miR-378c for HCC. The prognostic performance of miR-378c in HCC was assessed using the Kaplan-Meyer method and COX regression analysis. CCK-8 test for proliferation of HCC cell lines. The migration and invasion of HCC cell lines were measured by Transwell assay. Bioinformatics analysis was employed to analyze the possible target genes of miR-378c.

Results: Serum miR-378c were remarkably lower in HCC patients than in cirrhosis patients and healthy controls (p < 0.001). ROC curves indicated that serum miR-378c could effectively distinguish HCC patients from healthy controls and cirrhotic patients. Among HCC patients, those with high miR-378c expression had higher cumulative survival (p = 0.001), and COX analysis identified miR-378c as an independent prognostic biomarker for HCC. Overexpression of miR-378c significantly inhibited the proliferation, migration and invasion of MHCC97H and HepG2 cells (p < 0.01). Bioinformatics analysis of miR-378c target genes revealed that miR-378c target genes were enriched in tumor-associated pathways.

Conclusion: Serum miR-378c expression is decreased in HCC patients and strongly connected with poor prognosis. As a potential diagnostic and prognostic biomarker for HCC patients, it may provide new insights into the diagnosis and prognosis of HCC.

Ulcerative colitis (UC) is a chronic condition characterized by inflammation in the colon. Free radicals and oxidative stress play a significant role in the pathophysiology of UC. Excessive production of reactive oxygen species can damage the mitochondrial genome, leading to mutations such as the7436-bp deletion. The aim of this study was to identify the presence of the 7436-bp mtDNA deletion in patients with UC and its association with susceptibility to colon inflammation. This case-control study, included 195 patients with UC and 250 healthy individuals from the Iranian population. The Multiplex PCR method was used to detect the 7436-bp mtDNA deletion. Statistical analysis was performed using SPSS software. The frequency of 7436-bp mtDNA deletion in patients was 41.5% and 6.8% in healthy individuals. Statistical analysis showed a significant association between the frequency of the 7436-bp mtDNA deletion and UC (p = 0.016). Furthermore, a significant difference was found between the presence of this deletion and an increased risk of severe (p = 0.003) and extensive (p = 0.002) forms of UC. There was no statistically significant difference in the frequency of this deletion between younger patients and the control group. This study suggests that the presence of the 7436-bp mtDNA deletion is a risk factor for UC and plays a significant role in the pathogenesis of the disease. Further research involving larger and more diverse populations is necessary to validate or challenge these findings. Identifying these mutations can enhance our understanding of genetic factors influencing UC.

The hypervariable HVS-I and HVS-II regions of mitochondrial genome of 124 longevity individuals (age ≥ 90 years) and 46 non-longevity individuals (age ≤ 65 years) of purely Pashtun ethnicity were characterized for forensic purposes. Blood samples were collected from southern belt of Khyber Pakhtunkhwa (KP) province. For exploring the genetic architect of mitochondrial DNA of Pashtun longevity individuals. Sequence analysis revealed 16 major haplogroups and 56 sub-haplogroups in longevity persons and, 12 and 29 major and sub-haplogroups in non-longevity persons respectively. The 3 most common major haplogroups in longevity individuals were [M (25.0%), J (14.51%), D and U (13 = 10.48% each)], while in non-longevity human, these were [M (17.39%), H & T (15.21% each), and D (13.04%)]. Nineteen unique point mutations were identified not reported previously in reference sequence. More interestingly, the position of mutations found in non-longevity individuals were not observed in longevity individuals and vice versa. Data presented here may contribute to the accuracy of forensic mtDNA comparisons in the Pashtun of Pakistan. Social, cultural and unique territorial factors contribute to heterogeneous nature of Pashtun ethnic group.

Prostate cancer (PCa) is a frequently occurring malignant tumor affecting male reproductive system. miR-374a-5p was identified to participate in regulation of several tumors. The aim of the research was to discuss the influence for miR-374a-5p upon PCa progression and prognosis. A total of 112 PCa and 110 benign prostatic hyperplasia tissue samples were collected for the study. Real-time quantitative polymerase chain reaction was adopted to examine miR-374a-5p level in PCa tissues and cells. Kaplan-Meier and Cox model were applied to evaluate prognostic significance of miR-374a-5p for PCa. CCK8 and Transwell assays were carried out to analyze the efficacy of miR-374a-5p in PCa cell proliferation, migration and invasion. miR-374a-5p was under-expressed in PCa tissues and cells. Low expression of miR-374a-5p is linked to less favorable prognosis in PCa sufferers. Additionally, Cox analysis revealed that miR-374a-5p and TNM stage were two independent prognostic factors for PCa. Cellular assays showed that upregulating miR-374a-5p suppressed PCa cell proliferation, migration, and invasion.

Conversely, knockdown of miR-374a-5p facilitated PCa cell proliferation, migration, and invasion. miR-374a-5p expression decreased in PCa and was remarkably related to poor prognosis in PCa patients. miR-374a-5p acts in PCa by inhibiting cell proliferation, migration, and invasion. Consequently, miR-374a-5p has potential to act as a prognostic biomarker and a target for clinical therapeutic intervention in PCa.

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.