Plasma 8-Hydroxy-2'-Deoxyguanosine, a Potential Valuable Biomarker for Atrial Fibrosis Is Influenced by Polymorphism of DNA Methylation Gene.

BACKGROUND: Previous studies revealed a relationship between 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the occurrence/recurrence of atrial fibrillation (AF). This 2-part study aimed to validate whether DNA damage related to 8-OHdG is associated with left atrial (LA) fibrosis in AF patients quantified by voltage mapping (Part I), and to identify the underlying genetic components regulating the 8-OHdG level (Part II).Methods and Results: Plasma 8-OHdG determination, DNA extraction, and genotyping were conducted before catheter ablation. LA voltage mapping was performed under sinus rhythm. According to the percentage of low voltage area (LVA), patients were categorized as stage I (<5%), stage II (5-10%), stage III (10-20%), and stage IV (>20%). Part I included 209 AF patients. The 8-OHdG level showed an upward trend together with advanced LVA stage (stage I 8.1 [6.1, 10.5] ng/mL, stage II 8.5 [5.7, 14.1] ng/mL, stage III 14.3 [12.1, 16.5] ng/mL, stage IV 13.9 [10.5, 16.0] ng/mL, P<0.000). Part II included 175 of the 209 patients from Part I. Gene-set analysis based on genome-wide association study summary data identified that the gene set named 'DNA methylation on cytosine' was the only genetic component significantly associated with 8-OHdG concentration. CONCLUSIONS: Higher 8-OHdG levels may predict more advanced LVA of the LA in AF patients. DNA methylation is the putative genetic component underlying oxidative DNA damage in AF patients.

Progressive outcomes of bundle branch reentrant ventricular tachycardia in patients without structural heart disease.

BACKGROUND: Ablation strategies to treat bundle branch reentrant ventricular tachycardia (BBRT) are well described. However, reports of long-term follow-up outcomes in BBRT patients without structural heart disease (SHD) are limited. OBJECTIVE: The purpose of this study was to investigate the long-term follow-up prognosis of BBRT patients without SHD. METHODS: Changes in electrocardiographic and echocardiographic parameters were used to evaluate progression during follow-up. Potential pathogenic candidate variants were screened using a specific gene panel. RESULTS: Eleven consecutive BBRT patients without obvious SHD based on echocardiographic and cardiovascular magnetic resonance imaging results were enrolled. Median age was 20 (11-48) years, and median follow-up time was 72 months. During follow-up, PR interval [206 (158-360) ms vs 188 (158-300) ms; P = .018] and QRS duration [187 (155-240) ms vs 164 (130-178) ms; P = .008] each increased significantly compared with postablation. Right- and left-sided chamber dilation and reduced left ventricular ejection fraction (LVEF) also were observed. Clinical deterioration or events occurred in 8 patients: 1 sudden death; 3 both complete heart block and reduced LVEF; 2 significantly reduced LVEF; and 2 prolonged PR interval. Genetic testing results showed that 6 of 10 patients (excluding the patient with sudden death) had ≥1 potential pathogenic candidate variants. CONCLUSION: Further deterioration of His-Purkinje system conduction was observed in young BBRT patients without SHD after ablation. The His-Purkinje system may be the first target of genetic predisposition.

Role of the Notch1 signaling pathway in ischemic heart disease (Review).

Ischemic heart disease (IHD) is a prevalent cardiovascular disease characterized by the formation, progression and rupture of atherosclerotic plaque. The Notch signaling pathway is a key mechanism facilitating intercellular coordination. An increasing number of studies have revealed the significance of Notch signaling, particularly as regards Notch1. Of note, the existence of aberrant Notch1 signaling in IHD is universal, suggesting clinical significance. Thus, the present review summarizes the implications of Notch1 signaling in endothelial cells, vascular smooth muscle cells and macrophages in association with the development of IHD. The present review also examined the effects of Notch1 signaling on various remodeling stages of IHD consisting of reendothelialization, neovascularization, and myocardial fibrosis. Moreover, the participation of Notch1 signaling in conventional reperfusion treatments and cardiac regeneration therapies is discussed. On the whole, the present review aims to outline Notch1 signaling as a novel target which may be used to enhance the treatment efficacy for patients with IHD.

Right atrial tachycardia after atrial fibrillation ablation: prevalence, clinical characteristics, electrophysiological mechanisms, and long-term outcomes.

BACKGROUND: This study aims to evaluate the prevalence, clinical characteristics, electrophysiological mechanisms, and long-term outcomes of right atrial tachycardia (AT) in patients who underwent ablation for atrial fibrillation (AF). METHODS: From March 2010 to December 2020, 220 consecutive patients undergoing index AF ablation were referred for post-ablation AT recurrence. Thirty-five patients (35/220, 15.9%) with right AT recurrence (25 men; mean age 59.3 ± 10.2 years) were enrolled. These patients were divided into groups with right ATs exclusively (group 1) and right combined with left ATs (group 2). RESULTS: Fifty-three ATs were mapped in all patients, with thirty-nine ATs originating from the right atrium. The detailed distribution of all right ATs was 22 in the cavo-tricuspid isthmus (CTI), 6 in the ostium of superior vein cava (SVC), 4 in the right free wall, 4 in the right anterior atrial septum, 2 in coronary sinus ostium, and 1 in crista terminalis. Group 2 had a significantly higher incidence of typical atrial flutter (AFL) than group 1 (11/12, 90.9% vs. 12/24, 50.0%, P = 0.03). During the mean follow-up of 43.6 ± 25.2 months after the index AT ablation, the recurrence rate of AT/AF was 22.9% (8/35), and it was lower in group 1 than in group 2 (8.3% vs. 54.5%, P = 0.01). CONCLUSION: Right AT is relatively less common post-AF ablation. The CTI-dependent AFL and the ostium of SVC-derived focal AT constituted the major components of right ATs, suggesting the importance of ablation- and anatomy-related arrhythmogenic effects in the right atrium.

The interplay between IQGAP1 and small GTPases in cancer metastasis.

The metastatic spread of tumor cells to distant anatomical locations is a critical cause for disease progression and leads to more than 90 % of cancer-related deaths. IQ motif-containing GTPase-activating protein 1 (IQGAP1), a prominent regulator in the cancer metastasis process, is a scaffold protein that interacts with components of the cytoskeleton. As a critical node within the small GTPase network, IQGAP1 acts as a binding partner of several small GTPases, which in turn function as molecular switches to control most cellular processes, including cell migration and invasion. Given the significant interaction between IQGAP1 and small GTPases in cancer metastasis, we briefly elucidate the role of IQGAP1 in regulating cancer metastasis and the varied interactions existing between IQGAP1 and small GTPases. In addition, the potential regulators for IQGAP1 activity and its interaction with small GTPases are also incorporated in this review. Overall, we comprehensively summarize the role of IQGAP1 in cancer tumorigenicity and metastasis, which may be a potential anti-tumor target to restrain cancer progression.

Correction to: The interplay between HIF-1α and noncoding RNAs in cancer.

In the original publication of this manuscript [1], Fig. 2 contains incorrect labels and feedback loops. The revised version of Fig. 2 is shown below.

The interplay between HIF-1α and noncoding RNAs in cancer.

Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications.

Decreased expression of SLC16A12 mRNA predicts poor prognosis of patients with clear cell renal cell carcinoma.

Solute carrier family 16, member 12 (SLC16A12) is a highly -expressed protein in the kidney and has been reported to participate in the transport of creatine. However, the clinical values of SLC16A12 in clear cell renal cell carcinoma (ccRCC) have not been explored.SLC16A12 RNA-seq data and clinical information were downloaded from the Cancer Genome Atlas (TCGA) database. We compared its expression in ccRCC and paracancerous tissues, then the result was further validated with our cohort. The impact on the clinical significance of SLC16A12 in ccRCC was also assessed.Compared with paracancerous tissue, SLC16A12 was significantly downregulated in the tumor tissues both in mRNA and protein level. In TCGA cohort, SLC16A12 mRNA expression was associated with several clinicopathological parameters, including T stages (P < .001), M stages (P = .009), TNM stages (P < .001), and differentiated grades (P = .001). Kaplan-Meier analysis showed that the overall survival of patients with low expression of SLC16A12 mRNA was significantly worse than that of patients with high expression (P < .001). Furthermore, both univariate (HR = 0.371, 95%CI: 0.269-0.513, P < .001) and multivariate (HR = 0.485, 95%CI: 0.297-0.793, P = .004) Cox regression analyses suggested that low expression of SLC16A12 mRNA was an independent prognostic factor for patients with ccRCC.Overall, we uncovered that decreased expression of SLC16A12 is a poor prognostic factor for patients with ccRCC. SLC16A12 might be a potential biomarker and therapeutic target in ccRCC.

Colorimetric and visual detection of mercury(II) based on the suppression of the interaction of dithiothreitol with agar-stabilized silver-coated gold nanoparticles.

A colorimetric and visual method is described for the determination of mercury(II) ion. A gel consisting of agar-stabilized silver-coated gold nanoparticles (Au@Ag NPs) was prepared. The reaction with dithiothreitol (DTT) via thiol-Ag chemistry results in an orange to purple color change of the gel. However, in the presence of Hg(II), the reaction of DTT with the silver shells is suppressed due to the strong thiophilicity of Hg(II). The color of the gel changes from purple to red to orange in the presence of increasing concentrations of Hg(II). The Au@Ag NPs therefore are a viable optical probe for Hg(II) which can be detected in concentration as low as 78 nM via dual-wavelength ratiometric absorbance (A390/A520), and at 1 µM levels with bare eyes. The use of agar as a support is mandatory to prevent the aggregation of the NPs and also improves selectivity. The method was applied to the analysis of spiked samples, and recoveries ranged between 96.3 and 104%. The assay is easy, inexpensive, and in our perception represents an attractive tool for on-site visual detection of Hg(II). Graphical abstract Schematic of the assay. With increasing concentrations of Hg(II), the oxidative etching of silver shells caused by dithiothreitol (DTT) is gradually inhibited, and the color of agar-stabilized Au@Ag NP gel varies from purple to red, and finally to orange. This can be used for visual detection of Hg(II).