Nomogram to predict recurrence risk factors in patients with non-valvular paroxysmal atrial fibrillation after catheter radiofrequency ablation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is an effective method for controlling the heart rate of paroxysmal atrial fibrillation (PAF). However, recurrence is trouble under the RFCA. To gain a deeper understanding of the risk factors for recurrence in patients, we created a nomogram model to provide clinicians with treatment recommendations. METHODS: A total of two hundred thirty-three patients with PAF treated with RFCA at Guizhou Medical University Hospital between January 2021 and December 2022 were consecutively included in this study, and after 1 year of follow-up coverage, 166 patients met the nadir inclusion criteria. Patients with AF were divided into an AF recurrence group and a non-recurrence group. The nomogram was constructed using univariate and multivariate logistic regression analyses. By calculating the area under the curve, we analyzed the predictive ability of the risk scores (AUC). In addition, the performance of the nomogram in terms of calibration, discrimination, and clinical utility was evaluated. RESULTS: At the 12-month follow-up, 48 patients (28.92%) experienced a recurrence of AF after RFCA, while 118 patients (71.08%) maintained a sinus rhythm. In addition to age, sex, and TRV, LAD, and TTPG were independent predictors of recurrence of RFCA. The c-index of the nomogram predicted AF recurrence with an accuracy of .723, showing good decision curves and a calibrated nomogram, as determined by internal validation using a bootstrap sample size of 1000. CONCLUSION: We created a nomogram based on multifactorial logistic regression analysis to estimate the probability of recurrence in patients with atrial fibrillation 1 year after catheter ablation. This plot can be utilized by clinicians to predict the likelihood of recurrence.

BST-1 aggravates aldosterone-induced cardiac hypertrophy via the Ca2+ /CaN/NFATc3 pathway.

BST-1 (bone marrow stromal cell antigen-1) is thought to be a key molecule involved in regulating the functional activity of cells in various tissues and organs. BST-1 can catalyze the hydrolysis of nicotinamide adenine dinucleotide (NAD+) to produce cyclic ADP ribose (cADPR), which activates the activity of intracellular Ca2+ signaling. Currently, the role of BST-1 regulation of Ca2+ signaling pathway in pathological myocardial hypertrophy is unclear. We found elevated expression of BST-1 in cardiac hypertrophy tissues of spontaneously hypertensive rats in our vivo study, subsequently; the mechanism of BST-1 action on myocardial hypertrophy was explored in vitro experiment. We used aldosterone (ALD) to induce H9C2 cellular hypertrophy. cADPR levels and intracellular Ca2+ concentrations declined and calcium-regulated neurophosphatase (CaN) activity and protein expression were decreased after BST-1 knockdown. And then activated T-cell nuclear factor (NFATc3) entry nucleus was inhibited. All of the above resulted in that H9C2 cells size was reduced by rhodamine-phalloidin staining. Thus, BST-1 may exacerbate cardiac hypertrophy by activating the Ca2+/CaN/NFATc3 pathway.

Comprehensive transcriptome and methylome analysis delineates the biological basis of hair follicle development and wool-related traits in Merino sheep.

BACKGROUND: Characterization of the molecular mechanisms underlying hair follicle development is of paramount importance in the genetic improvement of wool-related traits in sheep and skin-related traits in humans. The Merino is the most important breed of fine-wooled sheep in the world. In this study, we systematically investigated the complexity of sheep hair follicle development by integrating transcriptome and methylome datasets from Merino sheep skin. RESULTS: We analysed 72 sequence datasets, including DNA methylome and the whole transcriptome of four gene types, i.e. protein-coding genes (PCGs), lncRNAs, circRNAs, and miRNAs, across four embryonic days (E65, E85, E105, and E135) and two postnatal days (P7 and P30) from the skin tissue of 18 Merino sheep. We revealed distinct expression profiles of these four gene types across six hair follicle developmental stages, and demonstrated their complex interactions with DNA methylation. PCGs with stage-specific expression or regulated by stage-specific lncRNAs, circRNAs, and miRNAs were significantly enriched in epithelial differentiation and hair follicle morphogenesis. Regulatory network and gene co-expression analyses identified key transcripts controlling hair follicle development. We further predicted transcriptional factors (e.g. KLF4, LEF1, HOXC13, RBPJ, VDR, RARA, and STAT3) with stage-specific involvement in hair follicle morphogenesis. Through integrating these stage-specific genomic features with results from genome-wide association studies (GWAS) of five wool-related traits in 7135 Merino sheep, we detected developmental stages and genes that were relevant with wool-related traits in sheep. For instance, genes that were specifically upregulated at E105 were significantly associated with most of wool-related traits. A phenome-wide association study (PheWAS) demonstrated that candidate genes of wool-related traits (e.g. SPHK1, GHR, PPP1R27, CSRP2, EEF1A2, and PTPN1) in sheep were also significantly associated with dermatological, metabolic, and immune traits in humans. CONCLUSIONS: Our study provides novel insights into the molecular basis of hair follicle morphogenesis and will serve as a foundation to improve breeding for wool traits in sheep. It also indicates the importance of studying gene expression in the normal development of organs in understanding the genetic architecture of economically important traits in livestock. The datasets generated here are useful resources for functionally annotating the sheep genome, and for elucidating early skin development in mammals, including humans.

Lipoamide Attenuates Hypertensive Myocardial Hypertrophy Through PI3K/Akt-Mediated Nrf2 Signaling Pathway.

The process of myocardial hypertrophy in hypertension can lead to excessive activation of oxidative stress. Lipoamide (ALM) has significant antioxidant and anti-inflammatory effects. This study aimed to investigate the effects of ALM on hypertension-induced cardiac hypertrophy, as well as explore its underlying mechanisms. We evaluated the effects of ALM on spontaneously hypertensive rats and rat cardiomyocytes treated with Ang II. We found that ALM was not effective in lowering blood pressure in SHR, but it attenuated hypertension-mediated cardiac fibrosis, oxidative stress, inflammation, and hypertrophy in rats. After that, in cultured H9C2 cells stimulated with Ang II, ALM increased the expression of antioxidant proteins that were decreased in the Ang II group. ALM also alleviated cell hypertrophy and the accumulation of ROS, while LY294002 partially abrogated these effects. Collectively, these results demonstrate that ALM could alleviate oxidative stress in cardiac hypertrophy, potentially through the activation of the PI3K/Akt-mediated Nrf2 signaling pathway.

Identification of anti-photoaging components of Olea europaea leaves based on spectrum-effect relationship.

In this study, to identify bioactive components of Olea europaea leaves extract (OLE), chemometrics analyses including bivariate correlation analysis and partial least squares regression were used to establish the relationships between the chromatograms and anti-photoaging effect of OLE samples. Firstly, the fingerprint of olive leaves extract was determined by high-performance liquid chromatography (HPLC). Photoaging models of HaCaT cells were established by UVB irradiation. The photoaging resistance of OLE was evaluated by cell viability using the MTT assay. Chemometrics analyses showed that compounds 14, 19, 20, 24, 26, and 28 might be the major anti-photoaging components of OLE. Furthermore, after separation by HSCCC and NMR identification, compound 19 is luteoloside and compound 24 is oleuropein. Oleuropein and luteoloside were docked with collagenase (MMP-1), stromelysin (MMP-3), and gelatinase (MMP-9), respectively. The results showed that oleuropein and luteoloside inhibited their activity by directly interacting with MMP-1, MMP-3, and MMP-9, thereby exhibiting anti-photoaging activity. The current bioassay and spectrum-effect relationships are proper for associating sample quality with the active ingredient, and our finding would provide foundation and further understanding of the quality evaluation and quality control of Olea europaea.

Differential Methylation and Transcriptome Integration Analysis Identified Differential Methylation Annotation Genes and Functional Research Related to Hair Follicle Development in Sheep.

Hair follicle growth and development are a complex and long-term physiological process, which is regulated by a variety of physical factors and signal pathways. Increasing the understanding of the epigenetic regulation and function of candidate genes related to hair follicle development will help to better understand the molecular regulatory mechanisms of hair follicle development. In this study, the methylated DNA immunoprecipitation sequencing (MeDIP-seq) was used to obtain the genome-wide methylation map of the hair follicular development of Super Merino sheep in six stages (fetal skin tissue at 65d, 85d, 105d, 135d, 7d, and 30d after birth). Combined with the results of previous RNA-sequencing, 65 genes were screened out that were both differential methylation and differential expression, including EDN1, LAMC2, NR1D1, RORB, MyOZ3, and WNT2 gene. Differential methylation genes were enriched in Wnt, TNF, TGF-beta, and other signaling pathways related to hair follicle development. The bisulfite sequencing PCR results and MeDIP-seq were basically consistent, indicating that the sequencing results were accurate. As a key gene in the Wnt signaling pathway, both differential methylation and expression gene identified by MeDIP-seq and RNA-seq, further exploration of the function of WNT2 gene revealed that the DNA methylation of exon 5 (CpG11 site) promoted the expression of WNT2 gene. The overexpression vector of lentivirus pLEX-MCS-WNT2 was constructed, and WNT2 gene effectively promoted the proliferation of sheep skin fibroblasts. The results showed that WNT2 gene could promote the growth and development of skin and hair follicles. The results of this study will provide a theoretical basis for further research on sheep hair follicle development and gene regulation mechanisms.