Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism.

BACKGROUND: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. METHODS: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. RESULTS: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. CONCLUSION: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.

The role of left atrium posterior wall isolation in patients undergoing catheter ablation for atrial fibrillation.

The posterior left atrium (LAPW) is an important substrate for initiation and maintenance of atrial fibrillation (AF). While it has been proposed as a potential target for preventing recurrence of atrial tachyarrhythmias, it remains unclear whether electrical silence of LAPW offers additional benefits over pulmonary vein isolation (PVI) alone. We conducted a systematic review of PubMed, Medline, Embase, and Cochrane databases and identified 21 eligible studies, encompassing 1514 patients assigned to PVI + posterior wall isolation (PWI) group and 1629 patients assigned to PVI group. Over a median follow-up of 12 months, adjunctive PWI significantly improved the atrial tachyarrhythmia-free survival by 14 % in comparison to PVI alone [relative risk (RR): 1.14, 95 % confidence interval (CI): 1.04 to 1.25, p = 0.004]. This improvement was mainly attributed to a pronounced benefit for patients with persistent AF. In addition, patients undergoing PVI + PWI had a longer procedure time [weighted mean difference (WMD): 23.85, 95 % CI: 12.68 to 35.01, p < 0.001], ablation time (WMD: 9.27, 95 % CI: 5.19 to 13.54, p < 0.001), and a nearly negligible increase in fluoroscopic exposure (WMD: 2.69, 95 % CI: -0.23 to 5.62, p = 0.071). There was no increased risk of procedure-related complications between these approaches (RR: 1.06, 95 % CI: 0.71 to 1.57, p = 0.787). Compared with PVI alone, PWI adjunctive to PVI exhibited a higher procedure success of sinus rhythm maintenance in persistent AF during an index catheter ablation. Meanwhile, elongated procedure time and ablation time did not compromise the safety of extensive ablation strategy with additional PWI.

The protective effect of vagus nerve stimulation against myocardial ischemia/reperfusion injury: pooled review from preclinical studies.

Aims: Myocardial ischemia-reperfusion (I/R) injury markedly undermines the protective benefits of revascularization, contributing to ventricular dysfunction and mortality. Due to complex mechanisms, no efficient ways exist to prevent cardiomyocyte reperfusion damage. Vagus nerve stimulation (VNS) appears as a potential therapeutic intervention to alleviate myocardial I/R injury. Hence, this meta-analysis intends to elucidate the potential cellular and molecular mechanisms underpinning the beneficial impact of VNS, along with its prospective clinical implications. Methods and Results: A literature search of MEDLINE, PubMed, Embase, and Cochrane Database yielded 10 articles that satisfied the inclusion criteria. VNS was significantly correlated with a reduced infarct size following myocardial I/R injury [Weighed mean difference (WMD): 25.24, 95% confidence interval (CI): 32.24 to 18.23, p < 0.001] when compared to the control group. Despite high heterogeneity (I2 = 95.3%, p < 0.001), sensitivity and subgroup analyses corroborated the robust efficacy of VNS in limiting infarct expansion. Moreover, meta-regression failed to identify significant influences of pre-specified covariates (i.e., stimulation type or site, VNS duration, condition, and species) on the primary estimates. Notably, VNS considerably impeded ventricular remodeling and cardiac dysfunction, as evidenced by improved left ventricular ejection fraction (LVEF) (WMD: 10.12, 95% CI: 4.28; 15.97, p = 0.001) and end-diastolic pressure (EDP) (WMD: 5.79, 95% CI: 9.84; -1.74, p = 0.005) during the reperfusion phase. Conclusion: VNS offers a protective role against myocardial I/R injury and emerges as a promising therapeutic strategy for future clinical application.

[Developing near infrared spectroscopy calibration model of molar ratio between methanol and isobutylene by support vector regression].

In petrochemical industries, the molar ratio between methanol and isobutylene is one of the most important control parameters in methyl tertiary butyl ether (MTBE) production plant. However, traditional on-line gas chromatography method is difficult to use in practice because of its high maintenance and low speed. On-line near infrared spectroscopy is hopeful to become an excellent alternative method for determining the parameter due to its rapidness, convenience, and less maintenance. Because of the nonlinearity of the measured parameter and near infrared spectra, support vector regression, a novel powerful nonlinear calibration method, was used to build calibration model in the present paper. Compared with the results of partial least squares (PLS) and artificial neural network (ANN) method, the prediction accuracy of support vector regression model is high enough to meet the demand for process control of MTBE unit. This calibration method can be applied to real online analysis of the molar ratio between methanol and isobutylene by near infrared spectroscopy.