Periprocedural, short-term, and long-term outcomes following transcatheter tricuspid valve repair: a systemic review and meta-analysis.

Background: There has been an increasing use of transcatheter tricuspid valve repair (TTVR) recently. However, the periprocedural, short-term, and long-term outcomes of TTVR remain unclear. Objectives: To determine the clinical outcomes in patients with significant tricuspid regurgitation undergoing TTVR. Design: Systematic review and meta-analysis. Data Source and Methods: The systematic review and meta-analysis is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and EMBASE were searched for clinical trials and observational studies until March 2022. Studies reporting the incidence of clinical outcomes after TTVR were included. The clinical outcomes included periprocedural, short-term (in-hospital or within 30 days), and long-term (>6-month follow-up) outcomes. The primary outcome was all-cause mortality whereas the secondary outcomes included technical success, procedural success, cardiovascular mortality, rehospitalization for heart failure (HHF), major bleeding, and single leaflet device attachment. The incidence of these outcomes across studies was pooled by a random-effects model. Results: A total of 21 studies with 896 patients were included. A total of 729 (81.4%) patients underwent isolated TTVR while only 167 (18.6%) patients underwent combined mitral and tricuspid valve repair. Over 80% of the patients used coaptation devices while approximately 20% used annuloplasty devices. The median follow-up duration was 365 days. Technical and procedural success was high at 93.9% and 82.1%, respectively. The pooled perioperative, short-term, and long-term all-cause mortality for patients undergoing TTVR was 1.0%, 3.3%, and 14.1%, respectively. The long-term cardiovascular mortality rate was 5.3% while the HHF rate was 21.5%. Major bleeding and single leaflet device attachment were two major complications, accounting for 14.3% and 6.4%, respectively, during long-term follow-up. Conclusion: TTVR is associated with high procedural success and low procedural and short-term mortality. However, all-cause mortality, cardiovascular mortality, and HHF rates remain high during long-term follow-up. Registration: PROSPERO (CRD42022310020).

Design and Discovery of Novel Cyclic Peptides as EDPs-EBP Interaction Inhibitors for the Treatment of Liver Fibrosis.

Liver fibrosis is the undesirable result of excessive deposition of the extracellular matrix (ECM), and elastin is known as one of the key ECM components. Under specific pathological conditions, elastin undergoes degradation to produce elastin-derived peptides (EDPs), which bind to elastin-binding protein (EBP) to activate corresponding signal pathways, thus accelerating fibrosis progression. Herein, we describe the discovery of novel cyclic peptides that function as potent and stable inhibitors to interfere with the peptide-protein interaction between EDPs and EBP. Remarkably, CXJ-2 exhibited potent activities to inhibit the PI3K/ERK pathway and decrease hepatic stellate cell proliferation and migration. The subsequent in vivo study demonstrated that CXJ-2 possessed potent antifibrotic efficacy in ameliorating CCl4-induced liver fibrosis. This work provides a successful pharmacological strategy for the development of novel inhibitors of EDPs-EBP interaction, which sheds new light on how cyclic peptides disrupt peptide-protein interaction and may also provide new structure-oriented therapeutic candidates in liver fibrosis.

A positive feedback loop of SIRT1 and miR17HG promotes the repair of DNA double-stranded breaks.

Long noncoding RNAs (lncRNAs) have emerged as critical regulators for gene expression in multiple levels and thus are involved in various physiological and pathological processes. Sirtuin 1 (SIRT1) has been established to exert key roles in the diverse biological process through deacetylation of substrates, including DNA damage repair. Nevertheless, the regulatory relationship between SIRT1 and lncRNAs, and the effect of lncRNA on SIRT1-mediated functions were still far to be elucidated. We herein uncovered that lncRNA miR17HG was notably down-regulated in SIRT1-deficient cells, and significantly up-regulated after ectopic expression of SIRT1. Subsequently, the results of dual luciferase reporter (DLR) showed that SIRT1 dramatically enhanced the promoter activity of the miR-17-92 cluster. Furthermore, we specifically knocked down the previous demonstrated transcription factor for the miR-17-92 cluster, C-Myc, which was the validated substrate of SIRT1. As expected, miR17HG and miR-17-92 miRNAs were evidently down-regulated after silencing of C-Myc; and silencing of C-Myc significantly reversed the effect of SIRT1 on miR17HG expression, suggesting that SIRT1 endowed cells with elevated miR17HG expression through stabilization of C-Myc. What is more, silencing of miR17HG significantly inhibited the repair of DNA DSBs, while enforced expression of miR17HG promoted DSBs repair. Fascinatingly, overexpression of miR17HG evidently enhanced the deacetylation activity of SIRT1, while silencing of miR17HG conferred diminished deacetylation activity. In addition, the results of RIP unraveled the physical interaction between miR17HG and SIRT1. Taken together, we presented evidences that miR17HG and SIRT1 probably formed a positive feedback loop, which exerted a crucial effect on DSBs repair.

Capillary electrophoresis absorption detection using fiber-loop ring-down spectroscopy.

The application of phase-shift, fiber-loop, ring-down spectroscopy (PS-FLRDS) as an on-line detector for capillary electrophoresis (CE) of biomolecules is demonstrated. CE was conducted using a custom-designed capillary/fiber interface coupled to an absorption detector, which is based on the ring-down of an optical signal in a closed fiber waveguide loop. The ring-down times were obtained by measuring the phase difference between intensity modulated light entering and exiting the fiber loop. The incorporation of a microlens to enhance transmission through the sample gap led to an improvement of the sensitivity by up to 80% compared to the square-cut fiber and a reduction in the detection limit. The performance of the PS-FLRDS absorption technique as an online detector was characterized by flow injection through a capillary. Good repeatability and linear response were obtained, and the detection limit using the lensed fiber/capillary interface system was determined to be alpha(min) = 1.6 cm(-1) for an absorption path of approximately 30 microm. PS-FLRDS coupled to CE was also applied to the analysis of human serum albumin (HSA) by using a NIR dye as a noncovalent label. The excess free dye and the dye/protein complex were resolved. The labeling coefficient was determined to be approximately 6, and good repeatability of peak areas (RSD = 8.7%) was obtained for the analysis of HSA. Furthermore, an excellent linear response (R2 > 0.99) was obtained between the peak areas and concentrations of HSA. The detection limit of labeled HSA was determined to be 1.67 microM.

Phase-shift fiber-loop ring-down spectroscopy.

Fiber-loop ring-down spectroscopy (FLRDS) is a recently developed absorption spectroscopic technique suitable for very small liquid samples. It is based on measurements of the optical decay constant of laser intensity in a loop made of optical waveguide material. This decay constant changes as small liquid samples containing absorbing species are introduced into the loop. In this report, it is demonstrated that one can also obtain the optical decay constant using a continuous wave laser beam that is intensity modulated and then coupled into an optical fiber loop. The inherent exponential decay in the fiber loop introduces a phase shift of the light emitted from the loop with respect to the pumping beam. By measuring this phase shift, one can readily determine the concentration of the analyte introduced between the two fiber ends and a model is established to describe the relationship. It is demonstrated that this technique, dubbed phase-shift fiber-loop ring-down spectroscopy (PS-FLRDS), is well suited as an absorption detector for any flow system in which the optical absorption path is limited by the instrument architecture. By measuring the phase angle as a function of concentration of 1,1'-diethyl-4,4'-dicarbocyanine iodide in dimethyl sulfoxide, the detection limit was determined as approximately 6 microM for a 30-40-microm absorption path. A temporal resolution of approximately 100 ms was demonstrated by a rapid displacement of the solutions between the two fiber ends. Proof-of-principle use of the PS-FLRDS detection in capillary flow systems using a commercial four-way microcross established that the alignment of the fiber and the capillary can be made simple and effective, while retaining both a low detection limit and a fast response.

[Determination of sildenafil in medicines for erectile dysfunction by capillary electrophoresis].

A method has been developed for the determination of sildenafil in the medicines for erectile dysfunction by capillary electrophoresis. The samples were analyzed with 60 mmol/L NaH2PO4(pH 5.0) running buffer at 35 degrees C capillary temperature and 30 kV voltage. A linear calibration was obtained from 0.07 g/L to 1.05 g/L of sildenafil (r = 0.9985) with the RSD of 4.7% for peak area, and the average recovery was 97.4%. The results were compared with those of HPLC, showing that the method is precise, simple and cost-effective, and can be used as a complementary method to HPLC.