SGLT2 inhibition, venous thrombolism, and death due to cardiac causes: a mediation Mendelian randomization study

ObjectiveTo investigate the causal role of venous thrombolism mediating sodium-glucose cotransporter 2 (SGLT2) inhibition in death due to cardiac causes using Mendelian randomization (MR).MethodsA two-sample two-step MR was used to determine (1) the causal effects of SGLT2 inhibition on death due to cardiac causes; (2) the causal effects of venous thrombolism on death due to cardiac causes; and (3) the mediation effects of venous thrombolism. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Additionally, employing MR to investigate the causal association between SGLT2 inhibition and cardiac arrest as well as coronary heart disease (CHD).ResultsSGLT2 inhibition was associated with a lower risk of death due to cardiac causes (odds ratio [OR] = 0.983, [95% CI = 0.972, 0.993], P = 0.0016). Venous thrombolism was associated with death due to cardiac causes ([OR] = 1.031, [95% CI = 1.005, 1.057], P = 0.0199). Mediation analysis showed evidence of indirect effect of SGLT2 inhibition on death due to cardiac causes through venous thrombolism [β = −0.0015, (95% CI = −0.0032 −0.0002), P = 0.042], with a mediated proportion of 8.9% (95% CI = 1.2%, 18.7%) of the total. Furthermore, SGLT2 inhibition was linked to a lower risk of cardiac arrest ([OR] = 0.097, [95% CI = 0.013, 0.742], P = 0.025). SGLT2 inhibition was linked to a lower risk of CHD ([OR] = 0.957, [95% CI = 0.932, 0.982], P = 0.0009).ConclusionsOur study identified the causal roles of SGLT2 inhibition in venous thrombolism. SGLT2 inhibition may influence death due to cardiac causes through venous thrombolism. Additionally, SGLT2 inhibition was associated with reduced risk of cardiac arrest and CHD

Quantitative flow ratio-guided surgical intervention in symptomatic myocardial bridging

Background: Patients with myocardial bridging (MB) are associated with adverse cardiovascular events, but a decision to perform surgical intervention, especially for patients with systolic intermediate stenosis, is a difficult clinical issue. Fractional flow reserve (FFR) represents a novel method for the functional evaluation of coronary stenosis, but the relationship between FFR and MB remains controversial because of the cyclic dynamic stenosis of MB. Quantitative flow ratio (QFR) is a novel index allowing fast assessment of FFR from a diagnostic coronary angiography. This study aimed to investigate the relationship between QFR and MB patients and to further develop a prediction model of QFR-guided surgical intervention for these patients.Methods: Forty-five symptomatic lone MB patients who had undergone coronary angiography were consecutively enrolled in this study. MB was located in the middle of left anterior descending artery with intermediate stenosis during systole. The patients were retrospectively divided into a medical therapy group or a surgical therapy group. Systolic geometry based QFR (SG-QFR) and diastolic geometry based QFR (DG-QFR) were calculated based on three-dimensional quantitative coronary angiography and patient-specific flow velocity. Subsequently, time-averaged QFR (TA-QFR) is defined as the average of SG-QFR and DG-QFR.Results: Receiver operating characteristic curve analysis revealed that TA-QFR (AUC = 0.91; 95% CI: 0.79–0.98) was found to be the best pre-operative index for surgical intervention to MB, when compared with DG-QFR (AUC = 0.69; 95% CI: 0.53–0.82; difference: 0.22; 95% CI: 0.04–0.41; p = 0.02) and SG-QFR (AUC = 0.87; 95% CI: 0.74–0.95; difference: 0.04; 95% CI: 0.00–0.08; p = 0.03).Conclusions: TA-QFR improved the performance of functional evaluation in MB patients with intermediate stenosis during systole and is useful for guiding surgical intervention

An improved saliency detection algorithm based on Itti’s model

Kad ljudi promatraju slike, mehanizam vizualne pažnje (VAM) automatski zanemaruje nepotrebnu informaciju i pažnju usmjerava na najvažnije predmete. Postoje brojni računalni modeli za otkrivanje najistaknutijeg područja slike usmjeravanjem pažnje od dna slike prema gore. U ovom se radu predlaže poboljšani računalni model vizualne pažnje zasnovan na Itti modelu, a sastoji se od tri komponente. Najprije se s značajke nižeg nivoa osnovne slike izdvajaju iz područja boje CIELa*b* umjesto područja boje RGB; poslije toga se značajke slike rastavljaju u valićaste piramide pomoću valićaste osnove višeskalne pretvorbe. Kao treće, primjenjuje se nova strategija za sastavljanje svih upadljivih linija u završnu mapu istaknutih elemenata s različitim težinama, koje su proporcionalne doprinosu svake pojedinačne istaknute karakteristike. U usporedbi s Itti modelom, exsperimenti dokazuju da je pristup predložen u ovome radu učinkovitiji.Visual attention mechanism (VAM) automatically ignores the superfluous information and pays attention to the most significant objects when people are watching the pictures. There are numerous bottom-up visual attention computational models to detect the salient area of an image. In this paper, an improved visual attention computational model based on Itti’s model is proposed, which is comprised of three components. Firstly, the lower-level primitive image features s are extracted from CIELa*b* color space instead of RGB color space; secondly, the feature images are decomposed into wavelet pyramids by wavelet-based multi-scale transform. Thirdly, a new strategy is used to combine all conspicuity maps into a final saliency map with different weights, which are proportional to the contribution of each conspicuity map. Compared with Itti’s models, subjective experiments prove that the approach proposed in this paper is more effective

Inhibitory effect of microRNA34a on retinal pigment epithelial cell proliferation and migration,”

Citation: Hou Q, Tang J, Wang Z, et al. Inhibitory effect of microRNA-34a on retinal pigment epithelial cell proliferation and migration. Invest Ophthalmol Vis Sci. 2013;54:6481-6488. DOI:10.1167/iovs.13-11873 PURPOSE. Retinal pigment epithelial (RPE) cells play important roles in ophthalmologic diseases such as proliferative vitreoretinopathy, AMD, and diabetic retinopathy. MicroRNA34a (miR-34a) has been reported to be important in the regulation of cell proliferation, migration, differentiation, and apoptosis. In this study, we explored the effects of miR-34a on RPE cells. METHODS. The expression level of miR-34a in subconfluent and postconfluent ARPE-19 cells was investigated with quantitative real-time PCR. MicroRNA mimic and small interfering RNA (siRNA) were transiently transfected into RPE cells. Transfected RPE cells were analyzed with WST-1 proliferation assay, and their migration was analyzed with transwell assay and in vitro scratch study. The expression or activation of target proteins was detected by Western blotting. RESULTS. MicroRNA-34a was significantly downregulated in subconfluent ARPE-19 cells compared with postconfluent cells. Introduction of miR-34a inhibited the proliferation and migratory ability of RPE cells without obvious cell apoptosis. In miR-34a transfected cells, many important proliferation and/or migration related molecules such as c-Met, CDK2, CDK4, CDK6, E2F1, and phosphorylated-Cdc2 (p-Cdc2) were downregulated. Small interfering RNA designed to target c-Met also inhibited the proliferation and migration of RPE cells and downregulated CDK2, CDK6, E2F1, and p-Cdc2. CONCLUSIONS. MicroRNA-34a is downregulated in subconfluent RPE cells. MicroRNA-34a can inhibit the proliferation and migration of RPE cells through downregulation of its targets c-Met and other cell cycle-related molecules. Our results indicated that miR-34a is involved in the regulation of RPE cells

GPR48-Induced keratinocyte proliferation occurs through HB-EGF mediated EGFR transactivation

AbstractGPR48 can mediate keratinocyte proliferation and migration. Our investigations showed that AG1478, an inhibitor of EGFR tyrosine kinase, could block GPR48-mediated cellular processes. AG1478 treatment of Gpr48+/+ cells also decreased phosphorylation of EGFR, ERK and STAT3. Subsequent screening using conditioned media immunodepleted of EGFR ligands identified HB-EGF as the ligand responsible for phosphorylation of EGFR, ERK and STAT3. HB-EGF was reduced in Gpr48−/− cell culture medium, but its addition restored the phosphorylation of EGFR, ERK, STAT3, as well as cell proliferation. Confirmation that GPR48 mediates EGFR signaling pathway through HB-EGF was subsequently performed using an inhibitor of HB-EGF