Ursolic Acid Formulations Effectively Induce Apoptosis and Limit Inflammation in the Psoriasis Models In Vitro.

Psoriasis, a prevalent inflammatory skin disorder affecting a significant percentage of the global population, poses challenges in its management, necessitating the exploration of novel cost-effective and widely accessible therapeutic options. This study investigates the potential of ursolic acid (UA), a triterpenoid known for its anti-inflammatory and pro-apoptotic properties, in addressing psoriasis-related inflammation and keratinocyte hyperproliferation. The research involved in vitro models employing skin and immune cells to assess the effects of UA on psoriasis-associated inflammation. The presented research demonstrates the limiting effects of UA on IL-6 and IL-8 production in response to the inflammatory stimuli and limiting effects on the expression of psoriatic biomarkers S100A7, S100A8, and S100A9. Further, the study reveals promising outcomes, demonstrating UA's ability to mitigate inflammatory responses and hyperproliferation of keratinocytes by the induction of non-inflammatory apoptosis, as well as a lack of the negative influence on other cell types, including immune cells. Considering the limitations of UA's poor solubility, hybrid systems were designed to enhance its bioavailability and developed as hybrid nano-emulsion and bi-gel topical systems to enhance bioavailability and effectiveness of UA. One of them in particular-bi-gel-demonstrated high effectiveness in limiting the pathological response of keratinocytes to pro-psoriatic stimulation; this was even more prominent than with ursolic acid alone. Our results indicate that topical formulations of ursolic acid exhibit desirable anti-inflammatory activity in vitro and may be further employed for topical psoriasis treatment.

Comparison of long-term outcomes and risk factors of aortic stenosis treatment in patients undergoing transcatheter aortic valve implantation and surgical aortic valve replacement.

BACKGROUND: Aortic stenosis (AS) is the most common valvular heart disease and untreated has a bleak prognosis. The only effective method of treatment is valve replacement, surgical (SAVR), or transcatheter (TAVI). AIMS: We decided to analyze outcomes and predictors of long-term mortality in patients undergoing TAVI and SAVR. METHODS: A retrospective analysis of 1229 patients with advanced AS, comprising TAVI (n = 211), SAVR (n = 556), SAVR, and additional procedures (n = 462), operated on from 2014 to 2018, was performed. RESULTS: No significant differences between SAVR and TAVI were found for 24-month mortality in groups of consecutive patients. Postoperative stroke or transient ischemic attack (TIA), chronic obstructive pulmonary disease (COPD), and transfusion of red blood cells (RBCs) were independent predictors of 1-year mortality after SAVR. The above-mentioned factors regarding the increased estimated surgery risk in the EuroSCORE II ( > 4%) were predictors of 2-years mortality after SAVR. Risk factors for 6- and 12-month mortality after TAVI were EuroSCORE II, new onset of atrial fibrillation (NOAF), and the increased RBC distribution width (RDW). Postoperative respiratory failure was an independent risk factor for 6-, 12- and 24-month mortality in both groups of patients. CONCLUSIONS: There were no significant differences regarding prognosis after TAVI and SAVR at the 24-month follow-up in the propensity score matching model. Independent predictive factors of late mortality after both procedures were EuroScore II and respiratory failure. Independent predictive factors of late mortality specific for TAVI were NOAF, increased RDW, and for SAVR: TIA, stroke, COPD, and RBC transfusion.

Computed tomography assessment of the aortic root morphology in predicting the development of paravalvular leak following transcatheter aortic valve implantation.

Introduction: Transcatheter aortic valve implantation (TAVI) is an effective treatment of significant aortic stenosis. Paravalvular leaks (PVLs) are one of the most common complications after the procedure. Objectives: The aim of this study was to assess whether the aortic root morphology affects the occurrence of PVL after TAVI. Patients and methods: We enrolled 50 patients with bicuspid and 50 patients with tricuspid aortic valve who underwent multislice computed tomography (MSCT) and transthoracic echocardiography prior to TAVI. The dimensions of the aortic root were assessed by MSCT. PVL after TAVI was assessed by transthoracic echocardiography. Patients were divided in 2 groups according to the PVL severity: less than moderate PVL (n = 80) and moderate or worse PVL (n = 20), and comparisons between the groups were performed. Results: Patients with at least moderate PVL, compared with those with less than moderate PVL, had greater mean (SD) area (5.2 [1.1] cm2 vs 4.7 [0.8] cm2; P = 0.02), perimeter (8.4 [0.9] cm vs 7.9 [0.7] cm; P = 0.01), and long axis (29.5 [2.7] mm vs 28 [2.7] mm; P = 0.04) of the aortic annulus and greater mean (SD) area (5.3 [1.3] cm2 vs 4.7 [1.1] cm2; P = 0.04) and perimeter (8.6 [1.1] cm vs 8.1 [0.9] cm; P = 0.02) of the left ventricular outflow tract. In multivariable analysis, bicuspid aortic valve disease, interventricular septum hypertrophy, greater left ventricular outflow tract, and postdilatation were significant predictors of moderate PVL following TAVI. Conclusions: The assessment of the aortic root morphology with MSCT can be helpful in predicting PVL after TAVI.

Patients scheduled for TAVI tend to form abnormal fibrin clots more resistant to lysis: the impact of age.

BACKGROUND: Fibrin accumulation within the stenotic leaflets associated with impaired fibrinolysis was observed in severe aortic stenosis (AS). Little is known about fibrin clot properties in patients scheduled for transcatheter aortic valve implantation (TAVI). AIMS: We investigated whether TAVI patients display a more prothrombotic state, including suppressed fibrinolytic capacity compared to those undergoing surgery. METHODS: We enrolled patients with advanced AS without significant atherosclerotic vascular disease scheduled for TAVI (n = 45) or surgical aortic valve replacement (SAVR, n = 59). Plasma fibrin clot features, including clot permeability (Ks) reflecting an average pore size, and lysis potential (Lys50), along with thrombin generation were determined off anticoagulation within 12 hours before the procedure. RESULTS: TAVI patients compared to SAVR had prolonged Lys50 (median 420 [IQR, interquartile range, 337-480] seconds vs 379 [337-428] seconds; P = 0.045) and formed denser clots, reflected by lower Ks (3.66 [3.05-4.84] vs 4.36 [3.6-5.27] × 10-9 cm2; P = 0.02), but after adjustment for age the latter difference was no longer significant. Apart from age, concomitant diabetes mellitus, or chronic kidney disease, prolonged Lys50 was an independent predictor of indication for TAVI in AS patients on multivariate regression analysis. There was a delayed start of thrombin generation in TAVI patients (lag time, 4.5 [3.8-6.3] minutes vs 4.2 [3.3-4.7] minutes; P = 0.035), without other differences in thrombin generation parameters. CONCLUSIONS: This study is the first to show that patients scheduled for TAVI are characterized by prothrombotic fibrin clot properties including denser fibrin meshwork and more resistant to lysis compared with those undergoing SAVR, which might explain in part increased thromboembolic risk following TAVI.

Pulmonary artery aneurysm as a result of group 2 pulmonary artery hypertension in a patient with significant mitral and aortic valve disease - review and case report.

Aneurysms are uncommon, but potentially life-threatening abnormalities of the pulmonary arteries. Aneurysm of the main pulmonary artery (MPA) defined as MPA diameter over 40 mm was reported in 1 : 14 000 autopsies. The most frequent location is the main pulmonary artery (89% of cases), whereas the maximum described diameter is 106-170 mm. Clinical manifestations are usually nonspecific or asymptomatic. Right heart failure symptoms, pulmonary regurgitation, trachea or bronchi compression or pulmonary emboli caused by enlarged MPA are the most commonly described clinical manifestations. Pulmonary artery aneurysm dissection is an uncommon complication but associated with a high mortality rate. Unfortunately, guidelines regulating the optimal time for the surgical intervention still have not been developed. We present the history of 76-year-old patient suffering from an aneurysm of the pulmonary artery (74 × 61 mm), as well as mitral and aortic valve disease, who was successfully operated on in our hospital.