Emergently Alteration of Procedural Strategy During Transcatheter Aortic Valve Replacement to Prevent Coronary Occlusion: A Case Report

BackgroundCoronary occlusion is an uncommon but fatal complication of transcatheter aortic valve replacement (TAVR) with a poor prognosis.Case PresentationA patient with symptomatic severe bicuspid aortic valve stenosis was admitted to a high-volume center specializing in transfemoral TAVR with self-expanding valves. No anatomical risk factors of coronary occlusion were identified on pre-procedural computed tomography analysis. The patient was scheduled for a transfemoral TAVR with a self-expanding valve. Balloon pre-dilatation prior to prosthesis implantation was routinely used for assessing the supra-annular structure and assessing the risk of coronary occlusion. Immediately after the tubular balloon inflation, fluoroscopy revealed that the right coronary artery was not visible, and the flow in the left coronary artery was reduced. The patient would be at high-risk of coronary occlusion if a long stent self-expanding valve was implanted. Therefore, our heart team decided to suspend the ongoing procedure. A transapical TAVR with a 23 mm J-valve was performed 3 days later. The prosthesis was deployed at a proper position without blocking the coronary ostia and the final fluoroscopy showed normal flow in bilateral coronary arteries with the same filling as preoperatively.DiscussionOur successful case highlights the importance of a comprehensive assessment of coronary risk and a thorough understanding of the TAVR procedure for the heart team. A short-stent prosthesis is feasible for patients at high risk of coronary occlusion. Most importantly TAVR should be called off even if the catheter has been introduced when an extremely high risk of coronary obstruction is identified during the procedure and no solution can be found

HECT, UBA and WWE domain containing 1 represses cholesterol efflux during CD4+ T cell activation in Sjögren’s syndrome

Introduction: Sjögren’s syndrome (SS) is a chronic autoimmune disorder characterized by exocrine gland dysfunction, leading to loss of salivary function. Histological analysis of salivary glands from SS patients reveals a high infiltration of immune cells, particularly activated CD4+ T cells. Thus, interventions targeting abnormal activation of CD4+ T cells may provide promising therapeutic strategies for SS. Here, we demonstrate that Hect, uba, and wwe domain containing 1 (HUWE1), a member of the eukaryotic Hect E3 ubiquitin ligase family, plays a critical role in CD4+ T-cell activation and SS pathophysiology.Methods: In the context of HUWE1 inhibition, we investigated the impact of the HUWE1 inhibitor BI8626 and sh-Huwe1 on CD4+ T cells in mice, focusing on the assessment of activation levels, proliferation capacity, and cholesterol abundance. Furthermore, we examined the therapeutic potential of BI8626 in NOD/ShiLtj mice and evaluated its efficacy as a treatment strategy.Results: Inhibition of HUWE1 reduces ABCA1 ubiquitination and promotes cholesterol efflux, decreasing intracellular cholesterol and reducing the expression of phosphorylated ZAP-70, CD25, and other activation markers, culminating in the suppressed proliferation of CD4+ T cells. Moreover, pharmacological inhibition of HUWE1 significantly reduces CD4+ T-cell infiltration in the submandibular glands and improves salivary flow rate in NOD/ShiLtj mice.Conclusion: These findings suggest that HUWE1 may regulate CD4+ T-cell activation and SS development by modulating ABCA1-mediated cholesterol efflux and presents a promising target for SS treatment

The effect of reactively-sputtered alumina films on the oxidation resistance of CoCrAlY coatings

Thin alumina films have found applications in electronic circuits and cutting tools and have been recently explored as protective coatings against high temperature oxidation, but these studies have been relatively rare. In this study, amorphous alumina films 3.5 µm thick were produced by reactive sputtering on Co-30Cr-6Al-0.5Y coatings, using a pure aluminum target in Ar + O2 atmosphere. Isothermal oxidation tests were carried out at 1000-1100 °C in static air. The results showed that the alumina films improved the oxidation resistance at all testing temperatures. At 1000°C, the Co-30Cr-6Al-0.5Y coating could form pure alumina scale on its surface, but the reactively-sputtered alumina films reduced the oxidation rate. At 1100 °C, the Co-30Cr-6Al-0.5Y coating could not form pure alumina scale, as a result of a severe internal oxidation of aluminum along the columnar defects. The scales were composed of Al2O3, Cr2O3 and TiO2, which were not so protective as pure alumina scales. On the contrary, the Co-30Cr- 6Al-0.5Y coatings with 3.5 µm preformed alumina films exhibited excellent oxidation resistance at 1100 °C. Only minor amounts of TiO2 were detected on the surface. Moreover, the reactively-sputtered alumina films were very adherent to the CoCrAlY coatings. At 1000 °C no spallation was found, while at 1100 °C only a little spallation produced during cooling was observed

The neuroprotective functions of petroleum ether extract from Tibetan turnip (Brassica rapa L.) against cerebral ischemic stroke

Background: Brassica rapa L. (turnip) is an ancient plant grown on the Tibetan Plateau, which possesses functions of heat-clearing and toxin, enhancing oxygen. The primary objective of this study is to assess the potential protective effect of petroleum ether extract of turnip (PET) against ischemia and hypoxia. Basic procedures: Total extract of turnip (TET) was extracted 3 times with petroleum ether at a ratio of 1:1 and the PET was concentrated and identified by UHPLC-MS. Pharmacological and drug-like properties prediction of major compounds of PET were determined by the SwissADME tool. The protein–protein interaction test for PET-Cerebral Ischemic Stroke-Oxidative Damage (PET-CIS-OD) common targets were calculated by the SRTING giant database. The molecular function, biological process and cell composition of core targets were analyzed by ClueGo and CluePedia. KEGG pathway analysis were used for calculating the potential pathway affected by the PET-CIS-OD common targets. Molecular docking were measured by AutoDockTools 1.5.7 and PyMol. Oxygen-Glucose Deprivation/Reperfusion (OGD/R) model were established for evaluating the changes of the OD markers. Western blotting was used to verify the core proteins in signaling pathways obtained by network pharmacology. Main findings: PET intervention increased antioxidant ability in HT22 cells. Furthermore, PET could effectively recovered the COXIV expression, inhibit the Bax levels (p < 0.01), strengthen the Bcl-2 levels (p < 0.05) in HT22 cells after OGD/R injury. Our calculation results and experimental results indicated that PET may act as a key intervention in CIS by enhancing the level of phospho-PI3K (p < 0.001), phospho-Akt (p < 0.01) and phospho-mTOR (p < 0.01) and lessening the levle of phospho-P38 (p < 0.01) and HIF-1α (p < 0.05). Conclusions: Our study systematically explored the potential function and regulatory mechanism of PET in CIS for the first time. The results indicated that PET may play neuroprotective effect against CIS by regulating PI3K/Akt/mTOR signaling pathway and MAPK signaling pathway, and exerting antioxidant and anti-apoptotic effects on OGD/R injury

Healthy regulation of Tibetan Brassica rapa L. polysaccharides on alleviating hyperlipidemia: A rodent study

Hyperlipidemia is a common metabolic disorder, which can lead to obesity, hypertension, diabetes, atherosclerosis and other diseases. Studies have shown that polysaccharides absorbed by the intestinal tract can regulate blood lipids and facilitate the growth of intestinal flora. This article aims to investigate whether Tibetan turnip polysaccharide (TTP) plays a protective role in blood lipid and intestinal health via hepatic and intestinal axes. Here we show that TTP helps to reduce the size of adipocytes and the accumulation of liver fat, playing a dose-dependent effect on ADPN levels, suggesting an effect on lipid metabolism regulation. Meantime, TTP intervention results in the downregulation of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and serum inflammatory factors (interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), implying that TTP suppresses the progression of inflammation in the body. The expression of key enzymes associated with cholesterol and triglyceride synthesis, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), peroxisome proliferator-activated receptors γ (PPARγ), acetyl-CoA carboxylase (ACC), fatty acid synthetase (FAS) and sterol-regulatory element binding proteins-1c (SREBP-1c), can be modulated by TTP. Furthermore, TTP also alleviates the damage to intestinal tissues caused by high-fat diet, restores the integrity of the intestinal barrier, improves the composition and abundance of the intestinal flora and increases the levels of SCFAs. This study provides a theoretical basis for the regulation of body rhythm by functional foods and potential intervention in patients with hyperlipidemia

Integrative analysis of the ST6GALNAC family identifies GATA2-upregulated ST6GALNAC5 as an adverse prognostic biomarker promoting prostate cancer cell invasion

Abstract Background ST6GALNAC family members function as sialyltransferases and have been implicated in cancer progression. However, their aberrant expression levels, prognostic values and specific roles in metastatic prostate cancer (PCa) remain largely unclear. Methods Two independent public datasets (TCGA-PRAD and GSE21032), containing 648 PCa samples in total, were employed to comprehensively examine the mRNA expression changes of ST6GALNAC family members in PCa, as well as their associations with clinicopathological parameters and prognosis. The dysregulation of ST6GALNAC5 was further validated in a mouse PCa model and human PCa samples from our cohort (n = 64) by immunohistochemistry (IHC). Gene Set Enrichment Analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and drug sensitivity analyses were performed to enrich the biological processes most related to ST6GALNAC5. Sulforhodamine B, transwell, luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to examine the PCa cell proliferation, invasion and transcriptional regulation, respectively. Results Systematical investigation of six ST6GALNAC family members in public datasets revealed that ST6GALNAC5 was the only gene consistently and significantly upregulated in metastatic PCa, and ST6GALNAC5 overexpression was also positively associated with Gleason score and predicted poor prognosis in PCa patients. IHC results showed that (1) ST6GALNAC5 protein expression was increased in prostatic intraepithelial neoplasia and further elevated in PCa from a PbCre;Pten F/F mouse model; (2) overexpressed ST6GALNAC5 protein was confirmed in human PCa samples comparing with benign prostatic hyperplasia samples from our cohort (p < 0.001); (3) ST6GALNAC5 overexpression was significantly correlated with perineural invasion of PCa. Moreover, we first found transcription factor GATA2 positively and directly regulated ST6GALNAC5 expression at transcriptional level. ST6GALNAC5 overexpression could partially reverse GATA2-depletion-induced inhibition of PCa cell invasion. The GATA2-ST6GALNAC5 signature exhibited better prediction on the poor prognosis in PCa patients than GATA2 or ST6GALNAC5 alone. Conclusions Our results indicated that GATA2-upregulated ST6GALNAC5 might serve as an adverse prognostic biomarker promoting prostate cancer cell invasion

SS-31 Protects Liver from Ischemia-Reperfusion Injury via Modulating Macrophage Polarization

Ischemia-reperfusion injury (IRI) is a common complication in liver surgeries. It is a focus to discover effective treatments to reduce ischemia-reperfusion injury. Previous studies show that oxidative stress and inflammation response contribute to the liver damage during IRI. SS-31 is an innovated mitochondrial-targeted antioxidant peptide shown to scavenge reactive oxygen species and decrease oxidative stress, but the protective effects of SS-31 against hepatic IRI are not well understood. The aim of our study is to investigate whether SS-31 could protect the liver from damages induced by IRI and understand the protective mechanism. The results showed that SS-31 treatment can significantly attenuate liver injury during IRI, proved by HE staining, serum ALT/AST, and TUNEL staining which can assess the degree of liver damage. Meanwhile, we find that oxidative stress and inflammation were significantly suppressed after SS-31 administration. Furthermore, the mechanism revealed that SS-31 can directly decrease ROS production and regulate STAT1/STAT3 signaling in macrophages, thus inhibiting macrophage M1 polarization. The proinflammation cytokines are then significantly reduced, which suppress inflammation response in the liver. Taken together, our study discovered that SS-31 can regulate macrophage polarization through ROS scavenging and STAT1/STAT3 signaling to ameliorate liver injury; the protective effects against hepatic IRI suggest that SS-31 may be an appropriate treatment for liver IRI in the clinic

Cerebral Ischemic Lesions after Transcatheter Aortic Valve Implantation in Patients with Non-Calcific Aortic Stenosis

Evidence for transcatheter aortic valve implantation (TAVI) is scarce among patients with non-calcific aortic stenosis, and it is not known whether aortic valve calcification is associated with new cerebral ischemic lesions (CILs) that are detected by diffusion-weighted magnetic resonance imaging. So, our study enrolled 328 patients who underwent transfemoral TAVI using a self-expanding valve between December 2016 and June 2021 from the TORCH registry (NCT02803294). A total of 34 patients were finally confirmed as non-calcific AS and the remaining 294 patients were included in the calcific AS group. Incidence of new CILs (70.6% vs. 85.7%, p = 0.022), number of lesions (2.0 vs. 3.0, p = 0.010), and lesions volume (105.0 mm3 vs. 200.0 mm3, p = 0.047) was significantly lower in the non-calcific AS group. However, the maximum and average lesion volumes were comparable between two groups. Non-calcific AS was associated with lower risk for developing new CILs by univariate logistic regression analysis [Odds ratio (OR): 0.040, 95% confident interval (CI): 0.18&ndash;0.90, p = 0.026] and multivariate analysis (OR: 0.031, 95% CI: 0.13&ndash;0.76, p = 0.010). In summary, non-calcific AS patients had a lower risk of developing new cerebral ischemic infarction after TAVI compared to calcific AS patients. However, new ischemic lesions were still found in over 70% of patients

Trimethylamine N-Oxide Levels Are Associated with Severe Aortic Stenosis and Predict Long-Term Adverse Outcome

Objective: Trimethylamine N-oxide (TMAO), a pathological microbial metabolite, is demonstrated to be related to cardiovascular diseases. This study was (1) to investigate the association between TMAO and aortic stenosis and (2) to determine the prognostic value of TMAO for predicting mortality after transcatheter aortic valve replacement (TAVR). Methods: 299 consecutive patients (77 (72–81) years, 58.2% male, Society of Thoracic Surgeons (STS) score 5.8 (4.9–9.3)) with severe aortic stenosis and 711 patients (59 (52–66) years, 51.9% male) without aortic stenosis were included in this retrospective study. A total of 126 pairs of patients were assembled by Propensity Score Matching. The primary outcome was all-cause mortality using survival analyses stratified by TMAO quartiles. Results: Patients with severe aortic stenosis had higher TMAO levels (3.18 (1.77–6.91) μmol/L vs. 1.78 (1.14–2.68) μmol/L, p p = 0.028) and higher late cumulative mortality (34.2% vs. 19.1%, log-rank p = 0.004). In Cox regression multivariate analysis, higher TMAO level remained an independent predictor (hazard ratio 1.788; 95% CI 1.064–3.005, p = 0.028) of all-cause mortality after adjusting for STS score, N-terminal pro b-type natriuretic peptide, and maximum velocity. Conclusions: The TMAO level was higher in aortic stenosis patients. Elevated TMAO was associated with poor adverse outcome after TAVR