Stanniocalcin-1 Regulates Re-Epithelialization in Human Keratinocytes

Stanniocalcin-1 (STC1), a glycoprotein hormone, is believed to be involved in various biological processes such as inflammation, oxidative responses and cell migration. Riding on these emerging evidences, we hypothesized that STC1 may participate in the re-epithelialization during wound healing. Re-epithelialization is a critical step that involves keratinocyte lamellipodia (e-lam) formation, followed by cell migration. In this study, staurosporine (STS) treatment induced human keratinocyte (HaCaT) e-lam formation on fibronectin matrix and migration via the activation of focal adhesion kinase (FAK), the surge of intracellular calcium level [Ca2+]i and the inactivation of Akt. In accompanied with these migratory features, a time- and dose-dependent increase in STC1 expression was detected. STC1 gene expression was found not the downstream target of FAK-signaling as illustrated by FAK inhibition using PF573228. The reduction of [Ca2+]i by BAPTA/AM blocked the STS-mediated keratinocyte migration and STC1 gene expression. Alternatively the increase of [Ca2+]i by ionomycin exerted promotional effect on STS-induced STC1 gene expression. The inhibition of Akt by SH6 and GSK3β by lithium chloride (LiCl) could respectively induce and inhibit the STS-mediated e-lam formation, cell migration and STC1 gene expression. The STS-mediated e-lam formation and cell migration were notably hindered or induced respectively by STC1 knockdown or overexpression. This notion was further supported by the scratched wound assay. Collectively the findings provide the first evidence that STC1 promotes re-epithelialization in wound healing

Genome-Wide Profile of Pleural Mesothelioma versus Parietal and Visceral Pleura: The Emerging Gene Portrait of the Mesothelioma Phenotype

Malignant pleural mesothelioma is considered an almost incurable tumour with increasing incidence worldwide. It usually develops in the parietal pleura, from mesothelial lining or submesothelial cells, subsequently invading the visceral pleura. Chromosomal and genomic aberrations of mesothelioma are diverse and heterogenous. Genome-wide profiling of mesothelioma versus parietal and visceral normal pleural tissue could thus reveal novel genes and pathways explaining its aggressive phenotype.Well-characterised tissue from five mesothelioma patients and normal parietal and visceral pleural samples from six non-cancer patients were profiled by Affymetrix oligoarray of 38 500 genes. The lists of differentially expressed genes tested for overrepresentation in KEGG PATHWAYS (Kyoto Encyclopedia of Genes and Genomes) and GO (gene ontology) terms revealed large differences of expression between visceral and parietal pleura, and both tissues differed from mesothelioma. Cell growth and intrinsic resistance in tumour versus parietal pleura was reflected in highly overexpressed cell cycle, mitosis, replication, DNA repair and anti-apoptosis genes. Several genes of the “salvage pathway” that recycle nucleobases were overexpressed, among them TYMS, encoding thymidylate synthase, the main target of the antifolate drug pemetrexed that is active in mesothelioma. Circadian rhythm genes were expressed in favour of tumour growth. The local invasive, non-metastatic phenotype of mesothelioma, could partly be due to overexpression of the known metastasis suppressors NME1 and NME2. Down-regulation of several tumour suppressor genes could contribute to mesothelioma progression. Genes involved in cell communication were down-regulated, indicating that mesothelioma may shield itself from the immune system. Similarly, in non-cancer parietal versus visceral pleura signal transduction, soluble transporter and adhesion genes were down-regulated. This could represent a genetical platform of the parietal pleura propensity to develop mesothelioma.Genome-wide microarray approach using complex human tissue samples revealed novel expression patterns, reflecting some important features of mesothelioma biology that should be further explored

Outcomes of coronary artery bypass surgery using modified del Nido cardioplegia in patients with poor ventricular function

Abstract Background del Nido cardioplegia (DN) has been shown to be safe in adult patients undergoing isolated coronary artery bypass grafting with normal left ventricular ejection fraction. We sought to determine whether it was also safe in adult patients with diminished left ventricular function. Methods All patients with preoperative left ventricular ejection fraction ≤ 40% undergoing isolated coronary artery bypass grafting between 1/1/2019 and 7/10/2022 were retrospectively analyzed. Off-pump and beating heart cases were excluded. Patients were divided by surgeon preference between conventional cardioplegia (CCP) and DN. Baseline and intraoperative characteristics and short-term postoperative outcomes were compared. Results Six surgeons performed 829 isolated coronary artery bypass operations during the study. Two-hundred seventy-two met study criteria. Three surgeons used exclusively CCP for the duration of the study, two used exclusively DN and one switched from CCP to DN mid-way through. Group totals were: CCP n = 181 and DN n = 91. There were no significant differences in baseline characteristics including mean left ventricular ejection fraction (CCP 32.5 ± 7.4% vs. DN 33.4 ± 7.29%, p = 0.939). Other than a significant decrease in bypass time for DN (113.20 ± 37.2 vs. 122.43 ± 34.3 min, p = 0.043) there were no intergroup differences in urgency, number of grafts, ischemic time or incidence of blood transfusion. Postoperative outcomes between CCP and DN were similar including incidence of atrial fibrillation (12.2% vs. 8.8%, p = 0.403), intensive care length of stay (3.7 ± 2.3 vs. 4.3 ± 3.7 days, p = 0.886), total length of stay (5.7 ± 3.7 vs. 6.3 ± 4.4 days, p = 0.922) and 30-day mortality (3.85% vs. 1.10%, p = 0.205). Conclusion Compared to conventional cardioplegia, del Nido cardioplegia provides equivalent short-term outcomes in patients with low left ventricular ejection fraction undergoing isolated coronary artery bypass grafting

Mammographic mass classification according to Bi‐RADS lexicon

The goal of this study is to propose a computer‐aided diagnosis system to differentiate between four breast imaging reporting and data system (Bi‐RADS) classes in digitised mammograms. This system is inspired by the approach of the doctor during the radiologic examination as it was agreed in BI‐RADS, where masses are described by their form, their boundary and their density. The segmentation of masses in the authors’ approach is manual because it is supposed that the detection is already made. When the segmented region is available, the features extraction process can be carried out. 22 visual characteristics are automatically computed from shape, edge and textural properties; only one human feature is used in this study, which is the patient's age. Classification is finally done using a multi‐layer perceptron according to two separate schemes; the first one consists of classify masses to distinguish between the four BI‐RADS classes (2, 3, 4 and 5). In the second one the authors classify abnormalities on two classes (benign and malign). The proposed approach has been evaluated on 480 mammographic masses extracted from the digital database for screening mammography, and the obtained results are encouraging