A representative of arylcyanomethylenequinone oximes effectively inhibits growth and formation of hyphae in Candida albicans and influences the activity of protein kinases in vitro

In this study, we applied various assays to reveal new activities of phenylcyanomethylenequinone oxime-4-(hydroxyimino) cyclohexa-2,5-dien-1-ylidene](phenyl)ethanenitrile (4-AN) for potential anti-microbial applications. These assays demonstrated (a) the antimicrobial effect on bacterial and fungal cultures, (b) the effect on the in vitro activity of the kinase CK2, (c) toxicity towards human erythrocytes, the Caco-2 cancer cell line, and embryonic development of Zebrafish. We demonstrated the activity of 4-AN against selected bacteria and Candida spp. The MIC ranging from 4?µg/ml to 125?µg/ml proved effective in inhibition of formation of hyphae and cell aggregation in Candida, which was demonstrated at the cytological level. Noteworthy, 4-AN was found to inhibit the CK2 kinase with moderate potency. Moreover, at low concentrations, it did not exert any evident toxic effects on human erythrocytes, Caco-2 cells, or Zebrafish embryos. 4-AN can be a potential candidate as a novel drug against Candida infections.     

In Silico Screening-Level Prioritization of 8468 Chemicals Produced in OECD Countries to Identify Potential Planetary Boundary Threats

Bulletin of Environmental Contamination and Toxicology - Legislation such as the Stockholm Convention and REACH aim to identify and regulate the production and use of chemicals that qualify as...     

Extracellular vesicles or free circulating DNA: where to search for BRAF and cKIT mutations?

Clinical evidence in oncology argues for the advantages of performing molecular analysis of blood biomarkers to provide information about systemic changes and tumor heterogeneity.Whereas the diagnostic value of cell-free circulating DNA (fcDNA) has successfully been demonstrated in several studies, DNA enclosed in extracellular vesicles (EV) has only recently been described, and its potential diagnostic value is unclear. We established a protocol for separation of EV and fc fractions and tested for presence of mutant BRAFV600E mediating resistance to Vemurafenib and cKITD816V mediating resistance to Imatinib in blood of patients with melanoma and mastocytosis. Our results show that EV contain significantly higher amounts of total DNA as compared to the fc fraction. However, about ten-fold higher copy numbers of the wild type and mutant BRAF and cKIT were detected in the fcDNA fraction supporting its diagnostic value and pointing to differences in fc and EV DNA content.     

Droplet digital PCR revealed high concordance between primary tumors and lymph node metastases in multiplex screening of KRAS mutations in colorectal cancer

Clinical and Experimental Medicine - The proto-oncogene KRAS belongs among the most frequently mutated genes in all types of cancer and is also very important oncogene related to colorectal tumors....     

Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study

Clinical and Experimental Medicine - Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud’s phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of...     

microRNA expression profile in Smooth Muscle Cells isolated from thoracic aortic aneurysm samples

PurposeThoracic aortic aneurysm (TAA) is a cardiovascular disease characterized by increased aortic diameter, treated with surgery and endovascular therapy in order to avoid aortic dissection or rupture. The mechanism of TAA formation has not been thoroughly studied and many factors have been proposed to drive its progression; however strong focus is attributed to modification of smooth muscle cells (SMCs). Latest research indicates, that microRNAs (miRNAs) may play a significant role in TAA development – these are multifunctional molecules consisting of 19–24 nucleotides involved in regulation of the gene expression level related to many biological processes, i.e. cardiovascular disease pathophysiology, immunity or inflammation.Materials and methodsPrimary SMCs were isolated from aortic scraps of TAA patients and age- and sex-matched healthy controls. Purity of isolated SMCs was determined by flow cytometry using specific markers: α-SMA, CALP, MHC and VIM. Real-time polymerase chain reaction (RT-PCR) was conducted for miRNA analysis.ResultsWe established an isolation protocol and investigated the miRNA expression level in SMCs isolated from aneurysmal and non-aneurysmal aortic samples. We identified that let-7 g (0.71-fold, p = 0.01), miR-130a (0.40-fold, p = 0.04), and miR-221 (0.49-fold, p = 0.05) significantly differed between TAA patients and healthy controls.ConclusionsFurther studies are required to improve our understanding of the pathophysiology underlying TAA, which may aid the development of novel, targeted therapies. The pivotal role of miRNAs in the cardiovascular system provides a new perspective on the pathophysiology of thoracic aortic aneurysms.     

Can hepatokines be regarded as novel non-invasive serum biomarkers of intrahepatic lipid content in obese children?

PurposeHepatokines are proteins produced by the liver and involved in regulating glucose and lipid metabolism. However, their role as the biomarkers of intrahepatic lipid content is not clear. The aim of the study was to evaluate the serum concentration of selected hepatokines: fibroblast growth factor-21 (FGF-21), selenoprotein P (SELENOP) and sex hormone-binding globulin (SHBG) in obese children.Patients and methodsThe cross-sectional study included 86 obese children with suspected liver disease. Nonalcoholic fatty liver disease (NAFLD) was diagnosed in children with liver steatosis in ultrasound with elevated alanine aminotransferase (ALT) serum activity and excluded other liver diseases. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (¹H-MRS).ResultsThe concentration of FGF-21 and SELENOP was significantly higher and SHBG significantly lower in children with NAFLD compared to controls. Only FGF-21 level was significantly higher in NAFLD children than in obese patients without NAFLD. The significant positive correlation of FGF-21 with ALT, gamma glutamyltransferase (GGT), triglycerides, homeostatic model assessment–insulin resistance (HOMA-IR), the degree of liver steatosis in ultrasound and TILC in ¹H-MRS were found. The ability of serum FGF-21 to diagnose severe liver steatosis was significant.ConclusionsFGF-21 can be considered as a suitable biomarker in predicting TILC and fatty liver in obese children.     

High Graft-versus-Host Disease-Free,Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia: A Nationwide Swedish Cohort Study

Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients. In total, 68 patients underwent SCT, and 63% of them had failed immunosuppressive therapy. We found that, with a median follow-up of 109 months (range, 35 to 192 months), 5-year overall survival (OS) for all patients was 86.8%, whereas graft-versus-host disease-free, relapse/rejection-free survival (GRFS) at 5 years was 69.1%. There was no survival impact regarding the donor type or stem cell source. Patients aged ≥40 years had a higher transplant-related mortality (29.4% versus 7.8%; P = .023), which translated into a lower 5-year OS: 70.6% versus 92.2% (P = .022) and a trend of lower GRFS (52.9% versus 74.5%; P = .069). In conclusion, we found in this real-world setting that both OS and GRFS were high, but SCT for patients with AA aged ≥40 years is problematic, and clinical trials addressing this issue are warranted.