BEL \u3b2\u2010Trefoil Reduces the Migration Ability of RUNX2 Expressing Melanoma Cells in Xenotransplanted Zebrafish

RUNX2, a master osteogenic transcript ion factor, is overexpressed in several cancer cells; in melanoma it promotes cells migration and invasion as well as neoangiogenesis. The annual mortality rates related to metastatic melanoma are high and novel agents are needed to improve melanoma patients\u2019 survival. It has been shown that lectins specifically target malignant cells since they present the Thomsen\u2013Friedenreich antigen. This disaccharide is hidden in normal cells, while it allows selective lectins binding in transformed cells. Recently, an edible lectin named BEL \u3b2-trefoil has been obtained from the wild mushroom Boletus edulis. Our previous study showed BEL \u3b2-trefoil effects on transcription factor RUNX2 downregulation as well as on the migration ability in melanoma cells treated in vitro. Therefore, to better understand the role of this lectin, we investigated the BEL \u3b2-trefoil effects in a zebrafish in vivo model, transplanted with human melanoma cells expressing RUNX2. Our data showed that BEL \u3b2-trefoil is able to spread in the tissues and to reduce the formation of metastases in melanoma xenotransplanted zebrafish. In conclusion, BEL \u3b2-trefoil can be considered an effective biomolecule to counteract melanoma disease

Increased Gene Expression of RUNX2 and SOX9 in Mesenchymal Circulating Progenitors Is Associated with Autophagy during Physical Activity

Lack of physical exercise is considered an important risk factor for chronic diseases. On the contrary, physical exercise reduces the morbidity rates of obesity, diabetes, bone disease, and hypertension. In order to gain novel molecular and cellular clues, we analyzed the effects of physical exercise on differentiation of mesenchymal circulating progenitor cells (M-CPCs) obtained from runners. We also investigated autophagy and telomerase-related gene expression to evaluate the involvement of specific cellular functions in the differentiation process. We performed cellular and molecular analyses in M-CPCs, obtained by a depletion method, of 22 subjects before (PRE RUN) and after (POST RUN) a half marathon performance. In order to prove our findings, we performed also in vitro analyses by testing the effects of runners' sera on a human bone marrow-derived mesenchymal stem (hBM-MSC) cell line. PCR array analyses of PRE RUN versus POST RUN M-CPC total RNAs put in evidence several genes which appeared to be modulated by physical activity. Our results showed that physical exercise promotes differentiation. Osteogenesis-related genes as RUNX2, MSX1, and SPP1 appeared to be upregulated after the run; data showed also increased levels of BMP2 and BMP6 expressions. SOX9, COL2A1, and COMP gene enhanced expression suggested the induction of chondrocytic differentiation as well. The expression of telomerase-associated genes and of two autophagy-related genes, ATG3 and ULK1, was also affected and correlated positively with MSC differentiation. These data highlight an attractive cellular scenario, outlining the role of autophagic response to physical exercise and suggesting new insights into the benefits of physical exercise in counteracting chronic degenerative conditions

The recurrent causal mutation for osteogenesis imperfecta type V occurs at a highly methylated CpG dinucleotide within the IFITM5 gene

Recent studies have identified the molecular defect underlying autosomal dominant osteogenesis imperfecta (OI) type V. Unlike all other OI types, which are characterized by high genetic heterogeneity, OI type V appears consistently associated to a unique de novo C>T transition within the 5\u2032 UTR of the IFITM5 gene. Although the precise frequency of OI type V is not known, this recurrent base substitution may well represent a mutational hotspot in the human genome. We show that it occurs at a CpG dinucleotide that is highly methylated in several tissues and particularly in the sperm DNA, suggesting a mutational mechanism common to other de novo recurrent dominant mutations

Clodronate as a Therapeutic Strategy against Osteoarthritis

Osteoarthritis (OA), the most prevalent musculoskeletal pathology, is mainly characterized by the progressive degradation of articular cartilage due to an imbalance between anabolic and catabolic processes. Consequently, OA has been associated with defects in the chondrocitic differentiation of progenitor stem cells (PSCs). In addition, SOX9 is the transcription factor responsible for PSCs chondrogenic commitment. To evaluate the effects of the non-amino bisphosphonate clodronate in OA patients we investigated SOX9 gene expression in circulating progenitor cells (CPCs) and in an in vitro OA model. We evaluated pain intensity, mental and physical performance in OA patients, as well as serum biomarkers related to bone metabolism. In addition, in order to improve therapeutic strategies, we assayed nanoparticle-embedded clodronate (NPs-clo) in an in vitro model of chondrogenic differentiation. Our data showed upregulation of SOX9 gene expression upon treatment, suggesting an increase in chondrocytic commitment. Clodronate also reduced osteoarticular pain and improved mental and physical performance in patients. Furthermore, NPs-clo stimulated SOX9 expression more efficaciously than clodronate alone. Clodronate may therefore be considered a good therapeutic tool against OA; its formulation in nanoparticles may represent a promising challenge to counteract cartilage degeneration

Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy

Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy.BackgroundCritical illness leading to multi-organ dysfunction syndrome (MODS) and associated acute renal failure (ARF) is less common in children compared to adult patients. As a result, many issues plague the pediatric ARF outcome literature, including a relative lack of prospective study, a lack of modality stratification in subject populations and inconsistent controls for patient illness severity in outcome analysis.MethodsWe now report data from the first multicenter study to assess the outcome of pediatric patients with MODS receiving continuous renal replacement therapy (CRRT). One hundred twenty of 157 Registry patients (63 male/57 female) experienced MODS during their course.ResultsOne hundred sixteen patients had complete data available for analysis. The most common causes leading to CRRT were sepsis (N = 47; 39.2%) and cardiogenic shock (N = 24; 20%). Overall survival was 51.7%. Pediatric Risk of Mortality (PRISM 2) score, central venous pressure (CVP), and% fluid overload (%FO) at CRRT initiation were significantly lower for survivors versus nonsurvivors. Multivariate analysis controlling for severity of illness using PRISM 2 at CRRT initiation revealed that%FO was still significantly lower for survivors versus nonsurvivors (P < 0.05) even for patients receiving both mechanical ventilation and vasoactive pressors. We speculate that increased fluid administration from PICU admission to CRRT initiation is an independent risk factor for mortality in pediatric patients with MODS receiving CRRT.ConclusionWe suggest that after initial resuscitative efforts, an increased emphasis should be placed on early initiation of CRRT and inotropic agent use over fluid administration to maintain acceptable blood pressure

Ancient DNA from domestic animal species remains : preliminary approaches

DNA analysis from ancient and old remains offers new tools to answer archaeozoological questions and investigate the origin of the genetic variability in domestic animal species. Molecular genetics techniques contribute to identify the species supporting classical osteological studies and to establish the relationship to modern species and breeds. Mitochondrial DNA (mtDNA) sequences are useful to reconstruct the history of maternal lineages comparing haplotype variations of present and old DNA samples. Mitochondrial data from modern cattle populations show a high diversity in Anatolia and in the Middle East supporting a near-Eastern matrilineal centre of origin. On the contrary in Europe a single family of mitochondrial haplotypes strongly dominates. A number of recent studies reported the successful recovery of ancient and old nuclear DNA (nuDNA) sequences. Such studies represent an important breakthrough, as nuDNA can be used for the characterisation of genetic loci directly involved in phenotypic traits, answering challenging questions. A bright example is offered by the study on the single nuclear exon of melanocortin type 1 receptor gene from a ca. 43,000 years old mammoth bone from Siberia, showing that mammoth populations were polymorphic with regard to hair colour, harbouring both dark and light haired animals. In contrast, these studies on ancient and old DNA sequences need great caution, due to the analytical problems caused by post-mortem damage of DNA, contamination from exogenous sources of mt- and nuDNA, and the consequent reliability of observed polymorphisms. The present research describes the preliminary analytical approach to DNA study of faunal remains (103 animal bones of different domestic species: Bos taurus 51; Ovis aries/Capra hircus 39; Sus scrofa/Sus domesticus 10; Gallus gallus 1; Equus caballus/Equus sp. 2), collected in seven archaeological sites located within the province of Trento, in the Alpine region of Trentino Alto-Adige (N-E Italy). The chosen sites, dating from the Bronze Age to the late Middle Ages, display different settlement typology and include Iron Age retic houses, votive Bronze Age contexts, a 4th century roman villa and several 13th century medieval buildings. Archaeozoological data will be collected on species, skeletal parts, age of slaughter, method of butchery, evidence of bone working and presence of paleopathologies. We describe the analytical procedure used in preparing and collecting samples and in extracting and analysing DNA from a subset of the bones previously described

Rivaroxaban:Xarelto® - Recommendations for pharmacists

Rivaroxaban is one of the new oral anticoagulants (NOACs) (recommended as reference treatments when a long-term anticoagulation is needed). It has many potential advantages in comparison with Vitamin K Antagonists (VKA). It has a predictable anticoagulant effect and does not theoretically require biological monitoring. It is also characterized by less food and drug interactions. However, due to major risks associated with over- and under-dosage, its optimal use in patients should be carefully followed by health care professionals. The aim of this article is to provide recommendations for pharmacists on the practical use of Xarelto® in its different approved indications. This document is adapted from the practical user guide of rivaroxaban which was developed by an independent group of Belgian experts in the field of thrombosis and haemostasis