The Placenta as a Source of Human Material for Neuronal Repair.

Stem cell therapy has the potential to meet unsolved problems in tissue repair and regeneration, particularly in the neural tissues. However, an optimal source has not yet been found. Growing evidence indicates that positive effects produced in vivo by mesenchymal stem cells (MSCs) can be due not only to their plasticity but also to secreted molecules including extracellular vesicles (EVs) and the extracellular matrix (ECM).

Diagnostic and Prognostic Markers for Pancreatitis and Pancreatic Ductal Adenocarcinoma.

Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas.

G Protein-Coupled Receptors and the Rise of Type 2 Diabetes in Children.

The human genome counts hundreds of GPCRs specialized to sense thousands of different extracellular cues, including light, odorants and nutrients in addition to hormones. Primordial GPCRs were likely glucose transporters that became sensors to monitor the abundance of nutrients and direct the cell to switch from aerobic metabolism to fermentation. Human β cells express multiple GPCRs that contribute to regulate glucose homeostasis, cooperating with many others expressed by a variety of cell types and tissues.

Landscape of Druggable Molecular Pathways Downstream of Genomic CDH1/Cadherin-1 Alterations in Gastric Cancer.

Loss of CDH1/Cadherin-1 is a common step towards the acquisition of an abnormal epithelial phenotype. In gastric cancer (GC), mutation and/or downregulation of CDH1/Cadherin-1 is recurrent in sporadic and hereditary diffuse GC type. To approach the molecular events downstream of CDH1/Cadherin-1 alterations and their relevance in gastric carcinogenesis, we queried public databases for genetic and DNA methylation data in search of molecular signatures with a still-uncertain role in the pathological mechanism of GC.

cAMP Response Element-Binding Protein Controls the Appearance of Neuron-Like Traits in Chorion Mesenchymal Cells.

Background: Mesenchymal stromal cells (MSC) from bone marrow have been reported to undergo the initial phases of neural differentiation in response to an increase of intracellular cAMP. We investigated the possibility that a similar effect applies to chorion-derived MSC.

Methods: The intracellular concentration of cAMP was increased either by forskolin, to promote its synthesis, or by inhibitors of its degradation.

High Values of Drain Fluid Epidermal Growth Factor and Transforming Growth Factor-Beta Are Associated with the Development of Pancreatic Fistula after Pancreatoduodenectomy.

Introduction: Postoperative inflammatory response may act as a major determinant of anastomotic failure after pancreaticoduodenectomy. In this pilot study, we investigated the potential role of drain fluid cytokines in predicting postoperative pancreatic fistula (POPF).

Methods: Drain fluid TGF-β, IGF-1, EGF, and IL-6, together with serum amylase and drain fluid amylase, were measured on POD1 and correlated with the development of POPF.

Physical Activity Modulates miRNAs Levels and Enhances MYOD Expression in Myoblasts.

Stem cells functions are regulated by different factors and non-conding RNAs, such as microRNA. MiRNAsplay an important role in modulating the expression of genes involved in the commitment and differentiation of progenitor cells. MiRNAs are post transcriptional regulators which may be modulated by physical exercise.

Circulating tumour DNA: a challenging innovation to develop "precision onco-surgery" in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the third leading cause of cancer-related mortality within the next decade. Management of PDAC remains challenging with limited effective treatment options and a dismal long-term prognosis. Liquid biopsy and circulating biomarkers seem to be promising to improve the multidisciplinary approach in PDAC treatment.

Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model.

Pancreatic cancer (PC) represents an intriguing topic for researchers. To date, the prognosis of metastasized PC is poor with just 7% of patients exceeding a five-year survival period. Thus, molecular modifications of existing drugs should be developed to change the course of the disease.

Gα15 in early onset of pancreatic ductal adenocarcinoma.

The GNA15 gene is ectopically expressed in human pancreatic ductal adenocarcinoma cancer cells. The encoded Gα15 protein can promiscuously redirect GPCR signaling toward pathways with oncogenic potential. We sought to describe the distribution of GNA15 in adenocarcinoma from human pancreatic specimens and to analyze the mechanism driving abnormal expression and the consequences on signaling and clinical follow-up.

Knockout mouse models reveal the contributions of G protein subunits to complement C5a receptor-mediated chemotaxis.

G protein-coupled receptor signaling is required for the navigation of immune cells along chemoattractant gradients. However, chemoattractant receptors may couple to more than one type of heterotrimeric G protein, each of which consists of a Gα, Gβ, and Gγ subunit, making it difficult to delineate the critical signaling pathways. Here, we used knockout mouse models and time-lapse microscopy to elucidate Gα and Gβ subunits contributing to complement C5a receptor-mediated chemotaxis.

A Potential Role of RUNX2- RUNT Domain in Modulating the Expression of Genes Involved in Bone Metastases: An In Vitro Study with Melanoma Cells.

Ectopic expression of RUNX2 has been reported in several tumors. In melanoma cells, the RUNT domain of RUNX2 increases cell proliferation and migration. Due to the strong link between RUNX2 and skeletal development, we hypothesized that the RUNT domain may be involved in the modulation of mechanisms associated with melanoma bone metastasis.

Cocoa Flavonoids Reduce Inflammation and Oxidative Stress in a Myocardial Ischemia-Reperfusion Experimental Model.

Consumption of flavonoid-rich nutraceuticals has been associated with a reduction in coronary events. The present study analyzed the effects of cocoa flavonols on myocardial injury following acute coronary ischemia-reperfusion (I/R). A commercially available cocoa extract was identified by chromatographic mass spectrometry.

Publisher Correction: Runx2 stimulates neoangiogenesis through the Runt domain in melanoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Methylation Dynamics of and Its Impact on Cancer.

5-methyl cytosine (5mC) is a key epigenetic mark entwined with gene expression and the specification of cellular phenotypes. Its distribution around gene promoters sets a barrier for transcriptional enhancers or inhibitor proteins binding to their target sequences. As a result, an additional level of regulation is added to the signals that organize the access to the chromatin and its structural components.

Runx2 stimulates neoangiogenesis through the Runt domain in melanoma.

Runx2 is a transcription factor involved in melanoma cell migration and proliferation. Here, we extended the analysis of Runt domain of Runx2 in melanoma cells to deepen understanding of the underlying mechanisms. By the CRISPR/Cas9 system we generated the Runt KO melanoma cells 3G8.

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration.

The mortality rate for malignant melanoma (MM) is very high, since it is highly invasive and resistant to chemotherapeutic treatments. The modulation of some transcription factors affects cellular processes in MM. In particular, a higher expression of the osteogenic master gene RUNX2 has been reported in melanoma cells, compared to normal melanocytes.

A single amino acid substitution in CXCL12 confers functional selectivity at the beta-arrestin level.

CXCL12/CXCR4 axis relies on both heterotrimeric G protein and β-arrestin coupling to trigger downstream responses. G protein activation allows for calcium flux, chemotaxis and early extracellular-signal regulated kinases 1/2 (ERK1/2) phosphorylation, whereas β-arrestin recruitment leads to late signaling, receptor desensitization and internalization. Together they may regulate the balance between transactivation and transinhibition of epithelial growth factor receptor 1 (HER1).

An integrated approach identifies new oncotargets in melanoma.

Melanoma is an aggressive skin cancer; an early detection of the primary tumor may improve its prognosis. Despite many genes have been shown to be involved in melanoma, the full framework of melanoma transformation has not been completely explored. The characterization of pathways involved in tumor restraint in models may help to identify oncotarget genes.

The curious case of Gαs gain-of-function in neoplasia.

Background: Mutations activating the α subunit of heterotrimeric Gs protein are associated with a number of highly specific pathological molecular phenotypes. One of the best characterized is the McCune Albright syndrome. The disease presents with an increased incidence of neoplasias in specific tissues.

Immunomodulation after radiofrequency ablation of locally advanced pancreatic cancer by monitoring the immune response in 10 patients.

Objective/background: RFA of pancreatic cancer has been demonstrated to be feasible and safe with a positive impact on survival. The aim was to investigate whether an immune reaction is activated after locally advanced pancreatic cancer (LAPC) ablation.

Methods: Peripheral Blood samples were obtained preoperatively and on post-operative days 3-30.

GNAS Mutations: Drivers or Co-Pilots? Yet, Promising Diagnostic Biomarkers.

Over 25 years ago, GNAS mutations were discovered associated with McCune-Albright syndrome (MAS) and pituitary tumors. The mutant gene, encoding the heterotrimeric Gs protein, was named 'derived from Gs Protein' (gsp) oncogene. For a long time, gsp remained associated with specific endocrine tumors.

Pleiotropic effects of sphingosine-1-phosphate signaling to control human chorionic mesenchymal stem cell physiology.

Chorionic stem cells represent a promising opportunity for regenerative medicine. A deeper understanding of the stimuli that regulate their physiology, could lead to innovative clinical approaches. We revealed the presence of multiple sphingosine-1-phosphate (S1P) receptor isoforms in chorion-derived mesenchymal stem cells (CMSCs).

Characterization and Expression of Sphingosine 1-Phosphate Receptors in Human and Rat Heart.

Sphingosine 1-phosphate (S1P), sphingolipid derivatives are known anti-inflammatory, anti-apoptotic, and anti-oxidant agent. S1P have been demonstrated to have a role in the cardiovascular system. The purpose of this study was to understand the precise expression and distribution of S1P receptors (S1PRs) in human and rat cardiovascular tissues to know the significance and possible implementation of our experimental studies in rat models.