Natural antimicrobial peptide complexes in the fighting of antibiotic resistant biofilms: Calliphora vicina medicinal maggots.

Biofilms, sedimented microbial communities embedded in a biopolymer matrix cause vast majority of human bacterial infections and many severe complications such as chronic inflammatory diseases and cancer. Biofilms' resistance to the host immunity and antibiotics makes this kind of infection particularly intractable. Antimicrobial peptides (AMPs) are a ubiquitous facet of innate immunity in animals.

First Characterization of Human Amniotic Fluid Stem Cell Extracellular Vesicles as a Powerful Paracrine Tool Endowed with Regenerative Potential.

Human amniotic fluid stem cells (hAFS) have shown a distinct secretory profile and significant regenerative potential in several preclinical models of disease. Nevertheless, little is known about the detailed characterization of their secretome. Herein we show for the first time that hAFS actively release extracellular vesicles (EV) endowed with significant paracrine potential and regenerative effect.

Effects on Energy Metabolism of Two Guanidine Molecules, (Boc) -Creatine and Metformin.

Several enzymes are involved in the energy production, becoming a possible target for new anti-cancer drugs. In this paper, we used biochemical and in silico studies to evaluate the effects of two guanidine molecules, (Boc) -creatine and metformin, on creatine kinase, an enzyme involved in the regulation of intracellular energy levels. Our results show that both drugs inhibit creatine kinase activity; however, (Boc) -creatine displays a competitive inhibition, while metformin acts with a non-competitive mechanism.

N-heterocyclic carbene complexes of silver and gold as novel tools against breast cancer progression.

Aim: Metal carbenic complexes have received considerable attention in both the catalysis and biological fields for their potential applications in cancer and antimicrobial therapies.

Results: A small series of new silver and gold N-heterocyclic carbene complexes has been designed and synthesized. Among the tested complexes, one compound was particularly active in inhibiting anchorage-dependent and -independent breast cancer proliferation, and inducing cell apoptosis via a mitochondria-related process.

Multifaceted properties of 1,4-dimethylcarbazoles: Focus on trimethoxybenzamide and trimethoxyphenylurea derivatives as novel human topoisomerase II inhibitors.

Natural or synthetic carbazole derivatives have recently attracted the attention of the scientific world because of their multiple biological activity, leading to an increase of designed, synthesized and studied analogues. In this paper, four 1,4-dimethylcarbazole derivatives, analogues of Ellipticine, have been investigated for their ability to block cancer cells growth, with low effects on the proliferation of normal cells. DNA topoisomerases inhibition assays, docking simulations, stability studies and effects on a membrane model are reported.

Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition.

Natural killer (NK) cells play a key role in immunity, but how HLA class I (HLA-I) and killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1) polymorphism impacts disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were screened for reactivity against a panel of HLA-I molecules. This revealed different and distinct hierarchies of specificity for each KIR3DL1 allotype, with KIR3DL1*005 recognizing the widest array of HLA-I ligands.

Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling.

G protein-coupled receptors (GPCRs) are cell surface proteins mainly involved in signal transmission; however, they play a role also in several pathophysiological conditions. Chemically heterogeneous molecules like peptides, hormones, lipids, and neurotransmitters activate second messengers and induce several biological responses by binding to these seven transmembrane receptors, which are coupled to heterotrimeric G proteins. Recently, additional molecular mechanisms have been involved in GPCR-mediated signaling, leading to an intricate network of transduction pathways.

Macromolecular Modelling and Docking Simulations for the Discovery of Selective GPER Ligands.

Estrogens influence multiple physiological processes and are implicated in many diseases as well. Cellular responses to estrogens are mainly mediated by the estrogen receptors (ER)α and ERβ, which act as ligand-activated transcription factors. Recently, a member of the G protein-coupled receptor (GPCR) superfamily, namely GPER/GPR30, has been identified as a further mediator of estrogen signalling in different pathophysiological conditions, including cancer.

Transgenic mice overexpressing arginase 1 in monocytic cell lineage are affected by lympho-myeloproliferative disorders and disseminated intravascular coagulation.

Arginase (ARG) is a metabolic enzyme present in two isoforms that hydrolyze l-arginine to urea and ornithine. In humans, ARG isoform 1 is also expressed in cells of the myeloid lineage. ARG activity promotes tumour growth and inhibits T lymphocyte activation.

A Novel Serum 4-microRNA Signature for Lung Cancer Detection.

The aim of this study was to identify differentially-expressed miRNAs in the serum of non-small cell lung cancer (NSCLC) patients that might be a clinically-useful tool for lung cancer early detection. We performed miRNA expression profile analysis using TaqMan OpenArray Human panel in a discovery set of 70 serum samples obtained at lung tumor resection and 22 non-cancer subjects (NC). Selected serum miRNAs were then validated by quantitative PCR using an independent validation set of serum samples from LC patients (n = 84) and NC (n = 23).

Sequential use of vinorelbine followed by gefitinib enhances the antitumor effect in NSCLC cell lines poorly responsive to reversible EGFR tyrosine kinase inhibitors.

Preclinical studies have suggested that combining cytotoxic agents with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to treat EGFR-mutated tumors may increase their inhibitory effect depending on the order of drug administration. The antitumor efficacy of different treatment sequences using vinorelbine (VNB) and gefitinib (GEF) was investigated both in vitro and in vivo in non-small cell lung cancer (NSCLC) cell lines with the rationale of potentially translating these findings into the clinical setting. The EGFR-wild-type A549 and the EGFR-mutated (exon 21 L858R/exon 20 T790M) H1975 cell lines were treated as follows: GEF followed by VNB, VNB followed by GEF and the two drugs applied individually or concurrently.

Transcriptome meta-analysis of lung cancer reveals recurrent aberrations in NRG1 and Hippo pathway genes.

Lung cancer is emerging as a paradigm for disease molecular subtyping, facilitating targeted therapy based on driving somatic alterations. Here we perform transcriptome analysis of 153 samples representing lung adenocarcinomas, squamous cell carcinomas, large cell lung cancer, adenoid cystic carcinomas and cell lines. By integrating our data with The Cancer Genome Atlas and published sources, we analyse 753 lung cancer samples for gene fusions and other transcriptomic alterations.

Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT).

N-alkyl carbazole derivatives as new tools for Alzheimer's disease: preliminary studies.

Alzheimer's disease (AD) is a progressive and age-related neurodegenerative disorder affecting brain cells and is the most common form of "dementia", because of the cognitive detriment which takes place. Neuronal disruption represents its major feature, due to the cytosolic accumulation of amyloid β-peptide (Aβ) which leads to senile plaques formation and intracellular neurofibrillary tangles. Many studies have focused on the design and therapeutic use of new molecules able to inhibit Aβ aggregation.

Incidence of hepatitis in patients with evidence of past or current hepatitis B or C during chemotherapy for early breast cancer.

Aim/background: Few data are available about the prevalence of hepatitis B and C infections in early breast cancer patients and its impact on systemic treatments. The objectives of this study were to determine the incidence of positive serology for hepatitis B and C in women with early breast cancer and to assess the clinical course and its impact on liver function during adjuvant treatments.

Patients And Methods: we retrospectively reviewed hepatitis B and C serology [HBs antigen (HBsAg), HBc antibodies (HBcAb), HBs antibodies (HBsAb) and HC (HCV) antibodies] in 746 consecutive patients with early breast cancer treated at our Institution between 2009 and 2011.

Stromal cells from human decidua exert a strong inhibitory effect on NK cell function and dendritic cell differentiation.

Stromal cells (SC) are an important component of decidual tissues where they are in strict proximity with both NK and CD14(+) myelomonocytic cells that play a role in the maintenance of pregnancy. In this study we analyzed whether decidual SC (DSC) could exert a regulatory role on NK and CD14(+) cells that migrate from peripheral blood (PB) to decidua during pregnancy. We show that DSCs inhibit the IL15-mediated up-regulation of major activating NK receptors in PB-derived NK cells.

Selective role of mevalonate pathway in regulating perforin but not FasL and TNFalpha release in human Natural Killer cells.

We have analyzed the effects of fluvastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase involved in mevalonate synthesis, on human NK cell-mediated anti-tumor cytolysis. Fluvastatin inhibited the activation of the small guanosin triphosphate binding protein (GTP) RhoA and the consequent actin redistribution induced by ligation of LFA1 involved in NK-tumor target cell adhesion. Also, fluvastatin reduced ganglioside M1 rafts formation triggered through the engagement of NK cell activating receptors as FcγRIIIA (CD16), NKG2D and DNAM1.

Randomised phase 3 open-label trial of first-line treatment with gemcitabine in association with docetaxel or paclitaxel in women with metastatic breast cancer: a comparison of different schedules and treatments.

Background: This open-label study compared docetaxel/gemcitabine vs. paclitaxel/gemcitabine and a weekly (W) vs. 3-weekly (3 W) schedule in metastatic breast cancer (MBC).