Enhancing Drug Delivery Efficacy Through Bilayer Coating of Zirconium-Based Metal-Organic Frameworks: Sustained Release and Improved Chemical Stability and Cellular Uptake for Cancer Therapy.

The development of nanoparticle (NP)-based drug carriers has presented an exciting opportunity to address challenges in oncology. Among the 100,000 available possibilities, zirconium-based metal-organic frameworks (MOFs) have emerged as promising candidates in biomedical applications. Zr-MOFs can be easily synthesized as small-size NPs compatible with intravenous injection, whereas the ease of decorating their external surfaces with functional groups allows for targeted treatment.

Mutations causing premature termination codons discriminate and generate cellular and clinical variability in HHT.

For monogenic diseases caused by pathogenic loss-of-function DNA variants, attention focuses on dysregulated gene-specific pathways, usually considering molecular subtypes together within causal genes. To better understand phenotypic variability in hereditary hemorrhagic telangiectasia (HHT), we subcategorized pathogenic DNA variants in ENG/endoglin, ACVRL1/ALK1, and SMAD4 if they generated premature termination codons (PTCs) subject to nonsense-mediated decay. In 3 patient cohorts, a PTC-based classification system explained some previously puzzling hemorrhage variability.

Vitamin D impact in affecting clozapine plasma exposure: A potential contribution of seasonality.

Schizophrenia affects approximately 24 million people worldwide and clozapine is the most effective antipsychotic drug. Nevertheless, its use in therapy is limited due to adverse effects.Therapeutic drug monitoring is a clinical tool useful to reduce the clozapine toxicity.

A roadmap for the characterization of energy metabolism in human cardiomyocytes derived from induced pluripotent stem cells.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are an increasingly employed model in cardiac research and drug discovery. As cellular metabolism plays an integral role in determining phenotype, the characterization of the metabolic profile of hiPSC-CM during maturation is crucial for their translational application. In this study we employ a combination of methods including extracellular flux, C-glucose enrichment and targeted metabolomics to characterize the metabolic profile of hiPSC-CM during their maturation in culture from 6 weeks, up to 12 weeks.

Cardiomyocyte protein O-GlcNAcylation is regulated by GFAT1 not GFAT2.

In response to cardiac injury, increased activity of the hexosamine biosynthesis pathway (HBP) is linked with cytoprotective as well as adverse effects depending on the type and duration of injury. Glutamine-fructose amidotransferase (GFAT; gene name gfpt) is the rate-limiting enzyme that controls flux through HBP. Two protein isoforms exist in the heart called GFAT1 and GFAT2.

The integrated stress response in pulmonary disease.

The respiratory tract and its resident immune cells face daily exposure to stress, both from without and from within. Inhaled pathogens, including severe acute respiratory syndrome coronavirus 2, and toxins from pollution trigger a cellular defence system that reduces protein synthesis to minimise viral replication or the accumulation of misfolded proteins. Simultaneously, a gene expression programme enhances antioxidant and protein folding machineries in the lung.

A Xenogenic Bone Derivative as a Potential Adjuvant for Bone Regeneration and Implant Osseointegration: An Study.

Several clinical conditions may limit the success of bone regeneration and/or implant osseointegration. For this reason, many compounds have been tested for their ability to stimulate this biological process. Synthetic hydroxyapatite (HA), mimicking natural bone hydroxyapatite, and extra-cellular matrix proteins, such as type I collagen, are potential candidates.

Transcriptional Activation of Pericentromeric Satellite Repeats and Disruption of Centromeric Clustering upon Proteasome Inhibition.

Heterochromatinisation of pericentromeres, which in mice consist of arrays of major satellite repeats, are important for centromere formation and maintenance of genome stability. The dysregulation of this process has been linked to genomic stress and various cancers. Here we show in mice that the proteasome binds to major satellite repeats and proteasome inhibition by MG132 results in their transcriptional de-repression; this de-repression is independent of cell-cycle perturbation.

[Linee guida flebo-linfologiche SIF-SICVE 2016 della Società Italiana di Flebologia e della Società Italiana di Chirurgia Vascolare ed Endovascolare].

Phlebology is not a specialty for its own in Italy. Phlebological patients are treated by vascular and general surgeons, dermatologists, phlebologists, angiologists, internists and even general practitioners. Even tough guidelines present a series of recommendations based on evidence-based medicine, guidelines may also be a tool to unify the diagnostic and therapeutic approach in a vast medical field like phlebology.

Extracting order from heterogeneity: A report on the EpiGeneSys workshop "Single Cell Epigenetics" in Montpellier, June 11-12, 2015.

Understanding epigenetic modifications to chromatin that regulate gene expression and cell-fate decisions is now possible in single cells thanks to recent technological advances. As interdisciplinary approaches are required to derive biological principles, this workshop brought together some of Europe's leading researchers in single-cell epigenetics to share technologies and biological insights.

Osteo-promoting activity of OSTEOPLANT ANGIOSTAD in vitro.

Aim: There is an increasing need for an appropriate and readily-available material to reconstruct large bone defects, one of the most significant problems in the dental and maxillo-facial fields. The in vitro study examines the effects of OSTEOPLANT ANGIOSTAD, a product developed to increase osteoinductivity.

Methods: The product's biological properties were assessed by examining: the viability of cultured bone-marrow mesenchymal stem cells (MSC) through the methylthiazol tetrazolium assay; transforming growth factor (TGF)-b release by these cells through the enzyme-linked immunosorbent assay (ELISA) and the migration capacity of MSC and endothelial cells, by the in vitro wound closure test and transwell-migration assay, respectively.

The VenaTech LP permanent caval filter: effectiveness and safety in the prevention of pulmonary embolism--a European multicenter study.

Purpose: To evaluate (i) the appropriateness, safety, and patient outcomes after placement of the VenaTech LP caval filter and (ii) the success of filter insertion through various venous access routes.

Materials And Methods: An open multicenter prospective observational study was conducted in 12 European centers, including an initial part limited to four centers. Patients with common indications were eligible for inclusion after approval by an independent ethics committee.

Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis.

Aim: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC).

Methods: Gastric tissue from a patient with severe idiopathic gastroparesis unresponsive to medical treatment and requiring surgery was analyzed by conventional histology and immunohistochemistry.

Results: Gastric pacemaker cells expressing Kit receptor had completely disappeared while the local level of stem cell factor, the essential ligand for its development and maintenance, was increased.

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes.

Autocrine/paracrine stimulation of KIT has been observed in colorectal carcinoma (CRC) cell lines. We investigated the expression of KIT and stem cell factor (SCF) in CRC in comparison with premalignant colon lesions and normal colonic mucosa to assess the prognostic and therapeutic relevance of this receptor/ligand system in CRC. Transcript levels of c-kit and the two SCF splicing variants were determined quantitatively by real-time RT-PCR using cDNA obtained from normal, premalignant and malignant snap frozen colon tissue specimens.

Antagonistic interactions between gemcitabine and 5-fluorouracil in the human pancreatic carcinoma cell line Capan-2.

Although the recently-developed Gemcitabine (GEM) has renewed interest in clinical research in pancreatic carcinoma, it offers modest improvement of tumor-related symptoms and marginal survival advantage, even when combined with other currently-available chemotherapeutic agents such as 5-Fluorouracil (5-FU). We hypothesized that this disappointing result could be due to an interaction between the two drugs affecting cytotoxic activity. We measured in-vitro growth inhibition, cell cycle distribution, gene and protein expression of apoptosis regulators bcl-2, bcl-x and survivin, NFkappaB and telomerase activities of human pancreatic carcinoma cell line Capan-2 following exposure to GEM and 5-FU singly or combined, by MTT assay and median effect analysis, flow cytometry, real-time RT-PCR, Western blotting, electrophoretic mobility shift assay (EMSA) and telomeric repeat amplification protocol (TRAP) assay, respectively.

Cooperative induction of a tolerogenic dendritic cell phenotype by cytokines secreted by pancreatic carcinoma cells.

Ag presentation by dendritic cells (DC) is essential to effective antitumor T cell responses in cancer patients. Depending on their origin, maturation state, and the ambient cytokine milieu, DC can differentiate into distinct subpopulations, which preferentially either induce Th1 cell activation (CD11c+,CD123- myeloid DC (MDC)) or immunosuppressive T cell development (CD11c-,CD123+ plasmacytoid DC (PDC)). The present study was undertaken to characterize the effects of pancreatic carcinoma cell-derived cytokines on immature monocyte-derived DC (iMo-DC) in vitro and in vivo.

Increased intrathecal TGF-beta1, but not IL-12, IFN-gamma and IL-10 levels in Alzheimer's disease patients.

An inflammatory response has been hypothesised to be involved in the pathogenesis of primary dementias, above all Alzheimer's disease (AD). This study was aimed at evaluating interleukin (IL)-12 and a panel of related cytokine levels in paired CSF and sera of demented patients. IL-12 (p70 heterodimer and total IL-12 p40 chain), interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta1 levels were measured in 30 patients with probable Alzheimer's disease (PrAD), 57 patients with other dementing disorders, including probable vascular dementia (PrVD), Parkinson's disease (PD) and normal pressure hydrocephalus (NPH), and 25 cognitively normal control subjects.

[High serum levels of Transforming Growth Factor-beta1, Interleukin-10 and Vascular Endothelial Growth Factor in pancreatic adenocarcinoma patients].

Background: Pancreatic adenocarcinomas are among the most aggressive types of cancer with an extremely poor diagnosis. Since this type of cancer is not well amenable to chemo- and radiotherapy or immunotherapy, surgical resection remains the only feasible treatment to date. Transforming Growth Factor (TGF)-beta and Interleukin (IL)-10 are potent immunomodulators that have been shown to suppress several aspects of the immune response.

[Esophageal motility disorders].

Esophageal motility abnormalities are usually diagnosed when esophageal manometry is performed in patients with unexplained non-cardiac chest pain, non obstructive dysphagia or as a part of the preoperative evaluation for surgery of gastroesophageal reflux. Classification of these abnormalities has been a subject of controversy. These esophageal contraction abnormalities can be separated manometrically from the motor pattern seen in normal subjects, however, their clinical relevance is still unclear and debated.

[Biological aspects of pancreatic cancer].

Pancreatic ductal carcinoma still is an aggressive disease with a fatal prognosis due to late diagnosis and resistance to pharmacological and surgical treatments. Molecular investigations of pancreatic cancer are complicated by the restricted accessibility of the organ for biopsies. However, recent studies have indicated that pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells.

Botulinum toxin treatment of oesophageal achalasia in the old old and oldest old: a 1-year follow-up study.

Background: Intrasphincteric injection of botulinum toxin (BTX) has become one of the most frequent therapeutic approaches for the treatment of oesophageal achalasia. This treatment seems particularly effective in elderly patients who are not candidates for more invasive procedures.

Aims: There are few or no data on BTX treatment of achalasia in the old old and oldest old.

Interstitial cells of Cajal, enteric nerves, and glial cells in colonic diverticular disease.

Background: Colonic diverticular disease (diverticulosis) is a common disorder in Western countries. Although its pathogenesis is probably multifactorial, motor abnormalities of the large bowel are thought to play an important role. However, little is known about the basic mechanism that may underlie abnormal colon motility in diverticulosis.

Circulating vascular endothelial growth factor and interferon-gamma-inducible protein-10 levels in pancreatic cancer during chemotherapy.

Background: Chemotherapeutic anticancer properties are thought to derive from apoptosis pathway activation and/or cell division arrest, but animal models have also evidenced anti-angiogenic activity in some agents.

Patients And Methods: The impact of gemcitabine, irinotecan and oxaliplatin + 5-FU upon the serum markers vascular endothelial growth factor (VEGF) (pro-angiogenic) and IFN-gamma-inducible protein (IP)-10 (anti-angiogenic) was evaluated by ELISA in locally advanced and/or metastatic cancer versus clinical efficacy and survival.

Results: Patients had higher serum levels of both markers versus controls.

Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens: implications for survival.

Cytokine shedding by tumor cells into the local microenvironment modulates host immune response, tumor growth, and metastasis. The study aimed to verify the hypothesis that the immunological microenvironment of pancreatic carcinoma exists in a prevalently immunosuppressive state, influencing survival. We analyzed expression profiles of pro-inflammatory (IL-1beta, IL-2, IL-6, IL-8, IL-12 p40, IL-18 and IFN-gamma) and anti-inflammatory (IL-10, IL-11, IL-13 and TGF-beta isoforms) cytokines.