Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.

Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors.

HAPLN1 potentiates peritoneal metastasis in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Metastatic spreading is promoted by cancer cell plasticity, yet its regulation by the microenvironment is incompletely understood. Here, we show that the presence of hyaluronan and proteoglycan link protein-1 (HAPLN1) in the extracellular matrix enhances tumor cell plasticity and PDAC metastasis.

Semaphorin 3C exacerbates liver fibrosis.

Background And Aims: Chronic liver disease is a growing epidemic, leading to fibrosis and cirrhosis. TGF-β is the pivotal profibrogenic cytokine that activates HSC, yet other molecules can modulate TGF-β signaling during liver fibrosis. Expression of the axon guidance molecules semaphorins (SEMAs), which signal through plexins and neuropilins (NRPs), have been associated with liver fibrosis in HBV-induced chronic hepatitis.

Endothelial RBPJ Is Essential for the Education of Tumor-Associated Macrophages.

Unlabelled: Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic cancers worldwide. EOC cells educate tumor-associated macrophages (TAM) through CD44-mediated cholesterol depletion to generate an immunosuppressive tumor microenvironment (TME). In addition, tumor cells frequently activate Notch1 receptors on endothelial cells (EC) to facilitate metastasis.

Hepatocyte-specific activity of TSC22D4 triggers progressive NAFLD by impairing mitochondrial function.

Objective: Fibrotic organ responses have recently been identified as long-term complications in diabetes. Indeed, insulin resistance and aberrant hepatic lipid accumulation represent driving features of progressive non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis and non-alcoholic steatohepatitis (NASH) to fibrosis. Effective pharmacological regimens to stop progressive liver disease are still lacking to-date.

Synthesis of Silver Modified Bioactive Glassy Materials with Antibacterial Properties via Facile and Low-Temperature Route.

There is an increasing clinical need to develop novel biomaterials that combine regenerative and biocidal properties. In this work, we present the preparation of silver/silica-based glassy bioactive (ABG) compositions via a facile, fast (20 h), and low temperature (80 °C) approach and their characterization. The fabrication process included the synthesis of the bioactive glass (BG) particles followed by the surface modification of the bioactive glass with silver nanoparticles.

MARCH9-mediated ubiquitination regulates MHC I export from the TGN.

Given the heterogeneous nature of antigens, major histocompatibility complex class I (MHC I) intracellular transport intersects with multiple degradation pathways for efficient peptide loading and presentation to cytotoxic T cells. MHC I loading with peptides in the endoplasmic reticulum (ER) is a tightly regulated process, while post-ER intracellular transport is considered to occur by default, leading to peptide-bearing MHC I delivery to the plasma membrane. We show here that MHC I traffic is submitted to a previously uncharacterized sorting step at the trans Golgi network (TGN), dependent on the ubiquitination of its cytoplasmic tail lysine residues.

Using iPS Cells toward the Understanding of Parkinson's Disease.

Cellular reprogramming of somatic cells to human pluripotent stem cells (iPSC) represents an efficient tool for in vitro modeling of human brain diseases and provides an innovative opportunity in the identification of new therapeutic drugs. Patient-specific iPSC can be differentiated into disease-relevant cell types, including neurons, carrying the genetic background of the donor and enabling de novo generation of human models of genetically complex disorders. Parkinson's disease (PD) is the second most common age-related progressive neurodegenerative disease, which is mainly characterized by nigrostriatal dopaminergic (DA) neuron degeneration and synaptic dysfunction.

MHC-II ubiquitination.

Ubiquitinated protein detection is often troublesome since in most cases this modification reduces the half-life of targeted proteins, inducing their degradation. Furthermore, ubiquitination is reversible thanks to the action of highly specific deubiquitinases present in all eukaryotic cells. MHC molecules ubiquitination has been demonstrated to be a key event in the regulation of the potent immunostimulatory properties of activated human dendritic cells.

Autophagy inhibition promotes defective neosynthesized proteins storage in ALIS, and induces redirection toward proteasome processing and MHCI-restricted presentation.

A significant portion of newly synthesized protein fails to fold properly and is quickly degraded. These defective ribosomal products (DRiPs) are substrates for the ubiquitin-proteasome system (UPS) and give rise to a large fraction of peptides presented by major histocompatibility complex class I molecules (MHCI). Here, we showed that DRiPs are also autophagy substrates, which accumulate upon autophagy inhibition in aggresome-like-induced structures (ALIS).