MT1-MMP and TIMP-2 are first expressed in the colon glands after a single dose of azoxymethane (AOM).

Tissue inhibitor of metalloproteinase-2 (TIMP-2) and membrane-type 1-matrix metalloproteinase (MT1-MMP) are always expressed during the cancer process. The aim was to identify which regions of the colon mucosa MT1-MMP and TIMP-2 begin to express themselves, as well as to establish their expression in relation to cell proliferation and mucin production. After intraperitoneal injection of 15 mg/kg of azoxymethane (AOM) at 4, 12, and 20 weeks, histological sections of the middle segment of the rat colon mucosa were evaluated by immunohistochemistry for cell proliferation and expression of MT1-MMP and TIMP-2 and histochemistry for mucin.

Long non-coding RNA CASC2 regulates osteoblasts matrix mineralization.

Long non-coding RNAs (lncRNAs) are master regulators of gene expression and have recently emerged as potential innovative therapeutic targets. The deregulation of lncRNA expression patterns has been associated with age-related and noncommunicable diseases in the bone tissue, including osteoporosis and tumors. However, the specific role of lncRNAs in physiological or pathological conditions in the bone tissue still needs to be further clarified, for their exploitation as therapeutic tools.

Pro-inflammatory polarization and colorectal cancer modulate alternative and intronic polyadenylation in primary human macrophages.

Introduction: Macrophages are essential cells of the immune system that alter their inflammatory profile depending on their microenvironment. Alternative polyadenylation in the 3'UTR (3'UTR-APA) and intronic polyadenylation (IPA) are mechanisms that modulate gene expression, particularly in cancer and activated immune cells. Yet, how polarization and colorectal cancer (CRC) cells affect 3'UTR-APA and IPA in primary human macrophages was unclear.

Long non-coding RNA H19 regulates matrisome signature and impacts cell behavior on MSC-engineered extracellular matrices.

Background: The vast and promising class of long non-coding RNAs (lncRNAs) has been under investigation for distinct therapeutic applications. Nevertheless, their role as molecular drivers of bone regeneration remains poorly studied. The lncRNA H19 mediates osteogenic differentiation of Mesenchymal Stem/Stromal Cells (MSCs) through the control of intracellular pathways.

Neuroprotective effects on microglia and insights into the structure-activity relationship of an antioxidant peptide isolated from Pelophylax perezi.

Tryptophyllins constitute a heterogeneous group of peptides that are one of the first classes of peptides identified from amphibian's skin secretions. Here, we report the structural characterization and antioxidant properties of a novel tryptophyllin-like peptide, named PpT-2, isolated from the Iberian green frog Pelophylax perezi. The skin secretion of P.

TNF-alpha-induced microglia activation requires miR-342: impact on NF-kB signaling and neurotoxicity.

Growing evidences suggest that sustained neuroinflammation, caused by microglia overactivation, is implicated in the development and aggravation of several neurological and psychiatric disorders. In some pathological conditions, microglia produce increased levels of cytotoxic and inflammatory mediators, such as tumor necrosis factor alpha (TNF-α), which can reactivate microglia in a positive feedback mechanism. However, specific molecular mediators that can be effectively targeted to control TNF-α-mediated microglia overactivation, are yet to be uncovered.

The Antioxidant Peptide Salamandrin-I: First Bioactive Peptide Identified from Skin Secretion of Salamandra Genus (Salamandra salamandra).

Amphibian skin is a multifunctional organ that plays key roles in defense, breathing, and water balance. In this study, skin secretion samples of the fire salamander (Salamandra salamandra) were separated using RP-HPLC and de novo sequenced using MALDI-TOF MS/MS. Next, we used an in silico platform to screen antioxidant molecules in the framework of density functional theory.

miR-99a in bone homeostasis: Regulating osteogenic lineage commitment and osteoclast differentiation.

Background: The tight coupling between osteoblasts and osteoclasts is essential to maintain bone homeostasis. Deregulation of this process leads to loss and deterioration of the bone tissue causing diseases, such as osteoporosis. MicroRNAs are able to control bone-related mechanisms and have been explored as therapeutic tools.

Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects.

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches.

Cell Cycle Kinase Polo Is Controlled by a Widespread 3' Untranslated Region Regulatory Sequence in Drosophila melanogaster.

Alternative polyadenylation generates transcriptomic diversity, although the physiological impact and regulatory mechanisms involved are still poorly understood. The cell cycle kinase Polo is controlled by alternative polyadenylation in the 3' untranslated region (3'UTR), with critical physiological consequences. Here, we characterized the molecular mechanisms required for alternative polyadenylation.

Xanthohumol inhibits cell proliferation and induces apoptosis in human thyroid cells.

The cell growth inhibitory potential of xanthohumol (XN), a natural prenylflavonoid present in hops and beer, on human papillary thyroid cancer cells is reported. We demonstrate that XN decreases the proliferation of TPC-1 cancer cells in a dose and time dependent manners. At low concentration (10 μM) XN was shown to significantly inhibit carcinogenesis by a mechanism that stops or slows down cell division, preserving the viability of the cells.

Transcription elongation rate has a tissue-specific impact on alternative cleavage and polyadenylation in .

Alternative polyadenylation (APA) is a mechanism that generates multiple mRNA isoforms with different 3'UTRs and/or coding sequences from a single gene. Here, using 3' region extraction and deep sequencing (3'READS), we have systematically mapped cleavage and polyadenylation sites (PASs) in , expanding the total repertoire of PASs previously identified for the species, especially those located in A-rich genomic sequences. -element analysis revealed distinct sequence motifs around fly PASs when compared to mammalian ones, including the greater enrichment of upstream UAUA elements and the less prominent presence of downstream UGUG elements.

Neutral PEGylated liposomal formulation for efficient folate-mediated delivery of MCL1 siRNA to activated macrophages.

Cationic liposomes are efficient vectors for systemic delivery of therapeutic small interfering RNA (siRNA), taking advantage of RNA interference (RNAi), a naturally occurring gene-silencing mechanism in mammalian cells. However, toxicity at high concentrations, short circulating half-lives and lack of specificity restrict their successful application in a wider scale. The purpose of this study was to evaluate the efficiency of neutral liposomes containing polyethylene glycol (PEG) to encapsulate siRNA in their aqueous core.

Expression of Rac1 alternative 3' UTRs is a cell specific mechanism with a function in dendrite outgrowth in cortical neurons.

The differential expression of mRNAs containing tandem alternative 3' UTRs, achieved by mechanisms of alternative polyadenylation and post-transcriptional regulation, has been correlated with a variety of cellular states. In differentiated cells and brain tissues there is a general use of distal polyadenylation signals, originating mRNAs with longer 3' UTRs, in contrast with proliferating cells and other tissues such as testis, where most mRNAs contain shorter 3' UTRs. Although cell type and state are relevant in many biological processes, how these mechanisms occur in specific brain cell types is still poorly understood.

Assessment of liposome disruption to quantify drug delivery in vitro.

Efficient liposome disruption inside the cells is a key for success with any type of drug delivery system. The efficacy of drug delivery is currently evaluated by direct visualization of labeled liposomes internalized by cells, not addressing objectively the release and distribution of the drug. Here, we propose a novel method to easily assess liposome disruption and drug release into the cytoplasm.

Enhancing Methotrexate Tolerance with Folate Tagged Liposomes in Arthritic Mice.

Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy.

Peptide Anchor for Folate-Targeted Liposomal Delivery.

Specific folate receptors are abundantly overexpressed in chronically activated macrophages and in most cancer cells. Directed folate receptor targeting using liposomes is usually achieved using folate linked to a phospholipid or cholesterol anchor. This link is formed using a large spacer like polyethylene glycol.

Identification of thyroid hormone receptor active compounds using a quantitative high-throughput screening platform.

To adapt the use of GH3.TRE-Luc reporter gene cell line for a quantitative high-throughput screening (qHTS) platform, we miniaturized the reporter gene assay to a 1536-well plate format. 1280 chemicals from the Library of Pharmacologically Active Compounds (LOPAC) and the National Toxicology Program (NTP) 1408 compound collection were analyzed to identify potential thyroid hormone receptor (TR) agonists and antagonists.

Liposome and protein based stealth nanoparticles.

Liposomes and protein based nanoparticles were tuned with different polymers and glycolipids to improve stealth and thus decrease their clearance by macrophages. Liposomes were coated with polyethylene glycol (PEG) and brain-tissue-derived monosialoganglioside (GM1). Bovine serum albumin (BSA) nanoparticles were produced incorporating a PEGylated surfactant (PEG-surfactant).

NanoSIMS50 - a powerful tool to elucidate cellular localization of halogenated organic compounds.

Persistent organic pollutants are widely distributed in the environment and lots of toxicological data are available. However, little is known on the intracellular fate of such compounds. Here a method applying secondary ion mass spectrometry is described that can be used to visualize cellular localization of halogenated compounds and to semi-quantitatively calculate concentrations of such compounds.

Detection of thyroid hormone receptor disruptors by a novel stable in vitro reporter gene assay.

A stable luciferase reporter gene assay was developed based on the thyroid hormone responsive rat pituitary tumor GH3 cell line that constitutively expresses both thyroid hormone receptor isoforms. Stable transfection of the pGL4CP-SV40-2xtaDR4 construct into the GH3 cells resulted in a highly sensitive cell line (GH3.TRE-Luc), which was further optimized into an assay that allowed the detection of Triiodothyronine (T(3)) and Thyroxine (T(4)) concentrations in the picomolar range after only 24 h of exposure.

Cytoskeletal architecture differentially controls post-transcriptional processing of IL-6 and IL-8 mRNA in airway epithelial-like cells.

Airway epithelial cells are critically dependent on an intact cytoskeleton for innate defense functions. There are various pathophysiological conditions that affect the cytoskeletal architecture. We studied the effect of cytoskeletal distortion in polarized airway epithelial-like NCI-H292 cells on inflammatory gene expression, exemplified by interleukin(IL)-6 and IL-8.