Development of -(4-(1-Imidazol-1-yl)phenyl)-4-chlorobenzenesulfonamide, a Novel Potent Inhibitor of β-Catenin with Enhanced Antitumor Activity and Metabolic Stability.

The potential as a cancer therapeutic target of the recently reported hotspot binding region close to Lys508 of the β-catenin armadillo repeat domain was not exhaustively explored. In order to get more insight, we synthesized novel -(heterocyclylphenyl)benzenesulfonamides -. The new compounds significantly inhibited Wnt-dependent transcription as well as SW480 and HCT116 cancer cell proliferation.

N-acetyl-L-cysteine reduces testis ROS in obese fathers but fails in protecting offspring from acquisition of epigenetic traits at and ICR loci.

Introduction: Paternal nutrition before conception has a marked impact on offspring's risk of developing metabolic disorders during adulthood. Research on human cohorts and animal models has shown that paternal obesity alters sperm epigenetics (DNA methylation, protamine-to-histone replacement, and non-coding RNA content), leading to adverse health outcomes in the offspring. So far, the mechanistic events that translate paternal nutrition into sperm epigenetic changes remain unclear.

Controlled Cultivation Confers Synergistic Activity on Muscle Cell Homeostasis, Metabolism and Antioxidant Defense in Primary Human Myoblasts.

L. is recognized for its adaptogenic properties and ability to promote muscle health, function and recovery from exercise. The plethora of biological effects of this plant is ascribed to the synergism existing among the molecules composing its phytocomplex.

Metabolites from Aerial Parts of as Modulators of Targets Related to Metabolic Syndrome.

A detailed phytochemical investigation has been carried out on the aerial parts of leading to the isolation of 29 pure compounds, mainly belonging to the amorfrutin and polyphenol classes. Among them, the new amorfrutin N () and exiguaflavone L () were isolated and their structures elucidated by means of HR-ESIMS and NMR. All the isolated compounds were investigated for modulation of mitochondrial activity and stimulation of glucose uptake via GLUT transporters, two metabolic processes involved in intracellular glucose homeostasis, which, therefore, correlate with the incidence of metabolic syndrome.

A fluorescent probe with an ultra-rapid response to nitric oxide.

Nitric oxide (NO) is a diatomic inorganic free radical ubiquitous in mammalian tissues and cells that plays a multifaceted role in a variety of physiological and pathophysiological processes. The strict dependence of the biological effects of NO on its concentration makes its real-time monitoring crucial. In view of the reactivity of NO with multiple bio-targets, the development of NO sensors that associate a fast response rate with selectivity and sensitivity is very challenging.

Glucose Uptake-Stimulating Metabolites from Aerial Parts of .

A comprehensive phytochemical investigation of aerial parts obtained from L. led to the isolation of 14 terpenoids (-) and nine polyphenols (-). The sesquiterpenoid group (-) included three structural families, namely, elemanolides (-), eudesmanolides ( and ), and germacranolides (-) with four unreported secondary metabolites (-), whose structure has been determined by extensive spectroscopic analysis, including 1D/2D NMR, HR-MS, and chemical conversion.

Severe isolated exudative vitreoretinopathy caused by biallelic FZD4 variants.

Familial exudative vitreoretinopathy (FEVR) is linked to disruption of the Norrin/Frizzled-4 signaling pathway, which plays an important role in retinal angiogenesis. Severe or complete knock-down of proteins in the pathway also causes syndromic forms of the condition. Both heterozygous and biallelic pathogenic variants in the FZD4 gene, encoding the pathway's key protein frizzled-4, are known to cause FEVR.

Agri-Food Waste Recycling for Healthy Remedies: Biomedical Potential of Nutraceuticals from Unripe Tomatoes ( L.).

Unripe tomatoes represent an agri-food waste resulting from industrial by-processing products of tomatoes, yielding products with a high content of bioactive compounds with potential nutraceutical properties. The food-matrix biological properties are attributed to the high steroidal glycoalkaloid (SGA) content. Among them, α-tomatine is the main SGA reported in unripe green tomatoes.

Thyroid Hormone Regulates the Lipid Content of Muscle Fibers, Thus Affecting Physical Exercise Performance.

Skeletal muscle (SkM) lipid composition plays an essential role in physiological muscle maintenance and exercise performance. Thyroid hormones (THs) regulate muscle formation and fuel energy utilization by modulating carbohydrates and lipid and protein metabolism. The best-known effects of THs in SkM include the promotion of mitochondrial biogenesis, the fiber-type switch from oxidative to glycolytic fibers, and enhanced angiogenesis.

Novel -(Heterocyclylphenyl)benzensulfonamide Sharing an Unreported Binding Site with T-Cell Factor 4 at the β-Catenin Armadillo Repeats Domain as an Anticancer Agent.

Despite intensive efforts, no inhibitors of the Wnt/β-catenin signaling pathway have been approved so far for the clinical treatment of cancer. We synthesized novel -(heterocyclylphenyl)benzenesulfonamides as β-catenin inhibitors. Compounds - showed strong inhibition of the luciferase activity.

Red-Light-Photosensitized NO Release and Its Monitoring in Cancer Cells with Biodegradable Polymeric Nanoparticles.

The role of nitric oxide (NO) as an "unconventional" therapeutic and the strict dependence of biological effects on its concentration require the generation of NO with precise spatiotemporal control. The development of precursors and strategies to activate NO release by excitation in the so-called "therapeutic window" with highly biocompatible and tissue-penetrating red light is desirable and challenging. Herein, we demonstrate that one-photon red-light excitation of Verteporfin, a clinically approved photosensitizer (PS) for photodynamic therapy, activates NO release, in a catalytic fashion, from an otherwise blue-light activatable NO photodonor (NOPD) with an improvement of about 300 nm toward longer and more biocompatible wavelengths.

Exploring a peptide nucleic acid-based antisense approach for CD5 targeting in chronic lymphocytic leukemia.

We herein report an innovative antisense approach based on Peptide Nucleic Acids (PNAs) to down-modulate CD5 expression levels in chronic lymphocytic leukemia (CLL). Using bioinformatics tools, we selected a 12-mer tract of the CD5 mRNA as the molecular target and synthesized the complementary and control PNA strands bearing a serine phosphate dipeptide tail to enhance their water solubility and bioavailability. The specific recognition of the 12-mer DNA strand, corresponding to the target mRNA sequence by the complementary PNA strand, was confirmed by non-denaturing polyacrylamide gel electrophoresis, thermal difference spectroscopy, circular dichroism (CD), and CD melting studies.

ZNF224 Protein: Multifaceted Functions Based on Its Molecular Partners.

The transcription factor ZNF224 is a Kruppel-like zinc finger protein that consists of 707 amino acids and contains 19 tandemly repeated CH zinc finger domains that mediate DNA binding and protein-protein interactions. ZNF224 was originally identified as a transcriptional repressor of genes involved in energy metabolism, and it was demonstrated that ZNF224-mediated transcriptional repression needs the interaction of its KRAB repressor domain with the co-repressor KAP1 and its zinc finger domains 1-3 with the arginine methyltransferase PRMT5. Furthermore, the protein ZNF255 was identified as an alternative isoform of ZNF224 that possesses different domain compositions mediating distinctive functional interactions.

ZNF224 is a mediator of TGF-β pro-oncogenic function in melanoma.

The zinc finger protein ZNF224 plays a dual role in cancer, operating as both tumour suppressor and oncogenic factor depending on cellular and molecular partners. In this research we investigated the role of ZNF224 in melanoma, a highly invasive and metastatic cancer, and provided evidence for the involvement of ZNF224 in the TGF-β signalling as a mediator of the TGF-β pro-oncogenic function. Our results showed that ZNF224, whose expression increased in melanoma cell lines after TGF-β stimulation, potentiated the activation induced by TGF-β on its target genes involved in epithelial-mesenchymal transition (EMT).

The expression of inhibitor of bruton's tyrosine kinase gene is progressively up regulated in the clinical course of chronic lymphocytic leukaemia conferring resistance to apoptosis.

Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy with a variable clinical outcome. Biomarkers of CLL progression are required for optimising prognosis and therapy. The Inhibitor of Bruton's tyrosine kinase-isoform α (IBTKα) gene encodes a substrate receptor of Cullin 3-dependent E3 ubiquitin ligase, and promotes cell survival in response to the reticulum stress.