Search results for "beta"
showing 10 items of 3374 documents
Metal Ions and Metal Complexes in Alzheimer's Disease.
2015
Background: Alzheimer’s disease (AD) is the most common form of dementia that seriously affects daily life. Even if AD pathogenesis is still subject of debate, it is generally accepted that cerebral cortex plaques formed by aggregated amyloid-β (Aβ) peptides can be considered a characteristic pathological hallmark. It is well known that metal ions play an important role in the aggregation process of Aβ. Methods: This review focuses on the anti-Aβ aggregation activity of chelating ligands as well as on the use of metal complexes as diagnostic probes and as potential drugs. Conclusion: While chelating agents, such as curcumin or flavonoid derivatives, are currently used to capture metal ions …
Fluorinated Chaperone−β-Cyclodextrin Formulations for β-Glucocerebrosidase Activity Enhancement in Neuronopathic Gaucher Disease
2017
Amphiphilic glycomimetics encompassing a rigid, undistortable nor-tropane skeleton based on 1,6-anhydro-L-idonojirimycin and a polyfluorinated antenna, when formulated as the corresponding inclusion complexes with β-cyclodextrin (βCD), have been shown to behave as pharmacological chaperones (PCs) that efficiently rescue lysosomal β- glucocerebrosidase mutants associated to the neuronopathic variants of Gaucher disease (GD), including the highly refractory L444P/L444P and L444P/P415R single nucleotide polymorphs, in patient fibroblasts. The body of work here presented includes the design criteria for the PC prototype, the synthesis of a series of candidates, the characterization of the PC:βC…
Tremblaya phenacola PPER: an evolutionary beta-gammaproteobacterium collage
2017
Many insects rely on bacterial endosymbionts to obtain nutrients that are scarce in their highly specialized diets. The most surprising example corresponds to the endosymbiotic system found in mealybugs from subfamily Pseudococcinae in which two bacteria, the betaproteobacterium 'Candidatus Tremblaya princeps' and a gammaproteobacterium, maintain a nested endosymbiotic consortium. In the sister subfamily Phenacoccinae, however, a single beta-endosymbiont, 'Candidatus Tremblaya phenacola', has been described. In a previous study, we detected a trpB gene of gammaproteobacterial origin in 'Ca. Tremblaya phenacola' from two Phenacoccus species, apparently indicating an unusual case of horizonta…
Impact of Elastin-Derived Peptide VGVAPG on Matrix Metalloprotease-2 and -9 and the Tissue Inhibitor of Metalloproteinase-1, -2, -3 and -4 mRNA Expre…
2018
Degradation products of elastin, i.e. elastin-derived peptides (EDPs), are involved in various physiological and pathological processes. EDPs are detectable in cerebrospinal fluid in healthy people and in patients after ischemic stroke. However, to date, no studies concerning the role of EDP in the nervous system were conducted. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play important roles during the repair phases of cerebral ischemia, particularly during angiogenesis and reestablishment of cerebral blood flow. Therefore, the aim of this study was to investigate the impact of the specific elastin-derived peptide VGVAPG on Mmp-2, -9 and Timp-1, -2,…
Dibutyl Phthalate (DBP)-Induced Apoptosis and Neurotoxicity are Mediated via the Aryl Hydrocarbon Receptor (AhR) but not by Estrogen Receptor Alpha (…
2016
Dibutyl phthalate (di-n-butyl phthalate, DBP) is one of the most commonly used phthalate esters. DBP is widely used as a plasticizer in a variety of household industries and consumer products. Because phthalates are not chemically bound to products, they can easily leak out to enter the environment. DBP can pass through the placental and blood–brain barriers due to its chemical structure, but little is known about its mechanism of action in neuronal cells. This study demonstrated the toxic and apoptotic effects of DBP in mouse neocortical neurons in primary cultures. DBP stimulated caspase-3 and LDH activities as well as ROS formation in a concentration (10 nM–100 µM) and time-dependent (3–…
Anti-inflammatory and cognitive effects of interferon-β1a (IFNβ1a) in a rat model of Alzheimer’s disease
2018
Background: Aβ 1-42 peptide abnormal production is associated with the development and maintenance of neuroinflammation and oxidative stress in brains from Alzheimer disease (AD) patients. Suppression of neuroinflammation may then represent a suitable therapeutic target in AD. We evaluated the efficacy of IFNβ1a in attenuating cognitive impairment and inflammation in an animal model of AD. Methods: A rat model of AD was obtained by intra-hippocampal injection of Aβ 1-42 peptide (23 μg/2 μl). After 6 days, 3.6 μg of IFNβ1a was given subcutaneously (s.c.) for 12 days. Using the novel object recognition (NOR) test, we evaluated changes in cognitive function. Measurement of pro-inflammatory or …
Alternative Splice Forms of CYLD Mediate Ubiquitination of SMAD7 to Prevent TGFB Signaling and Promote Colitis
2018
Background & Aims The CYLD lysine 63 deubiquitinase gene (CYLD) encodes tumor suppressor protein that is mutated in familial cylindromatosus, and variants have been associated with Crohn disease (CD). Splice forms of CYLD that lack exons 7 and 8 regulate transcription factors and functions of immune cells. We examined the expression of splice forms of CYLD in colon tissues from patients with CD and their effects in mice. Methods We performed immunohistochemical analyses of colon tissues from patients with untreated CD and patients without inflammatory bowel diseases (controls). We obtained mice that expressed splice forms of CYLD (sCYLD mice) without or with SMAD7 (sCYLD/SMAD7 mice) from tr…
Hypoxia-Induced miR-675-5p Supports β-Catenin Nuclear Localization by Regulating GSK3-β Activity in Colorectal Cancer Cell Lines
2020
The reduction of oxygen partial pressure in growing tumors triggers numerous survival strategies driven by the transcription factor complex HIF1 (Hypoxia Inducible Factor-1). Recent evidence revealed that HIF1 promotes rapid and effective phenotypic changes through the induction of non-coding RNAs, whose contribution has not yet been fully described. Here we investigated the role of the hypoxia-induced, long non-coding RNA H19 (lncH19) and its intragenic miRNA (miR-675-5p) into HIF1-Wnt crosstalk. During hypoxic stimulation, colorectal cancer cell lines up-regulated the levels of both the lncH19 and its intragenic miR-675-5p. Loss of expression experiments revealed that miR-675-5p inhibitio…
Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation
2015
Unwinding DNA and unleasing inflammation Fighting infections often comes with collateral damage, which sometimes can be deadly. For instance, in septic shock, the overwhelming release of inflammatory mediators drives multi-organ failure. Rialdi et al. now report a potential new therapeutic target for controlling excessive inflammation: the DNA unwinding enzyme topoisomerase I (Top1) (see the Perspective by Pope and Medzhitov). Upon infection, Top1 specifically localizes to the promoters of pathogen-induced genes and promotes their transcription by helping to recruit RNA polymerase II. Pharmacological inhibition of Top1 in a therapeutic setting increased survival in several mouse models of s…
In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment
2016
Abstract: An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expre…