Search results for "IPT"

The JAK2 pathway is activated in idiopathic pulmonary fibrosis

2018

Background: Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal fibrotic disorder, with no curative therapies. The signal transducer and activator of transcription 3 (STAT3) protein is activated in lung fibroblasts and alveolar type II cells (ATII), thereby contributing to lung fibrosis in IPF. Although activation of Janus kinase 2 (JAK2) has been implicated in proliferative disorders, its role in IPF is unknown. The aim of this study was to analyze JAK2 activation in IPF, and to determine whether JAK2/STAT3 inhibition is a potential therapeutic strategy for this disease. Methods and results: JAK2/p-JAK2 and STAT3/pSTAT3 expression was evaluated using quantitative …

SOX2 expression diminishes with ageing in several tissues in mice and humans.

2017

SOX2 (Sex-determining region Y box 2) is a transcription factor expressed in several foetal and adult tissues and its deregulated activity has been linked to chronic diseases associated with ageing. Nevertheless, the level of SOX2 expression in aged individuals at the tissue level has not previously been examined. In this work, we show that SOX2 expression decreases significantly in the brain with ageing, in both humans and rodents. The administration of resveratrol for 6 months in mice partly attenuated this reduction. We also identified an age-related decline in SOX2 mRNA and protein expression in several other organs, namely, the lung, heart, kidney, spleen and liver. Moreover, periphera…

The utility of measuring tear film break-up time for prescribing contact lenses.

2017

Abstract Purpose To evaluate the clinical value of non-invasive keratograph tear film breakup time (NIKBUT) in the assessment of pre-corneal and pre-lens tear film quality for prescribing contact lenses (CLs). Methods Forty-six subjects aged 25.5 ± 4.3 (mean ± standard deviation) years were recruited. Visual acuity (VA), anterior eye health checks and NIKBUT were evaluated. On the following day, subjects were fitted with a daily Silicon Hydrogel (SiHy) CL in one eye and a Hydrogel (Hy) CL in the other. After four hours one material for both eyes was chosen based on a qualitative analysis which included VA, CL fitting and comfort. Information about the first and the mean NIKBUT was then cont…

Annulate Lamellae in a Desmoplastic Small Round Cell Tumor

2016

Solitary Fibrous Tumor of the Vulva: Report of 2 Cases, Including a De Novo Dedifferentiated Solitary Fibrous Tumor Diagnosed After Molecular Demonst…

2018

Solitary fibrous tumor (SFT) is a neoplasm of fibroblastic lineage that has been documented in almost every anatomic location. Vulval SFT is very rare with only 10 cases reported to date. We present 2 additional SFTs located in the vulva, in adult women of 59 and 25 yr of age. The first showed a classic morphology and immunophenotype with uniform and strong STAT6 nuclear expression. The other one was a spindle-cell de novo dedifferentiated SFT with heterogeneous nuclear and cytoplasmic STAT6 staining, which could only be correctly diagnosed after molecular analysis with demonstration of a NAB2-STAT6 gene fusion. This genetic aberration is considered to represent the major pathogenic driver …

Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion.

2016

Pre-eclampsia (PE), which affects ∼8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes. The results showed a significant expansion of the CTB layer. The cells displayed enhanced expression of stage-specific antigens that extravillous CTBs normally upregulate as they exit the placenta. Transcriptomics revealed the dysregulated expression of many genes (e.g. placental proteins, markers of oxidative stress). We confirmed an sPE-related incr…

Indicaxanthin from Opuntia ficus indica (L. Mill) Inhibits Oxidized LDL-Mediated Human Endothelial Cell Dysfunction through Inhibition of NF-κB Activ…

2019

Oxidized low-density lipoproteins (oxLDL) play a pivotal role in the etiopathogenesis of atherosclerosis through the activation of inflammatory signaling events eventually leading to endothelial dysfunction and senescence. In the present work, we investigated the effects of indicaxanthin, a bioavailable, redox-modulating phytochemical from Opuntia ficus indica fruits, with anti-inflammatory activity, against oxLDL-induced endothelial dysfunction. Human umbilical vein cord cells (HUVEC) were stimulated with human oxLDL, and the effects of indicaxanthin were evaluated in a range between 5 and 20 μM, consistent with its plasma level after a fruit meal (7 μM). Pretreatment with indicaxanthin si…

Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging.

2016

24 páginas, 7 figuras. Borras C, et al. Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging. Aging (Albany NY). 2016 Oct 28;8(12):3185-3208. doi: 10.18632/aging.101078.

Longevity-related molecular pathways are subject to midlife “switch” in humans

2019

Emerging evidence indicates that molecular aging may follow nonlinear or discontinuous trajectories. Whether this occurs in human neuromuscular tissue, particularly for the noncoding transcriptome, and independent of metabolic and aerobic capacities, is unknown. Applying our novel RNA method to quantify tissue coding and long noncoding RNA (lncRNA), we identified ~800 transcripts tracking with age up to ~60 years in human muscle and brain. In silico analysis demonstrated that this temporary linear “signature” was regulated by drugs, which reduce mortality or extend life span in model organisms, including 24 inhibitors of the IGF‐1/PI3K/mTOR pathway that mimicked, and 5 activators that oppos…

Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus.

2018

The cholinergic system plays a crucial role in modulating in the central nervous system physiological responses such as neurogenesis, neuronal differentiation, synaptic plasticity, and neuroprotection. In a recent study, we showed that Oxotremorine-M, a non-selective muscarinic acetylcholine receptor agonist, is able to transactivate the fibroblast growth factor receptor and to produce a significant increase in the hippocampal primary neurite outgrowth. In the present study we aimed to explore in the rat hippocampus the possible effect of acute or chronic treatment with Oxotremorine-M on some heat shock proteins (Hsp60, Hsp70, Hsp90) and on activation of related transcription factor heat sh…