Search results for "Sense"

Missense Mutations of Human Hsp60: A Computational Analysis to Unveil Their Pathological Significance

2020

Two chaperonopathies have been linked to mutations in the human hsp60 (hHsp60; HSPD1) gene, but other existing variants might cause diseases, even if there is no comprehensive information about this possibility. To fill this vacuum, which might be at the basis of misdiagnoses or simply ignorance of chaperonopathies in patients who would benefit by proper identification of their ailments, we searched the sequenced human genomes available in public databases to determine the range of missense mutations in the single hsp60 gene. A total of 224 missense mutations were identified, including those already characterized. Detailed examination of these mutations was carried out to assess their possi…

MUC4 is overexpressed in idiopathic pulmonary fibrosis and collaborates with transforming growth factor β inducing fibrotic responses.

2021

Several mucins are implicated in idiopathic pulmonary fibrosis (IPF); however, there is no evidence regarding the role of MUC4 in the development of IPF. Here we demonstrated that MUC4 was overexpressed in IPF patients (n = 22) compared with healthy subjects (n = 21) and located in pulmonary arteries, bronchial epithelial cells, fibroblasts, and hyperplastic alveolar type II cells. Decreased expression of MUC4 using siRNA–MUC4 inhibited the mesenchymal/myofibroblast transformations of alveolar type II A549 cells and lung fibroblasts, as well as cell senescence and fibroblast proliferation induced by TGF-β1. The induction of the overexpression of MUC4 increased the effects of TGF-β1 on mesen…

Loss-of-function and missense variants in NSD2 cause decreased methylation activity and are associated with a distinct developmental phenotype

2021

Purpose Despite a few recent reports of patients harboring truncating variants in NSD2, a gene considered critical for the Wolf–Hirschhorn syndrome (WHS) phenotype, the clinical spectrum associated with NSD2 pathogenic variants remains poorly understood. Methods We collected a comprehensive series of 18 unpublished patients carrying heterozygous missense, elongating, or truncating NSD2 variants; compared their clinical data to the typical WHS phenotype after pooling them with ten previously described patients; and assessed the underlying molecular mechanism by structural modeling and measuring methylation activity in vitro. Results The core NSD2-associated phenotype includes mostly mild dev…

Hearing Without Neuroglobin.

2017

Abstract Neuroglobin (Ngb) is a member of the globin family of respiratory proteins, which was recently observed in many neurons of the auditory pathways. Up to now, however, nothing was known about the role of Ngb in hearing processes. We therefore studied auditory function by recording distortion-product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABRs) in wild-type (C57BL/6N) and Ngb-knockout mice. In KO mice, DPOAE thresholds were moderately augmented in the range of 5–18 kHz, reaching statistical significance at 8 and 10 kHz, while the ABR thresholds were not different between groups. The activation of the efferent system by an additional noise given to the contrala…

2018

Diabetic retinopathy is a common complication of diabetes mellitus, which appears in one third of all diabetic patients and is a prominent cause of vision loss. First discovered as a microvascular disease, intensive research in the field identified inflammation and neurodegeneration to be part of diabetic retinopathy. Microglia, the resident monocytes of the retina, are activated due to a complex interplay between the different cell types of the retina and diverse pathological pathways. The trigger for developing diabetic retinopathy is diabetes-induced hyperglycemia, accompanied by leukostasis and vascular leakages. Transcriptional changes in activated microglia, mediated via the nuclear f…

2017

Purpose of this study was to investigate firstly specific proteomic changes within the retina in the course of an animal glaucoma model and to identify secondly new approaches for neuroprotective, therapeutic options in glaucoma by addressing those specific changes. Intraocular pressure was elevated through cauterization of episcleral veins in adult Sprague Dawley rats. Molecular and morphological changes were surveyed using mass spectrometry, optical coherence tomography as well as immunohistochemical cross section- and flat mount stainings. By quantifying more than 1500 retinal proteins, it was found that the HspB5 protein and numerous beta-crystallins showed a uniform and unique shifting…

2018

Purpose Since the role of short- and long-term intraocular pressure (IOP) fluctuation as a predictor of glaucoma progression is still controversial, the purpose of this study was to investigate the role of IOP fluctuation in a non-selected patient cohort. Materials and methods Two-hundred and forty eyes of 120 glaucoma patients (51% female) with a mean age of 64.5 years were included. Inclusion criteria were at least a visual field (VF) and a 48-hour diurnal phasing of IOP including nocturnal measurement. Glaucoma progression was defined as - if available - confirmed progression of reproducible VF defects in at least three VF examinations or increase of cup area on optic nerve imaging (Heid…

Neuroprotective and Anti-Inflammatory Effects of a Hydrophilic Saffron Extract in a Model of Glaucoma

2019

Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells (RGCs). An increase in the intraocular pressure is the principal risk factor for such loss, but controlling this pressure does not always prevent glaucomatous damage. Activation of immune cells resident in the retina (microglia) may contribute to RGC death. Thus, a substance with anti-inflammatory activity may protect against RGC degeneration. This study investigated the neuroprotective and anti-inflammatory effects of a hydrophilic saffron extract standardized to 3% crocin content in a mouse model of unilateral, laser-induced ocular hypertension (OHT). Treatment with saffron extract decreased microg…

In vitro comparison of passive and continuous ultrasonic irrigation in curved root canals

2016

BACKGROUND The efficacy of endodontic irrigation procedures can be compromised by the complexity of the root canal system. Delivering irrigants to the apical third of curved canals presents a particular challenge to endodontists. This study compared the effects of two ultrasonic irrigation techniques on the penetration of sodium hypochlorite into the main canal and simulated lateral canals of curved roots in extracted teeth. MATERIAL AND METHODS Two sets of simulated lateral canals were created at 2, 4, and 6 mm from the working length in 60 single-rooted teeth (6 canals/tooth, n = 360 canals). The teeth were randomly divided into three experimental irrigation groups: group 1 (n = 20), posi…

Reply to Comment on: 'Corneal confocal scanning laser microscopy in patients with dry eye disease treated with topical cyclosporine'

2017

Reply to Comment on: ‘Corneal confocal scanning laser microscopy in patients with dry eye disease treated with topical cyclosporine’