Search results for "Prohibitins"
showing 10 items of 18 documents
Targeting prohibitins with chemical ligands inhibits KRAS-mediated lung tumours.
2017
KRAS is one of the most frequently mutated oncogenes in human non-small cell lung cancers (NSCLCs). RAS proteins trigger multiple effector signalling pathways including the highly conserved RAF-MAPK pathway. CRAF, a direct RAS effector protein, is required for KRAS-mediated tumourigenesis. Thus, the molecular mechanisms driving the activation of CRAF are intensively studied. Prohibitin 1 (PHB1) is an evolutionarily conserved adaptor protein and interaction of CRAF with PHB1 at the plasma membrane is essential for CRAF activation. Here, we demonstrate that PHB1 is highly expressed in NSCLC patients and correlates with poor survival. Targeting of PHB1 with two chemical ligands (rocaglamide an…
Electrospun poly(hydroxybutyrate) scaffolds promote engraftment of human skin equivalents via macrophage M2 polarization and angiogenesis.
2018
Human dermo-epidermal skin equivalents (DE) comprising in vitro expanded autologous keratinocytes and fibroblasts are a good option for massive burn treatment. However, the lengthy expansion time required to obtain sufficient surface to cover an extensive burn together with the challenging surgical procedure limits their clinical use. The integration of DE and biodegradable scaffolds has been proposed in an effort to enhance their mechanical properties. Here, it is shown that poly(hydroxybutyrate) electrospun scaffolds (PHB) present good biocompatibility both in vitro and in vivo and are superior to poly-epsilon-caprolactone electrospun scaffolds as a substrate for skin reconstruction. Impl…
Targeting prohibitins at the cell surface prevents Th17-mediated autoimmunity.
2018
T helper (Th)17 cells represent a unique subset of CD4(+) T cells and are vital for clearance of extracellular pathogens including bacteria and fungi. However, Th17 cells are also involved in orchestrating autoimmunity. By employing quantitative surface proteomics, we found that the evolutionarily conserved prohibitins (PHB1/2) are highly expressed on the surface of both murine and human Th17 cells. Increased expression of PHBs at the cell surface contributed to enhanced CRAF/MAPK activation in Th17 cells. Targeting surface‐expressed PHBs on Th17 cells with ligands such as Vi polysaccharide (Typhim vaccine) inhibited CRAF‐MAPK pathway, reduced interleukin (IL)‐17 expression and ameliorated …
Expression of host defense scavenger receptors in spondylarthropathy
2001
Objective Reactive arthritis (ReA) is postulated to be caused by a defective host defense against gram-negative bacteria. HLA–B27 could play a role in this process, but does not account for the many HLA–B27 negative patients. The objective of this study was to test the expression of 3 macrophage scavenger receptors (SRs) that are responsible for innate immunity against gram-negative bacteria: SR class A type I (SR-AI), SR-AII, and the macrophage receptor with collagenous structure (MARCO). We postulate that defects in such receptors might also contribute to the host risk factors that increase the predisposition to ReA and perhaps other subtypes of spondylarthropathy (SpA). Methods Periphera…
Salivary testosterone is related to both handedness and degree of linguistic lateralization in normal women.
2003
The aim of this study was to test the hypothesis that individual differences in testosterone (T) are associated with different patterns of linguistic lateralization and hand preference. Twenty left-handed (LH) and 19 right-handed (RH) women filled in a handedness questionnaire and performed a consonant–vowel dichotic listening test (DL-CV). Salivary T was measured by radioimmunoassay (RIA). LH women showed significantly lower mean salivary T than RH women. T levels were negatively correlated with the absolute value of the DL laterality index. Subjects with right ear advantage (REA) were classified into strongly and weakly lateralized following Wexler et al. method (Brain Lang. 13 (1981) 13)…
Corpus callosum function in verbal dichotic listening: inferences from a longitudinal follow-up of Relapsing-Remitting Multiple Sclerosis patients.
2009
This study conducted a follow-up of 13 early-onset slightly disabled Relapsing-Remitting Multiple Sclerosis (RRMS) patients within an year, evaluating both CC area measurements in a midsagittal Magnetic Resonance (MR) image, and Dichotic Listening (DL) testing with stop consonant vowel (C-V) syllables. Patients showed a significant progressive loss of posterior CC areas (isthmus and splenium) related to increasing EDSS scores and an enhancing right ear advantage (REA) over time. A significant correlation between posterior CC areas and DL scores emerged in both evaluations, being negative for the right and positive for the left ear. The pattern of correlations suggests that the CC can serve …
Multiclonal Synovial T Cell Response toYersinia enterocoliticain Reactive Arthritis: TheYersinia61-kDa Heat-Shock Protein Is Not the Major Target Ant…
1993
The T cell response to bacterial antigens plays a major role in the pathogenesis of reactive arthritis (ReA) following enteric infections with Yersinia enterocolitica. To study the antigen specificity of the T cells at the site of inflammation, the response of cloned T cells from the synovial fluid of 2 patients with ReA to partially purified antigens of Yersinia enterocolitica was determined. The clones showed different patterns of response to various fractions, indicating a multiclonal response to Yersinia antigens, and these specificities differed in the 2 patients. Some T cells were specific for Y. enterocolitica; some cross-reacted with other enterobacteria. Proteins of 14 and 19 kDa c…
What happens when we get angry? Hormonal, cardiovascular and asymmetrical brain responses
2010
This study aimed to evaluate neuroendocrine and cardiovascular responses together with changes in brain asymmetry following an anger mood induction laboratory task. Previous research has shown an increase in heart rate and blood pressure when anger is experienced. Increased testosterone and decreased cortisol in response to anger and aggressive behavior have also been reported. With regard to asymmetrical frontal brain activity and emotion, the valence model links negative affect (as anger) to the right hemisphere while the motivational direction model links approach-related emotions (as anger) to the left hemisphere. From the subjective perception and from the neuroendocrine and cardiovasc…
Increased cortisol and decreased right ear advantage (REA) in dichotic listening following a negative mood induction.
2005
This study aimed to evaluate neuroendocrine responses and changes in perceptual asymmetry following an induced negative affect. Cortisol increasing in response to negative affect has been reported, while current brain models of emotion processing link negative affect to the right hemisphere. In this study, the Velten Mood Induction Procedure was used to generate neutral or negative affect in 44 healthy subjects. The PANAS scales were used to assess self-reported mood. A consonant-vowel dichotic listening (DL) test was applied after the neutral and negative affect inductions, and levels of salivary cortisol were determined by radioimmunoassay. For the negative affect condition, and congruent…
IL 10.G microsatellites mark promoter haplotypes associated with protection against the development of reactive arthritis in Finnish patients.
2001
Objective To investigate the association of microsatellites and single-nucleotide promoter polymorphisms (SNPs) in the gene for the cytokine interleukin-10 (IL-10) with susceptibility to and outcome of reactive arthritis (ReA). Methods From genomic DNA, IL-10 microsatellites G and R and IL-10 promoter polymorphisms at positions −1087 and −524 were typed by polymerase chain reaction, automated fragment length analysis, and restriction fragment digestion in 85 Finnish patients with ReA and 62 HLA–B27–positive Finnish controls. ReA patients had been followed up for 20 years. Genotypes and haplotypes of IL-10 were correlated with distinct features of the disease course, such as triggering agent…