Search results for "Disorders"
showing 10 items of 4560 documents
Effect of ω-3 Polyunsaturated Fatty Acids-Derived Bioactive Lipids on Metabolic Disorders
2021
Arachidonic acid (ARA) is an important ω-6 polyunsaturated fatty acid (PUFA), and docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA) are three well-known ω-3 PUFAs. These fatty acids can be metabolized into a number of bioactive lipids. Eicosanoids derived from ARA have drawn great attention because of their important and complex biofunctions. Although EPA, DHA and n-3 DPA have also shown powerful biofunctions, we have fewer studies of metabolites derived from them than those from ARA. Recently, growing research has focused on the bioaction of ω-3 PUFA-derived metabolites, which indicates their great potential for treating metabolic disorders. Mo…
A conditional inducible JAK2V617F transgenic mouse model reveals myeloproliferative disease that is reversible upon switching off transgene expressio…
2019
Aberrant activation of the JAK/STAT pathway is thought to be the critical event in the pathogenesis of the chronic myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia and primary myelofibrosis. The most frequent genetic alteration in these pathologies is the activating JAK2V617F mutation, and expression of the mutant gene in mouse models was shown to cause a phenotype resembling the human diseases. Given the body of genetic evidence, it has come as a sobering finding that JAK inhibitor therapy only modestly suppresses the JAK2V617F allele burden, despite showing clear benefits in terms of reducing splenomegaly and constitutional symptoms in patients. To gain a better …
Indomethacin blocks the increased conditioned rewarding effects of cocaine induced by repeated social defeat
2018
It is well established that repeated social defeat stress can induce negative long-term consequences such as increased anxiety-like behavior and enhances the reinforcing effect of psychostimulants in rodents. In the current study, we evaluated how the immune system may play a role in these long-term effects of stress. A total of 148 OF1 mice were divided into different experimental groups according to stress condition (exploration or social defeat) and pre-treatment (saline, 5 or 10 mg/kg of the anti-inflammatory indomethacin) before each social defeat or exploration episode. Three weeks after the last social defeat, anxiety was evaluated using an elevated plus maze paradigm. After this tes…
Emerging Roles of RNA 3′-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders
2020
A crucial feature of gene expression involves RNA processing to produce 3′ ends through a process termed 3′ end cleavage and polyadenylation (CPA). This ensures the nascent RNA molecule can exit the nucleus and be translated to ultimately give rise to a protein which can execute a function. Further, alternative polyadenylation (APA) can produce distinct transcript isoforms, profoundly expanding the complexity of the transcriptome. CPA is carried out by multi-component protein complexes interacting with multiple RNA motifs and is tightly coupled to transcription, other steps of RNA processing, and even epigenetic modifications. CPA and APA contribute to the maintenance of a multitude of dive…
Microbiome restoration diet improves digestion, cognition and physical and emotional wellbeing
2017
Manipulating gut bacteria in the microbiome, through the use of probiotics and prebiotics, has been found to have an influence on both physical and emotional wellbeing. This study uses a dietary manipulation 'The Gut Makeover' designed to elicit positive changes to the gut bacteria within the microbiome. 21 healthy participants undertook 'The Gut Makeover' for a four week period. Weight and various aspects of health were assessed pre and post intervention using the Functional Medicine Medical Symptoms Questionnaire (MSQ). Paired sample t-tests revealed a significant reduction in self-reported weight at the end of the intervention. Adverse medical symptoms related to digestion, cognition and…
Violent offending in borderline personality disorder and attention deficit/hyperactivity disorder.
2018
Abstract The prevalence of borderline personality disorder (BPD) and attention deficit/hyperactivity disorder (ADHD) is significantly higher among offenders compared to the prevalence found in the general population. Both disorders share important diagnostic characteristics and thus it has been suggested that they might follow a common developmental pathway. In this narrative review, we first discuss the potential links of disorder inherent symptoms such as impulsivity and emotion regulation difficulties and how they might elevate the risk of violent delinquency. We continue with highlighting that comorbidities particularly from the antisocial spectrum as well as comorbid substance use diso…
Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathw…
2018
AbstractHutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder that leads to premature aging. In this study, we used induced pluripotent stem cells to investigate the hypopigmentation phenotypes observed in patients with progeria. Accordingly, two iPS cell lines were derived from cells from HGPS patients and differentiated into melanocytes. Measurements of melanin content revealed a lower synthesis of melanin in HGPS melanocytes as compared to non-pathologic cells. Analysis of the melanosome maturation process by electron microscopy revealed a lower percentage of mature, fully pigmented melanosomes. Finally, a functional rescue experiment revealed the direct role of progerin…
PTEN recruitment controls synaptic and cognitive function in Alzheimer's models
2016
Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cognitive deficits ranging from mild impairment to full-blown dementia in Alzheimer's disease. Aβ appears to skew synaptic plasticity events toward depression. We found that inhibition of PTEN, a lipid phosphatase that is essential to long-term depression, rescued normal synaptic function and cognition in cellular and animal models of Alzheimer's disease. Conversely, transgenic mice that overexpressed PTEN displayed synaptic depression that mimicked and occluded Aβ-induced depression. Mechanistically, Aβ triggers a PDZ-dependent recruitment of PTEN into the postsynaptic compartment. Using a PTEN kno…
The endoplasmic reticulum unfolded protein response in neurodegenerative disorders and its potential therapeutic significance
2017
In eukaryotic cells, the endoplasmic reticulum (ER) is the cell compartment involved in secretory protein translocation and quality control of secretory protein folding. Different conditions can alter ER function, resulting in the accumulation of unfolded or misfolded proteins within the ER lumen. Such a condition, known as ER stress, elicits an integrated adaptive response known as the unfolded protein response (UPR) that aims to restore proteostasis within the secretory pathway. Conversely, in prolonged cell stress or insufficient adaptive response, UPR signaling causes cell death. ER dysfunctions are involved and contribute to neuronal degeneration in several human diseases, including Al…
Allopurinol partially prevents disuse muscle atrophy in mice and humans
2018
AbstractDisuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The pro…