Search results for "Loi"
showing 10 items of 4617 documents
Mice are not Men: ADAM30 Findings Emphasize a Broader Look Towards Murine Alzheimer's Disease Models
2016
Due to the growing population of people at advanced age, the number of patients affected by Alzheimer's disease (AD) is increasing tremendously. In 2015 about 46.8 million people suffered from AD worldwide which is estimated to increase to 131.5 million by 2050. Brains of AD patients all show a common histopathology; they are marked by an atrophy and degeneration that is caused by a severe loss of neurons and synapses (Braak and Del Tredici, 2012). Moreover, so-called extracellular senile plaques that consist of predominantly amyloid β (Aβ) peptides can be detected in the grey matter where they surround neurons. Since generation of Aβ peptides is hypothesized to play a major role in AD path…
Subchronic administration of auranofin reduced amyloid-β plaque pathology in a transgenic APPNL-G-F/NL-G-F mouse model
2020
Abstract Alzheimer’s disease (AD) is the most common cause of dementia. Neuropathological processes, including the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles, and neuroinflammation, lead to cognitive impairment at middle and eventually later stages of AD progression. Over the last decade, focused efforts have explored repurposed drug approaches for AD pathophysiological mechanisms. Recently, auranofin, an anti-inflammatory drug, was shown to have therapeutic potential in a number of diseases in addition to rheumatoid arthritis. Surprisingly, no data regarding the effects of auranofin on cognitive deficits in AD mice or the influence of auranofin on Aβ pathology and n…
Unusual presentation of blastic plasmacytoid dendritic cell neoplasm: Pitfalls in other hematolymphoid neoplasms
2020
Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare CD4+/CD56+ hematological malignancy with aggressive clinical course and poor prognosis. Histologically, BPDCN is characterized by a diffuse, monomorphous infiltration of cutaneous, subcutaneous, and sometimes other tissues such as lymph nodes and bone marrow, by medium-sized neoplastic cells with blastoid morphology. Typically, there is absence of lymphocytic infiltrate. Diagnosis relies on immunophenotypic expression of CD4, CD56, and the more specific markers of plasmacytoid dendritic cells CD123, CD303/BDCA2, and TCL1. We report a case of a 57-year-old man who presented a 4 cm-long solitary, erythemateous lesion on t…
Autosomal recessive truncatingMAB21L1mutation associated with a syndromic scrotal agenesis
2016
We report on a boy with a rare malformative association of scrotum agenesis, ophthalmological anomalies, cerebellar malformation, facial dysmorphism and global development delay. The reported patient was carrying a homozygous frameshift in MAB21L1 detected by whole-exome sequencing, considered as the most likely disease-causing variant. Mab21l1 knockout mice present a strikingly similar malformative association of ophthalmological malformations of the anterior chamber and preputial glands hypoplasia. We hypothesize that MAB21L1 haploinsufficiency cause a previously undescribed syndrome with scrotal agenesis, ophthalmological anomalies, facial dysmorphism and gross psychomotor delay as remar…
NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement
2018
Background: NKX2-1 related disorders (also known as brain-lung-thyroid syndrome or benign hereditary chorea 1) are associated with a wide spectrum of symptoms. The core features are various movement disorders, characteristically chorea, less frequently myoclonus, dystonia, ataxia; thyroid disease; and lung involvement. The full triad is present in 50% of affected individuals. Numerous additional symptoms may be associated, although many of these were reported only in single cases. Pituitary dysfunction was ambiguously linked to NKX2-1 haploinsufficiency previously. Case Presentation: We examined two members of a family with motor developmental delay, mixed movement disorder (myoclonus, dyst…
Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells.
2016
Background & Aims Wheat amylase-trypsin inhibitors (ATIs) are nutritional activators of innate immunity, via activation of the toll-like receptor 4 (TLR4) on myeloid cells. We aimed to characterize the biologic activity of ATIs in various foods and their effect on intestinal inflammation. Methods We selected 38 different gluten-containing and gluten-free products, either unprocessed (such as wheat, rye, barley, quinoa, amaranth, soya, lentils, and rice) or processed (such as pizza, pasta, bread, and biscuits). ATIs were extracted and their biological activities determined in TLR4-responsive mouse and human cell lines. Effects of oral ATIs on intestinal inflammation were determined in health…
Amyloid in Alzheimer’s Disease: Guilty Beyond Reasonable Doubt?
2017
Recently failed antiamyloidogenic trials call for an objective reassessment of the dominating amyloid cascade hypothesis of Alzheimer's disease (AD). Ongoing efforts focusing on amyloid β protein (Aβ), its deposition, and its removal need to be complemented by more intensive research in new directions. Those may either integrate amyloid pathology or will propose pathogenetic routes independent of Aβ in the search for the causes of AD.
Identification of Phlogacantholide C as a Novel ADAM10 Enhancer from Traditional Chinese Medicinal Plants
2016
Background: Alzheimer’s disease is one of the most prevalent dementias in the elderly population with increasing numbers of patients. One pivotal hallmark of this disorder is the deposition of protein aggregates stemming from neurotoxic amyloid-beta peptides. Synthesis of those peptides has been efficiently prevented in AD model mice by activation of an enzyme called alpha-secretase. Therefore, drugs with the capability to increase the expression of this enzyme, named ADAM10, have been suggested as a valuable therapeutic medication. Methods: We investigated 69 substances from a drug library derived from traditional Chinese medicine by luciferase reporter assay in human neuronal cells for th…
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…
MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation
2017
Summary Most patients with advanced triple-negative breast cancer (TNBC) develop drug resistance. MYC and MCL1 are frequently co-amplified in drug-resistant TNBC after neoadjuvant chemotherapy. Herein, we demonstrate that MYC and MCL1 cooperate in the maintenance of chemotherapy-resistant cancer stem cells (CSCs) in TNBC. MYC and MCL1 increased mitochondrial oxidative phosphorylation (mtOXPHOS) and the generation of reactive oxygen species (ROS), processes involved in maintenance of CSCs. A mutant of MCL1 that cannot localize in mitochondria reduced mtOXPHOS, ROS levels, and drug-resistant CSCs without affecting the anti-apoptotic function of MCL1. Increased levels of ROS, a by-product of a…