Search results for "Hip"

Dlk1 dosage regulates hippocampal neurogenesis and cognition

2021

Significance Generation of new neurons occurs normally in the adult brain in two locations: the subventricular zone (SVZ) in the walls of the lateral ventricles and the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus. Neurogenesis in the adult hippocampus has been implicated in cognitive functions such as learning, memory, and recovery of stress response. Imprinted genes are highly prevalent in the brain and have adult and developmental important functions. Genetic deletion of the imprinted gene Dlk1 from either parental allele shows that DLK1 is a key mediator of quiescence in adult hippocampal NSCs. Additionally, Dlk1 is exquisitely dosage sensitive in the brain with p…

Mechanisms Underlying Memory Consolidation by Adult-Born Neurons During Sleep

2020

The mammalian hippocampus generates new neurons that incorporate into existing neuronal networks throughout the lifespan, which bestows a unique form of cellular plasticity to the memory system. Recently, we found that hippocampal adult-born neurons (ABNs) that were active during learning reactivate during subsequent rapid eye movement (REM) sleep and provided causal evidence that ABN activity during REM sleep is necessary for memory consolidation. Here, we describe the potential underlying mechanisms by highlighting distinct characteristics of ABNs including decoupled firing from local oscillations and ability to undergo profound synaptic remodeling in response to experience. We further di…

Hippocampal hyperexcitability is modulated by microtubule-active agent: evidence from in vivo and in vitro epilepsy models in the rat

2016

The involvement of microtubule dynamics on bioelectric activity of neurons and neurotransmission represents a fascinating target of research in the context of neural excitability. It has been reported that alteration of microtubule cytoskeleton can lead to profound modifications of neural functioning, with a putative impact on hyperexcitability phenomena. Altogether, in the present study we pointed at exploring the outcomes of modulating the degree of microtubule polymerization in two electrophysiological epileptiform activity in the rat hippocampus. To this aim, we used in vivo Maximal Dentate Activation (MDA) and in vitro hippocampal epileptiform bursting activity (HEBA) paradigms to asse…

New 3-Aryl-2-(2-Thienyl)acrylonitriles with High Activity against Hepatoma Cells

2021

New 2-(thien-2-yl)-acrylonitriles with putative kinase inhibitory activity were prepared and tested for their antineoplastic efficacy in hepatoma models. Four out of the 14 derivatives were shown to inhibit hepatoma cell proliferation at (sub-)micromolar concentrations with IC50 values below that of the clinically relevant multikinase inhibitor sorafenib, which served as a reference. Colony formation assays as well as primary in vivo examinations of hepatoma tumors grown on the chorioallantoic membrane of fertilized chicken eggs (CAM assay) confirmed the excellent antineoplastic efficacy of the new derivatives. Their mode of action included an induction of apoptotic capsase-3 activity, whil…

Anticancer properties of 5Z-(4- fuorobenzylidene)-2-(4- hydroxyphenylamino)-thiazol-4-one

2019

Abstract4-thiazolidinones, which are privileged structures in medicinal chemistry, comprise the well-known class of heterocycles and are a source of new drug-like compounds. Undoubtedly, the 5-bulky-substituted-2,4-thiazolidinediones - a class of antihyperglycemic glitazones, which are peroxisome proliferator-activated receptor gamma (PPARγ) agonists, are the most described group among them. As there are various chemically distinct 4-thiazolidinones, different subtypes have been selected for studies; however, their main pharmacological profiles are similar. The aim of this study was to evaluate the anticancer activity of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one (Les-2…

2019

Epileptic activity without visible convulsions is common in Alzheimer's disease (AD) and may contribute adversely to the disease progress and symptoms. Transgenic mice with amyloid plaque pathology also display epileptic seizures, but those are too infrequent to assess the effect of anti-epileptic treatments. Besides spontaneous seizures, these mice also display frequent epileptic spiking in epidural EEG recordings, and these have provided a means to test potential drug treatment to AD-related epilepsy. However, the origin of EEG spikes in transgenic AD model mice has remained elusive, which makes it difficult to relate electrophysiology with underlying pathology at the cellular and molecul…

Molecular Signatures Associated with Treatment of Triple-Negative MDA-MB231 Breast Cancer Cells with Histone Deacetylase Inhibitors JAHA and SAHA

2017

Jay Amin Hydroxamic Acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA’s cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 M. JAHA’s lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction and autophagy mechanisms. In order to glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination of…

Prospecting for cytotoxic and antiprotozoal 4-aryl-4H-chromenes and 10-aryldihydropyrano[2,3-f]chromenes.

2018

Different studies reported that genetic predisposition or metabolic dysfunction are the risk factors for cancer. Infectious parasitic diseases were listed among factors that predispose to cancer. Because of the resemblance between the life cycle of cancer cells and some parasites, this study aimed to prepare pyran derivatives with cytotoxic and antiprotozoal potencies. Therefore, 7 chromenes, 10 pyranocoumarins, and an unexpected intermediate were obtained from a multi-reagent one-pot reaction. These compounds were evaluated for their cytotoxicity on sensitive and resistant leukemia cancer cells lines and against two protozoan parasites, namely Trypanosoma cruzi and Leishmania amazonensis a…

Estrogenic activity of zearalenone, α-zearalenol and β-zearalenol assessed using the E-Screen assay in MCF-7 cells

2017

Mycotoxins, including zearalenone (ZEA), can occur worldwide in cereals. They can enter the food chain and cause several health disorders. ZEA and its derivatives (α-zearalenol, α-ZOL and β-zearalenol, β-ZOL) have structural analogy to estrogen, thus they can bind to estrogen receptors (ERs). In order to characterize the estrogenic activity of ZEA, α-ZOL and β-ZOL, the proliferation of ER-positive human breast cancer cells (MCF-7) exposed to these mycotoxins was measured. After exposure at levels ranging from 6.25 to 25 µM, cell proliferation was evaluated by using the E-Screen bioassay. In accordance with previous studies, our results show the estrogenic activity of ZEA, α-ZOL and β-ZOL in…

Bistacrines as potential antitrypanosomal agents

2017

Human African Trypanosomiasis (HAT) is caused by two subspecies of the genus Trypanosoma, namely Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. The disease is fatal if left untreated and therapy is limited due to only five non-adequate drugs currently available. In preliminary studies, dimeric tacrine derivatives were found to inhibit parasite growth with IC50-values in the nanomolar concentration range. This prompted the synthesis of a small, but smart library of monomeric and dimeric tacrine-type compounds and their evaluation of antiprotozoal activity. Rhodesain, a lysosomal cathepsin-L like cysteine protease of T. brucei rhodesiense is essential for parasite survival a…