Search results for "Harm"

Differential glutamatergic and GABAergic contributions to the tetrad effects of Δ9-tetrahydrocannabinol revealed by cell-type-specific reconstitution…

2020

Δ9-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa, exerts its actions through the endocannabinoid system by stimulation of the cannabinoid type 1 (CB1) receptor. The widespread distribution of this receptor in different neuronal cell types and the plethora of functions that is modulated by the endocannabinoid system explain the versatility of the effects of THC. However, the cell types involved in the different THC effects are still not fully known. Conditional CB1 receptor knock-out mice were previously used to identify CB1 receptor subpopulations that are "necessary" for the tetrad effects of a high dose of THC: hypothermia, hypolocomotion, catalepsy and …

Cardiac β3‐adrenoceptors—A role in human pathophysiology?

2019

As β3 -adrenoceptors were first demonstrated to be expressed in adipose tissue they have received much attention for their metabolic effects in obesity and diabetes. After the existence of this subtype had been suggested to be present in the heart, studies focused on its role in cardiac function. While the presence and functional role of β3 -adrenoceptors in the heart has not uniformly been detected, there is a broad consensus that they become up-regulated in pathological conditions associated with increased sympathetic activity such as heart failure and diabetes. When detected, the β3 -adrenceptor has been demonstrated to mediate negative inotropic effects in an inhibitory G protein-depend…

Vitamin K3 chloro derivative (VKT-2) inhibits HDAC6, activates autophagy and apoptosis, and inhibits aggresome formation in hepatocellular carcinoma …

2020

Epigenetics plays a vital role in regulating gene expression and determining the specific phenotypes of eukaryotic cells. Histone deacetylases (HDACs) are important epigenetic regulatory proteins effecting multiple biological functions. Particularly, HDAC6 has become a promising anti-cancer drug target because of its regulation of cell mobility, protein trafficking, degradation of misfolded proteins, cell growth, apoptosis, and metastasis. In this study, we identified one out of six vitamin K3 derivatives, VKT-2, as HDAC6 inhibitor using molecular docking and cell viability assays in HDAC6-overexpressing HuH-7 cancer cells. Microscale thermophoresis and HDAC6 enzymatic assays revealed that …

Cocaine-induced changes in CX3CL1 and inflammatory signaling pathways in the hippocampus: Association with IL1β

2020

Cocaine induces neuroinflammatory response and interleukin-1 beta (IL1β) is suggested a final effector for many cocaine-induced inflammatory signals. Recently, the chemokine fractalkine (CX3CL1) has been reported to regulate hippocampus-dependent neuroinflammation and synaptic plasticity via CX3C-receptor 1 (CX3CR1), but little is known about the impact of cocaine. This study is mainly focused on the characterization of CX3CL1, IL1β and relevant inflammatory signal transduction pathways in the hippocampus in acute and repeated cocaine-treated male mice. Complementarily, the rewarding properties of cocaine were also assessed in Cx3cr1-knockout (KO) mice using a conditioned place preference (…

Cardenolides: Insights from chemical structure and pharmacological utility

2019

Cardiac glycosides (CGs) are a class of naturally occurring steroid-like compounds, and members of this class have been in clinical use for more than 1500 years. They have been used in folk medicine as arrow poisons, abortifacients, heart tonics, emetics, and diuretics as well as in other applications. The major use of CGs today is based on their ability to inhibit the membrane-bound Na

European countries in the race to attract successful biopharma investment: Winners and laggers

2021

The post-coronavirus era will open myriad opportunities for the biopharma industry. However, the extent to which each country will take advantage of this promising new scenario will largely depend on its position in a few key areas. Here, we offer an overview of the European countries that are winning and those that are lagging behind in the race to attract the greatest investment in this industry and to attain the highest rate of successful new ventures. Our results highlight the vital importance of a sound, active funding base, especially in terms of venture capital. Our findings also suggests that general scientific foundations are not enough to secure an advantage in new venture formati…

α1-adrenoceptor activity of β-adrenoceptor ligands – An expected drug property with limited clinical relevance

2020

Many β-adrenoceptor agonists and antagonists including several clinically used drugs have been reported to also exhibit binding to α1-adrenoceptors. Such promiscuity within the adrenoceptor family appears to occur more often than off-target effects of drugs in general. It should not be considered surprising based on the amino acid homology among the nine adrenoceptor subtypes including the counter-ions for binding the endogenous catecholamines. When β-adrenoceptor ligands also bind to α1-adrenoceptors, they almost always act as antagonists, regardless of being agonists or antagonists at the β-adrenoceptor. The α1-adrenoceptor affinity of β-adrenoceptor ligands in most cases is at least one,…

Paracetamol – An old drug with new mechanisms of action

2020

Paracetamol (acetaminophen) is the most commonly used over-the-counter (OTC) drug in the world. Despite its popularity and use for many years, the safety of its application and its mechanism of action are still unclear. Currently, it is believed that paracetamol is a multidirectional drug and at least several metabolic pathways are involved in its analgesic and antipyretic action. The mechanism of paracetamol action consists in inhibition of cyclooxygenases (COX-1, COX-2, and COX-3) and involvement in the endocannabinoid system and serotonergic pathways. Additionally, paracetamol influences transient receptor potential (TRP) channels and voltage-gated Kv7 potassium channels and inhibits T-t…

Chrysophanol- and nepodin-8-O-β-D-glucopyranoside from Rumex acetosella, the cytotoxicity towards drug sensitive and multi- drug resistant T leukaemi…

2016

2019

Background: Focal dystonias are severe and disabling movement disorders of a still unclear origin. The structural brain networks associated with focal dystonia have not been well characterized. Here, we investigated structural brain network fingerprints in patients with blepharospasm (BSP) compared with those with hemifacial spasm (HFS), and healthy controls (HC). The patients were also examined following treatment with botulinum neurotoxin (BoNT). Methods: This study included matched groups of 13 BSP patients, 13 HFS patients, and 13 HC. We measured patients using structural-magnetic resonance imaging (MRI) at baseline and after one month BoNT treatment, at time points of maximal and minim…