Lopezrose6398
The amplitude and implicit time of OP1, OP2, OP3 and OP4 were evaluated.
Cannabis users showed a significant decrease in OP2 amplitude (p=0.029, Mann-Whitney test) and OP3 amplitude (p=0.024, Mann-Whitney test). No significant difference was found between the groups for OP1 and OP4 amplitude or for the implicit time of oscillatory potentials.
These results reflect the impact of regular cannabis use on amacrine cells function. They highlight abnormalities in dopaminergic transmission and are similar to those found in Parkinson's disease. Oscillatory potentials could be used as markers of central dopaminergic modulation.
These results reflect the impact of regular cannabis use on amacrine cells function. They highlight abnormalities in dopaminergic transmission and are similar to those found in Parkinson's disease. Oscillatory potentials could be used as markers of central dopaminergic modulation.
Vascular endothelial growth factor (VEGF), is upregulated in tumor cells and thus became a potential therapeutic target for anti-cancer drugs. Recent reports suggested the use of Doxorubicin (Dox) with VEGF-targeting siRNAs for an enhanced decrease in VEGF expression. Besides, VEGF-B gene therapy was found to suppress the cardiotoxicity effects of Dox. On the other hand, even though Dox is a commonly used anti-cancer agent, its mechanism of actions isn't completely mapped out. Herein, the interactions between a G4 structure formed by the VEGF promoter region Pu
and Dox were investigated.
The Dox-G4 interactions were examined via competition dialysis, UV-vis Absorption, Circular Dichroism (CD) and Fluorescence spectroscopy.
The results demonstrated that Dox was stabilizing the VEGF Pu
G4 structure and the calculated association constant for VEGF Pu
-G4 complex (K
=7.50×10
) was very close to the reported K
values for Dox-dsDNA complexes. Additionally, the competition dialysis experiments revealed the selectivity of Dox to Pu
compared to other G4 structures formed in telomeric repeats and promoter regions such as BCL-2 and C-myc.
Dox exhibits strong and selective association with VEGF Pu
G4 structure that was comparable to its well-known association with dsDNA.
The results presented here might be useful in the general area of antitumor drug-DNA interactions. Doxorubicin's significant affinity to VEGF Pu
G4 might be one of the plausible mechanisms behind its anti-tumor activity.
The results presented here might be useful in the general area of antitumor drug-DNA interactions. Doxorubicin's significant affinity to VEGF Pu22 G4 might be one of the plausible mechanisms behind its anti-tumor activity.Resistance to DNA-damaging agents is one of the main reasons for the low survival of cervical cancer patients. Previous reports have suggested that the Cdc25A oncoprotein significantly affects the level of susceptibility to DNA-damaging agents, but the molecular mechanism remains unclear. In this study, we used Western blot and flow cytometry analyses to demonstrate that the deubiquitinating enzyme HAUSP stabilizes Cdc25A protein level. Furthermore, in a co-immunoprecipitation assay, we found that HAUSP interacts with and deubiquitinates Cdc25A both exogenously and endogenously. HAUSP extends the half-life of the Cdc25A protein by circumventing turnover. HAUSP knockout in HeLa cells using the CRISPR/Cas9 system caused a significant delay in Cdc25A-mediated cell cycle progression, cell migration, and colony formation and attenuated tumor progression in a mouse xenograft model. Furthermore, HAUSP-mediated stabilization of the Cdc25A protein produced enhanced resistance to DNA-damaging agents. Overall, our study suggests that targeting Cdc25A and HAUSP could be a promising combinatorial approach to halt progression and minimize antineoplastic resistance in cervical cancer.Epithelial-mesenchymal transition (EMT) is considered as the key mechanism involved in cancer metastasis. Several studies showed that various cell membrane calcium channels play different roles in cancer metastasis. In the present study, the potential role of ATPase plasma membrane Ca2+ transporting 4 (PMCA4) in regulating EMT in gastric cancer (GC) was investigated. GC patients who underwent radical surgery were enrolled in this study. In vitro human GC cell lines MKN45 and NCI-N87 were used, and MKN45 cells were injected in nude mice to evaluate tumor development. Our results showed that low PMCA4 expression was associated with advanced TNM stage and poor prognosis in GC patients. Knockdown of PMCA4 suppressed E-cadherin, grainyhead like 2 (GRHL2) and ovo-like 1 (OVOL1) expression, up-regulated vimentin expression, increased migration and invasion ability, and promoted the resistance to cytotoxic drug. Furthermore, GC cells displayed an elongated fibroblastoid morphology when PMCA4 was knockdown. PMCA4 overexpression resulted in an up-regulated E-cadherin expression and decreased migration and invasion ability. In vivo metastasis assay showed that PMCA4 overexpression resulted in a decreased incidence of lung metastasis. PMCA4 inhibition increased ZEB1 expression and nuclear accumulation of nuclear factor of activated T-cell isoform c1 (NFATc1). EMT induced by PMCA4 inhibition could be prevented by the knockdown of NFATc1 or ZEB1. In addition, cyclosporine A prevented EMT induced by PMCA4 inhibition by suppressing the NFATc1-ZEB1 pathway. Our data identified a novel mechanism in the regulation of EMT in GC, and provided a novel target in the treatment of EMT subtype in GC.Neutrophils exhibit rapid cell spreading and phagocytosis, both requiring a large apparent increase in the cell surface area. The wrinkled surface topography of these cells may provide the membrane reservoir for this. Here, the effects of manipulation of the neutrophil cell surface topography on phagocytosis and cell spreading were established. Chemical expansion of the plasma membrane or osmotic swelling had no effects. However, osmotic shrinking of neutrophils inhibited both cell spreading and phagocytosis. Triggering a Ca2+ signal in osmotically shrunk cells (by IP3 uncaging) evoked tubular blebs instead of full cell spreading. Phagocytosis was halted at the phagocytic cup stage by osmotic shrinking induced after the phagocytic Ca2+ signalling. Restoration of isotonicity was able to restore complete phagocytosis. These data thus provide evidence that the wrinkled neutrophil surface topography provides the membrane reservoir to increase the available cell surface area for phagocytosis and spreading by neutrophils.Small conductance calcium-activated potassium channels (SKs) are solely activated by intracellular Ca2+ and their activation leads to potassium efflux, thereby repolarizing/hyperpolarizing membrane potential. Thus, these channels play a critical role in synaptic transmission, and consequently in information transmission along the neuronal circuits expressing them. SKs are widely but not homogeneously distributed in the central nervous system (CNS). Activation of SKs requires submicromolar cytoplasmic Ca2+ concentrations, which are reached following either Ca2+ release from intracellular Ca2+ stores or influx through Ca2+ permeable membrane channels. Both Ca2+ sensitivity and synaptic levels of SKs are regulated by protein kinases and phosphatases, and degradation pathways. SKs in turn control the activity of multiple Ca2+ channels. They are therefore critically involved in coordinating diverse Ca2+ signaling pathways and controlling Ca2+ signal amplitude and duration. This review highlights recent advances in our understanding of the regulation of SK2 channels and of their roles in normal brain functions, including synaptic plasticity, learning and memory, and rhythmic activities. It will also discuss how alterations in their expression and regulation might contribute to various brain disorders such as Angelman Syndrome, Alzheimer's disease and Parkinson's disease.Estrogens modulate different physiological functions, including reproduction, inflammation, bone formation, energy expenditure, and food intake. In this review, we highlight the effect of estrogens on food intake regulation and the latest literature on intracellular estrogen signaling. In addition, gut satiety hormones, such as cholecystokinin, glucagon-like peptide 1 and leptin are essential to regulate ingestive behaviors in the postprandial period. These peripheral signals are sensed by vagal afferent terminals in the gut wall and transmitted to the hindbrain axis. Here we 1. review the role of the vagus-hindbrain axis in response to gut satiety signals and 2. consider the potential synergistic effects of estrogens on gut satiety signals at the level of vagal afferent neurons and nuclei located in the hindbrain. Understanding the action of estrogens in gut-brain axis provides a potential strategy to develop estrogen-based therapies for metabolic diseases and emphasizes the importance of sex difference in the treatment of obesity.As human-modified landscapes encroach into natural habitats, wildlife face a reduction in natural food sources but also gain access to calorie-rich, human-derived foods. However, research into the energetics of wildlife living within and adjacent to urban and rural landscapes is lacking. C-peptide - a proxy for insulin production and a diagnostic tool for assessing pancreatic function in humans and domestic animals - can be quantified non-invasively from urine (uCP) and may provide a way to investigate the energetic correlates of living in human-altered landscapes. UCP is increasingly used in studies of primate energetics, and here we examine predictors of variation in uCP levels in n = 17 wild chacma baboons (Papio ursinus) living at the urban edge on the Cape Peninsula, South Africa. We find that uCP was positively associated with food provisioning and negatively with night fasting. UCP levels were comparable between winter and summer but significantly lower during spring, possibly driven by consumption of energy-rich seeds during summer and more human-derived foods during winter. UCP was elevated in pregnant females and similar for lactating and cycling females. We find no effect of dominance rank on uCP. Samples collected with synthetic Salivettes had significantly lower uCP levels than directly pipetted samples. Overall, our results indicate that uCP is a reliable, non-invasive measure of energy balance and intake in baboons, and suggest potential energetic benefits of living at the urban edge. More broadly, studies of uCP may offer unique insight into the environmental control of hormone-behaviour relationships in species crossing natural and urban environments.Gonadotropic hormones coordinate processes in diverse tissues regulating animal reproductive physiology and behavior. Juvenile hormone (JH) is the ancient and most common gonadotropin in insects, but not in advanced eusocial honey bees and some ants. Trichostatin A cost To start probing the evolutionary basis of this change, we combined endocrine manipulations, transcriptomics, and behavioral analyses to study JH regulated processes in a bumble bee showing a relatively simple level of eusociality. We found that in worker fat body, more JH-regulated genes were up- rather than down-regulated, and enriched for metabolic and biosynthetic pathways. This transcriptomic pattern is consistent with earlier evidence that JH is the major gonadotropin in bumble bees. In the brain, more JH-regulated genes were down- rather than up-regulated and enriched for protein turnover pathways. Brain ribosomal protein gene expression shows a similar trend of downregulation in dominant workers, which naturally have high JH titers. In other species, similar downregulation of protein turnover is found in aging brains or under stress, associated with compromised long-term memory and health.
