Search results for "pines"
showing 10 items of 421 documents
GABAergic System in Action: Connection to Gastrointestinal Stress-related Disorders.
2017
Background: Currently, treatment of stress-related gastrointestinal disorders, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), is mainly symptomatic since there is no drug on the market that solves effectively diverse disease symptoms and comorbid states. Thus, recently GABA receptors have been identified within gastrointestinal system and it has been recognized that among various GABAergic drugs some of them influence gastrointestinal stress-related diseases. Firstly, benzodiazepines have been investigated due to their diverse effects: neuroimmunomodulatory, relief of visceral pain and anxiolytic action. Conclusion: The present review brings findings on the exp…
Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery
2020
Cathepsin S (CatS) is a secreted cysteine protease that cleaves certain extracellular matrix proteins, regulates antigen presentation in antigen-presenting cells (APC), and promotes M2-type macrophage and dendritic cell polarization. CatS is overexpressed in many solid cancers, and overall, it appears to promote an immune-suppressive and tumor-promoting microenvironment. While most data suggest that CatS inhibition or knockdown promotes anti-cancer immunity, cell-specific inhibition, especially in myeloid cells, appears to be important for therapeutic efficacy. This makes the design of CatS selective inhibitors and their targeting to tumor-associated M2-type macrophages (TAM) and DC an attr…
Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation
2015
Unwinding DNA and unleasing inflammation Fighting infections often comes with collateral damage, which sometimes can be deadly. For instance, in septic shock, the overwhelming release of inflammatory mediators drives multi-organ failure. Rialdi et al. now report a potential new therapeutic target for controlling excessive inflammation: the DNA unwinding enzyme topoisomerase I (Top1) (see the Perspective by Pope and Medzhitov). Upon infection, Top1 specifically localizes to the promoters of pathogen-induced genes and promotes their transcription by helping to recruit RNA polymerase II. Pharmacological inhibition of Top1 in a therapeutic setting increased survival in several mouse models of s…
Development of novel 1,4-benzodiazepine-based Michael acceptors as antitrypanosomal agents
2016
Novel 1,4-benzodiazepines, endowed with a Michael acceptor moiety, were designed taking advantage of a computational prediction of their pharmacokinetic parameters. Among all the synthesized derivatives, we identified a new lead compound (i.e., 4a), bearing a vinyl ketone warhead and endowed with a promising antitrypanosomal activity against Trypanosoma brucei brucei (IC50 = 5.29 µM), coupled with a lack of cytotoxicity towards mammalian cells (TC50>100 µM).
Modulating Neuronal Competition Dynamics in the Dentate Gyrus to Rejuvenate Aging Memory Circuits.
2015
The neural circuit mechanisms underlying the integration and functions of adult-born dentate granule cell (DGCs) are poorly understood. Adult-born DGCs are thought to compete with mature DGCs for inputs to integrate. Transient genetic overexpression of a negative regulator of dendritic spines, Kruppel-like factor 9 (Klf9), in mature DGCs enhanced integration of adult-born DGCs and increased NSC activation. Reversal of Klf9 overexpression in mature DGCs restored spines and activity and reset neuronal competition dynamics and NSC activation, leaving the DG modified by a functionally integrated, expanded cohort of age-matched adult-born DGCs. Spine elimination by inducible deletion of Rac1 in …
Development and validation of the Healthy-Unhealthy Music Scale.
2015
Background Music is an integral part of life in youth, and although it has been acknowledged that musical behavior reflects broader psychosocial aspects of adolescent behavior, no measurement instruments have been specifically designed for assessing musical engagement as an indicator of adolescent wellbeing and/or symptomatology. This study was conducted in order to develop and validate a scale for assessing musical engagement as an indicator of proneness for depression in youth. Method Items were developed based on the literature and a prior grounded theory analysis and three surveys (N = 54, N = 187, N = 211) were conducted to select, refine, test, and validate the items. Scale structure …
Meditation and happiness: Mindfulness and self-compassion may mediate the meditation–happiness relationship
2015
Mindfulness and self-compassion are emerging as crucial constructs in mental health research. Recent studies have shown that both mindfulness and self-compassion skills may play important roles in well-being and positive emotions associated with mindfulness training. Studies are needed to explain this relationship and to determine what facets may be correlating and mediating the meditation-happiness relationship. The aim of this study was to explore the meditation-happiness relationship and examine which mindfulness and self compassion facets are better predictors of happiness. A total of 365 participants completed an assessment protocol composed of: the Five Facets of Mindfulness Questionn…
A stochastic dynamical social model involving a human happiness index
2018
[EN] This paper presents a new human happiness index built through five dimensions: development, freedom, solidarity, justice and peace. These five dimensions are evaluated through quantitative variables obtained from the Human Development Reports, World Data Bank and Eurostat. The new happiness index has been built following the guidelines set by the Human Development Reports of the UN for the construction of quality indices, and it has been compared on a set of 13 EU countries with the Overall Life Satisfaction Index, which is used by the UN. Moreover, the new index has been included in a dynamic mathematical model through the demographic rates to study the evolution of the population. Th…
The Complex Interaction Between the Major Sleep Symptoms, the Severity of Obstructive Sleep Apnea, and Sleep Quality
2021
Introduction: Little information exists in the general population whether clinical presentation phenotypes of obstructive sleep apnea (OSA) differ in terms of sleep quality and comorbidities.Aim: The purpose of our study was to assess possible differences between symptomatic and asymptomatic OSA patients concerning syndrome's severity, patients' sleep quality, and comorbidities.Subjects and methods: First, in a nationwide, stratified, epidemiological survey, 4,118 Cypriot adult participants were interviewed about sleep habits and complaints. In the second stage of the survey, 264 randomly selected adults underwent a type III sleep study for possible OSA. Additionally, they completed the Gre…
Cellular mechanisms of IL-17-induced blood-brain barrier disruption.
2009
Recently T-helper 17 (Th17) cells were demonstrated to disrupt the blood-brain barrier (BBB) by the action of IL-17A. The aim of the present study was to examine the mechanisms that underlie IL-17A-induced BBB breakdown. Barrier integrity was analyzed in the murine brain endothelial cell line bEnd.3 by measuring the electrical resistance values using electrical call impedance sensing technology. Furthermore, in-cell Western blots, fluorescence imaging, and monocyte adhesion and transendothelial migration assays were performed. Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice. IL-17A induced NADPH oxidase- or xanthine oxidase-dependent reactive oxygen species (ROS)…