Zobrazení zdroje stránky Klemmensenstrand8264

The neuropeptide oxytocin (OT) has been shown to play a modulatory role in nociception. However, analgesic effects of OT in chronic pain conditions remain elusive and the neural underpinnings have not yet been investigated in humans. Here, we conducted an exploratory, randomized, placebo-controlled, cross-over study to examine effects of intranasal OT in male patients suffering from chronic low back pain (CBP) versus healthy controls (HC). N&nbsp;=&nbsp;22 participants with CBP and 22&nbsp;HCs were scanned using functional magnetic resonance imaging (fMRI) while they continuously rated either spontaneously occurring back pain or acute thermal pain stimuli applied to the lower back. During heat pain processing we found that OT versus PL attenuated pain intensity ratings and increased BOLD responses in the caudate nucleus of the striatum in CBP versus HCs. Spontaneously experienced pain in contrast to heat pain was associated with activation changes in the medial frontal cortex (MFC) and the anterior cingulate cortex (ACC) as reported in previous studies. However, we did not observe OT effects on spontaneously experienced pain in CBP patients. Overall, our preliminary data may suggest that the striatum is a key structure underlying the pain-modulating effects of OT in patients with chronic pain and adds to the growing evidence linking the neuropeptide to pain modulation in humans. Further studies on neuronal OT effects in larger samples of chronic back pain patients are needed to understand probable mechanisms of OT effects in chronic pain. Enhancer of zeste homolog 2 (EZH2), a subunit of the polycomb repressive complex 2 (PRC2), is associated with seizure development and epileptogenesis, however, the underlying mechanism of the process remains to be elucidated. This study focused on exploring whether EZH2 regulated gamma-aminobutyric acid (GABA)-mediated neurotransmission during seizure generation. Hyperthermia-induced seizures were generated in Sprague-Dawley (SD) rats using a hot (43.5&nbsp;°C) bath method, and seizure severity was evaluated according to the Racine scale. The effect of treatment with the EZH2 pharmacological inhibitor GSK 126 on the GABA and pro-inflammatory cytokine levels was tested using enzyme-linked immunosorbent assay (ELISA). Miniature inhibitory postsynaptic currents (mIPSCs) were recorded using whole-cell patch clamp. In this study, our results showed that intracerebroventricular (i.c.v) injection of the EZH2 pharmacological inhibitor GSK 126 (10&nbsp;nM) increased seizure severity and shortened seizure latency in a rat model of FS, and these effects were accompanied by reduced GABA content. [https://www.selleckchem.com/products/azd5153-6-hydroxy-2-naphthoic-acid.html AZD-5153 6-hydroxy-2-naphthoic nmr] Furthermore, GSK 126 (1&nbsp;μM) treatment decreased the mean amplitude and frequency of the mIPSCs in cultured hippocampal neurons subjected to hyperthermia. Importantly, the same results were also obtained in cultured neurons infected with lentivirus carrying EZH2 shRNA. In addition, a significant increase in the pro-inflammatory cytokine (IL-1β and TNF-α) levels was observed in rats after GSK 126 treatment, and IL-1β administration increased seizure severity, suggesting that the inflammatory response was involved in the regulation of seizure development by EZH2. This study helps clarify the role of EZH2 in FS and supports EZH2 administration as an effective target for the management of seizure generation. Attentional bias to food stimuli may contribute to the etiology and/or maintenance of overweight and obesity. We conducted a literature review and meta-analysis per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify the effect size associated with attentional bias to palatable food in persons with overweight/obesity across the age spectrum. Included studies measured attentional bias to food stimuli using two reaction-time tasks (dot-probe, emotional Stroop), eye-tracking methodology, and/or event-related potentials. Meta-analysis showed that persons with overweight/obesity did not differ from persons with a healthy weight on any of the following automatic and maintained attention to food stimuli measured by the dot-probe task (Hedge's gautomatic&nbsp;=&nbsp;-0.355, 95% CI&nbsp;=&nbsp;-0.383, 0.486; and Hedge's gmaintained&nbsp;=&nbsp;0.006, 95% CI&nbsp;=&nbsp;-0.187, 0.199); attentional bias to food stimuli measured by the emotional Stroop task (Hedge's g&nbsp;=&nbsp;0.184, 95% CI&nbsp;=&nbsp;-0.283, 0.651); and attentional bias to food images on gaze-direction and gaze-duration bias eye-tracking metrics (Hedge's gdirection&nbsp;=&nbsp;0.317, 95% CI&nbsp;=&nbsp;-0.096, 0.729; and Hedge's gduration&nbsp;=&nbsp;0.056, 95% CI&nbsp;=&nbsp;-0.296, 0.407). Systematic review of preliminary event-related potentials research suggested automatic, but not maintained, attention to food images in persons with overweight/obesity. Limitations of past attentional bias research in overweight/obesity, such as poor reliability of measures and lack of consideration of moderators, such as binge eating and degree of overweight/obesity, preclude the ability to draw firm conclusions. We recommend implementation of empirically based methods for improving psychometric properties of attentional bias measures and examination of potential moderators so that the field can understand whether attentional bias to food is truly greater in overweight/obesity. BACKGROUND Interactions between TNF ligand superfamily and TNF receptor superfamily play critical roles in B cell development and maturation. A proliferation-inducing ligand (APRIL), a member of the TNF ligand superfamily, is secreted from myeloid cells and known to induce the differentiation of memory B cells to plasmacytes. OBJECTIVE To elucidate the role of APRIL in B cell differentiation and immunoglobulin production through the analysis of complete APRIL deficiency in human. METHODS We performed whole exome sequencing (WES) in an adult common variable immunodeficiency patient. His parents were in a consanguineous marriage. TNFSF13 mRNA and protein expression were analyzed in the primary cells and plasma from the patient and in cDNA-transfected cells and supernatants of the cultures in vitro. Immunological analysis was performed using flow cytometry and next generation sequencing. Monocyte-derived dendritic cells differentiated from induced pluripotent stem cells (iPS-moDCs) were co-cultured with memory B cells from healthy controls to examine in vitro plasmacyte differentiation.