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https://www.readbyqxmd.com/read/28738332/neuroprogression-and-immune-activation-in-major-depressive-disorder
#1
Jeffrey H Meyer
Traditionally, the neurobiology of major depressive disorder (MDD) has been largely considered from the perspective of the state of major depressive episodes (MDE) versus being in remission, but the current accumulation of disease markers, largely acquired cross-sectionally, is strongly suggestive of neuroprogressive aspects of MDD. This chapter focuses on the changes in disease markers involved in the reorganization of the nervous system in MDD, including the translocator protein (TSPO; an index of microglial activation), glial fibrillary acidic protein (GFAP; an index of astroglial activation), [11C]harmine (a marker of monoamine oxidase A; MAO-A), and several other indices (metabotropic glutamate receptor 5 [mGluR5], excitatory amino acid transporters, and magnetic resonance imaging spectroscopy measurements) of glutamate dysregulation...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28735612/cutaneous-glucocorticoidogenesis-and-cortisol-signaling-are-defective-in-psoriasis
#2
Andrzej T Slominski, Anna A Brożyna, Robert C Tuckey
Hannen et al. report that cutaneous glucocorticoidogenesis and expression of glucocorticoid receptors are inhibited in psoriatic skin. These findings substantiate the previous concept that deficient feedback of local proopiomelanocortin and glucocorticoids on cutaneous immunity contributes to inflammatory and autoimmune dermatoses. Restoration of efficient endogenous glucocorticoid signaling represents a realistic goal in treating psoriasis.
August 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28734893/genetic-polymorphisms-in-cyp2a6-are-associated-with-a-risk-of-cigarette-smoking-and-predispose-to-smoking-at-younger-ages
#3
Gloria Pérez-Rubio, Luis Alberto López-Flores, Alejandra Ramírez-Venegas, Valeri Noé-Díaz, Leonor García-Gómez, Enrique Ambrocio-Ortiz, Candelaria Sánchez-Romero, Rafael De Jesús Hernández-Zenteno, Raúl Humberto Sansores, Ramcés Falfán-Valencia
Nicotine is the main component of cigarettes that causes addiction, which is considered a complex disease, and genetic factors have been proposed to be involved in the development of addiction. The CYP2A6 gene encodes the main enzyme responsible for nicotine metabolism. Depending on the study population, different genetic variants of CYP2A6 associated with cigarette smoking have been described. Therefore, we evaluated the possible association between SNPs in CYP2A6 with cigarette smoking and nicotine addiction-related variables in Mexican mestizo smokers...
July 19, 2017: Gene
https://www.readbyqxmd.com/read/28733598/role-of-hdac9-foxo1-axis-in-the-transcriptional-program-associated-with-hepatic-gluconeogenesis
#4
Jizheng Chen, Zhilei Zhang, Ning Wang, Min Guo, Xiumei Chi, Yu Pan, Jing Jiang, Junqi Niu, Sulaiman Ksimu, John Zhong Li, Xinwen Chen, Qian Wang
Histone deacetylase 9 (HDAC9) regulates hepatic gluconeogenesis by deacetylating Forkhead box O 1 (FoxO1). HDAC9 upregulation is involved in hepatitis C virus (HCV)-associated exaggerated gluconeogenesis. Herein, we found in addition to FoxO1, HDAC9 also regulates other gluconeogenic transcription factors, including peroxisomeproliferator-activated receptor-γ coactivator-1α (PGC-1α), cyclic AMP-responsive element-binding protein (CREB), and glucocorticoid receptor (GR). Unlike FoxO1, which is regulated by post-translational modification responses to HDAC9, HDAC9 regulates PGC-1α, CREB and GR by altering gene expression...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733463/tlr4-and-c5ar-crosstalk-in-dendritic-cells-induces-a-core-regulatory-network-of-rsk2-pi3k%C3%AE-sgk1-and-foxo-transcription-factors
#5
Anouk Zaal, Benjamin Nota, Kat S Moore, Miranda Dieker, S Marieke van Ham, Anja Ten Brinke
Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation...
July 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28732502/chronic-glucocorticoid-exposure-activates-bk-nlrp1-signal-involving-in-hippocampal-neuron-damage
#6
Biqiong Zhang, Yaodong Zhang, Wenning Wu, Tanzhen Xu, Yanyan Yin, Junyan Zhang, Dake Huang, Weizu Li
BACKGROUND: Neuroinflammation mediated by NLRP1 (nucleotide-binding oligomerization domain (NOD)-like receptor protein 1) inflammasome plays an important role in many neurological diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). Our previous studies showed that chronic glucocorticoid (GC) exposure increased brain inflammation via NLRP1 inflammasome and induce neurodegeneration. However, little is known about the mechanism of chronic GC exposure on NLRP1 inflammasome activation in hippocampal neurons...
July 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28732066/inhibition-of-pulmonary-%C3%AE-carotene-15-15-oxygenase-expression-by-glucocorticoid-involves-ppar%C3%AE
#7
Xiaoming Gong, Raju Marisiddaiah, Lewis P Rubin
β-carotene 15,15'-oxygenase (BCO1) catalyzes the first step in the conversion of dietary provitamin A carotenoids to vitamin A. This enzyme is expressed in a variety of developing and adult tissues, suggesting that its activity may regulate local retinoid synthesis. Vitamin A and related compounds (retinoids) are critical regulators of lung epithelial development, integrity, and injury repair. A balance between the actions of retinoids and glucocorticoids (GCs) promotes normal lung development and, in particular, alveolarization...
2017: PloS One
https://www.readbyqxmd.com/read/28729456/mechanistic-multi-tissue-modeling-of-gilz-regulation-integrating-circadian-gene-expression-with-receptor-mediated-corticosteroid-pharmacodynamics
#8
Vivaswath S Ayyar, Debra C DuBois, Richard R Almon, William J Jusko
The glucocorticoid-induced leucine zipper (GILZ) is an important mediator of anti-inflammatory corticosteroid action. The pharmacokinetic/pharmacodynamic/pharmacogenomic effects of acute and chronic methylprednisolone (MPL) dosing on the tissue-specific dynamics of GILZ expression were examined in rats. A mechanism-based model was developed to investigate and integrate the role of MPL and circadian rhythms on the transcriptional enhancement of GILZ in multiple tissues. Animals received a single 50 mg/kg intramuscular bolus or a seven-day 0...
July 20, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28729227/computational-and-experimental-prediction-of-molecules-involved-in-the-anti-melanoma-action-of-berberine
#9
Bin Liu, Xiu-Qiong Fu, Ting Li, Tao Su, Hui Guo, Pei-Li Zhu, Anfernee Kai-Wing Tse, Shi-Ming Liu, Zhi-Ling Yu
ETHNOPHARMACOLOGIC RELEVANCE: Berberine (BBR) is a naturally occurring alkaloid compound that can be found in Chinese medicinal herbs such as Rhizoma Coptidis and Phellodendri Cortex. These BBR containing herbs are commonly used by Chinese medicine doctors to treat cancers including melanoma. In this study, we explored proteins potentially involved in the anti-melanoma effects of BBR using an integrative computational and experimental approach. MATERIALS AND METHODS: Target proteins of BBR were predicted using the reverse pharmacophore screening, molecular docking and molecular dynamics...
July 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28729116/convergence-of-glycogen-synthase-kinase-3%C3%AE-and-gr-signaling-in-response-to-fluoxetine-treatment-in-chronically-stressed-female-and-male-rats
#10
Milos Mitic, Zeljka Brkic, Iva Lukic, Miroslav Adzic
Accumulating evidence strongly suggest that impaired glucocorticoid receptor (GR) signaling is involved in stress-related mood disorders, and nominate GR as a potential target for antidepressants (ADs). It is known that different classes of ADs affects the GR action via modifying its phosphorylation, while the mechanism through which ADs alter GR phosphorylation targeted by GSK3β, a kinase modulated via serotonin neurotransmission, are unclear. On this basis, we investigated whether GSK3β-GR signaling could be a convergence point of fluoxetine action on brain function and behavior, by examining its effect on GSK3β targeted-GR phosphorylation on threonine 171 (pGR171), and expression of GR-regulated genes in the hippocampus of female and male rats exposed to chronic isolation stress...
July 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28728455/asparagine-preserves-intestinal-barrier-function-from-lps-induced-injury-and-regulates-crf-crfr-signaling-pathway
#11
Huiling Zhu, Dingan Pi, Weibo Leng, Xiuying Wang, Chien-An Andy Hu, Yongqing Hou, Jianglin Xiong, Chunwei Wang, Qin Qin, Yulan Liu
Stress causes intestinal inflammation and barrier dysfunction. Corticotrophin-releasing factor (CRF)/CRF receptor (CRFR) signaling pathway has been shown to be important for stress-induced intestinal mucosal alteration. L-Asparagine (ASN) is a powerful stimulator of ornithine decarboxylase and cell proliferation in a variety of cell types, including colonic cells. In the present study, we investigated whether dietary ASN supplementation could alleviate the damage of intestinal barrier function caused by LPS through modulation of CRF/CRFR signaling pathway...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28727940/intestinal-transit-time-and-cortisol-mediated-stress-in-zebrafish
#12
Clayton Brady, Maxwell Denora, Ian Shannon, Karl J Clark, Adam Rich
Intestinal motility, the spontaneous and rhythmic smooth muscle contraction, is a complex process that is regulated by overlapping and redundant regulatory mechanisms. Primary regulators intrinsic to the gastrointestinal tract include interstitial cells of Cajal, enteric neurons, and smooth muscle cells. Extrinsic primary regulators include the autonomic nervous system, immune system, and the endocrine system. Due to this complexity, a reductionist approach may be inappropriate if the ultimate goal is to understand motility regulation in vivo...
July 20, 2017: Zebrafish
https://www.readbyqxmd.com/read/28727040/genome-wide-association-studies-and-meta-analysis-reveal-novel-quantitative-trait-loci-and-pleiotropic-loci-for-swine-head-related-traits
#13
H Chen, T Huang, Z Zhang, B Yang, C Jiang, J Wu, Z Zhou, H Zheng, W Xin, M Huang, M Zhang, C Chen, J Ren, H Ai, L Huang
The pig is an important domestic animal that provides a larger amount of meat and serves as a biomedical animal model for human. Head and facial features are closely linked to identity recognition in mammal communication. To uncover the genetic architecture of swine head and facial features, we constructed 5 experimental pig populations and accurately measured 10 traits related to head and facial features, for which genome-wide association studies and meta-analysis were later carried out. As a result, we identified a total of 24 loci harboring 437 SNP on 8 swine chromosomes (SSC) that surpassed suggestively significant levels, of which 17 loci on 6 chromosomes exceeded the 5% genome-wide significance thresholds...
June 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28726773/t-cell-autonomous-death-induced-by-regeneration-of-inert-glucocorticoid-metabolites
#14
Lourdes Rocamora-Reverte, Holger M Reichardt, Andreas Villunger, GJan Wiegers
Glucocorticoids (GC) are essential regulators of T-cell development and function. Activation of the immune system increases systemic adrenal-derived GC levels which downregulate immune activity as part of a negative feedback control system. Increasing evidence shows, however, that GC can also be derived from extra-adrenal sources such as the thymus or intestine, thus providing local control of GC-mediated effects. The thymus reportedly produces GC, but whether thymic epithelial cells or thymocytes produce GC acting either in an autocrine or paracrine fashion is not clear...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28720427/the-challenges-and-promise-of-targeting-the-liver-x-receptors-for-treatment-of-inflammatory-disease
#15
REVIEW
Michael B Fessler
The Liver X Receptors (LXRs) are oxysterol-activated transcription factors that upregulate a suite of genes that together promote coordinated mobilization of excess cholesterol from cells and from the body. The LXRs, like other nuclear receptors, are anti-inflammatory, inhibiting signal-dependent induction of pro-inflammatory genes by nuclear factor-κB, activating protein-1, and other transcription factors. Synthetic LXR agonists have been shown to ameliorate atherosclerosis and a wide range of inflammatory disorders in preclinical animal models...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28717104/dexamethasone-induced-hepatomegaly-and-steatosis-in-larval-zebrafish
#16
Guojun Yin, Liping Cao, Jinliang Du, Rui Jia, Takio Kitazawa, Akira Kubota, Hiroki Teraoka
Fish hepatobiliary syndrome, characterized by hepatomegaly and fatty liver, has been frequently reported in many cultured fish species and has caused a dramatic economic loss in China. Glucocorticoids are thought to be important non-nutritional factors for hepatomegaly and fatty liver development. In the present study, a dexamethasone-induced zebrafish model of fatty liver and hepatomegaly was established, and the role of glucocorticoid receptor (GR) in the development of hepatomegaly and fatty liver was investigated using developing zebrafish...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28716937/altered-metabotropic-glutamate-receptor-5-markers-in-ptsd-in-vivo-and-postmortem-evidence
#17
Sophie E Holmes, Matthew J Girgenti, Margaret T Davis, Robert H Pietrzak, Nicole DellaGioia, Nabeel Nabulsi, David Matuskey, Steven Southwick, Ronald S Duman, Richard E Carson, John H Krystal, Irina Esterlis
Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used [(18)F]FPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28714605/epigenetic-alterations-and-prenatal-maternal-depression
#18
REVIEW
Zsofia Nemoda, Moshe Szyf
Major depressive disorder of the mother affects 6 to 17% of pregnancies worldwide and can lead to negative outcomes, such as preterm delivery and later mental health problems of the child. It has been proposed that developmental programming has long-lasting effects in the offspring that might be mediated by epigenetic mechanisms, such as DNA methylation. Altered stress regulation or impaired immunological function of the mother can potentially affect DNA methylation processes of the fetus, changing gene expression levels in utero...
July 17, 2017: Birth defects research
https://www.readbyqxmd.com/read/28713045/cortisol-elevation-post-hatch-affects-behavioural-performance-in-zebrafish-larvae
#19
Carol Best, Mathilakath M Vijayan
Maternal cortisol is essential for cortisol stress axis development and de novo production of this steroid commences only after hatch in zebrafish (Danio rerio). However, very little is known about the effect of elevated cortisol levels, during the critical period of stress axis activation, on larval performance. We tested the hypothesis that elevated cortisol levels post-hatch affect behavioural performance and this is mediated by glucocorticoid receptor activation in zebrafish larvae. The behavioural response included measuring larval activity in response to alternating light and dark cycles, as well as thigmotaxis...
July 13, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28711928/dexamethasone-affects-cell-growth-apoptosis-chemosensitivity-of-colon-cancer-via-glucocorticoid-receptor-%C3%AE-nf-%C3%AE%C2%BAb
#20
Jianming He, Jinming Zhou, Weiwen Yang, Qi Zhou, Xi Liang, Xueli Pang, Jianjun Li, Feng Pan, Houjie Liang
Glucocorticoids are effective to treat lymphoma and leukemia. Their effect in colon cancer remains far from clear. Here, we found that glucocorticoid receptor (GR) α protein level was dramatically lower in colon cancer than in lymphoma. Colon cell lines LoVo and HCT116 were GRα-rich and GRα was not detectable in HT29 or SW480. Dexamethasone significantly inhibited cell growth of GRα-rich cell lines and did not significantly affect GRα-negative cell lines. Dexamethasone induced apoptosis and increased chemosensitivity of GRα-rich cell lines...
June 28, 2017: Oncotarget
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