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https://www.readbyqxmd.com/read/28806736/unravelling-the-interplay-of-sphingolipids-and-tgf-%C3%AE-signaling-in-the-human-corneal-stroma
#1
Sarah E Nicholas, Tyler G Rowsey, Shrestha Priyadarsini, Nawajes A Mandal, Dimitrios Karamichos
PURPOSE: To delineate the role of Sphingolipids (SPLs) in the human cornea and their cross-talks with transforming growth factor beta (TGF-β) in order to develop novel, non-invasive therapies. METHODS: Human corneal fibroblasts (HCFs) were harvested from healthy donors, stimulated with Vitamin C to promote extracellular matrix assembly, treated with exogenous sphingosine-1-phosphate (S1P) or sphingosine kinase inhibitor 2 (SPHK I2) and isolated after 4 weeks for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28806404/rig-i-and-il-6-are-negative-feedback-regulators-of-sting-induced-by-double-stranded-dna
#2
Xueling Wu, Jun Yang, Tao Na, Kehua Zhang, Andrew M Davidoff, Bao-Zhu Yuan, Youchun Wang
The stimulator of interferon genes (STING) protein has emerged as a critical signal transduction molecule in the innate immune response. Sustained activation of the STING signaling induced by cytosolic DNA has been considered to be the cause of a variety of autoimmune diseases characterized by uncontrolled inflammation. Therefore, it is important to understand the molecular basis of the regulation of STING signaling pathway. Here we demonstrate that the STING protein undergoes a proteasome-mediated degradation in human diploid cell (HDC) lines including MRC-5 following the transfection of double-stranded DNA (dsDNA)...
2017: PloS One
https://www.readbyqxmd.com/read/28806392/kaempferol-alleviates-the-interleukin-1%C3%AE-induced-inflammation-in-rat-osteoarthritis-chondrocytes-via-suppression-of-nf-%C3%AE%C2%BAb
#3
Zhengling Zhuang, Guangqun Ye, Bin Huang
BACKGROUND This study was designed to examine the anti-inflammatory and anti-osteoarthritis (OA) effects of kaempferol in rat articular chondrocytes stimulated with interleukin-1β. MATERIAL AND METHODS Rat articular chondrocytes cultures were treated with interleukin-1β alone or with kaempferol (25, 50, 100, and 200 μM) and interleukin-1β. The effect of kaempferol on chondrocyte cells viability was measured by MTT assay. The effect on prostaglandin E2 (PGE2) and nitric oxide (NO) level were also assessed using the ELISA and Griess reagent, respectively, for kaempferol activity...
August 14, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28805972/in-vitro-pharmacological-characterization-of-a-novel-unbiased-nop-receptor-selective-nonpeptide-agonist-at-403
#4
Federica Ferrari, Davide Malfacini, Blair V Journigan, Mark F Bird, Claudio Trapella, Remo Guerrini, David G Lambert, Girolamo Calo', Nurulain T Zaveri
Nociceptin/orphanin FQ (N/OFQ) regulates several biological functions via selective activation of the N/OFQ receptor (NOP), a member of the opioid receptor family. We recently identified a new high affinity and highly selective NOP agonist AT-403. In this study, we characterized the functional profile of AT-403 and compared it to other known nonpeptide NOP agonists Ro 65-6570, Ro 2q, SCH-221510, MCOPPB, AT-202 and SCH-486757, using the following assays: GTPγ[(35) S] stimulated binding, calcium mobilization assay in cells-expressing human NOP or classical opioid receptors and chimeric G proteins, bioluminescence resonance energy transfer (BRET) based assay for studying NOP receptor interaction with G protein and arrestin, and the electrically stimulated mouse vas deferens bioassay...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28804863/personalised-immunomodulating-treatments-for-graves-disease-fact-or-fiction
#5
Tristan Mirko Struja, Alexander Kutz, Stefan Fischli, Christian Meier, Beat Müller, Philipp Schütz
Although Graves' disease has been recognised for more than 100 years, its physiopathological mechanisms are incompletely understood. Treatment strategies today mainly focus on suppression of thyroid hormone production by use of antithyroid drugs or radio-iodine, but neglect the underlying immunological mechanisms. Although Graves' disease is often seen as a prototype for an autoimmune mechanism, it is more likely to be a heterogeneous syndrome showing characteristics of both autoimmunity and immunodeficiency...
August 14, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28803443/solasodine-inhibits-human-colorectal-cancer-cells-via-suppression-of-akt-gsk-3%C3%AE-%C3%AE-catenin-pathway
#6
Yu-Wen Zhuang, Cun-En Wu, Jin-Yong Zhou, Xu Chen, Jian Wu, Shan Jiang, Hai-Yan Peng, Xi Zou, Jia-Yun Liu, Da-Peng Wu, Tao Gong, Ming-Hao Qi, Tian Xue, Shen-Lin Liu, Hui Cai
Solasodine is a main active component isolated from Solanum incanum L, who performs a wide range of functions containing anti-oxidant, anti-infection and neurogenesis promotion. In this study, we explored the influence of solasodine on three types of human colorectal cancer (CRC) cell lines. The consequences displayed that solasodine apparently prohibited CRC cell proliferation dose- and time-dependently and impeded CRC cell motility by downregulating Matrix metalloprotease (MMPs). Besides, solasodine was investigated to fuel caspase-cascade reaction and increase the ratio between Bax and Bcl-2 so as to induce CRC cell apoptosis...
August 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28803174/intraoperative-vascular-neuromonitoring-in-patients-with-subarachnoid-hemorrhage-a-pilot-study-using-combined-laser-doppler-spectrophotometry
#7
Emilija Schmitz, Barbara Bischoff, Dennis Wolf, Hubert Schmitt, Ilker Y Eyupoglu, Karl Roessler, Michael Buchfelder, Björn Sommer
OBJECTIVE: Intraoperative monitoring of cerebral microcirculation in patients with subarachnoid hemorrhage (SAH) may predict the postoperative neurological outcome. In this pilot study, we examined the value of a novel non-invasive real-time measurement technique to detect changes in local microcirculation. METHODS: We used the laser-Doppler spectrophotometry system "Oxygen-to-see(O2C)" in 14 patients with SAH Hunt & Hess grade 2 to 5, who underwent microsurgical clipping of cerebral aneurysms...
August 9, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28803066/a-novel-ripk1-inhibitor-that-prevents-retinal-degeneration-in-a-rat-glaucoma-model
#8
Yun-Ju Do, Jee-Won Sul, Ki-Hong Jang, Nam Sook Kang, Young-Hoon Kim, Young-Gwan Kim, Eunhee Kim
In glaucoma, retinal ganglion cells (RGCs) are exposed to ischemic stress with elevation of the intraocular pressure and are subsequently lost. Necroptosis, a type of regulated necrosis, is known to play a pivotal role in this loss. We observed that receptor-interacting protein kinase 1 (RIPK1), the key player of necroptosis, was activated by diverse ischemic stresses, including TCZ, chemical hypoxia (CH), and oxygen glucose deprivation (OGD). In this study, we introduce a RIPK1-inhibitory compound (RIC) with a novel scaffold...
August 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28802833/new-pro-resolving-n-3-mediators-bridge-resolution-of-infectious-inflammation-to-tissue-regeneration
#9
REVIEW
Charles N Serhan, Nan Chiang, Jesmond Dalli
While protective, the acute inflammatory response when uncontrolled can lead to further tissue damage and chronic inflammation that is now widely recognized to play important roles in many commonly occurring diseases, such as cardiovascular disease, neurodegenerative diseases, metabolic syndrome, and many other diseases of significant public health concern. The ideal response to initial challenges of the host is complete resolution of the acute inflammatory response, which is now recognized to be a biosynthetically active process governed by specialized pro-resolving mediators (SPM)...
August 9, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28802127/investigations-on-the-molecular-mode-of-action-of-the-novel-immunostimulator-zelnate-activation-of-the-cgas-sting-pathway-in-mammalian-cells
#10
Thomas Ilg
Bovine respiratory disease (BRD) is usually prevented or treated with vaccines and/or antibiotics. The use of antibiotics is, however, of concern due to the potential promotion of microbial resistance and the occurrence of residues. Recently an alternative aid in the treatment of BRD, the cationic lipid/bacterial plasmid DNA liposome-based immunomodulator ZelNate, has entered the veterinary market. In the present study, we provide data on the molecular mode of action of ZelNate. Despite the presence of numerous non-methylated CpG motifs in its plasmid DNA, ZelNate proved to be inactive on human and mouse toll-like receptor 9 (TLR9) in cell culture, in both recombinant and natural cellular receptor settings...
August 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28801620/a-novel-aldosterone-antagonist-limits-renal-injury-in-5-6-nephrectomy
#11
Clarice K Fujihara, M C Kowala, M D Breyer, Claudia R Sena, Mariliza V Rodrigues, Simone C A Arias, Camilla Fanelli, Denise M Malheiros, P K Jadhav, Chahrzad Montrose-Rafizadeh, Jose E Krieger, Roberto Zatz
Aldosterone antagonists slow the progression of chronic kidney disease (CKD), but their use is limited by hyperkalemia, especially when associated with RAS inhibitors. We examined the renoprotective effects of Ly, a novel non-steroidal mineralocorticoid receptor (MR) blocker, through two experimental protocols: In Protocol 1, male Munich-Wistar rats underwent 5/6 renal ablation (Nx), being divided into: Nx+V, receiving vehicle, Nx+Eple, given eplerenone, 150 mg/kg/day, and Nx+Ly, given Ly, 20 mg/kg/day...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801552/gene-location-expression-and-function-of-fndc5-in-meishan-pigs
#12
Chunbo Cai, Gaojun Xiao, Lili Qian, Shengwang Jiang, Biao Li, Shanshan Xie, Ting Gao, Xiaorong An, Wentao Cui, Kui Li
Irisin is a new muscular regulatory factor that is generated by the cleavage of its precursor protein fibronectin type III domain-containing protein 5 (FNDC5). Irisin promotes fat consumption due to its stimulatory role in the browning of the adipocytes in mice. Currently, there is no report on FNDC5 functions in pigs as model animals. In this study, we investigated the expression patterns and functions of FNDC5 in Meishan pigs. Our results showed that FNDC5 gene in Meishan pigs contains five transcripts, all of which can be translated into functional intact irisin proteins...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801532/activation-of-nkx2-5-calr-p53-signaling-pathway-by-hyperglycemia-induces-cardiac-remodeling-and-dysfunction-in-adult-zebrafish
#13
Sun Yanyi, Wang Qiuyun, Fang Yuehua, Wu Chunfang, Lu Guoping, Chen Zhenyue
Hyperglycemia is an independent risk factor for diabetic cardiomyopathy in humans; however, the underlying mechanisms have not been thoroughly elucidated. Zebrafish (Danio rerio) was used in this study as a novel vertebrate model to explore the signaling pathways of human adult cardiomyopathy. Hyperglycemia was induced by alternately immersing adult zebrafish in a glucose solution or water. The hyperglycemic fish gradually exhibited some hallmarks of cardiomyopathy such as myocardial hypertrophy and apoptosis, myofibril loss, fetal gene reactivation, and severe arrhythmia...
August 11, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28801252/measuring-the-effects-of-attention-to-individual-fingertips-in-somatosensory-cortex-using-ultra-high-field-7t-fmri
#14
Alexander M Puckett, Saskia Bollmann, Markus Barth, Ross Cunnington
Attention to sensory information has been shown to modulate the neuronal processing of that information. For example, visuospatial attention acts by modulating responses at retinotopically appropriate regions of visual cortex (Puckett and DeYoe, 2015; Tootell et al. 1998). Much less, however, is known about the neuronal processing associated with attending to other modalities of sensory information. One reason for this is that visual cortex is relatively large, and therefore easier to access non-invasively in humans using tools such as functional magnetic resonance imaging (fMRI)...
August 8, 2017: NeuroImage
https://www.readbyqxmd.com/read/28801250/decoding-fmri-activity-in-the-time-domain-improves-classification-performance
#15
REVIEW
João Loula, Gaël Varoquaux, Bertrand Thirion
Most current functional Magnetic Resonance Imaging (fMRI) decoding analyses rely on statistical summaries of the data resulting from a deconvolution approach: each stimulation event is associated with a brain response. This standard approach leads to simple learning procedures, yet it is ill-suited for decoding events with short inter-stimulus intervals. In order to overcome this issue, we propose a novel framework that separates the spatial and temporal components of the prediction by decoding the fMRI time-series continuously, i...
August 8, 2017: NeuroImage
https://www.readbyqxmd.com/read/28800474/nps-2143-a-selective-calcium-sensing-receptor-antagonist-inhibits-lipopolysaccharide-induced-pulmonary-inflammation
#16
Jae-Won Lee, Hyun Ah Park, Ok-Kyoung Kwon, Ji-Won Park, Gilhye Lee, Hee Jae Lee, Seung Jin Lee, Sei-Ryang Oh, Kyung-Seop Ahn
NPS 2143, a novel and selective antagonist of calcium-sensing receptor (CaSR) has been reported to possess anti-inflammatory activity. In the present study, we examined the protective effect of NPS 2143 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). NPS 2143 pretreatment significantly inhibited the influx of inflammatory cells and the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung of mice with LPS-induced ALI. NPS 2143 decreased the levels of neutrophil elastase (NE) and protein concentration in the bronchoalveolar lavage fluid (BALF)...
August 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28800402/extracellular-matrix-cartilage-allograft-and-particulate-cartilage-allograft-for-osteochondral-lesions-of-the-knee-and-ankle-joints-a-systematic-review
#17
Dexter Seow, Youichi Yasui, Eoghan T Hurley, Andrew W Ross, Christopher D Murawski, Yoshiharu Shimozono, John G Kennedy
BACKGROUND: Extracellular matrix cartilage allografts (EMCAs) and particulate cartilage allografts (PCAs) are relatively new biologics that may improve the quality of cartilage regeneration after bone marrow stimulation. The increasing popularity of these novel biologics in the treatment of osteochondral lesions (OCLs) of the knee and ankle joints prompts a systematic evaluation of their efficacies. PURPOSE: The purpose of this systematic review was to clarify the effectiveness of EMCAs and PCAs on cartilage regeneration...
August 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28799896/neurosecretory-protein-gl-stimulates-food-intake-de-novo-lipogenesis-and-onset-of-obesity
#18
Eiko Iwakoshi-Ukena, Kenshiro Shikano, Kunihiro Kondo, Shusuke Taniuchi, Megumi Furumitsu, Yuta Ochi, Tsutomu Sasaki, Shiki Okamoto, George E Bentley, Lance J Kriegsfeld, Yasuhiko Minokoshi, Kazuyoshi Ukena
Mechanisms underlying the central regulation of food intake and fat accumulation are not fully understood. We found that neurosecretory protein GL (NPGL), a newly-identified neuropeptide, increased food intake and white adipose tissue (WAT) in rats. NPGL-precursor gene overexpression in the hypothalamus caused increases in food intake, WAT, body mass, and circulating insulin when fed a high calorie diet. Intracerebroventricular administration of NPGL induced de novo lipogenesis in WAT, increased insulin, and it selectively induced carbohydrate intake...
August 11, 2017: ELife
https://www.readbyqxmd.com/read/28799616/quantitative-investigation-of-mda-mb-231-breast-cancer-cell-motility-dependence-on-epidermal-growth-factor-concentration-and-its-gradient
#19
Tanzila Islam, Haluk Resat
Enhanced cell motility is one of the primary features of cancer. Accumulated evidence demonstrates that Epidermal Growth Factor Receptor (EGFR) mediated pathways play an important role in breast cancer cell proliferation and migration. We have quantified the MDA-MB-231 breast cancer cell migration in response to the stimulation of EGFR pathways with their ligand EGF to determine how the cell motility of MDA-MB-231 cells depends on the ligand concentration and gradient. Analysis at the single cell level combined with mathematical modeling and the ability to vary the ligand concentration and gradients locally using microfluidic devices allowed us to separate the unique contributions of ligand concentration and ligand gradient to cell motility...
August 11, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28798726/systems-biology-analysis-of-temporal-in-vivo-brucella-melitensis-and-bovine-transcriptomes-predicts-host-pathogen-protein-protein-interactions
#20
Carlos A Rossetti, Kenneth L Drake, Sara D Lawhon, Jairo S Nunes, Tamara Gull, Sangeeta Khare, Leslie G Adams
To date, fewer than 200 gene-products have been identified as Brucella virulence factors, and most were characterized individually without considering how they are temporally and coordinately expressed or secreted during the infection process. Here, we describe and analyze the in vivo temporal transcriptional profile of Brucella melitensis during the initial 4 h interaction with cattle. Pathway analysis revealed an activation of the "Two component system" providing evidence that the in vivo Brucella sense and actively regulate their metabolism through the transition to an intracellular lifestyle...
2017: Frontiers in Microbiology
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