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https://www.readbyqxmd.com/read/28430654/alpha-ketoglutarate-suppresses-the-nf-%C3%AE%C2%BAb-mediated-inflammatory-pathway-and-enhances-the-pxr-regulated-detoxification-pathway
#1
Liuqin He, Huan Li, Niu Huang, Xihong Zhou, Junquan Tian, Tiejun Li, Jing Wu, Yanan Tian, Yulong Yin, Kang Yao
Alpha-ketoglutarate (AKG) is a critical nutritional factor in the maintenance of intestinal homeostasis. However, the relative mechanism of AKG has not been well understood. It was recently shown that the interaction between nuclear factor kappa B (NF-κB)-mediated inflammatory pathway and pregnane X receptor (PXR)-regulated detoxification pathway is a check and balance mechanism for keeping the homeostatic state of the intestine, preventing the onset of intestinal inflammation which may lead to cancer. In the current study we used lipopolysaccharide (LPS)-challenged piglet and intestinal porcine epithelial cells-J2 models to investigate the effects of dietary AKG supplementation on the intestinal immune system and PXR regulated target expression...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430652/inflammatory-factor-tnf-%C3%AE-promotes-the-growth-of-breast-cancer-via-the-positive-feedback-loop-of-tnfr1-nf-%C3%AE%C2%BAb-and-or-p38-p-stat3-hbxip-tnfr1
#2
Xiaoli Cai, Can Cao, Jiong Li, Fuquan Chen, Shuqin Zhang, Bowen Liu, Weiying Zhang, Xiaodong Zhang, Lihong Ye
In the connection between inflammation and cancer development, tumor necrosis factor-alpha (TNF-α) contributes to the tumorigenesis. However, the underlying mechanism remains poorly understood. In this study, we report that TNF-α enhances the growth of breast cancer through up-regulation of oncoprotein hepatitis B X-interacting protein (HBXIP). Our data showed that the levels of TNF-α were positively related to those of HBXIP in clinical breast cancer tissues. Moreover, TNF-α could up-regulate HBXIP in breast cancer cells...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425121/role-of-the-dynorphin-kappa-opioid-receptor-system-in-the-motivational-effects-of-ethanol
#3
Rachel I Anderson, Howard C Becker
Evidence has demonstrated that dynorphin (DYN) and the kappa opioid receptor (KOR) system contribute to various psychiatric disorders, including anxiety, depression, and addiction. More recently, this endogenous opioid system has received increased attention as a potential therapeutic target for treating alcohol use disorders. In this review, we provide an overview and synthesis of preclinical studies examining the influence of alcohol (ethanol) exposure on DYN/KOR expression and function, as well as studies examining the effects of DYN/KOR manipulation on ethanol's rewarding and aversive properties...
April 20, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28424593/phospholipase-a2-of-peroxiredoxin-6-plays-a-critical-role-in-cerebral-ischemia-reperfusion-inflammatory-injury
#4
Yu Shanshan, Jiang Beibei, Tan Li, Gao Minna, Lei Shipeng, Peng Li, Zhao Yong
Microglia-mediated inflammation is an important step in the progression of cerebral ischemia/reperfusion injury and the associated production of receptors of immunomoudulation, including Toll-like receptors (TLRs). Peroxiredoxin 6 (Prdx6) has been demonstrated as the endogenous antioxidant protein for its peroxidase properties. However, the role of the independent phospholipase A2 (iPLA2) activity of Prdx6 in stroke has not been well studied. In this study, we evaluated whether blocking the calcium-iPLA2 activity of Prdx6 using siRNA and inhibitors (1-hexadecyl-3-(trifluoroethgl)-sn-glycerol-2 phosphomethanol, MJ33) would have a critical effect on inflammatory brain damage...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28423553/low-vitamin-d-status-is-associated-with-inflammation-in-patients-with-prostate-cancer
#5
Dong-Dong Xie, Yuan-Hua Chen, Shen Xu, Cheng Zhang, Da-Ming Wang, Hua Wang, Lei Chen, Zhi-Hui Zhang, Mi-Zhen Xia, De-Xiang Xu, De-Xin Yu
Vitamin D deficiency has been associated with increased risks of prostate cancer. Nevertheless, the mechanisms remain unclear. The aim of this study was to analyze the association among prostate cancer, vitamin D status and inflammation. Sixty patients with newly diagnosed prostate cancer and 120 age-matched controls were recruited for this study. Vitamin D status was evaluated and serum inflammatory molecules were measured. Serum 25-(OH)D was lower in patients with prostate cancer. Moreover, serum 25(OH)D was lower in patients with severe prostate cancer than patients with mild and moderate prostate cancer...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422768/mechanisms-involved-in-secondary-cardiac-dysfunction-in-animal-models-of-trauma-and-haemorrhagic-shock
#6
Nick M Wilson, Johanna Wall, Veena Naganathar, Karim Brohi, Henry D De'Ath
Clinical evidence reveals the existence of a trauma induced secondary cardiac injury (TISCI) which is associated with poor patient outcomes. The mechanisms leading to TISCI in injured patients are uncertain. Conversely, animal models of trauma haemorrhage have repeatedly demonstrated significant cardiac dysfunction following injury, and highlighted mechanisms through which this might occur. The aim of this review was to provide an overview of the animal studies describing TISCI and its pathophysiology.Basic science models of trauma show evidence of innate immune system activation via Toll-Iike receptors (TLRs), the exact protagonists of which remain unclear...
April 18, 2017: Shock
https://www.readbyqxmd.com/read/28421819/il-4-induces-the-il17rb-gene-transcription-in-monocytic-cells-with-coordinate-autocrine-il-25-signaling
#7
Nathaniel M Weathington, Shreya S Kanth, Qiaoke Gong, James Londino, Akihiko Hoji, Mauricio Rojas, John Trudeau, Sally Wenzel, Rama K Mallampalli
IL-25 and IL-4 signaling in the setting of infection or allergic responses can drive Type 2 inflammation. IL-25 requires the IL-17 receptor B (IL-17Rb) to mediate signaling through nuclear factor kappa B transcriptional activation. Despite the known coexistence of these two cytokines in the Type 2 inflammatory environment, collaborative signaling between the IL-4 and IL-25 axes is poorly explored. Here we demonstrate IL-4 induction of both IL-25 and IL-17Rb protein in human lung tissue culture, primary alveolar macrophages, and the THP-1 monocytic cell line...
April 19, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28421541/systemic-inflammation-as-a-driver-of-brain-injury-the-astrocyte-as-an-emerging-player
#8
Bruna Bellaver, João Paulo Dos Santos, Douglas Teixeira Leffa, Larissa Daniele Bobermin, Paola Haack Amaral Roppa, Iraci Lucena da Silva Torres, Carlos-Alberto Gonçalves, Diogo Onofre Souza, André Quincozes-Santos
Severe systemic inflammation has strong effects on brain functions, promoting permanent neurocognitive dysfunction and high mortality rates. Additionally, hippocampal damage seems to be directly involved in this process and astrocytes play an important role in neuroinflammation and in the neuroimmune response. However, the contribution of the astrocytes to the pathology of acute brain dysfunction is not well understood. Recently, our group established a protocol for obtaining astrocyte cultures from mature brain to allow the characterization of these cells and their functions under pathologic conditions...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28421075/activation-of-adhesion-gpcr-emr2-adgre2-induces-macrophage-differentiation-and-inflammatory-responses-via-g%C3%AE-16-akt-mapk-nf-%C3%AE%C2%BAb-signaling-pathways
#9
Kuan-Yu I, Yi-Shu Huang, Ching-Hsun Hu, Wen-Yi Tseng, Chia-Hsin Cheng, Martin Stacey, Siamon Gordon, Gin-Wen Chang, Hsi-Hsien Lin
EMR2/ADGRE2 is a human myeloid-restricted adhesion G protein-coupled receptor critically implicated in vibratory urticaria, a rare type of allergy caused by vibration-induced mast cell activation. In addition, EMR2 is also highly expressed by monocyte/macrophages and has been linked to neutrophil migration and activation. Despite these findings, little is known of EMR2-mediated signaling and its role in myeloid biology. In this report, we show that activation of EMR2 via a receptor-specific monoclonal antibody promotes the differentiation of human THP-1 monocytic cell line and induces the expression of pro-inflammatory mediators, including IL-8, TNF-α, and MMP-9...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28420351/prognostic-significance-of-trail-r3-and-ccr-2-expression-in-tumor-epithelial-cells-of-patients-with-early-breast-cancer
#10
Vivian Labovsky, Leandro Marcelo Martinez, Kevin Mauro Davies, María de Luján Calcagno, Hernán García-Rivello, Alejandra Wernicke, Leonardo Feldman, Ayelén Matas, María Belén Giorello, Francisco Raúl Borzone, Hosoon Choi, Scott C Howard, Norma Alejandra Chasseing
BACKGROUND: Tumor epithelial cells (TEpCs) and spindle-shaped stromal cells, not associated with the vasculature, of patients with early breast cancer express osteoprotegerin (OPG), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), receptor activator of nuclear factor kappa B ligand, stromal cell derived factor-1, interleukin-6, macrophage colony stimulating factor, chemokine (C-C motif) ligand-2 (CCL-2) and their receptors at significantly higher levels compared with non-neoplastic breast tissues...
April 18, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28416991/can-denosumab-be-a-substitute-competitor-or-complement-to-bisphosphonates
#11
REVIEW
Su Young Kim, Hwoe Gyeong Ok, Christof Birkenmaier, Kyung Hoon Kim
Osteoblasts, originating from mesenchymal cells, make the receptor activator of the nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in order to control differentiation of activated osteoclasts, originating from hematopoietic stem cells. When the RANKL binds to the RANK of the pre-osteoclasts or mature osteoclasts, bone resorption increases. On the contrary, when OPG binds to the RANK, bone resorption decreases. Denosumab (AMG 162), like OPG (a decoy receptor), binds to the RANKL, and reduces binding between the RANK and the RANKL resulting in inhibition of osteoclastogenesis and reduction of bone resorption...
April 2017: Korean Journal of Pain
https://www.readbyqxmd.com/read/28415742/androgen-receptor-amplification-is-concordant-between-circulating-tumor-cells-and-biopsies-from-men-undergoing-treatment-for-metastatic-castration-resistant-prostate-cancer
#12
Jennifer Podolak, Kristi Eilers, Timothy Newby, Rachel Slottke, Erin Tucker, Susan B Olson, Hui-Wen Lue, Jack Youngren, Rahul Aggarwal, Eric J Small, Julie N Graff, Joshi J Alumkal, Tomasz M Beer, George V Thomas
Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH)...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414795/negative-feedback-loop-of-bone-resorption-by-nfatc1-dependent-induction-of-cadm1
#13
Shinya Nakamura, Takuma Koyama, Naohiro Izawa, Seitaro Nomura, Takanori Fujita, Yasunori Omata, Takashi Minami, Morio Matsumoto, Masaya Nakamura, Eriko Fujita-Jimbo, Takashi Momoi, Takeshi Miyamoto, Hiroyuki Aburatani, Sakae Tanaka
Trimethylation of histone H3 lysine 4 and lysine 27 (H3K4me3 and H3K27me3) at gene promoter regions critically regulates gene expression. Key developmental genes tend to exhibit changes in histone modification patterns from the H3K4me3/H3K27me3 bivalent pattern to the H3K4me3 monovalent pattern. Using comprehensive chromatin immunoprecipitation followed by sequencing in bone marrow-derived macrophages (BMMs) and mature osteoclasts, we found that cell surface adhesion molecule 1 (Cadm1) is a direct target of nuclear factor of activated T cells 1 (NFATc1) and exhibits a bivalent histone pattern in BMMs and a monovalent pattern in osteoclasts...
2017: PloS One
https://www.readbyqxmd.com/read/28414309/tumor-derived-fibulin-3-activates-pro-invasive-nf-%C3%AE%C2%BAb-signaling-in-glioblastoma-cells-and-their-microenvironment
#14
M S Nandhu, A Kwiatkowska, V Bhaskaran, J Hayes, B Hu, M S Viapiano
Molecular profiling of glioblastomas has revealed the presence of key signaling hubs that contribute to tumor progression and acquisition of resistance. One of these main signaling mechanisms is the nuclear factor-kappa B (NF-κB) pathway, which integrates multiple extracellular signals into transcriptional programs for tumor growth, invasion and maintenance of the tumor-initiating population. We show here that an extracellular protein released by glioblastoma cells, fibulin-3, drives oncogenic NF-κB in the tumor and increases NF-κB activation in peritumoral astrocytes...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28411440/tweak-fn14-promotes-pro-inflammatory-cytokine-secretion-in-hepatic-stellate-cells-via-nf-%C3%AE%C2%BAb-stat3-pathways
#15
Aixiu Wang, Feng Zhang, Hui Xu, Mingcui Xu, Yu Cao, Chen Wang, Yuanyuan Xu, Min Su, Ming Zhang, Yuzheng Zhuge
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) have been associated with liver disease. Hepatic stellate cells (HSCs) play a critical role in the hepatic wound-healing response after liver injury, but there is little information available on the role of the TWEAK/Fn14 pathway in human HSCs. In this study, we explored the role of TWEAK/Fn14 in activated human HSCs. The LX-2 cells were treated with TWEAK, and the expression of pro-inflammatory cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR)...
April 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28404943/melatonin-protects-against-blood-brain-barrier-damage-by-inhibiting-the-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway-after-lps-treatment-in-neonatal-rats
#16
Yingying Hu, Zhouguang Wang, Shulin Pan, Hongyu Zhang, Mingchu Fang, Huai Jiang, Hao Zhang, Zhengzheng Gao, Kebin Xu, Zhenmao Li, Jian Xiao, Zhenlang Lin
Hypoxic-ischemic and inflammatory (HII) induces the disruption of blood-brain barrier (BBB) which leads to inflammatory responses and neuronal cell death, resulting in brain secondary damage. Previous studies showed that melatonin produced potent neuroprotective effects in neonatal hypoxic-ischaemic models. However, the relationship between BBB disruption and melatonin in HII was still unclear. The present study therefore investigated the beneficial effects of melatonin on BBB after HII and the underlying mechanisms...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402252/constitutive-activation-of-kappa-opioid-receptors-at-ventral-tegmental-area-inhibitory-synapses-following-acute-stress
#17
Abigail M Polter, Kelsey Barcomb, Rudy W Chen, Paige M Dingess, Nicholas M Graziane, Travis E Brown, Julie A Kauer
Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress induces prolonged activation of κORs. This is mediated by activation of the receptor during the stressor followed by a persistent, ligand-independent constitutive activation of the κOR itself. This lasting change in function is not seen at κORs at neighboring excitatory synapses, suggesting distinct time courses and mechanisms of regulation of different subsets of κORs...
April 12, 2017: ELife
https://www.readbyqxmd.com/read/28401756/gpcr-activation-and-endocytosis-induced-by-a-2d-material-agonist
#18
Wei-Tao Dou, Ya Kong, Xiao-Peng He, Guo-Rong Chen, Yi Zang, Jia Li, He Tian
Agonist-induced activation and endocytosis of G protein-coupled receptors (GPCRs) are crucial for a number of physiological and pathological processes. However, tools that are available for probing GPCR endocytosis have been insufficient. Here, we developed a two-dimensional (2D) material agonist by supramolecular self-assembly between an endogenous agonist of κ-opioid receptor (KOR) and 2D molybdenum disulfide. The 2D material agonist has proven to be amenable for eliciting GPCR activation and endocytosis in cells stably expressing KOR rather than in those without KOR expression...
April 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28400633/new-targeted-treatments-for-cutaneous-t-cell-lymphomas
#19
Martine Bagot
Cutaneous T-cell lymphomas (CTCLs) represent a group of rare and heterogeneous diseases that are very difficult to treat at advanced stages. The development of monoclonal antibodies is a new hope for the treatment of these diseases. Alemtuzumab (Campath) is a humanized IgG1 kappa monoclonal antibody specific for CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may frequently induce long-term remissions in patients with Sezary syndrome but high-dose treatments lead to severe cytopenia, immune depletion, and opportunistic infections...
March 2017: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/28398106/interleukin-12-il-12-induces-receptor-activator-of-nuclear-factor-kappa-b-ligand-rankl-expression-by-human-periodontal-ligament-cells
#20
Benjar Issaranggun Na Ayuthaya, Vincent Everts, Prasit Pavasant
BACKGROUND: An increased level of the pro-inflammatory cytokine interleukin-12 (IL-12) correlates with the severity of periodontitis. Yet, a possible role of IL-12 in periodontal disease has not been clarified. The aim of this study was to investigate whether IL-12 affects the expression of receptor activator of nuclear factor kappa-B ligand (RANKL), a potent osteoclast-stimulating factor, by human periodontal ligament (hPDL) cells. METHODS: To determine the effect of IL-12, hPDL cells were incubated with recombinant human IL-12 (p70) in a dose- (0-10 ng/ml) and time-dependent manner...
March 3, 2017: Journal of Periodontology
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