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https://www.readbyqxmd.com/read/28096440/tnf-signaling-in-peritoneal-mesothelial-cells-pivotal-role-of-cflipl
#1
Willie M Lüdemann, Danijela Heide, Lars Kihm, Martin Zeier, Peter Scheurich, Vedat Schwenger, Julia Ranzinger
♦ Background: Peritoneal dialysis (PD) coincides with high concentrations of proinflammatory cytokines, such as tumor necrosis factor (TNF), in the peritoneal cavity. During treatment, chronic inflammatory processes lead to damage of the peritoneal membrane and a subsequent ultrafiltration failure. Human peritoneal mesothelial cells (HPMCs) play a central role as mediators and targets of PD-related inflammatory changes. Although TNF Receptor 1 (TNFR1) is expressed in high numbers on the cells, TNF-induced apoptosis is inhibited...
January 17, 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/28088788/dual-syk-jak-inhibition-overcomes-ibrutinib-resistance-in-chronic-lymphocytic-leukemia-cerdulatinib-but-not-ibrutinib-induces-apoptosis-of-tumor-cells-protected-by-the-microenvironment
#2
Ailin Guo, Pin Lu, Greg Coffey, Pamela Conley, Anjali Pandey, Y Lynn Wang
Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL. However, the drug, to a large extent, does not cause cell death directly and does not eradicate CLL malignant clones. Inability to eradicate CLL has fostered resistance generation. Once patients become resistant, they do poorly with a median survival of 3-4 months. Novel therapeutic strategies are needed to prevent resistance, improve treatment outcome and ultimately cure the disease. Herein, we explore dual targeting of the BCR and JAK-STAT pathways with a novel single agent, cerdulatinib, which selectively inhibits both SYK (a BCR component) and JAK kinases...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28078252/the-evaluation-of-the-effect-of-herbal-extract-on-osteoarthritis-in-vitro-and-in-vivo-study
#3
Jaeyong Kim, Siyoung Yang, Chul-Yung Choi
In this study, the anti-osteoarthritis effects of Cynanchum wilfordii, Phlomis umbrosa, and Angelica gigas extract (CPAE), observed and confirmed in previously clinical studies were further investigated by in vitro and in vivo studies. Anabolic biomarkers related to healthy cartilage maintenance, such as aggrecan, type II collagen α-1 (Col2a1), sex determining region Y-box-9 (Sox-9), and catabolic biomarkers related to osteoarthritis, such as cyclooxygenase-2 (Cox-2), matrix metalloproteinase-13 (Mmp13), and nuclear factor kappa-light-chain-enhancer of activated B cells (Nfκb), were evaluated by quantitative reverse transcriptase polymerase chain reaction and reporter gene assay...
December 2016: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/28077651/bromodomain-containing-4-brd4-couples-nf%C3%AE%C2%BAb-rela-with-airway-inflammation-and-the-irf-rig-i-amplification-loop-in-respiratory-syncytial-virus-infection
#4
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Roberto P Garofalo, Allan R Brasier
: The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to Respiratory Syncytial Virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NFκB/RelA. BRD4 is functionally required for expression of the NFκB-dependent inflammatory gene regulatory network (GRN), including the IFN Response Factor (IRFs)-1 and -7 that mediate a cross-talk pathway for RIG-I upregulation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077357/triglyceride-rich-lipoprotein-lipolysis-products-increase-blood-brain-barrier-transfer-coefficient-and-induce-astrocyte-lipid-droplets-and-cell-stress
#5
Linda L Lee, Hnin Hnin Aung, Dennis W Wilson, Steven E Anderson, John C Rutledge, Jennifer M Rutkowsky
Elevation of blood triglycerides, primarily as triglyceride-rich lipoproteins (TGRL), has been linked to cerebrovascular inflammation, vascular dementia, and Alzheimer's disease (AD). Brain microvascular endothelial cells and astrocytes, two cell components of the neurovascular unit, participate in controlling blood-brain barrier (BBB) permeability and regulating neurovascular unit homeostasis. Our studies showed that infusion of high physiological concentrations of TGRL lipolysis products (TGRL + lipoprotein lipase) activate and injure brain endothelial cells and transiently increases the BBB transfer coefficient (Ki=permeability x surface area/volume) in vivo...
January 11, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28077028/ferulic-acid-suppresses-expression-of-tryptophan-metabolic-key-enzyme-indoleamine-2-3-dioxygenase-via-nf%C3%AE%C2%BAb-and-p38-mapk-in-lipopolysaccharide-stimulated-microglial-cells
#6
Manami Koshiguchi, Hitoshi Komazaki, Shizuka Hirai, Yukari Egashira
Ferulic acid (FA) is a phenol compound found in plants that has anti-inflammatory properties. Indoleamine 2, 3-dioxygenase (IDO) is a tryptophan catabolic enzyme induced in immune cells, including glial cells, during inflammation. Enhanced IDO expression leads to reduced tryptophan levels and increased levels of toxic metabolites, including quinolinic acid. Therefore, inhibition of IDO expression may be effective in suppressing progression of neurodegenerative diseases. In this study, we examined the effect of FA in microglial cells on IDO expression levels and related inflammatory signal molecules...
January 12, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28069387/leptin-receptor-knockout-induced-depression-like-behaviors-and-attenuated-antidepressant-effects-of-exercise-are-associated-with-stat3-socs3-signaling
#7
Weina Liu, Jiatong Liu, Jie Xia, Xiangli Xue, Hongmei Wang, Zhengtang Qi, Liu Ji
Relatively little has been known about pathophysiological mechanisms contributing to the development of neuropsychiatric symptoms in the context of metabolic syndrome. Impaired leptin signaling activation in db/db mice has been proposed as a potential link between behavioral and metabolic disorders. Our previous studies have shown that exercise has the beneficial effects on a depression-like and insulin-resistant state in mice. The present study aimed to determine whether and how leptin receptor knockout (db/db) induces depression-like behaviors, and to identify the antidepressant effects of swimming exercise in db/db mice...
January 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28068431/cil-102-induced-cell-cycle-arrest-and-apoptosis-in-colorectal-cancer-cells-via-upregulation-of-p21-and-gadd45
#8
Wen-Shih Huang, Yi-Hung Kuo, Hsing-Chun Kuo, Meng-Chiao Hsieh, Cheng-Yi Huang, Ko-Chao Lee, Kam-Fai Lee, Chien-Heng Shen, Shui-Yi Tung, Chih-Chuan Teng
CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone) is a well-known, major active agent of the alkaloid derivative of Camptotheca acuminata with valuable biological properties, including anti-tumorigenic activity. In this study, we investigated the molecular mechanisms by which CIL-102 mediated the induction of cell death, and we performed cell cycle G2/M arrest to clarify molecular changes in colorectal cancer cells (CRC). Treatment of DLD-1 cells with CIL-102 resulted in triggering the extrinsic apoptosis pathway through the activation of Fas-L, caspase-8 and the induction of Bid cleavage and cytochrome c release in a time-dependent manner...
2017: PloS One
https://www.readbyqxmd.com/read/28066139/regulation-of-vascular-smooth-muscle-phenotype-by-cross-regulation-of-kr%C3%A3-ppel-like-factors
#9
Jung Min Ha, Sung Ji Yun, Seo Yeon Jin, Hye Sun Lee, Sun Ja Kim, Hwa Kyoung Shin, Sun Sik Bae
Regulation of vascular smooth muscle cell (VSMC) phenotype plays an essential role in many cardiovascular diseases. In the present study, we provide evidence that krüppel-like factor 8 (KLF8) is essential for tumor necrosis factor α (TNFα)-induced phenotypic conversion of VSMC obtained from thoracic aorta from 4-week-old SD rats. Stimulation of the contractile phenotype of VSMCs with TNFα significantly reduced the VSMC marker gene expression and KLF8. The gene expression of KLF8 was blocked by TNFα stimulation in an ERK-dependent manner...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28063927/deubiquitinase-usp12-promotes-lps-induced-macrophage-responses-through-inhibition-of-i%C3%AE%C2%BAb%C3%AE
#10
Tapan Kumar Singh Nayak, Neeraja P Alamuru-Yellapragada, Kishore V L Parsa
Post translational modifications, ubiquitination and its reversal by deubiquitination play an important role in regulating innate immune system. USP12 is a poorly studied deubiquitinase reported to regulate T-cell receptor signaling however the functional role of USP12 in macrophages, the principal architects of inflammation, is unknown. Thus, in this study we probed the involvement of USP12 in macrophage mediated inflammatory responses using bacterial endotoxin, LPS, as the model system. Here, we observed that the expression of USP12 was altered in time dependent manner in LPS stimulated RAW 264...
January 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28063919/proteomic-analysis-of-the-protective-effects-of-aqueous-bark-extract-of-terminalia-arjuna-roxb-on-isoproterenol-induced-cardiac-hypertrophy-in-rats
#11
Santosh Kumar, Md Jahangir Alam, Pankaj Prabhakar, Sayeed Ahmad, Subir K Maulik, Manish Sharma, Shyamal K Goswami
ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous bark extract of Terminalia arjuna (TA) has been in use as an ethnomedicine for cardiovascular ailments in the Indian subcontinent for centuries. Studies using hemodynamic, ROS scavenging and anti-inflammatory parameters in animal models have shown its anti-atherogenic, hypotensive, inotropic, anti-inflammatory effects. However, details analysis on its effects on established molecular and cell biological markers are a prerequisite for its wider acceptance to the medical community...
January 4, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28062921/targeted-deletion-of-traf2-allows-immunosuppression-free-islet-allograft-survival-in-mice
#12
Jeanette E Villanueva, Stacey N Walters, Mitsuru Saito, Elisabeth K Malle, Nathan W Zammit, Katherine A Watson, Robert Brink, Nicole L La Gruta, Stephen I Alexander, Shane T Grey
AIMS/HYPOTHESIS: Administration of anti-CD40 ligand (CD40L) antibodies has been reported to allow long-term islet allograft survival in non-human primates without the need for exogenous immunosuppression. However, the use of anti-CD40L antibodies was associated with thromboembolic complications. Targeting downstream intracellular components shared between CD40 and other TNF family co-stimulatory molecules could bypass these complications. TNF receptor associated factor 2 (TRAF2) integrates multiple TNF receptor family signalling pathways that are critical for T cell activation and may be a central node of alloimmune responses...
January 6, 2017: Diabetologia
https://www.readbyqxmd.com/read/28060735/the-natural-compound-fucoidan-from-new-zealand-undaria-pinnatifida-synergizes-with-the-erbb-inhibitor-lapatinib-enhancing-melanoma-growth-inhibition
#13
Varsha Thakur, Jun Lu, Giuseppe Roscilli, Luigi Aurisicchio, Manuela Cappelletti, Emiliano Pavoni, William Lindsey White, Barbara Bedogni
Melanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28057758/down-regulation-of-claudin-2-expression-and-proliferation-by-epigenetic-inhibitors-in-human-lung-adenocarcinoma-a549-cells
#14
Asami Hichino, Miki Okamoto, Saeko Taga, Risa Akizuki, Satoshi Endo, Toshiyuki Matsunaga, Akira Ikari
Claudin-2 is highly expressed in lung adenocarcinoma tissues and increases proliferation in adenocarcinoma cells. The chemicals which reduce claudin-2 expression may have anti-cancer effect, but such therapeutic medicines have not been developed. We found that azacitidine (AZA), a DNA methylation inhibitor, and trichostatin A (TSA) and sodium butyrate (NaB), histone deacetylase (HDAC) inhibitors, decrease claudin-2 levels. The effect of AZA was mediated by the inhibition of phosphorylated Akt and NFκB. LY-294002, an inhibitor of phosphatidyl inositol-3 kinase (PI3K), and BAY 11-7082, an NF-κB inhibitor, decreased claudin-2 levels...
January 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28056810/porphyromonas-gingivalis-activates-nf%C3%AE%C2%BAb-and-mapk-pathways-in-human-oral-epithelial-cells
#15
Sabine Groeger, Fabian Jarzina, Eugen Domann, Joerg Meyle
BACKGROUND: The bacterial biofilm at the gingival margin induces a host immune reaction. In this local inflammation epithelial cells defend the host against bacterial challenge. Porphyromonas gingivalis (P. gingivalis), a keystone pathogen, infects epithelial cells. The aim of this study was to investigate the activation of signaling cascades in primary epithelial cells and oral cancer cell lines by a profiler PCR array. RESULTS: After infection with P. gingivalis membranes the RNA of 16 to 33 of 84 key genes involved in the antibacterial immune response was up-regulated, amongst them were IKBKB (NF-κB signaling pathway), IRF5 (TLR signaling) and JUN, MAP2K4, MAPK14 and MAPK8 (MAPK pathway) in SCC-25 cells and IKBKB, IRF5, JUN, MAP2K4, MAPK14 and MAPK8 in PHGK...
January 5, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28056773/transcriptomic-analysis-of-human-norovirus-ns1-2-protein-highlights-a-multifunctional-role-in-murine-monocytes
#16
Zabeen Lateef, Gregory Gimenez, Estelle S Baker, Vernon K Ward
BACKGROUND: The GII.4 Sydney 2012 strain of human norovirus (HuNoV) is a pandemic strain that is responsible for the majority of norovirus outbreaks in healthcare settings. The function of the non-structural (NS)1-2 protein from HuNoV is unknown. RESULTS: In silico analysis of human norovirus NS1-2 protein showed that it shares features with the murine NS1-2 protein, including a disordered region, a transmembrane domain and H-box and NC sequence motifs. The proteins also contain caspase cleavage and phosphorylation sites, indicating that processing and phosphorylation may be a conserved feature of norovirus NS1-2 proteins...
January 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28051269/disturbed-endometrial-nf-%C3%AE%C2%BAb-expression-in-women-with-recurrent-implantation-failure
#17
A Ersahin, M Acet, T Acet, Y Yavuz
OBJECTIVE: This study was planned to investigate whether expression levels of endometrial NF-κB1 and NFκB p65 changes in women with recurrent implantation failure (RIF). PATIENTS AND METHODS: The study group consists of 30 RIF patients having at least three previous failed IVF cycles. The control group comprises of 30 patients having one or no previous failed attempt. Endometrial samples were obtained from all participants during hysteroscopy at the late follicular phase...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28041958/srebp1-contributes-to-resolution-of-pro-inflammatory-tlr4-signaling-by-reprogramming-fatty-acid-metabolism
#18
Yumiko Oishi, Nathanael J Spann, Verena M Link, Evan D Muse, Tobias Strid, Chantle Edillor, Matthew J Kolar, Takashi Matsuzaka, Sumio Hayakawa, Jenhan Tao, Minna U Kaikkonen, Aaron F Carlin, Michael T Lam, Ichiro Manabe, Hitoshi Shimano, Alan Saghatelian, Christopher K Glass
Macrophages play pivotal roles in both the induction and resolution phases of inflammatory processes. Macrophages have been shown to synthesize anti-inflammatory fatty acids in an LXR-dependent manner, but whether the production of these species contributes to the resolution phase of inflammatory responses has not been established. Here, we identify a biphasic program of gene expression that drives production of anti-inflammatory fatty acids 12-24 hr following TLR4 activation and contributes to downregulation of mRNAs encoding pro-inflammatory mediators...
December 21, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28039193/short-term-intense-exercise-training-reduces-stress-markers-and-alters-the-transcriptional-response-to-exercise-in-skeletal-muscle
#19
James Matthew Hinkley, Adam R Konopka, Miranda K Suer, Matthew P Harber
The purpose of this investigation was to examine the influence of short-term intense endurance training on cycling performance, along with the acute and chronic signaling responses of skeletal muscle stress and stability markers. Ten recreationally active subjects (25 ± 2 yr, 79 ± 3 kg, 47 ± 2 ml·kg·min-1) were studied before and after a 12-day cycling protocol to examine the effects of short-term intense (70-100% VO2max) exercise training on resting and exercise-induced regulation of molecular factors related to skeletal muscle cellular stress and protein stability...
December 30, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28039001/paliperidone-reverts-toll-like-receptor-3-signaling-pathway-activation-and-cognitive-deficits-in-a-maternal-immune-activation-mouse-model-of-schizophrenia
#20
Karina S MacDowell, Eva Munarriz-Cuezva, Javier R Caso, José L M Madrigal, Arantzazu Zabala, J Javier Meana, Borja García-Bueno, Juan C Leza
The pathophysiology of psychotic disorders is multifactorial, including alterations in the immune system caused by exogenous or endogenous factors. Epidemiological and experimental studies indicate that infections during the gestational period represent a risk factor to develop schizophrenia (SZ) along lifetime. Here, we tested the hypothesis that the antipsychotic paliperidone regulates immune-related brain effects in an experimental model of SZ. A well described prenatal immune activation model of SZ in mice by maternal injection of the viral mimetic poly(I:C) during pregnancy was used...
December 28, 2016: Neuropharmacology
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