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https://www.readbyqxmd.com/read/29330524/nf-%C3%AE%C2%BAb-inducing-kinase-is-a-therapeutic-target-for-systemic-lupus-erythematosus
#1
Hans D Brightbill, Eric Suto, Nicole Blaquiere, Nandhini Ramamoorthi, Swathi Sujatha-Bhaskar, Emily B Gogol, Georgette M Castanedo, Benjamin T Jackson, Youngsu C Kwon, Susan Haller, Justin Lesch, Karin Bents, Christine Everett, Pawan Bir Kohli, Sandra Linge, Laura Christian, Kathy Barrett, Allan Jaochico, Leonid M Berezhkovskiy, Peter W Fan, Zora Modrusan, Kelli Veliz, Michael J Townsend, Jason DeVoss, Adam R Johnson, Robert Godemann, Wyne P Lee, Cary D Austin, Brent S McKenzie, Jason A Hackney, James J Crawford, Steven T Staben, Moulay H Alaoui Ismaili, Lawren C Wu, Nico Ghilardi
NF-κB-inducing kinase (NIK) mediates non-canonical NF-κB signaling downstream of multiple TNF family members, including BAFF, TWEAK, CD40, and OX40, which are implicated in the pathogenesis of systemic lupus erythematosus (SLE). Here, we show that experimental lupus in NZB/W F1 mice can be treated with a highly selective and potent NIK small molecule inhibitor. Both in vitro as well as in vivo, NIK inhibition recapitulates the pharmacological effects of BAFF blockade, which is clinically efficacious in SLE...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29288771/s-allyl-cysteine-regulates-the-tnf%C3%AE-induced-muscle-wasting-by-suppressing-proteolysis-and-regulating-the-inflammatory-molecules-in-skeletal-muscle-myotubes
#2
Vikas Dutt, Vikram Saini, Prachi Gupta, Nirmaljeet Kaur, Manju Bala, Ravindra Gujar, Anita Grewal, Sanjeev Gupta, Anita Dua, Ashwani Mittal
BACKGROUND: Elevated levels of inflammatory molecules are the key players in muscle wasting/atrophy leading to human morbidity. TNFα is a well-known pro-inflammatory cytokine implicated in the pathogenesis of muscle wasting under diverse clinical settings. S-allyl cysteine (SAC), an active component of garlic (Allium sativum), has established anti-oxidant and anti-inflammatory effects in various cell types. However, the impact of SAC on skeletal muscle pathology remains unexplored. Owing to the known anti-inflammatory properties of SAC, we investigate whether pre-treatment with SAC has a protective role in TNFα induced atrophy in cultured myotubes...
December 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29285249/retinol-dehydrogenase-10-promotes-development-and-progression-of-human-glioma-via-the-tweak-nf-%C3%AE%C2%BAb-axis
#3
Feng Guan, Liang Wang, Shuyu Hao, Zhen Wu, Jian Bai, Zhuang Kang, Quan Zhou, Hong Chang, Hui Yin, Da Li, Kaibin Tian, Junpeng Ma, Guijun Zhang, Junting Zhang
Retinol dehydrogenase-10 (RDH10) is a member of the short-chain dehydrogenase/reductase family, which plays an important role in retinoic acid (RA) synthesis. Here, we show that RDH10 is highly expressed in human gliomas, and its expression correlates with tumor grade and patient survival times. In vitro, lentivirus-mediated shRNA knockdown of RDH10 suppressed glioma cell proliferation, survival, and invasiveness and cell cycle progression. In vivo, RDH10 knockdown reduced glioma growth in nude mice. Microarray analysis revealed that RDH10 silencing reduces expression of TNFRSF12A (Fn14), TNFSF12 (TWEAK), TRAF3, IKBKB (IKK-β), and BMPR2, while it increases expression of TRAF1, NFKBIA (IκBα), NFKBIE (IκBε), and TNFAIP3...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29283134/winrop-algorithm-for-prediction-of-sight-threatening-retinopathy-of-prematurity-initial-experience-in-indian-preterm-infants
#4
Gaurav Sanghi, Anil Narang, Sunny Narula, Mangat R Dogra
PURPOSE: To determine the efficacy of the online monitoring tool, WINROP (https://winrop.com/) in detecting sight-threatening type 1 retinopathy of prematurity (ROP) in Indian preterm infants. METHODS: Birth weight, gestational age, and weekly weight measurements of seventy preterm infants (<32 weeks gestation) born between June 2014 and August 2016 were entered into WINROP algorithm. Based on weekly weight gain, WINROP algorithm signaled an alarm to indicate that the infant is at risk for sight-threatening Type 1 ROP...
January 2018: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29251323/investigation-of-the-role-of-tumor-necrosis-factor-like-weak-inducer-of-apoptosis-in-non-small-cell-lung-cancer
#5
Wei-An Chang, Meng-Chi Yen, Jen-Yu Hung, Chih-Jen Yang, Shu-Fang Jian, I-Jeng Yeh, Kuan-Ting Liu, Ya-Ling Hsu, Po-Lin Kuo
Several of the soluble inflammatory molecules such as cytokines and chemokines are involved in the regulation of cancer behaviors. Tumor necrosis factor (TNF)‑like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily and is a ligand of fibroblast growth factor inducible 14 (Fn14). TWEAK/Fn14 signaling pathways promote tumor progression in several types of human cancer. In the present study, we investigated the role of TWEAK through bioinformatic assay, in vitro experiments, and serum levels in patients with non‑small cell lung cancer (NSCLC)...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29249219/the-role-of-the-tumor-necrosis-factor-tnf-related-weak-inducer-of-apoptosis-tweak-in-offspring-exposed-to-prenatal-hypoxia
#6
L M Reyes, A Shah, A Quon, J S Morton, S T Davidge
Exposure to prenatal hypoxia in rats leads to intrauterine growth restriction (IUGR), decreases fetal cardiomyocyte proliferation and increases the risk to develop cardiovascular diseases (CVD) later in life. The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) induces cardiomyocyte proliferation through activation of the fibroblast growth factor-inducible molecule 14 (Fn-14) receptor. The TWEAK/Fn-14 pathway becomes quiescent shortly after birth, however, it becomes upregulated with CVD; suggesting that it could be a link between the increased susceptibility to CVD in pregnancies complicated by hypoxia/IUGR...
December 18, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/29201025/regulation-of-neuroinflammation-what-role-for-the-tumor-necrosis-factor-like-weak-inducer-of-apoptosis-fn14-pathway
#7
REVIEW
Audrey Boulamery, Sophie Desplat-Jégo
Observed in many central nervous system diseases, neuroinflammation (NI) proceeds from peripheral immune cell infiltration into the parenchyma, from cytokine secretion and from oxidative stress. Astrocytes and microglia also get activated and proliferate. NI manifestations and consequences depend on its context and on the acute or chronic aspect of the disease. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 pathway has been involved in chronic human inflammatory pathologies such as neurodegenerative, autoimmune, or malignant diseases...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29190740/correlation-of-serum-cytokines-chemokines-growth-factors-and-enzymes-with-periodontal-disease-parameters
#8
Jeneen Panezai, Ambereen Ghaffar, Mohammad Altamash, Karl-Gösta Sundqvist, Per-Erik Engström, Anders Larsson
BACKGROUND: Periodontal disease (PD) is characterized by inflammatory tissue destruction in tooth supporting apparatus. Many studies indicate that the underlying pathogenesis is in concordance with rheumatoid arthritis (RA) sharing immune-inflammatory events affect both diseases. The aim of this study was to investigate serum cytokines, chemokines, growth factors, enzymes and costimulatory proteins in association with periodontal conditions in PD and RA subjects. MATERIALS & METHODS: Periodontal examination was performed in RA (n = 38), PD (n = 38) and healthy subjects (n = 14)...
2017: PloS One
https://www.readbyqxmd.com/read/29171852/steering-on-surface-reactions-with-self-assembly-strategy
#9
Xiong Zhou, Jingxin Dai, Kai Wu
The control of assembly structures that subsequently help achieve viable functionalities has been one of the key motivations for the exploration of surface molecular assembly. In terms of its functionality and applicability, the assembly is explored as a strategy to steer on-surface reactions primarily by two methods: assembly-assisted and assembly-involved reactions. The functions of the self-assembly strategy are threefold: tweaking reaction selectivities, steering reaction pathways, and directing reaction sites...
November 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29151827/tumor-necrosis-factor-like-weak-inducer-of-apoptosis-regulates-quadriceps-muscle-atrophy-and-fiber-type-alteration-in-a-rat-model-of-chronic-obstructive-pulmonary-disease
#10
Jun-Juan Lu, Qing Wang, Li Hua Xie, Qiang Zhang, Sheng Hua Sun
Background: In chronic obstructive pulmonary disease (COPD), weakness and muscle mass loss of the quadriceps muscle has been demonstrated to predict survival and mortality rates of patients. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), as a member of the TNF superfamily, has recently been identified as a key regulator of skeletal muscle wasting and metabolic dysfunction. So our aim was to study the role of TWEAK during quadriceps muscle atrophy and fiber-type transformation in COPD model rats and its possible pathway...
2017: Tobacco Induced Diseases
https://www.readbyqxmd.com/read/29143982/tweak-fn14-interaction-induces-proliferation-and-migration-in-human-airway-smooth-muscle-cells-via-activating-the-nf-%C3%AE%C2%BAb-pathway
#11
Cuimin Zhu, Leguo Zhang, Zhiming Liu, Chen Li, Yajie Bai
Asthma, an increasingly common chronic disease among children, are characterized by airway remodeling, which is partly attributed to the proliferation and migration of airway smooth muscle cell (ASMC). The purpose of the present study was to investigate potential roles and mechanisms of the tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible molecule 14 (Fn14) axis on cell proliferation and migration in HASMCs. Compared to HASMCs from non-asthmatic patients, those from asthmatic patients showed elevated expression levels of both Fn14 and TWEAK...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29137708/smartphone-based-non-invasive-salivary-glucose-biosensor
#12
Anuradha Soni, Sandeep Kumar Jha
The present work deals with the development of a non-invasive optical glucose biosensor using saliva samples and a smartphone. The sensor was fabricated with a simple methodology by immobilization of Glucose oxidase enzyme along with a pH responsive dye on a filter paper based strip. The strip changes color upon reaction with glucose present in saliva and the color changes were detected using a smartphone camera through RGB profiling. This standalone biosensor showed good sensitivity and low interference while operating within 20 s response time...
December 15, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29130664/-prediction-value-of-tweak-fn14-in-crohn-s-disease-with-intestinal-fibrosis
#13
Ting Xu, Yan Yang, Li Zhao, Dan-Dan Zhou, Yan Zhang
OBJECTIVE: To investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/ fibroblast growth factorinducible 14 (Fn14) in the serum and colon tissue of Crohn's disease (CD) and to elucidate whether the expression of TWEAK/Fn14 can be used as an indicator for intestinal fibrosis. METHODS: Blood samples from 67 CD patients and 33 healthy controls were collected to measure the level of TWEAK by ELISA. Meanwhile,colon samples from 29 CD patients received colectomy and the normal colon tissues from 15 patients with colon cancer were included...
September 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29107125/degradation-of-extracellular-matrix-regulates-osteoblast-migration-a-microfluidic-based-study
#14
N Movilla, C Borau, C Valero, J M García-Aznar
Bone regeneration is strongly dependent on the capacity of cells to move in a 3D microenvironment, where a large cascade of signals is activated. To improve the understanding of this complex process and to advance in the knowledge of the role of each specific signal, it is fundamental to analyze the impact of each factor independently. Microfluidic-based cell culture is an appropriate technology to achieve this objective, because it allows recreating realistic 3D local microenvironments by taking into account the extracellular matrix, cells and chemical gradients in an independent or combined scenario...
October 26, 2017: Bone
https://www.readbyqxmd.com/read/29102620/levels-of-cytokines-in-serum-associate-with-development-of-hepatocellular-carcinoma-in-patients-with-hcv-infection-treated-with-direct-acting-antivirals
#15
Jose D Debes, Marjolein van Tilborg, Zwier M A Groothuismink, Bettina E Hansen, Julian Schulze Zur Wiesch, Johann von Felden, Robert J de Knegt, Andre Boonstra
Concern has arisen about development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection treated with direct-acting antivirals (DAAs). To identify patients at risk for HCC, we evaluated serum levels of immune mediators before, during, and after DAA treatment of HCV infection. Our study included 13 patients who developed HCC within 18 months after treatment (3 with HCC recurrence and 10 with new HCC) and 10 patients who did not develop HCC (controls), within at least 24 months of treatment (median, 26 months)...
November 1, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29096001/hybrids-and-horizontal-transfer-introgression-allows-adaptive-allele-discovery
#16
Roswitha Schmickl, Sarah Marburger, Sian Bray, Levi Yant
Evolution has devised countless remarkable solutions to diverse challenges. Understanding the mechanistic basis of these solutions provides insights into how biological systems can be subtly tweaked without maladaptive consequences. The knowledge gained from illuminating these mechanisms is equally important to our understanding of fundamental evolutionary mechanisms as it is to our hopes of developing truly rational plant breeding and synthetic biology. In particular, modern population genomic approaches are proving very powerful in the detection of candidate alleles for mediating consequential adaptations that can be tested functionally...
October 31, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29095436/rna-sequencing-based-comparative-analysis-of-human-hepatic-progenitor-cells-and-their-niche-from-alcoholic-steatohepatitis-livers
#17
An Ceulemans, Stefaan Verhulst, Matthias Van Haele, Olivier Govaere, Juan-Jose Ventura, Leo A van Grunsven, Tania Roskams
Hepatic progenitor cells (HPCs) are small cells with a relative large oval nucleus and a scanty cytoplasm situated in the canals of Hering that express markers of (immature) hepatocytes and cholangiocytes. HPCs are present in large numbers in alcoholic steatohepatitis (ASH), one of the leading causes of chronic liver disease. To date, the mechanisms responsible for proliferation and differentiation of human HPCs are still poorly understood and the role of HPCs in ASH development is unknown. In this study, we aimed to characterise human HPCs and their interactions with other cells through comparison, on both protein and RNA level, of HPC-enriched cell populations from adult human liver tissue using different isolation methods...
November 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29075649/enavatuzumab-a-humanized-anti-tweak-receptor-monoclonal-antibody-exerts-antitumor-activity-through-attracting-and-activating-innate-immune-effector-cells
#18
Shiming Ye, Melvin I Fox, Nicole A Belmar, Mien Sho, Debra T Chao, Donghee Choi, Yuni Fang, Vivian Zhao, Stephen F Keller, Gary C Starling, Patricia A Culp
Enavatuzumab is a humanized IgG1 anti-TWEAK receptor monoclonal antibody that was evaluated in a phase I clinical study for the treatment of solid malignancies. The current study was to determine whether and how myeloid effector cells were involved in postulated mechanisms for its potent antitumor activity in xenograft models. The initial evidence for a role of effector cells was obtained in a subset of tumor xenograft mouse models whose response to enavatuzumab relied on the binding of Fc of the antibody to Fcγ receptor...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29068159/sputum-tweak-expression-correlates-with-severity-and-degree-of-control-in-noneosinophilic-childhood-asthma
#19
Soo Yeon Kim, Jong Deok Kim, In Suk Sol, Min Jung Kim, Mi Na Kim, Jung Yeon Hong, Hye Ran Kim, Yoon Hee Kim, Yong Ju Lee, Kyung Won Kim, Myung Hyun Sohn
BACKGROUND: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to play a role in the pathogenesis of various inflammatory diseases. However, no study has been performed on childhood asthma. METHODS: Ninety-five children with asthma and 78 controls aged 5-18 years were included. Sputum induction, pulmonary function test (PFT), and methacholine challenge test were performed. The subjects were divided into the eosinophilic airway (EA) and non-EA (NEA) groups based on sputum analysis and into the high and low TWEAK groups according to the TWEAK cutoff level (263...
October 25, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/29054986/phase-1-study-of-enavatuzumab-a-first-in-class-humanized-monoclonal-antibody-targeting-the-tweak-receptor-in-patients-with-advanced-solid-tumors
#20
Elaine T Lam, S Gail Eckhardt, Wells Messersmith, Antonio Jimeno, Cindy L O'Bryant, Ramesh K Ramanathan, Glen J Weiss, Manpreet Chadha, Abbie Oey, Han Ting Ding, Patricia A Culp, Stephan F Keller, Vivian Y Zhao, L Claire Tsao, Anil Singhal, Kyle D Holen, Daniel D Von Hoff
This phase I study evaluates the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics, and preliminary anticancer activity of enavatuzumab, a humanized IgG1 antibody to the TWEAK receptor, in patients with advanced solid malignancies. Patients received escalating doses of enavatuzumab given intravenously over 60 minutes every 2 weeks. Blood was obtained for PK and biomarker assessment. Three patients were enrolled per dose level in a standard 3+3 design with response assessment by RECIST version 1...
October 20, 2017: Molecular Cancer Therapeutics
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