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https://www.readbyqxmd.com/read/28748627/genetic-ablation-of-carbonic-anhydrase-ix-disrupts-gastric-barrier-function-via-claudin-18-downregulation-and-acid-backflux
#1
Taolang Li, Xuemei Liu, Brigitte Riederer, Katerina Nikolovska, Anurag Kumar Singh, Kari A Mäkelä, Anna Seidler, Yongjian Liu, Gerolf Gros, Helmut Bartels, Karl Heinz Herzig, Ursula Seidler
AIM: The study aims to explore the molecular mechanisms for the parietal cell loss and fundic hyperplasia observed in gastric mucosa of mice lacking the carbonic anhydrase 9 (CAIX). METHODS: We assessed the ability of CAIX knockout and WT gastric surface epithelial cells to withstand luminal acid load by measuring the pHi of exteriorized gastric mucosa in vivousing two photon confocal laser scanning microscopy. Cytokines and claudin-18A2 expression was analyzed by RT-PCR...
July 27, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28747553/krt8-upregulation-promotes-tumor-metastasis-and-is-predictive-of-a-poor-prognosis-in-clear-cell-renal-cell-carcinoma
#2
Hai-Song Tan, Wei-Hua Jiang, Yi He, De-Sheng Wang, Zhen-Jie Wu, Deng-Shuang Wu, Li Gao, Yi Bao, Jia-Zi Shi, Bing Liu, Li-Jun Ma, Lin-Hui Wang
Keratin 8 (KRT8) plays an essential role in the development and metastasis of multiple human cancers. However, its role in clear cell renal cell carcinoma (ccRCC) remains unexplored. Here, we investigated the expression pattern, clinical significance, and function of KRT8 in ccRCC. KRT8 mRNA and protein levels were determined in two large cohorts using quantitative real-time polymerase chain reaction (qRT-PCR) and tissue microarray (TMA) immunohistochemistry (IHC), respectively. We found that KRT8 expression was upregulated in ccRCC and vein tumor thrombi (VTTs)...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747427/a-biallelic-mutation-in-il6st-encoding-the-gp130-co-receptor-causes-immunodeficiency-and-craniosynostosis
#3
Tobias Schwerd, Stephen R F Twigg, Dominik Aschenbrenner, Santiago Manrique, Kerry A Miller, Indira B Taylor, Melania Capitani, Simon J McGowan, Elizabeth Sweeney, Astrid Weber, Liye Chen, Paul Bowness, Andrew Riordan, Andrew Cant, Alexandra F Freeman, Joshua D Milner, Steven M Holland, Natalie Frede, Miryam Müller, Dirk Schmidt-Arras, Bodo Grimbacher, Steven A Wall, E Yvonne Jones, Andrew O M Wilkie, Holm H Uhlig
Multiple cytokines, including interleukin 6 (IL-6), IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF), signal via the common GP130 cytokine receptor subunit. In this study, we describe a patient with a homozygous mutation of IL6ST (encoding GP130 p.N404Y) who presented with recurrent infections, eczema, bronchiectasis, high IgE, eosinophilia, defective B cell memory, and an impaired acute-phase response, as well as skeletal abnormalities including craniosynostosis. The p.N404Y missense substitution is associated with loss of IL-6, IL-11, IL-27, and OSM signaling but a largely intact LIF response...
July 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28735867/cleavage-of-the-interleukin-11-receptor-induces-processing-of-its-c-terminal-fragments-by-the-gamma-secretase-and-the-proteasome
#4
Juliane Lokau, Charlotte M Flynn, Christoph Garbers
The cytokine Interleukin-11 (IL-11) signals through the membrane-bound IL-11 receptor (IL-11R), which is expressed in a cell-type specific manner. We have recently shown that the metalloprotease ADAM10 can cleave the IL-11R. The liberated soluble IL-11R (sIL-11R) ectodomain can bind its ligand, and the resulting IL-11/sIL-11R complex can activate cells that do not express the IL-11R (trans-signaling). In this study, we show that the remaining C-terminal fragment (CTF1) after ADAM10-mediated cleavage is subsequently cleaved within the membrane by the gamma-secretase complex, and that the resulting shorter CTF2 is further degraded by the proteasome...
July 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28714957/il-11-contribution-to-tumorigenesis-in-an-nrf2-addiction-cancer-model
#5
H Kitamura, Y Onodera, S Murakami, T Suzuki, H Motohashi
The interaction between cancer cells and their microenvironment is an important determinant of the pathological nature of cancers, particularly their tumorigenic abilities. The KEAP1-NRF2 system, originally identified as a critical defense mechanism against oxidative stress, is often dysregulated in various human cancers forming solid tumors, resulting in the aberrant activation of NRF2. Increased accumulation of NRF2 in cancers is strongly associated with the poor prognoses of cancer patients, including those with lung and breast cancers...
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28708884/a-jak1-2-inhibitor-baricitinib-inhibits-osteoclastogenesis-by-suppressing-rankl-expression-in-osteoblasts-in-vitro
#6
Kohei Murakami, Yasuhiro Kobayashi, Shunsuke Uehara, Takako Suzuki, Masanori Koide, Teruhito Yamashita, Midori Nakamura, Naoyuki Takahashi, Hiroyuki Kato, Nobuyuki Udagawa, Yukio Nakamura
The Janus kinases (Jaks) are hubs in the signaling process of more than 50 cytokine or hormone receptors. However, the function of Jak in bone metabolism remains to be elucidated. Here, we showed that the inhibition of Jak1 and/or Jak2 in osteoblast-lineage cells led to impaired osteoclastogenesis due to the reduced expression of receptor activator of nuclear factor-κB ligand (RANKL). Murine calvaria-derived osteoblasts induced differentiation of bone marrow cells into osteoclasts in the presence of 1,25-dihydroxyvitamin D3 (1,25D3) and prostaglandin E2 (PGE2) in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28707573/synthesis-radiosynthesis-and-metabolism-of-131i-y-c-cgrraggsc
#7
Jilai Xie, Donghui Pan, Mudan Lu, Xuan Chen, Yu Chen, Ting Zhang, Yan Xie, Huan Zhou, Lu Liu, Min Yang, Jiajun Wang, Daozhen Chen
BACKGROUND: The formation of the complex interleukin-11(IL-11) and IL-11 receptor (IL-11R) is closely related with tumor progression. Binding of IL-11 to the IL-11 receptor α-chain (IL-11Rα) has been suggested as a target for human cancer. The cyclic peptide c(CGRRAGGSC) is a mimic of IL-11. OBJECTIVE: To explore 131I-Y-c(CGRRAGGSC) synthesis and radiosynthesis, and metabolism in SKOV3 tumor-bearing mice. METHOD: In this study, 131I labeled c(CGRRAGGSC) was designed and characterized...
July 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28698375/bmtp-11-is-active-in-preclinical-models-of-human-osteosarcoma-and-a-candidate-targeted-drug-for-clinical-translation
#8
Valerae O Lewis, Eswaran Devarajan, Marina Cardó-Vila, Dafydd G Thomas, Eugenie S Kleinerman, Serena Marchiò, Richard L Sidman, Renata Pasqualini, Wadih Arap
Osteosarcoma occurs predominantly in children and young adults. High-grade tumors require multidisciplinary treatment consisting of chemotherapy in the neoadjuvant and adjuvant settings, along with surgical intervention. Despite this approach, death from respiratory failure secondary to the development and progression of pulmonary metastases remains a significant problem. Here, we identify the IL-11 receptor α subunit (IL-11Rα) as a cell surface marker of tumor progression that correlates with poor prognosis in patients with osteosarcoma...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28686677/mdr1a-deficiency-restrains-tumor-growth-in-murine-colitis-associated-carcinogenesis
#9
Eva Maria Hennenberg, Annette Eyking, Henning Reis, Elke Cario
Patients with Ulcerative Colitis (UC) have an increased risk to develop colitis-associated colorectal cancer (CAC). Here, we found that protein expression of ABCB1 (ATP Binding Cassette Subfamily B Member 1) / MDR1 (multidrug resistance 1) was diminished in the intestinal mucosa of patients with active UC with or without CAC, but not in non-UC patients with sporadic colon cancer. We investigated the consequences of ABCB1/MDR1 loss-of-function in a common murine model for CAC (AOM/DSS). Mice deficient in MDR1A (MDR1A KO) showed enhanced intratumoral inflammation and cellular damage, which were associated with reduced colonic tumor size and decreased degree of dysplasia, when compared to wild-type (WT)...
2017: PloS One
https://www.readbyqxmd.com/read/28647515/a-phytoestrogen-supplement-prevents-the-altered-gene-expression-associated-with-pregnancy-implantation-induced-by-il-1%C3%AE-in-endometrial-epithelial-cells
#10
Sayaka Suzuki, Noe Nakashima, Masakatsu Kageyama, Kazuo Yamagata
Phytoestrogens stimulate expression of the uterine estrogen receptor and regulate uterine functions in reproductive tissues. However, comprehensive understanding of the beneficial impacts of phytoestrogens on uterine biology at the molecular level remains unexplored. Interleukin-1β (IL-1β) expression is increased in the inflamed decidua and is associated with first trimester pregnancy loss. AglyMax-Sup has the same composition as that of the phytoestrogen supplement AglyMax but with added vitamins and other components...
June 21, 2017: Reproductive Biology
https://www.readbyqxmd.com/read/28630024/proteolytic-control-of-interleukin-11-and-interleukin-6-biology
#11
REVIEW
Juliane Lokau, Maria Agthe, Charlotte M Flynn, Christoph Garbers
Interleukin-11 (IL-11) and IL-6 are secreted glycoproteins which fulfill important homeostatic functions. Activation of target cells occurs via membrane-bound IL-11 and IL-6 receptors (IL-11R and IL-6R, respectively). Formation of IL-11/IL-11R and IL-6/IL-6R complexes triggers the recruitment of a homodimer of the ubiquitously expressed signal-transducing β-receptor gp130 (classic signaling). IL-11R and IL-6R can be shed by several proteases, albeit with different preferences and specificities, and these soluble receptors (sIL-11R and sIL-6R) act as agonists and can activate in principle all cells via gp130...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28620096/interleukin-6-family-cytokines
#12
Stefan Rose-John
The interleukin (IL)-6 family cytokines is a group of cytokines consisting of IL-6, IL-11, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), cardiotrophin 1 (CT-1), cardiotrophin-like cytokine (CLC), and IL-27. They are grouped into one family because the receptor complex of each cytokine contains two (IL-6 and IL-11) or one molecule (all others cytokines) of the signaling receptor subunit gp130. IL-6 family cytokines have overlapping but also distinct biologic activities and are involved among others in the regulation of the hepatic acute phase reaction, in B-cell stimulation, in the regulation of the balance between regulatory and effector T cells, in metabolic regulation, and in many neural functions...
June 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28596035/the-pharmacokinetic-and-pharmacodynamic-properties-of-site-specific-pegylated-genetically-modified-recombinant-human-interleukin-11-in-normal-and-thrombocytopenic-monkeys
#13
Shan-Shan Ma, Seong-Hyun Ho, Su-Yong Ma, Yue-Juan Li, Kai-Tong Li, Xiao-Chuang Tang, Guang-Rong Zhao, Song-Shan Xu
In order to improve the pharmacokinetic and pharmacodynamic properties of recombinant human interleukin-11 mutein (mIL-11) and to reduce the frequency of administration, we examined the feasibility of chemical modification of mIL-11 by methoxy polyethylene glycol succinimidyl carbonate (mPEG-SC). PEG-mIL-11 was prepared by a pH controlled amine specific method. Bioactivity of the protein was determined in a IL-11-dependent in vitro bioassay, its pharmacodynamic and pharmacokinetic properties were investigated by using normal and thrombocytopenic monkey models...
June 5, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28552376/involvement-of-stat1-in-proliferation-and-invasiveness-of-trophoblastic-cells
#14
Francisco Lázaro Pereira de Sousa, Wittaya Chaiwangyen, Diana M Morales-Prieto, Stephanie Ospina-Prieto, Maja Weber, Stella M Photini, Nelson Sass, Silvia Daher, Ekkehard Schleussner, Udo R Markert
Trophoblast proliferation and invasion are controlled by cytokines and growth factors present at the implantation site. Members of the Interleukin-6 (IL-6) family of cytokines trigger their effects through activation of intracellular cascades including the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathway. Functions of several STAT molecules in trophoblast cells have been described, but the role of STAT1 remained unclear. Here, potential functions of STAT1 and its activation by Oncostatin M (OSM) have been investigated in an in vitro model...
May 25, 2017: Reproductive Biology
https://www.readbyqxmd.com/read/28546021/sodium-butyrate-improved-intestinal-immune-function-associated-with-nf-%C3%AE%C2%BAb-and-p38mapk-signalling-pathways-in-young-grass-carp-ctenopharyngodon-idella
#15
Li Tian, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Fei Xie, Lin Feng
The present study evaluated the effect of dietary sodium butyrate (SB) supplementation on the growth and immune function in the proximal intestine (PI), middle intestine (MI) and distal intestine (DI) of young grass carp (Ctenopharyngodon idella). The fish were fed one powdery sodium butyrate (PSB) diet (1000.0 mg kg(-1) diet) and five graded levels of microencapsulated sodium butyrate (MSB) diets: 0.0 (control), 500.0, 1000.0, 1500.0 and 2000.0 mg kg(-1) diet for 60 days. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila...
May 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28521851/regulation-of-interleukin-11-expression-in-ovulatory-follicles-of-the-rat-ovary
#16
You-Jee Jang, You-Jee Jang, Jae-Il Park, Jae-Il Park, Seong-Eun Jeong, Seong-Eun Jeong, You-Mi Seo, You-Mi Seo, Phuong T M Dam, Phuong T M Dam, Young-Woo Seo, Young-Woo Seo, Bum-Chae Choi, Bum-Chae Choi, Sang-Jin Song, Sang-Jin Song, Sang-Young Chun, Sang-Young Chun, Moon-Kyoung Cho, Moon-Kyoung Cho
The aim of the present study was to examine the regulation of interleukin (IL)-11 expression, as well as the role of IL-11, during ovulation in gonadotropin-primed immature rats. Injection of equine chorionic gonadotropin (eCG), followed by human CG (hCG) to induce superovulation stimulated expression of the Il11 gene in theca cells within 6h, as revealed by northern blot and in situ hybridisation analyses. Real-time reverse transcription-polymerase chain reaction analysis showed that the IL-11 receptor, α subunit gene was expressed in granulosa and theca cells and that injection of hCG had no effect on its expression...
May 19, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28487027/interleukin-11-up-regulates-endoplasmic-reticulum-stress-induced-target-pdia4-in-human-first-trimester-placenta-and-in%C3%A2-vivo-in-mice
#17
A L Winship, K Sorby, J Correia, A Rainczuk, J Yap, E Dimitriadis
Interleukin (IL)11 is a crucial factor for human trophoblast function and placentation. Elevated levels are associated with pregnancy complications including preeclampsia, intrauterine growth restriction (IUGR) and preterm birth. However, the regulation of IL11 in the placenta has not been investigated. We examined the effect of pro-inflammatory cytokines IL1β and TNFα, as well as low oxygen tension (2%) on IL11 levels in first trimester placental villous explants. IL1β upregulated IL11 mRNA and protein, while TNFα and low oxygen had no effect...
May 2017: Placenta
https://www.readbyqxmd.com/read/28486793/inflammatory-bowel-disease-updates-on-molecular-targets-for-biologics
#18
REVIEW
Konstantinos H Katsanos, Konstantinos A Papadakis
Therapy for inflammatory bowel disease (IBD) has changed, with several new agents being evaluated. The era of anti-tumor necrosis factor (anti-TNF) antibody therapy saw remarkable progress in IBD therapy. Some patients, however, do not respond to anti-TNF treatment, or their response decreases over time. This phenomenon highlights the need to identify new molecular targets for therapy in IBD. The targets of new therapeutic molecules in IBD must aim to restore immune dysregulation by the inhibition of proinflammatory cytokines (TNF-α, interleukin [IL]-6, IL-13, IL-17, IL-18, and IL-21) and augmentation of the effect of anti-inflammatory cytokines (IL-10, IL-11, and transforming growth factor β) and to pursue new anti-inflammatory targets, such as regulatory T-cell therapy, Smad7 antisense, Janus-activated kinase inhibition, Toll-like receptor stimulation, leukocyte adhesion, and blockade of T-cell homing via integrins and mucosal addressin cellular adhesion molecule-1...
July 15, 2017: Gut and Liver
https://www.readbyqxmd.com/read/28473863/role-of-acupoint-area-collagen-fibers-in-anti-inflammation-of-acupuncture-lifting-and-thrusting-manipulation
#19
Fan Wang, Guang-Wei Cui, Le Kuai, Jian-Min Xu, Ting-Ting Zhang, Huai-Jin Cheng, Hong-Sheng Dong, Gui-Rong Dong
The role of the acupoint area collagen fibers in the efficacy of acupuncture lifting and thrusting (L&T) manipulation will be explored in this paper. 30 male NZW rabbits were randomly divided into 6 groups: sham operation group (Group N), model group (Group M), acupuncture without manipulation group (Group W), acupuncture L&T manipulation group (Group A), collagenase pretreatment group (Group JM), and collagenase pretreatment + acupuncture L&T manipulation group (Group JA). The bacterial endotoxin was used to generate the rabbit fever models...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28469796/low-dose-radiation-modulates-human-mesenchymal-stem-cell-proliferation-through-regulating-cdk-and-rb
#20
Lei Yang, Ziling Liu, Chen Chen, Xiaofeng Cong, Zhi Li, Shasha Zhao, Meng Ren
Low-dose radiation (LDR) has been known to stimulate cell proliferation. The effect of LDR on human bone marrow mesenchymal stem cells (BMSCs), however, remains to be determined. The current study, therefore, aimed to investigate the effect of LDR on human BMSC proliferation and its mechanisms. To accomplish this, human BMSCs were isolated from ribs and cultured with or without exposition to LDR (75 mGy) for 24 h. Cell proliferation was assessed by MTT assay, the cytokines secreted by the BMSCs were quantified by ELISA, and the proteins associated with cell proliferation and cell cycle were evaluated by immunoblot analysis...
2017: American Journal of Translational Research
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