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https://www.readbyqxmd.com/read/29352220/soce-induced-calcium-overload-regulates-autophagy-in-acute-pancreatitis-via-calcineurin-activation
#1
Zhen-Dong Zhu, Tao Yu, Hua-Jing Liu, Jing Jin, Jun He
Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that is characterized by inflammation, edema, vacuolization and necrosis, which has significant morbidity and lethality. The pathogenesis of AP has not been established completely. An early and critical feature of AP is the aberrant signaling of Calcium (Ca2+) within the pancreatic acinar cell, termed Ca2+ overload. Store-operated Ca2+ (SOC) channels are the principal Ca2+ influx channels that contribute to Ca2+ overload in pancreatic acinar cells...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348878/identification-of-cancer-prognosis-associated-functional-modules-using-differential-co-expression-networks
#2
Wenshuai Yu, Shengjie Zhao, Yongcui Wang, Brian Nlong Zhao, Weiling Zhao, Xiaobo Zhou
The rapid accumulation of cancer-related data owing to high-throughput technologies has provided unprecedented choices to understand the progression of cancer and discover functional networks in multiple cancers. Establishment of co-expression networks will help us to discover the systemic properties of carcinogenesis features and regulatory mechanisms of multiple cancers. Here, we proposed a computational workflow to identify differentially co-expressed gene modules across 8 cancer types by using combined gene differential expression analysis methods and a higher-order generalized singular value decomposition...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29337215/anti-angiogenic-effects-of-qingdu-granule-on-breast-cancer-through-inhibiting-nfat-signaling-pathway
#3
Xin Zhao, Jinyu Liu, Lili Feng, Shasha Ge, Shijun Yang, Chen Chen, Xiaoya Li, Lin Peng, Yuxue Mu, Yueqi Wang, Daozhao Gu, Yi Guo, Geng Lin, Bo Deng, Zhiqiang Cheng, Dayong Cai
ETHNOPHARMACOLOGICAL RELEVANCE: Qingdu granule (QDG), a traditional Chinese herbal prescription, had anti-tumor effect on breast cancer. However the underlying mechanism of QDG was unclear. THE AIM OF THIS STUDY: The present study aimed to investigate whether QDG could inhibit angiogenesis of breast cancer via acting on nuclear factor of activated T-cells (NFAT) signaling pathway. This was implicated in human umbilical vein endothelial cells (HUVECs) in vitro and breast cancer xenograft model in vivo...
January 11, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29335207/synthesis-and-biological-evaluation-of-3-2-aminoethyl-uracil-derivatives-as-gonadotropin-releasing-hormone-gnrh-receptor-antagonists
#4
Seon-Mi Kim, Minhee Lee, So Young Lee, Soo-Min Lee, Eun Jeong Kim, Jae Sun Kim, Jihyae Ann, Jiyoun Lee, Jeewoo Lee
We investigated a series of uracil analogues by introducing various substituents on the phenyl ring of the N-3 aminoethyl side chain and evaluated their antagonistic activity against human gonadotropin-releasing hormone (GnRH) receptors. Analogues with substituents at the ortho or meta position demonstrated potent in vitro antagonistic activity. Specifically, the introduction of a 2-OMe group enhanced nuclear factor of activated T-cells (NFAT) inhibition up to 6-fold compared to the unsubstituted analogue...
January 2, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29330284/novel-intergenically-spliced-chimera-nfatc3-pla2g15-is-associated-with-aggressive-t-all-biology-and-outcome
#5
Jonathan Bond, Christine Tran Quang, Guillaume Hypolite, Mohamed Belhocine, Aurélie Bergon, Gaëlle Cordonnier, Jacques Ghysdael, Elizabeth Macintyre, Nicolas Boissel, Salvatore Spicuglia, Vahid Asnafi
Leukemias are frequently characterized by the expression of oncogenic fusion chimeras that normally arise due to chromosomal rearrangements. Intergenically-spliced chimeric RNAs (ISCs) are transcribed in the absence of structural genomic changes, and aberrant ISC expression is now recognized as a potential driver of cancer. To better understand these potential oncogenic drivers, high-throughput RNA-sequencing (RNA-seq) was performed on T-acute lymphoblastic leukemia (T-ALL) patient specimens (n=24) and candidate T-ALL-related ISCs were identified (n=55; a median of 4 per patient)...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29324390/nfat-1-hyper-activation-by-methionine-enkephalin-menk-significantly-induces-cell-apoptosis-of-rats-c6-glioma-in-vivo-and-in-vitro
#6
Wei-Cheng Lu, Hui Xie, Xin-Xin Tie, Ruizhe Wang, An-Hua Wu, Feng-Ping Shan
The aim of the work was to investigate the effect and possible mechanism of MENK on the growth of rat C6 glioma in vivo or in vitro. Our findings showed that MENK could inhibit the growth of rat C6 glioma, prolong median survival times in tumor-bearing rats, and induce glioma cell apoptosis. Moreover, MENK could increase the activities of caspase-3, caspase-8 and caspase-9. It also increased the expression of Fas, FasL, Bax, while decreased the expression of Bcl-2. We further confirmed that MENK could increase opioid receptors MOR and DOR expressions, Ca2+ influx into the cytoplasm, and a substantial increase of NFAT1accumulation in the nuclei in C6 glioma cell...
January 8, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29316218/local-administration-of-nuclear-factor-of-activated-t-cells-nfat-c1-inhibitor-to-suppress-early-resorption-and-inflammation-induced-by-bone-morphogenetic-protein-2
#7
Ri Youn Kim, Yeju Seong, Tae Hyung Cho, Beomseok Lee, In Sook Kim, Soon Jung Hwang
Nuclear factor of activated T cells (NFAT)-c1 is known as a key regulator in osteoclast differentiation and immune response. This study is a follow-up to our previous study showing the anti-resorptive activity of VIVIT, a peptide type NFATc1 inhibitor, using absorbable collagen sponge (ACS). This study aimed to investigate the effective concentration range of local VIVIT that suppresses early excessive osteoclast activation and inflammation induced by high-dose recombinant human bone morphogenetic protein (rhBMP)-2 and concomitantly enhances bone healing in a rat critical-sized calvaria defect model...
January 9, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29308531/transcriptional-network-systems-in-cartilage-development-and-disease
#8
REVIEW
Riko Nishimura, Kenji Hata, Eriko Nakamura, Tomohiko Murakami, Yoshifumi Takahata
Transcription factors play important roles in the regulation of cartilage development by controlling the expression of chondrogenic genes. Genetic studies have revealed that Sox9/Sox5/Sox6, Runx2/Runx3 and Osterix in particular are essential for the sequential steps of cartilage development. Importantly, these transcription factors form network systems that are also required for appropriate cartilage development. Molecular cloning approaches have largely contributed to the identification of several transcriptional partners for Sox9 and Runx2 during cartilage development...
January 8, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29305867/binding-of-pick1-pdz-domain-with-calcineurin-b-regulates-osteoclast-differentiation
#9
Yuya Kamano, Jun Watanabe, Tsutomu Iida, Takeru Kondo, Hiroko Okawa, Hirofumi Yatani, Makio Saeki, Hiroshi Egusa
The calcineurin/nuclear factor of activated T cell (NFAT) signaling pathway plays a major role in osteoclast differentiation; however, the proteins that react with the calcineurin-NFAT complex in osteoclasts to regulate osteoclastogenesis remain unclear. Here, we present evidence that PICK1 also positively regulates calcineurin B in osteoclasts to activate NFAT to promote osteoclastogenesis. mRNA and protein expression of PICK1 in murine primary bone marrow macrophages (BMMs) was significantly increased during RANKL-induced osteoclast differentiation...
January 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29305012/regulation-of-gene-transcription-following-stimulation-of-transient-receptor-potential-trp-channels
#10
Gerald Thiel, Andrea Lesch, Sandra Rubil, Tobias M Backes, Oliver G Rössler
Transient receptor potential (TRP) channels belong to a heterogeneous superfamily of cation channels that are involved in the regulation of numerous biological functions, including regulation of Ca2+ and glucose homeostasis, tumorigenesis, temperature, and pain sensation. To understand the functions of TRP channels, their associated intracellular signaling pathways and molecular targets have to be identified on the cellular level. Stimulation of TRP channels frequently induces an influx of Ca2+ ions into the cells and the subsequent activation of protein kinases...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29301753/exosomes-associated-with-human-ovarian-tumors-harbor-a-reversible-checkpoint-of-t-cell-responses
#11
Gautam N Shenoy, Jenni L Loyall, Orla Maguire, Vandana Iyer, Raymond J Kelleher, Hans Minderman, Paul K Wallace, Kunle Odunsi, Sathy V Balu-Iyer, Richard B Bankert
Nano-sized membrane-encapsulated extracellular vesicles isolated from the ascites fluids of ovarian cancer patients are identified as exosomes based on their biophysical and compositional characteristics. We report here that T cells pulsed with these tumor-associated exosomes during TCR-dependent activation inhibit various activation endpoints including translocation of NFkB and NFAT into the nucleus, upregulation of CD69 and CD107a, production of cytokines and cell proliferation. Additionally, the activation of virus-specific CD8+ T cells that are stimulated with the cognate viral peptides presented in the context of class I MHC is also suppressed by the exosomes...
January 4, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29299971/the-role-of-the-fas-fasl-signaling-pathway-in-environmental-toxicant-induced-testicular-cell-apoptosis-an-update
#12
Mei Wang, Ping Su
The Fas/FasL signaling pathway is one of the major pathways that regulate apoptosis. Increasing studies have shown that the activation of the Fas/FasL signaling pathway is closely associated with testicular cell apoptosis. However, the mechanism involved is still unclear. We discuss recent findings regarding the molecular mechanisms by which environmental toxicants induce testicular pathology via Fas/FasL signaling. These findings suggest that Fas/FasL signaling is employed to impact the sensitivity (a response to external factors) of germ cells, disrupt steroidogenic hormone and cytokine metabolism mediated by Sertoli cells, and elicit the activation of NFAT (nuclear factor of activated T-cells) in Leydig cell apoptosis...
January 4, 2018: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29298707/shuang-huang-lian-prevents-basophilic-granulocyte-activation-to-suppress-th2-immunity
#13
Qiaoling Fei, Yixin Han, Ruijuan Qi, Yuan Gao, Lei Fang, Rui Hou, Runlan Cai, Yun Qi
BACKGROUND: Basophilic granulocytes (BGs) not only initiate the induction of Th2 cell differentiation, but also amplify the ongoing Th2 response. Shuang-Huang-Lian (SHL) is clinically used for relieving type I hypersensitivity by continuous treatment for several weeks. METHODS: ELISA, flow cytometry, magnetic activated cell sorting, isoelectric precipitation, hybridoma technique, transfection and luciferase reporter assay were used in this study. The statistical analysis was performed using a one-way ANOVA...
January 3, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29288897/increased-trpc6-expression-is-associated-with-tubular-epithelial-cell-proliferation-and-inflammation-in-diabetic-nephropathy
#14
Yanqin Fu, Chongxian Wang, Dongming Zhang, Yaping Xin, Jun Li, Yuanyuan Zhang, Xiaojing Chu
Although TRPC6 expression is shown to be significantly elevated in a rat model diabetic nephropathy (DN), its expression and role in human DN are unclear. We thus explored the role of TRPC6 in the pathophysiology of tubular epithelial cell injury following DN. HK-2 cells were cultured in a high-glucose medium to induce a DN cell model. Ad-TRPC6 and TRP6 siRNA were transfected to overexpress and knock down TRPC6. We found that TRPC6 expression was significantly upregulated in DN tissues and cells. TRPC6 siRNA inhibited cell proliferation and promoted cell apoptosis in HK-2 cells treated with high glucose, whereas Ad-TRPC6 showed the opposite effect...
December 27, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29288626/the-p2x7-receptor-a-main-player-in-inflammation
#15
REVIEW
Elena Adinolfi, Anna Lisa Giuliani, Elena De Marchi, Anna Pegoraro, Elisa Orioli, Francesco Di Virgilio
Damage associated molecular patterns (DAMPs) are intracellular molecules released from infected or injured cells to activate inflammatory and reparatory responses. One of the most ancient and conserved DAMPs is extracellular ATP (eATP) that exerts its phlogistic activity mainly through activation of the P2X7 receptor (P2X7R). The P2X7 is an ATP gated ion channel, expressed by most immune cells, including the monocyte-derived cell lineages, T and B lymphocytes an their precursors. Here we give an overview of recent and established literature on the role of P2X7R in septic and sterile inflammation...
December 27, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29259004/a-transgenic-dual-luciferase-reporter-mouse-for-longitudinal-and-functional-monitoring-of-t-cells-in-vivo
#16
Martin Szyska, Stefanie Herda, Stefanie Althoff, Andreas Heimann, Josefine Russ, Daniele D'Abundo, Tra My Dang, Isabell Durieux, Bernd Dörken, Thomas Blankenstein, Il-Kang Na
Adoptive T-cell therapy (ATT) efficacy is limited when targeting large solid tumors. The evaluation of ATT outcomes using accessory treatment would greatly benefit from an in vivo monitoring tool, allowing the detection of functional parameters of transferred T cells. Here, we generated transgenic bioluminescence imaging of T cells (BLITC) mice expressing an NFAT-dependent click-beetle luciferase and a constitutive Renilla luciferase, which supports concomitant in vivo analysis of migration and activation of T cells...
December 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29248490/acetylation-regulates-the-mkk4-jnk-pathway-in-t-cell-receptor-signaling
#17
Yukihide Matsui, Taku Kuwabara, Toyonobu Eguchi, Koichi Nakajima, Motonari Kondo
T cell functions are regulated by multiple signaling cascades, including the MKK4-JNK (c-Jun NH2 terminal kinase) pathway. However, the mechanism regulating the MKK4-JNK axis in T cells remains unclear. Herein, we demonstrated that protein acetylation modulates JNK activity induced by T cell receptor (TCR) activation. The acetyltransferase, CREB-binding protein (CBP), is transported from the nucleus to the cytoplasm in response to TCR cross-linking. To investigate the role of CBP in TCR signaling, we overexpressed CBP in the cytoplasm of Jurkat cells, a human T lymphocyte line...
December 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/29246953/ca2-dependent-regulation-of-nfatc1-via-kca3-1-in-inflammatory-osteoclastogenesis
#18
Eva M Grössinger, Mincheol Kang, Laura Bouchareychas, Ritu Sarin, Dominik R Haudenschild, Laura N Borodinsky, Iannis E Adamopoulos
In inflammatory arthritis, the dysregulation of osteoclast activity by proinflammatory cytokines, including TNF, interferes with bone remodeling during inflammation through Ca2+-dependent mechanisms causing pathological bone loss. Ca2+-dependent CREB/c-fos activation via Ca2+-calmodulin kinase IV (CaMKIV) induces transcriptional regulation of osteoclast-specific genes via NFATc1, which facilitate bone resorption. In leukocytes, Ca2+ regulation of NFAT-dependent gene expression oftentimes involves the activity of the Ca2+-activated K+ channel KCa3...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29225169/inhibition-of-orai1-mediated-ca2-entry-limits-endothelial-cell-inflammation-by-suppressing-calcineurin-nfatc4-signaling-pathway
#19
Bei-Xin Yu, Jia-Ni Yuan, Fei-Ran Zhang, Ying-Ying Liu, Ting-Ting Zhang, Kai Li, Xiao-Fei Lv, Jia-Guo Zhou, Lin-Yan Huang, Jin-Yan Shang, Si-Jia Liang
Orai1-dependent Ca2+ entry plays an essential role in inflammatory response through regulating T cell and macrophage activation and neutrophil infiltration. However, whether Orai1 Ca2+ entry contributes to endothelial activation, one of the early steps of vascular inflammation, remains elusive. In the present study, we observed that knockdown of Orai1 reduced, whereas overexpression of Orai1 potentiated, TNFα-induced expression of adhesion molecules such as ICAM-1 and VCAM-1 in HUVECs, and subsequently blocked adhesion of monocyte to HUVECs...
December 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29223733/mitochondrial-pore-opening-and-loss-of-ca2-exchanger-nclx-levels-occur-after-frataxin-depletion
#20
R Purroy, E Britti, F Delaspre, J Tamarit, J Ros
Frataxin-deficient neonatal rat cardiomyocytes and dorsal root ganglia neurons have been used as cell models of Friedreich ataxia. In previous work we show that frataxin depletion resulted in mitochondrial swelling and lipid droplet accumulation in cardiomyocytes, and compromised DRG neurons survival. Now, we show that these cells display reduced levels of the mitochondrial calcium transporter NCLX that can be restored by calcium-chelating agents and by external addition of frataxin fused to TAT peptide. Also, the transcription factor NFAT3, involved in cardiac hypertrophy and apoptosis, becomes activated by dephosphorylation in both cardiomyocytes and DRG neurons...
December 6, 2017: Biochimica et Biophysica Acta
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