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https://www.readbyqxmd.com/read/28215636/sirtuin-6-prevents-matrix-degradation-through-inhibition-of-the-nf-%C3%AE%C2%BAb-pathway-in-intervertebral-disc-degeneration
#1
Liang Kang, Jia Hu, Yuxiong Weng, Jie Jia, Yukun Zhang
Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation...
February 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28214650/2-methoxyestradiol-protects-against-igg-immune-complex-induced-acute-lung-injury-by-blocking-nf-%C3%AE%C2%BAb-and-ccaat-enhancer-binding-protein-%C3%AE-activities
#2
Chunguang Yan, Yanfei Shen, Qiqing Sun, Dong Yuan, Huifang Tang, Hongwei Gao
Increasing evidences indicate that 2-Methoxyestradiol (2ME2) plays an essential role in protecting against inflammatory responses. However, its effect on IgG immune complex (IC)-induced acute lung injury (ALI) remains enigmatic. In the study, by using i.p. administration of 2ME2, we evaluated its influence on IgG IC-induced pulmonary injury in mice. We found that during IgG IC-induced ALI, mice treated by 2ME2 displayed a substantial decrease in vascular permeability and neutrophil influx (represented by myeloperoxidase activity) when compared with their counterparts receiving vehicle treatment...
February 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28214558/small-heterodimer-partner-shp-contributes-to-insulin-resistance-in-cardiomyocytes
#3
Ricardo Rodríguez-Calvo, Dipanjan Chanda, Yvonne Oligschlaeger, Marie Miglianico, Will A Coumans, Emma Barroso, Marta Tajes, Joost Jfp Luiken, Jan Fc Glatz, Manuel Vázquez-Carrera, Dietbert Neumann
Small heterodimer partner (SHP) is an atypical nuclear receptor expressed in heart that has been shown to inhibit the hypertrophic response. Here, we assessed the role of SHP in cardiac metabolism and inflammation. Mice fed a high-fat diet (HFD) displayed glucose intolerance accompanied by increased cardiac mRNA levels of Shp. In HL-1 cardiomyocytes, SHP overexpression inhibited both basal and insulin-stimulated glucose uptake and impaired the insulin signalling pathway (evidenced by reduced AKT and AS160 phosphorylation), similar to insulin resistant cells generated by high palmitate/high insulin treatment (HP/HI; 500μM/100nM)...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28209986/nf-%C3%AE%C2%BAb-signaling-regulates-cell-autonomous-regulation-of-cxcl10-in-breast-cancer-4t1-cells
#4
Won Jong Jin, Bongjun Kim, Darong Kim, Hea-Young Park Choo, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee
The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells...
February 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28204822/melittin-inhibits-osteoclast-formation-through-the-downregulation-of-the-rankl-rank-signaling-pathway-and-the-inhibition-of-interleukin-1%C3%AE-in-murine-macrophages
#5
Jung-Yoon Choe, Seong-Kyu Kim
Melittin is a major toxic component of bee venom (Apis mellifera). It is not known whether melittin is involved in bone metabolism and osteoclastogenesis. The aim of this study was to determine the role of melittin in the regulation of osteoclastogenesis. In vitro osteoclastogenesis assays were performed using mouse RAW 264.7 cells and bone marrow-derived macrophages (BMMs) treated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Morphologic and functional analyses for osteoclast-like multinucleated cells (MNCs) were performed by tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and pit formation methods...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28204810/htlv-1-basic-leucine-zipper-factor-downregulates-cyclin%C3%A2-d1-expression-via-interactions-with-nf-%C3%AE%C2%BAb
#6
Yunyun Ma, Bo Zhang, Dong Wang, Lili Qian, Xianmei Song, Xueyin Wang, Chaokuan Yang, Guoqiang Zhao
Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus. It can cause adult T cell leukemia (ATL) and other diseases. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ), which is encoded by the minus-strand of the provirus, is expressed in all cases of ATL and involved in T cell proliferation. However, the exact mechanism underlying its growth-promoting activity is poorly understood. Herein, we demonstrated that HBZ suppressed cyclin D1 expression by inhibiting the nuclear factor (NF)-κB signaling pathway...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202068/the-dna-damage-response-promotes-polyomavirus-jc-infection-by-nucleus-to-cytoplasm-nf-kappab-activation
#7
Martyn K White, Anna Bellizzi, Gabriele Ibba, Valeria Pietropaolo, Anna T Palamara, Hassen S Wollebo
BACKGROUND: Infection of glial cells by human neurotropic polyomavirus JC (JCV), the causative agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML), rapidly inflicts damage to cellular DNA. This activates DNA damage response (DDR) signaling including induction of expression of DNA repair factor Rad51. We previously reported that Rad51 co-operates with the transcription factor NF-κB p65 to activate JCV early transcription. Thus Rad51 induction by JCV infection may provide positive feedback for viral activation early in JCV infection...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28196866/sglt2-expression-is-increased-in-human-diabetic-nephropathy-sglt2-inhibition-decreases-renal-lipid-accumulation-inflammation-and-the-development-of-nephropathy-in-diabetic-mice
#8
Xiaoxin X Wang, Jonathan Levi, Yuhuan Luo, Komuraiah Myakala, Michal Herman-Edelstein, Liru Qiu, Dong Wang, Yingqiong Peng, Almut Grenz, Scott Lucia, Evgenia Dobrinskikh, Vivette D D'Agati, Hermann Koepsell, Jeffrey B Kopp, Avi Rosenberg, Moshe Levi
There is very limited human renal sodium gradient dependent glucose transporter protein SGLT2 mRNA and protein expression data reported in the literature. Aim 1 of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice which had no changes in renal SGLT-2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28188806/role-of-ccl20-mediated-immune-cell-recruitment-in-nf-%C3%AE%C2%BAb-mediated-trail-resistance-of-pancreatic-cancer
#9
Claudia Geismann, Frauke Grohmann, Anita Dreher, Robert Häsler, Philip Rosenstiel, Karen Legler, Charlotte Hauser, Jan Hendrik Egberts, Bence Sipos, Stefan Schreiber, Andreas Linkermann, Zonera Hassan, Günter Schneider, Heiner Schäfer, Alexander Arlt
Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers. From a clinical view, the transcription factor NF-κB is of particular importance, since this pathway confers apoptosis resistance and limits drug efficacy. Whereas the role of the most abundant NF-κB subunit p65/RelA in therapeutic resistance is well documented, only little knowledge of the RelA downstream targets and their functional relevance in TRAIL mediated apoptosis in PDAC is available. In the present study TRAIL resistant and sensitive PDAC cell lines were analyzed for differentially expressed RelA target genes, to define RelA downstream targets mediating TRAIL resistance...
February 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28181483/nf-%C3%AE%C2%BAb-regulates-neuronal-ankyrin-g-via-a-negative-feedback-loop
#10
Hans-Georg König, Robert Schwamborn, Silke Andresen, Sinéad Kinsella, Orla Watters, Beau Fenner, Jochen H M Prehn
The axon initial segment (AIS) is a neuronal compartment defined by ankyrin-G expression. We here demonstrate that the IKK-complex co-localizes and interacts with the cytoskeletal anchor protein ankyrin-G in immunoprecipitation and proximity-ligation experiments in cortical neurons. Overexpression of the 270 kDa variant of ankyrin-G suppressed, while gene-silencing of ankyrin-G expression increased nuclear factor-κB (NF-κB) activity in primary neurons, suggesting that ankyrin-G sequesters the transcription factor in the AIS...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179530/japanese-encephalitis-virus-ns5-inhibits-the-type-i-interferon-production-by-blocking-the-nuclear-translocation-of-irf3-and-nf-%C3%AE%C2%BAb
#11
Jing Ye, Zheng Chen, Yunchuan Li, Zikai Zhao, Wen He, Ali Zohaib, Yunfeng Song, Chenglin Deng, Bo Zhang, Huanchun Chen, Shengbo Cao
The type I interferon (IFN) response is part of a first-line defense against viral infection. To initiate replication, viruses have developed powerful evasion strategies to counteract host IFN responses. In present study, we found that Japanese encephalitis virus (JEV) NS5 protein could inhibit double strand RNA (dsRNA)-induced IFN-β expression in a dose-dependent manner. Our data further demonstrated that JEV NS5 suppressed the activation of IFN transcriptional factors, IRF3 and NF-κB. However, there was no defect in the phosphorylation of IRF3 and degradation of IκB, an upstream inhibitor of NF-κB, upon NS5 expression, indicating a direct inhibition of the nuclear localization of IRF3 and NF-κB by NS5...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28178219/altholactone-inhibits-nf-%C3%AE%C2%BAb-and-stat3-activation-and-induces-reactive-oxygen-species-mediated-apoptosis-in-prostate-cancer-du145-cells
#12
Chunwa Jiang, Muqaddas Masood, Azhar Rasul, Wei Wei, Ya Wang, Muhammad Ali, Muhammad Mustaqeem, Jiang Li, Xiaomeng Li
Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play pivotal roles in the cell survival of many human tumors. The objective of this study was to elucidate the mechanism of action of altholactone against prostate cancer DU145 cells and to evaluate whether its effects are mediated by inhibition of NF-κB and STAT3 activity...
February 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28173803/hypoxia-inducible-microrna-224-promotes-the-cell-growth-migration-and-invasion-by-directly-targeting-rassf8-in-gastric-cancer
#13
Chuan He, Libo Wang, Jiantao Zhang, Hong Xu
BACKGROUND: Hypoxia plays an important role in the development of various cancers. MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression and modulate the tumorigenesis, including gastric cancer. However, the roles and molecular mechanism of miR-224 in gastric cancer under hypoxia remain poorly understood. METHOD: Real-time PCR and Northern blot assay were used to examine the effects of hypoxia and HIF-1α on miR-224 expression. Luciferase and ChIP assays were performed to determine whether miR-224 was a transcriptional target of HIF-1α...
February 7, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28167257/tetradecanol-reduces-el-4-t-cell-growth-by-the-down-regulation-of-nf-%C3%AE%C2%BAb-mediated-il-2-secretion
#14
Jung Up Park, Bok Yun Kang, Hwa-Jeong Lee, Sunoh Kim, Donghyuck Bae, Jong-Hwan Park, Young Ran Kim
Tetradecanol is a straight-chain saturated fatty alcohol purified from Dendropanax morbifera leaves. We found that tetradecanol (30μM) reduced specifically the growth of T cells such as EL-4 T cell and isolated murine CD4(+) T cells. In this study, we investigated the effects of tetradecanol on the regulation of interlukin-2 (IL-2), a potent T cell growth factor. Tetradecanol significantly inhibited IL-2 secretion in EL-4 T cells activated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io) and also in isolated murine CD4(+) T cells activated with anti-CD3 and anti-CD28 antibodies...
February 3, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28159925/mirna-1246-induces-pro-inflammatory-responses-in-mesenchymal-stem-stromal-cells-by-regulating-pka-and-pp2a
#15
Alexander Bott, Nese Erdem, Shalom Lerrer, Agnes Hotz-Wagenblatt, Christian Breunig, Khalid Abnaof, Angelika Wörner, Heike Wilhelm, Ewald Münstermann, Adit Ben-Baruch, Stefan Wiemann
The tumor microenvironment (TME) has an impact on breast cancer progression by creating a pro-inflammatory milieu within the tumor. However, little is known about the roles of miRNAs in cells of the TME during this process. We identified six putative oncomiRs in a breast cancer dataset, all strongly correlating with poor overall patient survival. Out of the six candidates, miR-1246 was upregulated in aggressive breast cancer subtypes and expressed at highest levels in mesenchymal stem/stroma cells (MSCs). Functionally, miR-1246 led to a p65-dependent increase in transcription and release of pro-inflammatory mediators IL-6, CCL2 and CCL5 in MSCs, and increased NF-κB activity...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28155253/characterization-of-key-transcription-factors-as-molecular-signatures-of-hpv-positive-and-hpv-negative-oral-cancers
#16
Gaurav Verma, Kanchan Vishnoi, Abhishek Tyagi, Mohit Jadli, Tejveer Singh, Ankit Goel, Ankita Sharma, Kiran Agarwal, Subhash Chandra Prasad, Durgatosh Pandey, Shashi Sharma, Ravi Mehrotra, Sukh Mahendra Singh, Alok Chandra Bharti
Prior studies established constitutively active AP-1, NF-κB, and STAT3 signaling in oral cancer. Differential expression/activation of specific members of these transcription factors has been documented in HPV-positive oral lesions that respond better to therapy. We performed a comprehensive analysis of differentially expressed, transcriptionally active members of these pivotal signaling mediators to develop specific signatures of HPV-positive and HPV-negative oral lesions by immunohistochemical method that is applicable in low-resource settings...
February 3, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28153721/mir-138-indirectly-regulates-the-mdr1-promoter-by-nf-%C3%AE%C2%BAb-p65-silencing
#17
J L Requenez-Contreras, E S López-Castillejos, R Hernández-Flores, M A Moreno-Eutimio, J T Granados-Riveron, G U Martinez-Ruiz, G Aquino-Jarquin
MicroRNAs (miRNAs) are known to mediate post-transcriptional gene silencing in the cytoplasm and recent evidence indicates that may also possess nuclear roles in regulating gene expression. A previous study showed that miR-138 is involved in the multidrug resistance of leukemia cells through down-regulation of the drug efflux pump P-glycoprotein (P-gp), the protein encoded by the human multidrug-resistant ABCB1/MDR1 gene. However, the transcriptional regulatory mechanisms responsible remain to be elucidated...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28150717/wogonin-reversed-resistant-human-myelogenous-leukemia-cells-via-inhibiting-nrf2-signaling-by-stat3-nf-%C3%AE%C2%BAb-inactivation
#18
Xuefen Xu, Xiaobo Zhang, Yi Zhang, Lin Yang, Yicheng Liu, Shaoliang Huang, Lu Lu, Lingyi Kong, Zhiyu Li, Qinglong Guo, Li Zhao
Constitutive NF-E2-related factor 2 (Nrf2, NFE2L2) activation has been recently reported to play a pivotal role in enhancing cell survival and resistance to anticancer drugs in many tumors. Wogonin had strong reversal potency via reduction of Nrf2 mRNA in Adriamycin (ADR)-induced resistant human chronic myelogenous leukemia (CML) K562/A02, but the mechanism of reduction of Nrf2 mRNA was still unclear. In this study, we aimed to delineate the mechanism by which Wogonin suppressed transcription of Nrf2 in resistant CML cells and further evaluate the reversal effects of Wogonin on the established animal models...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28127806/ethanol-extract-of-potentilla-supina-linne-suppresses-lps-induced-inflammatory-responses-through-nf-%C3%AE%C2%BAb-and-ap-1-inactivation-in-macrophages-and-in-endotoxic-mice
#19
Hae-Jun Lee, Ji-Sun Shin, Kyoung-Goo Lee, Sang Cheol Park, Young Pyo Jang, Jung-Hwan Nam, Kyung-Tae Lee
In this study, we investigated the antiinflammatory effects of ethanol extracts of Potentilla. supina Linne (EPS) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and septic mice. EPS suppressed LPS-induced nitric oxide, prostaglandin E2 , TNF-α, interleukin-6 and interleukin-1β at production and mRNA levels in LPS-induced RAW 264.7 macrophages. Consistent with these observations, EPS attenuated the expressions of inducible nitric oxide synthase and cyclooxygenase-2 by downregulation of their promoter activities...
January 27, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28123321/in%C3%A2-vitro-antioxidative-and-anti-inflammatory-effects-of-the-compound-k-rich-fraction-biogf1k-prepared-from-panax-ginseng
#20
Muhammad Jahangir Hossen, Yong Deog Hong, Kwang-Soo Baek, Sulgi Yoo, Yo Han Hong, Ji Hye Kim, Jeong-Oog Lee, Donghyun Kim, Junseong Park, Jae Youl Cho
BACKGROUND: BIOGF1K, a compound K-rich fraction prepared from the root of Panax ginseng, is widely used for cosmetic purposes in Korea. We investigated the functional mechanisms of the anti-inflammatory and antioxidative activities of BIOGF1K by discovering target enzymes through various molecular studies. METHODS: We explored the inhibitory mechanisms of BIOGF1K using lipopolysaccharide-mediated inflammatory responses, reporter gene assays involving overexpression of toll-like receptor adaptor molecules, and immunoblotting analysis...
January 2017: Journal of Ginseng Research
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