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https://www.readbyqxmd.com/read/29240787/brd3-4-inhibition-and-flt3-ligand-deprivation-target-pathways-that-are-essential-for-the-survival-of-human-mll-af9-leukemic-cells
#1
Marco Carretta, Annet Z Brouwers-Vos, Matthieu Bosman, Sarah J Horton, Joost H A Martens, Edo Vellenga, Jan Jacob Schuringa
In the present work we aimed to identify targetable signaling networks in human MLL-AF9 leukemias. We show that MLL-AF9 cells critically depend on FLT3-ligand induced pathways as well as on BRD3/4 for their survival. We evaluated the in vitro and in vivo efficacy of the BRD3/4 inhibitor I-BET151 in various human MLL-AF9 (primary) models and patient samples and analyzed the transcriptome changes following treatment. To further understand the mode of action of BRD3/4 inhibition, we performed ChIP-seq experiments on the MLL-AF9 complex in THP1 cells and compared it to RNA-seq data of I-BET151 treated cells...
2017: PloS One
https://www.readbyqxmd.com/read/29237453/human-microglia-and-astrocytes-constitutively-express-the-neurokinin-1-receptor-and-functionally-respond-to-substance-p
#2
Amanda R Burmeister, M Brittany Johnson, Vinita S Chauhan, Megan J Moerdyk-Schauwecker, Ada D Young, Ian D Cooley, Alejandra N Martinez, Geeta Ramesh, Mario T Philipp, Ian Marriott
BACKGROUND: The tachykinin substance P (SP) is recognized to exacerbate inflammation at peripheral sites via its target receptor, neurokinin 1 receptor (NK-1R), expressed by leukocytes. More recently, SP/NK-1R interactions have been associated with severe neuroinflammation and neuronal damage. We have previously demonstrated that NK-1R antagonists can limit neuroinflammatory damage in a mouse model of bacterial meningitis. Furthermore, we have since shown that these agents can attenuate bacteria-induced neuronal and glial inflammatory mediator production in nonhuman primate (NHP) brain explants and isolated neuronal cells, and following in vivo infection...
December 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29236306/rs4705342-polymorphism-is-involved-in-the-tumorigenesis-of-hbv-positive-hcc-by-altering-the-binding-affinity-of-hbv-induced-nf-kb-with-the-promoter-region-of-microrna-143
#3
Yin Xiuli, Sun Shiying, Zhao Junyan, Yang Jing, Lei Xiaofei, Xu Changqing, Li Kun
BACKGROUND: The objective of this study was to explore the role of rs4705342 located in the miR-143 promoter in relation to the control of HBV positive HCC and the underlying molecular mechanism. METHOD: A luciferase assay was performed to explore the factors which influenced miR-143 transcription activity and the target gene of miR-143. This would further be confirmed by ChIP assay. Western-blot and real-time PCR were performed to identify the relationship between miR-143 and ORP8...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29230104/metformin-sensitizes-non-small-cell-lung-cancer-cells-to-an-epigallocatechin-3-gallate-egcg-treatment-by-suppressing-the-nrf2-ho-1-signaling-pathway
#4
Chenxiao Yu, Yang Jiao, Jiao Xue, Qi Zhang, Hongying Yang, Ligang Xing, Guangxia Chen, Jinchang Wu, Shuyu Zhang, Wei Zhu, Jianping Cao
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, is widely studied as a cancer chemopreventive agent with potential anti-cancer effects. The NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is considered to mediate cellular resistance to EGCG. Metformin, a classical antidiabetic drug, has been shown to prevent cancer progression. Researchers have not reported whether metformin potentiates the anti-cancer efficacy of EGCG...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29229421/the-amino-analogue-of-%C3%AE-boswellic-acid-efficiently-attenuates-the-release-of-pro-inflammatory-mediators-than-its-parent-compound-through-the-suppression-of-nf-%C3%AE%C2%BAb-i%C3%AE%C2%BAb%C3%AE-signalling-axis
#5
Shilpa Gupta, Aitizaz Ul Ahsan, Abubakar Wani, Vidushi Khajuria, Lone A Nazir, Simmi Sharma, Asha Bhagat, Parduman Raj Sharma, Subhash Bhardwaj, Kaiser J Peerzada, Bhahwal Ali Shah, Zabeer Ahmed
Natural product derivatives have proven to be cutting edge window for drug discovery and development. BA-25 (3-α-o-acetoxy-4β-amino-11-oxo-24-norurs-12-ene) an amino analogue of β-boswellic acid exhibited inhibition of TNF-α and IL-6 in THP-1 cells as demonstrated previously, however, the effect on principal inflammatory mediators such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and the pathways that mediate this function remains unknown. This study was designed to examine the comparative anti-inflammatory activity of BA-25 with its parent compound, β boswellic acid both in vitro and in vivo...
December 8, 2017: Cytokine
https://www.readbyqxmd.com/read/29228978/asiatic-acid-attenuates-methamphetamine-induced-neuroinflammation-and-neurotoxicity-through-blocking-of-nf-kb-stat3-erk-and-mitochondria-mediated-apoptosis-pathway
#6
Ji-Hyun Park, Young Ho Seo, Jung-Hee Jang, Chul-Ho Jeong, Sooyeun Lee, Byoungduck Park
BACKGROUND: Methamphetamine (METH) is a commonly abused drug that may result in neurotoxic effects. Recent studies have suggested that involvement of neuroinflammatory processes in brain dysfunction is induced by misuse of this drug. However, the mechanism underlying METH-induced inflammation and neurotoxicity in neurons is still unclear. In this study, we investigated whether asiatic acid (AA) effected METH-mediated neuroinflammation and neurotoxicity in dopaminergic neuronal cells. And we further determined whether the effect involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) pathway...
December 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29228370/a-nf-%C3%AE%C2%BAb-signature-predicts-low-grade-glioma-prognosis-a-precision-medicine-approach-based-on-patient-derived-stem-cells
#7
Tamara Ius, Yari Ciani, Maria Elisabetta Ruaro, Miriam Isola, Marisa Sorrentino, Michela Bulfoni, Veronica Candotti, Cecilia Correcig, Evgenia Bourkoula, Ivana Manini, Enrico Pegolo, Damiano Mangoni, Stefania Marzinotto, Slobodanka Radovic, Barbara Toffoletto, Federica Caponnetto, Andrea Zanello, Laura Mariuzzi, Carla Di Loreto, Antonio Paolo Beltrami, Silvano Piazza, Miran Skrap, Daniela Cesselli
Background: While recent genome wide association studies have suggested novel low-grade glioma (LGG) stratification models based on a molecular classification, we explored the potential clinical utility of patient-derived cells. Specifically, we assayed glioma-associated stem cells (GASC) that are patient-derived stem cells representative of the glioma microenvironment. Methods: By next generation sequencing, we analyzed the transcriptional profile of GASC derived from patients that underwent anaplastic transformation either within 48 months (GASC-BAD) or ≥7 years (GASC-GOOD) after surgery...
December 7, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29227581/aging-of-lymphoid-organs-can-photobiomodulation-reverse-age-associated-thymic-involution-via-stimulation-of-extrapineal-melatonin-synthesis-and-bone-marrow-stem-cells
#8
REVIEW
Denis Odinokov, Michael R Hamblin
Thymic atrophy and the subsequent reduction in T cell production are the most noticeable age-related changes affecting lymphoid organs in the immune system. In fact thymic involution has been described as "programmed aging". New therapeutic approaches such as photobiomodulation (PBM) may reduce or reverse these changes. PBM (also known as low-level laser therapy or LLLT) involves the delivery of non-thermal levels of red or near-infrared light that are absorbed by mitochondrial chromophores, in order to prevent tissue death and stimulate healing and regeneration...
December 11, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/29226952/differential-expression-of-micrornas-let-7a-mir-125b-mir-100-and-mir-21-and-interaction-with-nf-kb-pathway-genes-in-periodontitis-pathogenesis
#9
Venugopal Priyanka, Koshy Teena, Lavu Vamsi, Ranga Rao Suresh, Ramasamy Selvaraj, Hariharan Samyukta, Venkatesan Vettriselvi
Periodontitis is a chronic inflammatory disease which is caused by destruction of the tissues that surrounds and supports the tooth. Deregulation of microRNAs has been reported to cause several inflammatory diseases such as autoimmune disease, chronic periodontitis and cancer. In the present study, we have investigated the expression pattern of microRNAs let-7a, miR-125b, miR-100, miR-21 and RNA-binding protein LIN-28A among healthy individuals and chronic periodontitis patients. Total RNA was isolated from gingival tissue samples collected from 100 healthy individuals and 100 chronic periodontitis patients...
December 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29225581/protective-effect-of-unacylated-ghrelin-on-compression-induced-skeletal-muscle-injury-mediated-by-sirt1-signaling
#10
Felix N Ugwu, Angus P Yu, Thomas K Sin, Bjorn T Tam, Christopher W Lai, S C Wong, Parco M Siu
Unacylated ghrelin, the predominant form of circulating ghrelin, protects myotubes from cell death, which is a known attribute of pressure ulcers. In this study, we investigated whether unacylated ghrelin protects skeletal muscle from pressure-induced deep tissue injury by abolishing necroptosis and apoptosis signaling and whether these effects were mediated by SIRT1 pathway. Fifteen adult Sprague Dawley rats were assigned to receive saline or unacylated ghrelin with or without EX527 (a SIRT1 inhibitor). Animals underwent two 6-h compression cycles with 100 mmHg static pressure applied over the mid-tibialis region of the right limb whereas the left uncompressed limb served as the intra-animal control...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29221197/rank-expression-in-ebv-positive-nasopharyngeal-carcinoma-metastasis-a-ready-to-treat-target
#11
Carlo Resteghini, Salvatore Alfieri, Pasquale Quattrone, Francesca Dominoni, Giovanna Garzone, Ester Orlandi, Laura Locati, Cristiana Bergamini, Donata Galbiati, Nicola Alessandro Iacovelli, Carlo Fallai, Lisa Licitra, Paolo Bossi
Epstein Barr Virus (EBV) related Nasopharyngeal Carcinoma (NPC), is an highly chemo- and radiosensitive endemic malignancy in southeast Asia. More than one third of locally advanced cases relapse after curative treatment, especially because of bone, liver and lung metastases. Lymphocyte sub-populations favour EBV-associated carcinogenesis and tumour progression and several strategies aim to reverse this phenomenon. Receptor activator of NF-kB (RANK) and its Ligand (RANKL), key regulator of bone metabolisms, are expressed in several malignancies and tumor-infiltrating Tregs...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29214600/apoptosis-induction-by-alantolactone-in-breast-cancer-mda-mb-231-cells-through-reactive-oxygen-species-mediated-mitochondrion-dependent-pathway
#12
Li Cui, Weiquan Bu, Jie Song, Liang Feng, Tingting Xu, Dan Liu, Wenbo Ding, Jianhua Wang, Changyang Li, Binge Ma, Yi Luo, Ziyu Jiang, Chengcheng Wang, Juan Chen, Jian Hou, Hongmei Yan, Lei Yang, Xiaobin Jia
Alantolactone is a sesquiterpene lactone isolated from Inula helenium L. Although alantolactone possesses anti-inflammation and apoptosis-induction activities, the underlying mechanism of anti-cancer effect on human breast cancer cells remains largely unknown. In this study, we explored the possibility of alantolactone as an apoptosis-inducing cytotoxic agent using MDA-MB-231 cells as in vitro model. Alantolactone significantly induced its apoptosis, demonstrated by cell cycle analysis, annexin V-APC/7-AAD double staining and dUTP nick end labeling...
December 6, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29214369/ginkgolide-k-promotes-the-clearance-of-a53t-mutation-alpha-synuclein-in-sh-sy5y-cells
#13
Wenbo Yu, Sheng Chen, Liang Cao, Jie Tang, Wei Xiao, Baoguo Xiao
Alpha-synuclein (α-syn) is associated to Parkinson's disease (PD). The aggregated form of α-syn has potential neurotoxicity. Thus, the clearance of α-syn aggregation is a plausible strategy to delay disease progression of PD. In our study, we found that the treatment of Ginkgolide B (GB) and Ginkgolide K (GK) reduced cell death, and enhanced cell proliferation in SH-SY5Y cells, which overexpressed A53T mutant α-syn. Surprisingly, GK, but not GB, promoted the clearance of A53T α-syn, which can be abolished by autophagy inhibitor 3-methyladenine, indicating that GK-induced autophagy intervened in the clearance of A53T α-syn...
December 6, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29214163/protective-effects-of-pyridoxamine-supplementation-in-the-early-stages-of-diet-induced-kidney-dysfunction
#14
F Chiazza, A S Cento, D Collotta, D Nigro, G Rosa, F Baratta, V Bitonto, J C Cutrin, M Aragno, R Mastrocola, M Collino
Pyridoxamine, a structural analog of vitamin B6 that exerts antiglycative effects, has been proposed as supplementary approach in patients with initial diabetic nephropathy. However, the molecular mechanism(s) underlying its protective role has been so far slightly examined. C57Bl/6J mice were fed with a standard diet (SD) or a diet enriched in fat and fructose (HD) for 12 weeks. After 3 weeks, two subgroups of SD and HD mice started pyridoxamine supplementation (150 mg/kg/day) in the drinking water. HD fed mice showed increased body weight and impaired glucose tolerance, whereas pyridoxamine administration significantly improved insulin sensitivity, but not body weight, and reduced diet-induced increase in serum creatinine and urine albumin...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29212573/knockdown-of-nf-%C3%AE%C2%BAb1-by-shrna-inhibits-the-growth-of-renal-cell-carcinoma-in-vitro-and-in-vivo
#15
Amanda Ikegami, Luiz Felipe S Teixeira, Marina S Braga, Matheus Henrique Dos S Dias, Eduardo C Lopes, Maria Helena Bellini
Renal cell carcinoma (RCC) accounts for approximately 2-3% of human malignancies and is the most aggressive among urologic tumors. Biological heterogeneity, drug resistance and chemotherapy side effects are the biggest obstacles to the effective treatment of RCC. The NF-кB transcription factor is one of several molecules identified to be responsible for the aggressive phenotype of this tumor. In the past decade, several studies have demonstrated the activation of NF-kB in RCC, and many implicated NF-κB1 (p50) as an important molecule in tumor progression and metastasis...
December 1, 2017: Oncology Research
https://www.readbyqxmd.com/read/29211284/effects-of-triethylene-glycol-dimethacrylate-tegdma-on-the-odontoclastic-differentiation-ability-of-human-dental-pulp-cells
#16
Zeynep Öncel Torun, Deniz Torun, Barış Baykal, Ali Öztuna, Fatih Yeşildal, Ferit Avcu
OBJECTIVES: The primary purpose of this study was to examine the effects of triethylene glycol dimethacrylate (TEGDMA) on odontoclastic differentiation in the dental pulp tissue. MATERIAL AND METHODS: The effects of different TEGDMA dosages on the odontoclastic differentiation capability of dental pulp cells were analyzed in vitro using the following methodologies: i) flow cytometry and tartrate-resistant acid phosphatase (TRAP) staining; ii) apoptotic effects using Annexin V staining; iii) mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor (NF)-kB ligand (RANKL) genes by quantitative Real-time PCR (qRT-PCR); and iv) OPG and RANKL protein expression by enzyme-linked immunosorbent assay (ELISA)...
November 2017: Journal of Applied Oral Science: Revista FOB
https://www.readbyqxmd.com/read/29209318/the-major-chromoblastomycosis-etiologic-agent-fonsecaea-pedrosoi-activates-the-nlrp3-inflammasome
#17
Raffael Júnio Araújo de Castro, Isaque Medeiros Siqueira, Márcio Sousa Jerônimo, Angelina Maria Moreschi Basso, Paulo Henrique de Holanda Veloso Junior, Kelly Grace Magalhães, Luiza Chaves Leonhardt, Stephan Alberto Machado de Oliveira, Pedro Henrique Bürgel, Aldo Henrique Tavares, Anamélia Lorenzetti Bocca
Fonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), one of the most prevalent subcutaneous mycosis in tropical and subtropical countries. CBM is a poorly characterized chronic infection that commonly starts after transcutaneous inoculation of conidia and saprophytic hyphae of F. pedrosoi. Recently, we have shown that unlike conidia, hyphae and muriform cells (the parasitic morphotype) of F. pedrosoi promotes an intense inflammatory response pattern in vivo, which comprises the production of an inflammasome-derived cytokine, IL-1β...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29208272/biosynthesis-of-cerium-oxide-nanoparticles-and-their-effect-on-lipopolysaccharide-lps-induced-sepsis-mortality-and-associated-hepatic-dysfunction-in-male-sprague-dawley-rats
#18
Guoqiang Chen, Yunfei Xu
The fetal/life challenging Sepsis is an urgent medical disaster which have developed "blood poisoning". The sepsis is one of the disorders of organs which cause death in patients. The investigational models that mimicchemical change of sepsis in human bodywereessential. We have synthesized CeO2 NPs using eco-friendly method using plant extract. The characterization of synthesized CeO2 NPs was studied using UV-Vis, FTIR, XRD, SEM, EDX and TEM analysis. The results were confirmed that the synthesized CeO2 was in nano size with spherical shape...
February 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29202868/sp-a2-contributes-to-mirna-mediated-sex-differences-in-response-to-oxidative-stress-pro-inflammatory-anti-apoptotic-and-anti-oxidant-pathways-are-involved
#19
George T Noutsios, Nithyananda Thorenoor, Xuesheng Zhang, David S Phelps, Todd M Umstead, Faryal Durrani, Joanna Floros
BACKGROUND: Human innate host defense molecules, surfactant protein A1 (SP-A1), and SP-A2 differentially affect the function and proteome of the alveolar macrophage (AM). We hypothesized that SP-A genes differentially regulate the AM miRNome. METHODS: Humanized transgenic mice expressing SP-A1 and SP-A2 were subjected to O3-induced oxidative stress (OxS) or filtered air (FA), AMs were isolated, and miRNA levels were measured. RESULTS: In SP-A2 males, we found significant changes in miRNome in terms of sex and sex-OxS effects, with 11 miRNAs differentially expressed under OxS...
December 4, 2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/29198328/the-role-of-nuclear-factor-kappa-b-signaling-in-human-cervical-cancer
#20
REVIEW
Sam Tilborghs, Jerome Corthouts, Yannick Verhoeven, David Arias, Christian Rolfo, Xuan Bich Trinh, Peter A van Dam
Background The Nuclear Factor kappaB (NF-kB) family consists of transcription factors that play a complex and essential role in the regulation of immune responses and inflammation. NF-kB has recently generated considerable interest as it has been implicated in human cancer initiation, progression and resistance to treatment. In the present comprehensive review the different aspects of NF-kB signaling in the carcinogenesis of cancer of the uterine cervix are discussed. NF-kB functions as part of a network, which determines the pattern of its effects on the expression of several other genes (such as crosstalks with reactive oxygen species, p53, STAT3 and miRNAS) and thus its function...
December 2017: Critical Reviews in Oncology/hematology
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