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https://www.readbyqxmd.com/read/28927258/a-proteomics-based-approach-reveals-differential-regulation-of-visceral-adipose-tissue-proteins-between-metabolically-healthy-and-unhealthy-obese-patients
#1
Assim A Alfadda, Afshan Masood, Mohammed Y Al-Naami, Pierre Chaurand, Hicham Benabdelkamel
Obesity and the metabolic disorders that constitute metabolic syndrome are a primary cause of morbidity and mortality in the world. Nonetheless, the changes in the proteins and the underlying molecular pathways involved in the relevant pathogenesis are poorly understood.In this study a proteomic analysis of the visceral adipose tissue isolated from metabolically healthy and unhealthy obese patients was used to identify presence of altered pathway(s) leading to metabolic dysfunction. Samples were obtained from 18 obese patients undergoing bariatric surgery and were subdivided into two groups based on the presence or absence of comorbidities as defined by the International Diabetes Federation...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28927158/regulation-of-htra2-on-wt1-gene-expression-under-imatinib-stimulation-and-its-effects-on-the-cell-biology-of-k562-cells
#2
Lixia Zhang, Yan Li, Xiaoyan Li, Qing Zhang, Shaowei Qiu, Qi Zhang, Min Wang, Haiyan Xing, Qing Rao, Zheng Tian, Kejing Tang, Jianxiang Wang, Yingchang Mi
The aim of the present study was to investigate the regulation of Wilms Tumor 1 (WT1) by serine protease high-temperature requirement protein A2 (HtrA2), a member of the Htr family, in K562 cells. In addition, the study aimed to observe the effect of this regulation on cell biological functions and its associated mechanisms. Expression of WT1 and HtrA2 mRNA, and proteins following imatinib and the HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryl iodine]-1, 3-diphenyl-2-thiobarbituric acid (UCF-101) treatment was detected with reverse transcription-quantitative polymerase chain reaction and western blot analysis...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927117/salvia-miltiorrhiza-extract-inhibits-tpa-induced-mmp-9-expression-and-invasion-through-the-mapk-ap-1-signaling-pathway-in-human-breast-cancer-mcf-7-cells
#3
Jeong-Mi Kim, Eun-Mi Noh, Hyun-Kyung Song, Minok Lee, Soo Ho Lee, Sueng Hyuk Park, Chan-Keun Ahn, Guem-San Lee, Eui-Baek Byun, Beom-Su Jang, Kang-Beom Kwon, Young-Rae Lee
Cancer cell invasion is crucial for metastasis. A major factor in the capacity of cancer cell invasion is the activation of matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix. Salvia miltiorrhiza has been used as a promotion for blood circulation to remove blood stasis. Numerous previous studies have demonstrated that S. miltiorrhiza extracts (SME) decrease lipid levels and inhibit inflammation. However, the mechanism behind the effect of SME on breast cancer invasion has not been identified...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927069/overexpression-of-reic-dkk-3-suppresses-the-expression-of-cd147-and-inhibits-the-proliferation-of-human-bladder-cancer-cells
#4
Yuhei Horikawa, Masami Watanabe, Takuya Sadahira, Yuichi Ariyoshi, Yasuyuki Kobayashi, Motoo Araki, Koichiro Wada, Kazuhiko Ochiai, Shun-Ai Li, Yasutomo Nasu
Our group previously developed an adenoviral vector encoding the REIC/Dkk-3 gene (Ad-REIC), a tumor suppressor, for cancer gene therapy. The Ad-REIC agent induces apoptosis and inhibits invasion in a number of cancer cell lines; however, the molecular mechanisms underlying its effects remain unclear. Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a key molecule that promotes cancer proliferation and invasion. In order to elucidate the therapeutic mechanism of Ad-REIC, its effect on the expression of CD147 in human bladder cancer KK47 cells was investigated...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926923/involvement-of-mapk-nf-%C3%AE%C2%BAb-signal-transduction-pathways-camellia-japonica-mitigates-inflammation-and-gastric-ulcer
#5
Md Rashedunnabi Akanda, Byung-Yong Park
Gastric ulcer is an important risk factor for human health globally. Camellia japonica (CJ) is a plant of which the fruits are used as traditional phytomedicine for inflammatory and immunomodulatory diseases; however, the underlying molecular mechanism has not been clarified. The present study aimed to investigate the immunopharmacological activities of Camellia japonica and validate its pharmacological targets. To evaluate the protective roles of Camellia japonica on LPS-induced inflammation in RAW 264.7 cells and HCl/EtOH-induced gastric ulcer in mice; we applied 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), nitric oxide (NO), reactive oxygen species (ROS), histopathology, malondialdehyde (MDA), quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and western blot analyses...
September 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28926106/oroxyloside-inhibits-angiogenesis-through-suppressing-internalization-of-vegfr2-flk-1-in-endothelial-cells
#6
Kai Zhao, Xiaorui Li, Binyan Lin, Dawei Yang, Yuxin Zhou, Zhiyu Li, Qinglong Guo, Na Lu
Increasing flavonoids have been reported to possess anti-angiogenic effects. Inhibition of angiogenesis plays a critical role in the treatment of cancer, especially in advanced metastatic cancer. In this study, we assessed the effect of Oroxylin A-7-glucuronide (Oroxyloside), a main metabolite of Oroxylin A, on angiogenesis in human endothelial cell-like EA.hy926 cells. Oroxyloside suppressed the migration and tube formation of EA.hy926 cells. Meanwhile, microvessels sprouting from aortic rings and new blood vessels on the chicken chorioallantoic membrane (CAM) were also inhibited...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28926092/key-genes-regulating-the-liposecretion-process-of-mature-adipocytes
#7
Giulia Maurizi, Tiina Petäistö, Angela Maurizi, Lucio Della Guardia
White mature adipocytes (MAs) are plastic cells able to reversibly transdifferentiate toward fibroblast-like cells maintaining stem cell gene signatures. The main morphologic aspect of this transdifferentiation process, called liposecretion, is the secretion of large lipid droplets and the development of organelles necessary for exocrine secretion. There is a considerable interest in the adipocyte plastic properties involving liposecretion process, but the molecular details are incompletely explored. This review analyzes the gene expression of MAs isolated from human subcutaneous fat tissue with respect to bone marrow (BM)-derived mesenchymal stem cells (MSC) focusing on gene regulatory pathways involved into cellular morphology changes, cellular proliferation and transports of molecules through the membrane, suggesting potential ways to guide liposecretion...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28925592/defining-a-microrna-mrna-interaction-map-for-calcineurin-inhibitor-induced-nephrotoxicity
#8
Christopher J Benway, John Iacomini
Calcineurin inhibitors induce nephrotoxicity through poorly understood mechanisms thereby limiting their use in transplantation and other diseases. Here we define a microRNA (miRNA)-messenger RNA (mRNA) interaction map that facilitates exploration into the role of miRNAs in cyclosporine-induced nephrotoxicity (CIN) and the gene pathways they regulate. Using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP), we isolated RNAs associated with Argonaute 2 in the RNA-Induced Silencing Complex (RISC) of cyclosporine A (CsA) treated and control human proximal tubule cells and identified mRNAs undergoing active targeting by miRNAs...
September 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28925510/mir-30a-5p-ameliorates-spinal-cord-injury-induced-inflammatory-responses-and-oxidative-stress-by-targeting-neurod-1-through-mapk-erk-signaling
#9
Xiaodong Fu, Yi Shen, Weili Wang, Xiaomiao Li
Spinal cord injury (SCI) is a major disability requiring more effective treatment than is currently available. MicroRNAs have been shown to effectively regulate gene expression at the translational level. The aim of the present study was to explore the potential role of miR-30-5p and possible mechanism in SCI. We found that miR-30-5p was notably down-regulated, while Neurod 1 expression was highly elevated in microglia from the mouse model of SCI. Additionally, overexpression of miR-30a-5p significantly suppressed inflammatory responses as reflected by an decrease in the secretion of the cytokines TNF-α, IL-1β and IL-10 triggered by SCI...
September 19, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28925397/coactosin-like-protein-clp-cotl1-suppresses-breast-cancer-growth-through-activation-of-il-24-perp-and-inhibition-of-non-canonical-tgf%C3%AE-signaling
#10
L Xia, X Xiao, W L Liu, Y Song, T J J Liu, Y J Li, E Zacksenhaus, X J Hao, Y Ben-David
Coactosin-like protein (CLP, or Cotl1), is an F-actin-binding protein, whose role in cancer is largely unknown. Here we show that CLP/Cotl1 is highly expressed in a rat epithelial breast cancer cell line (FE1.3) compared with its mesenchymal counterpart (FE1.2). Knockdown of CLP/Cotl1 in FE1.3 cells increased cell proliferation, whereas its overexpression in FE1.2 cells inhibited proliferation in culture and reduced tumor growth in xenograft assays in mice. Mechanistically, we identified two major pathways through which CLP/Cotl1 exerts its suppressive effects...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28925389/ptsd-blood-transcriptome-mega-analysis-shared-inflammatory-pathways-across-biological-sex-and-modes-of-trauma
#11
Michael S Breen, Daniel S Tylee, Adam X Maihofer, Thomas C Neylan, Divya Mehta, Elisabeth Binder, Sharon D Chandler, Jonathan L Hess, William S Kremen, Victoria B Risbrough, Christopher H Woelk, Dewleen G Baker, Caroline M Nievergelt, Ming T Tsuang, Joseph D Buxbaum, Stephen J Glatt
Transcriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas...
September 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28925164/-effects-of-icariin-on-proliferation-of-vascular-smooth-muscle-cell-induced-by-ox-ldl-via-impacting-mapk-signaling-pathway
#12
Yan-Wu Hu, Hai-Tao Li, Kai Liu, Meng-Tong Yan, Yang Zhang, Li-Qun Ren
This paper was aimed to study the effects of icariin (ICA) on the proliferation of vascular smooth muscle cell (VSMC) induced by oxidized low density lipoprotein (ox-LDL), and the molecular mechanism of the expression of proliferating cell nuclear antigen (PCNA) and MAPK signaling pathway. In this study, VSMC was induced by ox-LDL (50 mg•L⁻¹),the effect of ICA on the proliferation of VSMC was detected by MTT assay, Western blot and Real-time PCR. The results showed that after stimulation of ox-LDL, the proliferation activity of VSMC was increased, S phase, G₂/M phase cells were increased, G₀/G₁ phase cells were decreased, PCNA protein expression was enhanced; ICA (40, 20, 10 μmol•L⁻¹) could effectively inhibit ox-LDL-induced VSMC proliferation, S phase and G₂/M phase cells were decreased, the percentage of cells in G₀/G₁ phase were increased, PCNA expression was decreased, p38MAPK and ERK1/2 activation were inhibited...
October 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28924376/verteporfin-inhibits-cell-proliferation-and-induces-apoptosis-in-human-leukemia-nb4-cells-without-light-activation
#13
Min Chen, Liang Zhong, Shi-Fei Yao, Yi Zhao, Lu Liu, Lian-Wen Li, Ting Xu, Liu-Gen Gan, Chun-Lan Xiao, Zhi-Ling Shan, Bei-Zhong Liu
Background and Aims: Verteporfin (VP), clinically used in photodynamic therapy for neovascular macular degeneration, has recently been proven a suppressor of yes-associated protein (YAP) and has shown potential in anticancer treatment. However, its anti-human leukemia effects in NB4 cells remain unclear. In this study, we investigated the effects of VP on proliferation and apoptosis in human leukemia NB4 cells. Methods: NB4 cells were treated with VP for 24 h. The effects of VP on cell proliferation were determined using a Cell-Counting Kit-8 assay (CCK-8) assay and colony forming assay...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28924347/the-mechanisms-of-graphene-based-materials-induced-programmed-cell-death-a-review-of-apoptosis-autophagy-and-programmed-necrosis
#14
REVIEW
Lingling Ou, Shaoqiang Lin, Bin Song, Jia Liu, Renfa Lai, Longquan Shao
Graphene-based materials (GBMs) are widely used in many fields, including biomedicine. To date, much attention had been paid to the potential unexpected toxic effects of GBMs. Here, we review the recent literature regarding the impact of GBMs on programmed cell death (PCD). Apoptosis, autophagy, and programmed necrosis are three major PCDs. Mechanistic studies demonstrated that the mitochondrial pathways and MAPKs (JNK, ERK, and p38)- and TGF-β-related signaling pathways are implicated in GBMs-induced apoptosis...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28924177/loss-of-mapk-activated-protein-kinase-2-enables-potent-dendritic-cell-driven-anti-tumour-t-cell-response
#15
Klara Soukup, Angela Halfmann, Barbara Dillinger, Fiona Poyer, Katharina Martin, Bernadette Blauensteiner, Maximilian Kauer, Mario Kuttke, Gernot Schabbauer, Alexander M Dohnal
Maintaining dendritic cells (DC) in a state of dysfunction represents a key mechanism by which tumour cells evade recognition and elimination by the immune system. Limited knowledge about the intracellular mediators of DC dysfunction restricts success of therapies aimed at reactivating a DC-driven anti-tumour immune response. Using a cell type-specific murine knock-out model, we have identified MAPK-activated protein kinase 2 (MK2) as a major guardian of a suppressive DC phenotype in the melanoma tumour microenvironment...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924151/dna-methylomes-reveal-biological-networks-involved-in-human-eye-development-functions-and-associated-disorders
#16
María Berdasco, Antonio Gómez, Marcos J Rubio, Jaume Català-Mora, Vicente Zanón-Moreno, Miguel Lopez, Cristina Hernández, Shigeo Yoshida, Takahito Nakama, Keijiro Ishikawa, Tatsuro Ishibashi, Amina M Boubekeur, Lotfi Louhibi, Miguel A Pujana, Sergi Sayols, Fernando Setien, Dolores Corella, Carmen de Torres, Andreu Parareda, Jaume Mora, Ling Zhao, Kang Zhang, Matilde E Lleonart, Javier Alonso, Rafael Simó, Josep M Caminal, Manel Esteller
This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923937/direct-engagement-of-the-pi3k-pathway-by-mutant-kit-dominates-oncogenic-signaling-in-gastrointestinal-stromal-tumor
#17
Benedikt Bosbach, Ferdinand Rossi, Yasemin Yozgat, Jennifer Loo, Jennifer Q Zhang, Georgina Berrozpe, Katherine Warpinski, Imke Ehlers, Darren Veach, Andrew Kwok, Katia Manova, Cristina R Antonescu, Ronald P DeMatteo, Peter Besmer
Gastrointestinal stromal tumors (GISTs) predominantly harbor activating mutations in the receptor tyrosine kinase KIT. To genetically dissect in vivo the requirement of different signal transduction pathways emanating from KIT for tumorigenesis, the oncogenic Kit(V558Δ) mutation was combined with point mutations abrogating specific phosphorylation sites on KIT. Compared with single-mutant Kit(V558Δ/+) mice, double-mutant Kit(V558Δ;Y567F/Y567F) knock-in mice lacking the SRC family kinase-binding site on KIT (pY567) exhibited attenuated MAPK signaling and tumor growth...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923912/exploiting-drug-addiction-mechanisms-to-select-against-mapki-resistant-melanoma
#18
Aayoung Hong, Gatien Moriceau, Lu Sun, Shirley Lomeli, Marco Piva, Robert Damoiseaux, Sheri L Holmen, Norman E Sharpless, Willy Hugo, Roger S Lo
Melanoma resistant to MAPK inhibitor(s) (MAPKi) displays loss-of-fitness upon experimental MAPKi withdrawal and, clinically, may be re-sensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi-addiction in MAPKi-resistant MUTBRAF or MUTNRAS melanoma. MAPKi-addiction phenotypes evident upon drug-withdrawal spanned transient cell-cycle slow-down to cell-death responses, the latter of which required a robust p-ERK rebound. Generally, drug withdrawal-induced p-ERK rebound up-regulated p38-FRA1-JUNB-CDKN1A and down-regulated proliferation, but only a robust p-ERK rebound resulted in DNA damage and parthanatos-related cell death...
September 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28923783/bmp7-induced-pten-inhibits-akt-and-prevents-renal-fibrosis
#19
Debra F Higgins, Leah Ewart, Enda Masterson, Sadhbh Tennant, Gleb Grebnev, Marco Prunotto, Sylvia Pomposiello, Karin Conde-Knape, Finian M Martin, Catherine Godson
Bone morphogenetic protein-7 (BMP-7) counteracts pro-fibrotic effects of TGFβ1 in cultured renal cells and protects from fibrosis in acute and chronic renal injury models. Using the unilateral ureteral obstruction (UUO) model of chronic renal fibrosis, we investigated the effect of exogenous-rhBMP-7 on pro-fibrotic signaling pathways mediated by TGFβ1 and hypoxia. Mice undergoing UUO were treated with vehicle or rhBMP-7 (300μg/kg i.p.) every other day for eight days and kidneys analysed for markers of fibrosis and SMAD, MAPK, and PI3K signaling...
September 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28923383/design-synthesis-and-structure-activity-relationship-studies-of-a-focused-library-of-pyrimidine-moiety-with-anti-proliferative-and-anti-metastasis-activities-in-triple-negative-breast-cancer
#20
Dahong Yao, Yuxin Zhou, Lingjuan Zhu, Liang Ouyang, Jin Zhang, Yingnan Jiang, Yuqian Zhao, Dejuan Sun, Shilin Yang, Yang Yu, Jinhui Wang
Triple-negative breast cancer (TNBC) is a clinical conundrum with distinct clinical and pathologic features, which is characterized by high aggression, poor prognosis, and lack of targeted therapies. In this study, based on the structural features of type II kinase inhibitors, we designed and synthesized a focused library of 41 pyrimidine derivatives possessing potent anti-proliferation activity, Y29 showed the most potent activity against MDA-MB-231 cells. Subsequently, we carried out target prediction, homology modeling, molecular docking, dynamics simulation and determination of enzymatic activity...
September 15, 2017: European Journal of Medicinal Chemistry
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