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https://www.readbyqxmd.com/read/27906181/stat6-deficiency-ameliorates-graves-disease-severity-by-suppressing-thyroid-epithelial-cell-hyperplasia
#1
Xuechao Jiang, Bingbing Zha, Xiaoming Liu, Ronghua Liu, Jun Liu, Enyu Huang, Tingting Qian, Jiajing Liu, Zhiming Wang, Dan Zhang, Luman Wang, Yiwei Chu
Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27903966/pde5-inhibitors-enhance-the-lethality-of-pemetrexed-through-inhibition-of-multiple-chaperone-proteins-and-via-the-actions-of-cyclic-gmp-and-nitric-oxide
#2
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Sarah Gordon, Paul Dent
Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α - ATF4 - CHOP - Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 - XBP-1 - chaperone induction pathway; and activated a toxic eIF2α - CHOP - DR4 / DR5 / CD95 induction pathway. [Pemetrexed + sildenafil] reduced the expression of c-FLIP-s, MCL-1 and BCL-XL that was blocked in a cell-type -dependent fashion by either over-expression of HSP90 / GRP78 / HSP70 / HSP27 or by blockade of eIF2α-CHOP signaling...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27897419/exercise-restores-muscle-stem-cell-mobilization-regenerative-capacity-and-muscle-metabolic-alterations-via-adiponectin-adipor1-activation-in-samp10-mice
#3
Aiko Inoue, Xian Wu Cheng, Zhe Huang, Lina Hu, Ryosuke Kikuchi, Haiying Jiang, Limei Piao, Takeshi Sasaki, Kohji Itakura, Hongxian Wu, Guangxian Zhao, Yanna Lei, Guang Yang, Enbo Zhu, Xiang Li, Kohji Sato, Teruhiko Koike, Masafumi Kuzuya
BACKGROUND: Exercise train (ET) stimulates muscle response in pathological conditions, including aging. The molecular mechanisms by which exercise improves impaired adiponectin/adiponectin receptor 1 (AdipoR1)-related muscle actions associated with aging are poorly understood. Here we observed that in a senescence-accelerated mouse prone 10 (SAMP10) model, long-term ET modulated muscle-regenerative actions. METHODS: 25-week-old male SAMP10 mice were randomly assigned to the control and the ET (45 min/time, 3/week) groups for 4 months...
November 29, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27896224/in-vitro-apoptotic-effects-of-farnesyltransferase-blockade-in-acute-myeloid-leukemia-cells
#4
V Giudice, P Ricci, L Marino, M Rocco, G Villani, M Langella, L Manente, E Seneca, I Ferrara, L Pezzullo, B Serio, C Selleri
Farnesyltransferase inhibitors (FTIs) are a class of oral anti-cancer drugs currently tested in phase I-II clinical trials for treatment of hematological malignancies. The in vitro effects of various FTIs (alpha-hydroxyfarnesylphosphonic acid, manumycin-A and SCH66336) were tested on CD34(+) KG1a cell line and in primary acute myeloid leukemia (AML) cells from 64 patients. By cell viability and clonogeneic methylcellulose assays, FTIs showed a significant inhibitory activity in CD34(+) KG1a and primary bone marrow (BM) leukemic cells from 56% of AML patients...
November 2016: Translational Medicine @ UniSa
https://www.readbyqxmd.com/read/27888624/rhoa-regulates-resistance-to-irinotecan-by-regulating-membrane-transporter-and-apoptosis-signaling-in-colorectal-cancer
#5
Huang Ruihua, Zhang Mengyi, Zhao Chong, Qiu Meng, Ma Xin, Tang Qiulin, Bi Feng, Liu Ming
Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. While surgery remains the mainstay of treatment in early stage CRC, chemotherapy is usually given to prolong the overall survival and improve the quality of life for metastatic colorectal cancer (mCRC). But drug resistance is one of the major hurdles of mCRC treatment, and the underlying mechanisms are still largely unknown. In this study, we show that, compared with parental cells, RhoA is up-regulated in irinotecan (CPT-11)-resistant CRC cells...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888447/the-regulation-of-the-mitochondrial-apoptotic-pathway-by-glucocorticoid-receptor-in-collaboration-with-bcl-2-family-proteins-in-developing-t-cells
#6
Lilla Prenek, Ferenc Boldizsár, Réka Kugyelka, Emese Ugor, Gergely Berta, Péter Németh, Timea Berki
Glucocorticoids (GC) are important in the regulation of selection and apoptosis of CD4(+)CD8(+) double-positive (DP) thymocytes. The pronounced GC-sensitivity of DP thymocytes, observed earlier, might be due to the combination of classical (genomic) and alternative (non-genomic) glucocorticoid receptor (GR) signaling events modifying activation or apoptotic pathways. In particular, the previously demonstrated mitochondrial translocation of activated GR in DP thymocytes offered a fascinating explanation for their pronounced GC-induced apoptosis sensitivity...
November 26, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27887917/microrna-136-inhibits-cancer-stem-cell-activity-and-enhances-the-anti-tumor-effect-of-paclitaxel-against-chemoresistant-ovarian-cancer-cells-by-targeting-notch3
#7
Ju-Yeon Jeong, Hae-Youn Kang, Tae-Heon Kim, Gwang-Il Kim, Jin-Hyung Huh, Ah-Young Kwon, Se-Wha Kim, Sang-Geun Jung, Hee-Jung An
To identify microRNAs (miRNAs) regulating Notch3 expression in association with paclitaxel resistance, candidate miRNAs targeting Notch3 were predicted using TargetScan. We found that miR-136 directly targets Notch3, and miR-136 was significantly downregulated in OSC tissues relative to normal control tissues, and low expression of miR-136 correlated with poor overall in ovarian cancer patients. Artificial miR-136 overexpression significantly reduced cell viability, proliferation, CSC spheroid formation, and angiogenesis, and increased apoptosis in paclitaxel-resistant SKpac cells compared with the effects of paclitaxel alone...
November 22, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27886335/microrna-421-induces-apoptosis-of-c-33a-cervical-cancer-cells-via-down-regulation-of-bcl-xl
#8
X J Lai, X Y Cheng, L D Hu
Cervical cancer is a life-threatening condition. MicroRNAs (miRNAs) can promote or inhibit cell death and proliferation. The present study investigated the effect of miRNA 421 on the growth and apoptosis of cervical cancer cells. miRNA 421 and control miRNA were synthesized and transfected into c-33a cervical cancer cells. A thiazolyl blue tetrazolium bromide assay, caspase-3 activity, and flow cytometry were used to study the effects of miRNA 421 on c-33a cell growth, and apoptosis. Small interfering RNA targeting Bcl-xL was synthesized and transfected into c-33a cells along with miRNA 421...
November 21, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27881007/egcg-sensitizes-human-nasopharyngeal-carcinoma-cells-to-trail-mediated-apoptosis-by-activation-nf-%C3%AE%C2%BAb
#9
P Li, S Li, D Yin, J Li, L Wang, C Huang, X Yang
Aim of presented study was to investigate whether EGCG could sensitize TRAIL resistant NPC cells to TRAIL-mediated apoptosis. Three human NPC cell-lines CNE-1, CNE-2, C666-1 and a non-transformed nasopharyngeal epithelium cell-line NP-69 were treated with EGCG or/and TRAIL. The apoptosis and TRAIL receptors were determined by flow cytometric analysis. The protein expression was determined by western blotting. Mitochondrial transmembrane potential was dertemined by DiOC6 (3). C666-1 cell-line was the only one that resistant to TRAIL and selected to be treated with EGCG...
November 24, 2016: Neoplasma
https://www.readbyqxmd.com/read/27878744/protective-effect-of-saccharomyces-boulardii-on-deoxynivalenol-induced-injury-of-porcine-macrophage-via-attenuating-p38-mapk-signal-pathway
#10
Chao Chang, Kun Wang, Sheng-Nan Zhou, Xue-Dong Wang, Jin-E Wu
The aims of our study were to evaluate the effects of Saccharomyces boulardii (S. boulardii) on deoxynivalenol (DON)-induced injury in porcine alveolar macrophage cells (PAMCs) and to explore the underlying mechanisms. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis, ELISA, qRT-PCR, and western blot were performed to assess whether S. boulardii could prevent DON-induced injury by p38 mitogen-activated protein kinase (p38 MAPK) signal pathway. The results showed that pretreatment with 8 μM DON could decrease the viability of PAMC and significantly increase the apoptosis rate of PAMC, whereas S...
November 23, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27878290/-oleocanthal-exerts-anti-melanoma-activities-and-inhibits-stat3-signaling-pathway
#11
Yanli Gu, Jing Wang, Lixin Peng
Tumor angiogenesis, growth and metastasis are three closely related processes. We therefore explored the effects of (-)-oleocanthal (OC) on the three processes in melanoma and investigated underlying mechanisms. In vitro, OC suppressed proliferation, migration, invasion and induced apoptosis in melanoma cells. In addition, OC inhibited proliferation, migration, invasion and tube formation in human umbilical vascular endothelial cells. In vivo, it exhibited potent activity in suppressing tumor growth in a subcutaneous xenograft model...
November 23, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27865863/curcumin-promotes-the-oncoltyic-capacity-of-vesicular-stomatitis-virus-for-the-treatment-of-prostate-cancers
#12
Dylan J Fehl, Maryam Ahmed
Vesicular stomatitis virus (VSV) matrix (M) protein mutants have been studied as oncolytic agents due to their capacity to effectively kill cancer cells while exhibiting low virulence in vivo. Despite encouraging results, many cancer cells maintain resistance to oncolytic VSV mutants in part due to residual antiviral responses. We sought to determine whether combination of VSV with natural agents with anti-tumor properties, such as curcumin, resveratrol, and flavokavain B, would enhance tumor cell killing in a prostate cancer model...
November 16, 2016: Virus Research
https://www.readbyqxmd.com/read/27863431/synergistic-antitumor-activity-of-the-combination-of-salubrinal-and-rapamycin-against-human-cholangiocarcinoma-cells
#13
Xiaofang Zhao, Chunyan Zhang, Hong Zhou, Bin Xiao, Ying Cheng, Jinju Wang, Fuli Yao, Chunyan Duan, Run Chen, Youping Liu, Chunhong Feng, Hong Li, Jing Li, Rongyang Dai
Less is known about the roles of eukaryotic initiation factor alpha (eIF2α) in cholangiocarcinoma (CCA). Here, we report that eIF2α inhibitor salubrinal inhibits the proliferation of human CCA cells. Clinical application of mammalian target of rapamycin (mTOR) inhibitors only has moderate antitumor efficacy. Therefore, combination approaches may be required for effective clinical use of mTOR inhibitors. Here, we investigated the efficacy of the combination of salubrinal and rapamycin in the treatment of CCA...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27855137/garcinol-upregulates-gabaa-and-gad65-expression-modulates-bdnf-trkb-pathway-to-reduce-seizures-in-pentylenetetrazole-ptz-induced-epilepsy
#14
Fang Hao, Li-Hua Jia, Xiao-Wan Li, Ying-Rui Zhang, Xue-Wu Liu
BACKGROUND Epilepsy is the most predominant neurological disorder characterized by recurrent seizures. Despite treatment with antiepileptic drugs, epilepsy still is a challenge to treat, due to the associated adverse effects of the drugs. Previous investigations have shown critical roles of BDNF-TrkB signalling and expression of glutamic acid decarboxylase 65 (GAD65) and GABAA in the brain during epilepsy. Thus, drugs that could modulate BDNF-TrkB signal and expression of GAD65 and GABAA could aid in therapy...
November 17, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27853755/differential-stress-response-mechanisms-in-right-and-left-ventricles
#15
Makhosazane Zungu-Edmondson, Yuichiro J Suzuki
Right ventricular (RV) failure is the major cause of death among patients with pulmonary hypertension. However, differences between the RV and left ventricle (LV) of the adult heart have not been defined, despite myocytes from these two ventricles originate from different progenitor cells. The lack of such knowledge interferes with developing therapeutic strategies to protect the RV. The goal of this study was to identify possible differences between stress responses in the RV and LV free walls of adult rats...
2016: Journal of Rare Diseases Research & Treatment
https://www.readbyqxmd.com/read/27852038/transcriptomic-metabolomic-reprogramming-in-egfr-mutant-nsclc-early-adaptive-drug-escape-linking-tgf%C3%AE-2-bioenergetics-mitochondrial-priming
#16
Praveena S Thiagarajan, Xiaoliang Wu, Wei Zhang, Ivy Shi, Rakesh Bagai, Patrick Leahy, Yan Feng, Martina Veigl, Daniel Lindner, David Danielpour, Lihong Yin, Rafael Rosell, Trever G Bivona, Zhenfeng Zhang, Patrick C Ma
The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent. The drug-escape cell states were analyzed by integrated transcriptomic and metabolomics profiling uncovering a central role for autocrine TGFβ2 in mediating cellular plasticity through profound cellular adaptive Omics reprogramming, with common mechanistic link to prosurvival mitochondrial priming...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27849335/mycotoxin-verrucarin-a-inhibits-proliferation-and-induces-apoptosis-in-prostate-cancer-cells-by-inhibiting-prosurvival-akt-nf-kb-mtor-signaling
#17
Yongbo Liu, Xiaohua Gao, Dorrah Deeb, Yiguan Zhang, Jiajiu Shaw, Frederick A Valeriote, Subhash C Gautam
Trichothecenes are powerful mycotoxins that inhibit protein synthesis and induce ribotoxic stress response in mammalian cells. Verrucarin A (VC-A) is a Type D macrocyclic mycotoxin which inhibits cell proliferation and induces apoptosis in cancer cells. However, the antitumor activity of VC-A for prostate cancer cells has not been investigated. The objective of the present study was to determine the anticancer activity and its mechanism of action in hormone-responsive (LNCaP) and hormone-refractory (PC-3) carcinoma of the prostate (CaP) cell lines...
November 2016: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/27834133/the-effects-of-colchicum-baytopiorum-on-regulatory-genes-of-apoptotic-and-autophagic-cell-death-in-hela-cells
#18
Özlem D Özsöylemez, Melek Öztürk, Nurhayat Sütlüpinar, Sera Kayacan, Matem Tunçdemir, Gül Özcan
BACKGROUND: The natural products have increasing important for the development of anticancer agents. Colchicum baytopiorum C.D.Brickell (C. baytopiorum), an endemic species for Turkey, contains colchicine and its derivatives. Stimulation of apoptotic and autophagy-mediated cell deaths are effective strategy for anticancer therapies. AIM: The aim of the study is to determine the role of the extract on both apoptotic and autophagic cell death in HeLa cell line. METHODS: The cell viability of C...
November 9, 2016: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/27830683/-expression-of-apoptosis-genes-in-the-brain-of-rats-with-genetically-defined-fear-induced-aggression
#19
T V Ilchibaeva, A S Tsybko, R V Kozhemyakina, V S Naumenko
The programmed cell death (or apoptosis) plays an important role both in developing and mature brains. Multiple data indicate the involvement of processes of apoptosis in mechanisms of different psychopathologies. At the same time, nothing is known about the role of apoptosis in the regulation of genetically defined aggression. In the present work, the expression of the genes that encode main pro- and antiapoptotic BAX and BCL-XL proteins, as well as caspase 3 (the main effector of apoptosis), in different brain structures of rats that were selected on a high aggression towards human (or its absence) was studied...
September 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27829861/itraq-based-proteomic-analysis-of-ginsenoside-f2-on-human-gastric-carcinoma-cells-sgc7901
#20
Qian Mao, Pin-Hu Zhang, Jie Yang, Jin-Di Xu, Ming Kong, Hong Shen, He Zhu, Min Bai, Li Zhou, Guang-Fu Li, Qiang Wang, Song-Lin Li
Ginsenoside F2 (F2), a protopanaxdiol type of saponin, was reported to inhibit human gastric cancer cells SGC7901. To better understand the molecular mechanisms of F2, an iTRAQ-based proteomics approach was applied to define protein expression profiles in SGC7901 cells in response to lower dose (20 μM) and shorter duration (12 hour) of F2 treatment, compared with previous study. 205 proteins were screened in terms of the change in their expression level which met our predefined criteria. Further bioinformatics and experiments demonstrated that F2 treatment downregulated PRR5 and RPS15 and upregulated RPL26, which are implicated in ribosomal protein-p53 signaling pathway...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
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