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https://www.readbyqxmd.com/read/29901128/downregulation-of-microrna%C3%A2-660-inhibits-cell-proliferation-and-invasion-in-osteosarcoma-by-directly-targeting-forkhead-box-o1
#1
Peng Zhang, Haifeng Gao, Qing Li, Xinlei Chen, Xifa Wu
The abnormal expression of microRNAs (miRNAs/miRs) has been observed in osteosarcoma (OS), and these differently expressed miRNAs contribute to the occurrence and development of OS by regulating various biological behaviours. Therefore, a comprehensive understanding of the detailed roles of aberrantly expressed miRNAs in OS progression may be favourable to the identification of promising therapeutic strategies for the treatment of patients with this malignancy. The present study demonstrated that miR‑660‑5p (miR‑660) expression was significantly upregulated in OS tissues and cell lines compared with that in normal adjacent tissues and normal human osteoblast hFOB1...
June 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29898687/pd-l1-assessment-in-pediatric-rhabdomyosarcoma-a-pilot-study
#2
Giulia Bertolini, Luca Bergamaschi, Andrea Ferrari, Salvatore L Renne, Paola Collini, Cecilia Gardelli, Marta Barisella, Giovanni Centonze, Stefano Chiaravalli, Cinzia Paolino, Massimo Milione, Maura Massimino, Michela Casanova, Patrizia Gasparini
BACKGROUND: Rhabdomyosarcomas (RMSs) are the most frequent soft tissue sarcoma in children and adolescents, defined by skeletal muscle differentiation and the status of FOXO1 fusions. In pediatric malignancies, in particular RMS, scant and controversial observations are reported about PD-L1 expression as a putative biomarker and few immune checkpoint clinical trials are conducted. METHODS: PD-L1 assessment was evaluated by immunohistochemistry (IHC) utilizing two anti-PDL1 antibodies, in a pilot cohort of 25 RMS...
June 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29896241/dendrobium-mixture-regulates-hepatic-gluconeogenesis-in-diabetic-rats-via-the-phosphoinositide-3-kinase-protein-kinase-b-signaling-pathway
#3
Xinjun Lin, Hong Shi, Yi Cui, Xiaoning Wang, Jieping Zhang, Wenzhen Yu, Min Wei
The present study aimed to evaluate the impact of dendrobium mixture (DMix) on the gene and protein expression of insulin signaling pathway-associated factors in the livers of diabetic rats. The molecular mechanisms by which DMix inhibits gluconeogenesis were also investigated. A total of 47 female Wistar rats were used in the present study. Of these, 11 rats were randomly selected as healthy controls and diabetes was induced in the remaining 36 rats by administering a high-fat and high-sugar diet for 6 weeks, followed by two intraperitoneal injections of streptozotocin...
July 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29894781/glycophagy-an-emerging-target-in-pathology
#4
REVIEW
Hong Zhao, Mingzhu Tang, Meiqing Liu, Linxi Chen
Autophagy, a highly conserved self-digestion process, is initially regarded as non-selectively sequestering and degradation cytoplasmic contents. Nowadays, many kinds of selective autophagy have been found in response to various physiological cues such as mitophagy, reticulophagy and glycophagy. Glycophagy, as a selective autophagy, plays a crucial role in maintaining glucose homeostasis in many tissues including heart, liver and skeletal muscles. Moreover, glycophagy is highly regulated by many signal pathways like the cyclic AMP protein kinase A/protein kinase A, PI3K-Akt/PKB-mTOR and Calcium...
June 9, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29894511/high-intensity-eccentric-training-ameliorates-muscle-wasting-in-colon-26-tumor-bearing-mice
#5
Daisuke Tatebayashi, Koichi Himori, Ryotaro Yamada, Yuki Ashida, Mitsunori Miyazaki, Takashi Yamada
Eccentric (ECC) contractions are used to maintain skeletal muscle mass and strength in healthy subjects and patients. Here we investigated the effects of ECC training induced by electrical stimulation (ES) on muscle wasting in colon 26 (C-26) tumor-bearing mice. Mice were divided into four groups: control (CNT), CNT + ECC, C-26, and C-26 + ECC. Cancer cachexia was induced by a subcutaneous injection of C-26 cells and developed for four weeks. In experiment 1, muscle protein synthesis rate and mammalian target of rapamycin complex (mTORC) 1 signaling were investigated six hours after one bout of ECC-ES (2 s contraction given every 6 s, 20°/s, 4 sets of 5 contractions)...
2018: PloS One
https://www.readbyqxmd.com/read/29891553/ck2-controls-th17-and-regulatory-t-cell-differentiation-through-inhibition-of-foxo1
#6
Sara A Gibson, Wei Yang, Zhaoqi Yan, Hongwei Qin, Etty N Benveniste
Growing evidence demonstrates that the highly conserved serine/threonine kinase CK2 promotes Th17 cell differentiation while suppressing the generation of Foxp3+ regulatory T cells (Tregs); however, the exact mechanism by which CK2 regulates the Th17/Treg axis remains unclear. CK2 can be composed of three distinct subunits: two catalytic subunits, CK2α and CK2α', and the regulatory subunit CK2β. We generated mice that lack the major catalytic subunit of CK2, CK2α, specifically in mature T cells using the distal Lck-Cre (CK2α-/- )...
June 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29890134/car-mediated-repression-of-cdkn1a-p21-is-accompanied-by-the-akt-activation
#7
Andrei A Yarushkin, Mark E Mazin, Anastasia Y Yunusova, Kseniya V Korchagina, Yuliya A Pustylnyak, Elena A Prokopyeva, Vladimir O Pustylnyak
It was shown that CAR participates in the regulation of many cell processes. Thus, the activation of CAR causes a proliferating effect in the liver, which provides grounds to consider CAR as a therapeutic target when having a partial resection of this organ. Even though a lot of work has been done on the function of CAR in regulating hepatocyte proliferation, very little has been done on its complex mediating mechanism. This study, therefore, showed that the liver growth resulting from CAR activation leads to the decline in the level of PTEN protein and subsequent Akt activation in mouse liver...
June 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29886768/human-chorionic-gonadotropin-induces-decidualization-of-ectopic-human-endometrium-more-effectively-than-forskolin-in-an-in-vivo-endometriosis-model
#8
Yvonne Koch, Pauline Wimberger, Ruth Grümmer
Endometriosis, characterized by the presence of endometrial tissue at ectopic sites, is a leading cause of pelvic pain and subfertility in women. The stromal compartment of the endometrium is considered to play a pivotal role in the establishment and persistence of endometriotic lesions, thus impaired decidualization of these cells may result in enhanced invasion capacity at ectopic sites. Consequently, stimulation of decidualization may alleviate this disease. To analyze the effect of systemically applied compounds on decidualization of ectopic endometrial tissue, endometriosis was induced by suturing human eutopic endometrium to the peritoneum of 22 NOD/SCID mice...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29885845/foxo1-mediated-autophagy-plays-an-important-role-in-the-neuroprotective-effects-of-hydrogen-in-a-rat-model-of-vascular-dementia
#9
Xin Jiang, Xiaoli Niu, Qingjun Guo, Yanhong Dong, Jing Xu, Nan Yin, Qianqian Qi, Yanqiu Jia, Liwei Gao, Qihui He, Peiyuan Lv
Vascular dementia (VD) is a heterogeneous group of brain disorders in which cognitive impairment is attributed to cerebrovascular pathologies. Autophagy, a self-cannibalization mechanism, has been demonstrated to be involved in VD progression. Molecular hydrogen is known for its powerful anti-oxidative, anti-apoptotic, and anti-inflammatory activities, and it is also involved in autophagy. However, the effects of hydrogen on VD remain unclear. The current study found that hydrogen-rich water (HRW) significantly alleviated spatial learning and memory impairments...
June 7, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29885786/oxidative-stress-reduces-trophoblast-foxo1-and-integrin-%C3%AE-3-expression-that-inhibits-cell-motility
#10
Chie-Pein Chen, Cheng-Yi Chen, Yi-Hsin Wu, Chia-Yu Chen
Preeclampsia is a serious pregnancy complication associated with placental oxidative stress and impaired trophoblast migration. The mechanism of defective trophoblast migration remains unknown. Forkhead O1 (FOXO1) is a transcription factor. Integrin β3 is involved in cell motility. We hypothesized that FOXO1 mediates expression of trophoblast integrin β3, which could be impaired by oxidative stress and have implications in preeclampsia. The expressions of FOXO1 and integrin β3 were significantly reduced in preeclamptic placentas (n=15) compared to that of controls (n=15; p<0...
June 7, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29880906/discovery-of-pancreastatin-inhibitor-psti8-for-the-treatment-of-insulin-resistance-and-diabetes-studies-in-rodent-models-of-diabetes-mellitus
#11
Zakir Hossain, Guru R Valicherla, Anand P Gupta, Anees A Syed, Mohammed Riyazuddin, Sharat Chandra, Mohammad I Siddiqi, Jiaur R Gayen
Pancreastatin (PST) is an endogenous peptide which regulates glucose and lipid metabolism in liver and adipose tissues. In type 2 diabetic patients, PST level is high and plays a crucial role in the negative regulation of insulin sensitivity. Novel therapeutic agents are needed to treat the diabetes and insulin resistance (IR) against the PST action. In this regard, we have investigated the PST inhibitor peptide-8 (PSTi8) action against diabetogenic PST. PSTi8 rescued PST-induced IR in HepG2 and 3T3L1 cells...
June 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29879025/systems-analysis-of-key-genes-and-pathways-in-the-progression-of-hepatocellular-carcinoma
#12
Yu-Kui Shang, Fanni Li, Yi Zhang, Ze-Kun Liu, Zi-Ling Wang, Huijie Bian, Zhi-Nan Chen
The carcinogenesis of hepatocellular carcinoma (HCC) is a complex process, starting from a chronically altered hepatic microenvironment due to liver cirrhosis and ultimately progressing to HCC. However, the sequential molecular alterations driving the malignant transformation in liver cirrhosis are not clearly defined.In this study, we obtained gene expression profiles of HCC, including 268 tumor tissues, 243 adjacent tumor tissues, and 40 cirrhotic tissues (GSE25097) from Gene Expression Omnibus (GEO), to comprehensively define changes in the transcriptome of HCC during the sequential evolution of liver cirrhosis into HCC...
June 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29873516/the-combinational-effect-of-e6-e7-sirna-and-anti-mir-182-on-apoptosis-induction-in-hpv16-positive-cervical-cells
#13
Hamidreza Javadi, Abbas Sahebghadam Lotfi, Saman Hosseinkhani, Hossein Mehrani, Jafar Amani, Zahra Soheila Soheili, Zahra Hojati, Mehdi Kamali
In the present research, we assumed that reducing the amounts of E6 and E7 oncoproteins by a specific siRNA sequence and recovering p53 and RB proteins, along with the recovery of the FOXO1 protein by applying anti-miR-182, would increase apoptosis and reduce proliferation rate in cancer cells. The HPV16-positive CaSki cervical cancer cell line was used. 48 hours after transfection of siRNA for targeting E6 and E7 oncoproteins and anti-miR-182, expression of its cellular targets p53, p21 and FOXO1 was assessed by real-time PCR, western blot analysis and immunocytofluorescence staining...
June 6, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29870523/effect-of-sirtuin-1-on-synaptic-plasticity-in-nucleus-accumbens-in-a-rat-model-of-heroin-addiction
#14
Baijuan Xia, Yixin Li, Rongrong Li, Dan Yin, Xingqiang Chen, Jie Li, Wenmei Liang
BACKGROUND Synaptic plasticity plays an important role in the process of addiction. This study investigated the relationship between synaptic plasticity and changes in addictive behavior and examined the expression of synaptic plasticity-associated proteins and genes in the nucleus accumbens (NAc) region in different rat models. MATERIAL AND METHODS Heroin addiction, SIRT1-overexpression, and SIRT1-silenced rat models were established. Polymerase chain reaction gene chip technology, immunohistochemistry, Western blotting, and transmission electron microscopy were used to detect changes in synaptic plasticity-related gene and protein expression, and changes in the ultrastructure of synapses, in the NAc...
June 5, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29869612/-pax3-foxo1-transgenic-zebrafish-models-identify-hes3-as-a-mediator-of-rhabdomyosarcoma-tumorigenesis
#15
Genevieve C Kendall, Sarah Watson, Lin Xu, Collette A LaVigne, Whitney Murchison, Dinesh Rakheja, Stephen X Skapek, Franck Tirode, Olivier Delattre, James F Amatruda
Alveolar rhabdomyosarcoma is a pediatric soft-tissue sarcoma caused by PAX3/7-FOXO1 fusion oncogenes and is characterized by impaired skeletal muscle development. We developed human PAX3-FOXO1 -driven zebrafish models of tumorigenesis and found that PAX3-FOXO1 exhibits discrete cell lineage susceptibility and transformation. Tumors developed by 1.6-19 months and were primitive neuroectodermal tumors or rhabdomyosarcoma. We applied this PAX3-FOXO1 transgenic zebrafish model to study how PAX3-FOXO1 leverages early developmental pathways for oncogenesis and found that her3 is a unique target...
June 5, 2018: ELife
https://www.readbyqxmd.com/read/29867972/transcriptional-control-of-th9-cells-role-of-foxo1-in-interleukin-9-induction
#16
REVIEW
Sakshi Malik, Amit Awasthi
Interleukin (IL) 9-producing helper T (Th) 9 cells play a major role in contributing immunity against extracellular pathogens. In addition, the role of Th9 cells was demonstrated in the pathogenesis of allergic, skin, and intestinal inflammation. The functions of Th9 cells were further extended in antitumor immune response, as Th9 cells were suggested to be potent antitumor Th cells. Given the pleotropic functions of IL-9 in various pathophysiological conditions, it is essential to understand the differentiation and stability of Th9 cells and other IL-9-producing T cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29867232/inactivating-hepatic-follistatin-alleviates-hyperglycemia
#17
Rongya Tao, Caixia Wang, Oliver Stöhr, Wei Qiu, Yue Hu, Ji Miao, X Charlie Dong, Sining Leng, Margaret Stefater, Nicholas Stylopoulos, Lin Lin, Kyle D Copps, Morris F White
Unsuppressed hepatic glucose production (HGP) contributes substantially to glucose intolerance and diabetes, which can be modeled by the genetic inactivation of hepatic insulin receptor substrate 1 (Irs1) and Irs2 (LDKO mice). We previously showed that glucose intolerance in LDKO mice is resolved by hepatic inactivation of the transcription factor FoxO1 (that is, LTKO mice)-even though the liver remains insensitive to insulin. Here, we report that insulin sensitivity in the white adipose tissue of LDKO mice is also impaired but is restored in LTKO mice in conjunction with normal suppression of HGP by insulin...
June 4, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29867200/decreased-expression-of-arhgap15-promotes-the-development-of-colorectal-cancer-through-pten-akt-foxo1-axis
#18
Shengli Pan, Yingying Deng, Jun Fu, Yuhao Zhang, Zhijin Zhang, Xiaokun Ru, Xianju Qin
Copious evidence demonstrates the crucial role of Rho GTPase-activating proteins in human malignancies. The downregulation of Rho GTPase-activating protein 15 (ARHGAP15), a Rac1-specific GAP, has been observed in glioma and pancreatic ductal adenocarcinoma. The present study explored the expression in colorectal cancer (CRC) by quantitative real-time PCR and immunohistochemistry analysis. The possible function of ARHGAP15 in CRC was investegated in vitro and in vivo. We found that ARHGAP15 expression was obviously lower in CRC specimens than in normal colonic mucosa...
June 4, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29867121/cross-talk-among-hmga1-and-foxo1-in-control-of-nuclear-insulin-signaling
#19
Eusebio Chiefari, Biagio Arcidiacono, Camillo Palmieri, Domenica Maria Corigliano, Valeria Maria Morittu, Domenico Britti, Michal Armoni, Daniela Patrizia Foti, Antonio Brunetti
As a mediator of insulin-regulated gene expression, the FoxO1 transcription factor represents a master regulator of liver glucose metabolism. We previously reported that the high-mobility group AT-hook 1 (HMGA1) protein, a molecular switch for the insulin receptor gene, functions also as a downstream target of the insulin receptor signaling pathway, representing a critical nuclear mediator of insulin function. Here, we investigated whether a functional relationship existed between FoxO1 and HMGA1, which might help explain insulin-mediated gene transcription in the liver...
June 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29861864/-ppp2r1a-regulated-by-pax3-foxo1-fusion-contributes-to-the-acquisition-of-aggressive-behavior-in-pax3-foxo1-positive-alveolar-rhabdomyosarcoma
#20
Keisuke Akaike, Yoshiyuki Suehara, Shinji Kohsaka, Takuo Hayashi, Yu Tanabe, Saiko Kazuno, Kenta Mukaihara, Midori Toda-Ishii, Taisei Kurihara, Youngji Kim, Taketo Okubo, Yasuhide Hayashi, Kazuya Takamochi, Fumiyuki Takahashi, Kazuo Kaneko, Marc Ladanyi, Tsuyoshi Saito
To better characterize the oncogenic role of the PAX3-FOXO1 fusion protein in the acquisition of aggressive behavior in ARMS, we employed a proteomic approach using a PAX3-FOXO1 knockdown system in ARMS cell lines. This approach revealed a protein list consisting of 107 consistently upregulated and 114 consistently downregulated proteins that were expected to be regulated by PAX3-FOXO1 fusion protein. Furthermore, we identified 16 upregulated and 17 downregulated critical proteins based on a data-mining analysis...
May 18, 2018: Oncotarget
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