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https://www.readbyqxmd.com/read/29775231/dna-methylation-and-foxo3a-regulate-phlpp1-expression-in-chondrocytes
#1
Clara M Castillejo Becerra, Anna M Mattson, David H H Molstad, Ian M Lorang, Jennifer J Westendorf, Elizabeth W Bradley
The protein phosphatase Phlpp1 is an essential enzyme for proper chondrocyte function. Altered Phlpp1 levels are associated with cancer and degenerative diseases such as osteoarthritis. While much is known about the post-transcriptional mechanisms controlling Phlpp1 levels, transcriptional regulation of the Phlpp1 gene locus is underexplored. We previously showed that CpG methylation of the PHLPP1 promoter is lower in osteoarthritic cartilage than in normal cartilage, and indirectly correlates with gene expression...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29773601/combinatorial-targeting-of-xpo1-and-flt3-exerts-synergistic-anti-leukemia-effects-through-induction-of-differentiation-and-apoptosis-in-flt3-mutated-acute-myeloid-leukemias-from-concept-to-clinical-trial
#2
Weiguo Zhang, Charlie Ly, Jo Ishizawa, Hong Mu, Vivian Ruvolo, Sharon Shacham, Naval Daver, Michael Andreeff
Targeted therapies against FLT3-mutated acute myeloid leukemia have shown limited clinical efficacy primarily because of the acquisition of secondary mutations in FLT3 and persistent activation of downstream pro-survival pathways such as MEK/ERK, PI3K/AKT, and STAT5. Activation of these additional kinases may also result in phosphorylation of tumor suppressor proteins promoting their nuclear export. Thus, co-targeting nuclear export proteins (i.e., XPO1) and FLT3 concomitantly may be therapeutically effective...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29767250/diosmetin-suppresses-human-prostate-cancer-cell-proliferation-through-the-induction-of-apoptosis-and-cell-cycle-arrest
#3
Christine Oak, Ahmad O Khalifa, Ilaha Isali, Natarajan Bhaskaran, Ethan Walker, Sanjeev Shukla
Diosmetin, a plant flavonoid, has been shown to exert promising effects on prostate cancer cells as an anti‑proliferative and anticancer agent. In this study, using western blot analysis for protein expression and flow cytometry for cell cycle analysis, we determined that the treatment of the LNCaP and PC‑3 prostate cancer cells with diosmetin resulted in a marked decrease in cyclin D1, Cdk2 and Cdk4 expression levels (these proteins remain active in the G0‑G1 phases of the cell cycle). These changes were accompanied by a decrease in c-Myc and Bcl-2 expression, and by an increase in Bax, p27Kip1 and FOXO3a protein expression, which suggests the potential modulatory effects of diosmetin on protein transcription...
May 16, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29761857/downregulated-expression-of-microrna-329-inhibits-apoptosis-of-nigral-dopaminergic-neurons-by-regulating-cdkn2d-expression-via-the-foxo3a-signaling-pathway-in-rats-with-parkinson-s-disease
#4
Yuan-Yuan Liu, Yi-Nan Zhang, Qing-Shan Yang
Parkinson's disease (PD) is a common neurodegenerative disorder due to the loss of dopaminergic neurons in the substantia nigra. This study focuses on the effect of microRNA-329 (miR-329) on nigral dopaminergic neurons in a rat model of PD via the FoxO3a signaling pathway by binding to CDKN2D. Brain tissues from the substantia nigra were taken from the rats in two groups. TUNEL staining was used to observe tyrosine hydroxylase (TH)-positive neurons. Nigral dopaminergic neurons were randomized into the normal, blank, negative control (NC), miR-329 mimics, miR-329 inhibitors, small interfering (siRNA)-CDKN2D, and miR-329 inhibitors + siRNA-CDKN2D groups...
May 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29760954/the-p53-activator-overcomes-resistance-to-alk-inhibitors-by-regulating-p53-target-selectivity-in-alk-driven-neuroblastomas
#5
Makoto Miyazaki, Ryo Otomo, Yuko Matsushima-Hibiya, Hidenobu Suzuki, Ayana Nakajima, Naomi Abe, Arata Tomiyama, Koichi Ichimura, Koichi Matsuda, Toshiki Watanabe, Takahiro Ochiya, Hitoshi Nakagama, Ryuichi Sakai, Masato Enari
Anaplastic lymphoma kinase (ALK) is an oncogenic receptor tyrosine kinase that is activated by gene amplification and mutation in neuroblastomas. ALK inhibitors can delay the progression of ALK-driven cancers, but are of limited use owing to ALK inhibitor resistance. Here, we show that resistance to ALK inhibitor in ALK-driven neuroblastomas can be attenuated by combination treatment with a p53 activator. Either ALK inhibition or p53 activator treatment induced cell cycle arrest, whereas combination treatment induced apoptosis, and prevented tumour relapse both in vitro and in vivo...
2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29753766/licorice-flavonoid-oil-enhances-muscle-mass-in-kk-a-y-mice
#6
Yasukiyo Yoshioka, Yoko Yamashita, Hideyuki Kishida, Kaku Nakagawa, Hitoshi Ashida
AIMS: Muscle mass is regulated by the balance between the synthesis and degradation of muscle proteins. Loss of skeletal muscle mass is associated with an increased risk of developing metabolic diseases such as obesity and type 2 diabetes mellitus. The aim of this study was to clarify the effects of licorice flavonoid oil on muscle mass in KK-Ay /Ta mice. MAIN METHODS: Male genetically type II diabetic KK-Ay /Ta mice received 0, 1, or 1.5 g/kg BW of licorice flavonoid oil by mouth once daily for 4 weeks...
May 10, 2018: Life Sciences
https://www.readbyqxmd.com/read/29736225/molecular-changes-in-obese-and-depressive-patients-are-similar-to-neurodegenerative-disorders
#7
Laleh Habibi, Abbas Tafakhori, Rasoul Hadiani, Maryam Maserat-Mashhadi, Zeinab Kafrash, Shahla Torabi, Mohammad Azhdarzadeh, Seyed Mohammad Akrami, Morteza Mahmoudi, Rasoul Dinarvand
Background: Neurodegenerative disorders (NDs) are categorized as multifactorial conditions with different molecular and environmental causes. Disturbance of important signaling pathways, such as energy metabolism and inflammation induced by environmental agents, is involved in the pathophysiology of NDs. It has been proposed that changes in the lifestyle and nutrition (metabolism) during mid-life could trigger and accumulate cellular and molecular damages resulting in NDs during aging. Methods: In order to test the hypothesis, we investigated the expression level of two energy metabolism-related [forkhead box O1 (FOXO1) and forkhead box O3 (FOXO3A)] and two pro-inflammatory cytokines [interleukin 1β (IL-1β) and IL-6] genes, using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR)...
October 7, 2017: Iranian Journal of Neurology
https://www.readbyqxmd.com/read/29724080/conessine-treatment-reduces-dexamethasone-induced-muscle-atrophy-by-regulating-murf1-and-atrogin-1-expression
#8
Hyunju Kim, Minsu Jang, Rackhyun Park, Daum Jo, Inho Choi, Joonho Choe, Won Keun Oh, Junsoo Park
Conessine, a steroidal alkaloid, is a potent histamine H3 antagonist with antimalarial activity. We recently reported that conessine treatment interferes with H₂O₂-induced cell death by regulating autophagy. However, the cellular signaling pathways involved in conessine treatment are not fully understood. Here, we report that conessine reduces muscle atrophy by interfering with the expression of atrophy-related ubiquitin ligases MuRF-1 and atrogin-1. Promoter reporter assay revealed that conessine treatment inhibits FoxO3a-dependent transcription, NF-κB-dependent transcription, and p53-dependent transcription...
April 28, 2018: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29716743/foxo3a-reverses-the-cisplatin-resistance-in-ovarian-cancer
#9
Mudan Lu, Xuan Chen, Jianping Xiao, Jingying Xiang, Lan Yang, Daozhen Chen
OBJECTIVE: Ovarian cancer is one of the most serious disease in female reproductive system. Platinum is the first-line drug for the treatment of ovarian cancer, while the resistance of platinum drug in clinical hindered the relief ovarian cancer. Our previous study found that decreased FOXO3a might be a poor prognosis in human ovarian cancer. In this research, we study whether FOXO3a was involved in the mechanism of platinum drug resistance. METHODS: The CCK-8 and FACS analysis were used to monitor the survival of ovarian cancer, and the FOXO3a expression was detected by western-blot...
April 28, 2018: Archives of Medical Research
https://www.readbyqxmd.com/read/29686375/requirement-of-gsk-3-for-puma-induction-upon-loss-of-pro-survival-pi3k-signaling
#10
Florian Schubert, Juliane Rapp, Prisca Brauns-Schubert, Lisa Schlicher, Kerstin Stock, Manuela Wissler, Martina Weiß, Céline Charvet, Christoph Borner, Ulrich Maurer
Growth factor withdrawal induces rapid apoptosis via mitochondrial outer membrane permeabilization. We had previously observed that cell death of IL-3-dependent Ba/F3 cells, induced by removal of the growth factor, required the activity of the kinase GSK-3. Employing CRISPR/Cas9-mediated gene knockout, we aimed to identify pro-apoptotic GSK-3 regulated factors in this process. Knockout of either Puma or Bim demonstrated that the induction of Puma, but not Bim, was crucial for apoptosis induced by IL-3 deprivation...
April 23, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29676828/%C3%AE-arrestin1-medieated-inhibition-of-foxo3a-contributes-the-prostate-cancer-cell-growth-in-vitro-and-in-vivo
#11
Zhenzhen Kong, Tuo Deng, Mengping Zhang, Zhijian Zhao, Yang Liu, Lianmin Luo, Chao Cai, Wenqi Wu, Xiaolu Duan
Recently, β-arrestin1 has been indicated as a prostate cancer promoter via promoting cell proliferation and epithelial to mesenchymal transition (EMT), but its underlying mechanism remains unclear. Here, our data revealed that β-arrestin1 could promote cell growth via inhibiting the transcriptional activity and expression of FOXO3a in prostate cancer cells in vitro and in vivo. In detail, we found that β-arrestin1 could promote the cell and tumor growth of prostate cancer, and β-arrestin1 expression represented a negative correlation with FOXO3a expression but not FOXO1 expression in prostate cancer cell lines and tissues...
April 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29670681/diaphragm-muscle-weakness-following-acute-sustained-hypoxic-stress-in-the-mouse-is-prevented-by-pretreatment-with-n-acetyl-cysteine
#12
Andrew J O'Leary, Sarah E Drummond, Deirdre Edge, Ken D O'Halloran
Oxygen deficit (hypoxia) is a major feature of cardiorespiratory diseases characterized by diaphragm dysfunction, yet the putative role of hypoxic stress as a driver of diaphragm dysfunction is understudied. We explored the cellular and functional consequences of sustained hypoxic stress in a mouse model. Adult male mice were exposed to 8 hours of normoxia, or hypoxia (FiO2  = 0.10) with or without antioxidant pretreatment (N-acetyl cysteine, 200 mg/kg i.p.). Ventilation and metabolism were measured. Diaphragm muscle contractile function, myofibre size and distribution, gene expression, protein signalling cascades, and oxidative stress (TBARS) were determined...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29669588/correction-to-mir-182-5p-promotes-hepatocellular-carcinoma-progression-by-repressing-foxo3a
#13
Man-Qing Cao, A-Bin You, Xiao-Dong Zhu, Wei Zhang, Yuan-Yuan Zhang, Shi-Zhe Zhang, Kei-Wei Zhang, Hao Cai, Wen-Kai Shi, Xiao-Long Li, Kang-Shuai Li, Dong-Mei Gao, De-Ning Ma, Bo-Gen Ye, Cheng-Hao Wang, Cheng-Dong Qin, Hui-Chan Sun, Ti Zhang, Zhao-You Tang
The original article [1] contains an error in Fig. 5a whereby the Western blot bands representing CyclinD1 have mistakenly been duplicated over the Western blot bands intended to represent SGK.
April 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29662632/regulation-of-breast-cancer-induced-bone-disease-by-cancer-specific-ikk%C3%AE
#14
Silvia Marino, Ryan T Bishop, Mattia Capulli, Antonia Sophocleous, John G Logan, Patrick Mollat, Barbara Mognetti, Luca Ventura, Andrew H Sims, Nadia Rucci, Stuart H Ralston, Aymen I Idris
NFκB is implicated in breast cancer bone metastasis and skeletal remodelling. However, the role of IKKβ, a key component of the canonical NFκB pathway, in the regulation of breast cancer osteolytic metastasis has not been investigated. Here, we describe the cancer-specific contribution of IKKβ to bone metastasis, skeletal tumour growth and osteolysis associated with breast cancer. IKKβ is highly expressed in invasive breast tumours and its level of expression was higher in patients with bone metastasis...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29655682/pristimerin-a-naturally-occurring-triterpenoid-attenuates-tumorigenesis-in-experimental-colitis-associated-colon-cancer
#15
Ju-Hyung Park, Jin-Kyung Kim
BACKGROUND: Pristimerin is a quinonemethide triterpenoid with anti-cancer, anti-angiogenic, anti-inflammatory and anti-protozoal activity. However, the therapeutic role of pristimerin in colitis-associated colorectal carcinogenesis is unknown. PURPOSE: We sought to examine the therapeutic effects of pristimerin on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). The goal was to identify the potential mechanism of action underlying the pharmacological activity of pristimerin...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29628875/profiling-of-long-non-coding-rnas-and-mrnas-by-rna-sequencing-in-the-hippocampi-of-adult-mice-following-propofol-sedation
#16
Jun Fan, Quan Zhou, Yan Li, Xiuling Song, Jijie Hu, Zaisheng Qin, Jing Tang, Tao Tao
Propofol is a frequently used intravenous anesthetic agent. The impairment caused by propofol on the neural system, especially the hippocampus, has been widely reported. However, the molecular mechanism underlying the effects of propofol on learning and memory functions in the hippocampus is still unclear. In the present study we performed lncRNA and mRNA analysis in the hippocampi of adult mice, after propofol sedation, through RNA-Sequencing (RNA-Seq). A total of 146 differentially expressed lncRNAs and 1103 mRNAs were identified...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29627834/effects-of-long-non-coding-rna-linc00963-on-renal-interstitial-fibrosis-and-oxidative-stress-of-rats-with-chronic-renal-failure-via-the-foxo-signaling-pathway
#17
Wen Chen, Lei Zhang, Zhong-Qi Zhou, Yue-Qin Ren, Li-Na Sun, Yu-Lin Man, Zhong-Wei Ma, Zhi-Kui Wang
BACKGROUND/AIMS: Chronic renal failure (CRF) is usually associated with chronic diseases such as congestive heart failure and diabetes mellitus, the prevalence of which is increased with age. This study is designed to investigate the role of long intergenic non-coding RNA (lincRNA) LINC00963 in renal interstitial fibrosis (RIF) and oxidative stress (OS) of CRF via the forkhead box O (FoxO) signaling pathway. METHODS: Microarray data and annotated probe files related to CRF were downloaded by retrieving Gene Expression Omnibus (GEO) database to screen differentially expressed lncRNA...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29622768/role-of-phospholipase-d-in-the-lifespan-of-caenorhabditis-elegans
#18
Jeong-Hwan Park, Jeong-Woo Park, Ju-Hyeon Lee, Dong-Yun Kim, Jeong-Hoon Hahm, Young-Seuk Bae
We have previously shown that phospholipase D (PLD) downregulation accelerates cellular senescence, which is widely believed to play an important role in aging, by stimulating reactive oxygen species (ROS) accumulation in human cells. In this study, we examined the role of PLD in aging using the nematode Caenorhabditis elegans. The mRNA level of pld-1 was found to be inversely correlated with aging. RNAi-mediated knockdown of pld-1 expression in nematodes enhanced ROS and lipofuscin accumulation and decreased lifespan, motility, and resistance to stress compared to that in nematodes treated with control RNAi...
April 6, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29618792/subcutaneous-ehrlich-ascites-carcinoma-mice-model-for-studying-cancer-induced-cardiomyopathy
#19
Sneha Mishra, Ankit Kumar Tamta, Mohsen Sarikhani, Perumal Arumugam Desingu, Shruti M Kizkekra, Anwit Shriniwas Pandit, Shweta Kumar, Danish Khan, Sathees C Raghavan, Nagalingam R Sundaresan
Cardiomyopathy is one of the characteristic features of cancer. In this study, we establish a suitable model to study breast cancer-induced cardiomyopathy in mice. We used Ehrlich Ascites Carcinoma cells to induce subcutaneous tumor in 129/SvJ mice and studied its effect on heart function. In Ehrlich Ascites Carcinoma bearing mice, we found significant reduction in left ventricle wall thickness, ejection fraction, and fractional shortening increase in left ventricle internal diameter. We found higher muscle atrophy, degeneration, fibrosis, expression of cell-adhesion molecules and cell death in tumor-bearing mice hearts...
April 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29615995/htlv-1-alters-t-cells-for-viral-persistence-and-transmission
#20
REVIEW
Azusa Tanaka, Masao Matsuoka
Human T-cell leukemia virus type 1 (HTLV-1) was the first retrovirus to be discovered as a causative agent of adult T-cell leukemia-lymphoma (ATL) and chronic inflammatory diseases. Two viral factors, Tax and HTLV-1 bZIP factor (HBZ), are thought to be involved in the leukemogenesis of ATL. Tax expression is frequently lost due to DNA methylation in the promoter region, genetic changes to the tax gene, and deletion of the 5' long terminal repeat (LTR) in approximately half of all ATL cases. On the other hand, HBZ is expressed in all ATL cases...
2018: Frontiers in Microbiology
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