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https://www.readbyqxmd.com/read/28213398/foxo-integration-of-insulin-signaling-with-glucose-and-lipid-metabolism
#1
Sojin Lee, Henry H Dong
The forkhead box O family consists of FoxO1, FoxO3, FoxO4 and FoxO6 proteins in mammals. Expressed ubiquitously in the body, the four FoxO isoforms share in common the amino DNA binding domain, known as "forkhead box" domain. They mediate the inhibitory action of insulin or insulin-like growth factor on key functions involved in cell metabolism, growth, differentiation, oxidative stress, senescence, autophagy and aging. Genetic mutations in FoxO genes or abnormal expression of FoxO proteins are associated with metabolic disease, cancer or altered lifespan in humans and animals...
February 17, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28213137/foxo1-is-a-downstream-effector-of-isl1-in-direct-pathway-striatal-projection-neuron-development-within-the-embryonic-mouse-telencephalon
#2
R R Waclaw, L A Ehrman, P Merchan-Sala, V Kohli, D Nardini, K Campbell
Recent studies have shown that the LIM-homeodomain transcription factor Isl1 is required for the survival and differentiation of direct pathway striatonigral neurons during embryonic development. The downstream effectors of Isl1 in these processes are presently unknown. We show here that Foxo1, a transcription factor that has been implicated in cell survival, is expressed in striatal projection neurons (SPNs) that derive from the Isl1 lineage (i.e. direct pathway SPNs). Moreover, Isl1 conditional knockouts (cKOs) show a severe loss of Foxo1 expression at E15...
February 14, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28211035/resveratrol-decreases-foxo-protein-expression-through-pi3k-akt-dependent-pathway-inhibition-in-h2o2-treated-synoviocytes
#3
Bin Xu, Gaoyuan Wang, Junqiang Zhang, Wei Cao, Xiaoyu Chen
The aim of this study was to investigate the effects of resveratrol (Res) on hydrogen peroxide (H2O2)-treated fibroblast-like synoviocytes (FLSs) in vitro. We studied the phosphoinositide 3-kinase (PI3K)-Akt pathway inhibition-mediated effects of Res on forkhead box O (FoXO) mRNA expression levels. FLS viability was determined by Cell Counting Kit-8 (CCK-8) assay, and FLS apoptosis was measured by terminal deoxyribo nucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry...
February 17, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28207827/replication-of-snp-associations-with-keratoconus-in-a-czech-cohort
#4
Petra Liskova, Lubica Dudakova, Anna Krepelova, Jiri Klema, Pirro G Hysi
INTRODUCTION: Keratoconus is a relatively frequent disease leading to severe visual impairment. Existing therapies are imperfect and clinical management may benefit from improved understanding of mechanisms leading to this disease. We aim to investigate the replication of 11 single nucleotide polymorphisms (SNPs) with keratoconus. METHODS: SNPs from loci previously found in association with keratoconus were genotyped in 165 keratoconus cases of Caucasian Czech origin (108 males and 57 females) and 193 population and gender-matched controls...
2017: PloS One
https://www.readbyqxmd.com/read/28202394/platelet-rich-plasma-prp-induces-chondroprotection-via-increasing-autophagy-anti-inflammatory-markers-and-decreasing-apoptosis-in-human-osteoarthritic-cartilage
#5
Mayssam Moussa, Daniel Lajeunesse, George Hilal, Oula El Atat, Gaby Haykal, Rim Serhal, Antonio Chalhoub, Charbel Khalil, Nada Alaaeddine
OBJECTIVES: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration...
February 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28198424/human-ido-competent-long-lived-immunoregulatory-dendritic-cells-induced-by-intracellular-pathogen-and-their-fate-in-humanized-mice
#6
Rajeev K Tyagi, Brodie Miles, Rajesh Parmar, Neeraj K Garg, Sarat K Dalai, Babak Baban, Christopher W Cutler
Targeting of myeloid-dendritic cell receptor DC-SIGN by numerous chronic infectious agents, including Porphyromonas gingivalis, is shown to drive-differentiation of monocytes into dysfunctional mDCs. These mDCs exhibit alterations of their fine-tuned homeostatic function and contribute to dysregulated immune-responses. Here, we utilize P. gingivalis mutant strains to show that pathogen-differentiated mDCs from primary human-monocytes display anti-apoptotic profile, exhibited by elevated phosphorylated-Foxo1, phosphorylated-Akt1, and decreased Bim-expression...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194443/sustained-inflammation-after-pericyte-depletion-induces-irreversible-blood-retina-barrier-breakdown
#7
Shuntaro Ogura, Kaori Kurata, Yuki Hattori, Hiroshi Takase, Toshina Ishiguro-Oonuma, Yoonha Hwang, Soyeon Ahn, Inwon Park, Wataru Ikeda, Sentaro Kusuhara, Yoko Fukushima, Hiromi Nara, Hideto Sakai, Takashi Fujiwara, Jun Matsushita, Masatsugu Ema, Masanori Hirashima, Takashi Minami, Masabumi Shibuya, Nobuyuki Takakura, Pilhan Kim, Takaki Miyata, Yuichiro Ogura, Akiyoshi Uemura
In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28193293/loss-of-chromosome-13-material-in-cellular-angiofibromas-indicates-pathogenetic-similarity-with-spindle-cell-lipomas
#8
Ioannis Panagopoulos, Ludmila Gorunova, Bodil Bjerkehagen, Kristin Andersen, Marius Lund-Iversen, Sverre Heim
BACKGROUND: Cellular angiofibroma is a rare benign mesenchymal neoplasm with morphological and immunohistochemical similarities to spindle cell lipoma. Karyotypic information on cellular angiofibroma is restricted to one case only which showed loss of material from chromosomes 13 and 16. A few other studies using fluorescence in situ hybridization showed deletions of the RB1 and FOXO1 loci, both of which are located in chromosome band 13q14. We present here cytogenetic data on two cellular angiofibromas with an abnormal karyotype...
February 13, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28188753/mir-498-in-oesophageal-squamous-cell-carcinoma-clinicopathological-impacts-and-functional-interactions
#9
Farhadul Islam, Vinod Gopalan, Simon Law, Johnny Cheuk-On Tang, Kwok-Wah Chan, Alfred King-Yin Lam
MicroRNA-498 plays a crucial role in progression of many carcinomas. The signalling pathways that miR-498 modulates carcinogenesis are still unknown. Also, miR-498 associated molecular pathogenesis has never been studied in the oesophageal squamous cell carcinoma (ESCC). Herein, we aimed to examine the expression and functional roles of miR-498 in the ESCC as well as its influences on the clinicopathological features in patients with ESCC. Expression of miR-498 was investigated in 93 ESCC tissues and five ESCC cell lines using quantitative real-time polymerase chain reaction...
February 8, 2017: Human Pathology
https://www.readbyqxmd.com/read/28186649/bone-morphogenetic-protein-7-bmp-7-augments-insulin-sensitivity-in-mice-with-type-ii-diabetes-mellitus-by-potentiating-pi3k-akt-pathway
#10
Tandrika Chattopadhyay, Rajiv Ranjan Singh, Sarika Gupta, Avadhesha Surolia
A direct link between development of insulin resistance and the presence of chronic inflammation, in case of obesity exists, with cytokines playing an important role in glucose metabolism. Members of TGF-β superfamily, including bone morphogenetic proteins (BMPs), have been shown to be involved in islet morphogenesis, establishment of β-cell mass and adipose cell fate determination. Here, we demonstrate a novel and direct role of BMP-4 and -7 in the regulation of glucose homeostasis and insulin resistance...
February 10, 2017: BioFactors
https://www.readbyqxmd.com/read/28186136/foxo1-suppressed-mir-424-regulates-the-proliferation-and-osteogenic-differentiation-of-mscs-by-targeting-fgf2-under-oxidative-stress
#11
Liangping Li, Qihua Qi, Jiaquan Luo, Sheng Huang, Zemin Ling, Manman Gao, Zhiyu Zhou, Maik Stiehler, Xuenong Zou
Recently, microRNAs (miRNAs) have been identified as key regulators of the proliferation and differentiation of mesenchymal stem cells (MSCs). Our previous in vivo study and other in vitro studies using miRNA microarrays suggest that miR-424 is involved in the regulation of bone formation. However, the role and mechanism of miR-424 in bone formation still remain unknown. Here, we identified that the downregulation of miR-424 mediates bone formation under oxidative stress, and we explored its underlying mechanism...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28163294/metabolic-suppression-by-3-iodothyronamine-induced-muscle-cell-atrophy-via-activation-of-foxo-proteasome-signaling-and-downregulation-of-akt1-s6k-signaling
#12
Hyunwoo Ju, Taewan Kim, Chan-Moon Chung, Junsoo Park, Takeshi Nikawa, Kyoungsook Park, Inho Choi
The homeostasis of muscle properties depends on both physical and metabolic stresses. Whereas physical stress entails metabolic response for muscle homeostasis, the latter does not necessarily involve the former and may thus solely affect the homeostasis. We here report that metabolic suppression by the hypometabolic agent 3-iodothyronamine (T1AM) induced muscle cell atrophy without physical stress. We observed that the oxygen consumption rate of C2C12 myotubes decreased 40% upon treatment with 75 μM T1AM for 6 h versus 10% in the vehicle (dimethyl sulfoxide) control...
February 3, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28161531/skeletal-muscle-vitamin-d-in-patients-with-end-stage-osteoarthritis-of-the-knee
#13
Tara C Brennan-Speranza, David Mor, Rebecca S Mason, John R Bartlett, Gustavo Duque, Itamar Levinger, Pazit Levinger
Muscle function is often impaired in patients with knee osteoarthritis (OA), with reduced strength and increased pain. The role of vitamin D and the vitamin D-endocrine pathway in muscle health has recently been placed in the spotlight, with various groups reporting positive effects on muscle development, function and health. Recently, it has been shown that uptake into muscle of the specialized vitamin D binding protein (DBP) is dependent on the endocytic receptor, megalin. Here we analyse circulating vitamin D, and muscle DBP, megalin and the cognate vitamin D receptor (VDR) in patients with knee OA and compare them to asymptomatic controls...
February 1, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28161489/antiproliferative-effects-of-bortezomib-in-endothelial-cells-transformed-by-viral-g-protein-coupled-receptor-associated-to-kaposi-s-sarcoma
#14
A Suares, M Mori Sequeiros Garcia, C Paz, V González-Pardo
The Kaposi's Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi Sarcoma. We have previously demonstrated that the proteasome inhibitor Bortezomib inhibits NF-κB pathway, which is required for tumor maintenance in endothelial cells that express vGPCR (vGPCR cells). In this work, we further investigated Bortezomib anti-proliferative mechanism of action. We demonstrated that Bortezomib decreases vGPCR cell number in a dose-dependent manner and induces cell morphology changes...
February 1, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28160461/foxo1-malat1-mir-26a-5p-feedback-loop-mediates-proliferation-and-migration-in-osteosarcoma-cells
#15
Juntao Wang, Guodong Sun
MiR-26a has been found to be downregulated in osteosarcoma (OS) compared with normal control tissues and has been shownto be able to suppress the malignant behaviors of OS cells. The underlying mechanism, nevertheless, remains unknown. Here, in our study, the long non-coding RNA MALAT1, confirmed to be significantly up-regulated in OS, was firstly shown to be capable of promoting proliferation and migration by directly suppressing miR-26a-5p in OS cells. In addition, we've identified Forkhead Box O 1 (FOXO1) was a transcriptional factor of MALAT1 that can negatively regulate MALAT1...
February 3, 2017: Oncology Research
https://www.readbyqxmd.com/read/28138962/pax3-foxo1-is-essential-for-tumour-initiation-and-maintenance-but-not-recurrence-in-a-human-myoblast-model-of-rhabdomyosarcoma
#16
Puspa R Pandey, Bishwanath Chatterjee, Mary E Olanich, Javed Khan, Markku M Miettinen, Stephen M Hewitt, Frederic G Barr
The PAX3-FOXO1 fusion gene is generated by a 2;13 chromosomal translocation and is a characteristic feature of an aggressive subset of rhabdomyosarcoma (RMS). To dissect the mechanism of oncogene action during RMS tumourigenesis and progression, doxycycline-inducible PAX3-FOXO1 and constitutive MYCN expression constructs were introduced into immortalised human myoblasts. Though myoblasts expressing PAX3-FOXO1 or MYCN alone were not transformed in focus formation assays, combined PAX3-FOXO1 and MYCN expression resulted in transformation...
January 31, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28137761/comprehensive-transcriptome-and-mutational-profiling-of-endemic-burkitt-lymphoma-reveals-ebv-type-specific-differences
#17
Yasin Kaymaz, Cliff I Oduor, Hongbo Yu, Juliana A Otieno, John M Ong'echa, Ann M Moormann, Jeffrey A Bailey
: Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barr virus (EBV), unlike sporadic Burkitt Lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using RNA sequencing (RNAseq) from multiple primary eBL tumors compared to sBL tumors...
January 30, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28137614/selective-deletion-of-pten-in-theca-interstitial-cells-leads-to-androgen-excess-and-ovarian-dysfunction-in-mice
#18
Zi-Jian Lan, M S Krause, S D Redding, X Li, G Z Wu, H X Zhou, H C Bohler, C Ko, A J Cooney, Junmei Zhou, Z M Lei
Theca cell-selective Pten mutation (tPtenMT) in mice resulted in increases in PDK1 and Akt phosphorylation, indicating an over-activation of PI3K signaling in the ovaries. These mice displayed elevated androgen levels, ovary enlargement, antral follicle accumulation, early fertility loss and increased expression of Lhcgr and genes that are crucial to androgenesis. These abnormalities were partially reversed by treatments of PI3K or Akt inhibitor. LH actions in Pten deficient theca cells were potentiated. The phosphorylation of Foxo1 was increased, while the binding of Foxo1 to forkhead response elements in the Lhcgr promoter was reduced in tPtenMT theca cells, implying a mechanism by which PI3K/Akt-induced upregulation of Lhcgr in theca cells might be mediated by reducing the inhibitory effect of Foxo1 on the Lhcgr promoter...
January 28, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28135285/dysregulation-of-in-vitro-decidualization-of-human-endometrial-stromal-cells-by-insulin-via-transcriptional-inhibition-of-forkhead-box-protein-o1
#19
Dorina Ujvari, Ivika Jakson, Shabnam Babayeva, Daniel Salamon, Bence Rethi, Sebastian Gidlöf, Angelica Lindén Hirschberg
Insulin resistance and compensatory hyperinsulinemia are characteristic features of obesity and polycystic ovary syndrome, and both are associated with reduced fertility and implantation. There is little knowledge about the effect of insulin on the decidualization process and previous findings are contradictory. We investigated the effect of insulin on the regulation of forkhead box protein O1 (FOXO1), one of the most important transcription factors during decidualization. Endometrial stromal cells were isolated from six healthy, regularly menstruating women and decidualized in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28134973/fucosterol-isolated-from-ecklonia-stolonifera-inhibits-adipogenesis-through-modulation-of-foxo1-pathway-in-3t3-l1-adipocytes
#20
Ji-Hyun Lee, Hyun Ah Jung, Min Jae Kang, Jae Sue Choi, Gun-Do Kim
OBJECTIVES: The purpose of this study was to investigate the effects of fucosterol on adipogenesis of 3T3-L1 preadipocytes and its underlying mechanisms. METHODS: Fucosterol, isolated from brown algae, Ecklonia stolonifera. We investigated the levels of lipid accumulation using Oil Red O staining. We conducted Western blot analysis to investigate regulatory effects of fucosterol on expression of phosphoinositide 3-kinase (PI3K), Akt, extracellular signal-regulated kinase (ERK), forkhead box protein O 1 (FoxO1) in 3T3-L1 adipocytes...
January 30, 2017: Journal of Pharmacy and Pharmacology
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