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https://www.readbyqxmd.com/read/29156807/halofuginone-inhibits-tgf-%C3%AE-bmp-signaling-and-in-combination-with-zoledronic-acid-enhances-inhibition-of-breast-cancer-bone-metastasis
#1
Patricia Juárez, Pierrick G J Fournier, Khalid S Mohammad, Ryan C McKenna, Holly W Davis, Xiang H Peng, Maria Niewolna, Alain Mauviel, John M Chirgwin, Theresa A Guise
More efficient therapies that target multiple molecular mechanisms are needed for the treatment of incurable bone metastases. Halofuginone is a plant alkaloid-derivative with antiangiogenic and antiproliferative effects. Here we demonstrate that halofuginone is an effective therapy for the treatment of bone metastases, through multiple actions that include inhibition of TGFβ and BMP-signaling. Halofuginone blocked TGF-β-signaling in MDA-MB-231 and PC3 cells showed by inhibition of TGF-β-induced Smad-reporter, phosphorylation of Smad-proteins, and expression of TGF-β-regulated metastatic genes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154973/inhibition-of-bmp-signaling-overcomes-acquired-resistance-to-cetuximab-in-oral-squamous-cell-carcinomas
#2
Jinlong Yin, Ji-Eun Jung, Sun Il Choi, Sung Soo Kim, Young Taek Oh, Tae-Hoon Kim, Eunji Choi, Sun Joo Lee, Hana Kim, Eun Ok Kim, Yu Sun Lee, Hee Jin Chang, Joo Yong Park, Yeejeong Kim, Tak Yun, Kyun Heo, Youn-Jae Kim, Hyunggee Kim, Yun-Hee Kim, Jong Bae Park, Sung Weon Choi
Despite expressing high levels of the epidermal growth factor receptor (EGFR), a majority of oral squamous cell carcinoma (OSCC) patients show limited response to cetuximab and ultimately develop drug resistance. However, mechanism underlying cetuximab resistance in OSCC is not clearly understood. Here, using a mouse orthotopic xenograft model of OSCC, we show that BMP7-p-Smad1/5/8 signaling contributes to cetuximab resistance. Tumor cells isolated from the recurrent cetuximab-resistant xenograft models exhibited low EGFR expression but extremely high levels of phosphorylated Smad-1, -5, and -8 (p-Smad1/5/8)...
November 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29150938/regulation-of-calcification-in-human-aortic-smooth-muscle-cells-infected-with-high-glucose-treated-porphyromonas-gingivalis
#3
Te-Chuan Chen, Chien-Tsong Lin, Shao-Ju Chien, Shun-Fu Chang, Cheng-Nan Chen
Porphyromonas (P.) gingivalis infection leading to the periodontitis has been associated with the development of systemic diseases, including cardiovascular diseases and diabetes. However, the effect of a high concentration of glucose (HG) on the invasion efficiency of P. gingivalis and the consequent modulation of pathogenesis in vascular cells, especially in the vascular smooth muscle cells (VSMCs), remains unclear. Hence, the aim of this study was to investigate whether treating P. gingivalis with HG could change its invasion capability and result in VSMC calcification and the underlying mechanism...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29129645/incretins-modulate-progesterone-biosynthesis-by-regulating-bone-morphogenetic-protein-activity-in-rat-granulosa-cells
#4
Yuki Nishiyama, Toru Hasegawa, Shiho Fujita, Nahoko Iwata, Satoko Nagao, Takeshi Hosoya, Kenichi Inagaki, Jun Wada, Fumio Otsuka
The effects of incretins on ovarian steroidogenesis have not been clarified. In this study, we investigated the effects of incretins, including GIP and GLP-1, on ovarian steroidogenesis using rat primary granulosa cells. Treatment with incretins significantly suppressed progesterone synthesis in the presence of FSH, and the effect of GIP was more potent than that of GLP-1. In contrast, incretins had no significant effect on estrogen synthesis by rat granulosa cells. In accordance with the effects of incretins on steroidogenesis, GIP and GLP-1 suppressed the expression of progesterogenic factors and enzymes, including StAR, P450scc, 3βHSD, but not P450arom, and cellular cAMP synthesis induced by FSH...
November 9, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29117254/link-n-the-missing-link-towards-intervertebral-disc-repair-is-species-specific
#5
Frances C Bach, Lisanne T Laagland, Michael P Grant, Laura B Creemers, Keita Ito, Björn P Meij, Fackson Mwale, Marianna A Tryfonidou
INTRODUCTION: Degeneration of the intervertebral disc (IVD) is a frequent cause for back pain in humans and dogs. Link-N stabilizes proteoglycan aggregates in cartilaginous tissues and exerts growth factor-like effects. The human variant of Link-N facilitates IVD regeneration in several species in vitro by inducing Smad1 signaling, but it is not clear whether this is species specific. Dogs with IVD disease could possibly benefit from Link-N treatment, but Link-N has not been tested on canine IVD cells...
2017: PloS One
https://www.readbyqxmd.com/read/29113455/hdac1-governs-iron-homeostasis-independent-of-histone-deacetylation-in-iron-overload-murine-models
#6
Xiangju Yin, Qian Wu, Jitender Monga, Enjun Xie, Hao Wang, Shufen Wang, Huizhen Zhang, Zhan-You Wang, Tianhua Zhou, Yunjun Shi, Jack Rogers, Hening Lin, Junxia Min, Fudi Wang
AIMS: Iron overload disorders are common and could lead to significant morbidity and mortality worldwide. Due to limited treatment options, there is a great need to develop novel strategies to remove the excess body iron. To discover potential epigenetic modulator in hepcidin upregulation and subsequently decreasing iron burden, we performed an epigenetic screen. The in vivo effects of the identified compounds were further tested in iron-overload mouse models, including Hfe-/-, Hjv-/- and hepatocyte-specific Smad4 knockout (Smad4fl/fl;Alb-Cre+) mice...
November 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29100273/mir-26a-contributes-to-the-pdgf-bb-induced-phenotypic-switch-of-vascular-smooth-muscle-cells-by-suppressing-smad1
#7
Xiaoyan Yang, Mei Dong, Hao Wen, Xiaoling Liu, Meng Zhang, Lianyue Ma, Cheng Zhang, Xiaorong Luan, Huixia Lu, Yun Zhang
The phenotypic switch of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, such as atherosclerosis and post-angioplasty restenosis. Small non-coding microRNAs (miRNAs) have emerged as critical modulators of VSMC function. In the present study, miR-26a was significantly increased in cultured VSMCs stimulated by platelet-derived growth factor-BB (PDGF-BB) and in arteries with neointimal lesion formation. Moreover, we demonstrated that miR-26a regulates the expression of VSMC differentiation marker genes such as α-smooth muscle actin (α-SMA), calponin and smooth muscle myosin heavy chain (SM-MHC) in PDGF-BB-treated VSMCs...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29094227/down-regulation-of-noggin-and-mir-138-coordinately-promote-osteogenesis-of-mesenchymal-stem-cells
#8
Xing-Kun Sun, Jin Zhou, Lei Zhang, Tian Ma, Yu-Han Wang, Yan-Mei Yang, Yan-Ting Tang, Hong Li, Li-Jun Wang
Mesenchymal stem cells (MSCs) can differentiate to osteocytes under suitable conditions. In recent years, micro-nucleotides have been progressively used to modulate gene expression in cells due to the consideration of safety. Our present study aimed to investigate whether co-delivery of Noggin-siRNA and antimiR-138 enhances the osteogenic effect of MSCs. Using a murine MSC line, C3H/10T1/2 cells, the delivery efficiency of Noggin-siRNA and antimiR-138 into MSCs was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR)...
December 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29091893/isoflurane-post-conditioning-down-regulates-expression-of-aquaporin-4-in-rats-with-cerebral-ischemia-reperfusion-injury-and-is-possibly-related-to-bone-morphogenetic-protein-4-smad1-5-8-signaling-pathway
#9
Min Yuan, Mingyue Ge, Jiangwen Yin, Zhigang Dai, Liping Xie, Yan Li, Xuejiao Liu, Li Peng, Guixing Zhang, Junqiang Si, Ketao Ma, Sheng Wang
AIM: Aquaporins (AQPs) are water-channels that play important roles in brain water homeostasis and cerebral edema induced by brain injury. This study aimed to investigate the relationship between AQP4, bone morphogenetic protein 4 (BMP4)/Smad1/5/8 signaling pathway and isoflurane post-conditiong, which has effects on brain edema in rats with cerebral ischemia/reperfusion (I/R) injury. METHODS: Cerebral I/R injury was induced in rats by using the middle cerebral artery occlusion (MCAO) model for 90min, followed by 24h of reperfusion...
October 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29091322/a-novel-diterpenoid-suppresses-osteoclastogenesis-and-promotes-osteogenesis-by-inhibiting-ifrd1-and-i%C3%AE%C2%BAb%C3%AE-mediated-p65-nuclear-translocation
#10
Zi'ang Xie, Hejun Yu, Xuewu Sun, Pan Tang, Zhiwei Jie, Shuai Chen, Jiying Wang, An Qin, Shunwu Fan
Osteoporosis develops due to impaired bone formation and/or excessive bone resorption. Although the pharmacological treatment of osteoporosis has been extensively developed, alternative treatments are still needed. Here, we showed that oridonin (ORI), a diterpenoid isolated from Rabdosia rubescens, can suppress osteoclastogenesis and enhance osteogenesis. ORI inhibited the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption through the inhibition of p65 nuclear translocation...
November 1, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29089047/whole-exome-sequencing-in-342-congenital-cardiac-left-sided-lesion-cases-reveals-extensive-genetic-heterogeneity-and-complex-inheritance-patterns
#11
Alexander H Li, Neil A Hanchard, Dieter Furthner, Susan Fernbach, Mahshid Azamian, Annarita Nicosia, Jill Rosenfeld, Donna Muzny, Lisa C A D'Alessandro, Shaine Morris, Shalini Jhangiani, Dhaval R Parekh, Wayne J Franklin, Mark Lewin, Jeffrey A Towbin, Daniel J Penny, Charles D Fraser, James F Martin, Christine Eng, James R Lupski, Richard A Gibbs, Eric Boerwinkle, John W Belmont
BACKGROUND: Left-sided lesions (LSLs) account for an important fraction of severe congenital cardiovascular malformations (CVMs). The genetic contributions to LSLs are complex, and the mutations that cause these malformations span several diverse biological signaling pathways: TGFB, NOTCH, SHH, and more. Here, we use whole exome sequence data generated in 342 LSL cases to identify likely damaging variants in putative candidate CVM genes. METHODS: Using a series of bioinformatics filters, we focused on genes harboring population-rare, putative loss-of-function (LOF), and predicted damaging variants in 1760 CVM candidate genes constructed a priori from the literature and model organism databases...
October 31, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29044189/tgf-%C3%AE-signalling-and-peg10-are-mutually-exclusive-and-inhibitory-in-chondrosarcoma-cells
#12
Naohiro Shinohara, Shingo Maeda, Yuhei Yahiro, Daisuke Sakuma, Kanehiro Matsuyama, Katsuyuki Imamura, Ichiro Kawamura, Takao Setoguchi, Yasuhiro Ishidou, Satoshi Nagano, Setsuro Komiya
Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers. Here, we found highly active transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signalling in human chondrosarcomas compared with enchondromas by immunohistochemistry of phosphorylated SMAD3 and SMAD1/5. In contrast, the chondrogenic master regulator SOX9 was dramatically down-regulated in grade 1 chondrosarcoma. Paternally expressed gene 10 (PEG10) was identified by microarray analysis as a gene overexpressed in chondrosarcoma SW1353 and Hs 819...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29039519/runx3-plays-an-important-role-in-mediating-the-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells
#13
Yufeng Wang, Qiaoling Feng, Caixia Ji, Xiaohua Liu, Li Li, Jinyong Luo
Although bone morphogenetic protein 9 (BMP9) is highly capable of promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) both in vitro and in vivo, the molecular mechanisms involved remain to be fully elucidated. Runt-related transcription factor (RUNX)3 is an essential regulator of osteoblast/chondrocyte maturation. However, the exact role of RUNX3 in BMP9 osteoinductive activity is unknown. In this study, we sought to investigate the functional role of RUNX3 in the BMP9-induced osteogenic differentiation of MSCs...
September 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29037671/blue-mussel-mytilus-edulis-protein-hydrolysate-promotes-mouse-mesenchymal-stem-cell-differentiation-into-osteoblasts-through-up-regulation-of-bone-morphogenetic-protein
#14
Jun-Ho Hyung, Chang-Bum Ahn, Jae-Young Je
Seafood provides a range of health benefits due to its high-protein level. In this study, the osteogenic effect of blue mussel (Mytilus edulis) protein hydrolysates (BMPH) on osteoblast differentiation were examined using mouse mesenchymal stem cells (MSCs). A preparation we called BMPH<1kDa which showed the highest osteogenic effect in MSCs, was prepared by peptic hydrolysis. BMPH<1kDa treatment stimulated osteoblast differentiation with alkaline phosphatase (ALP) induction, osteocalcin and type I collagen activity as well as calcium deposition...
March 1, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29027119/mollugin-enhances-the-osteogenic-action-of-bmp-2-via-the-p38-smad-signaling-pathway
#15
Seong-Hee Moon, Ikyon Kim, Seong Hwan Kim
Bone morphogenetic protein 2 (BMP-2) has been used clinically to encourage bone regeneration; although, there can be major side effects with larger doses. Therefore, there is a need to identify new small molecules to potentiate the osteogenic action of BMP-2. In this study, we investigated the effect of mollugin on bone formation in murine bi-potential mesenchymal progenitor C2C12 cells by combination with BMP-2. We found mollugin could enhance the BMP-2-mediated osteoblast differentiation of C2C12 cells. This was accompanied by the induction of other osteogenic BMPs...
October 12, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29026072/dynamic-regulation-of-canonical-tgf%C3%AE-signalling-by-endothelial-transcription-factor-erg-protects-from-liver-fibrogenesis
#16
Neil P Dufton, Claire R Peghaire, Lourdes Osuna-Almagro, Claudio Raimondi, Viktoria Kalna, Abhishek Chuahan, Gwilym Webb, Youwen Yang, Graeme M Birdsey, Patricia Lalor, Justin C Mason, David H Adams, Anna M Randi
The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access to DNA. Ablation of ERG expression results in endothelial-to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC-specific constitutive hemi-deficient (Erg (cEC-Het) ) and inducible homozygous deficient mice (Erg (iEC-KO) ), in a SMAD3-dependent manner...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29018799/truseq-based-gene-expression-analysis-of-formalin-fixed-paraffin-embedded-ffpe-cutaneous-t-cell-lymphoma-samples-subgroup-analysis-results-and-elucidation-of-biases-from-ffpe-sample-processing-on-the-truseq-platform
#17
Philippe Lefrançois, Michael T Tetzlaff, Linda Moreau, Andrew K Watters, Elena Netchiporouk, Nathalie Provost, Martin Gilbert, Xiao Ni, Denis Sasseville, Madeleine Duvic, Ivan V Litvinov
Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of malignancies with courses ranging from indolent to potentially lethal. We recently studied in a 157 patient cohort gene expression profiles generated by the TruSeq targeted RNA gene expression sequencing. We observed that the sequencing library quality and depth from formalin-fixed paraffin-embedded (FFPE) skin samples were significantly lower when biopsies were obtained prior to 2009. We also observed that the fresh CTCL samples clustered together, even though they included stage I-IV disease...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28992339/stat3-inhibition-attenuates-the-progressive-phenotypes-of-alport-syndrome-mouse-model
#18
Tsubasa Yokota, Kohei Omachi, Mary Ann Suico, Misato Kamura, Haruka Kojima, Ryosuke Fukuda, Keishi Motomura, Keisuke Teramoto, Shota Kaseda, Jun Kuwazuru, Toru Takeo, Naomi Nakagata, Tsuyoshi Shuto, Hirofumi Kai
Background: Alport syndrome (AS) is a hereditary, progressive nephritis caused by mutation of type IV collagen. Previous studies have shown that activation of signal transducer and activator of transcription 3 (STAT3) exacerbates other renal diseases, but whether STAT3 activation exacerbates AS pathology is still unknown. Here we aim to investigate the involvement of STAT3 in the progression of AS. Method: Phosphorylated STAT3 expression was assessed by immunoblotting analysis of kidneys and glomeruli of an AS mouse model ( Col4a5 G5X mutant)...
August 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28983616/abnormal-expression-levels-of-bmp15-smad1-are-associated-with-granulosa-cell-apoptosis-in-patients-with-polycystic-ovary-syndrome
#19
Xiangrong Cui, Xuan Jing, Xueqing Wu, Xingyu Bi, Junfen Liu, Zhijing Long, Xiuping Zhang, Dongdong Zhang, Hongxiang Jia, Dan Su, Kai Huo
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects reproductive dysfunction and metabolism in women of childbearing age. An increasing number of studies have suggested that the bone morphogenetic protein 15 (BMP15) signalling pathway serves an important role in the pathogenesis of PCOS; however, the full mechanism remains unknown. The present study revealed that intrinsic follicular dysplasia may be associated with regulation disorders of ovarian granulosa cell apoptosis. Compared with the control group, body mass index, luteinising hormone and testosterone levels were significantly increased (P<0...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28981455/a-unique-tgfb1-driven-genomic-program-links-astrocytosis-low-grade-inflammation-and-partial-demyelination-in-spinal-cord-periplaques-from-progressive-multiple-sclerosis-patients
#20
Serge Nataf, Marc Barritault, Laurent Pays
We previously reported that, in multiple sclerosis (MS) patients with a progressive form of the disease, spinal cord periplaques extend distance away from plaque borders and are characterized by the co-occurrence of partial demyelination, astrocytosis and low-grade inflammation. However, transcriptomic analyses did not allow providing a comprehensive view of molecular events in astrocytes vs. oligodendrocytes. Here, we re-assessed our transcriptomic data and performed co-expression analyses to characterize astrocyte vs...
October 5, 2017: International Journal of Molecular Sciences
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