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Masami Hayashi, Kayo Yoshida, Kohei Kitada, Akane Kizu, Daisuke Tachibana, Mitsuru Fukui, Takashi Morita, Masayasu Koyama
PURPOSE: To study the outcomes of mouse preimplantation embryos irradiated with low doses of X-rays (≤ 1 Gy) and investigate apoptosis and pluripotency of the irradiated embryos. METHODS: Mouse embryos at the 2-cell stage were collected for in vitro culture. After reaching the 8-cell stage, embryos were irradiated with various low doses of X-rays (0-1 Gy). Blastocysts with a normal appearance were transferred into a pseudopregnant uterus. The developmental rate to blastocysts and the survival rate following embryo transfer were examined...
March 16, 2018: Journal of Assisted Reproduction and Genetics
Zsofia Miskolczi, Michael P Smith, Emily J Rowling, Jennifer Ferguson, Jorge Barriuso, Claudia Wellbrock
Despite the general focus on an invasive and de-differentiated phenotype as main driver of cancer metastasis, in melanoma patients many metastatic lesions display a high degree of pigmentation, indicative for a differentiated phenotype. Indeed, studies in mice and fish show that melanoma cells switch to a differentiated phenotype at secondary sites, possibly because in melanoma differentiation is closely linked to proliferation through the lineage-specific transcriptional master regulator MITF. Importantly, while a lot of effort has gone into identifying factors that induce the de-differentiated/invasive phenotype, it is not well understood how the switch to the differentiated/proliferative phenotype is controlled...
March 16, 2018: Oncogene
Saber Ben Mimoun, Alain Mauviel
The ubiquitous distribution of both Hippo and TGF-ß signaling cascade components and their critical implication in tissue homeostasis and disease has led to the discovery of a remarkable slew of interesting and unique features regarding their functional crosstalks. Upstream cellular cues regulating the Hippo pathway, including cell-cell contacts and apico-basal cell polarity have been well characterized. Herein, we provide an overview of the published models of compartmentalized signaling crosstalk mechanisms between Hippo signaling and the TGF-ß/SMAD pathway...
March 12, 2018: International Journal of Biochemistry & Cell Biology
Yu Wu, Ze-Yang Ding, Guan-Nan Jin, Yi-Xiao Xiong, Bin Yu, Yi-Min Sun, Wei Wang, Hui-Fang Liang, Bixiang Zhang, Xiao-Ping Chen
Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA)...
March 12, 2018: Biochimie
Fumio Otsuka
The bone morphogenetic protein (BMP) system in the ovary plays a physiological role as a luteinization inhibitor in growing follicles. BMP-6 secreted from oocytes and granulosa cells can exert an inhibitory effect on follicle-stimulating hormone (FSH) actions by suppressing adenylate cyclase activity downstream of the FSH receptor. The inhibition of FSH-induced progesterone production by BMP-6 is impaired by melatonin treatment in granulosa cells. Intracellular Smad signaling induced by BMP-6 is suppressed by melatonin, suggesting that melatonin has a regulatory role in BMP receptor signaling in granulosa cells...
2018: Vitamins and Hormones
Vu Huy Luong, Takenao Chino, Noritaka Oyama, Takashi Matsushita, Yoko Sasaki, Dai Ogura, Shin-Ichiro Niwa, Tanima Biswas, Akiyuki Hamasaki, Mikako Fujita, Yoshinari Okamoto, Masami Otsuka, Hironobu Ihn, Minoru Hasegawa
BACKGROUND: Transforming growth factor-β (TGF-β)/Smad signaling is well known to play a critical role in the pathogenesis of systemic sclerosis (SSc). We previously developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect. The purpose of the present study was to clarify the effects of this drug in human skin fibroblasts and in a preclinical model of SSc. METHODS: The effects of HPH-15 on expression of extracellular matrix components and TGF-β signaling in human dermal fibroblasts were analyzed...
March 15, 2018: Arthritis Research & Therapy
Meixiang Zhang, Justine Ngo, Filomena Pirozzi, Ying-Pu Sun, Anthony Wynshaw-Boris
BACKGROUND: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages...
March 15, 2018: Stem Cell Research & Therapy
Cynthia de la Fuente, Chelsea Pinkham, Deemah Dabbagh, Brett Beitzel, Aura Garrison, Gustavo Palacios, Kimberley Alex Hodge, Emanuel F Petricoin, Connie Schmaljohn, Catherine E Campbell, Aarthi Narayanan, Kylene Kehn-Hall
[This corrects the article DOI: 10.1371/journal.pone.0191983.].
2018: PloS One
Liang Liang, Ming Zeng, Haixia Pan, Hao Liu, Yangke He
Previous studies have demonstrated that nicotinamide N-methyltransferase (NNMT) is aberrantly expressed in a number of tumors. In the present study, it was demonstrated that the gene and protein levels of NNMT were significantly increased in gastric cancer cells. Furthermore, upregulation of NNMT significantly increased the expression of mesenchymal markers, including α-smooth muscle actin (SMA), vimentin and fibronectin, but decreased the levels of epithelial cadherin. Since transforming growth factor (TGF)-β1 may serve a key function in epithelial-mesenchymal transition (EMT), the effects of NNMT on the expression of TGF-β1 were investigated in BGC-823 cells...
April 2018: Oncology Letters
Guangzhong Xu, Kai Li, Nengwei Zhang, Bin Zhu, Guosheng Feng, Qing Fan
Colorectal cancer is a common malignancy with a high prevalence and associated mortality rate. However, the preclinical tools currently used for drug development are insufficient. The aim of the present study was to establish and characterize a specific patient-derived colon cancer xenograft (PDCCX) mouse model for drug testing. Primary colon tumors were obtained from 10 patients by surgical resection, and tumor tissues were subsequently grafted into nude mice followed by consecutive passages. Primary tumors and xenograft tumors were collected and processed for DNA sequencing, histological evaluation and immunohistochemical staining...
April 2018: Oncology Letters
Tulika Mitra, Parash Prasad, Pritha Mukherjee, Susri Ray Chaudhuri, Urmi Chatterji, Sib S Roy
Ovarian cancer (OC) is the fourth most common gynecological malignancy due to its highly aggressive, recurrent, and drug-resistant nature. The last two features are rendered by the presence of cancer stem cells (CSCs). Factors like TGFβ1 and their downstream signaling pathways are upregulated in most cancers and are known to induce EMT and stemness, but the exact mechanisms underlying the process remain unelucidated. In our study, TGFβ1 induced enhanced stem-like properties like high expression of the pluripotent markers SOX2, OCT4a, and NANOG, along with CD44, and CD117 in the OC cells...
March 14, 2018: Journal of Cellular Biochemistry
Jun Wei, Roberta G Marangoni, Feng Fang, Wenxia Wang, Jingang Huang, Joerg H W Distler, John Varga
The mechanisms underlying persistent fibroblast activation and myofibroblast phenoconversion in underlying multi-organ fibrosis in systemic sclerosis (SSc) remain incompletely understood, hindering effective therapies to slow or reverse the process. Cyclin-dependent kinase 5 (CDK5) is a pleiotropic member of the CDK family originally identified in neuronal cells. In contrast to other CDKs, CDK5 activity depends on its CDK5R1 subunit p35. Here we demonstrate that expression of p35 and CDK5 activity are induced by TGF-ß in fibroblasts and adipocytic cell types...
February 13, 2018: Oncotarget
Cui Zhang, Liang Li, Yuanda Jiang, Cuicui Wang, Baoming Geng, Yanqiu Wang, Jianling Chen, Fei Liu, Peng Qiu, Guangjie Zhai, Ping Chen, Renfu Quan, Jinfu Wang
Bone formation is linked with osteogenic differentiation of mesenchymal stem cells (MSCs) in the bone marrow. Microgravity in spaceflight is known to reduce bone formation. In this study, we used a real microgravity environment of the SJ-10 Recoverable Scientific Satellite to examine the effects of space microgravity on the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). hMSCs were induced toward osteogenic differentiation for 2 and 7 d in a cell culture device mounted on the SJ-10 Satellite...
March 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Xing Zhang, Zhong-Hua Xu, Hua Xie, Ya-Wen Sun, Jun Liu, Yin-Bi Zhao
Osteosarcoma is one of the most common primary malignant bone tumors. The inhibitor of growth family of protein 5 has been identified as a tumor suppressor in many cancers. In this study, we confirmed the downregulation of the both inhibitor of growth family of protein 5 and messenger RNA levels in cancer tissues using Western blot and real-time polymerase chain reaction. In order to find the antitumor roles of inhibitor of growth family of protein 5, osteosarcoma cells, HOS, and MG63 were transfected with the plasmid pCDNA-3...
January 1, 2018: Technology in Cancer Research & Treatment
Gui Pan, Haojie Hao, Jianping Liu
The transplantation of insulin-producing cells (IPCs) or pancreatic progenitor cells is a theoretical therapy for diabetes with insulin insufficiency. Isolated hepatocytes from newborn rats (within 24 h after birth) were progressively induced into IPCs using 5-aza-2'-deoxycytidine, Trichostatin A, retinoic acid, insulin-transferrin-selenium, and nicotinamide. We transplanted Pdx1+ pancreatic progenitors into STZ-induced diabetic mice and found the decreased blood glucose and increased insulin level in comparison with diabetic model...
March 7, 2018: Biochemical and Biophysical Research Communications
Aijaz A John, Ravi Prakash, Jyoti Kureel, Divya Singh
We report the role of miR-1187 in regulation of osteoblast functions. Over-expression of miR-1187 inhibited osteoblast differentiation. Target prediction analysis tools and experimental validation by luciferase 3' UTR reporter assay identified BMPR-II and ArhGEF-9 as direct targets of miR-1187. ArhGEF-9 activates Cdc42 which has a major role in actin reorganization. BMP-2 also induces actin polymerization. Role of miR-1187 in actin reorganization was determined by western blotting, immunofluorescence, and in vivo gene silencing studies...
March 9, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Tadayoshi Hayata, Masahiko Chiga, Yoichi Ezura, Makoto Asashima, Hidetaka Katabuchi, Ryuichi Nishinakamura, Masaki Noda
In mammals, the ovarian follicles are regulated at least in part by bone morphogenetic protein (BMP) family members. Dullard (also known as Ctdnep1) gene encodes a phosphatase that suppresses BMP signaling by inactivating or degrading BMP receptors. Here we report that the Col1a1-Cre-induced Dullard mutant mice displayed hemorrhagic ovarian cysts, with red blood cells accumulated in the follicles, resulting in infertility. Cells expressing Cre driven by Col1a1 2.3-kb promoter and their descendants were found in granulosa cells in the ovary and in Sertoli cells in the testis...
March 9, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Lin Chen, Tian Yang, De-Wen Lu, Hui Zhao, Ya-Long Feng, Hua Chen, Dan-Qian Chen, Nosratola D Vaziri, Ying-Yong Zhao
Chronic kidney disease (CKD) has emerged as a major cause of morbidity and mortality worldwide. Interstitial fibrosis, glomerulosclerosis and inflammation play the central role in the pathogenesis and progression of CKD to end stage renal disease (ESRD). Transforming growth factor-β1 (TGF-β1) is the central mediator of renal fibrosis and numerous studies have focused on inhibition of TGF-β1 and its downstream targets for treatment of kidney disease. However, blockade of TGF-β1 has not been effective in the treatment of CKD patients...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Guanghui Qian, Xiaohan Hu, Gen Li, Yueyue Ding, Liyan Zhu, Hui Zheng, Mei Li, Zhiheng Li, Jian Pan, Yiping Li, Gang Li, Chun Yang, Ying Liu, Yi Xie, Haitao Lv
Protein ubiquitination and deubiquitination enzymes are widely involved in innate immune responses. The ubiquitin specific protease 25 (USP25), a deubiquitinating enzyme, has been demonstrated to play an important role in virus infection and immunity. However, how USP25 is degraded and regulated by E3 ubiquitin ligases remains poorly understood. Here, we identified Smad ubiquitin regulatory factor 1(Smurf1) as a first novel E3 ubiquitin ligase of USP25. Smurf1 overexpression decreases USP25 protein turnover, and the E3 ligase enzymatic activity of Smurf1 is required for USP25 degradation...
March 5, 2018: Biochemical and Biophysical Research Communications
Xiu-Hua Yang, Feng Guo
The incidence of vulvar squamous cell carcinoma (VSCC) has increased annually over the last decade. MicroRNAs (miRNAs/miRs) serve an important role in tumor progression and development. Our previous microarray studies have revealed that miR‑3147 was overexpressed in VSCC. However, its function and underlying mechanism in VSCC remain unknown. In the present study, it was confirmed by reverse transcription‑quantitative polymerase chain reaction that the expression of miR‑3147 was markedly upregulated in VSCC tissues...
March 7, 2018: Molecular Medicine Reports
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