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https://www.readbyqxmd.com/read/28109119/serotonin-transporter-protects-the-placental-cells-against-apoptosis-in-caspase-3-independent-pathway
#1
Coedy Hadden, Tariq Fahmi, Anthonya Cooper, Alena V Savenka, Vladimir V Lupashin, Drucilla J Roberts, Luc Maroteaux, Sylvie Hauguel-de Mouzon, Fusun Kilic
Serotonin (5-HT) and its specific transporter, SERT play important roles in pregnancy. Using placentas dissected from 18d gestational SERT-knock out (KO), peripheral 5-HT (TPH1)-KO and wild-type (WT) mice, we explored the role of 5-HT and SERT in placental functions in detail. An abnormal thick band of fibrosis and necrosis under the giant cell layer in SERT-KO placentas appeared only moderately in TPH1-KO and minimally present in WT placentas. The majority of the changes were located at the junctional zone of the placentas in SERT...
January 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28109089/betulinic-acid-inhibits-cell-proliferation-in-human-oral-squamous-cell-carcinoma-via-modulating-ros-regulated-p53-signaling
#2
Huan Shen, Li Liu, Yongjin Yang, Wenxing Xun, Kewen Wei, Guang Zeng
Oral squamous cell carcinoma (OSCC) is a common cancer of the head and neck. Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid. The present study was designed to explore the effects of BA on OSCC KB cell proliferation <em>in vitro</em> and implanted tumor growth <em>in vivo</em> and to examine the possible molecular mechanisms. The results showed that BA dose-dependently inhibited KB cell proliferation and decreased implanted tumor volume. In addition, BA significantly promoted mitochondrial apoptosis, as reflected by increase of TUNEL-positive cells and activities of caspase 3 and 9, increase of Bax expression and decrease of Bcl-2 expression and mitochondrial oxygen consumption rate...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28109086/grade-dependent-expression-of-nima-related-kinase-2-in-glioma-and-its-cellular-upregulatory-activity-on-proliferation-and-invasion
#3
Li Tian, Peng Cheng, Huaiyu Sun, Yulin Wang, Lei Zhang, Zongze Guo
Glioma is one of the most common tumors in central nervous system. The median life expectancy for glioma patients is only 13-15 months. NIMA-related expressed kinase 2 (NEK2) is a kind of serine-threonine kinases and involves in carcinogenesis and progression of cancer, however, the specific roles in the glioma remains unknown. We found the high expression of NEK2 was positively correlated with deteriorated severity of glioma. Therefore, we sought to investigate the effects of NEK2 on U87 and U251 cells. To explore the expression of NEK2 and alteration of signaling pathway factors, qRT-PCR and Western blot analysis were performed...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28108672/stromal-interaction-molecule-1-stim1-regulates-growth-cell-cycle-and-apoptosis-of-human-tongue-squamous-carcinoma-cells
#4
Xiaobo Cui, Laixiao Song, Yunfei Bai, Yaping Wang, Boqian Wang, Wei Wang
Oral tongue squamous carcinoma (OTSCC) is the most common type of cancer of oral carcinomas. However, the molecular mechanism by which OTSCC development is not fully identified. Stromal interaction molecule 1 (STIM1) is a transmembrane protein, mainly located in the endoplasmic reticulum (ER). STIM1 is involved in several types of cancers. Here we report that STIM1 contributes to the development of human OTSCC. We knocked down STIM1 in OTSCC cell line Tca-8113 with lentivirus-mediated shRNA and found that SITM1 knockdown repressed the proliferation of Tca-8113 cells...
January 20, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28108609/visualization-and-quantification-of-browning-using-a-ucp1-2a-luciferase-knock-in-mouse-model
#5
Liufeng Mao, Baoming Nie, Tao Nie, Xiaoyan Hui, Xuefei Gao, Xiaoliang Lin, Xin Liu, Yong Xu, Xiaofeng Tang, Ran Yuan, Kuai Li, Peng Li, Ke Ding, Yu Wang, Aimin Xu, Jian Fei, Weiping Han, Pentao Liu, Lise Madsen, Karsten Kristiansen, Zhiguang Zhou, Sheng Ding, Donghai Wu
Both mammals and adult humans possess classic brown adipocytes and beige adipocytes, and the amount and activity of these adipocytes are considered key factors in combating obesity and its associated metabolic diseases. Uncoupling protein 1 (Ucp1) is the functional marker of both brown and beige adipocytes. To facilitate a reliable, easy, and sensitive measurement of Ucp1 expression both in vivo and in vitro, we generated a Ucp1-2A-luciferase knock-in mouse by deleting the stop codon for the mouse Ucp1 gene and replacing it with a 2A peptide...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28108311/rip1-and-rip3-contribute-to-shikonin-induced-dna-double-strand-breaks-in-glioma-cells-via-increase-of-intracellular-reactive-oxygen-species
#6
Zijian Zhou, Bin Lu, Chen Wang, Zongqi Wang, Tianfei Luo, Meihua Piao, Fankai Meng, Guangfan Chi, Yinan Luo, Pengfei Ge
Shikonin has been reported to induce glioma cell death via necroptosis, a type of programmed necrosis primarily mediated by RIP1 and RIP3. Although RIP1 and RIP3 are found to regulate some features of necrosis such as energy depletion and cellular membrane disruption, it remains unclear whether RIP1 and RIP3 could modulate DNA double strand breaks (DSBs), which is a crucial event leading to chromatinolysis. In this study, we used glioma cell lines and mice model of xenograft glioma to investigate the roles of RIP1 and RIP3 in shikonin-induced DNA DSBs...
January 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28108300/transforming-growth-factor-beta-inducible-early-gene-1-tieg1-represses-smad7-mediated-activation-of-tgf-%C3%AE-1-smad-signaling-in-keloid-pathogenesis
#7
Zhi-Cheng Hu, Fen Shi, Peng Liu, Jian Zhang, Dong Guo, Xiao-Ling Cao, Chu-Fen Chen, Shanqiang Qu, Jia-Yuan Zhu, Bing Tang
Transforming growth factor β (TGF-β)/Smad signaling plays a key role in excessive fibrosis and keloid formations. Smad7 is a negative feedback regulator that prevents activation of TGF-β/Smad signaling. However, the regulatory mechanism for Smad7 in the keloid pathogenic process remains elusive. Here, we show that expression of TGF-β inducible early gene-1 (TIEG1) is markedly higher in keloid fibroblasts (KFs), while protein, mRNA, and promoter activity levels of Smad7 are decreased. When TIEG1 was knocked down with small interfering RNA (siRNA), both the promoter activity and protein expression of Smad7 were increased, while collagen production and the proliferation, migration, and invasion of KFs were decreased...
January 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28107650/acetylation-enhances-tet2-function-in-protecting-against-abnormal-dna-methylation-during-oxidative-stress
#8
Yang W Zhang, Zhihong Wang, Wenbing Xie, Yi Cai, Limin Xia, Hariharan Easwaran, Jianjun Luo, Ray-Whay Chiu Yen, Yana Li, Stephen B Baylin
TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this abnormality. TET2 removes aberrant DNAm during OS through interacting with DNA methyltransferases (DNMTs) in a "Yin-Yang" complex targeted to chromatin and enhanced by p300 mediated TET2 acetylation...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28107503/osteopontin-affects-insulin-vesicle-localization-and-ca2-homeostasis-in-pancreatic-beta-cells-from-female-mice
#9
Anna Wendt, Inês G Mollet, Anki Knutsson, Victor S Bolmgren, Anna Hultgårdh-Nilsson, Maria F Gomez, Lena Eliasson
Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28107502/rnai-based-functional-genomics-identifies-new-virulence-determinants-in-mucormycosis
#10
Trung Anh Trieu, María Isabel Navarro-Mendoza, Carlos Pérez-Arques, Marta Sanchis, Javier Capilla, Patricia Navarro-Rodriguez, Loida Lopez-Fernandez, Santiago Torres-Martínez, Victoriano Garre, Rosa María Ruiz-Vázquez, Francisco E Nicolás
Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales...
January 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28107458/neuropilin-1-involvement-in-choroidal-and-retinal-neovascularisation
#11
Patricia Fernández-Robredo, Senthil Selvam, Michael B Powner, Dawn A Sim, Marcus Fruttiger
PURPOSE: Inhibiting VEGF is the gold standard treatment for neovascular age-related macular degeneration (AMD). It is also effective in preventing retinal oedema and neovascularisation (NV) in diabetic retinopathy (DR) and retinal vein occlusions (RVO). Neuropilin 1 (Nrp1) is a co-receptor for VEGF and many other growth factors, and therefore a possible alternative drug target in intra ocular neovascular disease. Here we assessed choroidal and retinal NV in an inducible, endothelial specific knock out model for Nrp1...
2017: PloS One
https://www.readbyqxmd.com/read/28107427/serine-phosphorylation-of-slp76-is-dispensable-for-t-cell-development-but-modulates-helper-t-cell-function
#12
Victor H Navas, Céline Cuche, Andres Alcover, Vincenzo Di Bartolo
The adapter protein SLP76 is a key orchestrator of T cell receptor (TCR) signal transduction. We previously identified a negative feedback loop that modulates T cell activation, involving phosphorylation of Ser376 of SLP76 by the hematopoietic progenitor kinase 1 (HPK1). However, the physiological relevance of this regulatory mechanism was still unknown. To address this question, we generated a SLP76-S376A-expressing knock-in mouse strain and investigated the effects of Ser376 mutation on T cell development and function...
2017: PloS One
https://www.readbyqxmd.com/read/28107390/melanoma-cell-adhesion-and-migration-is-modulated-by-the-uronyl-2-o-sulfotransferase
#13
Katerina Nikolovska, Dorothe Spillmann, Jörg Haier, Andrea Ladányi, Christian Stock, Daniela G Seidler
Although the vast majority of melanomas are characterized by a high metastatic potential, if detected early, melanoma can have a good prognostic outcome. However, once metastasised, the prognosis is bleak. We showed previously that uronyl-2-O sulfotransferase (Ust) and 2-O sulfation of chondroitin/dermatan sulfate (CS/DS) are involved in cell migration. To demonstrate an impact of 2-O sulfation in metastasis we knocked-down Ust in mouse melanoma cells. This significantly reduced the amount of Ust protein and enzyme activity...
2017: PloS One
https://www.readbyqxmd.com/read/28107345/syk-regulates-neutrophilic-airway-hyper-responsiveness-in-a-chronic-mouse-model-of-allergic-airways-inflammation
#14
Sepehr Salehi, Xiaomin Wang, Stephen Juvet, Jeremy A Scott, Chung-Wai Chow
BACKGROUND: Asthma is a chronic inflammatory disease characterized by airways hyper-responsiveness (AHR), reversible airway obstruction, and airway inflammation and remodeling. We previously showed that Syk modulates methacholine-induced airways contractility in naïve mice and in mice with allergic airways inflammation. We hypothesize that Syk plays a role in the pathogenesis of AHR; this was evaluated in a chronic 8-week mouse model of house dust mite (HDM)-induced allergic airways inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28106731/hypoxia-inducible-factor-1%C3%AE-promotes-endogenous-adaptive-response-in-rat-model-of-chronic-cerebral-hypoperfusion
#15
Ying Yang, Jieyang Ju, Min Deng, Jing Wang, Hui Liu, Li Xiong, Junjian Zhang
Hypoxia inducible factor 1α (HIF-1α), a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH) triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106724/osteocalcin-mediates-biomineralization-during-osteogenic-maturation-in-human-mesenchymal-stromal-cells
#16
Yu-Tzu Tsao, Yi-Jeng Huang, Hao-Hsiang Wu, Yu-An Liu, Yi-Shiuan Liu, Oscar K Lee
There is a growing interest in cell therapies using mesenchymal stromal cells (MSCs) for repairing bone defects. MSCs have the ability to differentiate into osteoprogenitors and osteoblasts as well as to form calcified bone matrix. However, the molecular mechanisms governing mineralization during osteogenic differentiation remain unclear. Non-collagenous proteins in the extracellular matrix are believed to control different aspects of the mineralization. Since osteocalcin is the most abundant non-collagenous bone matrix protein, the purpose of this study is to investigate the roles of osteocalcin in mineral species production during osteogenesis of MSCs...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106321/conserved-two-component-hik34-rre1-module-directly-activates-heat-stress-inducible-transcription-of-major-chaperone-and-other-genes-in-synechococcus-elongatus-pcc-7942
#17
Ikki Kobayashi, Satoru Watanabe, Yu Kanesaki, Tomohiro Shimada, Hirofumi Yoshikawa, Kan Tanaka
Bacteria and other organisms, including cyanobacteria, employ two-component signal transducing modules comprising histidine kinases and response regulators to acclimate to changing environments. While the number and composition of these modules differ among cyanobacteria, two response regulators that contain DNA binding domains, RpaB and Rre1, are conserved in all sequenced cyanobacterial genomes and are essential for viability. Although RpaB negatively or positively regulates high light and other stress-responsive gene expression, little is known about the function of Rre1...
January 20, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28106276/crispr-cas9-mediated-deletion-of-c1eis-inhibits-chicken-embryonic-stem-cell-differentiation-into-male-germ-cells-gallus-gallus
#18
Qisheng Zuo, Kai Jin, Yingjie Wang, Jiuzhou Song, Yani Zhang, Bichun Li
We previously found that C1EIS is preferentially expressed in Chicken spermatogonial stem cells (SSCs) by RNA sequencing (RNA-seq), so our current study focused on C1EIS's role in Chicken embryonic stem cells (ESCs) differentiation into male germ cells. We constructed a CRISPR/Cas9 vector targeting C1EIS. T7 endonuclease I (T7EI) digestion method and sequencing of TA cloning were used to detect the knock-out efficiency of the Single guide RNA (sgRNA) after the cas9/gRNA vector transfected into D fibroblasts 1(DF-1), ESCs and Chicken embryos...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106162/heterogeneous-nuclear-ribonucleoprotein-m-associates-with-mtorc2-and-regulates-muscle-differentiation
#19
Wei-Yen Chen, Chia-Lung Lin, Jen-Hua Chuang, Fu-Yu Chiu, Yun-Ya Sun, Mei-Chih Liang, Yenshou Lin
Mammalian target of rapamycin (mTOR) plays a range of crucial roles in cell survival, growth, proliferation, metabolism, and morphology. However, mTOR forms two distinct complexes, mTOR complex 1 and mTOR complex 2 (mTORC1 and mTORC2), via association with a series of different components; this allows the complexes to execute their wide range of functions. This study explores further the composition of the mTORC2 complex. Utilizing Rictor knock-out cells, immunoprecipitation and mass spectrometry, a novel Rictor associated protein, heterogeneous nuclear ribonucleoprotein M (hnRNP M), was identified...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106097/lancl-proteins-are-not-involved-in-lanthionine-synthesis-in-mammals
#20
Chang He, Min Zeng, Debapriya Dutta, Tong Hee Koh, Jie Chen, Wilfred A van der Donk
LanC-like (LanCL) proteins are mammalian homologs of bacterial LanC enzymes, which catalyze the addition of the thiol of Cys to dehydrated Ser residues during the biosynthesis of lanthipeptides, a class of natural products formed by post-translational modification of precursor peptides. The functions of LanCL proteins are currently unclear. A recent proposal suggested that LanCL1 catalyzes the addition of the Cys of glutathione to protein- or peptide-bound dehydroalanine (Dha) to form lanthionine, analogous to the reaction catalyzed by LanC in bacteria...
January 20, 2017: Scientific Reports
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