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https://www.readbyqxmd.com/read/29351577/effects-of-excess-thromboxane-a2-on-placental-development-and-nutrient-transporters-in-a-mus-musculus-model-of-fetal-growth-restriction
#1
Karen J Gibbins, Katherine N Gibson-Corley, Ashley S Brown, Matthew Wieben, Richard C Law, Camille M Fung
Hypertensive disease of pregnancy (HDP) with placental insufficiency is the most common cause of fetal growth restriction (FGR) in the developed world. Despite the known negative consequences of HDP both to the mother and fetus, little is known about the longitudinal placental changes that occur as HDP progresses in pregnancy. This is because longitudinal sampling of human placentae during each gestation is impossible. Therefore, using a mouse model of thromboxane A2-analog infusion to mimic human HDP in the last trimester, we calculated placental efficiencies based on fetal and placental weights, quantified spongiotrophoblast and labyrinth thicknesses and vascular density within these layers, examined whether hypoxia signaling pathway involving vascular endothelial growth factor A (VEGFA) and its receptors (VEGFR1, VEGFR2) and matrix metalloproteinases (MMPs) contributed to vascular change, and examined nutrient transporter abundance including glucose transporters 1 and 3 (GLUT1, GLUT3), neutral amino acid transporters 1, 2, and 4 (SNAT1, SNAT2, and SNAT4), fatty acid transporters 2 and 4 (FATP2, FATP4) and fatty acid translocase (CD36) from embryonic day 15...
January 17, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29351421/increased-insulin-clearance-in-mice-with-double-deletion-of-glucagon-like-peptide-1-and-glucose-dependent-insulinotropic-polypeptide-receptors
#2
Andrea Tura, Roberto Bizzotto, Yuichiro Yamada, Yutaka Seino, Giovanni Pacini, Bo Ahren
To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO (n=31) and wild-type (WT) C57BL6J mice (n=45) were intravenously injected with D-glucose (0.35 g/kg). Blood was sampled for 50 minutes and assayed for glucose, insulin and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection...
January 3, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29351372/a-preclinical-population-pharmacokinetic-model-for-anti-cd20-cd3-t-cell-dependent-bispecific-antibodies
#3
Gregory Z Ferl, Arthur Reyes, Liping L Sun, Melissa Cheu, Amy Oldendorp, Saroja Ramanujan, Eric G Stefanich
CD20 is a cell-surface receptor expressed by healthy and neoplastic B cells and is a well-established target for biologics used to treat B-cell malignancies. Pharmacokinetic (PK) and pharmacodynamic (PD) data for the anti-CD20/CD3 T-cell-dependent bispecific antibody BTCT4465A were collected in transgenic mouse and nonhuman primate (NHP) studies. Pronounced nonlinearity in drug elimination was observed in the murine studies, and time-varying, nonlinear PK was observed in NHPs, where three empirical drug elimination terms were identified using a mixed-effects modeling approach: i) a constant nonsaturable linear clearance term (7 mL/day/kg); ii) a rapidly decaying time-varying, linear clearance term (t½  = 1...
January 19, 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/29351317/hafts-are-novel-lncrna-transcripts-from-aflatoxin-exposure
#4
B Alex Merrick, Justin S Chang, Dhiral P Phadke, Meredith A Bostrom, Ruchir R Shah, Xinguo Wang, Oksana Gordon, Garron M Wright
The transcriptome can reveal insights into precancer biology. We recently conducted RNA-Seq analysis on liver RNA from male rats exposed to the carcinogen, aflatoxin B1 (AFB1), for 90 days prior to liver tumor onset. Among >1,000 differentially expressed transcripts, several novel, unannotated Cufflinks-assembled transcripts, or HAfTs (Hepatic Aflatoxin Transcripts) were found. We hypothesized PCR-cloning and RACE (rapid amplification of cDNA ends) could further HAfT identification. Sanger data was obtained for 6 transcripts by PCR and 16 transcripts by 5'- and 3'-RACE...
2018: PloS One
https://www.readbyqxmd.com/read/29351245/exposure-to-ambient-air-particles-increases-the-risk-of-mental-disorder-findings-from-a-natural-experiment-in-beijing
#5
Zhen Jia, Yongjie Wei, Xiaoqian Li, Lixin Yang, Huijie Liu, Chen Guo, Lulu Zhang, Nannan Li, Shaojuan Guo, Yan Qian, Zhigang Li
Epidemiology studies indicated that air pollution has been associated with adverse neurological effects in human. Moreover, the secretion of glucocorticoid (GC) affects the mood regulation, and the negative feedback of hippocampal glucocorticoid receptors (GR) inhibits the GC secretion. Meanwhile, the over secretion of GC can interfere the immune system and induce neurotoxicity. In the present study, the human test showed that the secretion of the cortisol in plasma was elevated after exposure in heavy air pollution...
January 19, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29351057/global-gene-expression-response-in-mouse-models-of-dna-repair-deficiency-after-gamma-irradiation
#6
Nils Rudqvist, Evagelia C Laiakis, Shanaz A Ghandhi, Suresh Kumar, Jeffrey D Knotts, Mashkura Chowdhury, Albert J Fornace, Sally A Amundson
In the event of an improvised nuclear device or "dirty bomb" in a highly populated area, potentially hundreds of thousands of people will require screening to ensure that exposed individuals receive appropriate treatment. For this reason, there is a need to develop tools for high-throughput radiation biodosimetry. Gene expression represents an emerging approach to biodosimetry and could potentially provide an estimate of both absorbed dose and individual radiation-induced injury. Since approximately 2-4% of humans are thought to be radiosensitive, and would suffer greater radiological injury at a given dose than members of the general population, it is of interest to explore the potential impact of such sensitivity on the biodosimetric gene expression signatures being developed...
January 19, 2018: Radiation Research
https://www.readbyqxmd.com/read/29350998/overexpression-of-the-neuronal-human-pro-renin-receptor-mediates-angiotensin-ii-independent-blood-pressure-regulation-in-the-central-nervous-system
#7
Hua Peng, Dane D Jensen, Wencheng Li, Michelle N Sullivan, Sophie A Buller, Caleb J Worker, Silvana G Cooper, Shiqi Zheng, Scott Earley, Curt D Sigmund, Yumei Feng
Despite advances in anti-hypertensive therapeutics, at least 15-20% of hypertensive patients have resistant hypertension through mechanisms that remain poorly understood. In this study, we provide a new mechanism for regulation of blood pressure (BP) in the central nervous system (CNS) by the (pro)renin receptor (PRR), a recently identified component of the renin-angiotensin system (RAS) that mediates angiotensin II (Ang II) formation in the CNS. Although the PRR also mediates Ang II-independent signaling, the importance of these pathways in BP regulation is unknown...
December 15, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29350886/the-cell-biology-and-molecular-genetics-of-m%C3%A3-llerian-duct-development
#8
REVIEW
Zahida Yesmin Roly, Brendan Backhouse, Andrew Cutting, Tiong Yang Tan, Andrew H Sinclair, Katie L Ayers, Andrew T Major, Craig A Smith
The Müllerian ducts are part of the embryonic urogenital system. They give rise to mature structures that serve a critical function in the transport and development of the oocyte and/or embryo. In most vertebrates, both sexes initially develop Müllerian ducts during embryogenesis, but they regress in males under the influence of testis-derived Anti-Müllerian Hormone (AMH). A number of regulatory factors have been shown to be essential for proper duct development, including Bmp and Wnt signaling molecules, together with homeodomain transcription factors such as PAX2 and LIM1...
January 19, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/29350802/cellular-reprogramming-a-new-way-to-understand-aging-mechanisms
#9
REVIEW
Burcu Yener Ilce, Umut Cagin, Acelya Yilmazer
Increased life expectancy, due to the rise in life quality and the decline in mortality rates, is leading to a society in which the population aged 60 and over is growing more rapidly than the entire population. Although various models and model organisms have been employed to investigate the mechanism of aging, induced pluripotent stem cells (iPSCs) are useful candidates to study human aging and age-related human diseases. This work discusses how iPSCs can be used as an alternative to the model organisms such as yeast, Caenorhabditis elegans, Drosophila melanogaster, or the mouse...
January 19, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/29350308/the-ppar%C3%AE-agonist-efatutazone-delays-invasive-progression-and-induces-differentiation-of-ductal-carcinoma-in-situ
#10
Virginie Ory, William B Kietzman, Jacob Boeckelman, Bhaskar V Kallakury, Anton Wellstein, Priscilla A Furth, Anna T Riegel
PURPOSE: Ductal carcinoma in situ (DCIS) is a pre-invasive lesion of the breast considered a precursor of invasive ductal carcinoma. This study aimed to determine whether activated PPARγ acts as a tumor suppressor in human DCIS progression. METHODS: We utilized the high-affinity PPARγ agonist, efatutazone, to activate endogenous PPARγ in a well-defined model for the progression of basal (triple negative) DCIS, MCFDCIS cells, cultured under 2D and 3D conditions...
January 19, 2018: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29349894/assessment-of-the-potential-of-temporin-peptides-from-the-frog-rana-temporaria-ranidae-as-anti-diabetic-agents
#11
Vishal Musale, Bruno Casciaro, Maria Luisa Mangoni, Yasser H A Abdel-Wahab, Peter R Flatt, J Michael Conlon
Temporin A (FLPLIGRVLSGIL-NH2 ), temporin F (FLPLIGKVLSGIL-NH2 ), and temporin G (FFPVIGRILNGIL-NH2 ), first identified in skin secretions of the frog Rana temporaria, produced concentration-dependent stimulation of insulin release from BRIN-BD11 rat clonal β-cells at concentrations ≥1 nM, without cytotoxicity at concentrations up to 3 μM. Temporin A was the most effective. The mechanism of insulinotropic action did not involve an increase in intracellular Ca2+ concentrations. Temporins B, C, E, H, and K were either inactive or only weakly active...
January 19, 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29349567/hbeag-induces-the-expression-of-macrophage-mir-155-to-accelerate-liver-injury-via-promoting-production-of-inflammatory-cytokines
#12
Wenwen Wang, Hongjun Bian, Feifei Li, Xiao Li, Di Zhang, Shuohuan Sun, Shouyang Song, Qiang Zhu, Wanhua Ren, Chengyong Qin, Jianni Qi
Activation of Kupffer cells (KCs) induced that inflammatory cytokine production plays a central role in the pathogenesis of HBV infection. The previous studies from our and other laboratory demonstrated miRNAs can regulate TLR-inducing inflammatory responses to macrophage. However, the involvement of miRNAs in HBV-associated antigen-induced macrophage activation is still not thoroughly understood. Here, we evaluated the effects and mechanisms of miR-155 in HBV-associated antigen-induced macrophage activation...
January 18, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29349060/sost-deficiency-does-not-alter-bone-s-lacunar-or-vascular-porosity-in-mice
#13
Henry Mosey, Juan A Núñez, Alice Goring, Claire E Clarkin, Katherine A Staines, Peter D Lee, Andrew A Pitsillides, Behzad Javaheri
SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative regulator of bone formation. In humans, mutations in the SOST gene lead to skeletal overgrowth and increased bone mineral density, suggesting that SCLEROSTIN is a key regulator of bone mass. The function of SCLEROSTIN as an inhibitor of bone formation is further supported by Sost knockout (KO) mice which display a high bone mass with elevated bone formation. Previous studies have indicated that Sost exerts its effect on bone formation through Wnt-mediated regulation of osteoblast differentiation, proliferation, and activity...
September 13, 2017: Frontiers in Materials
https://www.readbyqxmd.com/read/29348628/fezf1-as1-mir-107-znf312b-axis-facilitates-progression-and-warburg-effect-in-pancreatic-ductal-adenocarcinoma
#14
Huilin Ye, Quanbo Zhou, Shangyou Zheng, Guolin Li, Qing Lin, Liangtao Ye, Yingxue Wang, Lusheng Wei, Xiaohui Zhao, Wenzhu Li, Zhiqiang Fu, Yimin Liu, Zhihua Li, Rufu Chen
Long non-coding RNAs (lncRNAs) play a pivotal role in pathological processes. However, little information has been published regarding the underlying functions and mechanisms of lncRNAs in pancreatic ductal adenocarcinoma (PDAC). A novel lncRNA FEZF1-AS1 and its sense-cognate gene ZNF312B were found to be highly expressed in human PDAC tissues and cell lines, which is associated with disease progression and predicts clinical outcome in PDAC patients. Of note, bioinformatics analysis, luciferase assays and RNA immunoprecipitation assays indicated that FEZF1-AS1 may act as an endogenous sponge by competing for miR-107, thereby modulating the derepression of ZNF312B...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348564/inhibition-of-wnt-%C3%AE-catenin-signaling-under-serum-starvation-and-hypoxia-induces-adipocytic-transdifferentiation-in-human-leiomyoma-cells
#15
Hiroshi Harada, Yojiro Tsuda, Kei Yabuki, Eisuke Shiba, Kazuyoshi Uchihashi, Atsuji Matsuyama, Yoshihisa Fujino, Toru Hachisuga, Masanori Hisaoka
Fatty metamorphosis is an uncommon alteration in uterine leiomyoma (i.e., lipoleiomyoma), and the pathogenetic mechanisms underlying this phenomenon remain poorly understood. Because a conditional deletion of β-catenin, a major transducer of the canonical Wingless/integrated (WNT) pathway, in the developing mouse uterus can induce adipogenesis in the myometrium, it is hypothesized that inhibition of the WNT/β-catenin signaling may be also involved in the development of fat cells within uterine leiomyoma. In the current study, which was performed to address this point, intracytoplasmic lipid droplets were detectable in cultured human leiomyoma cells by treatment with a potent tankyrase inhibitor, XAV939, which antagonizes β-catenin, in a serum-starved culture medium without additional adipogenesis-inducing agents or supplements, and showed increasing accumulation in a time-dependent manner...
January 18, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29348560/discovery-of-a-small-molecule-protein-kinase-c%C3%AE-selective-activator-with-promising-application-in-colon-cancer-therapy
#16
Cláudia Bessa, Joana Soares, Liliana Raimundo, Joana B Loureiro, Célia Gomes, Flávio Reis, Miguel L Soares, Daniel Santos, Chetna Dureja, Saumya R Chaudhuri, Cynthia Lopez-Haber, Marcelo G Kazanietz, Jorge Gonçalves, Maria F Simões, Patrícia Rijo, Lucília Saraiva
Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCδ-C1-domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348535/umbilical-cord-extracts-improve-osteoporotic-abnormalities-of-bone-marrow-derived-mesenchymal-stem-cells-and-promote-their-therapeutic-effects-on-ovariectomised-rats
#17
Akira Saito, Kanna Nagaishi, Kousuke Iba, Yuka Mizue, Takako Chikenji, Miho Otani, Masako Nakano, Kazusa Oyama, Toshihiko Yamashita, Mineko Fujimiya
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most valuable source of autologous cells for transplantation and tissue regeneration to treat osteoporosis. Although BM-MSCs are the primary cells responsible for maintaining bone metabolism and homeostasis, their regenerative ability may be attenuated in postmenopausal osteoporosis patients. Therefore, we first examined potential abnormalities of BM-MSCs in an oestrogen-deficient rat model constructed by ovariectomy (OVX-MSCs). Cell proliferation, mobilisation, and regulation of osteoclasts were downregulated in OVX-MSCs...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348487/h1-phgfk1-nanoparticles-exert-anti-tumoural-and-radiosensitising-effects-by-inhibition-of-met-in-glioblastoma
#18
Wenyan Zhang, Rui Duan, Jian Zhang, William K C Cheung, Xiaoge Gao, Raymond Zhang, Qing Zhang, Mengxue Wei, Gang Wang, Qian Zhang, Peng-Jin Mei, Hong-Lin Chen, Hsiangfu Kung, Marie C Lin, Zan Shen, Junnian Zheng, Longzhen Zhang, Hong Yao
BACKGROUND: The therapeutic resistance to ionising radiation (IR) and anti-angiogenesis mainly impair the prognosis of patients with glioblastoma. The primary and secondary MET aberrant activation is one crucial factor for these resistances. The kringle 1 domain of hepatocyte growth factor (HGFK1), an angiogenic inhibitor, contains a high-affinity binding domain of MET; however, its effects on glioblastoma remain elusive. METHODS: We formed the nanoparticles consisting of a folate receptor-targeted nanoparticle-mediated HGFK1 gene (H1/pHGFK1) and studied its anti-tumoural and radiosensitive activities in both subcutaneous and orthotopic human glioma cell-xenografted mouse models...
January 18, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29348467/efficacy-of-mek-inhibition-in-a-k-ras-driven-cholangiocarcinoma-preclinical-model
#19
Mingjie Dong, Xianqiong Liu, Katja Evert, Kirsten Utpatel, Michele Peters, Shanshan Zhang, Zhong Xu, Li Che, Antonio Cigliano, Silvia Ribback, Frank Dombrowski, Antonio Cossu, John Gordan, Diego F Calvisi, Matthias Evert, Yan Liu, Xin Chen
Intrahepatic cholangiocarcinoma (iCCA) is a deadly malignancy with limited treatment options. Gain-of-function mutations in K-Ras is a very frequent alteration, occurring in ~15 to 25% of human iCCA patients. Here, we established a new iCCA model by expressing activated forms of Notch1 (NICD) and K-Ras (K-RasV12D) in the mouse liver (K-Ras/NICD mice). Furthermore, we investigated the therapeutic potential of MEK inhibitors in vitro and in vivo using human CCA cell lines and K-Ras/NICD mice, respectively. Treatment with U0126, PD901, and Selumetinib MEK inhibitors triggered growth restraint in all CCA cell lines tested, with the most pronounced growth suppressive effects being observed in K-Ras mutant cells...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348462/piperlongumine-and-p53-reactivator-apr-246-selectively-induce-cell-death-in-hnscc-by-targeting-gstp1
#20
Wei Hang, Zhi-Xian Yin, Gang Liu, Qinghua Zeng, Xiang-Feng Shen, Qian-Hui Sun, Dong-Dong Li, Yong-Ping Jian, Yang-He Zhang, Yi-Shu Wang, Cheng-Shi Quan, Rui-Xun Zhao, Yu-Lin Li, Zhi-Xiang Xu
TP53 mutations frequently occur in head and neck squamous cell carcinoma (HNSCC) patients without human papillomavirus infection. The recurrence rate for these patients is distinctly high. It has been actively explored to identify agents that target TP53 mutations and restore wild-type (WT) TP53 activities in HNSCC. PRIMA-1 (p53-reactivation and induction of massive apoptosis-1) and its methylated analogue PRIMA-1Met (also called APR-246) were found to be able to reestablish the DNA-binding activity of p53 mutants and reinstate the functions of WT p53...
January 18, 2018: Oncogene
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