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https://www.readbyqxmd.com/read/29330760/oxidized-phospholipids-stimulate-production-of-stem-cell-factor-via-nrf2-dependent-mechanisms
#1
Taras Afonyushkin, Olga V Oskolkova, Valery N Bochkov
Receptor tyrosine kinase c-Kit and its ligand stem cell factor (SCF) regulate resident vascular wall cells and recruit circulating progenitors. We tested whether SCF may be induced by oxidized palmitoyl-arachidonoyl-phosphatidylcholine (OxPAPC) known to accumulate in atherosclerotic vessels. Gene expression analysis demonstrated OxPAPC-induced upregulation of SCF mRNA and protein in different types of endothelial cells (ECs). Elevated levels of SCF mRNA were observed in aortas of ApoE-/- knockout mice. ECs produced biologically active SCF because conditioned medium from OxPAPC-treated cells stimulated activation (phosphorylation) of c-Kit in naïve ECs...
January 12, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29330147/genetic-ablation-of-rbm38-promotes-lymphomagenesis-in-the-context-of-mutant-p53-by-downregulating-pten
#2
Jin Zhang, Enshun Xu, Cong Ren, Hee Jung Yang, Yanhong Zhang, Wenqiang Sun, Xiangmudong Kong, Weici Zhang, Mingyi Chen, Eric C Huang, Xinbin Chen
Mutant p53 exerts gain-of-function effects that drive metastatic progression and therapeutic resistance, but the basis for these effects remain obscure. The RNA binding protein RBM38 limits translation of mutant p53 and is often ablated in tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer susceptibility in mutant p53 knock-in mice, by shortening lifespan, altering tumor incidence and promoting T cell lymphomagenesis. Loss of Rbm38 enhanced mutant p53 expression and decreased expression of the tumor suppressor Pten, a key regulator of T cell development...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29324052/the-expression-profile-of-claudin-family-members-in-the-developing-mouse-lung-and-expression-alterations-resulting-from-exposure-to-secondhand-smoke-shs
#3
Joshua B Lewis, Felix R Jimenez, Brigham J Merrell, Brent Kimbler, Juan A Arroyo, Paul R Reynolds
Claudins are tight junctional proteins implicated in cell polarity and epithelial barrier maintenance. Claudin misregulation adversely impacts developmental aspects of cell differentiation and proliferation. The current research evaluated transcriptional expression for Claudins 1-11 and 18 in the developing murine lung at embryonic days (E) 14.5, 16.5, and 18.5 and at post-natal day (PN) 3 and PN15. Mouse lungs were also assessed by immunohistochemical analysis to qualitatively evaluate Claudin protein expression...
January 11, 2018: Experimental Lung Research
https://www.readbyqxmd.com/read/29323748/the-gain-of-function-mutation-e76k-in-shp2-promotes-cac-tumorigenesis-and-induces-emt-via-the-wnt-%C3%AE-catenin-signaling-pathway
#4
Qian Zhang, Rongrong Zhao, Chuling Fan, Xinyi Wang, Youzhi Xu, Yakun Liu, Siying Wang
SHP2 is encoded by the protein tyrosine phosphatase 11 (Ptpn11) gene. Several gain-of-function (GOF) mutations in Ptpn11 have been identified in human hematopoietic malignancies and solid tumors. In addition, the mutation rate for SHP2 is the highest for colorectal cancer (CRC) among solid tumors. The E76K GOF mutation is the most common and active SHP2 mutation; however, the pathogenic effects and function of this mutation in CRC tumor progression have not been well characterized. The Wnt/β-catenin (CTNNB1) signaling pathway is crucial for CRC, and excessive activation of this pathway has been observed in several tumors...
January 11, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29321644/cox-2-induces-oncogenic-micro-rna-mir655-in-human-breast-cancer
#5
Mousumi Majumder, Leanna Dunn, Ling Liu, Asma Hasan, Krista Vincent, Muriel Brackstone, David Hess, Peeyush K Lala
We show that Cyclooxygenase-2 over-expression induces an oncogenic microRNA miR655 in human breast cancer cells by activation of EP4. MiR655 expression positively correlated with COX-2 in genetically disparate breast cancer cell lines and increased in all cell lines when grown as spheroids, implicating its link with stem-like cells (SLCs). Ectopic miR655 over-expression in MCF7 and SKBR3 cells resulted in increased proliferation, migration, invasion, spheroid formation and Epithelial to Masenchymal transition (EMT)...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321331/germline-igm-is-sufficient-but-not-required-for-antibody-mediated-alphavirus-clearance-from-the-central-nervous-system
#6
Voraphoj Nilaratanakul, Jie Chen, Oanh Tran, Victoria K Baxter, Elizabeth M Troisi, Jane X Yeh, Diane E Griffin
Sindbis virus (SINV) infection of neurons in the brain and spinal cord in mice provides a model system for investigating recovery from encephalomyelitis and antibody-mediated clearance of virus from the central nervous system (CNS). To determine the roles of IgM and IgG in recovery, we compared the responses of immunoglobulin-deficient activation-induced adenosine deaminase (AID)-/-, secretory IgM (sIgM)-/- and AID-/- sIgM-/- double knock out (DKO) mice with wild-type (WT) C57BL/6 mice for disease, clearance of infectious virus and viral RNA from brain and spinal cord, antibody responses and B cell infiltration into the CNS...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29317733/in-vivo-sted-microscopy-visualizes-psd95-sub-structures-and-morphological-changes-over-several-hours-in-the-mouse-visual-cortex
#7
Waja Wegner, Alexander C Mott, Seth G N Grant, Heinz Steffens, Katrin I Willig
The post-synaptic density (PSD) is an electron dense region consisting of ~1000 proteins, found at the postsynaptic membrane of excitatory synapses, which varies in size depending upon synaptic strength. PSD95 is an abundant scaffolding protein in the PSD and assembles a family of supercomplexes comprised of neurotransmitter receptors, ion channels, as well as signalling and structural proteins. We use superresolution STED (STimulated Emission Depletion) nanoscopy to determine the size and shape of PSD95 in the anaesthetised mouse visual cortex...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29315632/food-allergen-sensitized-ccr9-lymphocytes-enhance-airways-allergic-inflammation-in-mice
#8
Laure Castan, Marie-Aude Cheminant, Luc Colas, Sophie Brouard, Antoine Magnan, Grégory Bouchaud
BACKGROUND: The mechanisms of the atopic march, characterized by a natural progression from food and cutaneous allergies to rhinitis and asthma, are still unknown. However, as several organs can be involved, chemokines and their receptors might be implicated in this process and may be instrumental factors. OBJECTIVES: We hypothesized that the T-cell gut-homing receptor CCR9 could be implicated in the evolution of allergic diseases. METHODS: We characterized the immune response and the role of CCR9 in a murine model combining food allergy to wheat gliadin and a model of acute airways inflammation in response to house dust mite...
January 9, 2018: Allergy
https://www.readbyqxmd.com/read/29315574/palmitate-induced-c-ebp-homologous-protein-activation-leads-to-nf-%C3%AE%C2%BAb-mediated-increase-in-bace1-activity-and-amyloid-beta-genesis
#9
Gurdeep Marwarha, Jared Schommer, Jonah Lund, Trevor Schommer, Othman Ghribi
The etiology of Alzheimer's disease (AD) is egregiously comprehended, but epidemiological studies have posited that diets rich in the saturated fatty acid palmitic acid (palmitate) are a significant risk factor. The production and accumulation of Amyloid-beta peptide (Aβ) is considered the core pathological molecular event in the pathogenesis of AD. The rate limiting step in Aβ genesis from Amyloid-β precursor protein (AβPP) is catalyzed by the enzyme β-site APP cleaving enzyme 1 (BACE1), the expression and enzymatic activity of which is significantly upregulated in the AD brain...
January 6, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29313816/osteopontin-regulates-dentin-and-alveolar-bone-development-and-mineralization
#10
B L Foster, M Ao, C R Salmon, M B Chavez, T N Kolli, A B Tran, E Y Chu, K R Kantovitz, M Yadav, S Narisawa, J L Millán, F H Nociti, M J Somerman
The periodontal complex is essential for tooth attachment and function and includes the mineralized tissues, cementum and alveolar bone, separated by the unmineralized periodontal ligament (PDL). To gain insights into factors regulating cementum-PDL and bone-PDL borders and protecting against ectopic calcification within the PDL, we employed a proteomic approach to analyze PDL tissue from progressive ankylosis knock-out (Ank-/-) mice, featuring reduced PPi, rapid cementogenesis, and excessive acellular cementum...
December 4, 2017: Bone
https://www.readbyqxmd.com/read/29312632/trib2-contributes-to-cisplatin-resistance-in-small-cell-lung-cancer
#11
Yuanxin Liang, Dong Yu, Roman Perez-Soler, Jim Klostergaard, Yiyu Zou
Small cell lung cancer (SCLC) is the most aggressive lung-cancer subtype and so far, no favorable therapeutic strategy has been established for chemo-resistant SCLC. Cisplatin is one of the most important components among all standard poly-chemotherapeutic regimens for SCLC; therefore, this study focused on revealing Cisplatin-resistance mechanism(s) in this disease. Cisplatin-resistant SCLC cells were generated in the NCI-H69 xenograft model in nude mice by continuous intravenous administration of Cisplatin; Cisplatin resistance of the tumor cells was confirmed by in vitro and in vivo tests, and the gene expression profile of the resistant cells was determined using microarray analysis...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311600/depdc5-deficiency-contributes-to-resistance-to-leucine-starvation-via-p62-accumulation-in-hepatocellular-carcinoma
#12
Yuki Mizuno, Shu Shimada, Yoshimitsu Akiyama, Shuichi Watanabe, Tomomi Aida, Kosuke Ogawa, Hiroaki Ono, Yusuke Mitsunori, Daisuke Ban, Atsushi Kudo, Shigeki Arii, Shoji Yamaoka, Minoru Tanabe, Shinji Tanaka
Decrease in blood concentration of branched-chain amino acids, especially leucine, is known to promote liver carcinogenesis in patients with chronic liver disease, but the mechanism is unclear. We herein established hepatocellular carcinoma (HCC) cells knocked out for DEPDC5 by using the CRISPR/Cas9 system, and elucidated that cell viability of the DEPDC5 knockout (DEPDC5-KO) cells was higher than that of the DEPDC5 wild-type (DEPDC5-WT) under leucine starvation. Considering that autophagy deficiency might be involved in acquired resistance to leucine deprivation, we observed reduction of LC3-II followed by accumulation of p62 in the DEPDC5-KO, which induced reactive oxygen species (ROS) tolerance...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311544/silencing-of-the-lncrna-zeb2-nat-facilitates-reprogramming-of-aged-fibroblasts-and-safeguards-stem-cell-pluripotency
#13
Bruno Bernardes de Jesus, Sérgio Pires Marinho, Sara Barros, António Sousa-Franco, Catarina Alves-Vale, Tânia Carvalho, Maria Carmo-Fonseca
Aging imposes a barrier to somatic cell reprogramming through poorly understood mechanisms. Here, we report that fibroblasts from old mice express higher levels of Zeb2, a transcription factor that activates epithelial-to-mesenchymal transition. Synthesis of Zeb2 protein is controlled by a natural antisense transcript named Zeb2-NAT. We show that transfection of adult fibroblasts with specific LNA Gapmers induces a robust downregulation of Zeb2-NAT transcripts and Zeb2 protein and enhances the reprogramming of old fibroblasts into pluripotent cells...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29310663/%C3%AE-synuclein-accumulation-and-gba-deficiency-due-to-l444p-gba-mutation-contributes-to-mptp-induced-parkinsonism
#14
Seung Pil Yun, Donghoon Kim, Sangjune Kim, SangMin Kim, Senthilkumar S Karuppagounder, Seung-Hwan Kwon, Saebom Lee, Tae-In Kam, Suhyun Lee, Sangwoo Ham, Jae Hong Park, Valina L Dawson, Ted M Dawson, Yunjong Lee, Han Seok Ko
BACKGROUND: Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors contribute to the pathogenesis of sporadic PD, we investigated the susceptibility of nigrostriatal dopamine (DA) neurons in L444P GBA heterozygous knock-in (GBA +/L444P ) mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective dopaminergic mitochondrial neurotoxin...
January 8, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29310441/dihydromyricetin-ameliorates-nonalcoholic-fatty-liver-disease-by-improving-mitochondrial-respiratory-capacity-and-redox-homeostasis-through-modulation-of-sirt3-signaling
#15
Xianglong Zeng, Jining Yang, Ou Hu, Juan Huang, Li Ran, Mengting Chen, Yu Zhang, Xi Zhou, Jundong Zhu, Qianyong Zhang, Long Yi, Mantian Mi
AIMS: Our previous clinical trial indicated that the flavonoid dihydromyricetin (DHM) could improve hepatic steatosis in patients with NAFLD, altough the potential mechanisms of these effects remained elusive. Here, we investigated the hepatoprotective role of DHM on high-fat diet (HFD)-induced NAFLD. RESULTS: DHM supplementation could effectively ameliorate the development of NAFLD by inhibiting hepatic lipids accumulation both in HFD-fed wild type mice and in palmitic acid (PA)-induced hepatocytes...
January 8, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29304082/striated-muscle-gene-therapy-for-the-treatment-of-lipoprotein-lipase-deficiency
#16
Katherine E Gadek, Hong Wang, Monica N Hall, Mitchell Sungello, Andrew Libby, Drew MacLaskey, Robert H Eckel, Bradley B Olwin
Excessive circulating triglycerides due to reduction or loss of lipoprotein lipase activity contribute to hypertriglyceridemia and increased risk for pancreatitis. The only gene therapy treatment for lipoprotein lipase deficiency decreases pancreatitis but minimally reduces hypertriglyceridemia. Synthesized in multiple tissues including striated muscle and adipose tissue, lipoprotein lipase is trafficked to blood vessel endothelial cells where it is anchored at the plasma membrane and hydrolyzes triglycerides into free fatty acids...
2018: PloS One
https://www.readbyqxmd.com/read/29303057/integrin-%C3%AE-v%C3%AE-3-is-essential-for-maintenance-of-decidua-tissue-homeostasis-and-of-natural-killer-cell-immune-tolerance-during-pregnancy
#17
Shaojuan Wang, Xiaoli Zhou, Jing Yang
Physiological functions of villous trophoblasts are essential for normal implantation and pregnancy, which are under fine regulations. Integrin αvβ3 has been shown to mediate cellular attachment of villous trophoblasts; however, the physiological functions of integrin αvβ3 in pregnancy have not been revealed. Here, we found that suppression of integrin αvβ3 in vivo by a small molecule inhibitor, SB-273005, resulted in abnormal pregnancy in mice. Mechanistically, suppression of integrin αvβ3 in vivo broke down the tissue homeostasis of the decidua, as revealed by disorganized histology and compromised cellular proliferation in the decidua...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29300914/local-klotho-enhances-neuronal-progenitor-proliferation-in-the-adult-hippocampus
#18
Felipe Salech, Lorena Varela-Nallar, Sebastián B Arredondo, Daniel B Bustamante, Gabriela A Andaur, Rodrigo Cisneros, Daniela P Ponce, Patricia Ayala, Nibaldo C Inestrosa, José L Valdés, María I Behrens, Andrés Couve
Klotho is an aging-related protein associated with hippocampal cognitive performance in mammals. Klotho regulates progenitor cell proliferation in non-neuronal tissues, but its role in adult hippocampal neurogenesis (AHN) has not been explored. Klotho expression in the adult mouse hippocampus was examined by immunofluorescence and PCR. AHN was evaluated in the hippocampus of klotho knock-out mice (KO), klotho KO/vitamin D-receptor mutant mice, and in a model of local klotho hippocampal knockdown. The recombinant Klotho effect on proliferation was measured in mouse-derived hippocampal neural progenitor cells...
December 30, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29299144/lincrna00273-promotes-cancer-metastasis-and-its-g-quadruplex-promoter-can-serve-as-a-novel-target-to-inhibit-cancer-invasiveness
#19
Samarjit Jana, Jagannath Jana, Kartick Patra, Soma Mondal, Jyotsna Bhat, Arnab Sarkar, Pallabi Sengupta, Anindya Biswas, Meghomukta Mukherjee, Satya Prakash Tripathi, Rahul Gangwal, Joyita Hazra, Abhay T Sangamwar, Gopeswar Mukherjee, Shamee Bhattacharjee, Deba Prasad Mandal, Subhrangsu Chatterjee
Discovery of anti-metastatic drugs is of immense clinical significance as metastasis is responsible for 90% of all cancer deaths. Here we report the inhibitory effect of a bis schiff base (M2) on cancer cell migration and invasion in vitro and in vivo. M2 has shown good solubility and permeability across the intestinal cell wall and hence can be classified as BCS (Biopharmaceutical classification system) class I. Microarray studies identified a long non coding intergenic RNA, LINC00273 as a novel molecular target of M2...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298895/endoplasmic-reticulum-stress-responses-in-mouse-models-of-alzheimer-disease-overexpression-paradigm-versus-knock-in-paradigm
#20
Shoko Hashimoto, Ayano Ishii, Naoko Kamano, Naoto Watamura, Takashi Saito, Toshio Oshima, Makoto Yokosuka, Takaomi C Saido
Endoplasmic reticulum (ER) stress is believed to play an important role in the etiology of Alzheimer disease (AD). The accumulation of misfolded proteins and perturbation of intracellular calcium homeostasis are thought to underlie the induction of ER stress, resulting in neuronal dysfunction and cell death. Several reports have shown an increased ER stress response in amyloid precursor protein (APP) and presenilin1 (PS1) double transgenic (Tg) AD mouse models. However, it remains unclear whether the ER stress observed in these mouse models is actually caused by AD pathology...
January 3, 2018: Journal of Biological Chemistry
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