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https://www.readbyqxmd.com/read/28814615/single-cell-gene-expression-of-the-bovine-blastocyst
#1
Veronica M Negrón-Pérez, Yanping Zhang, Peter J Hansen
The first two differentiation events in the blastocyst result in three cell types - epiblast, trophectoderm (TE), and hypoblast. The purpose here was to identify molecular markers for each cell type in the bovine and evaluate differences in gene expression among individual cells of each lineage. The cDNA from 67 individual cells from dissociated blastocysts was used to determine transcript abundance for 96 genes implicated as cell lineage markers in other species or potentially involved in developmental processes...
August 16, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28811522/the-lichen-secondary-metabolite-atranorin-suppresses-lung-cancer-cell-motility-and-tumorigenesis
#2
Rui Zhou, Yi Yang, So-Yeon Park, Thanh Thi Nguyen, Young-Woo Seo, Kyung Hwa Lee, Jae Hyuk Lee, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807941/the-rac-gtpase-in-cancer-from-old-concepts-to-new-paradigms
#3
Marcelo G Kazanietz, María-José Caloca
Rho family GTPases are critical regulators of cellular functions that play important roles in cancer progression. Aberrant activity of Rho small G-proteins, particularly Rac1 and their regulators, is a hallmark of cancer, and contributes to the tumorigenic and metastatic phenotypes of cancer cells. This review examines the multiple mechanisms leading to Rac1 hyperactivation, particularly focusing on emerging paradigms that involve gain-of-function mutations in Rac and guanine nucleotide exchange factors (GEFs), defects in Rac1 degradation, and mislocalization of Rac signaling components...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28806779/a-mutation-in-nischarin-causes-otitis-media-via-limk1-and-nf-%C3%AE%C2%BAb-pathways
#4
Michael Crompton, Tom Purnell, Hayley E Tyrer, Andrew Parker, Greg Ball, Rachel E Hardisty-Hughes, Richard Gale, Debbie Williams, Charlotte H Dean, Michelle M Simon, Ann-Marie Mallon, Sara Wells, Mahmood F Bhutta, Martin J Burton, Hilda Tateossian, Steve D M Brown
Otitis media (OM), inflammation of the middle ear (ME), is a common cause of conductive hearing impairment. Despite the importance of the disease, the aetiology of chronic and recurrent forms of middle ear inflammatory disease remains poorly understood. Studies of the human population suggest that there is a significant genetic component predisposing to the development of chronic OM, although the underlying genes are largely unknown. Using N-ethyl-N-nitrosourea mutagenesis we identified a recessive mouse mutant, edison, that spontaneously develops a conductive hearing loss due to chronic OM...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28805822/intrinsic-bet-inhibitor-resistance-in-spop-mutated-prostate-cancer-is-mediated-by-bet-protein-stabilization-and-akt-mtorc1-activation
#5
Pingzhao Zhang, Dejie Wang, Yu Zhao, Shancheng Ren, Kun Gao, Zhenqing Ye, Shangqian Wang, Chun-Wu Pan, Yasheng Zhu, Yuqian Yan, Yinhui Yang, Di Wu, Yundong He, Jun Zhang, Daru Lu, Xiuping Liu, Long Yu, Shimin Zhao, Yao Li, Dong Lin, Yuzhuo Wang, Liguo Wang, Yu Chen, Yinghao Sun, Chenji Wang, Haojie Huang
Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising anticancer therapies. The gene encoding the E3 ubiquitin ligase substrate-binding adaptor speckle-type POZ protein (SPOP) is the most frequently mutated in primary prostate cancer. Here we demonstrate that wild-type SPOP binds to and induces ubiquitination and proteasomal degradation of BET proteins (BRD2, BRD3 and BRD4) by recognizing a degron motif common among them. In contrast, prostate cancer-associated SPOP mutants show impaired binding to BET proteins, resulting in decreased proteasomal degradation and accumulation of these proteins in prostate cancer cell lines and patient specimens and causing resistance to BET inhibitors...
August 14, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28804948/nelumbo-nucifera-leaf-extract-treatment-attenuated-preneoplastic-lesions-and-oxidative-stress-in-the-livers-of-diethylnitrosamine-treated-rats
#6
Chi-Ting Horng, Chien-Wei Huang, Mon-Yuan Yang, Tzu-Hsin Chen, Yun-Ching Chang, Chau-Jong Wang
Lotus (Nelumbo nucifera Gaertn) possesses antioxidant, hepatoprotective, and anticancer potential. This study determined the protective role of aqueous extract from Nelumbo nucifera leaves (NLE) against N-diethylnitrosamine (DEN)-induced oxidative stress and hepatocellular carcinogenesis in a sample of Sprague-Dawley rats. NLE was fed orally to rats in which hepatic carcinoma was induced with DEN for 12 weeks. Five groups of 12 rats each were used for the study: Group I (control group) rats received distilled water; Group II rats were induced with DEN; Group III rats were induced with DEN and cotreated with 0...
August 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28804736/urokinase-type-plasminogen-activator-upa-and-its-receptor-upar-promote-neurorepair-in-the-ischemic-brain
#7
Paola Merino, Ariel Diaz, Manuel Yepes
Despite the fact that ischemic stroke has been considered a leading cause of mortality in the world, recent advances in our understanding of the pathophysiological mechanisms underlying the ischemic injury and the treatment of acute ischemic stroke patients have led to a sharp decrease in the number of stroke deaths. However, this decrease in stroke mortality has also led to an increase in the number of patients that survive the acute ischemic injury with different degrees of disability. Unfortunately, to this date we do not have an effective therapeutic strategy to promote neurological recovery in these growing population of stroke survivors...
2017: Receptors & Clinical Investigation
https://www.readbyqxmd.com/read/28803992/p-rex1-amplification-promotes-progression-of-cutaneous-melanoma-via-the-pak1-p38-mmp-2-pathway
#8
Jinhua Wang, Hajime Hirose, Guanhua Du, Kelly Chong, Eiji Kiyohara, Isaac P Witz, Dave S B Hoon
P-REX1 (PIP3-dependent Rac exchange factor-1) is a guanine nucleotide exchange factor that activates Rac by catalyzing exchange of GDP for GTP bound to Rac. Aberrant up-regulation of P-REX1 expression has a role in metastasis however, copy number (CN) and function of P-REX1 in cutaneous melanoma are unclear. To explore the role of P-REX1 in melanoma, SNP 6.0 and Exon 1.0 ST microarrays were assessed. There was a higher CN (2.82-fold change) of P-REX1 in melanoma cells than in melanocytes, and P-REX1 expression was significantly correlated with P-REX1 CN...
August 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28796249/rho-inhibition-by-lovastatin-affects-apoptosis-and-dsb-repair-of-primary-human-lung-cells-in-vitro-and-lung-tissue-in-vivo-following-fractionated-irradiation
#9
Verena Ziegler, Christian Henninger, Ioannis Simiantonakis, Marcel Buchholzer, Mohammad Reza Ahmadian, Wilfried Budach, Gerhard Fritz
Thoracic radiotherapy causes damage of normal lung tissue, which limits the cumulative radiation dose and, hence, confines the anticancer efficacy of radiotherapy and impacts the quality of life of tumor patients. Ras-homologous (Rho) small GTPases regulate multiple stress responses and cell death. Therefore, we investigated whether pharmacological targeting of Rho signaling by the HMG-CoA-reductase inhibitor lovastatin influences ionizing radiation (IR)-induced toxicity in primary human lung fibroblasts, lung epithelial and lung microvascular endothelial cells in vitro and subchronic mouse lung tissue damage following hypo-fractionated irradiation (4x4 Gy)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28791343/breast-cancer-associated-gene-3-interacts-with-rac1-and-augments-nf-%C3%AE%C2%BAb-signaling-in-vitro-but-has-no-effect-on-rankl-induced-bone-resorption-in-vivo
#10
Chen Yao, Kuan-Ping Yu, William Philbrick, Ben-Hua Sun, Christine Simpson, Changqing Zhang, Karl Insogna
Breast cancer-associated gene 3 (BCA3) is a recently identified adaptor protein whose functions are still being defined. BCA3 has been reported to be an important regulator of nuclear factor-κB (NF-κB) signaling. It has also been reported to interact with the small GTPase, Rac1. Consistent with that observation, in the present study, BCA3 was found to interact with nuclear Rac1 in 293 cells and influence NF-κB signaling. Additional experiments revealed that depending on cell type, BCA3 augmented, attenuated or had no effect on NF-κB signaling in vitro...
August 4, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28791339/identification-of-novel-genetic-etiology-and-key-molecular-pathways-for-seminoma-via-network-based-studies
#11
Yuanlei Chen, Chao Qi, Liqun Xia, Gonghui Li
Seminoma is the most common testicular malignant germ cell tumor which severely threaten male reproductive health. However, the pathogenesis and progression mechanisms are still unclear and little research is carried out to uncover the mechanism of this cancer. To identify gene signatures that are expected to converge on particular molecular pathways may drive the development of the core cancer characteristics in seminoma. We downloaded the gene expression profiles GSE18155 from GEO database and obtained the differentially expressed genes (DEGs)...
August 4, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28775097/platelet-derived-growth-factor-receptor-alpha-pdgfr%C3%AE-and-ras-related-c3-botulinum-toxin-substrate-1-rac1-regulate-mechano-responsiveness-of-lung-fibroblasts
#12
Stephen E McGowan, Diann M McCoy
Platelet-derived growth factor (PDGF)-A, which only signals through PDGF-receptor-alpha (PDGFRα) is required for secondary alveolar septal formation. Although PDGFRα distinguishes mesenchymal progenitor cells during the saccular stage, PDGFRα-expressing alveolar cells persist through adulthood. PDGF-A sustains proliferation, limits apoptosis, and maintains alpha-smooth muscle actin (αSMA) containing alveolar cells, which congregate at the alveolar entry ring at postnatal day (P)12. PDGFRα-expressing, αSMA-containing, alveolar cells re-distribute in the elongating septum, suggesting that they migrate to the alveolar entry rings where mechanical tension is higher...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28775002/kindlin-2-association-with-rho-gdp-dissociation-inhibitor-%C3%AE-suppresses-rac1-activation-and-podocyte-injury
#13
Ying Sun, Chen Guo, Ping Ma, Yumei Lai, Fan Yang, Jun Cai, Zhehao Cheng, Kuo Zhang, Zhongzhen Liu, Yeteng Tian, Yue Sheng, Ruijun Tian, Yi Deng, Guozhi Xiao, Chuanyue Wu
Alteration of podocyte behavior is critically involved in the development and progression of many forms of human glomerular diseases. The molecular mechanisms that control podocyte behavior, however, are not well understood. Here, we investigated the role of Kindlin-2, a component of cell-matrix adhesions, in podocyte behavior in vivo Ablation of Kindlin-2 in podocytes resulted in alteration of actin cytoskeletal organization, reduction of the levels of slit diaphragm proteins, effacement of podocyte foot processes, and ultimately massive proteinuria and death due to kidney failure...
August 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28772119/the-biology-of-forgetting-a-perspective
#14
REVIEW
Ronald L Davis, Yi Zhong
Pioneering research studies, beginning with those using Drosophila, have identified several molecular and cellular mechanisms for active forgetting. The currently known mechanisms for active forgetting include neurogenesis-based forgetting, interference-based forgetting, and intrinsic forgetting, the latter term describing the brain's chronic signaling systems that function to slowly degrade molecular and cellular memory traces. The best-characterized pathway for intrinsic forgetting includes "forgetting cells" that release dopamine onto engram cells, mobilizing a signaling pathway that terminates in the activation of Rac1/Cofilin to effect changes in the actin cytoskeleton and neuron/synapse structure...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28767310/disrupted-irf6-nme1-2-complexes-as-a-cause-of-cleft-lip-palate
#15
M T Parada-Sanchez, E Y Chu, L L Cox, S S Undurty, J M Standley, J C Murray, T C Cox
Mutations and common polymorphisms in interferon regulatory factor 6 ( IRF6) are associated with both syndromic and nonsyndromic forms of cleft lip/palate (CLP). To date, much of the focus on this transcription factor has been on identifying its direct targets and the gene regulatory network in which it operates. Notably, however, IRF6 is found predominantly in the cytoplasm, with its import into the nucleus tightly regulated like other members of the IRF family. To provide further insight into the role of IRF6 in the pathogenesis of CLP, we sought to identify direct IRF6 protein interactors using a combination of yeast 2-hybrid screens and co-immunoprecipitation assays...
August 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28765773/astaxanthin-induces-migration-in-human-skin-keratinocytes-via-rac1-activation-and-rhoa-inhibition
#16
Dakanda Ritto, Supita Tanasawet, Sawana Singkhorn, Wanwimol Klaypradit, Pilaiwanwadee Hutamekalin, Varomyalin Tipmanee, Wanida Sukketsiri
BACKGROUND/OBJECTIVES: Re-epithelialization has an important role in skin wound healing. Astaxanthin (ASX), a carotenoid found in crustaceans including shrimp, crab, and salmon, has been widely used for skin protection. Therefore, we investigated the effects of ASX on proliferation and migration of human skin keratinocyte cells and explored the mechanism associated with that migration. MATERIAL/METHOD: HaCaT keratinocyte cells were exposed to 0.25-1 µg/mL of ASX...
August 2017: Nutrition Research and Practice
https://www.readbyqxmd.com/read/28765370/three-dimensional-biomimetic-vascular-model-reveals-a-rhoa-rac1-and-n-cadherin-balance-in-mural-cell-endothelial-cell-regulated-barrier-function
#17
Stella Alimperti, Teodelinda Mirabella, Varnica Bajaj, William Polacheck, Dana M Pirone, Jeremy Duffield, Jeroen Eyckmans, Richard K Assoian, Christopher S Chen
The integrity of the endothelial barrier between circulating blood and tissue is important for blood vessel function and, ultimately, for organ homeostasis. Here, we developed a vessel-on-a-chip with perfused endothelialized channels lined with human bone marrow stromal cells, which adopt a mural cell-like phenotype that recapitulates barrier function of the vasculature. In this model, barrier function is compromised upon exposure to inflammatory factors such as LPS, thrombin, and TNFα, as has been observed in vivo...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28763746/rhein-ameliorates-adenomyosis-by-inhibiting-nf-%C3%AE%C2%BAb-and-%C3%AE-catenin-signaling-pathway
#18
Tingting Feng, Shaobin Wei, Yan Wang, Xianyun Fu, Ling Shi, Liyuan Qu, Xiaoxue Fan
In the present study, we examined the effects of rhein on pituitary gland implantation-induced adenomyosis, an animal model which mimics human adenomyosis. Oral administration of rhein dose-dependently attenuated hyperplastic and hypertrophic myometrium and improved adenomyosis. The activation of NF-κB and β-catenin signaling pathway was observed in the ectopic endometria. While, rhein dose dependently inhibited the expressions of p-p65, p-AKT and actived Rac1. As Rac1 activation controlled nuclear localization of β-catenin during canonical Wnt signaling, we found that the degradation complex of β-catenin was improved by rhein...
July 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28761330/epigenetic-memory-of-oxidative-stress-does-nephrilin-exert-its-protective-effects-via-rac1
#19
Desmond D Mascarenhas, David N Herndon, Istvan Arany
AIM: Nephrilin peptide, a designed inhibitor of Rictor complex (mTORC2), exerts pleiotropic protective effects in metabolic, xenobiotic and traumatic stress models. Stress can generate enduring epigenetic changes in gene function. In this work we examine the possibility that nephrilin treatment protects against acute and enduring global changes in oxidative metabolism, with a focus on the Rictor-complex-mediated activation of Rac1, a subunit of NADPH oxidase (Nox) via PKCs, Prex1 and p66shc...
2017: Biologics: Targets & Therapy
https://www.readbyqxmd.com/read/28761175/rock1-is-a-novel-rac1-effector-to-regulate-tubular-endocytic-membrane-formation-during-clathrin-independent-endocytosis
#20
David Soriano-Castell, Albert Chavero, Carles Rentero, Marta Bosch, Maite Vidal-Quadras, Albert Pol, Carlos Enrich, Francesc Tebar
Clathrin-dependent and -independent pathways contribute for β1-integrin endocytosis. This study defines a tubular membrane clathrin-independent endocytic network, induced with the calmodulin inhibitor W13, for β1-integrin internalization. This pathway is dependent on increased phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) levels and dynamin activity at the plasma membrane. Exogenous addition of PI(4,5)P2 or phosphatidylinositol-4-phosphate 5-kinase (PIP5K) expression mimicked W13-generated-tubules which are inhibited by active Rac1...
July 31, 2017: Scientific Reports
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