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https://www.readbyqxmd.com/read/28533362/cgas-is-essential-for-cellular-senescence
#1
Hui Yang, Hanze Wang, Junyao Ren, Qi Chen, Zhijian J Chen
Cellular senescence is a natural barrier to tumorigenesis and it contributes to the antitumor effects of several therapies, including radiation and chemotherapeutic drugs. Senescence also plays an important role in aging, fibrosis, and tissue repair. The DNA damage response is a key event leading to senescence, which is characterized by the senescence-associated secretory phenotype (SASP) that includes expression of inflammatory cytokines. Here we show that cGMP-AMP (cGAMP) synthase (cGAS), a cytosolic DNA sensor that activates innate immunity, is essential for senescence...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28531251/ca2-dependent-phosphoregulation-of-the-plasma-membrane-ca2-atpase-aca8-modulates-stimulus-induced-calcium-signatures
#2
Alex Costa, Laura Luoni, Claudia Adriana Marrano, Kenji Hashimoto, Philipp Köster, Sonia Giacometti, Maria Ida De Michelis, Jörg Kudla, Maria Cristina Bonza
Ca2+ signals are transient, hence, upon a stimulus-induced increase in cytosolic Ca2+ concentration, cells have to re-establish resting Ca2+ levels. Ca2+ extrusion is operated by a wealth of transporters, such as Ca2+ pumps and Ca2+/H+ antiporters, which often require a rise in Ca2+ concentration to be activated. Here, we report a regulatory fine-tuning mechanism of the Arabidopsis thaliana plasma membrane-localized Ca2+-ATPase isoform ACA8 that is mediated by calcineurin B-like protein (CBL) and CBL-interacting protein kinase (CIPK) complexes...
May 20, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28529930/the-central-role-of-ifi204-in-ifn-%C3%AE-release-and-autophagy-activation-during-mycobacterium-bovis-infection
#3
Liu Chunfa, Sun Xin, Li Qiang, Srinand Sreevatsan, Lifeng Yang, Deming Zhao, Xiangmei Zhou
Mycobacterium bovis (M. bovis) is the pathogen of animals and humans that can replicate in the phagosomes of myeloid cells. Cytosolic detection of bacterial products plays a crucial role in initiating the innate immune response, including autophagy activation and interferon-β (IFN-β) release. Although IFN-β release and autophagy activation have been reported during mycobacterium infection, the mechanisms underlying remains poorly defined. Here, we demonstrated that IFN-β release increases in macrophages exposed to M...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28529468/contrasting-patterns-of-nucleotide-polymorphism-suggest-different-selective-regimes-within-different-parts-of-the-pgic1-gene-in-festuca-ovina-l
#4
Yuan Li, Bengt Hansson, Lena Ghatnekar, Honor C Prentice
BACKGROUND: Phosphoglucose isomerase (PGI, EC 5.3.1.9) is an essential metabolic enzyme in all eukaryotes. An earlier study of the PgiC1 gene, which encodes cytosolic PGI in the grass Festuca ovina L., revealed a marked difference in the levels of nucleotide polymorphism between the 5' and 3' portions of the gene. METHODS: In the present study, we characterized the sequence polymorphism in F. ovina PgiC1 in more detail and examined possible explanations for the non-uniform pattern of nucleotide polymorphism across the gene...
2017: Hereditas
https://www.readbyqxmd.com/read/28527408/subcellular-localization-based-comparative-study-on-radioresistant-bacteria-a-novel-approach-to-mine-proteins-involve-in-radioresistance
#5
Divya Vishambra, Malay Srivastava, Kamal Dev, Varun Jaiswal
Radioresistant bacteria (RRB) are among the most radioresistant organisms and has a unique role in evolution. Along with the evolutionary role, radioresistant organisms play important role in paper industries, bioremediation, vaccine development and possibility in anti-aging and anti-cancer treatment. The study of radiation resistance in RRB was mainly focused on cytosolic mechanisms such as DNA repair mechanism, cell cleansing activity and high antioxidant activity. Although it was known that protein localized on outer areas of cell play role in resistance towards extreme condition but the mechanisms/proteins localized on the outer area of cells are not studied for radioresistance...
May 10, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28524163/dsdna-containing-exosomes-the-culprit-in-chemotherapy-induced-diarrhea
#6
Paul Kurywchak, Raghu Kalluri
Chemotherapy is a predominant strategy to treat cancer and is often associated with toxicities like severe diarrhea that puts patients at additional risk and can hinder treatment strategies. Lian et al. recently explored the immune-mediated mechanisms of Irinotecan-induced diarrhea in colorectal cancer and found that double-stranded DNA in small vesicles can launch inflammation pathways in immune cells through the cytosolic DNA sensor AIM2.
May 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28523573/activation-of-nlrp3-inflammasome-in-inflammatory-bowel-disease-differences-between-crohn-s-disease-and-ulcerative-colitis
#7
Lazaros-Dimitrios Lazaridis, Aikaterini Pistiki, Evangelos J Giamarellos-Bourboulis, Marianna Georgitsi, Georgia Damoraki, Dimitrios Polymeros, George D Dimitriadis, Konstantinos Triantafyllou
BACKGROUND: NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1β to IL-1β. AIMS: To investigate NLRP3 inflammasome activation in inflammatory bowel disease. METHODS: Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1β, IL-6, and TNFα were measured in cell supernatants and concentration of pro-IL-1β was measured in cell lysates...
May 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28523552/epigenetics-of-huntington-s-disease
#8
Silvia Bassi, Takshashila Tripathi, Alan Monziani, Francesca Di Leva, Marta Biagioli
Huntington's disease (HD) is a genetic, fatal autosomal dominant neurodegenerative disorder typically occurring in midlife with symptoms ranging from chorea, to dementia, to personality disturbances (Philos Trans R Soc Lond Ser B Biol Sci 354:957-961, 1999). HD is inherited in a dominant fashion, and the underlying mutation in all cases is a CAG trinucleotide repeat expansion within exon 1 of the HD gene (Cell 72:971-983, 1993). The expanded CAG repeat, translated into a lengthened glutamine tract at the amino terminus of the huntingtin protein, affects its structural properties and functional activities...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28504693/cyclin-dependent-kinase-7-is-a-therapeutic-target-in-high-grade-glioma
#9
S A Greenall, Y C Lim, C B Mitchell, K S Ensbey, B W Stringer, A L Wilding, G M O'Neill, K L McDonald, D J Gough, B W Day, T G Johns
High-grade glioma (HGG) is an incurable brain cancer. The transcriptomes of cells within HGG tumors are highly heterogeneous. This renders the tumors unresponsive or able to adapt to therapeutics targeted at single pathways, thereby causing treatment failure. To overcome this, we focused on cyclin-dependent kinase 7 (CDK7), a ubiquitously expressed molecule involved in two major drivers of HGG pathogenesis: cell cycle progression and RNA polymerase-II-based transcription. We tested the activity of THZ1, an irreversible CDK7 inhibitor, on patient-derived primary HGG cell lines and ex vivo HGG patient tissue slices, using proliferation assays, microarray analysis, high-resolution respirometry, cell cycle analysis and in vivo tumor orthografts...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28498480/miconazole-induces-apoptosis-via-the-death-receptor-5-dependent-and-mitochondrial-mediated-pathways-in-human-bladder-cancer-cells
#10
Sheau-Yun Yuan, Ming-Yuh Shiau, Yen-Chuan Ou, Yu-Chia Huang, Cheng-Che Chen, Chen-Li Cheng, Kun-Yuan Chiu, Shian-Shiang Wang, Kan-Jen Tsai
Miconazole (MIC), an antifungal agent, diplays anti‑tumorigenic activity in various types of human cancers, including bladder cancer, yet its mechanism of antitumor action is not well understood. In the present study, we demonstrated that, in a cell viability assay, MIC had a cytotoxic effect on human T24, J82 and TSGH-8301 bladder cancer cells in a dose- and time‑dependent manner, but did not exhibit significant toxicity toward human peripheral blood mononuclear cells. Cell cycle analysis revealed that MIC at concentrations of 25 and 50 µM significantly caused G0/G1 arrest in the TSGH-8301 and T24 cells, respectively...
April 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28498367/initiation-and-execution-mechanisms-of-necroptosis-an-overview
#11
REVIEW
Sasker Grootjans, Tom Vanden Berghe, Peter Vandenabeele
Necroptosis is a form of regulated cell death, which is induced by ligand binding to TNF family death domain receptors, pattern recognizing receptors and virus sensors. The common feature of these receptor systems is the implication of proteins, which contain a receptor interaction protein kinase (RIPK) homology interaction motif (RHIM) mediating recruitment and activation of receptor-interacting protein kinase 3 (RIPK3), which ultimately activates the necroptosis executioner mixed lineage kinase domain-like (MLKL)...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28482921/the-autocrine-role-of-proteoglycan-4-prg4-in-modulating-osteoarthritic-synoviocyte-proliferation-and-expression-of-matrix-degrading-enzymes
#12
Ali Alquraini, Maha Jamal, Ling Zhang, Tannin Schmidt, Gregory D Jay, Khaled A Elsaid
BACKGROUND: Lubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor. rhPRG4-CD44 interaction inhibits cytokine-induced rheumatoid arthritis synoviocyte proliferation. The objective of this study is to decipher the autocrine function of PRG4 in regulating osteoarthritic synoviocyte proliferation and expression of catabolic and pro-inflammatory mediators under basal and interleukin-1 beta (IL-1β)-stimulated conditions...
May 8, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28479956/a-single-zidovudine-azt-administration-delays-hepatic-cell-proliferation-by-altering-oxidative-state-in-the-regenerating-rat-liver
#13
Armando Butanda-Ochoa, Diego Rolando Hernández-Espinosa, Marisela Olguín-Martínez, Lourdes Sánchez-Sevilla, Mario R Rodríguez, Benito Chávez-Rentería, Alberto Aranda-Fraustro, Rolando Hernández-Muñoz
The 3'-azido-3'-deoxythymidine or Zidovudine (AZT) was the first antiretroviral drug used in the treatment of HIV patients, which has good effectiveness but also hepatotoxic side effects that include cell cycle arrest and oxidative/nitrative mitochondrial damage. Whether such an oxidative damage may affect the proliferative-regenerative capacity of liver remains to be clearly specified at doses commonly used in the clinical practice. In this study, we described the oxidative-proliferative effect of AZT administered at a common clinical dose in rat liver submitted to 70% partial hepatectomy (PH)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28476502/quercetin-suppresses-nlrp3-inflammasome-activation-in-epithelial-cells-triggered-by-escherichia-coli-o157-h7
#14
Yansong Xue, Min Du, Mei-Jun Zhu
Inflammatory responses elicited by LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is induced by a wide variety of stress signals including infectious agents and cellular disorders. E. coli O157:H7 causes serious gastrointestinal diseases that results in severe inflammation and oxidative stress, causing host cell damage. In this study, we found that E. coli O157:H7 infection induced NLRP3 assembly, caspase-1 activation and interleukin (IL)-1β and IL-18 release in Caco-2 cells. Infection also resulted in mitochondrial dysfunction with disrupted mitochondrial potential and mitochondrial complex-I activity, as well as the cytosolic release of cytochrome c and altered mitochondrial respiratory chain...
May 2, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28475463/immune-diseases-associated-with-trex1-and-sting-dysfunction
#15
Nan Yan
The innate immune system is the first line of defense against invading pathogens. One important feature of innate immune recognition is self versus nonself discrimination. The selectivity for microbial ligands is achieved through substrate motif specificity, spatial compartmentalization, and functions of negative regulators. Loss-of-function mutations in negative regulators or gain-of-function mutations in drivers of innate immune signaling have been associated with autoimmune diseases such as lupus, rheumatoid arthritis, inflammatory vasculopathy, and a variety of interferonopathies...
May 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28474358/e2f1interactive-with-brca1-pathway-induces-hcc-two-different-small-molecule-metabolism-or-cell-cycle-regulation-via-mitochondrion-or-cd4-t-to-cytosol
#16
Qingchun Chen, Lin Wang, Minghu Jiang, Juxiang Huang, Zhenfu Jiang, Haitao Feng, Zhili Ji
Breast cancer 1 (BRCA1) and E2F transcription factor 1 (E2F1) are related to metabolism and cell cycle regulation. However, the corresponding mechanism is not clear in HCC. High BRCA1 direct pathway was constructed with 11 molecules from E2F1 feedback-interactive network in HCC by GRNInfer based on 39 Pearson mutual positive corelation CC >0.25 molecules with E2F1. Integration of GRNInfer with GO, KEGG, BioCarta, GNF_U133A, UNIGENE_EST, Disease, GenMAPP databases by DAVID and MAS 3.0, E2F1 feedback-interactive BRCA1 indirect mitochondrion to cytosol pathway was identified as upstream LAPTM4B activation, feedback UNG, downstream BCAT1-HIST1H2AD-TK1 reflecting protein and DNA binding with enrichment of small molecule metabolism; The corresponding BRCA1 indirect membrane to cytosol pathway as upstream CCNB2-NUSAP1 activation, feedback TTK-HIST1H2BJ-CENPF, downstream MCM4-TK1 reflecting ATP and microtubule binding with enrichment of CD4+T-related cell cycle regulation in HCC...
May 5, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28469765/melatonin-treatment-enhances-therapeutic-effects-of-exosomes-against-acute-liver-ischemia-reperfusion-injury
#17
Cheuk-Kwan Sun, Chih-Hung Chen, Chia-Lo Chang, Hsin-Ju Chiang, Pei-Hsun Sung, Kuan-Hung Chen, Yi-Ling Chen, Sheng-Yi Chen, Gour-Shenq Kao, Hsueh-Wen Chang, Mel S Lee, Hon-Kan Yip
This study tests the hypothesis that combined melatonin and exogenic adipose mesenchymal stem cell (ADMSC)-derived exosome treatment offers superior protection against liver ischemia-reperfusion (LIR) injury compared to either alone. In vitro studies utilized a macrophage cell line (RAW) pretreated with lipopolysaccharide and hepatocytes pretreated with melatonin or exosomes before hypoxia treatment, while in vitro experiments involved analyses of liver specimens from male adult Sprague-Dawley rats (n = 50) equally categorized into sham controls (SC), LIR only, LIR-exosome (100 µg, 30 minute post-LIR), LIR-melatonin (20 mg/kg, 30 minute post-LIR and 50 mg/kg at 6 and 18 hours post-LIR), and LIR-exosome-melatonin groups...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28469477/crosstalk-between-apoptosis-and-autophagy-environmental-genotoxins-infection-and-innate-immunity
#18
REVIEW
Michael G Kemp
Autoimmune disorders constitute a major and growing health concern. However, the genetic and environmental factors that contribute to or exacerbate disease symptoms remain unclear. Type I interferons (IFNs) are known to break immune tolerance and be elevated in the serum of patients with autoimmune diseases such as lupus. Extensive work over the past decade has characterized the role of a protein termed stimulator of interferon genes, or STING, in mediating IFN expression and activation in response to cytosolic DNA and cyclic dinucleotides...
2017: Journal of Cell Death
https://www.readbyqxmd.com/read/28462492/interaction-of-silver-and-gold-nanoparticles-in-mammalian-cancer-as-real-topical-bullet-for-wound-healing-a-comparative-study
#19
Allur Subramaniyan Sivakumar, Chandran Krishnaraj, Sunirmal Sheet, Dileep Reddy Rampa, Da Rae Kang, Shah Ahmed Belal, Abhay Kumar, In Ho Hwang, Soon-Il Yun, Yang Soo Lee, Kwan Seob Shim
The present study evaluates in vitro cytotoxic effects and the mode of interaction of biologically synthesized Ag and Au nanoparticles (NPs) using Brassica oleracea L. var. capitata f. rubra (BOL) against HT-1080 cancer cells and bacterial cells as well as their wound healing efficacy using a mouse model. UV-visible spectroscopy, scanning electron microscopy, high-resolution transmission electron microscopy, and energy-dispersive X-ray analysis have ascertained the formation of nano-sized Ag and Au particles...
May 1, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28461497/folate-rescues-vitamin-b12-depletion-induced-inhibition-of-nuclear-thymidylate-biosynthesis-and-genome-instability
#20
Ashley M Palmer, Elena Kamynina, Martha S Field, Patrick J Stover
Clinical vitamin B12 deficiency can result in megaloblastic anemia, which results from the inhibition of DNA synthesis by trapping folate cofactors in the form of 5-methyltetrahydrofolate (5-methylTHF) and subsequent inhibition of de novo thymidylate (dTMP) biosynthesis. In the cytosol, vitamin B12 functions in the remethylation of homocysteine to methionine, which regenerates THF from 5-methylTHF. In the nucleus, THF is required for de novo dTMP biosynthesis, but it is not understood how 5-methylTHF accumulation in the cytosol impairs nuclear dTMP biosynthesis...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
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