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https://www.readbyqxmd.com/read/28936203/modulation-of-gut-microbiome-composition-and-function-in-experimental-colitis-treated-with-sulfasalazine
#1
Haihui Zheng, Mingyi Chen, Yuan Li, Yuanyuan Wang, Lin Wei, Ziqiong Liao, Mengxia Wang, Fangli Ma, Qiongfeng Liao, Zhiyong Xie
Inflammatory bowel disease (IBD) results from alterations in intestinal flora and the immune system. Sulfasalazine (SASP) is a sulfa antimicrobial used to treat IBD in clinic for years. However, how SASP affects gut microbes and its potential functions remains unclear. To investigate the relationships of SASP, IBD, and gut microbiome, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in rats, and analyzed the microbiota in the fecal samples, which come from the control group (treated with ethanol + saline), the model group (treated with TNBS-ethanol + saline) and the SASP group (treated with TNBS-ethanol + SASP), with 16S gene sequencing and followed up a subset sample using shotgun sequencing...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28921472/telomere-damage-response-and-low-grade-inflammation
#2
Lihui Wang, Xianhua Yu, Jun-Ping Liu
Telomeres at the ends of chromosomes safeguard genome integrity and stability in human nucleated cells. However, telomere repeats shed off during cell proliferation and other stress responses. Our recent studies show that telomere attrition induces not only epithelial stem cell senescence but also low-grade inflammation in the lungs. The senescence-associated low-grade inflammation (SALI) is characteristic of alveolar stem cell replicative senescence, increased proinflammatory and anti-inflammatory cytokines, infiltrated immune cells, and spillover effects...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28916310/dietary-restriction-delays-the-secretion-of-senescence-associated-secretory-phenotype-by-reducing-dna-damage-response-in-the-process-of-renal-aging
#3
Wenjuan Wang, Guangyan Cai, Xiangmei Chen
Dietary restriction (DR) has multiple and essential effects in protecting against DNA damage in model organisms. Persistent DNA damage plays a central role in the process of aging. Senescence-associated secretory phenotype (SASP), as a product of cellular aging, can accelerate the process of cellular senescence as a feedback. In this study, we directly observed whether a DR of 30% for 6months in aged rats could retard SASP by delaying the progression of DNA damage and also found the specific mechanism. The results revealed that a 30% DR could significantly improve renal pathology and some metabolic characteristics...
September 12, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28903474/nitric-oxide-heat-shock-protein-axis-in-menopausal-hot-flushes-neglected-metabolic-issues-of-chronic-inflammatory-diseases-associated-with-deranged-heat-shock-response
#4
Antônio Azambuja Miragem, Paulo Ivo Homem de Bittencourt
BACKGROUND: Although some unequivocal underlying mechanisms of menopausal hot flushes have been demonstrated in animal models, the paucity of similar approaches in humans impedes further mechanistic outcomes. Human studies might show some as yet unexpected physiological mechanisms of metabolic adaptation that permeate the phase of decreased oestrogen levels in both symptomatic and asymptomatic women. This is particularly relevant because both the severity and time span of hot flushes are associated with increased risk of chronic inflammatory disease...
September 1, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/28894697/the-potential-role-of-senescence-as-a-modulator-of-platelets-and-tumorigenesis
#5
Claudio A Valenzuela, Ricardo Quintanilla, Rodrigo Moore-Carrasco, Nelson E Brown
In addition to thrombus formation, alterations in platelet function are frequently observed in cancer patients. Importantly, both thrombus and tumor formation are influenced by age, although the mechanisms through which physiological aging modulates these processes remain poorly understood. In this context, the potential effects of senescent cells on platelet function represent pathophysiological mechanisms that deserve further exploration. Cellular senescence has traditionally been viewed as a barrier to tumorigenesis...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28892096/development-and-characterization-of-cholangioids-from-normal-and-diseased-human-cholangiocytes-as-an-in-vitro-model-to-study-primary-sclerosing-cholangitis
#6
Lorena Loarca, Thiago M De Assuncao, Nidhi Jalan-Sakrikar, Steve Bronk, Anuradha Krishnan, Bing Huang, Leslie Morton, Christy Trussoni, Lorena Marcano Bonilla, Eugene Krueger, Steve O'Hara, Patrick Splinter, Guang Shi, María José Lorenzo Pisarello, Gregory J Gores, Robert C Huebert, Nicholas F LaRusso
Primary sclerosing cholangitis (PSC) is an incurable, fibroinflammatory biliary disease for which there is no effective pharmacotherapy. We recently reported cholangiocyte senescence as an important phenotype in PSC while others showed that portal macrophages accumulate in PSC. Unfortunately, our ability to explore cholangiocyte senescence and macrophage accumulation has been hampered by limited in vitro models. Thus, our aim was to develop and characterize a three-dimensional (3D) model of normal and diseased bile ducts (cholangioids) starting with normal human cholangiocytes (NHC), senescent NHC (NHC-sen), and cholangiocytes from PSC patients...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28891967/ginsenoside-rg3-prevents-oxidative-stress-induced-astrocytic-senescence-and-ameliorates-senescence-paracrine-effects-on-glioblastoma
#7
Jingang Hou, Sunchang Kim, Changkeun Sung, Chulhee Choi
Senescent astrocytes in aging brain express senescence-associated secretory phenotype (SASP) and link with increased brain aging and its related diseases. In order to determine whether ginsenosides ameliorate the astrocytic senescence in vitro, human astrocytic CRT cells and primary rat astrocytes were used in the present study. Ginsenosides Rg1, Re, Rb1 and Rg3 (5 μg/mL) could effectively prevent the astrocytic senescence induced by H₂O₂ exposure. However, these ginsenosides did not reverse the astrocytic senescence...
September 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28860144/ipf-lung-fibroblasts-have-a-senescent-phenotype
#8
Diana Alvarez, Nayra Cardenes, Jacobo Sellares, Marta Bueno, Catherine Corey, Vidya Sagar Hanumanthu, Yating Peng, Hannah D'Cuhna, John Sembrat, Mehdi Nouraie, Swaroop Shanker, Chandler Caufield, Sruti Shiva, Mary Armanios, Ana L Mora, Mauricio Rojas
The mechanisms of aging that are involved in the development of idiopathic pulmonary fibrosis (IPF) are still unclear. Although it has been hypothesized that the proliferation and activation of human lung fibroblasts (hLF) are essential in IPF, no studies have assessed how this process works in an aging lung. Our goal was to elucidate if there were age-related changes on primary hLF isolated from IPF lungs compared to age-matched controls. We investigated several hallmarks of aging in hLF from IPF patients and age-matched controls...
August 31, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28855731/dna-sensing-in-senescence
#9
Marina Ruiz de Galarreta, Amaia Lujambio
Cellular senescence, a cell-autonomous growth arrest program, also executes pleiotropic non-cell-autonomous activities through the senescence-associated secretory phenotype (SASP). The innate cGAS-STING DNA-sensing pathway is now shown to regulate senescence by recognizing cytosolic DNA and inducing SASP factors, uncovering an unexpected link between these two previously unrelated pathways.
August 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28844647/unmasking-transcriptional-heterogeneity-in-senescent-cells
#10
Alejandra Hernandez-Segura, Tristan V de Jong, Simon Melov, Victor Guryev, Judith Campisi, Marco Demaria
Cellular senescence is a state of irreversibly arrested proliferation, often induced by genotoxic stress [1]. Senescent cells participate in a variety of physiological and pathological conditions, including tumor suppression [2], embryonic development [3, 4], tissue repair [5-8], and organismal aging [9]. The senescence program is variably characterized by several non-exclusive markers, including constitutive DNA damage response (DDR) signaling, senescence-associated β-galactosidase (SA-βgal) activity, increased expression of the cyclin-dependent kinase (CDK) inhibitors p16INK4A (CDKN2A) and p21CIP1 (CDKN1A), increased secretion of many bio-active factors (the senescence-associated secretory phenotype, or SASP), and reduced expression of the nuclear lamina protein LaminB1 (LMNB1) [1]...
September 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28838334/effects-of-curcumin-plus-soy-oligosaccharides-on-intestinal-flora-of-rats-with-ulcerative-colitis
#11
G Huang, L Ye, G Du, Y Huang, Y Wu, S Ge, Z Yang, G Zhu
To explore the therapeutic effect of curcumin (Cur) and soybean oligosaccharides (SBOS) on ulcerative colitis (UC) through testing the intestinal flora and ulcerative colitis (UC). 80 male SD rats were selected divided into four groups with 20 rats in each group: normal group, sulfasalazine (SASP) group, model group and group of curcumin plus soy oligosaccharide. All animals were treated for 4 weeks. In the fifth week rats were decapitated. Macroscopic damage scores of colonic mucosa were calculated. A 4mL blood sample was taken to detect the contents of serum tumor necrosis factor -α (TNF-α) and interleukin 8 (IL-8) by the double antibody sandwich ABC-ELISA method (enzyme-linked immunosorbent assay)...
August 15, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28837845/the-senescent-bystander-effect-is-caused-by-ros-activated-nf-%C3%AE%C2%BAb-signalling
#12
Glyn Nelson, Olena Kucheryavenko, James Wordsworth, Thomas von Zglinicki
Cell senescence is an important driver of the ageing process. The accumulation of senescent cells in tissues is accelerated by stress signals from senescent cells that induce DNA damage and ultimately senescence in bystander cells. We examine here the interplay of senescence-associated mitochondrial dysfunction (SAMD)-driven production of reactive oxygen species (ROS) and senescence-associated secretory phenotype (SASP) in causing the bystander effect. We show that in various modes of fibroblast senescence ROS are necessary and sufficient to activate the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which facilitates a large part of the SASP...
August 21, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28822679/spatial-and-temporal-control-of-senescence
#13
REVIEW
Yoko Ito, Matthew Hoare, Masashi Narita
Cellular senescence is an autonomous tumor suppressor mechanism leading to stable cell cycle arrest. Senescent cells are highly secretory, driving a range of different functions through the senescence-associated secretory phenotype (SASP). Recent findings have suggested that the composition of the SASP is dynamically and spatially regulated and that the changing composition of the SASP can determine the beneficial and detrimental aspects of the senescence program, tipping the balance to either an immunosuppressive/profibrotic environment or proinflammatory/fibrolytic state...
August 16, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28811647/biogenesis-of-pro-senescent-microparticles-by-endothelial-colony-forming-cells-from-premature-neonates-is-driven-by-sirt1-dependent-epigenetic-regulation-of-mkk6
#14
Stéphanie Simoncini, Anne-Line Chateau, Stéphane Robert, Dilyana Todorova, Catherine Yzydorzick, Romaric Lacroix, Isabelle Ligi, Laurence Louis, Richard Bachelier, Umberto Simeoni, Frédérique Magdinier, Françoise Dignat-George, Florence Sabatier
Senescent cells may exert detrimental effect on microenvironment through the secretion of soluble factors and the release of extracellular vesicles, such as microparticles, key actors in ageing and cardiovascular diseases. We previously reported that sirtuin-1 (SIRT1) deficiency drives accelerated senescence and dysfunction of endothelial colony-forming cells (ECFC) in PT neonates. Because preterm birth (PT) increases the risk for cardiovascular diseases during neonatal period as well as at adulthood, we hypothesized that SIRT1 deficiency could control the biogenesis of microparticles as part of a senescence-associated secretory phenotype (SASP) of PT-ECFC and investigated the related molecular mechanisms...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801702/paeonol-attenuates-aging-mrc-5-cells-and-inhibits-epithelial-mesenchymal-transition-of-premalignant-hacat-cells-induced-by-aging-mrc-5-cell-conditioned-medium
#15
Lihua Yang, Shangping Xing, Kun Wang, Hua Yi, Biaoyan Du
Senescence-associated secretory phenotype (SASP) factors, such as IL-6 and IL-8, are extremely critical in tissue microenvironment. Senescent human fibroblasts facilitate epithelial-mesenchymal transition (EMT) in premalignant epithelial cells mainly through the secretion of SASP factors. Meanwhile, premalignant human HaCaT Keratinocyte (HaCaT) cells as immortal epithelial cells are susceptible to malignant transformation. Paeonol, an herbal phenolic component found in peonies, exerts anti-aging and anti-tumor efficacies, while the molecular mechanisms of paeonol on EMT in premalignant HaCaT cells induced by SASP factors are unclear...
August 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28790310/p16-ink4a-deletion-ameliorated-renal-tubulointerstitial-injury-in-a-stress-induced-premature-senescence-model-of-bmi-1-deficiency
#16
Jianliang Jin, Jianguo Tao, Xin Gu, Zhenzhen Yu, Rong Wang, Guoping Zuo, Qing Li, Xianhui Lv, Dengshun Miao
To determine whether p16 (INK4a) deletion ameliorated renal tubulointerstitial injury by inhibiting a senescence-associated secretory phenotype (SASP) in Bmi-1-deficient (Bmi-1 (-/-)) mice, renal phenotypes were compared among 5-week-old Bmi-1 and p16 (INK4a) double-knockout, and Bmi-1 (-/-) and wild-type mice. Fifth-passage renal interstitial fibroblasts (RIFs) from the three groups were analyzed for senescence and proliferation. The effect of Bmi-1 deficiency on epithelial-to-mesenchymal transition (EMT) was examined in Bmi-1-knockdown human renal proximal tubular epithelial (HK2) cells, which were treated with concentrated conditioned medium (CM) from the fifth-passage renal interstitial fibroblasts (RIFs) of above three group mice or with exogenous TGF-β1...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775044/senolytic-drugs-target%C3%A2-alveolar-epithelial-cell-function-and-attenuate-experimental-lung-fibrosis-ex-vivo
#17
Mareike Lehmann, Martina Korfei, Kathrin Mutze, Stephan Klee, Wioletta Skronska-Wasek, Hani N Alsafadi, Chiharu Ota, Rita Costa, Herbert B Schiller, Michael Lindner, Darcy E Wagner, Andreas Günther, Melanie Königshoff
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases with age, and ageing-related mechanisms such as cellular senescence have been proposed as pathogenic drivers. The lung alveolar epithelium represents a major site of tissue injury in IPF and senescence of this cell population is probably detrimental to lung repair. However, the potential pathomechanisms of alveolar epithelial cell senescence and the impact of senolytic drugs on senescent lung cells and fibrosis remain unknown...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28763256/cytokine-profile-of-breast-cell-lines-after-different-radiation-doses
#18
Valentina Bravatà, Luigi Minafra, Giusi Irma Forte, Francesco Paolo Cammarata, Giorgio Russo, Federica Maria Di Maggio, Giuseppa Augello, Domenico Lio, Maria Carla Gilardi
PURPOSE: Ionizing radiation (IR) treatment activates inflammatory processes causing the release of a great amount of molecules able to affect the cell survival. The aim of this study was to analyze the cytokine signature of conditioned medium produced by non tumorigenic mammary epithelial cell line MCF10A, as well as MCF7 and MDA-MB-231 breast cancer cell lines, after single high doses of IR in order to understand their role in high radiation response. MATERIAL AND METHODS: We performed a cytokine profile of irradiated conditioned media of MCF10A, MCF7 and MDA-MB-231 cell lines treated with 9 or 23 Gy, by Luminex and ELISA analyses...
August 1, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28761796/the-salivary-gland-salivation-stimulating-peptide-from-locusta-migratoria-lom-sg-sasp-is-not-a-typical-neuropeptide
#19
Jan A Veenstra
The salivary gland salivation stimulating peptide was identified from the salivary glands of the migratory locust by its ability to stimulate cAMP production in the same tissue. The gene coding for this peptide has recently been identified and been shown to code for a precursor consisting of a signal peptide, several copies of the peptide separated by Lys-Arg doublets and a few other peptides. These data are consistent with it being a neuropeptide. However, antiserum raised to this peptide labels the acini of the salivary glands while RT-PCR only gives positive results in the salivary gland, but not in any ganglion of the central nervous system...
2017: PeerJ
https://www.readbyqxmd.com/read/28759028/innate-immune-sensing-of-cytosolic-chromatin-fragments-through-cgas-promotes-senescence
#20
Selene Glück, Baptiste Guey, Muhammet Fatih Gulen, Katharina Wolter, Tae-Won Kang, Niklas Arndt Schmacke, Anne Bridgeman, Jan Rehwinkel, Lars Zender, Andrea Ablasser
Cellular senescence is triggered by various distinct stresses and characterized by a permanent cell cycle arrest. Senescent cells secrete a variety of inflammatory factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The mechanism(s) underlying the regulation of the SASP remains incompletely understood. Here we define a role for innate DNA sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments in senescent cells...
September 2017: Nature Cell Biology
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