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https://www.readbyqxmd.com/read/28427150/senoptosis-non-lethal-dna-cleavage-as-a-route-to-deep-senescence
#1
Maja Studencka, Jörg Schaber
DNA-damage-induced apoptosis and cellular senescence are perceived as two distinct cell fates. We found that after ionizing radiation (IR)-induced DNA damage the majority (up to 70 %) of senescent human diploid fibroblasts (HDFs) were subjected to controlled cleavage of DNA, resulting in the establishment of a viable and stable sub-G1 population, i.e. deeply senescent cells. We show that in senescent HDFs this DNA cleavage is triggered by modest loss of the mitochondrial membrane potential, which is not sufficient to activate caspases, but strong enough to release mitochondrial endonuclease G (EndoG)...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425040/schiff-base-complexes-of-copper-and-zinc-as-potential-anti-colitic-compounds
#2
Elaine M Conner, John Reglinski, W Ewen Smith, I Jack Zeitlin
The design, synthesis and activity of polymodal compounds for the treatment of inflammatory bowel disease are reported. The compounds, being based on a metal-Schiff base motif, are designed to degrade during intestinal transit to release the bioactive components in the gut. The compounds have been developed sequential with the biomodal compounds combining copper or zinc with a salicylaldehyde adduct. These compounds were tested in a formalin induced colonic inflammation model in BK:A mice. From these studies a trimodal compound based on a zinc Schiff base analogue of sulfasalazine was designed...
April 19, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28416161/cellular-senescence-a-translational-perspective
#3
REVIEW
James L Kirkland, Tamara Tchkonia
Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP). Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience...
April 12, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28412724/the-quality-of-the-educational-environment-in-a-medical-college-in-saudi-arabia
#4
Abdullah H Altemani, Tarig H Merghani
Objectives: The study aimed to examine the quality of the educational environment in the Faculty of Medicine, University of Tabuk, Saudi Arabia, and to compare between male and female students using the Dundee Ready Educational Environment Measure (DREEM). Methods: We utilized a cross-sectional survey design.  Participants were 221 medical students (96 males and 125 females) from all classes (1st to 6th year). Each participant responded to a translated version of the DREEM questionnaire that measures five domains: students' perception of learning (SPL), students' perception of teachers (SPT), students' academic self-perception (SASP), students' perception of atmosphere (SPA), and students' social self-perception (SSSP)...
April 14, 2017: International Journal of Medical Education
https://www.readbyqxmd.com/read/28401730/dna-damage-and-senescence-in-osteoprogenitors-expressing-osx1-may-cause-their-decrease-with-age
#5
Ha-Neui Kim, Jianhui Chang, Lijian Shao, Li Han, Srividhya Iyer, Stavros C Manolagas, Charles A O'Brien, Robert L Jilka, Daohong Zhou, Maria Almeida
Age-related bone loss in mice results from a decrease in bone formation and an increase in cortical bone resorption. The former is accounted by a decrease in the number of postmitotic osteoblasts which synthesize the bone matrix and is thought to be the consequence of age-dependent changes in mesenchymal osteoblast progenitors. However, there are no specific markers for these progenitors, and conclusions rely on results from in vitro cultures of mixed cell populations. Moreover, the culprits of such changes remain unknown...
April 12, 2017: Aging Cell
https://www.readbyqxmd.com/read/28384888/perception-of-learning-environment-among-undergraduate-medical-students-in-two-different-medical-schools-through-dreem-and-jhles-questionnaire
#6
Parama Sengupta, Abhishek Sharma, Nina Das
INTRODUCTION: Assessment of learning environment is essential to assess the acceptability of the curriculum among students. Several tools are available to assess undergraduate medical students' perception of learning environment. Dundee Ready Education Environment Measure (DREEM) questionnaire is the most commonly used tool. Here, we have used both the widely used DREEM questionnaire and a relatively new questionnaire Johns Hopkins Learning Environment Scale (JHLES). AIM: Assessment of students' perception of learning environment of two eastern Indian medical schools using DREEM and JHLES questionnaire...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28378188/apigenin-suppresses-the-senescence-associated-secretory-phenotype-and-paracrine-effects-on-breast-cancer-cells
#7
Kevin M Perrott, Christopher D Wiley, Pierre-Yves Desprez, Judith Campisi
Apigenin (4',5,7,-trihydroxyflavone) is a flavonoid found in certain herbs, fruits, and vegetables. Apigenin can attenuate inflammation, which is associated with many chronic diseases of aging. Senescent cells-stressed cells that accumulate with age in mammals-display a pro-inflammatory senescence-associated secretory phenotype (SASP) that can drive or exacerbate several age-related pathologies, including cancer. Flavonoids, including apigenin, were recently shown to reduce the SASP of a human fibroblast strain induced to senesce by bleomycin...
April 4, 2017: GeroScience
https://www.readbyqxmd.com/read/28371119/rapamycin-inhibits-the-secretory-phenotype-of-senescent-cells-by-a-nrf2-independent-mechanism
#8
Rong Wang, Zhen Yu, Bharath Sunchu, James Shoaf, Ivana Dang, Stephanie Zhao, Kelsey Caples, Lynda Bradley, Laura M Beaver, Emily Ho, Christiane V Löhr, Viviana I Perez
Senescent cells contribute to age-related pathology and loss of function, and their selective removal improves physiological function and extends longevity. Rapamycin, an inhibitor of mTOR, inhibits cell senescence in vitro and increases longevity in several species. Nrf2 levels have been shown to decrease with aging and silencing Nrf2 gene induces premature senescence. Therefore, we explored whether Nrf2 is involved in the mechanism by which rapamycin delays cell senescence. In wild-type (WT) mouse fibroblasts, rapamycin increased the levels of Nrf2, and this correlates with the activation of autophagy and a reduction in the induction of cell senescence, as measured by SA-β-galactosidase (β-gal) staining, senescence-associated secretory phenotype (SASP), and p16 and p21 molecular markers...
March 31, 2017: Aging Cell
https://www.readbyqxmd.com/read/28341289/long-term-culture-with-lipopolysaccharide-induces-dose-dependent-cytostatic-and-cytotoxic-effects-in-thp-1-monocytes
#9
Jennifer Mytych, Maria Romerowicz-Misielak, Marek Koziorowski
Monocytes act as a first line of defence against invading pathogens and their dysfunctions seem to be a key factor in many immune disorders. However, the data on mechanisms underlying these dysfunctions remain elusive. In this study, we evaluated the effects of long-term (168h) lipopolysaccharide exposure on monocytes at low density cultures (1×10(5)cells/ml). Treatment with low dose LPS (≤5μg/ml) resulted in oxidative stress induction followed by p21 pathway activation, permanent cell cycle arrest and SASP development...
March 21, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28330601/mitochondria-in-cell-senescence-is-mitophagy-the-weakest-link
#10
REVIEW
Viktor I Korolchuk, Satomi Miwa, Bernadette Carroll, Thomas von Zglinicki
Cell senescence is increasingly recognized as a major contributor to the loss of health and fitness associated with aging. Senescent cells accumulate dysfunctional mitochondria; oxidative phosphorylation efficiency is decreased and reactive oxygen species production is increased. In this review we will discuss how the turnover of mitochondria (a term referred to as mitophagy) is perturbed in senescence contributing to mitochondrial accumulation and Senescence-Associated Mitochondrial Dysfunction (SAMD). We will further explore the subsequent cellular consequences; in particular SAMD appears to be necessary for at least part of the specific Senescence-Associated Secretory Phenotype (SASP) and may be responsible for tissue-level metabolic dysfunction that is associated with aging and obesity...
March 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28329136/chronic-resveratrol-treatment-inhibits-mrc5-fibroblast-sasp-related-protumoral-effects-on-melanoma-cells
#11
Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Silvia Peppicelli, Elisabetta Tanganelli, Gabriella Fibbi, Lisa Giovannelli, Mario Del Rosso, Alessandra Mocali
Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4...
January 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28325222/effects-of-ultra-high-dilutions-of-sodium-butyrate-on-viability-and-gene-expression-in-hek-293-cells
#12
Steven Olsen
BACKGROUND: Several recent studies reported the capability of high diluted homeopathic medicines to modulate gene expression in cell cultures. In line with these studies, we examined whether ultra-high dilutions (30C and 200C) of sodium butyrate (SB) can affect the expression levels of genes involved in acquisition of a senescence-associated secretory phenotype (SASP) in human embryonic kidney (HEK) 293 cells. METHODS: Cell viability was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay...
February 2017: Homeopathy: the Journal of the Faculty of Homeopathy
https://www.readbyqxmd.com/read/28320873/sav1-loss-induces-senescence-and-stat3-activation-coinciding-with-tubulointerstitial-fibrosis
#13
Janet Y Leung, Harper L Wilson, Kristin J Voltzke, Lindsay A Williams, Hyo Jin Lee, Sara E Wobker, William Y Kim
Tubulointerstitial fibrosis (TIF) is recognized as a final phenotypic manifestation in the transition from chronic kidney disease (CKD) to end-stage renal disease (ESRD). Here, we show that conditional inactivation of Sav1 in the mouse renal epithelium resulted in upregulated expression of profibrotic genes and TIF. Loss of Sav1 induced Stat3 activation and a senescence-associated secretory phenotype (SASP) that coincided with the development of tubulointerstitial fibrosis. Treatment of mice with the YAP inhibitor, Verteporfin (VP), inhibited activation of genes associated with senescence, SASP and activation of Stat3 as well as impeded the development of fibrosis...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28301010/effect-of-sonic-vibrations-on-bond-strength-of-fiberglass-posts-bonded-to-root-dentin
#14
Amanda Mahammad Mushashe, Rodrigo Otavio Jatahy Ferreira do Amaral, Carlos Eduardo Edwards Rezende, Flares Baratto Filho, Leonardo Fernandes da Cunha, Carla Castiglia Gonzaga
Sonic vibrations may improve the bond strength and durability of fiberglass posts by improving adhesive penetration into dentin as well as the cement flow. The objective of this study was to evaluate the effect of sonic vibrations on the bond strength between fiberglass posts and root dentin using the pull-out test. Bovine roots were endodontically treated and divided randomly into four groups (n=12): Group C - conventional cementation (control); Group SA - sonic vibration (Smart Sonic Device, FGM) of the adhesive system and conventional post accommodation; SP group - conventional adhesive application and sonic vibration of the post during accommodation; and SASP - sonic vibration of the system adhesive and the post during accommodation...
January 2017: Brazilian Dental Journal
https://www.readbyqxmd.com/read/28300842/cd95-ligand-induces-senescence-in-mismatch-repair-deficient-human-colon-cancer-via-chronic-caspase-mediated-induction-of-dna-damage
#15
Danielle A Raats, Nicola Frenkel, Susanne J van Schelven, Inne HMBorel Rinkes, Jamila Laoukili, Onno Kranenburg
CD95 is best known for its ability to induce apoptosis via a well-characterized pathway involving caspase-mediated proteolytic events. However, in apoptosis-resistant cell lines of diverse cancer types stimulation of CD95 primarily has pro-tumorigenic effects that affect many of the hallmarks of cancer. For instance, in colon cancer cells with a mutant KRAS gene CD95 primarily promotes invasion and metastasis. In the current study, we further investigated the context dependency of the consequences of CD95 activation in colon cancer...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28299617/methyl-caffeate-and-some-plant-constituents-inhibit-age-related-inflammation-effects-on-senescence-associated-secretory-phenotype-sasp-formation
#16
Hyun Lim, Byung Kyu Park, Sook Young Shin, Yong Soo Kwon, Hyun Pyo Kim
During aging, cells secrete molecules called senescence-associated secretory phenotype (SASP). They constitute chronic low-grade inflammation environment to adjacent cells and tissues. In order to find inhibiting agents of SASP formation, 113 plant constituents were incubated with BJ fibroblasts for 6 days after treatment with bleomycin. Several plant constituents showed considerable inhibition of IL-6 production, a representative SASP marker. These plant constituents included anthraquinones such as aurantio-obtusin, flavonoids including astragalin, iristectorigenin A, iristectorigenin B, linarin, lignans including lariciresinol 9-O-glucoside and eleutheroside E, phenylpropanoids such as caffeic acid and methyl caffeate, steroid (ophiopogonin), and others like centauroside, rhoifolin and scoparone...
March 15, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28286205/ochratoxin-a-induced-premature-senescence-in-human-renal-proximal-tubular-cells
#17
Xuan Yang, Sheng Liu, Chuchu Huang, Haomiao Wang, Yunbo Luo, Wentao Xu, Kunlun Huang
Ochratoxin A (OTA) has many nephrotoxic effects and is a promising compound for the study of nephrotoxicity. Human renal proximal tubular cells (HKC) are an important model for the study of renal reabsorption, renal physiology and pathology. Since the induction of OTA in renal senescence is largely unknown, whether OTA can induce renal senescence, especially at a sublethal dose, and the mechanism of OTA toxicity remain unclear. In our study, a sublethal dose of OTA led to an enhanced senescent phenotype, β-galactosidase staining and senescence associated secretory phenotype (SASP)...
March 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28273461/integrin-beta-3-regulates-cellular-senescence-by-activating-the-tgf-%C3%AE-pathway
#18
Valentina Rapisarda, Michela Borghesan, Veronica Miguela, Vesela Encheva, Ambrosius P Snijders, Amaia Lujambio, Ana O'Loghlen
Cellular senescence is an important in vivo mechanism that prevents the propagation of damaged cells. However, the precise mechanisms regulating senescence are not well characterized. Here, we find that ITGB3 (integrin beta 3 or β3) is regulated by the Polycomb protein CBX7. β3 expression accelerates the onset of senescence in human primary fibroblasts by activating the transforming growth factor β (TGF-β) pathway in a cell-autonomous and non-cell-autonomous manner. β3 levels are dynamically increased during oncogene-induced senescence (OIS) through CBX7 Polycomb regulation, and downregulation of β3 levels overrides OIS and therapy-induced senescence (TIS), independently of its ligand-binding activity...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28273155/tumor-stroma-with-senescence-associated-secretory-phenotype-in-steatohepatitic-hepatocellular-carcinoma
#19
Jee San Lee, Jeong Eun Yoo, Haeryoung Kim, Hyungjin Rhee, Myoung Ju Koh, Ji Hae Nahm, Jin Sub Choi, Kee-Ho Lee, Young Nyun Park
Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC), a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP) were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs)...
2017: PloS One
https://www.readbyqxmd.com/read/28260798/geniposide-ameliorates-tnbs-induced-experimental-colitis-in-rats-via-reducing-inflammatory-cytokine-release-and-restoring-impaired-intestinal-barrier-function
#20
Bin Xu, Yan-Li Li, Ming Xu, Chang-Chun Yu, Meng-Qiao Lian, Ze-Yao Tang, Chuan-Xun Li, Yuan Lin
Geniposide is an iridoid glycosides purified from the fruit of Gardenia jasminoides Ellis, which is known to have antiinflammatory, anti-oxidative and anti-tumor activities. The present study aimed to investigate the effects of geniposide on experimental rat colitis and to reveal the related mechanisms. Experimental rat colitis was induced by rectal administration of a TNBS solution. The rats were treated with geniposide (25, 50 mg·kg(-1)·d(-1), ig) or with sulfasalazine (SASP, 100 mg·kg(-1)·d(-1), ig) as positive control for 14 consecutive days...
March 6, 2017: Acta Pharmacologica Sinica
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