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cell aging

Julien Muffat, Yun Li, Rudolf Jaenisch
In vitro differentiation of human pluripotent stem cells provides a systematic platform to investigate the physiological development and function of the human nervous system, as well as the etiology and consequence when these processes go awry. Recent development in three-dimensional (3D) organotypic culture systems allows modeling of the complex structure formation of the human CNS, and the intricate interactions between various resident neuronal and glial cell types. Combined with an ever-expanding genome editing and regulation toolkit such as CRISPR/Cas9, it is now a possibility to study human neurological disease in the relevant molecular, cellular and anatomical context...
October 18, 2016: Current Opinion in Cell Biology
Ranjan Basak, Naveen Kumar Nair, Indraneel Mittra
There is extensive literature to show that nucleic acids can be taken up by cells under experimental conditions and that foetal DNA can be detected in maternal tissues. The uptaken DNA can integrate into host cell genomes and can be transcribed and translated into proteins. They can also cause chromosomal damage and karyotype alterations. Cell-free nucleic acids (cfNAs)-based non-invasive DNA diagnostic techniques are being extensively researched in the field of cancer with the potential to advance new prognostic parameters and direct treatment decisions...
October 12, 2016: Mutation Research
Siying Ren, Yongfeng Luo, Hui Chen, David Warburton, Hilaire C Lam, Larry Wang, Ping Chen, Elizabeth P Henske, Wei Shi
The tuberous sclerosis complex (TSC) proteins are critical negative regulators of the mTORC1 pathway. Germline mutations of TSC1 or TSC2 cause TSC, affecting multiple organs, including the kidney and lung, and causing substantial morbidity and mortality. The mechanisms of organ-specific disease in TSC remain incompletely understood, and the impact of TSC inactivation on mesenchymal lineage cells has not been specifically studied. We deleted Tsc2 specifically in mesoderm-derived mesenchymal cells of multiple organs in mice using the Dermo1-Cre driver...
October 18, 2016: American Journal of Pathology
Marie-Catherine Drigeard Desgarnier, Corinne Zinflou, Justin D Mallet, Sébastien P Gendron, Sébastien J Méthot, Patrick J Rochette
Purpose: Human chromosomes are protected at their end by a long portion of hexameric tandem repeats, the telomere. In somatic cells, telomere attrition caused by endogenous and exogenous oxidative stress as well as DNA replication can threaten genomic integrity and lead to the deterioration of tissue functions and an age-related physiological decline. The human eye is a complex organ in which cells of different ocular tissues are exposed to photo-oxidation, high mitochondrial metabolic activity, and/or replicative pressure...
October 1, 2016: Investigative Ophthalmology & Visual Science
Haibo Wang, Xiaokun Han, Eric Kunz, M Elizabeth Hartnett
Purpose: This study addresses the hypothesis that age-related stresses upregulate Thy-1 in choroidal endothelial cells (CECs) and contribute to CEC activation and migration, processes important in choroidal neovascularization (CNV). Methods: Measurements were made of Thy-1 protein (Western blot) in CECs and Thy-1 mRNA (real time quantitative PCR) in CECs treated with VEGF, CCL11, or PBS or in RPE/choroids from young or old donors or lasered or nonlasered mice. Immunolabeled Thy-1 in ocular sections was compared from young versus old human donor eyes or those with or without neovascular AMD or from lasered versus nonlasered mice...
October 1, 2016: Investigative Ophthalmology & Visual Science
Joseph B Fisher, Audrey Horst, Tina Wan, Min-Su Kim, John Auchampach, John Lough
Tat-interactive protein 60 (Tip60), encoded by the Kat5 gene, is a member of the MYST family of acetyltransferases. Cancer biology studies have shown that Tip60 induces the DNA damage response, apoptosis, and cell-cycle inhibition. Although Tip60 is expressed in the myocardium, its role in cardiomyocytes (CMs) is unclear. Earlier studies here showed that application of cardiac stress to globally targeted Kat5+/-haploinsufficient mice resulted in inhibition of apoptosis and activation of the CM cell-cycle, despite only modest reduction of Tip60 protein levels...
2016: PloS One
Neimar de Paula Silva, Rejane de Souza Reis, Rafael Garcia Cunha, Júlio Fernando Pinto Oliveira, Marceli de Oliveira Santos, Maria S Pombo-de-Oliveira, Beatriz de Camargo
BACKGROUND: Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics. METHODS: A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS) or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma)...
2016: PloS One
Charles A Pickens, Mariana de Fátima Albuquerque Pereira, Jenifer I Fenton
Dietary lipid intake can be associated with an increased risk for colorectal cancer depending on its composition. Carcinogenesis alters lipid metabolism to facilitate cell growth and survival. For instance, metabolites of polyunsaturated fatty acids (PUFAs) are associated with increasing colon cell proliferation. Moreover, precancerous colon lesions (i.e. adenomas) increase the risk for colorectal cancer. In this study, we investigated associations between plasma PUFAs and the number of colon polyps and polyp type (i...
October 20, 2016: European Journal of Cancer Prevention
Malgorzata Piechota, Piotr Sunderland, Adrianna Wysocka, Maria Nalberczak, Malgorzata A Sliwinska, Kasia Radwanska, Ewa Sikora
One of the features of cellular senescence is the activity of senescence-associated- β-galactosidase (SA-β-gal). The main purpose of this study was to evaluate this marker of senescence in aging neurons. We found that cortical neurons exhibited noticeable SA-β-gal activity quite early in culture. Many SA-β-gal-positive neurons were negative for another canonical marker of senescence, namely, double-strand DNA breaks (DSBs). Moreover, DDR signalling triggered by low doses of doxorubicin did not accelerate the appearance of neuronal SA-β-gal...
October 19, 2016: Oncotarget
Allegra T Aron, Morten O Loehr, Jana Bogena, Christopher J Chang
Iron is essential for sustaining life, as its ability to cycle between multiple oxidation states is critical for catalyzing chemical transformations in biological systems. However, without proper regulation, this same redox capacity can trigger oxidative stress events that contribute to aging along with diseases ranging from cancer to cardiovascular and neurodegenerative disorders. Despite its importance, methods for monitoring biological iron bound weakly to cellular ligands-the labile iron pool-to generate a response that preserves spatial and temporal information remain limited, owing to the potent fluorescence quenching ability of iron...
October 21, 2016: Journal of the American Chemical Society
Vesela Ivanova, Tihomir Dikov, Nadya Dimitrova
PURPOSE: To provide an overview of the morphologic subtypes of ovarian carcinomas in Bulgaria in relation to current healthcare organization using Bulgarian National Cancer Registry data. Further, we investigated hospital volume as a factor influencing the quality of care for patients with ovarian cancer. METHODS: Bulgarian National Cancer Registry ovarian carcinoma data were retrieved (2009-2011) and distribution of histologic types was analyzed. Cases were divided and compared with respect to main treatment: no surgery, surgery at hospitals dealing with ≥30 ovarian cancer patients/year (high volume), and surgery at hospitals dealing with <30 ovarian cancer patients/year (low volume)...
October 8, 2016: Tumori
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
R C Gerring, C T Ott, J M Curry, Z B Sargi, S T Wester
PurposeTo describe prognostic factors and survival outcomes in patients who underwent orbital exenteration for periocular non-melanoma cutaneous malignancies.MethodsThe authors performed an institutional review board-approved retrospective review of all patients who underwent orbital exenteration for non-melanoma periocular cutaneous malignancies at a tertiary care hospital system over a 10-year period. Patient demographics, tumor, and treatment data were recorded. Survival outcomes included disease-free survival (DFS) and overall survival (OS)...
October 21, 2016: Eye
Alexia Mopin, Virginie Driss, Carine Brinster
The intravenous injection of C1498 cells into syngeneic or congenic mice has been performed since 1941. These injections result in the development of acute leukemia. However, the nature of this disease has not been well documented in the literature. Here, we provide a technical protocol for characterizing C1498 cells in vitro and for determining the nature of the induced leukemia in vivo. The first part of this procedure is focused on determining the hematopoietic lineage and the stage of differentiation of cultured C1498 cells...
October 14, 2016: Journal of Visualized Experiments: JoVE
Giulia R Mosele, Gianfilippo Caggiari, Roberto M Scarpa, Carlo Doria
BACKGROUND: Renal cell carcinoma (RCC) is among the 10 most common cancers in both men and women. It comprises 2-3% of all malignancies. The most common site for metastasis from RCC is the lung (50% of patients), followed by the skeleton (20% to 50% of patients). METHODS: We retrospectively reviewed our consecutive series of 63 patients surgically treated for spinal metastases from RCC. The surgical treatment for spinal metastases varied in each patient. Factors influencing the choice of surgery included age, disease status, symptoms, morbidity of the patient, the location, the number of repetitive lesions and the existence of extra-osseous metastases...
October 21, 2016: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
Melinda Vass, Ágnes Diószegi, Norbert Németh, Viktória Sógor, Sándor Baráth, Eszter Szalai, László Módis, Soltész Pál
Rheopheresis is an extracorporal selective double-filtration procedure. In the first part of the treatment the blood is passes through the plasma filter, which separates blood cells from the plasma. Then the plasma flow to a second filter called MONET (Membranefiltration Optimised Novel Extracorporal Treatment). The MONET filter retains high molecular weight proteins such LDL, Lp(a), fibrinogen, α2 macroglobulin, vWF and IgM. Hereby the whole blood and plasma viscosity decrease, improves microcirculation, and has a positive effect on lipid profile as well...
October 15, 2016: Clinical Hemorheology and Microcirculation
J R Baker, C Vuppusetty, T Colley, Andriana I Papaioannou, P Fenwick, Louise Donnelly, K Ito, P J Barnes
Sirtuin-1 (SIRT1) and SIRT6, NAD(+)-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD...
October 21, 2016: Scientific Reports
Ayse Ayhan, Elisabetta Kuhn, Ren-Chin Wu, Hiroshi Ogawa, Asli Bahadirli-Talbott, Tsui-Lien Mao, Haruhiko Sugimura, Ie-Ming Shih, Tian-Li Wang
Ovarian clear cell carcinoma is a unique type of ovarian cancer, often derived from endometriosis, and advanced-stage disease has a dismal prognosis primarily due to the resistance to conventional chemotherapy. Previous studies have shown frequent somatic mutations in ARID1A, PIK3CA, hTERT promoter, and amplification of ZNF217; however, the molecular alterations that are associated with its aggressiveness remain largely unknown. This study examined and compared cyclin E1 expression in endometriosis-related ovarian tumors, with the aim of determining the relationship between hTERT mutations and ARID1A expression and evaluating the effects of these molecular alterations on patient survival...
October 21, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Shaher Bano Mirza, Ramin Ekhteiari Salmas, M Qaiser Fatmi, Serdar Durdagi
The Klotho is known as lifespan enhancing protein involved in antagonizing the effect of Wnt proteins. Wnt proteins are stem cell regulators, and uninterrupted exposure of Wnt proteins to the cell can cause stem and progenitor cell senescence, which may lead to aging. Keeping in mind the importance of Klotho in Wnt signaling, in silico approaches have been applied to study the important interactions between Klotho and Wnt3 and Wnt3a (wingless-type mouse mammary tumor virus (MMTV) integration site family members 3 and 3a)...
October 21, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
J M Koshy, S Mohan, D Deodhar, M John, A Oberoi, A Pannu
BACKGROUND: Though cryptococcal meningitis (CM) is recognized as a disease of the immunocompromised, studies have implicated that it also affect immunocompetent patients. METHODOLOGY: This was a cross sectional study conducted in the Department of Medicine of a tertiary teaching institution in North India. All the patients diagnosed with CM on the basis of detection of cryptococcal antigen or the presence of capsulated budding yeast cells on India ink preparation, from April 2009 to March2015 were included in the study...
October 2016: Journal of the Association of Physicians of India
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