SIRT3 and cancer: Tumor promoter or suppressor?

AbstractSirtuins (SIRT1–7), the mammalian homologues of the Sir2 gene in yeast, have emerging roles in age-related diseases, such as cardiac hypertrophy, diabetes, obesity, and cancer. However, the role of several sirtuin family members, including SIRT1 and SIRT3, in cancer has been controversial. The aim of this review is to explore and discuss the seemingly dichotomous role of SIRT3 in cancer biology with particular emphasis on its potential role as a tumor promoter and tumor suppressor. This review will also discuss the potential role of SIRT3 as a novel therapeutic target to treat cancer

Evaluation of Combustion Processes for Production of Feedstock Chemicals from Ammonium Sulfate and Ammonium Bisulfate

The combustion of ammonium bisulfate and ammonium sulfate solutions in hydrocarbon/air flames was studied under varied flame conditions. The objective of the study was to optimize the recovery of sulfur value from aqueous waste streams containing these salts. Combustion of ammonium sulfates yielded different sulfur species such as sulfur dioxide (SO2 ), hydrogen sulfide (H2S), and carbonyl sulfide (COS). The types of sulfur species obtained and their yields were dependent on the flame stoichiometry. When combustion was carried out in stochiometric flames or in flames with excess oxygen, the sulfur present in the salts was quantitatively converted to SO2 . However, these flames also produced nitrogen oxides (NOx ) above the 200ppm level. Combustion of ammonium sulfates in the sub-stoichiometric (oxygen-deficient) flames resulted in the formation of reduced sulfur species, particularly H2S. This species accounted for nearly 90% of the total sulfur present in the salts. Introduction of a secondary air stream in cooler regions of the combustor led to quantitative oxidation of H2 S and other reduced species such as COS to SO2. The SO2 obtained through the secondary oxidation contained nitrogen oxides at comparably lower levels

Disease-associated fibronectin matrix fragments trigger anoikis of human primary ligament cells: p53 and c-myc are suppressed

Inflammation in periodontal disease is characterized by the breakdown of the extracellular matrix. This study shows that an inflammation-associated matrix breakdown fragment of fibronectin (FN) induces anoikis of human periodontal ligament (PDL) cells. This 40 kDa fragment was identified in human inflammatory crevicular fluid and is associated with disease status. Previously, we reported that a similar recombinant FN fragment triggered apoptosis of PDL cells by an alternate apoptotic signaling pathway that requires transcriptional downregulation of p53 and c-myc. Thus, to determine whether the physiologically relevant 40 kDa fragment triggers apoptosis in these cells, the 40 kDa fragment was generated and studied for its apoptotic properties. The 40 kDa fragment induces apoptosis of PDL cells, and preincubation of cells with intact vitronectin, FN, and to a limited extent collagen I, rescue this apoptotic phenotype. These data suggest that the 40 kDa fragment prevents PDL cell spreading, thereby inducing anoikis. The signaling pathway also involves a downregulation in p53 and c-myc, as determined by Western blotting and real time quantitative PCR. These data indicate that an altered FN matrix as is elaborated in inflammation induces anoikis of resident cells and thus may contribute to disease progression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44344/1/10495_2005_Article_1880.pd

Existence of radial stationary solutions for a system in combustion theory

In this paper, we construct radially symmetric solutions of a nonlinear noncooperative elliptic system derived from a model for flame balls with radiation losses. This model is based on a one step kinetic reaction and our system is obtained by approximating the standard Arrehnius law by an ignition nonlinearity, and by simplifying the term that models radiation. We prove the existence of 2 solutions using degree theory

Association between oral health markers and decline in muscle strength and physical performance in later life: longitudinal analyses of two prospective cohorts from the UK and the USA.

BACKGROUND: Poor oral health could be associated with changes in musculoskeletal health over time. This aim of this study was to investigate the longitudinal relationship between oral health and decline in physical function in later life. METHODS: We did a prospective analysis of two cohorts of older adults (aged 70 years or older) including men from the British Regional Heart Study (BRHS; n=612), and men and women from the Health, Aging and Body Composition (Health ABC) Study (n=1572), followed up for about 8 years. Data were available for clinical or self-reported oral health measures, muscle (grip) strength, and physical performance (chair stand and gait speed). ANCOVA models were used to assess the association between oral health and follow-up physical function scores. Multivariate logistic regression models were used to examine the associations between oral health and decline in physical function over the follow-up period. In the BRHS, changes in oral health and physical function were also assessed. All models were adjusted for relevant sociodemographic, behavioural, and health-related factors. FINDINGS: In the BRHS, complete tooth loss and difficulty eating were associated with weaker grip strength at follow-up, and periodontal status was associated with decline in gait speed. In the Health ABC Study, complete tooth loss, poor self-rated oral health, and the presence of one oral health problem were associated with slower gait speed at follow-up. In both studies, dry mouth was associated with declines in physical function. In the BRHS, deterioration of dentition (tooth loss) over the follow-up period was associated with decline in chair stand speed (adjusted odds ratio 2·34 [95% CI 1·20-4·46]), as was deterioration in difficulty eating (2·41 [1·04-5·60]). INTERPRETATION: Oral health problems are associated with poorer physical function and greater decline in physical function in older adults, and could be an indicator of individuals at risk of reduced physical capacity and subsequent frailty and disability in later life. FUNDING: The Dunhill Medical Trust and the US National Institutes of Health-National Institute of Dental and Craniofacial Research

The CS1 segment of fibronectin is involved in human OSCC pathogenesis by mediating OSCC cell spreading, migration, and invasion

<p>Abstract</p> <p>Background</p> <p>The alternatively spliced V region or type III connecting segment III (IIICS) of fibronectin is important in early development, wound healing, and tumorigenesis, however, its role in oral cancer has not been fully investigated. Thus, we investigated the role of CS-1, a key site within the CSIII region of fibronectin, in human oral squamous cell carcinoma (OSCC).</p> <p>Methods</p> <p>To determine the expression of CS-1 in human normal and oral SCC tissue specimens immunohistochemical analyses were performed. The expression of CS1 was then associated with clinicopathological factors. To investigate the role of CS-1 in regulating OSCC cell spreading, migration and invasion, OSCC cells were assayed for spreading and migration in the presence of a CS-1 peptide or a CS-1 blocking peptide, and for invasion using Matrigel supplemented with these peptides. In addition, integrin α4siRNA or a focal adhesion kinase (FAK) anti-sense oligonucleotide was transfected into OSCC cells to examine the mechanistic role of integrin α4 or FAK in CS1-mediated cell spreading and migration, respectively.</p> <p>Results</p> <p>CS-1 expression levels were significantly higher in OSCC tissues compared to normal tissues (p < 0.05). Also, although, high levels of CS-1 expression were present in all OSCC tissue samples, low-grade tumors stained more intensely than high grade tumors. OSCC cell lines also expressed higher levels of CS-1 protein compared to normal human primary oral keratinocytes. There was no significant difference in total fibronectin expression between normal and OSCC tissues and cells. Inclusion of CS-1 in the in vitro assays enhanced OSCC cell spreading, migration and invasion, whereas the CS1 blocking peptide inhibited these processes. Suppression of integrin α4 significantly inhibited the CS1-mediated cell spreading. Furthermore, this migration was mediated by focal adhesion kinase (FAK), since FAK suppression significantly blocked the CS1-induced cell migration.</p> <p>Conclusion</p> <p>These data indicate that the CS-1 site of fibronectin is involved in oral cancer pathogenesis and in regulating OSCC cell spreading, migration and invasion.</p

Causal Modeling Using Network Ensemble Simulations of Genetic and Gene Expression Data Predicts Genes Involved in Rheumatoid Arthritis

Tumor necrosis factor α (TNF-α) is a key regulator of inflammation and rheumatoid arthritis (RA). TNF-α blocker therapies can be very effective for a substantial number of patients, but fail to work in one third of patients who show no or minimal response. It is therefore necessary to discover new molecular intervention points involved in TNF-α blocker treatment of rheumatoid arthritis patients. We describe a data analysis strategy for predicting gene expression measures that are critical for rheumatoid arthritis using a combination of comprehensive genotyping, whole blood gene expression profiles and the component clinical measures of the arthritis Disease Activity Score 28 (DAS28) score. Two separate network ensembles, each comprised of 1024 networks, were built from molecular measures from subjects before and 14 weeks after treatment with TNF-α blocker. The network ensemble built from pre-treated data captures TNF-α dependent mechanistic information, while the ensemble built from data collected under TNF-α blocker treatment captures TNF-α independent mechanisms. In silico simulations of targeted, personalized perturbations of gene expression measures from both network ensembles identify transcripts in three broad categories. Firstly, 22 transcripts are identified to have new roles in modulating the DAS28 score; secondly, there are 6 transcripts that could be alternative targets to TNF-α blocker therapies, including CD86 - a component of the signaling axis targeted by Abatacept (CTLA4-Ig), and finally, 59 transcripts that are predicted to modulate the count of tender or swollen joints but not sufficiently enough to have a significant impact on DAS28

Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular point. Part I: histological effects

<p>Abstract</p> <p>Background</p> <p>Temporomandibular joint (TMJ) arthritis in children causes alterations in craniomandibular growth. This abnormal growth may be prevented by an early anti-inflammatory intervention. We have previously shown that intra-articular (IA) corticosteroid reduces TMJ inflammation, but causes concurrent mandibular growth inhibition in young rabbits. Blockage of TNF-α has already proven its efficacy in children with juvenile idiopathic arthritis not responding to standard therapy. In this paper we evaluate the effect of IA etanercept compared to subcutaneous etanercept in antigen-induced TMJ-arthritis in rabbits on histological changes using histomorphometry and stereology. This article presents the data and discussion on the anti-inflammatory effects of systemic and IA etanercept. In Part II the data on the effects of systemic and IA etanercept on facial growth are presented.</p> <p>Methods</p> <p>Forty-two rabbits (10 weeks old) pre-sensitized with ovalbumin and locally induced inflammation in the temporomandibular joints were divided into three groups: a placebo group receiving IA saline injections in both joints one week after arthritis induction (n = 14), an IA etanercept group receiving 0.1 mg/kg etanercept per joint one week after arthritis induction (n = 14) and a systemic etanercept group receiving 0.8 mg/kg etanercept weekly throughout the 12-week study (n = 14). Arthritis was maintained by giving four inductions three weeks apart. Additional IA saline or etanercept injections were also given one week after the re-inductions. Histomorphometric and unbiased stereological methods (optical fractionator) were used to assess and estimate the inflammation in the joints.</p> <p>Results</p> <p>The histomorphometry showed synovial proliferation in all groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating with systemic etanercept but not with IA etanercept. Semi-quantitative assessments of synovial proliferation and subsynovial inflammation also showed reduced inflammation in the systemic etanercept group. However, the thickness of the synovial lining and volume of the subsynovial connective tissue showed no differences between the groups.</p> <p>Conclusion</p> <p>An anti-inflammatory effect of systemic etanercept on the synovial tissues in the temporomandibular joint was shown. However, IA etanercept at the given dose had no significant effect on the severity of chronic inflammation on the parameters here tested in ovalbumin antigen-induced arthritis.</p

Plant-made vaccines in support of the Millennium Development Goals

Vaccines are one of the most successful public health achievements of the last century. Systematic immunisation programs have reduced the burden of infectious diseases on a global scale. However, there are limitations to the current technology, which often requires costly infrastructure and long lead times for production. Furthermore, the requirement to keep vaccines within the cold-chain throughout manufacture, transport and storage is often impractical and prohibitively expensive in developing countries—the very regions where vaccines are most needed. In contrast, plant-made vaccines (PMVs) can be produced at a lower cost using basic greenhouse agricultural methods, and do not need to be kept within such narrow temperature ranges. This increases the feasibility of developing countries producing vaccines locally at a small-scale to target the specific needs of the region. Additionally, the ability of plant-production technologies to rapidly produce large quantities of strain-specific vaccine demonstrates their potential use in combating pandemics. PMVs are a proven technology that has the potential to play an important role in increasing global health, both in the context of the 2015 Millennium Development Goals and beyond