Evidence of Oxidative Stress and Secondary Mitochondrial Dysfunction in Metabolic and Non-Metabolic Disorders

Abstract: Mitochondrial dysfunction and oxidative stress have been implicated in the pathogenesis of a number of diseases and conditions. Oxidative stress occurs once the antioxidant defenses of the body become overwhelmed and are no longer able to detoxify reactive oxygen species (ROS). The ROS can then go unchallenged and are able to cause oxidative damage to cellular lipids, DNA and proteins, which will eventually result in cellular and organ dysfunction. Although not always the primary cause of disease, mitochondrial dysfunction as a secondary consequence disease of pathophysiology can result in increased ROS generation together with an impairment in cellular energy status. Mitochondrial dysfunction may result from either free radical-induced oxidative damage or direct impairment by the toxic metabolites which accumulate in certain metabolic diseases. In view of the importance of cellular antioxidant status, a number of therapeutic strategies have been employed in disorders associated with oxidative stress with a view to neutralising the ROS and reactive nitrogen species implicated in disease pathophysiology. Although successful in some cases, these adjunct therapies have yet to be incorporated into the clinical management of patients. The purpose of this review is to highlight the emerging evidence of oxidative stress, secondary mitochondrial dysfunction and antioxidant treatment efficacy in metabolic and non-metabolic diseases in which there is a current interest in these parameters

Paracrine Sonic Hedgehog Signalling by Prostate Cancer Cells Induces Osteoblast Differentiation

Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis

Paracrine Sonic Hedgehog Signalling by Prostate Cancer Cells Induces Osteoblast Differentiation

Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis

The effect of media and beauty standards on the body image of women with a visual disability

“The twentieth century has seen a huge upsurge in the importance placed by western society on physical beauty, particularly for women” (Wood “Perceptions of Feminine Beauty,” n.d.). Fashion industries, cosmetics, and plastic surgeries have all flourished on the importance society has placed on physical beauty. Marketing ploys from these industries often show tall, slender, white women who suggest cosmetics, diet regimens, and other beauty enhancements to successfully transform one’s aesthetic. With the fashion and media industries heavy reliance on visuals, there have been a plethora of evaluations conducted to examine the media’s influence on women’s body image. Yet, there has been little research conducted with non-able-bodied women, specifically women with visual disabilities, and the effects that the media has on their self-image. To determine this, I conducted semi-structured, in-depth interviews, with six college-aged blind or visually impaired women which focused on their lived experiences and exposure to the media. Recruiting participants through convenience sampling, I interpreted the data based on participants’ race, culture, and other common themes in response to their lived experiences. Results demonstrated participants had a positive self-image; contributors included their family, self, and partners. Keywords: disability, visual disability, body-image, women, medi

Paracrine sonic hedgehog signalling by prostate cancer cells induces osteoblast differentiation

<p>Abstract</p> <p>Background</p> <p>Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis.</p> <p>Results</p> <p>LNCaP human prostate cancer cells modified to overexpress Shh (designated LNShh cells) and MC3T3 mouse pre-osteoblasts were maintained as mixed populations within the same culture chamber. In this non-conventional mixed culture system, LNShh cells upregulated the expression of Shh target genes <it>Gli1 </it>and <it>Patched 1 </it>(<it>Ptc1</it>) in MC3T3 cells and this was inhibited by cyclopamine, a specific chemical inhibitor of hedgehog signalling. Concomitantly, MC3T3 cells exhibited time-dependent decreased cell proliferation, upregulated alkaline phosphatase <it>Akp2 </it>gene expression, and increased alkaline phosphatase activity indicative of early phase osteoblast differentiation. LNShh cell-induced differentiation was inhibited in MC3T3 cells stably transfected with a dominant negative form of Gli1, a transcription factor that mediates Shh signalling. Interestingly, LNShh cells did not significantly increase the endogenous expression of the osteoblast differentiation transcription factor <it>Runx2 </it>and its target genes <it>osteocalcin </it>and <it>osteopontin</it>. Consistent with these results, exogenous Shh peptide did not upregulate <it>Runx2 </it>expression in MC3T3 cells. However, <it>Runx2 </it>levels were increased in MC3T3 cells by ascorbic acid, a known stimulator of osteoblast differentiation.</p> <p>Conclusion</p> <p>Altogether, these data demonstrate that Shh-expressing prostate cancer cells can directly and specifically induce differentiation in pre-osteoblasts via a Gli1-dependent mechanism that does not require transcriptional upregulation of <it>Runx2</it>. Paracrine activation of the Shh pathway in osteoblast progenitors and subsequent induction of osteoblast differentiation could be a mechanism through which high levels of Shh expression in prostate carcinoma contribute to bone metastasis. Targeting of paracrine Shh signalling may provide an effective therapeutic strategy against prostate carcinoma metastasis in bone.</p

Focusing on the Learning for the English Language Learner

Educators are faced with the challenge of teaching an ever-changing student population. The classrooms are filled with students from culturally and linguistically diverse backgrounds and cultures. English Language Learners account for 12% of our student population (Garcia, Jensen, & Scribner, 2009). Providing English Language Learners with effective instruction that integrates both content area knowledge and English language acquisition is necessary. English Language Learners are relying on educators to teach them what they need to know in order to be successful in all academic areas in schools. The purpose of this study was to examine the systemic approach of SIOP as it relates to maximizing content and developing language with all learners when implemented with fidelity in the classroom. The focus of this study was two classrooms within an urban school district in Western Arkansas. Both schools’ demographics include 65% English Language Learners and more than 90% free and reduced lunch. Teachers in both classrooms have taught at least ten years in the district in a Title I school. The researcher used assessment data from the Development Reading and Spelling Analysis from the beginning and middle of the school year. In addition, the October and December ACT Aspire Interim assessment data from Reading and English was utilized. To ensure fidelity of the treatment and control group’s educational setting, the researcher used the Sheltered Observation Instruction Protocol rubric on two different occasions in each classroom. Teachers of English Language Learners must be expected to implement instructional strategies proven to be effective based on students’ individual language proficiency levels. Districts/schools need a systematic, comprehensive and practical approach to prepare and support teachers to work with English Language Learners. The Sheltered Instruction Observation Protocol features provide the strategies and framework to strengthen academic language and literacy development in all students

Carbothermal reduction of friable chromite in a small-scale transferred-arc furnace

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