Inflammatory signaling in skeletal muscle cell growth

This thesis examines the potential beneficial role of inflammation in skeletal muscle tissue. This work establishes cyclooxygenase pathway derived prostaglandins as key anabolic signalling molecules regulating skeletal muscle cell growth and examines changes in circulating inflammatory lipid mediators and intramuscular anabolic signaling in response to acute resistance exercise in humans.

Bone marrow chimeras and c-fms conditional ablation (mafia) mice reveal an essential role for resident myeloid cells in lipopolysaccharide/TLR4-induced corneal inflammation

The mammalian cornea contains an extensive network of resident macrophages and dendritic cells. To determine the role of these cells in LPS-induced corneal inflammation, TLR4−/− mice were sublethally irradiated and reconstituted with bone marrow cells from either enhanced GFP (eGFP)+/C57BL/6 or eGFP+/TLR4−/− mice. The corneal epithelium was abraded, LPS was added topically, and cellular infiltration to the corneal stroma and development of corneal haze were examined after 24 h. TLR4−/− mice reconstituted with C57BL/6, but not TLR4−/− bone marrow cells donor cells were found to cause infiltration of eGFP+ cells to the cornea, including neutrophils, and also increased corneal haze compared with saline-treated corneas. In a second experimental approach, corneas of transgenic macrophage Fas induced apoptosis (Mafia) mice were stimulated with LPS. These mice express eGFP and a suicide gene under control of the c-fms promoter, and systemic treatment with the FK506 dimerizer (AP20187) causes Fas-mediated apoptosis of monocytic cells. AP20187-treated mice had significantly fewer eGFP+ cells in the cornea than untreated mice. After stimulation with LPS neutrophil recruitment and development of corneal haze were impaired in AP20187-treated mice compared with untreated controls. Furthermore, LPS induced CXCL1/KC and IL-1α production within 4 h in corneas of untreated Mafia mice, which is before cellular infiltration; however, cytokine production was impaired after AP20187 treatment. Together, results from both experimental approaches demonstrate an essential role for resident corneal monocytic lineage cells (macrophages and dendritic cells) in development of corneal inflammation.

Impact of medical Qigong on quality of life, fatigue, mood and inflammation in cancer patients : a randomized controlled trial

Background: Substantial numbers of cancer patients use complementary medicine therapies, even without a supportive evidence base. This study aimed to evaluate in a randomized controlled trial, the use of Medical Qigong (MQ) compared with usual care to improve the quality of life (QOL) of cancer patients. Patients and methods: One hundred and sixty-two patients with a range of cancers were recruited. QOL and fatigue were measured by Functional Assessment of Cancer Therapy—General and Functional Assessment of Cancer Therapy—Fatigue, respectively, and mood status by Profile of Mood State. The inflammatory marker serum C-reactive protein (CRP) was monitored serially. Results: Regression analysis indicated that the MQ group significantly improved overall QOL (t144 = −5.761, P < 0.001), fatigue (t153 = −5.621, P < 0.001), mood disturbance (t122 =2.346, P = 0.021) and inflammation (CRP) (t99 = 2.042, P < 0.044) compared with usual care after controlling for baseline variables. Conclusions: This study indicates that MQ can improve cancer patients’ overall QOL and mood status and reduce specific side-effects of treatment. It may also produce physical benefits in the long term through reduced inflammation.

Mediators of dietary patterns in an intervention to improve early childhood nutrition

This thesis assessed the effect of a novel health promotion intervention on early childhood nutrition. It found that improved maternal nutrition knowledge and reduced maternal use of rewards in child feeding were important contributors to improving child dietary patterns.

Airway clearance of apoptotic cells in COPD

Apoptosis of bronchial epithelial cells and the phagocytic clearance of these cells by alveolar macrophages (a process termed efferocytosis) are integral processes leading to repair of airway epithelial injury. Efferocytosis allows for the removal of apoptotic material with minimal inflammation and prevents the development of secondary necrosis and ongoing inflammation. Defective efferocytosis and the increased presence of apoptotic cells have been identified in the airways of subjects with chronic obstructive pulmonary disease (COPD). There are three major potential causes for this accumulation of apoptotic cells: (i) increased apoptosis per se as a result of an increase in apoptotic mediators, (ii) defects in the recognition of apoptotic cells by AM and (iii) failure to clear the unwanted cells by the process of efferocytosis. The implications of these processes in COPD and novel treatment strategies aimed at improving clearance of apoptotic cells form the focus of the present review.

Glutathione peroxidase-1 reduces influenza A virus-induced lung inflammation

Oxidative stress caused by excessive reactive oxygen species production is implicated in influenza A virus–induced lung disease. Glutathione peroxidase (GPx)-1 is an antioxidant enzyme that may protect lungs from  such damage. The objective of this study was to determine if GPx-1 protects the lung against influenza A virus–induced lung inflammation in vivo.

A systematic review of intervention effects on potential mediators of children's physical activity

Background : Many interventions aiming to increase children’s physical activity have been developed and implemented in a variety of settings, and these interventions have previously been reviewed; however the focus of these reviews tends to be on the intervention effects on physical activity outcomes without consideration of the reasons and pathways leading to intervention success or otherwise.

To systematically review the efficacy of physical activity interventions targeting 5-12 year old children on potential mediators and, where possible, to calculate the size of the intervention effect on the potential mediator.

Methods : A systematic search identified intervention studies that reported outcomes on potential mediators of physical activity among 5-12 year old children. Original research articles published between 1985 and April 2012 were reviewed.

Results : Eighteen potential mediators were identified from 31 studies. Positive effects on cognitive/psychological potential mediators were reported in 15 out of 31 studies. Positive effects on social environmental potential mediators were reported in three out of seven studies, and no effects on the physical environment were reported. Although no studies were identified that performed a mediating analysis, 33 positive intervention effects were found on targeted potential mediators (with effect sizes ranging from small to large) and 73% of the time a positive effect on the physical activity outcome was reported.

Conclusions : Many studies have reported null intervention effects on potential mediators of children’s physical activity; however, it is important that intervention studies statistically examine the mediating effects of interventions so the most effective strategies can be implemented in future programs.

The role of nanomedicine in cell based therapeutics in cancer and inflammation.

Cell based therapeutics is one of the most rapidly advancing medical fields, bringing together a range of fields including transplantation, tissue engineering and regeneration, biomaterials and stem cell biology. However, traditional cell-based therapeutics have many limitations, one of which is their harmful effects exhibited on healthy body cells due to their lack of specificity. Nanomedicine is providing an alternative treatment strategy that is more targeted and specific to a range of diseases. Varying from polymers conjugated with drugs or tissue targeting molecules, to proteins encapsulated within a polymer shell, nanomedicine will without a doubt play a major role in designing effective cell-based therapeutics that can overcome certain classical problems. These may include from addressing the problem of non-specificity of contemporary treatments to overcoming mechanical barriers, such as crossing cell membranes. This review summarises the recent work on nano-based cell therapy as a regenerative agent and as a therapeutic for cancer and neurological diseases.