Qigong for the Management of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2MD) is a complex, chronic, metabolic disease with hyperglycemia arising from insulin resistance, progressive pancreatic beta cell failure, insufficient insulin secretion and increased hepatic glucose output. In the Chinese medicine theory, T2DM is often referred to as a form of Xiao Ke (消渴) or “wasting‐thirst disorder.” Genetic, dietary, lifestyle and environmental factors play a role in T2DM. People with a family history of diabetes or who are obese are at the highest risk of developing the disease. T2DM is often associated with hypertension, dyslipidemia and atherosclerosis and if not managed can lead to complications including cerebrovascular accident, peripheral vascular disease and nephropathy. T2DM can be well managed with biomedical and Chinese medicine treatment approaches. Lifestyle changes including appropriate diet and exercise are paramount in managing T2DM. Regular Qigong practice can be a beneficial part of one\u27s exercise routine for T2DM self‐care. Qigong exercise has shown promising results in clinical experience and in randomized, controlled pilot studies for affecting aspects of T2DM including positive associations between participation in Qigong and blood glucose, triglycerides, total cholesterol, weight, BMI and insulin resistance. This chapter looks at how traditional Chinese medicine (TCM) views diabetes as well as new understandings of how Qigong can support the management of T2DM

Role of genomic imprinting in cerebral cortex development

Genomic imprinting is an epigenetic process that leads to parent of origin-specific gene expression in a subset of genes. Imprinted genes are essential for brain development, and deregulation of imprinting is associated with neurodevelopmental diseases and the pathogenesis of psychiatric disorders. However, the cell-type specificity of imprinting at single cell resolution, and how imprinting and thus gene dosage regulates neuronal circuit assembly is still largely unknown. Here, MADM (Mosaic Analysis with Double Markers) technology was employed to assess genomic imprinting at single cell level. By visualizing MADM-induced uniparental disomies (UPDs) in distinct colors at single cell level in genetic mosaic animals, this experimental paradigm provides a unique quantitative platform to systematically assay the UPD-mediated imbalances in imprinted gene expression at unprecedented resolution. An experimental pipeline based on FACS, RNA-seq and bioinformatics analysis was established and applied to systematically map cell-type-specific ‘imprintomes’ in the mouse brain. The results revealed that parental-specific expression of imprinted genes per se is rarely cell-type-specific even at the individual cell level. Conversely, when we extended the comparison to downstream responses resulting from imbalanced imprinted gene expression, we discovered an unexpectedly high degree of cell-type specificity. Furthermore, we determined a novel function of genomic imprinting in cortical astrocyte production and in olfactory bulb (OB) granule cell generation. These results suggest important functional implication of genomic imprinting for generating cell-type diversity in the brain. In addition, MADM provides a powerful tool to study candidate genes by concomitant genetic manipulation and fluorescent labelling of single cells. MADM-based candidate gene approach was utilized to identify potential imprinted genes involved in the generation of cortical astrocytes and OB granule cells. We investigated p57Kip2, a maternally expressed gene and known cell cycle regulator. Although we found that p57Kip2 does not play a role in these processes, we detected an unexpected function of the paternal allele previously thought to be silent. Finally, we took advantage of a key property of MADM which is to allow unambiguous investigation of environmental impact on single cells. The experimental pipeline based on FACS and RNA-seq analysis of MADM-labeled cells was established to probe the functional differences of single cell loss of gene function compared to global loss of function on a transcriptional level. With this method, both common and distinct responses were isolated due to cell-autonomous and non-autonomous effects acting on genotypically identical cells. As a result, transcriptional changes were identified which result solely from the surrounding environment. Using the MADM technology to study genomic imprinting at single cell resolution, we have identified cell-type-specific gene expression, novel gene function and the impact of environment on single cell transcriptomes. Together, these provide important insights to the understanding of mechanisms regulating cell-type specificity and thus diversity in the brain

Cultural constructions of illness : the client and practitioner perspectives of traditional Chinese medicine. Perth Western Australia

An increased use of Complementary and alternate health care practices (CAM) and under which TCM is found assumed, is found in overseas countries and has become increasingly popular among Australian consumer. There has been a considerably increase in the consumer use of TCM over the past decade, but little is understood on the practice of the clinical encounter in TCM explained from the context within a clinic in western society.Investigation was made on how social and cultural processes have shaped people’s acceptance of TCM as a form of complementary health. Drawing from an ethnographic focus, the study explores the practice of TCM in several clinic settings in Perth. Attention is paid to the ways in which notions of health and illness are constructed by clients and practitioners. This study examined the interactions found in the process of ‘Kanbing’ from a TCM practice in Perth, Western Australia in order to understand how health practices are shaped by cultural and social processes. From an anthropological perspective, the ethnography of this study was guided an extended contact with the everyday clinical context of TCM, facilitated through participant observation, interviews with clients and practitioners and case study analysis. Interviews revealed perspectives from clients of non-Asian backgrounds to record the lived experiences of the encounters between the practitioner and client of TCM in the clinic. Participant observation took place over a two year period from February 2002 to March 2003 with further follow up work in the field conducted at intervals throughout 2004 and 2006 to gain additional data.The client centred interrelationships between practitioners of TCM, clients, and their perceptions, formed part of the interpretative process that informed the understanding of the cultural context from how an illness is described and explained through the process of Kanbing. My research was drawn from the reality of the encounter within the clinical context through participant observation within two western clinics of TCM. Thus the study makes a contribution to anthropology on the understanding of the structure and meaning found within the practice of traditional Chinese medicine in Australia

Why is Qi-Invigorating Therapy in Chinese Medicine Suitable for Mitochondrial Diseases? A Bioenergetic Perspective

The central player in bioenergetics is the mitochondrion. Bioenergetic dysfunction is emerging as a cornerstone for understanding the pathophysiology of mitochondrial diseases. Accompanying the depth of mitochondrial research and the rapid development of mitochondrial medicine, however, is rapid amplification of the number of mitochondrial diseases; mitochondrial dysfunction would undermine the function of cells, tissues, and organs, thereby causing cancer, diabetes, obesity, strokes, cardiovascular diseases, neurodegenerative diseases, and ageing, etc. Currently, there are no effective treatments; Western medicine is in crisis when it comes to mitochondrial diseases

CHANGES IN eIF2α PHOSPHORYLATION IN RESPONSE TO NUTRIENT DEFICIENCY AND OTHER STRESSORS IN FISH

The present study investigates the response of two teleost species to stressors as measured by phosphorylation of the α-subunit of the translational initiation factor, eIF2. The phosphorylation of the translational initiation factor, eIF2, on its α-subunit is an adaptive response to a variety of stressors in eukaryotes from protists to vertebrates. There are four eIF2α-specific kinases in most vertebrates, GCN2, PERK, PKR and HRI, each of which can be activated by different stressors. Two of these eIF2α-kinases, GCN2 and PERK, respond to changes in nutritional status. It was of particular interest to determine whether eIF2α phosphorylation can be used as an early marker to evaluate diets in fish. However, eIF2α phosphorylation could also be of use in monitoring other stressors of fish in aquaculture. The increase in global aquaculture production of fish has increased interest in the optimization of fish diets and health to increase production and sustainability. Studies were initiated in a zebrafish Danio rerio cell line, ZFL cells, to lay the groundwork for looking at eIF2α phosphorylation in fish and in species of more interest to aquaculture. All the eIF2α-kinases are present in the zebrafish genome and are expressed in ZFL cells. Two forms of eIF2α are expressed in ZFL cells, eIF2α-a and eIF2α-b, with eIF2α-b transcripts ~5-fold higher than those of eIF2α-a. The two gene products are 96 % identical at the amino acid level and are identical at the phosphorylation and kinase docking sites. Phosphorylation of eIF2α in ZFL cells is increased by a variety of agents/conditions; starvation, leucinol, endoplasmic reticulum stress, poly(I)poly(C) and N-methylprotoporphyrin, consistent with activation of the eIF2α kinases GCN2, PERK, PKR and HRI, respectively. Application of the same analyses to a new cell line from a marine fish, cobia Rachycentron canadum, shows that these cells are also responsive to activators of GCN2 and PERK. Cloning of eIF2α cDNA from cobia has shown close identity to the zebrafish eIF2αs. Although cobia has two eIF2α transcripts, the coding sequence of each is identical. Preliminary studies have shown that in cobia juveniles, diet, probiotics and water temperature all affect the phosphorylation state of eIF2α

Investigating the pathological mechanism of neuropathy in POEMS syndrome

POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin disorder) is a rare disease characterised by an inflammatory polyneuropathy an a monoclonal plasma cell dyscrasia. POEMS syndrome causes some of the most significant disability and mortality of any inflammatory neuropathy. The pathophysiology is unknown but recognised to be cytokine mediated, notably driven by vascular endothelial growth factor, however little is known about the other mediators at play. This thesis collates clinical data from the largest POEMS cohorti in Europe in order to study the characteristic disease features, optimise therapies and identify factors that influence outcome. Utilising our POEMS sample biobank, we carry out highly sensitive immunoassays to study the cytokines released in POEMS syndrome, and whether they correlate with disease activity. We go on to study the proteome of POEMS syndrome through mass spectrometry, to uncover the biological pathway involved and identify a number of novel, potentially pathogenic molecules. Fluid biomarkers of neuropathy in POEMS syndrome and related neuropathies are additionally explored. The development and optimisation of a homebrew immunoassay for peripherin, a peripheral nerve specific biomarker is detailed. The potential clinical utility of this biomarker is compared against that of serum neurofilament light. Finally, we attempt to model the neuropathogenesis of POEMS neuropathy in vitro using a novel human induced pleuripotent stem cell derived neuronal culture system