Atomic force microscopy on chromosomes, chromatin and DNA: A review

The purpose of this review is to discuss the achievements and progress that has been made in the use of atomic force microscopy in DNA related research in the last 25 years. For this review DNA related research is split up in chromosomal-, chromatin- and DNA focused research to achieve a logical flow from large- to smaller structures. The focus of this review is not only on the AFM as imaging tool but also on the AFM as measuring tool using force spectroscopy, as therein lays its greatest advantage and future. The amazing technological and experimental progress that has been made during the last 25 years is too extensive to fully cover in this review but some key developments and experiments have been described to give an overview of the evolution of AFM use from 'imaging tool' to 'measurement tool' on chromosomes, chromatin and DNA. © 2012

Generation of diverse neural cell types through direct conversion

A characteristic of neurological disorders is the loss of critical populations of cells that the body is unable to replace, thus there has been much interest in identifying methods of generating clinically relevant numbers of cells to replace those that have been damaged or lost. The process of neural direct conversion, in which cells of one lineage are converted into cells of a neural lineage without first inducing pluripotency, shows great potential, with evidence of the generation of a range of functional neural cell types both in vitro and in vivo, through viral and non-viral delivery of exogenous factors, as well as chemical induction methods. Induced neural cells have been proposed as an attractive alternative to neural cells derived from embryonic or induced pluripotent stem cells, with prospective roles in the investigation of neurological disorders, including neurodegenerative disease modelling, drug screening, and cellular replacement for regenerative medicine applications, however further investigations into improving the efficacy and safety of these methods need to be performed before neural direct conversion becomes a clinically viable option. In this review, we describe the generation of diverse neural cell types via direct conversion of somatic cells, with comparison against stem cell-based approaches, as well as discussion of their potential research and clinical application

Gene modification of mesenchymal stem cells and articular chondrocytes to enhance chondrogenesis

Current cell based treatment for articular cartilage and osteochondral defects are hampered by issues such as cellular dedifferentiation and hypertrophy of the resident or transplanted cells. The reduced expression of chondrogenic signalling molecules and transcription factors is a major contributing factor to changes in cell phenotype. Gene modification of chondrocytes may be one approach to redirect cells to their primary phenotype and recent advances in nonviral and viral gene delivery technologies have enabled the expression of these lost factors at high efficiency and specificity to regain chondrocyte function. This review focuses on the various candidate genes that encode signalling molecules and transcription factors that are specific for the enhancement of the chondrogenic phenotype and also how epigenetic regulators of chondrogenesis in the form of microRNA may also play an important role. © 2014 Saliya Gurusinghe and Padraig Strappe

Stem cell therapies for cardiovascular diseases: What does the future hold?

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality around the globe. In Australia, one in six people are affected by CVD and a total of 4.2 million people are suffering from heart disease, stroke or vascular disease. Coronary artery disease affects around 1.2 million Australians, many of whom develop chronic heart failure as a result of ischaemic cardiomyopathy. The management of CVD has evolved tremendously in the past three decades, but the majority of treatments are not curative. Pharmacotherapy, percutaneous coronary intervention and coronary bypass grafting are important therapeutic measures, but they are unable to repair the damaged myocytes or vascular structures. Stem-cell based therapies are designed to regenerate myocardium, and attenuate or reverse the remodelling of vascular structures; therefore they may fundamentally address the structural damage or cellular degeneration in CVD. For these reasons, there have been a significant number of preclinical and clinical studies conducted in this area in recent years

A comparison of RS4-type resistant starch to RS2-type resistant starch in suppressing oxidative stress in high-fat-diet-induced obese rats

The anti-obesity effects of two types of resistant starch (RS) in high-fat-diet-induced obese rats were investigated. The serum triglycerides, total cholesterol and malondialdehyde concentrations were significantly reduced, and the total antioxidant capacity, superoxide dismutase levels and glutathione peroxidase activity were increased by RS2 and RS4 consumption compared to the obesity group. A significant reduction in the serum glucose level and elevations in hepatic lipid metabolic enzyme activities were observed only for RS4 administration. Moreover, the expression levels of the fatty acid synthesis associated genes ACC and Fads1, the triglyceride synthesis and metabolism-related gene SREBP-1, the adipocyte differentiation gene PPARγ, the cholesterol synthesis associated gene HMGCR, and the gluconeogenesis associated gene GAPDH were all significantly down-regulated, whilst the lipid oxidation gene Acox1 and the liver function genes Gsta2, Nqo1, and Gclm were up-regulated in both administered groups. Additionally, RS4 performed well in up-regulating the expressions of Gsta2, Gsta3, Nqo1, and Egfr, and down-regulating LXRα, Igfbp1, and PML. RS4 exhibited great advantages in reducing oxidative stress compared with RS2

Endothelial progenitor cells and pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease characterised by lung endothelial cell dysfunction and vascular remodelling. A number of studies now suggest that endothelial progenitor cells (EPCs) may induce neovascularisation and could be a promising approach for cell based therapy for PAH. On the contrary EPCs may contribute to pulmonary vascular remodelling, particularly in end-stage pulmonary disease. This review article will provide a brief summary of the relationship between PAH and EPCs, the application of the EPCs to PAH and highlight the potential clinical application of the EPCs cell therapy to PAH. © 2014

Splice variants of the Alzheimer's disease beta-secretase, BACE1

Cleavage of the amyloid precursor protein by enzymes commonly referred to as β- and γ-secretase constitute an important process in the pathogenesis of Alzheimer's disease (AD). The regulation of this process is therefore an important subject of investigation. Numerous sources of endogenous regulation have been identified, and one of these is the relative abundance and regulation of splice variants of the β-secretase, BACE1 (β-site amyloid precursor protein cleaving enzyme 1). In this review, we will briefly discuss the main characteristics of BACE1, review the different variants of this enzyme that have been identified to date, and highlight their possible implication in AD. © 2012 Springer-Verlag Berlin Heidelberg

Functional peptides derived from rice bran proteins

Rice bran has been predominantly used in the feed industry, and only recently it has attracted greater attention in terms of human nutrition with increasing knowledge of its bioactivity. A growing interest is the analysis of physiologically active peptides derived from rice bran proteins. In this paper, the bioactivities of rice bran proteins hydrolysates and peptides are reviewed based on recent studies. These enzymatic hydrolysates and peptides exert various biological activities including antioxidant, antidiabetic, anticancer and inhibitory activity for angiotensin converting enzyme (ACE), which may ultimately prevent certain chronic diseases. Nevertheless, these functionalities can be highly associated with their corresponding structural characteristics, in particular specific sequences and molecular weight distribution. This article may facilitate the expansion of the prospective applications of the bioactive peptides in a number of fields and provide some clues of the relationship between peptides structure and functionality for future research. © 2017, © 2017 Taylor & Francis Group, LLC

Impact on the nutritional attributes of rice bran following various stabilization procedures.

Rice bran, a valuable byproduct of the rice milling process, has limitations in food industrial applications due to its instability during storage. This review summaries the methodology for stabilization and its impact on the nutritional properties of rice bran. A variety of treatments have been used and these include heat treatment, low-temperature storage, biological and chemical approaches and these will be discussed in terms of their ability to destroy/inhibit enzyme activity and improve storage performance of rice bran. More importantly, changes in the nutritional value of rice bran in terms of vitamins, polyphenols, tocopherols, flavonoids, free fatty acids caused by stabilization of rice bran will also be discussed. This review highlights the importance of appropriate design of processes for stabilization and controlling storage conditions to ensure quality of the rice bran and enhancing levels of phytochemicals in the bran for novel applications in functional foods

Suppression of dedifferentiation and hypertrophy in canine chondrocytes through lentiviral vector expression of Sox9 and induced pluripotency stem cell factors

© 2015, Springer Science+Business Media Dordrecht.Objectives: Prolonged in vitro culture of primary articular chondrocytes results in dedifferentiation to a fibroblast-like cell with reduced expression of the Sox9 transcription factor and the extracellular matrix protein collagen II. The ability to genetically-modify chondrocytes to allow both proliferation and maintenance of an articular phenotype may provide increased numbers of appropriate cells for regeneration of large cartilage defects. Results: Canine chondrocytes were expanded in monolayer culture and transduced with a lentiviral vector expressing Sox9 or in combination with a multicistronic lentiviral vector expressing the four induced pluripotency stem (iPS) cell factors, Oct4, Klf4, Sox2 and c-Myc (OSKM). 3D pellet cultures of transduced cells in the presence of TGFβ-3 revealed increased pellet size and higher levels of total glycosaminoglycan in both Sox9 and Sox9+ OSKM co-transduced chondrocytes compared to untransduced and green fluorescent protein expressing controls. Immunohistochemical detection of Sox9 and collagen II was evident in transduced cells (Sox9, OSKM, or Sox9+ OSKM) with very low levels in untransduced chondrocytes, demonstrating a dedifferentiated state (P < 0.01). The marker for chondrocyte hypertrophy, collagen X was highly expressed in Sox9 transduced chondrocytes but lower in OSKM or Sox9+ OSKM cells (P < 0.05). Conclusion: A combination of Sox9 and OSKM gene delivery to canine chondrocytes allows continuous proliferation in monolayer culture with a higher expression of col2a1 without an increase in the hypertrophy marker collagen X in 3D pellet cultures