ORCID Profile
0000-0003-1307-9398
Current Organisations
Deakin University
,
Institute for Research and Development in Health & Social care
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Publisher: Springer Science and Business Media LLC
Date: 06-02-2018
Publisher: Veterinary World
Date: 07-2019
DOI: 10.14202/VETWORLD.2019.994-997
Abstract: Background and Aim: Estrogen activity, a central component of reproductive growth, is regulated by the receptor proteins, estrogen receptor alpha (ERα), and ER beta (ERβ) in chickens as in many other species. ERα expresses predominantly in gonads. Although the expression of ERα in embryonic gonads has been studied in detail, the expression of ERα in post-hatching male gonads has not been studied adequately. Therefore, the current research was conducted to determine the post-hatching changes in the expression of ERα in the left gonads of male chickens with age. Materials and Methods: Shaver Brown male chickens were raised and cared for according to the management guide and sacrificed at the intervals of 1, 4, and 8 weeks of age. The total RNA was extracted from the left gonads using the Trizol method and reverse transcribed using a pair of gene-specific primers. Following polymerase chain reaction lification, the expression of ERα was quantified relative to the expression of the reference gene GAPDH. Results: The results showed that ERα expression significantly increases with age at p=0.0032. However, the increment of ERα expression from week 1 to week 4 was 2.04-fold and from week 4 to week 8 was 1.39-fold, with the later age reflecting a diminishing pattern in the increment. Conclusion: These results differentiate the post-hatching ERα expression of the left gonads of male chickens increase with age but with a diminishing gradient that may support their reproductive functions in later stages of life.
Publisher: MDPI AG
Date: 27-11-2019
DOI: 10.20944/PREPRINTS201911.0345.V1
Abstract: Cysteine cathepsins, a class of proteinaceous enzymes, regulate a wide variety of metabolic processes in human including protein breakdown and turnover and immune functions. Eleven cysteine cathepsins have been identified so far and a wide array of studies related to identifying their specific functions, regulation and distribution patterns in tissues have been conducted. However, in recent past, the association of cysteine cathepsins in occurrence and progression of cancers have been identified and this has caused unrest in scientists triggering them to investigate the physiology, biochemical pathways and interactions of these cathepsins in cancer metastasis and therefore has become a noteworthy topic of intensive research. This review focusses and collects together the published work on molecular functional and structural characterization studies that have been done so far on in vitro expression of genes encoding for cysteine cathepsins in the Escherichia coli bacterial expression system. Accordingly, it was found out that all cathepsins except for cathepsins K, C, H, X and W have been expressed this way and the majority of them were found to be expressed in E. coli BL21(DE3) pLysS expression host via pET3 expression vector. In addition, it was also noted that in most of the expression studies, the substrate that was used to validate the enzymatic activity of the recombinant enzyme that was produced was a cysteine residue along with a benzyloxy-carbonyl salt. Through this review, the authors suggest that there is a very high need that all cysteine cathepsins need to be characterized both structurally and functionally on a molecular platform to better understand their interactions including the biochemical pathways. It is also momentous that the mass production of the recombinant forms of these enzymes are facilitated via expression in such bacterial expression systems and in turn, would also provide a strong platform for the development and progression of studies related to human physiology including oncological studies such as cancer metastasis. Moreover, as per biochemical features of the enzymes that could be identified, the production of efficient inhibitors or inducers as per the necessity to improve health and promote wellbeing among the mankind could be facilitated.
Publisher: Springer Science and Business Media LLC
Date: 19-08-2020
DOI: 10.1007/S12035-020-02054-6
Abstract: Neurodegeneration leading to Parkinson’s disease (PD) and Alzheimer’s disease (AD) has become a major health burden globally. Current treatments mainly target controlling symptoms and there are no therapeutics available in clinical practice to preventing the neurodegeneration or inducing neuronal repairing. Thus, the demand of novel research for the two disorders is imperative. This literature review aims to provide a collection of published work on PD and AD and current uses of endocannabinoid system (ECS) as a potential drug target for neurodegeneration. PD is frequently treated with l -DOPA and deep brain stimulation. Recent gene modification and remodelling techniques, such as CRISPR through human embryonic stem cells and induced pluripotent stem cells, have shown promising strategy for personalised medicine. AD characterised by extracellular deposits of amyloid β-senile plaques and neurofibrillary tangles of tau protein commonly uses choline acetyltransferase enhancers as therapeutics. The ECS is currently being studied as PD and AD drug targets where overexpression of ECS receptors exerted neuroprotection against PD and reduced neuroinflammation in AD. The delta-9-tetrahydrocannabinoid (Δ 9 -THC) and cannabidiol (CBD) cannabinoids of plant Cannabis sativa have shown neuroprotection upon PD and AD animal models yet triggered toxic effects on patients when administered directly. Therefore, understanding the precise molecular cascade following cannabinoid treatment is suggested, focusing especially on gene expression to identify drug targets for preventing and repairing neurodegeneration.
Publisher: Elsevier BV
Date: 2021
Publisher: BMJ
Date: 10-2019
DOI: 10.1136/BMJOPEN-2019-029332
Abstract: Worldwide, 10%–20% of children and adolescents experience mental health conditions. However, most such disorders remain undiagnosed until adolescence or adulthood. Little is known about the factors that influence mental health in children and adolescents, especially in low and middle-income countries (LMIC), where environmental threats, such as poverty and war, may affect optimal neurodevelopment. Cohort studies provide important information on risks and resilience across the life course by enabling tracking of the effects of early life environment on health during childhood and beyond. Large birth cohort studies, including twin cohorts that can be aetiologically informative, have been conducted within high-income countries but are not generalisable to LMIC. There are limited longitudinal birth cohort studies in LMIC. We sought to enhance the volume of impactful research in Sri Lanka by establishing a Centre of Excellence for cohort studies. The aim is to establish a register of infant, child and adolescent twins, including mothers pregnant with twins, starting in the districts of Colombo (Western Province) and Vavuniya (Northern Province). We will gain consent from twins or parents for future research projects. This register will provide the platform to investigate the aetiology of mental illness and the impact of challenges to early brain development on future mental health. Using this register, we will be able to conduct research that will (1) expand existing research capacity on child and adolescent mental health and twin methods (2) further consolidate existing partnerships and (3) establish new collaborations. The initiative is underpinned by three pillars: high-quality research, ethics, and patient and public involvement and engagement (PPIE). Ethical approval for this study was obtained from the Ethics Review Committee of Sri Lanka Medical Association and Keele University’s Ethical Review Panel. In addition to journal publications, a range of PPIE activities have been conducted.
Publisher: MDPI AG
Date: 27-03-2020
DOI: 10.20944/PREPRINTS202003.0405.V1
Abstract: The effect of proteolytic enzymes including Cathepsin K, a cysteine cathepsin, in onset and progression of cancers in human has been research intensive. Cathepsin K involves in many aspects and stages of cancers including apoptosis, cell proliferation, cancer immunology, inflammatory cell recruitment to tumors and aiding in the process of mobilization of normal healthy cells from their tissue compartments assisting in metastasis and angiogenesis. The objective of this review is to collect together and summarize and analyze the biochemical and physiological pathways of how cathepsin K is involved in onset and progression of cancers with more emphasis on breast and prostate cancers and cathepsin K regulated mechanisms underlying metastasis of such cancers to bones. Information for the review was gathered through published literature from global databases such as Google Scholar, PUBMED and NCBI on different studies on physiological interactions between enzymatic activity of cathepsin K with cancers and metastasis to bones. Analysis of published studies reveal that immunohistochemical studies of breast cancer cells indicate that they overexpress cathepsin K resulting in induction of aberrant mechanisms of cell signaling in breast cancers, creating a higher tendency for their metastasis to bones. Immunohistochemical, immunoprecipitation and fluorgenic assays of several studies done on the association of the same enzymatic activity on prostate cancers shows elevated levels of cathepsin K. Lesions derived from prostate cancer cell masses were observed to undergo increased bone formation and resorption levels. Such resorption levels cause secretion of biological factors promoting tumor expansion. In addition, studies indicate that Cathepsin K was observed to be a key component promoting higher bone resorption levels in patients suffering from cancer. Authors suggest that, to completely understand the association of cathepsin K on cancerous cells and their mechanism in metastasis, distributary patterns of cathepsin K in healthy human tissues needs to be extensively studied initially. It is also suggested that metastasis of breast and prostate cancers to bone could be terminated and overcome by successful production of efficient and precise inhibitory therapeutics targeting the enzymatic activity of Cathepsin K with minimum unintended adverse health effects.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Sri Lanka
No related grants have been discovered for Ruwini Cooray.