A MicroRNA Guide for Clinicians and Basic Scientists : Background and Experimental Techniques
- Authors: Bernardo, Bianca , Charchar, Fadi , Lin, Ruby , McMullen, Julie
- Date: 2012
- Type: Text , Journal article
- Relation: Heart Lung and Circulation Vol. 21, no. 3 (2012), p. 131-142
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- Description: MicroRNAs (miRNAs) are short non-coding RNA molecules that are approximately 22 nucleotides in length. In the last 10. years, miRNA research and discovery has advanced at a rapid rate. This review provides a brief overview of the discovery and biology of miRNAs, and summarises some of the experimental techniques used for isolation, detection, target prediction, and regulation of miRNAs. We also outline experimental workflows for investigators new to the field, and discuss the diagnostic and therapeutic application of miRNAs. © 2011 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
MicroRNAs in a hypertrophic heart : From foetal life to adulthood
- Authors: Sadiq, Shahzad , Crowley, Tamsyn , Charchar, Fadi , Sanigorski, Andrew , Lewandowski, Paul
- Date: 2017
- Type: Text , Journal article
- Relation: Biological Reviews Vol. 92, no. 3 (2017), p. 1314-1331
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- Description: The heart is the first organ to form and undergoes adaptive remodelling with age. Ventricular hypertrophy is one such adaptation, which allows the heart to cope with an increase in cardiac demand. This adaptation is necessary as part of natural growth from foetal life to adulthood. It may also occur in response to resistance in blood flow due to various insults on the heart and vessels that accumulate with age. The heart can only compensate to this increase in workload to a certain extent without losing its functional architecture, ultimately resulting in heart failure. Many genes have been implicated in cardiac hypertrophy, however none have been shown conclusively to be responsible for pathological cardiac hypertrophy. MicroRNAs offer an alternative mechanism for cellular regulation by altering gene expression. Since 1993 when the function of a non-coding DNA sequence was first discovered in the model organism Caenorhabditis elegans, many microRNAs have been implicated in having a central role in numerous physiological and pathological cellular processes. The level of control these antisense oligonucleotides offer can often be exploited to manipulate the expression of target genes. Moreover, altered levels of microRNAs can serve as diagnostic biomarkers, with the prospect of diagnosing a disease process as early as during foetal life. Therefore, it is vital to ascertain and investigate the function of microRNAs that are involved in heart development and subsequent ventricular remodelling. Here we present an overview of the complicated network of microRNAs and their target genes that have previously been implicated in cardiogenesis and hypertrophy. It is interesting to note that microRNAs in both of these growth processes can be of possible remedial value to counter a similar disease pathophysiology.
MicroRNAs in essential hypertension and blood pressure regulation
- Authors: Marques, Francine , Charchar, Fadi
- Date: 2015
- Type: Text , Book chapter
- Relation: Advances in Experimental Medicine and Biology p. 215-235
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
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- Description: Unravelling the complete genetic predisposition to high blood pressure (BP) has proven to be challenging. This puzzle and the fact that coding regions of the genome account for less than 2 % of the entire human DNA support the hypothesis that mechanisms besides coding genes are likely to contribute to BP regulation. Non-coding RNAs, especially microRNAs, are emerging as key players of transcription regulation in both health and disease states. They control basic functions in virtually all cell types relevant to the cardiovascular system and, thus, a direct involvement with BP regulation is highly probable. Here we review the literature about microRNAs associated with regulation of BP and hypertension, highlighting investigations, methodology and difficulties arising in the field. These molecules are being studied for exploitation in diagnostics, prognostics and therapeutics in many diseases. There have been some studies that examined biological fl uid microRNAs as biomarkers for hypertension, but most remain inconclusive due to the small sample sizes and differences in methodological standardisation. Fewer studies have analysed tissue microRNA levels in vascular smooth muscle cells and the kidney. Others focused on the interaction between single nucleotide polymorphisms and microRNA binding sites. Studies in animals have shown that angiotensin II, high- salt diet and exercise change microRNA levels in hypertension. Treatment of spontaneously hypertensive rats with a miR-22 inhibitor and treatment of hypertensive Schlager BPH/2J mice with a miR-181a mimic decreased their BP. This supports the use of microRNAs as therapeutic targets in hypertension, and future studies should test the use of other microRNAs found in human association studies. In conclusion, there is a clear need of increased pace of human, animal and functional studies to help us understand the multifaceted roles of microRNAs as critical regulators of the development and physiology of BP. © Springer International Publishing Switzerland 2015. Funding Details: APP1052659, NHMRC, National Heart Foundation of Australia Funding Details: PF12M6785, National Heart Foundation of Australia
Development, validation, and use of a semi-quantitative food frequency questionnaire for assessing protein intake in Papua New Guinean Highlanders
- Authors: Morita, Ayako , Natsuhara, Kazumi , Tomitsuka, Eriko , Odani, Shingo , Baba, Jun , Tadokoro, Kiyoshi , Igai, Katsura , Greenhill, Andrew , Horwood, Paul , Soli, Kevin , Phuanukoonnon, Suparat , Siba, Peter , Umezaki, Masahiro
- Date: 2015
- Type: Text , Journal article
- Relation: American Journal of Human Biology Vol. 27, no. 3 (2015), p. 349-357
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- Description: Objectives: The aim of this article was to develop a semi-quantitative food frequency questionnaire (FFQ) and evaluate its validity to estimate habitual protein intake, and investigate current dietary protein intakes of Papua New Guinea (PNG) Highlanders. Methods: A 32-item FFQ was developed and tested among 135 healthy male and female volunteers. The FFQ-estimated daily total and animal protein intakes were compared with biomarkers and 3-day Weighed Food Records (WFR) by correlation analyses, Bland-Altman plot analyses and joint classification analyses. Results: The FFQ-estimated total protein intake significantly correlated with urinary nitrogen in the first morning void after adjusting urinary creatinine concentration (r=0.28, P<0.01) and the FFQ-estimated animal protein intake significantly correlated with the hair δ15N (Spearman's r=0.34, P<0.001). The limits of agreement were ±2.39 Z-score residuals for total protein intake and ±2.19 Z-score for animal protein intake, and intra-individual differences increased as protein intake increased. The classification into the same and adjacent quartiles was 66.0% for total protein intake and 73.6% for animal protein intake. Median daily total and animal protein intake estimates from the FFQ and the 3-day WFR showed a good agreement with differences of 0.2 and 4.9 g, respectively. None of the studied communities in the PNG Highlands met the biologically required protein intake; although the community closer to an urban center showed higher protein intake than the more remote communities. Conclusions: The newly developed 32-item FFQ for PNG Highlanders is applicable for evaluation of protein intake at the individual level. Am. J. Hum. Biol. 27:349-357, 2015. © 2014 Wiley Periodicals, Inc.
NAFLD in clinical practice : Can simple blood and anthropometric markers be used to detect change in liver fat measured by 1H-MRS?
- Authors: Keating, Shelley , Parker, Helen , Hickman, Ingrid , Gomersall, Sjaan , Wallen, Matthew , Coombes, Jeff , Macdonald, Graeme , George, Jacob , Johnson, Nathan
- Date: 2017
- Type: Text , Journal article
- Relation: Liver International Vol. 37, no. 12 (2017), p.1907-1915
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- Description: Background & Aims: Research in NAFLD management is commonly based on quantitative assessment of liver fat by proton-magnetic resonance spectroscopy (1H-MRS), and translation of this into clinical practice is currently limited by availability and expense. Novel steatosis biomarkers have been proposed for the prediction of liver fatness; however, whether these are suitable for detecting changes in liver fat is unknown. We aimed to determine the accuracy of these indices, and waist circumference (WC), in quantifying longitudinal change in 1H-MRS-quantified liver fat. Methods: We performed a secondary analysis using data from 97 overweight/obese adults (age: 39.7±11.5 years, body mass index: 30.7±4.4 kg/m2, liver fat: 6.0±4.8%, 65% male) who completed either an 8-week exercise or 12-week nutraceutical intervention, with varying degrees of change in liver fat. Baseline and post-intervention measures were liver fat (1H-MRS), NAFLD Liver Fat Score, Liver Fat Equation (LFE), Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), the Visceral Adiposity Index (VAI) and WC. Results: Only the change in HSI, FLI and WC was associated with change in liver fat; however, correlations were weak to moderate. There was no agreement between the LFE and 1H-MRS for detecting liver fat change. Only change in WC significantly affected change in liver fat (P<.001), and WC AUROC for the presence of steatosis was 0.65 and 0.78 for men and women respectively.Conclusions: Novel indices are limited in their ability to detect longitudinal change in liver fat. Waist circumference may offer modest utility as a surrogate to infer liver fat change with lifestyle interventions.
- Description: Background & Aims: Research in NAFLD management is commonly based on quantitative assessment of liver fat by proton-magnetic resonance spectroscopy (1H-MRS), and translation of this into clinical practice is currently limited by availability and expense. Novel steatosis biomarkers have been proposed for the prediction of liver fatness; however, whether these are suitable for detecting changes in liver fat is unknown. We aimed to determine the accuracy of these indices, and waist circumference (WC), in quantifying longitudinal change in 1H-MRS-quantified liver fat. Methods: We performed a secondary analysis using data from 97 overweight/obese adults (age: 39.7±11.5 years, body mass index: 30.7±4.4 kg/m2, liver fat: 6.0±4.8%, 65% male) who completed either an 8-week exercise or 12-week nutraceutical intervention, with varying degrees of change in liver fat. Baseline and post-intervention measures were liver fat (1H-MRS), NAFLD Liver Fat Score, Liver Fat Equation (LFE), Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), the Visceral Adiposity Index (VAI) and WC. Results: Only the change in HSI, FLI and WC was associated with change in liver fat; however, correlations were weak to moderate. There was no agreement between the LFE and 1H-MRS for detecting liver fat change. Only change in WC significantly affected change in liver fat (
Identification of tumor antigens in ovarian cancers using local and circulating tumor‐specific antibodies
- Authors: Duarte, Jessica , Quigley, Luke , Young, Anna , Hayashi, Masaru , Meeusen, Els
- Date: 2021
- Type: Text , Journal article
- Relation: International Journal of Molecular Sciences Vol. 22, no. 20 (2021), p.
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- Description: Ovarian cancers include several disease subtypes and patients often present with advanced metastatic disease and a poor prognosis. New biomarkers for early diagnosis and targeted therapy are, therefore, urgently required. This study uses antibodies produced locally in tumor-draining lymph nodes (ASC probes) of individual ovarian cancer patients to screen two separate protein microarray platforms and identify cognate tumor antigens. The resulting antigen profiles were unique for each individual cancer patient and were used to generate a 50‐antigen custom mi-croarray. Serum from a separate cohort of ovarian cancer patients encompassing four disease sub-types was screened on the custom array and we identified 28.8% of all ovarian cancers, with a higher sensitivity for mucinous (50.0%) and serous (40.0%) subtypes. Combining local and circulating antibodies with high‐density protein microarrays can identify novel, patient‐specific tumor‐associated antigens that may have diagnostic, prognostic or therapeutic uses in ovarian cancer. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Els Meeusen” is provided in this record**
Relationship between anti-DFS70 autoantibodies and oxidative stress
- Authors: Krzemień, Pawel , Kasperczyk, Slawomir , Banach, Maciej , Kasperczyk, Aleksandra , Dobrakowski, Michal , Tomasik, Tomasz , Windak, Adam , Mastej, Miroslaw , Catapano, Alberico , Ray, Kausik , Mikhailidis, Dimitri , Toth, Peter , Howard, George , Lip, Gregory , Tomaszewski, Maciej , Charchar, Fadi , Sattar, Naveed , Williams, Bryan , MacDonald, Thomas , Penson, Peter , Jóźwiak, J , Al-Shaer, B. , Andrusewicz, W. , Andrzejczuk-Rosa, M. , Anusz-Gaszewska, E. , Bagińska, A. , Balawajder, P. , Bańka, G. , Barańska-Skubisz, E. , Barbara Przyczyna, B.
- Date: 2022
- Type: Text , Journal article
- Relation: Biomarker Insights Vol. 17, no. (2022), p.
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- Description: Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes. © The Author(s) 2022. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
Stubborn exercise responders–where to next?
- Authors: Bell, Leo , Gabbett, Tim , Davis, Gregory , Wallen, Matthew , O’Brien, Brendan
- Date: 2022
- Type: Text , Journal article , Review
- Relation: Sports Vol. 10, no. 6 (2022), p.
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- Description: There is a wide variance in the magnitude of physiological adaptations after resistance or endurance training. The incidence of “non” or “poor” responders to training has been reported to represent as high as 40% of the project’s sample. However, the incidence of poor responders to training can be ameliorated with manipulation of either the training frequency, intensity, type and duration. Additionally, global non‐response to cardio‐respiratory fitness training is eliminated when evaluating several health measures beyond just the target variables as at least one or more measure improves. More research is required to determine if altering resistance training variables results in a more favourable response in individuals with an initial poor response to resistance training. Moreover, we recommend abandoning the term “poor” responders, as ultimately the magnitude of change in cardiorespiratory fitness in response to endurance training is similar in “poor” and “high” responders if the training frequency is subsequently increased. Therefore, we propose “stubborn” responders as a more appropriate term. Future research should focus on developing viable physiological and lifestyle screening tests that identify likely stubborn responders to conventional exercise training guidelines before the individual engages with training. Exerkines, DNA damage, metabolomic responses in blood, saliva and breath, gene sequence, gene expression and epigenetics are candidate biomarkers that warrant investigation into their relationship with traina-bility. Crucially, viable biomarker screening tests should show good construct validity to distinguish between different exercise loads, and possess excellent sensitivity and reliability. Furthermore “red flag” tests of likely poor responders to training should be practical to assess in clinical settings and be affordable and non‐invasive. Early identification of stubborn responders would enable op-timization of training programs from the onset of training to maintain exercise motivation and optimize the impact on training adaptations and health. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.