61 results match your criteria: "Monash Centre of Cardiovascular Research and Education in Therapeutics[Affiliation]"

Novel small-molecule compound VCP979 attenuates renal fibrosis in male rats with unilateral ureteral obstruction.

Exp Biol Med (Maywood)

February 2023

Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.

Renal fibrosis is a hallmark of chronic kidney disease, while efficient therapy against renal fibrosis is still lacking. In this study, we investigated the role of a novel small-molecule compound VCP979 on renal fibrosis and inflammation in a rat model of unilateral ureteral obstruction (UUO). One week after the UUO surgery, rats were administered VCP979 by gavage for one week, and after treatment, magnetic resonance imaging of T1rho mapping and histopathological analysis were performed to evaluate renal fibrosis and .

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Reducing White Adipose Tissue Browning Using p38α MAPK Inhibitors Ameliorates Cancer-Associated Cachexia as Assessed by Magnetic Resonance Imaging.

Nutrients

July 2022

Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing 210009, China.

Background: Up to 80% of pancreatic cancer patients suffer from cachexia. White adipose tissue (WAT) browning caused by the tumorigenicity and progression aggravates the cancer-associated cachexia (CAC). Cancer-initiated changes in the protein-38 mitogen-activated protein kinases (p38 MAPK) pathway are likely involved in the development of CAC.

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Importance: Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing.

Objective: To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA.

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The effect of dihydroceramide desaturase 1 inhibition on endothelial impairment induced by indoxyl sulfate.

Vascul Pharmacol

December 2021

Biomarker Discovery Laboratory, Baker Heart and Diabetes Research Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address:

Protein-bound uremic toxins (PBUTs) have adverse effects on vascular function, which is imperative in the progression of cardiovascular and renal diseases. The role of sphingolipids in PBUT-mediated vasculo-endothelial pathophysiology is unclear. This study assessed the therapeutic potential of dihydroceramide desaturase 1 (Des1) inhibition, the last enzyme involved in de novo ceramide synthesis, to mitigate the vascular effects of the PBUT indoxyl sulfate (IS).

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Background: Studies of insulin-like growth factor 1 (IGF-1) as a novel therapy for the treatment of cardiovascular diseases have proven promising. However, elevated IGF-1 levels have also been associated with poor patient outcomes in heart failure with reduced ejection fraction. IGF-1 therapy has additionally been shown to not be beneficial in the percutaneous coronary intervention setting.

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Sphingolipid imbalance and inflammatory effects induced by uremic toxins in heart and kidney cells are reversed by dihydroceramide desaturase 1 inhibition.

Toxicol Lett

October 2021

Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address:

Non-dialysable protein-bound uremic toxins (PBUTs) contribute to the development of cardiovascular disease (CVD) in chronic kidney disease (CKD) and vice versa. PBUTs have been shown to alter sphingolipid imbalance. Dihydroceramide desaturase 1 (Des1) is an important gatekeeper enzyme which controls the non-reversible conversion of sphingolipids, dihydroceramide, into ceramide.

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The sphingolipid de novo synthesis pathway, encompassing the sphingolipids, the enzymes and the cell membrane receptors, are being investigated for their role in diseases and as potential therapeutic targets. The intermediate sphingolipids such as dihydrosphingosine (dhSph) and sphingosine (Sph) have not been investigated due to them being thought of as precursors to other more active lipids such as ceramide (Cer) and sphingosine 1 phosphate (S1P). Here we investigated their effects in terms of collagen synthesis in primary rat neonatal cardiac fibroblasts (NCFs).

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Cardiac fibrosis and myocyte hypertrophy play contributory roles in the progression of diseases such as heart Failure (HF) through what is collectively termed cardiac remodelling. The phosphoinositide 3- kinase (PI3K), protein kinase B (Akt) and mammalian target for rapamycin (mTOR) signalling pathway (PI3K/Akt- mTOR) is an important pathway in protein synthesis, cell growth, cell proliferation, and lipid metabolism. The sphingolipid, dihydrosphingosine 1 phosphate (dhS1P) has been shown to bind to high density lipids in plasma.

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RE: Blockade of apoptosis signal-regulating kinase 1 ameliorates cardiac dysfunction in cardiorenal syndrome via enhancing angiogenesis.

Int J Cardiol

March 2021

Biomarker Discovery Laboratory, Baker Heart and Diabetes Research Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address:

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RE: ASK1, a new target in treating cardiorenal syndrome (CRS).

Int J Cardiol

October 2020

Biomarker Discovery Laboratory, Baker Heart and Diabetes Research Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address:

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Cardiac fibrosis and myocyte hypertrophy are hallmarks of the cardiac remodelling process in cardiomyopathies such as heart failure (HF). Dyslipidemia or dysregulation of lipids contribute to HF. The dysregulation of high density lipoproteins (HDL) could lead to altered levels of other lipid metabolites that are bound to it such as sphingosine-1- phosphate (S1P).

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Cardiorenal syndrome (CRS) is a multi-organ disease, encompassing heart, kidney and vascular system dysfunction. CRS is a worldwide problem, with high morbidity, mortality, and inflicts a significant burden on the health care system. The pathophysiology is complex, involving interactions between neurohormones, inflammatory processes, oxidative stress and metabolic derangements.

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Background: The New South Wales (NSW) Heart Failure Snapshot sought to provide a contemporaneous profile of patients admitted with acute heart failure. We have previously reported the baseline results, and this paper reports the 30-day and 12-month outcomes.

Methods: A prospective audit of consecutive patients admitted to 24 teaching hospitals across NSW and the Australian Capital Territory in July-August 2013 with acute heart failure.

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Effective interventions to improve the outcome of patients subjected to myocardial ischemia reperfusion (MI/R) are urgent in clinical settings. Tanshinone IIA (TSA) is reported to attenuate myocardial injury and improve ventricular remodeling post MI/R. Here, we evaluated the efficacy of AFC1 compound that is similar to TSA structure in murine MI/R models.

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Background: Risk prediction for patients with suspected coronary artery disease is complex due to the common occurrence of prior cardiovascular disease and extensive risk modification in primary care. Numerous markers have the potential to predict prognosis and guide management, but we currently lack robust 'real-world' evidence for their use.

Methods: Prospective, multicentre observational study of consecutive patients referred for elective coronary angiography.

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Molecular mechanisms of protein-bound uremic toxin-mediated cardiac, renal and vascular effects: underpinning intracellular targets for cardiorenal syndrome therapy.

Toxicol Lett

June 2019

Monash Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Baker Heart and Diabetes Research Institute, Melbourne, Victoria, Australia. Electronic address:

Cardiorenal syndrome (CRS) remains a global health burden with a lack of definitive and effective treatment. Protein-bound uremic toxin (PBUT) overload has been identified as a non-traditional risk factor for cardiac, renal and vascular dysfunction due to significant albumin-binding properties, rendering these solutes non-dialyzable upon the state of irreversible kidney dysfunction. Although limited, experimental studies have investigated possible mechanisms in PBUT-mediated cardiac, renal and vascular effects.

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The role of dihydrosphingolipids in disease.

Cell Mol Life Sci

March 2019

Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Dihydrosphingolipids refer to sphingolipids early in the biosynthetic pathway that do not contain a C4-trans-double bond in the sphingoid backbone: 3-ketosphinganine (3-ketoSph), dihydrosphingosine (dhSph), dihydrosphingosine-1-phosphate (dhS1P) and dihydroceramide (dhCer). Recent advances in research related to sphingolipid biochemistry have shed light on the importance of sphingolipids in terms of cellular signalling in health and disease. However, dihydrosphingolipids have received less attention and research is lacking especially in terms of their molecular mechanisms of action.

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Association of expression of ZNF606 gene from monocytes with the risk of coronary artery disease.

Clin Biochem

September 2018

Department of Cardiology, Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China; Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China; Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong 510282, China; Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, Guangdong 510282, China. Electronic address:

Aim: Messenger RNAs (mRNAs) play an important role in the pathogenesis of coronary artery disease (CAD). We evaluated the association of selected increase in mRNAs from monocytes with the risk of CAD.

Methods: Chip data (GSE9820) retrieved from Gene Expression Omnibus (GEO) was re-analyzed, and the selected candidate genes, meeting specific conditions, were up-regulated and verified for specific biomarkers of CAD within a prospective cohort study that recruited 194 individuals and subdivided into two groups: group Non-CAD (GN), n = 68 and group CAD (GC), n = 126.

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Background: Cross correlation analysis (CCA) using tissue Doppler imaging has been shown to be associated with outcome after cardiac resynchronization therapy (CRT) in patients with heart failure (HF) with wide QRS. However, its significance in patients with narrow QRS treated with CRT is unknown.

Objectives: The aim of the current study was to investigate the association of mechanical activation delay by CCA with study outcome in patients with HF enrolled in the EchoCRT trial.

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Inhibition of Apoptosis Signal-Regulating Kinase 1 Attenuates Myocyte Hypertrophy and Fibroblast Collagen Synthesis.

Heart Lung Circ

March 2019

Monash Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic, Australia; Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Background: Cardiac remodelling is a dynamic process whereby structural and functional changes occur within the heart in response to injury or inflammation. Recent studies have demonstrated reactive oxygen species sensitive MAPK, apoptosis signal-regulating kinase 1 (ASK1) plays a critical role in cardiac remodelling. This study aims to determine the effectiveness of small molecule ASK1 inhibitors on these processes and their therapeutic potential.

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Aims: We aimed to assess the cost effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of individuals with chronic heart failure and reduced-ejection fraction (HFrEF) from the perspective of the Swiss health care system.

Methods: The cost-effectiveness analysis was implemented as a lifelong regression-based cohort model. We compared sacubitril/valsartan with enalapril in chronic heart failure patients with HFrEF and New York-Heart Association Functional Classification II-IV symptoms.

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Objectives: This study sought to examine the safety of the dipeptidyl peptidase-4 inhibitor, vildagliptin, in patients with heart failure and reduced ejection fraction.

Background: Many patients with type 2 diabetes mellitus have heart failure and it is important to know about the safety of new treatments for diabetes in these individuals.

Methods: Patients 18 to 85 years of age with type 2 diabetes and heart failure (New York Heart Association functional class I to III and left ventricular ejection fraction [LVEF] <0.

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Objectives: This study aimed to assess analgesia provided by acupuncture, alone or in combination with pharmacotherapy, to patients presenting to emergency departments with acute low back pain, migraine or ankle sprain.

Design: A pragmatic, multicentre, randomised, assessor-blinded, equivalence and non-inferiority trial of analgesia, comparing acupuncture alone, acupuncture plus pharmacotherapy, and pharmacotherapy alone for alleviating pain in the emergency department. Setting, participants: Patients presenting to emergency departments in one of four tertiary hospitals in Melbourne with acute low back pain, migraine, or ankle sprain, and with a pain score on a 10-point verbal numerical rating scale (VNRS) of at least 4.

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Use of combined oral contraceptives (COCs) by women increases the risk of venous thromboembolism (VTE), which can have a major impact on an individuals' quality of life. VTE is also associated with an increase in healthcare costs. Our aim was to systematically review cost-effectiveness analyses (CEAs) considering any screening for risk of VTE in women using COCs.

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