Publications by authors named "Roan Louw"

Article Synopsis
  • Mitochondrial diseases, particularly those linked to complex I defects, currently have no cure, highlighting the need for better drug discovery methods.
  • *Induced pluripotent stem cells (iPSCs) can be genetically modified using CRISPR-Cas9, creating models like the NDUFS4 knockout (KO) that exhibit significant metabolic changes linked to mitochondrial dysfunction.
  • *Metabolomic profiling of NDUFS4 KO iPSCs revealed an increased NADH/NAD ratio, and treatment with β-lapachone improved the redox state, emphasizing the potential of iPSCs for developing new therapies for mitochondrial disorders.*
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The exposure to modifiable risk factors at young ages have been linked to premature fatal and non-fatal cardiovascular and kidney outcomes. The use of urinary metabolomics has shown strong predictability of kidney function and cardiovascular disease (CVD). We therefore determined the associations between estimated glomerular filtration rate (eGFR) and urinary metabolites in young adults with and without CVD risk factors.

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The contrasting relationships of plant and animal protein intake with blood pressure (BP) may be partially attributed to the differential non-protein (e.g., saturated fat and fibre) and amino acid (AA) compositions.

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HIV-exposed, uninfected (HEU) children present with suboptimal growth and a greater susceptibility to infection in early life when compared to HIV-unexposed, uninfected (HUU) children. The reasons for these findings are poorly understood. We used a metabolomics approach to investigate the metabolic differences between pregnant women living with HIV (PWLWH) and their HEU infants compared to the uninfected and unexposed controls.

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Background: Low-potassium intake is associated with a higher risk of type 2 diabetes and hypertension. Both conditions occur more frequently in Black populations, who also consume less potassium-rich foods.

Objectives: Using metabolomics to identify dysregulated metabolic pathways associated with low-potassium excretion may procure more accurate entry points for nutritional prevention and intervention for type 2 diabetes and hypertension.

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Some individuals are susceptible to accelerated biological ageing, resulting in premature alterations in arterial structure and function. Identifying early-onset vascular ageing characterised by arterial stiffening is vital for intervention and preventive strategies. We stratified and phenotyped healthy children (5-9 yrs) and young adults (20-30 yrs) into their vascular ageing extremes established by carotid-femoral pulse wave velocity (cfPWV) percentiles (i.

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Background And Aims: Risk factor exposure from young ages was shown to contribute to cardiovascular events - cardiac hypertrophy, which may be accompanied by an altered metabolism. To determine how early metabolic alterations associate with myocardial structural changes, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and a control group without CVD risk factors.

Methods And Results: We included healthy adults (N = 1202), aged 20-30 years, stratified based on risk factors, i.

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Article Synopsis
  • A ketogenic diet (KD) inhibits the mTOR pathway and can alleviate metabolic and inflammatory diseases, but chronic alcohol consumption may impact mTOR activity and metabolism.
  • The study aimed to evaluate the effects of a KD and alcohol on mTORC1 activity, systemic metabolism, and redox/inflammatory states in mice.
  • Results showed that a KD led to significant mTOR inhibition and reduced growth, while alcohol moderately enhanced mTOR inhibition in the context of a KD, affecting metabolic pathways and potentially protecting against bone loss due to chronic alcohol consumption.
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Various metabolomics studies have reported increased phenylalanine serum concentrations in SARS-CoV-2 positive cases and have correlated increased phenylalanine with COVID-19 severity. In this study, we report similar results based upon metabolomics analysis of serum collected from a South African cohort of adults with confirmed COVID-19. The novelty of this study is the inclusion of HIV positive cases in the African context.

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Article Synopsis
  • Animal breeding value can be influenced by the sex of the animal, with specific preferences for certain sexes in industries like horse breeding and wildlife management.
  • Ultrasonography is a common but invasive method to determine the sex of unborn animals, while molecular techniques using cell-free fetal DNA (cffDNA) show promise for less invasive and more reliable results.
  • The review discusses the current knowledge on cffDNA in animals, its diagnostic applications, limitations, and potential solutions to improve its implementation in animal husbandry and wildlife management.
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Introduction: Increased exposure to risk factors in the young and healthy contributes to arterial changes, which may be accompanied by an altered metabolism.

Objectives: To increase our understanding of early metabolic alterations and how they associate with markers of arterial stiffness, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and in a control group without CVD risk factors.

Methods: We included healthy black and white women and men (N = 1202), aged 20-30 years with a detailed CVD risk factor profile, reflecting obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036) and the control group (N = 166).

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With the global rollout of mother-to-child prevention programs for women living with HIV, vertical transmission has been all but eliminated in many countries. However, the number of children who are exposed in utero to HIV and antiretroviral therapy (ART) is ever-increasing. These children who are HIV-exposed-but-uninfected (CHEU) are now well recognized as having persistent health disparities compared to children who are HIV-unexposed-and-uninfected (CHUU).

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In Black populations excessive salt intake may exacerbate the genetic predisposition to hypertension and promote the early onset of cardiovascular disease. Ethnic differences in the interaction between sodium intake and the metabolome may play a part in hypertension and cardiovascular disease development. We determined (1) urinary amino acid and acylcarnitine profiles of young Black and White adults according to low, moderate, and high dietary salt intake, and (2) investigated the triad of salt intake, systolic blood pressure (SBP), and the associated metabolomics profile.

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Individuals with masked hypertension (MHT) have a greater risk of adverse cardiovascular outcomes than normotensive (NT) individuals. Exploring metabolomic differences between NT and MHT individuals may help provide a better understanding of the etiology of MHT. We analyzed data from 910 young participants (83% NT and 17% MHT) (mean age 24 ± 3 years) from the African-PREDICT and 210 older participants (63% NT and 37% MHT) from the SABPA (mean age 42 ± 9.

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Aim: Risk factors contributes to a dysregulated metabolism and may ultimately increase the predisposition for cardiovascular disease (CVD) development. To increase our understanding of mechanistic pathways associated with CVD risk, we profiled the urinary metabolome according to individual and clusters of CVD risk factors in comparison with a control group without any risk factors.

Methods And Results: Healthy black and white women and men ( N  = 1202), aged 20-30 years with a detailed CVD risk factor profile were included.

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Introduction: The value of metabolomics in multi-systemic mitochondrial disease research has been increasingly recognized, with the ability to investigate a variety of biofluids and tissues considered a particular advantage. Although minimally invasive biofluids are the generally favored sample type, it remains unknown whether systemic metabolomes provide a clear reflection of tissue-specific metabolic alterations.

Objectives: Here we cross-compare urine and tissue-specific metabolomes in the Ndufs4 knockout mouse model of Leigh syndrome-a complex neurometabolic MD defined by progressive focal lesions in specific brain regions-to identify and evaluate the extent of common and unique metabolic alterations on a systemic and brain regional level.

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Direct injury of mitochondrial respiratory chain (RC) complex I by Ndufs4 subunit mutations results in complex I deficiency (CID) and a progressive encephalomyopathy, known as Leigh syndrome. While mitochondrial, cytosolic and multi-organelle pathways are known to be involved in the neuromuscular LS pathogenesis, compartment-specific metabolomics has, to date, not been applied to murine models of CID. We thus hypothesized that sub-cellular metabolomics would be able to contribute organelle-specific insights to known Ndufs4 metabolic perturbations.

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The dysfunction of respiratory chain complex I (CI) is the most common form of mitochondrial disease that most often presents as Leigh syndrome (LS) in children - a severe neurometabolic disorder defined by progressive focal lesions in specific brain regions. The mechanisms underlying this region-specific vulnerability to CI deficiency, however, remain elusive. Here, we examined brain regional respiratory chain enzyme activities and metabolic profiles in a mouse model of LS with global CI deficiency to gain insight into regional vulnerability to neurodegeneration.

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Introduction: The m.3243A > G mitochondrial DNA mutation is one of the most common mitochondrial disease-causing mutations, with a carrier rate as high as 1:400. This point mutation affects the MT-TL1 gene, ultimately affecting the oxidative phosphorylation system and the cell's energy production.

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Mitochondrial diseases (MD), such as Leigh syndrome (LS), present with severe neurological and muscular phenotypes in patients, but have no known cure and limited treatment options. Based on their neuroprotective effects against other neurodegenerative diseases in vivo and their positive impact as an antioxidant against complex I deficiency in vitro, we investigated the potential protective effect of metallothioneins (MTs) in an Ndufs4 knockout mouse model (with a very similar phenotype to LS) crossed with an Mt1 overexpressing mouse model (TgMt1). Despite subtle reductions in the expression of neuroinflammatory markers GFAP and IBA1 in the vestibular nucleus and hippocampus, we found no improvement in survival, growth, locomotor activity, balance, or motor coordination in the Mt1 overexpressing Ndufs4 mice.

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Background And Aims: Increased left ventricular mass is an independent predictor for cardiovascular events, and shown to be higher in black than white populations. To gain a better understanding of early factors contributing to increased left ventricular mass in young black adults, we investigated metabolomic profiles, identified and compared metabolites that associated with left ventricular mass index in healthy black and white adults.

Methods And Results: We included normotensive black and white participants from the African-PREDICT study, with data on urinary metabolomics and echocardiography.

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Introduction: Mitochondria represent an important milieu for studying the pathogenesis of several major diseases. The need for organelle-level metabolic resolution exists, as mitochondrial/cytosolic metabolites are often diluted beyond detection limits in complex samples. Compartment-specific studies are still hindered by the lack of efficient, cost-effective fractioning methods-applicable to laboratories of all financial/analytical standing.

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Background And Aims: Black boys (6-8 years of age) were shown to have higher pulse wave velocity with potential early vascular compromise. We aimed to compare predefined urinary metabolites in black and white boys to explore associations of pulse wave velocity with these metabolites.

Methods And Results: We included 40 white and 40 black apparently healthy boys between the ages of 6 and 8 years.

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Mitochondrial disease (MD) is a group of rare inherited disorders with clinical heterogeneous phenotypes. Recent advances in next-generation sequencing (NGS) allow for rapid genetic diagnostics in patients who experience MD, resulting in significant strides in determining its etiology. This, however, has not been the case in many patient populations.

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Introduction: The analysis of limited-quantity samples remains a challenge associated with mouse models, especially for multi-platform metabolomics studies. Although inherently insensitive, the highly specific characteristics of nuclear magnetic resonance (NMR) spectroscopy make it an advantageous platform for global metabolite profiling, particularly in mitochondrial disease research.

Objectives: Show method equivalency between a well-established standard operating protocol (SOP) and our novel miniaturized H-NMR method.

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