108 results on '"Johnson, Rabia"'
Search Results
2. Wastewater monitoring can anchor global disease surveillance systems
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Ahmed, Warish, Amman, Fabian, Aruna, Olusola, Badilla-Aguilar, Andrei, Bar-Or, Itay, Bergthaler, Andreas, Bines, Julie E, Bivins, Aaron W, Boehm, Alexandria B, Brault, Jean-Martin, Burnet, Jean-Baptiste, Chapman, Joanne R, Chaudhuri, Angela, de Roda Husman, Ana Maria, Delatolla, Robert, Dennehy, John J, Diamond, Megan Beth, Donato, Celeste, Duizer, Erwin, Egwuenu, Abiodun, Erster, Oran, Fatta-Kassinos, Despo, Gaggero, Aldo, Gilpin, Deirdre F, Gilpin, Brent J, Graber, Tyson E, Green, Christopher A, Handley, Amanda, Hewitt, Joanne, Holm, Rochelle H, Insam, Heribert, Johnson, Marc C, Johnson, Rabia, Jones, Davey L, Julian, Timothy R, Jyothi, Asha, Keshaviah, Aparna, Kohn, Tamar, Kuhn, Katrin G, La Rosa, Giuseppina, Lesenfants, Marie, Manuel, Douglas G, D'Aoust, Patrick M, Markt, Rudolf, McGrath, John W, Medema, Gertjan, Moe, Christine L, Murni, Indah Kartika, Naser, Humood, Naughton, Colleen C, Ogorzaly, Leslie, Oktaria, Vicka, Ort, Christoph, Karaolia, Popi, Patel, Ekta H, Paterson, Steve, Rahman, Mahbubur, Rivera-Navarro, Pablo, Robinson, Alex, Santa-Maria, Monica C, Scarpino, Samuel V, Schmitt, Heike, Smith, Theodore, Stadler, Lauren B, Stassijns, Jorgen, Stenico, Alberta, Street, Renee A, Suffredini, Elisabetta, Susswein, Zachary, Trujillo, Monica, Wade, Matthew J, Wolfe, Marlene K, Yakubu, Habib, Zanoli Sato, Maria Ines, and Diamond, Megan B
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- 2023
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3. Tracking the circulating SARS-CoV-2 variant of concern in South Africa using wastewater-based epidemiology
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Johnson, Rabia, Sharma, Jyoti R., Ramharack, Pritika, Mangwana, Noluxabiso, Kinnear, Craig, Viraragavan, Amsha, Glanzmann, Brigitte, Louw, Johan, Abdelatif, Nada, Reddy, Tarylee, Surujlal-Naicker, Swastika, Nkambule, Sizwe, Mahlangeni, Nomfundo, Webster, Candice, Mdhluli, Mongezi, Gray, Glenda, Mathee, Angela, Preiser, Wolfgang, Muller, Christo, and Street, Renee
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- 2022
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4. The determination of the effect(s) of solute carrier family 22-member 2 (SLC22A2) haplotype variants on drug binding via molecular dynamic simulation systems
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Abrahams-October, Zainonesa, Johnson, Rabia, Benjeddou, Mongi, and Cloete, Ruben
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- 2022
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5. The effect of adiponectin in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the potential role of polyphenols in the modulation of adiponectin signaling
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Shabalala, Samukelisiwe C., Dludla, Phiwayinkosi V., Mabasa, Lawrence, Kappo, Abidemi P., Basson, Albertus K., Pheiffer, Carmen, and Johnson, Rabia
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- 2020
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6. Diet-induced hypothalamic dysfunction and metabolic disease, and the therapeutic potential of polyphenols
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Samodien, Ebrahim, Johnson, Rabia, Pheiffer, Carmen, Mabasa, Lawrence, Erasmus, Melisse, Louw, Johan, and Chellan, Nireshni
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- 2019
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7. Aspalathin ameliorates doxorubicin-induced oxidative stress in H9c2 cardiomyoblasts
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Shabalala, Samukelisiwe C., Dludla, Phiwayinkosi V., Muller, Christo J.F., Nxele, Xolisa, Kappo, Abidemi P., Louw, Johan, and Johnson, Rabia
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- 2019
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8. N-Acetyl cysteine ameliorates hyperglycemia-induced cardiomyocyte toxicity by improving mitochondrial energetics and enhancing endogenous Coenzyme Q9/10 levels
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Dludla, Phiwayinkosi V., Orlando, Patrick, Silvestri, Sonia, Mazibuko-Mbeje, Sithandiwe E., Johnson, Rabia, Marcheggiani, Fabio, Cirilli, Ilenia, Muller, Christo J.F., Louw, Johan, Obonye, Nnini, Nyawo, Thembeka, Nkambule, Bongani B., and Tiano, Luca
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- 2019
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9. Afriplex GRTTM extract attenuates hepatic steatosis in an in vitro model of NAFLD.
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Gabuza, Kwazi, Mabuda, Thendo I., Patel, Oelfah, Khuboni, Noxolo, van Aarde, Ruzayda, Riedel, Sylvia, Sangweni, Nonhlakanipho F., Windvogel, Shantal, Johnson, Rabia, and Muller, Christo J. F.
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FATTY liver ,NON-alcoholic fatty liver disease ,VITAMIN E ,OXIDATIVE stress ,LIVER cells ,INSULIN ,PROTEIN expression ,OLEIC acid - Abstract
Background: Currently, it is acknowledged that vitamin E, insulin sensitizers and anti-diabetic drugs are used to manage non-alcoholic fatty liver disease (NAFLD), however, these therapeutic interventions harbour adverse side effects. Pioglitazone, an anti-diabetic drug, is currently the most effective therapy to manage NAFLD. The use of natural medicines is widely embraced due to the lack of evidence of their negative side effects. Rooibos has been previously shown to decrease inflammation and oxidative stress in experimental models of diabetes, however, this is yet to be explored in a setting of NAFLD. This study was aimed at investigating the effects of an aspalathin-rich green rooibos extract (Afriplex GRT
TM ) against markers of hepatic oxidative stress, inflammation and apoptosis in an in vitro model of NAFLD. Methods: Oleic acid [1 mM] was used to induce hepatic steatosis in C3A liver cells. Thereafter, the therapeutic effect of Afriplex GRTTM , with or without pioglitazone, was determined by assessing its impact on cell viability, changes in mitochondrial membrane potential, intracellular lipid accumulation and the expression of genes and proteins (ChREBP, SREBF1, FASN, IRS1, SOD2, Caspase-3, GSTZ1, IRS1 and TNF-α) that are associated with the development of NAFLD. Results: Key findings showed that Afriplex GRTTM added to the medium alone or combined with pioglitazone, could effectively block hepatic lipid accumulation without inducing cytotoxicity in C3A liver cells exposed oleic acid. This positive outcome was consistent with effective regulation of genes involved in insulin signaling, as well as carbohydrate and lipid metabolism (IRS1, SREBF1 and ChREBP). Interestingly, in addition to reducing protein levels of an inflammatory marker (TNF-α), the Afriplex GRTTM could ameliorate oleic acid-induced hepatic steatotic damage by decreasing the protein expression of oxidative stress and apoptosis related markers such as GSTZ1 and caspase-3. Conclusion: Afriplex GRTTM reduced hepatic steatosis in oleic acid induced C3A liver cells by modulating SREBF1, ChREBP and IRS-1 gene expression. The extract may also play a role in alleviating inflammation by reducing TNF-α expression, suggesting that additional experiments are required for its development as a suitable therapeutic option against NAFLD. Importantly, further research is needed to explore its antioxidant role in this model. [ABSTRACT FROM AUTHOR]- Published
- 2024
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10. No Association Between AGT Gene Polymorphisms with Hypertension in a South African Population.
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Sharma, Jyoti Rajan, Fokkens, Hannah, Laubscher, Ria, Apalata, Teke Ruffin, Nomatshila, Sibusiso Cyprian, Alomatu, Samuel Yao, Strijdom, Hans, and Johnson, Rabia
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SOUTH Africans ,GENETIC polymorphisms ,SINGLE nucleotide polymorphisms ,HYPERTENSION ,LOW-income countries - Abstract
Purpose: Hypertension is a leading cause of cardiovascular-related morbidity and mortality worldwide, with a prevalence increasing at an alarming rate in both middle- and low-income countries. Various environmental and genetic factors have been attributed to play a significant role in the increasing prevalence of hypertension. Single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene are reported to have a significant association with hypertension; however, there are limited studies done on South African populations. Therefore, this case–control study aimed to investigate the association between AGT SNPs (rs2004776, rs3789678, rs5051 and rs7079) with hypertension in a study population of isiXhosa-speaking participants from the Eastern Cape Province in South Africa. Materials and Methods: The SNPs were genotyped in 250 hypertensive cases and 237 normotensive controls, using TaqMan genotyping assays. Results: For the SNP rs2004776, the frequency of CC genotype (18.4%) and C allele (44%) in hypertensive cases showed no significant differences (p = 0.52, χ 2 = 1.32), when compared to the normotensive control group (CC: 19.8% and C allele: 43%). Similar results were obtained for the genotypic and allelic frequencies between hypertensive cases and normotensive controls for rs3789678 (p = 0.88, χ 2=0.26) and rs5051 (p = 0.57, χ 2=1.12), and rs7079 (p = 0.33, χ 2=2.23). These findings demonstrate that there were no significant associations between the SNPs rs2004776, rs3789678, rs7079, rs5051 with hypertension in our study population. Conclusion: These findings suggest that AGT gene polymorphisms are not associated with the development of hypertension in the studied population. The present study represents the first genetic report to investigate the AGT gene polymorphisms with hypertension in an isiXhosa-speaking South African population. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Identification of potential biomarkers for predicting the early onset of diabetic cardiomyopathy in a mouse model
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Johnson, Rabia, Nxele, Xolisa, Cour, Martin, Sangweni, Nonhlakanipho, Jooste, Tracey, Hadebe, Nkanyiso, Samodien, Ebrahim, Benjeddou, Mongi, Mazino, Mikateko, Louw, Johan, and Lecour, Sandrine
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- 2020
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12. Narzędzia pomiarowe i przydatność analizy włosów w przesiewowej ocenie przestrzegania zaleceń dotyczących przyjmowania leków hipotensyjnych.
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Sharma, Jyoti R., Dludla, Phiwayinkosi V., Dwivedi, Girish, and Johnson, Rabia
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Copyright of Heart & Vascular Diseases / Choroby Serca & Naczyn is the property of VM Medica-VM Group (Via Medica) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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13. Molecular epidemiology of SARS-CoV-2 in Northern South Africa: wastewater surveillance from January 2021 to May 2022
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Mbang Tambe, Lisa Arrah, Mathobo, Phindulo, Matume, Nontokozo D., Munzhedzi, Mukhethwa, Edokpayi, Joshua Nosa, Viraragavan, Amsha, Glanzmann, Brigitte, Tebit, Denis M., Mavhandu-Ramarumo, Lufuno Grace, Street, Renee, Johnson, Rabia, Kinnear, Craig, and Bessong, Pascal Obong
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- 2023
14. Molecular basis of the anti-hyperglycemic activity of RA-3 in hyperlipidemic and streptozotocin-induced type 2 diabetes in rats
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Mabhida, Sihle Ephraim, Johnson, Rabia, Ndlovu, Musawenkosi, Louw, Johan, Opoku, Andrew, and Mosa, Rebamang Anthony
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- 2019
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15. Doxorubicin-Induced Cardiomyopathy: A Preliminary Study on the Cardioprotective Benefits of 7-Hydroxyflavanone.
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Sangweni, Nonhlakanipho F., Gabuza, Kwazi, van Aarde, Ruzayda, Mabasa, Lawrence, van Vuuren, Derick, Huisamen, Barbara, Barry, Reenen, and Johnson, Rabia
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DOXORUBICIN ,CARDIOMYOPATHIES ,BIOENERGETICS ,MEMBRANE potential ,MITOCHONDRIAL membranes ,CARDIOTONIC agents - Abstract
The therapeutic properties of flavonoids are reported to offer cardioprotective benefits against doxorubicin (Dox)-induced cardiotoxicity (DIC). In the current study, we aimed to investigate the prophylactic properties of 7-hydroxyflavanone (7H), a flavonoid with antioxidative properties, against DIC. An in vitro model of DIC was established by exposing H9c2 cardiomyoblasts to Dox for 6 days. Similarly, cells were also co-treated with 7H to assess its ability to mitigate DIC. The data obtained indicate that 7H, as a co-treatment, alleviates Dox-induced oxidative stress by enhancing total glutathione content (p ≤ 0.001) and superoxide dismutase activity (p ≤ 0.001) whilst decreasing ROS (p ≤ 0.001), malondialdehyde production (p ≤ 0.001) and the secretion of interleukin-6 (p ≤ 0.001). The data also showed an improvement in mitochondrial function as shown via enhanced bioenergetics, mitochondrial membrane potential, and PGC1-alpha (p ≤ 0.05) and pAMPK (p ≤ 0.001) expression. The cardioprotective potential of 7H was further highlighted by its ability attenuate Dox-induced caspase 3/7 activity (p ≤ 0.001), apoptosis (p ≤ 0.001) and necrosis (p ≤ 0.05). In conclusion, our findings demonstrated the cardioprotective benefits of 7H and thus suggests that it could be a suitable candidate cardioprotective agent against DIC. [ABSTRACT FROM AUTHOR]
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- 2023
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16. A Lanosteryl triterpene from Protorhus longifolia augments insulin signaling in type 1 diabetic rats
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Mabhida, Sihle Ephraim, Johnson, Rabia, Ndlovu, Musawenkosi, Sangweni, Nonhlakanipho Felicia, Louw, Johan, Opoku, Andrew, and Mosa, Rebamang Anthony
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- 2018
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17. Age-dependent development of left ventricular wall thickness in type 2 diabetic (db/db) mice is associated with elevated low-density lipoprotein and triglyceride serum levels
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Dludla, Phiwayinkosi V., Essop, M. Faadiel, Gabuza, Kwazi B., Muller, Christo J. F., Louw, Johan, and Johnson, Rabia
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- 2017
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18. Effects of fermented rooibos (Aspalathus linearis) on adipocyte differentiation
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Sanderson, Micheline, Mazibuko, Sithandiwe E., Joubert, Elizabeth, de Beer, Dalene, Johnson, Rabia, Pheiffer, Carmen, Louw, Johan, and Muller, Christo J.F.
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- 2014
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19. Wastewater-based SARS-CoV-2 airport surveillance: key trends at the Cape Town International Airport.
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Nkambule, Sizwe, Johnson, Rabia, Mathee, Angela, Mahlangeni, Nomfundo, Webster, Candice, Horn, Suranie, Mangwana, Noluxabiso, Dias, Stephanie, Sharma, Jyoti Rajan, Ramharack, Pritika, Louw, Johan, Reddy, Tarylee, Surujlal-Naicker, Swastika, Mdhluli, Mongezi, Gray, Glenda, Muller, Christo, and Street, Renee
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INTERNATIONAL airports , *COVID-19 pandemic , *SARS-CoV-2 , *COVID-19 , *AIRPORTS , *POLYMERASE chain reaction , *AIR travel , *BIOSECURITY - Abstract
Monitoring of SARS-CoV-2 RNA in wastewater has revealed the role of mobility in the transmission of coronavirus disease (COVID-19), and the surveillance of airport wastewater in cities across the world has demonstrated how travel entry points can give an indication of trends in transmission. This study undertook wastewater surveillance at the Cape Town International Airport (CTIA) to assess the use of a WBE approach to provide supplementary information on the presence of COVID-19 at a key air travel entry point in South Africa. Grab wastewater samples (n = 55) were collected from the CTIA wastewater pump station and analysed using quantitative real-time polymerase chain reaction (qRT-PCR) method. The study found a correlation between the wastewater data and clinical cases reported in the City of Cape Town during various time periods and during the peak of a COVID-19 wave. Highly elevated viral loads in the wastewater were observed at times there was increased mobility through the airport. The study also revealed elevated viral load levels at the airport despite the stricter restrictions and through the lower restrictions. The study findings indicate wastewater surveillance and airports can provide supplementary information to airport authorities to assess the impacts of imposed travel restrictions. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Aspalathin, a dihydrochalcone C-glucoside, protects H9c2 cardiomyocytes against high glucose induced shifts in substrate preference and apoptosis
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Johnson, Rabia, Dludla, Phiwayinkosi, Joubert, Elizabeth, February, Faghri, Mazibuko, Sithandiwe, Ghoor, Samira, Muller, Christo, and Louw, Johan
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- 2016
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21. Using Wastewater Surveillance to Compare COVID-19 Outbreaks during the Easter Holidays over a 2-Year Period in Cape Town, South Africa.
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Mahlangeni, Nomfundo, Street, Renée, Horn, Suranie, Mathee, Angela, Mangwana, Noluxabiso, Dias, Stephanie, Sharma, Jyoti Rajan, Ramharack, Pritika, Louw, Johan, Reddy, Tarylee, Surujlal-Naicker, Swastika, Nkambule, Sizwe, Webster, Candice, Mdhluli, Mongezi, Gray, Glenda, Muller, Christo, and Johnson, Rabia
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SARS-CoV-2 ,COVID-19 pandemic ,EASTER ,SEWAGE disposal plants - Abstract
Wastewater surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown to be an important approach to determine early outbreaks of infections. Wastewater-based epidemiology (WBE) is regarded as a complementary tool for monitoring SARS-CoV-2 trends in communities. In this study, the changes in the SARS-CoV-2 RNA levels in wastewater during Easter holidays in 2021 and 2022 in the City of Cape Town were monitored over nine weeks. Our findings showed a statistically significant difference in the SARS-CoV-2 RNA viral load between the study weeks over the Easter period in 2021 and 2022, except for study week 1 and 4. During the Easter week, 52% of the wastewater treatment plants moved from the lower (low viral RNA) category in 2021 to the higher (medium to very high viral RNA) categories in 2022. As a result, the median SARS-CoV-2 viral loads where higher during the Easter week in 2022 than Easter week in 2021 (p = 0.0052). Mixed-effects model showed an association between the SARS-CoV-2 RNA viral loads and Easter week over the Easter period in 2021 only (p < 0.01). The study highlights the potential of WBE to track outbreaks during the holiday period. [ABSTRACT FROM AUTHOR]
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- 2023
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22. Aspalathin improves glucose and lipid metabolism in 3T3-L1 adipocytes exposed to palmitate
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Mazibuko, Sithandiwe E., Joubert, Elizabeth, Johnson, Rabia, Louw, Johan, Opoku, Andrew R., and Muller, Christo J. F.
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- 2015
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23. Delineating the Spread and Prevalence of SARS-CoV-2 Omicron Sublineages (BA.1-BA.5) and Deltacron Using Wastewater in the Western Cape, South Africa.
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Johnson, Rabia, Mangwana, Noluxabiso, Sharma, Jyoti R, Muller, Christo J F, Malemela, Kholofelo, Mashau, Funanani, Dias, Stephanie, Ramharack, Pritika, Kinnear, Craig, Glanzmann, Brigitte, Viraragavan, Amsha, Louw, Johan, Surujlal-Naicker, Swastika, Nkambule, Sizwe, Webster, Candice, Mdhluli, Mongezi, Gray, Glenda, Mathee, Angela, Preiser, Wolfgang, and Vorster, Alvera
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This study was one of the first to detect Omicron sublineages BA.4 and BA.5 in wastewater from South Africa. Spearman rank correlation analysis confirmed a strong positive correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA in wastewater samples and clinical cases (r = 0.7749, P < .0001). SARS-CoV-2 viral load detected in wastewater, resulting from the Delta-driven third wave, was significantly higher than during the Omicron-driven fourth wave. Whole-genome sequencing confirmed presence of Omicron lineage defining mutations in wastewater with the first occurrence reported 23 November 2021 (BA.1 predominant). The variant spread rapidly, with prevalence of Omicron-positive wastewater samples rising to >80% by 10 January 2022 with BA.2 as the predominant sublineage by 10 March 2022, whilst on 18 April 2022 BA.4 and BA.5 were detected in selected wastewater sites. These findings demonstrate the value of wastewater-based epidemiology to monitor the spatiotemporal spread and potential origin of new Omicron sublineages. [ABSTRACT FROM AUTHOR]
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- 2022
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24. Detrimental Effects of Lipid Peroxidation in Type 2 Diabetes: Exploring the Neutralizing Influence of Antioxidants.
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Shabalala, Samukelisiwe C., Johnson, Rabia, Basson, Albertus K., Ziqubu, Khanyisani, Hlengwa, Nokulunga, Mthembu, Sinenhlanhla X. H., Mabhida, Sihle E., Mazibuko-Mbeje, Sithandiwe E., Hanser, Sidney, Cirilli, Ilenia, Tiano, Luca, and Dludla, Phiwayinkosi V.
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TYPE 2 diabetes ,LIPIDS ,SUPEROXIDE dismutase ,PEROXIDATION ,GLYCEMIC control ,GLUTATHIONE peroxidase ,REACTIVE oxygen species - Abstract
Lipid peroxidation, including its prominent byproducts such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE), has long been linked with worsened metabolic health in patients with type 2 diabetes (T2D). In fact, patients with T2D already display increased levels of lipids in circulation, including low-density lipoprotein-cholesterol and triglycerides, which are easily attacked by reactive oxygen molecules to give rise to lipid peroxidation. This process severely depletes intracellular antioxidants to cause excess generation of oxidative stress. This consequence mainly drives poor glycemic control and metabolic complications that are implicated in the development of cardiovascular disease. The current review explores the pathological relevance of elevated lipid peroxidation products in T2D, especially highlighting their potential role as biomarkers and therapeutic targets in disease severity. In addition, we briefly explain the implication of some prominent antioxidant enzymes/factors involved in the blockade of lipid peroxidation, including termination reactions that involve the effect of antioxidants, such as catalase, coenzyme Q
10 , glutathione peroxidase, and superoxide dismutase, as well as vitamins C and E. [ABSTRACT FROM AUTHOR]- Published
- 2022
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25. The association of MTHFR (rs1801133) with hypertension in an indigenous south African population.
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Mabhida, Sihle E., Sharma, Jyoti R., Apalata, Teke, Masilela, Charity, Nomatshila, Sibusiso, Mabasa, Lawrence, Fokkens, Hannah, Benjeddou, Mongi, Muhamed, Babu, Shabalala, Samukelisiwe, and Johnson, Rabia
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SOUTH Africans ,METHYLENETETRAHYDROFOLATE reductase ,GENETIC models ,DIASTOLIC blood pressure ,LOGISTIC regression analysis ,SMOKING statistics - Abstract
Aims: The current study sought to investigate the association between the methylenetetrahydrofolate reductase (MTHFR) variant (rs1801133) and the risk of developing hypertension (HTN) in an indigenous South African population. Methods: A total of 442 participants (hypertensive, n = 279 and nonhypertensive, n = 163) from the indigenous tribe residing in Mthatha, Eastern Cape (South Africa) were recruited. HTN was defined as a systolic (SBP) and diastolic blood pressure (DBP) of =130/80 mmHg following American Heart Association guidelines. The genotyping of MTHFR (rs1801133) was assessed using MassARRAY® System. Thereafter, the association between rs1801133 in various genetic models and HTN was determined by logistic regression model analysis. Furthermore, the interaction between rs1801133 and selected risk factors on HTN was performed using the open-source multifactor dimensionality reduction (MDR). Results: The low frequency of the T allele (5%) was also observed when compared with the C allele (95%) in both cases and controls. After adjusting for confounding factors (gender, smoking status, BMI, and blood glucose levels), there were no significant associations were observed between rs1801133 and the risk of HTN in all genetic models: genotypic (OR 0.75, 95% CI 0.29-1.95, p = 0.56), dominant (OR 0.86, 95% CI 0.35-2.16, p = 0.75), co-dominant (OR 1.33, 95% CI 0.51-3.48, p = 0.55) and allelic (OR 0.80, 95% CI 0.49-1.62, p = 0.70) in logistic regression analysis. However, a significant interaction was reported among rs1801133, age, and gender (p < 0.0001) with the risk of HTN. Conclusion: The present study reports on the lack of association between MTHFR (rs1801133) and the risk of HTN in an indigenous South African tribe. However, an interaction between gender, age, and rs1801133 was observed. Thus, future studies with a large sample size are required to further validate these findings. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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26. Characterization and Comparison of the Divergent Metabolic Consequences of High-Sugar and High-Fat Diets in Male Wistar Rats.
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Kotzé-Hörstmann, Liske, Cois, Annibale, Johnson, Rabia, Mabasa, Lawrence, Shabalala, Samukelisiwe, Van Jaarsveld, Paul J., and Gijsen, Hanél Sadie-Van
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HIGH-fat diet ,LABORATORY rats ,BODY composition ,LABORATORY rodents ,PRINCIPAL components analysis - Abstract
Diet-induced obesity (DIO) in laboratory rodents can serve as a model with which to study the pathophysiology of obesity, but obesogenic diets (high-sugar and/or high-fat) are often poorly characterised and simplistically aimed at inducing metabolic derangements for the purpose of testing the therapeutic capacity of natural products and other bioactive compounds. Consequently, our understanding of the divergent metabolic responses to different obesogenic diet formulations is limited. The aim of the present study was to characterise and compare differences in the metabolic responses induced by low-fat, medium-fat/high-sugar and high-fat diets in rats through multivariate statistical modelling. Young male Wistar rats were randomly assigned to CON (laboratory chow, low-fat), OB1 (high-sugar, medium-fat) or OB2 (high-fat) dietary groups (n = 24 each) for 17 weeks, after which metabolic responses were characterised. Projectionbased multivariate analyses (principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA)) were used to explore the associations between measures of body composition and metabolism. Furthermore, we conducted a systematic literature survey to examine reporting trends in rat dietary intervention studies, and to determine how the metabolic responses observed in the present study compared to other recently published studies. The OB1 and OB2 dietary regimens resulted in distinct metabolic profiles, with OB1 characterised by perturbations in insulin homeostasis and adipose tissue secretory function, while OB2 was characterised by altered lipid and liver metabolism. This work therefore confirms, by means of direct comparison, that differences in dietary composition have a profound impact on metabolic and pathophysiological outcomes in rodent models of DIO. However, through our literature survey we demonstrate that dietary composition is not reported in the majority of rat dietary intervention studies, suggesting that the impact of dietary composition is often not considered during study design or data interpretation. This hampers the usefulness of such studies to provide enhanced mechanistic insights into DIO, and also limits the translatability of such studies within the context of human obesity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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27. Molecular insights into the pathophysiology of doxorubicin-induced cardiotoxicity: a graphical representation.
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Sangweni, Nonhlakanipho F., Gabuza, Kwazi, Huisamen, Barbara, Mabasa, Lawrence, van Vuuren, Derick, and Johnson, Rabia
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CARDIOTOXICITY ,DOXORUBICIN ,HEART cells ,CELL death ,PATHOLOGICAL physiology ,CANCER cells ,OXIDANT status ,MYOCARDIUM - Abstract
A breakthrough in oncology research was the discovery of doxorubicin (Dox) in the 1960's. Unlike other chemotherapy drugs, Dox was determined to have a greater therapeutic index. Since its discovery, Dox has, in part, contributed to the 5–10-year survival increase in cancer patient outcomes. Unfortunately, despite its efficacy, both in adult and pediatric cancers, the clinical significance of Dox is tainted by its adverse side effects, which usually manifest as cardiotoxicity. The issue stems from Dox's lack of specificity which prevents it from accurately distinguishing between cancer cells and healthy cell lines, like cardiomyocytes. In addition, the high binding affinity of Dox to topoisomerases, which are abundantly found in cancer and cardiac cells in different isoforms, potentiates DNA damage. In both cell lines, Dox induces cytotoxicity by stimulating the production of pro-oxidants whilst inhibiting antioxidant enzymatic activity. Given that the cardiac muscle has an inherently low antioxidant capacity makes it susceptible to oxidative damage thereby, allowing the accumulation of Dox within the myocardium. Subsequently, Dox drives the activation of cell death pathways, such as ferroptosis, necroptosis and apoptosis by triggering numerous cellular responses that have been implicated in diseases. To date, the exact mechanism by which Dox induces the cardiotoxicity remains an aspect of much interest in cardio-oncology research. Hence, the current review summarizes the proposed mechanisms that are associated with the onset and progression of DIC. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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28. Methylenetetrahydrofolate Reductase Polymorphism (rs1801133) and the Risk of Hypertension among African Populations: A Narrative Synthesis of Literature.
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Mabhida, Sihle E., Muhamed, Babu, Sharma, Jyoti R., Apalata, Teke, Nomatshila, Sibusiso, Mabasa, Lawrence, Benjeddou, Mongi, Masilela, Charity, Ziqubu, Khanyisani, Shabalala, Samukelisiwe, and Johnson, Rabia
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METHYLENETETRAHYDROFOLATE reductase ,AFRICANS ,HYPERTENSION ,BLACK Africans ,HUMAN genome - Abstract
In this review, we have gathered and analyzed the available genetic evidence on the association between the methylenetetrahydrofolate reductase gene (MTHFR), rs1801133 and the risk of Hypertension (HTN) in African populations, which was further compared to the global data evidence. This review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and Human Genome Epidemiology Network (HuGENet) guidelines. Literature was retrieved through major search databases, including PubMed, Scopus, Web of Science, and African Journal Online. We identified 64 potential studies, of which 4 studies were from the African continent and 60 studies were reported globally. Among the studies conducted in Africa, only two (n = 2) reported a significant association between the MTHFR (rs1801133) and the risk of developing HTN. Only one (n = 1) study population was purely composed of black Africans, while others were of other ethnicities. Among studies conducted in other continents (n = 60), forty-seven (n = 47) studies reported a positive association between MTHFR (rs1801133) and the risk of developing HTN, whereas the remaining studies (n = 14) did not show a significant association. Available literature suggests an apparent association between rs1801133 and HTN in global regions; however, such information is still scarce in Africa, especially in the black African population. [ABSTRACT FROM AUTHOR]
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- 2022
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29. Sclerocarya birrea (Marula) Extract Inhibits Hepatic Steatosis in db/db Mice.
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Mabasa, Lawrence, Kotze, Anri, Shabalala, Samukelisiwe, Kimani, Clare, Gabuza, Kwazi, Johnson, Rabia, Sangweni, Nonhlakanipho F., Maharaj, Vinesh, and Muller, Christo J. F.
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- 2022
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30. Intestinal Barrier Function and Immune Homeostasis Are Missing Links in Obesity and Type 2 Diabetes Development.
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Riedel, Sylvia, Pheiffer, Carmen, Johnson, Rabia, Louw, Johan, and Muller, Christo J. F.
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TYPE 2 diabetes ,INTESTINES ,MICROBIAL metabolites ,HOMEOSTASIS ,METABOLIC disorders - Abstract
Noncommunicable diseases, such as type 2 diabetes (T2D), place a burden on healthcare systems worldwide. The rising prevalence of obesity, a major risk factor for T2D, is mainly attributed to the adoption of Westernized diets and lifestyle, which cause metabolic dysfunction and insulin resistance. Moreover, diet may also induce changes in the microbiota composition, thereby affecting intestinal immunity. The critical role of intestinal immunity and intestinal barrier function in the development of T2D is increasingly acknowledged, however, limited studies have investigated the link between intestinal function and metabolic disease. In this review, studies reporting specific roles of the intestinal immune system and intestinal epithelial cells (IECs) in metabolic disease are highlighted. Innate chemokine signaling, eosinophils, immunoglobulin A (IgA), T helper (Th) 17 cells and their cytokines were associated with obesity and/or dysregulated glucose homeostasis. Intestinal epithelial cells (IECs) emerged as critical modulators of obesity and glucose homeostasis through their effect on lipopolysaccharide (LPS) signaling and decontamination. Furthermore, IECs create a link between microbial metabolites and whole-body metabolic function. Future in depth studies of the intestinal immune system and IECs may provide new opportunities and targets to develop treatments and prevention strategies for obesity and T2D. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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31. Cafeteria diet induces global and Slc27a3-specific hypomethylation in male Wistar rats.
- Author
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Viraragavan, Amsha, Willmer, Tarryn, Patel, Oelfah, Basson, Albertus, Johnson, Rabia, and Pheiffer, Carmen
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LABORATORY rats ,EPIDERMAL growth factor receptors ,ADIPOSE tissues ,TYPE 2 diabetes ,TISSUE expansion - Abstract
Increased visceral adipose tissue (VAT) is associated with metabolic dysfunction, while subcutaneous adipose tissue (SAT) is considered protective. The mechanisms underlying these differences are not fully elucidated. This study aimed to investigate molecular differences in VAT and SAT of male Wistar rats fed a cafeteria diet (CD) or a standard rodent diet (STD) for three months. The expression of fatty acid metabolism genes was analysed by quantitative real-time PCR. Global and gene-specific DNA methylation was quantified using the Imprint® Methylated DNA Quantification Kit and pyrosequencing, respectively. Bodyweight, retroperitoneal fat mass, insulin resistance, leptin and triglyceride concentrations and adipocyte hypertrophy were higher in CD- compared to STD-fed rats. The expression of solute carrier family 27 member 3 (Slc27a3), a fatty acid transporter, was 9.6-fold higher in VAT and 6.3-fold lower in SAT of CD- versus STD-fed rats. Taqman probes confirmed increased Slc27a3 expression, while pyrosequencing showed Slc27a3 hypomethylation in VAT of CD- compared to STD-fed rats. The CD decreased global methylation in both VAT and SAT, although no depot differences were observed. Dysregulated fatty acid influx in VAT, in response to a CD, provides insight into the mechanisms underlying depot-differences in adipose tissue expansion during obesity and metabolic disease. Abbreviations: CD: cafeteria diet; E2F1: E2F Transcription Factor 1; EMSA: electrophoretic mobility shift assay; EGFR: epidermal growth factor receptor; GCF: GC-Rich Sequence DNA-Binding Factor; HOMA-IR: Homeostasis model for insulin resistance; NKX2-1: NK2 homeobox 1; PCR: Polymerase chain reaction; qRT-PCR: quantitative real-time PCR; RF: retroperitoneal fat; SAT: subcutaneous adipose tissue; Slc27a3: solute carrier family 27 member 3; STD: standard diet; TNFα: tumour necrosis factor alpha; TTS: transcriptional start site; T2D: Type 2 Diabetes; VAT: visceral adipose tissue; WT1 I: Wilms' tumour protein 1 [ABSTRACT FROM AUTHOR]
- Published
- 2021
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32. Metformin and heart failure–related outcomes in patients with or without diabetes: a systematic review of randomized controlled trials.
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Dludla, Phiwayinkosi V., Nyambuya, Tawanda M., Johnson, Rabia, Silvestri, Sonia, Orlando, Patrick, Mazibuko-Mbeje, Sithandiwe E., Gabuza, Kwazi B., Mxinwa, Vuyolwethu, Mokgalaboni, Kabelo, Tiano, Luca, Muller, Christo J. F., Louw, Johan, and Nkambule, Bongani B.
- Subjects
TREATMENT effectiveness ,RANDOMIZED controlled trials ,METFORMIN ,INSULIN resistance ,HEART failure ,VENTRICULAR ejection fraction - Abstract
Metformin is considered a safe anti-hyperglycemic drug for patients with type 2 diabetes (T2D); however, information on its impact on heart failure–related outcomes remains inconclusive. The current systematic review explored evidence from randomized clinical trials (RCTs) reporting on the impact of metformin in modulating heart failure–related markers in patients with or without T2D. Electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible studies. Included studies were those assessing the use of metformin as an intervention, and also containing the comparison group on placebo, and all articles had to report on measurable heart failure–related indices in individuals with or without T2D. The modified Downs and Black checklist was used to evaluate the risk of bias. Overall, nine studies met the inclusion criteria, enrolling a total of 2486 patients. Although summarized evidence showed that metformin did not affect left ventricular function, this antidiabetic drug could improve myocardial oxygen consumption concomitant to reducing prominent markers of heart failure such as n-terminal pro-brain natriuretic peptide and low-density lipoprotein levels, inconsistently between diabetic and nondiabetic patients. Effective modulation of some heart failure–related outcomes with metformin treatment was related to its beneficial effects in ameliorating insulin resistance and blocking pro-inflammatory markers such as the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11). Overall, although such beneficial effects were observed with metformin treatment, additional RCTs are necessary to improve our understanding on its modulatory effects on heart failure–related outcomes especially in diabetic patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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33. Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-Resistance Patterns
- Author
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van Rie, Annelies, Victor, Thomas C., Richardson, Madalene, Johnson, Rabia, van der Spuy, Gian D., Murray, Emma J., Beyers, Nulda, van Pittius, Nico C. Gey, van Helden, Paul D., and Warren, Robin M.
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- 2005
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34. The Prophylactic Effect of Pinocembrin Against Doxorubicin-Induced Cardiotoxicity in an In Vitro H9c2 Cell Model.
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Sangweni, Nonhlakanipho F., Moremane, Malebogo, Riedel, Sylvia, van Vuuren, Derick, Huisamen, Barbara, Mabasa, Lawrence, Barry, Reenen, and Johnson, Rabia
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CARDIOTOXICITY ,APOPTOSIS ,CANCER cells ,OXIDATIVE stress ,BIOENERGETICS ,AMED (Information retrieval system) - Abstract
Background: The clinical use of Doxorubicin (Dox) is significantly limited by its dose-dependent cardiotoxic side effect. Accumulative evidence suggests that the use of flavonoids, such as the antioxidative Pinocembrin (Pin), could be effective in the prevention of Dox-induced cardiotoxicity. Accordingly, we investigated the ability of pinocembrin (Pin) to attenuate Dox-induced cardiotoxicity in an in vitro H9c2 cardiomyoblast model. Methodology: The cardioprotective potential of Pin was established in H9c2 cells. Here, cells were treated with Dox (2μM), Dox (2μM) + Pin (1μM), and Dox (2μM) + Dexrazoxane (20μM) for 6 days. Thereafter, the safe co-administration of Pin with Dox, in a cancer environment, was investigated in MCF-7 breast cancer cells subjected to the same experimental conditions. Untreated cells served as the control. Subsequently, Pin's ability to attenuate Dox-mediated oxidative stress, impaired mitochondrial bioenergetics and potential, as well as aggravated apoptosis was quantified using biochemical assays. Results: The results demonstrated that co-treatment with Pin mitigates Dox-induced oxidative stress by alleviating the antioxidant enzyme activity of the H9c2 cells. Pin further reduced the rate of apoptosis and necrosis inferred by Dox by improving mitochondrial bioenergetics. Interestingly, Pin did not decrease the efficacy of Dox but, rather increased the rate of apoptosis and necrosis in Dox-treated MCF-7 cells. Conclusion: The findings presented in this study showed, for the first time, that Pin attenuates Dox-induced cardiotoxicity without reducing its chemotherapeutic effect. We propose that additional studies, using in vivo models, should be conducted to further investigate Pin as a suitable candidate in the prevention of the cardiovascular dysfunction inferred by Dox administration. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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35. Fermented rooibos extract attenuates hyperglycemia-induced myocardial oxidative damage by improving mitochondrial energetics and intracellular antioxidant capacity.
- Author
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Dludla, Phiwayinkosi V., Johnson, Rabia, Mazibuko-Mbeje, Sithandiwe E., Muller, Christo J.F., Louw, Johan, Joubert, Elizabeth, Orlando, Patrick, Silvestri, Sonia, Chellan, Nireshni, Nkambule, Bongani B., Essop, M. Faadiel, and Tiano, Luca
- Subjects
- *
OXIDANT status , *UBIQUINONES , *FREE fatty acids , *ELECTRON transport , *OXIDATIVE stress , *SUPEROXIDE dismutase , *HYPERGLYCEMIA , *STREPTOZOTOCIN - Abstract
• Fermented rooibos extract (FRE) protects cardiomyocytes hyperglycemia-induced oxidative damage. • However, the protective mechanism of action for FRE remains unknown. • FRE treatment improved FFA utilization and enhanced levels of intracellular antioxidants under hyperglycemic conditions. • FRE can control cardiac mitochondrial energetics under stimulated hyperglycemic conditions. • FRE to enhances intracellular coenzyme Q9 levels, a major component of the electron transport chain that plays a crucial role in maintaining efficient aerobic respiration and counteracting oxidative stress. Rooibos extracts, including its derived polyphenolic compounds, are increasingly explored for their ameliorative effects against diabetes-associated complications. An extract of 'fermented' (oxidized) rooibos (FRE) can protect cardiomyocytes from diabetic rats against oxidative stress-induced damage, however, its mechanism of action remains unknown. Using an established model of H9c2 cardiomyocytes exposed to high glucose concentrations, the current study elaborates on mechanisms associated with the cardioprotective effects of FRE, especially its impact on mitochondrial energetics and capacity to enhance intracellular antioxidants under hyperglycemic conditions. The results showed that exposure of H9c2 cardiomyocytes to elevated glucose concentrations induced a state of myocardial substrate inflexibility, characterized by altered free fatty acid (FFA) uptake and oxidation, followed by impaired mitochondrial energetics and accelerated oxidative stress-induced cardiac damage. Our data revealed that FRE ameliorated high glucose-induced abnormalities to a similar degree as metformin. Here FRE treatment improved FFA utilization and enhanced levels of intracellular antioxidants such as glutathione and superoxide dismutase. These are the first results to show that FRE can control cardiac mitochondrial energetics under stimulated hyperglycemic conditions. Of significant interest was the ability of FRE to enhance intracellular coenzyme Q 9 levels, a major component of the electron transport chain that plays a crucial role in maintaining efficient aerobic respiration and counteracting oxidative stress. The current results enhance our understanding of the potential protective properties of FRE against high glucose-induced cardiac damage, and also provides impetus for more studies to investigate the modulatory effect of FRE on mitochondrial-linked pathological abnormalities. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
36. Socio-demographic and modifiable risk factors of diabetes and hypertension among resource constrained patients from rural areas in Mdantsane Township in South Africa.
- Author
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Xhakaza, Lettilia, Abrahams-October, Zainonesa, Mohammednur, Mohammedmekin Mohammedseid, Pearce, Brendon, Adeniyi, Oladele Vincent, Johnson, Rabia, and Benjeddou, Mongi
- Published
- 2020
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37. Evaluation of the suitability of 19 pharmacogenomics biomarkers for individualized metformin therapy for type 2 diabetes patients.
- Author
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Xhakaza, Lettilia, Abrahams-October, Zainonesa, Pearce, Brendon, Masilela, Charity Mandisa, Adeniyi, Oladele Vincent, Johnson, Rabia, Ongole, Joven Jebio, and Benjeddou, Mongi
- Abstract
Objectives: Type 2 Diabetes mellitus is a progressive metabolic disease characterized by relative insulin insufficiency and insulin resistance resulting in hyperglycemia. Despite the widespread use of metformin, there is considerable variation in treatment response; with approximately one-third of patients failing to achieve adequate glycemic control. Studies have reported the involvement of single nucleotide polymorphisms and their interactions in genetic pathways i.e., pharmacodynamics and pharmacokinetics. This study aims to investigate the association between 19 pharmacogenetics biomarkers and response to metformin treatment. Methods: MassARRAY panels were designed and optimized by Inqaba Biotechnical Industries, to genotype 19 biomarkers for 140 type 2 diabetic outpatients. Results: The CT genotype of the rs12752688 polymorphism was significantly associated with increased response to metformin therapy after correction (OR=0.33, 95% CI [0.16–0.68], p-value=0.006). An association was also found between the GA genotype of SLC47A2 rs12943590 and a decreased response to metformin therapy after correction (OR=2.29, 95% CI [1.01–5.21], p-value=0.01). Conclusions: This is the first study investigating the association between genetic variants and responsiveness to medication for diabetic patients from the indigenous Nguni population in South Africa. It is suggested that rs12752688 and rs12943590 be included in pharmacogenomics profiling systems to individualize metformin therapy for diabetic patients from African populations. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
38. In Utero One‐Carbon Metabolism Interplay and Metabolic Syndrome in Cardiovascular Disease Risk Reduction.
- Author
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Mabasa, Lawrence, Samodien, Ebrahim, Sangweni, Nonhlakanipho F., Pheiffer, Carmen, Louw, Johan, and Johnson, Rabia
- Published
- 2020
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39. Diet‐induced DNA methylation within the hypothalamic arcuate nucleus and dysregulated leptin and insulin signaling in the pathophysiology of obesity.
- Author
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Samodien, Ebrahim, Pheiffer, Carmen, Erasmus, Melisse, Mabasa, Lawrence, Louw, Johan, and Johnson, Rabia
- Subjects
DNA methylation ,LEPTIN ,INSULIN ,PATHOLOGY ,OBESITY ,METABOLIC disorders - Abstract
Obesity rates continue to rise in an unprecedented manner in what could be the most rapid population‐scale shift in human phenotype ever to occur. Increased consumption of unhealthy, calorie‐dense foods, coupled with sedentary lifestyles, is the main factor contributing to a positive energy balance and the development of obesity. Leptin and insulin are key hormones implicated in pathogenesis of this disorder and are crucial for controlling whole‐body energy homeostasis. Their respective function is mediated by the counterbalance of anorexigenic and orexigenic neurons located within the hypothalamic arcuate nucleus. Dysregulation of leptin and insulin signaling pathways within this brain region may contribute not only to the development of obesity, but also systemically affect the peripheral organs, thereby manifesting as metabolic diseases. Although the exact mechanisms detailing how these hypothalamic nuclei contribute to disease pathology are still unclear, increasing evidence suggests that altered DNA methylation may be involved. This review evaluates animal studies that have demonstrated diet‐induced DNA methylation changes in genes that regulate energy homeostasis within the arcuate nucleus, and elucidates possible mechanisms causing hypothalamic leptin and insulin resistance leading to the development of obesity and metabolic diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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40. Aspalathin, a natural product with the potential to reverse hepatic insulin resistance by improving energy metabolism and mitochondrial respiration.
- Author
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Mazibuko-Mbeje, Sithandiwe E., Dludla, Phiwayinkosi V., Johnson, Rabia, Joubert, Elizabeth, Louw, Johan, Ziqubu, Khanyisani, Tiano, Luca, Silvestri, Sonia, Orlando, Patrick, Opoku, Andy R., and Muller, Christo J. F.
- Subjects
INSULIN resistance ,ENERGY metabolism ,RESPIRATION ,PROTEIN kinase B ,NATURAL products ,LIVER cells - Abstract
Aspalathin is a rooibos flavonoid with established blood glucose lowering properties, however, its efficacy to moderate complications associated with hepatic insulin resistance is unknown. To study such effects, C3A liver cells exposed to palmitate were used as a model of hepatic insulin resistance. These hepatocytes displayed impaired substrate metabolism, including reduced glucose transport and free fatty acid uptake. These defects included impaired insulin signaling, evident through reduced phosphatidylinositol-4,5-bisphosphate 3-kinase/ protein kinase B (PI3K/AKT) protein expression, and mitochondrial dysfunction, depicted by a lower mitochondrial respiration rate. Aspalathin was able to ameliorate these defects by correcting altered substrate metabolism, improving insulin signaling and mitochondrial bioenergetics. Activation of 5ʹ-adenosine monophosphate-activated protein kinase (AMPK) may be a plausible mechanism by which aspalathin increases hepatic energy expenditure. Overall, these results encourage further studies assessing the potential use of aspalathin as a nutraceutical to improve hepatocellular energy expenditure, and reverse metabolic disease-associated complications. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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41. Pharmacogenomics of amlodipine and hydrochlorothiazide therapy and the quest for improved control of hypertension: a mini review.
- Author
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Johnson, Rabia, Dludla, Phiwayinkosi, Mabhida, Sihle, Benjeddou, Mongi, Louw, Johan, and February, Faghri
- Abstract
Blood pressure (BP) is a complex trait that is regulated by multiple physiological pathways and include but is not limited to extracellular fluid volume homeostasis, cardiac contractility, and vascular tone through renal, neural, or endocrine systems. Uncontrolled hypertension (HTN) has been associated with an increased mortality risk. Therefore, understanding the genetics that underpins and influence BP regulation will have a major impact on public health. Moreover, uncontrolled HTN has been linked to inter-individual variation in the drugs' response and this has been associated with an individual's genetics architecture. However, the identification of candidate genes that underpin the genetic basis of HTN remains a major challenge. To date, few variants associated with inter-individual BP regulation have been identified and replicated. Research in this field has accelerated over the past 5 years as a direct result of on-going genome-wide association studies (GWAS) and the progress in the identification of rare gene variants and mutations, epigenetic markers, and the regulatory pathways involved in the pathophysiology of BP. In this review we describe and enhance our current understanding of how genetic variants account for the observed variability in BP response in patients on first-line antihypertensive drugs, amlodipine and hydrochlorothiazide. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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42. Lanosteryl triterpenes from Protorhus longifolia as a cardioprotective agent: a mini review.
- Author
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Sangweni, Nonhlakanipho F., Dludla, Phiwayinkosi V., Mosa, Rebamang A., Kappo, Abidemi P., Opoku, Andy, Muller, Christo J. F., and Johnson, Rabia
- Abstract
The epidemic of cardiovascular diseases is a global phenomenon that is exaggerated by the growing prevalence of diabetes mellitus. Coronary artery disease and diabetic cardiomyopathy are the major cardiovascular complications responsible for exacerbated myocardial infarction in diabetic individuals. Increasing research has identified hyperglycemia and hyperlipidemia as key factors driving the augmentation of oxidative stress and a pro-inflammatory response that usually results in increased fibrosis and reduced cardiac efficiency. While current antidiabetic agents remain active in attenuating diabetes-associated complications, overtime, their efficacy proves limited in protecting the hearts of diabetic individuals. This has led to a considerable increase in the number of natural products that are screened for their antidiabetic and cardioprotective properties. These natural products may present essential ameliorative properties relevant to their use as a monotherapy or as an adjunct to current drug agents in combating diabetes and its associated cardiovascular complications. Recent findings have suggested that triterpenes isolated from Protorhus longifolia (Benrh.) Engl., a plant species endemic to Southern Africa, display strong antioxidant and antidiabetic properties that may potentially protect against diabetes-induced cardiovascular complications. Thus, in addition to discussing the pathophysiology associated with diabetes-induced cardiovascular injury, available evidence pertaining to the cardiovascular protective potential of lanosteryl triterpenes from Protorhus longifolia will be discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
43. SOUTH AFRICAN SOCIETY FOR CARDIOVASCULAR RESEARCH (SASCAR).
- Author
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Johnson, Rabia
- Subjects
- *
CARDIOVASCULAR diseases , *MEDICAL research , *HEART metabolism disorders , *CARDIO-oncology , *CARDIOVASCULAR agents - Published
- 2023
44. A Systematic Review on the Protective Effect of N-Acetyl Cysteine Against Diabetes-Associated Cardiovascular Complications.
- Author
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Dludla, Phiwayinkosi V., Dias, Stephanie C., Obonye, Nnini, Johnson, Rabia, Louw, Johan, and Nkambule, Bongani B.
- Subjects
DIABETES complications ,ISCHEMIA prevention ,MYOCARDIAL infarction risk factors ,CARDIOVASCULAR diseases risk factors ,MEDICAL databases ,INFORMATION storage & retrieval systems ,MEDICAL information storage & retrieval systems ,MEDLINE ,ONLINE information services ,SYSTEMATIC reviews ,OXIDATIVE stress ,RANDOMIZED controlled trials ,ACETYLCYSTEINE ,PHARMACODYNAMICS - Abstract
Introduction: Heart failure is the leading cause of death in patients with diabetes. No treatment currently exists to specifically protect these patients at risk of developing cardiovascular complications. Accelerated oxidative stress-induced tissue damage due to persistent hyperglycemia is one of the major factors implicated in deteriorated cardiac function within a diabetic state. N-acetyl cysteine (NAC), through its enhanced capacity to endogenously synthesize glutathione, a potent antioxidant, has displayed abundant health-promoting properties and has a favorable safety profile.Objective: An increasing number of experimental studies have reported on the strong ameliorative properties of NAC. We systematically reviewed the data on the cardioprotective potential of this compound to provide an informative summary.Methods: Two independent reviewers systematically searched major databases, including PubMed, Cochrane Library, Google scholar, and Embase for available studies reporting on the ameliorative effects of NAC as a monotherapy or in combination with other therapies against diabetes-associated cardiovascular complications. We used the ARRIVE and JBI appraisal guidelines to assess the quality of individual studies included in the review. A meta-analysis could not be performed because the included studies were heterogeneous and data from randomized clinical trials were unavailable.Results: Most studies support the ameliorative potential of NAC against a number of diabetes-associated complications, including oxidative stress. We discuss future prospects, such as identification of additional molecular mechanisms implicated in diabetes-induced cardiac damage, and highlight limitations, such as insufficient studies reporting on the comparative effect of NAC with common glucose-lowering therapies. Information on the comparative analysis of NAC, in terms of dose selection, administration mode, and its effect on different cardiovascular-related markers is important for translation into clinical studies.Conclusions: NAC exhibits strong potential for the protection of the diabetic heart at risk of myocardial infarction through inhibition of oxidative stress. The effect of NAC in preventing both ischemia and non-ischemic-associated cardiac damage is also of interest. Consistency in dose selection in most studies reported remains important in dose translation for clinical relevance. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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45. Aspalathin Reverts Doxorubicin-Induced Cardiotoxicity through Increased Autophagy and Decreased Expression of p53/mTOR/p62 Signaling.
- Author
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Johnson, Rabia, Shabalala, Samukelisiwe, Louw, Johan, Kappo, Abidemi Paul, and Muller, Christo John Frederick
- Subjects
- *
DOXORUBICIN , *TUMOR proteins , *ADENOSINE monophosphate , *PROTEIN kinases , *NUCLEOPORINS , *MTOR protein - Abstract
Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 (p62), and the mammalian target of rapamycin (mTOR) are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone C-glucoside has been shown to activate AMPK while decreasing the expression of p53. However, the role that aspalathin could play in the inhibition of Dox-induced cardiotoxicity through increased autophagy flux remained unexplored. H9c2 cardiomyocytes and Caov-3 ovarian cancer cells were cultured in Dulbecco's Modified Eagle's medium and treated with or without Dox for five days. Thereafter, cells exposed to 0.2 μM Dox were co-treated with either 20 μM Dexrazozane (Dexra) or 0.2 μM aspalathin (ASP) daily for 5 days. Results obtained showed that ASP mediates its cytoprotective effect in a p53-dependent manner, by increasing the Bcl-2/Bax ratio and decreasing apoptosis. The latter effect was diminished through ASP-induced activation of autophagy-related genes (Atgs) with an associated decrease in p62 through induction of AMPK and Fox01. Furthermore, we showed that ASP was able to potentiate this effect without decreasing the anti-cancer efficacy of Dox, as could be observed in Caov-3 ovarian cancer cells. Taken together, the data presented in this study provides a credible mechanism by which ASP co-treatment could protect the myocardium from Dox-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
46. Age-dependent development of left ventricular wall thickness in type 2 diabetic ( db/ db) mice is associated with elevated low-density lipoprotein and triglyceride serum levels.
- Author
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Dludla, Phiwayinkosi, Essop, M., Gabuza, Kwazi, Muller, Christo, Louw, Johan, and Johnson, Rabia
- Subjects
TYPE 2 diabetes ,LOW density lipoproteins ,TRIGLYCERIDES ,CAUSES of death ,BLOOD serum analysis ,DIABETIC cardiomyopathy ,LABORATORY mice - Abstract
Diabetic cardiomyopathy (DCM) is a disease of heart muscle that remains one of the leading causes of death in diabetic individuals. Shifts in substrate preference resulting in aberrant serum lipid content and enlarged left ventricular wall thickness are well-established characteristics associated with the development of DCM. As underlying mechanisms driving the onset of the DCM remain relatively unclear, this study sought to characterize age-dependent development of left ventricular (LV) wall thickness in diabetic ( db/ db) mice. Such data were compared with low-density lipoprotein (LDL) and triglyceride serum levels to assess whether any correlation exists between the parameters here investigated. For methods, db/ db mice together with nondiabetic controls ( n = six per group) were monitored from the age of 6-16 weeks. Mice were terminated each week to measure body weights, heart weights, liver weights, tibia length, and fasting plasma glucose levels. Heart tissues were stained with haematoxylin and eosin to measure LV wall and interventricular septum thickness together with an assessment of myocardial remodeling. Serum was collected weekly and used to measure LDL and triglyceride levels. Results showed that db/ db mice presented significantly increased body weights, liver/body weight, and fasting plasma glucose levels from the age of 6-16 weeks. They further displayed a marked enlargement of LV wall and interventricular septum thickness from the age of 11 weeks, while increased heart weight/tibia length was recorded only from week 16. From week 11, the LV wall and interventricular septum thickness results corresponded with cardiac remodeling and raised LDL and triglyceride serum levels. In summary, age-dependent development of LV wall thickness in db/ db mice is partially associated with increased LDL and triglyceride levels, elucidating a potential pathophysiological mechanism. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
47. Hyperglycemia-induced oxidative stress and heart disease-cardioprotective effects of rooibos flavonoids and phenylpyruvic acid-2-O-β-D-glucoside.
- Author
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Dludla, Phiwayinkosi V., Joubert, Elizabeth, Muller, Christo J. F., Louw, Johan, and Johnson, Rabia
- Subjects
CARDIOVASCULAR disease prevention ,DIABETES complications ,HYPERGLYCEMIA prevention ,CORONARY heart disease prevention ,MYOCARDIAL infarction ,HEART failure ,MEDICINAL plants ,ALTERNATIVE medicine ,ANTIOXIDANTS ,APOPTOSIS ,FLAVONOIDS ,POLYPHENOLS ,PHYTOCHEMICALS ,OXIDATIVE stress ,NUCLEAR proteins ,PREVENTION - Abstract
Diabetic patients are at an increased risk of developing heart failure when compared to their non-diabetic counter parts. Accumulative evidence suggests chronic hyperglycemia to be central in the development of myocardial infarction in these patients. At present, there are limited therapies aimed at specifically protecting the diabetic heart at risk from hyperglycemia-induced injury. Oxidative stress, through over production of free radical species, has been hypothesized to alter mitochondrial function and abnormally augment the activity of the NADPH oxidase enzyme system resulting in accelerated myocardial injury within a diabetic state. This has led to a dramatic increase in the exploration of plant-derived materials known to possess antioxidative properties. Several edible plants contain various natural constituents, including polyphenols that may counteract oxidative-induced tissue damage through their modulatory effects of intracellular signaling pathways. Rooibos, an indigenous South African plant, well-known for its use as herbal tea, is increasingly studied for its metabolic benefits. Prospective studies linking diet rich in polyphenols from rooibos to reduced diabetes associated cardiovascular complications have not been extensively assessed. Aspalathin, a flavonoid, and phenylpyruvic acid-2-O-β-D-glucoside, a phenolic precursor, are some of the major compounds found in rooibos that can ameliorate hyperglycemia-induced cardiomyocyte damage in vitro. While the latter has demonstrated potential to protect against cell apoptosis, the proposed mechanism of action of aspalathin is linked to its capacity to enhance the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)expression,an intracellular antioxidant response element. Thus, here we review literature on the potential cardioprotective properties of flavonoids and a phenylpropenoic acid found in rooibos against diabetes-induced oxidative injury. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
48. Cardioprotective potential of N-acetyl cysteine against hyperglycaemia-induced oxidative damage: a protocol for a systematic review.
- Author
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Dludla, Phiwayinkosi V., Nkambule, Bongani B., Dias, Stephanie C., and Johnson, Rabia
- Subjects
ACETYLCYSTEINE ,OXIDATIVE stress ,DIABETIC cardiomyopathy ,CARDIOTONIC agents ,ANTIOXIDANTS ,PREVENTION - Abstract
Background: Hyperglycaemia-induced oxidative damage is a well-established factor implicated in the development of diabetic cardiomyopathy (DCM) in diabetic individuals. Some of the well-known characteristics of DCM include increased myocardial left ventricular wall thickness and remodelling that result in reduced cardiac efficiency. To prevent this, an increasing number of pharmacological compounds such as N-acetyl cysteine (NAC) are explored for their antioxidant properties. A few studies have shown that NAC can ameliorate hyperglycaemia-induced oxidative damage within the heart. Hence, the objective of this review is to synthesise the available evidence pertaining to the cardioprotective role of NAC against hyperglycaemia-induced oxidative damage and thus prevent DCM. Methods: This systematic review protocol will be reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement. We will perform a comprehensive search on major databases such as EMBASE, Cochrane Library, PubMed and Google scholar for original research articles published from January 1960 to March 2017. We will only report on literature that is available in English. Two authors will independently screen for eligible studies using pre-defined criteria, and data extraction will be done in duplicate. All discrepancies will be resolved by consensus or consultation of a third reviewer. The quality of studies will be checked using Cochrane Risk of Bias Assessment Tool and The Joanna Briggs Institute (JBI) Critical Appraisal tools for non-randomised experimental studies. Heterogeneity across studies will be assessed using the Cochrane Q statistic and the inconsistency index (I²). We will use the random effects model to calculate a pooled estimate. Discussion: Although several studies have shown that NAC can ameliorate hyperglycaemia-induced oxidative damage within the heart, this systematic review will be the first pre-registered synthesis of data to identify the cardioprotective potential of NAC against hyperglycaemia-induced oxidative damage. This result will help guide future research evaluating the cardioprotective role of NAC against DCM and better identify possible mechanisms of action for NAC to prevent oxidative damage with a diabetic heart. [ABSTRACT FROM AUTHOR]
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- 2017
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49. The Transcription Profile Unveils the Cardio-Protective Effect of Aspalathin against Lipid Toxicity in an In Vitro H9c2 Model.
- Author
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Johnson, Rabia, Dludla, Phiwayinkosi V., Muller, Christo J. F., Huisamen, Barbara, Essop, M. Faadiel, and Louw, Johan
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HYPERGLYCEMIA treatment , *HYPERGLYCEMIA , *GENE regulatory networks , *APOPTOSIS , *CARDIOTONIC agents , *NUCLEIC acid isolation methods , *GENETICS - Abstract
Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocyte model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 h before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, CD36, Cpt1, Pparg, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results suggest that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparg and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis. [ABSTRACT FROM AUTHOR]
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- 2017
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50. Aspalathin Protects the Heart against Hyperglycemia-Induced Oxidative Damage by Up-Regulating Nrf2 Expression.
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Dludla, Phiwayinkosi V., Muller, Christo J. F., Joubert, Elizabeth, Louw, Johan, Essop, M. Faadiel, Gabuza, Kwazi B., Ghoor, Samira, Huisamen, Barbara, and Johnson, Rabia
- Abstract
Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress, and apoptosis. The protective mechanism of ASP remains unknown. However, as one of possible, it is well known that phytochemical flavonoids reduce oxidative stress via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation resulting in up-regulation of antioxidant genes and enzymes. Therefore, we hypothesized that ASP protects the myocardium against HG- and hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice, respectively. Using an oxidative stress RT
2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for six weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for six weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced oxidative stress through activation of Nrf2 and its downstream target genes. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
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