Browsing by Author "Sharma, Jyoti R."
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Item The association of mthfr (rs1801133) with hypertension in an indigenous South African population(Frontiers Media, 2022) Mabhida, Sihle E.; Sharma, Jyoti R.; Apalata, TekeThe 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.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).Item An insight into the mechanism of holamine- and funtumine-induced cell death in cancer cells(MDPI, 2020) Badmus, Jelili A.; Ekpo, E. O.; Sharma, Jyoti R.Holamine and funtumine, steroidal alkaloids with strong and diverse pharmacological activities are commonly found in the Apocynaceae family of Holarrhena. The selective anti-proliferative and cell cycle arrest effects of holamine and funtumine on cancer cells have been previously reported. The present study evaluated the anti-proliferative mechanism of action of these two steroidal alkaloids on cancer cell lines (HT-29, MCF-7 and HeLa) by exploring the mitochondrial depolarization effects, reactive oxygen species (ROS) induction, apoptosis, F-actin perturbation, and inhibition of topoisomerase-I. The apoptosis-inducing effects of the compounds were studied by flow cytometry using the APOPercentageTM dye and Caspase-3/7 Glo assay kit. The two compounds showed a significantly greater cytotoxicity in cancer cells compared to non-cancer (normal) fibroblasts. The observed antiproliferative effects of the two alkaloids presumably are facilitated through the stimulation of apoptosis. The apoptotic effect was elicited through the modulation of mitochondrial function, elevated ROS production, and caspase-3/7 activation. Both compounds also induced F-actin disorganization and inhibited topoisomerase-I activity. Although holamine and funtumine appear to have translational potential for the development of novel anticancer agents, further mechanistic and molecular studies are recommended to fully understand their anticancer effects.Item Synthesis of biogenic gold nanoparticles from terminalia mantaly extracts and the evaluation of their in vitro cytotoxic effects in cancer cells(MDPI, 202-09-12) Sharma, Jyoti R.; Sibuyi, Nicole Remaliah Samantha; Majoumouo, Michele StellaScientists have demonstrated the potential of plant materials as 'green' reducing and stabilizing agents for the synthesis of gold nanoparticles (AuNPs) and opened new ecofriendly horizons to develop effective and less harmful treatment strategies. The current study demonstrated the use of Terminalia mantaly (TM) extracts to synthesize AuNPs with enhanced cytotoxic effects. The TM-AuNPs were synthesized at 25 and 70 °C using water (WTM) and methanolic (MTM) extracts of the leaf, root and stem/bark parts of the plant. The TM-AuNPs were characterized using UV-visible spectrophotometry, dynamic light scattering (DLS), transmission electron microscopy, energy dispersive X-ray (EDX), selection area electron diffraction (SAED) and Fourier transform infrared (FTIR) spectroscopy. Majority of the TM-AuNPs were spherical with a mean diameter between 22.5 and 43 nm and were also crystalline in nature. The cytotoxic effects of TM-AuNPs were investigated in cancer (Caco-2, MCF-7 and HepG2) and non-cancer (KMST-6) cell lines using the MTT assay. While the plant extracts showed some cytotoxicity towards the cancer cells, some of the TM-AuNPs were even more toxic to the cells. The IC50 values (concentrations of the AuNPs that inhibited 50% cell growth) as low as 0.18 µg/mL were found for TM-AuNPs synthesized using the root extract of the plant. Moreover, some of the TM-AuNPs demonstrated selective toxicity towards specific cancer cell types. The study demonstrates the potential of TM extracts to produce AuNPs and describe the optimal conditions for AuNPs using TM extracts. The toxicity of some the TM-AuNPs can possibly be explored in the future as an antitumor treatment.