UWCScholar :: Browsing by Author "Benjeddou, Mongi"

Browsing by Author "Benjeddou, Mongi"

Now showing 1 - 20 of 30

Cross-sectional study of the association of 5 single nucleotide polymorphisms with enalapril treatment response among South African adults with hypertension
(NLM (Medline), 2021-11-19) Masilela, Charity; Pearce, Brendon; Ongole, Joven J.; Adeniyi, Oladele V.; Johnson, Rabia; Benjeddou, Mongi
This study investigates the association of 5 single nucleotide polymorphisms (SNPs) in selected genes (ABO, VEGFA, BDKRB2, NOS3, and ADRB2) with blood pressure (BP) response to enalapril. The study further assessed genetic interactions that exist within these genes and their implications in enalapril treatment response among South African adults with hypertension.A total of 284 participants belonging to the Nguni tribe of South Africa on continuous treatment for hypertension were recruited. Five SNPs in enalapril pharmacogenes were selected and genotyped using MassArray. Uncontrolled hypertension was defined as BP ≥140/90 mm Hg. The association between genotypes, alleles, and BP response to treatment was determined by fitting multivariate logistic regression model analysis, and genetic interactions between SNPs were assessed by multifactor dimensionality reduction.Majority of the study participants were female (75.00%), Xhosa (78.87%), and had uncontrolled hypertension (69.37%). All 5 SNPs were exclusively detected among Swati and Zulu participants. In the multivariate (adjusted) logistic model analysis, ADRB2 rs1042714 GC (adjusted odds ratio [AOR] = 2.31; 95% confidence interval [CI] 1.02-5.23; P = .044) and BDKRB2 rs1799722 CT (AOR = 2.74; 95% CI 1.19-6.28; P = .017) were independently associated with controlled hypertension in response to enalapril. While the C allele of VEGFA rs699947 (AOR = 0.37; 95% CI 0.15-0.94; P = .037) was significantly associated with uncontrolled hypertension. A significant interaction between rs699947, rs495828, and rs2070744 (cross-validation consistency = 10/10; P = .0005) in response to enalapril was observed.We confirmed the association of rs1042714 (ADRB2) and rs1799722 (BDKRB2) with controlled hypertension and established an interaction between rs699947 (VEGFA), rs495828 (ABO), and rs2070744 (NOS3) with BP response to enalapril. Our findings have provided substantial evidence for the use of SNPs as predictors for enalapril response among South Africans adults with hypertension. Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
Development and validation of a pharmacogenomics profiling panel suitable for personalizing Metformin therapy
(University of the Western Cape, 2019) Xhakaza, Lettilia; Benjeddou, Mongi
The burden of non-communicable diseases (NCDs) in South Africa is predicted to increase substantially in the next decades if the necessary preventative measures are not taken. The two most common NCDs associated with rapid mortality increase are diabetes mellitus (DM) and hypertension (HTN). Both of these diseases, i.e DM and HTN, can be a result of a combination of modifiable risk factors (behavioral) and non-modifiable risk factors (genetic, physiological, and environmental). New strategies implemented to manage these diseases should include addressing both modifiable and non-modifiable risk factors for patients with NCDs. The aim of this study was to contribute to the reduction of incidence of uncontrolled T2DM among patients taking metformin as a first-line anti-diabetic drug, through the development of individualized therapy for this drug. When implemented, this could be one of the healthcare strategies to address non-modifiable risk factors for patients with T2DM as an important NCD. The first objective of the study was to explore the prevalence and risk factors of DM and HTN in South Africa, especially within the economically disadvantaged population.
Development and validation of a pharmacogenomics profiling panel suitable for personalizing metformin therapy
(University of the Western Cape, 2019) Xhakaza, Lettilia; Benjeddou, Mongi
The burden of non-communicable diseases (NCDs) in South Africa is predicted to increase substantially in the next decades if the necessary preventative measures are not taken. The two most common NCDs associated with rapid mortality increase are diabetes mellitus (DM) and hypertension (HTN). Both of these diseases, i.e DM and HTN, can be a result of a combination of modifiable risk factors (behavioral) and non-modifiable risk factors (genetic, physiological, and environmental). New strategies implemented to manage these diseases should include addressing both modifiable and non-modifiable risk factors for patients with NCDs. The aim of this study was to contribute to the reduction of incidence of uncontrolled T2DM among patients taking metformin as a first-line anti-diabetic drug, through the development of individualized therapy for this drug. When implemented, this could be one of the healthcare strategies to address non-modifiable risk factors for patients with T2DM as an important NCD. The first objective of the study was to explore the prevalence and risk factors of DM and HTN in South Africa, especially within the economically disadvantaged population.
Development and validation of Non-CODIS miniSTR genotyping systems suitable for forensic case work in South Africa
(University of the Western Cape, 2010) Abrahams, Zainonesa; Benjeddou, Mongi; Dept. of Biotechnology; Faculty of Science
The objective of this study was to develop and validate a six Non-CODIS miniSTR genotyping system and to determine its suitability for forensic casework in South Africa. In Non-CODIS miniSTR genotyping systems, smaller PCR products are amplified and the primers are positioned as close as possible to the repeat region. For this reason, these systems can be valuable in a variety of scenarios including complex paternity cases, missing persons work, and mass fatality disasters.
Development of genotyping systems for pharmacogenomics profiling
(University of the Western Cape, 2016) Eshumani, Fatima A.; Benjeddou, Mongi; Kirby, Bronwyn
Genetic variability in genes encoding drug metabolizing enzymes, transporters and targets are known to be the main factors of inter-individual differences in therapeutic outcome. Genetic factors are estimated to be responsible for about 15-30% of inter-individual variation in drug disposition and response. Single-nucleotide polymorphisms (SNPs) are the most prevalent class of genetic variation that could explain the variability in drug efficacy and undesired side effects for patients. The aims of this study were to develop and evaluate the performance of robust and high throughput techniques for genotyping ten polymorphisms related to anticancer drugs and ten polymorphisms related to cholesterol lowering drugs. SNaPshot minisequencing and high resolution melt analysis (HRM) genotyping panels were developed, optimized, and their performances were evaluated and compared. SNaPshot minisequencing systems were developed and successfully optimized for the genotyping of ten SNPs associated with anticancer drug therapy, and ten SNPs associated with cholesterol lowering drugs. These systems were used to genotype the selected SNPs in 130 healthy Cape Admixed participants residing in Cape Town, South Africa. Population genetics data obtained for the studied SNPs were analysed using several statistical analysis software tools. Important population genetic parameters were calculated. Among others, allelic and genotypic frequencies were determined and compared with other populations in the world. High resolution melt analysis (HRM) genotyping panels were developed, optimized and their performance were evaluated and compared to the SNaPshot assays. HRM was explored as an alternative inexpensive and rapid methodology to genotype five SNPs related to anticancer therapy and five SNPs related to cholesterol lowering therapy (statins). Unlike the SNaPshot assays, rigorous optimization was required for the detection heterozygous genotypes via HRM. Both assays were validated using direct sequencing and compared to each other. The HRM system is a closed tube, cheap and (theoretically) rapid method for identifying genetic variations. HRM was however found to be more time consuming, needed further optimization, primer redesigning and more evaluation. The developed genotyping systems could be further validated using clinical samples from patients. This could help in optimizing drug therapy for cancer and cholesterol treatment.
Development of infectious transcripts and genome manipulation of black queen-cell virus of honey bees
(Microbiology Society, 2002) Benjeddou, Mongi; Leat, Neil; Allsopp, Mike
The South African isolate of Black queen-cell virus (BQCV), a honey bee virus, was previously found to have an 8550 nucleotide genome excluding the poly(A) tail. Its genome contained two ORFs, a 5«-proximal ORF encoding a putative replicase protein and a 3«-proximal ORF encoding a capsid polyprotein. Long reverse transcription (RT)–PCR was used to produce infectious transcripts for BQCV and to manipulate its genome. Primers were designed for the amplification of the complete genome, the in vitro transcription of infectious RNA and PCR-directed mutagenesis. An 18-mer antisense primer was designed for RT to produce full-length single-stranded cDNA (ss cDNA). Unpurified ss cDNA from the RT reaction mixture was used directly as a template to amplify the full genome by long high-fidelity PCR. The SP6 promoter sequence was introduced into the sense primer to transcribe RNA directly from the amplicon. RNA was transcribed in vitro with and without the presence of a cap analogue and injected directly into bee pupae, which were then incubated for 8 days. In vitro transcripts were infectious but the presence of a cap analogue did not increase the amount of virus recovered.
Development of molecular tools for honeybee virus research: the South African contribution
(Academic Journals, 2003) Davison, Sean; Leat, Neil; Benjeddou, Mongi
Increasing knowledge of the association of honeybee viruses with other honeybee parasites, primarily the ectoparasitic mite Varroa destructor, and their implication in the mass mortality of honeybee colonies has resulted in increasing awareness and interest in honeybee viruses. In addition the identification, monitoring and prevention of spread of bee viruses is of considerable importance, particularly when considering the lack of information on the natural incidence of virus infections in honeybee populations worldwide. A total of eighteen honeybee viruses have been identified and physically characterized. Most of them have physical features resembling picornaviruses, and are referred to as picorna-like viruses. The complete genome sequences of four picorna-like honeybee viruses, namely Acute Bee Paralysis Virus (ABPV), Black Queen Cell Virus (BQCV), Sacbrood Virus (SBV) and Deformed Wing Virus (DWV) have been determined. The availability of this sequence data has lead to great advances in the studies on honeybee viruses. In particular, the development of a reverse genetics system for BQCV, will open new opportunities for studies directed at understanding the molecular biology, persistence, pathogenesis, and interaction of these bee viruses with other parasites. This review focuses on the contribution of the Honeybee Virus Research Group (HBVRG), from the University of the Western Cape of South Africa, in the development of molecular tools for the study of molecular biology and pathology of these viruses.
Development of Y-STR genotyping systems suitable for sexual assault cases in South Africa
(University of the Western Cape, 2010) Cloete, Kevin Wesley; Benjeddou, Mongi; Dept. of Biotechnology; Faculty of Science
Sexual assault is a significant problem facing the South African society. In this context, efficient but also affordable genotyping systems are needed for positive identification of criminals in incidences of sexual violence. The aim of this study was therefore to develop non-commercial Y-STR genotyping systems suitable for sexual assault cases in South Africa. Y-chromosome STR loci constituting the minimal haplotype are still the most widely used loci in investigating sexual assault cases despite the fact that DYS391 and DYS392 have shown low levels of polymorphism in Xhosa populations in Cape Town. The minimal haplotype was, therefore, further investigated in the Cape Muslim population. The Cape Muslim population generally exhibited high GD values among all the South African populations. These values were higher than 0.5 for most loci, and ranged from 0.447 for DYS391 to 0.957 for DYS385. The highest number of alleles in most loci was also recorded in this population. The overall assessment of the minimal haplotype has shown that this system is still a useful in investigating sexual assault case in many South African subpopulations. Therefore the exercise of internal validation of the minimal haplotype system was successfully carried out in the laboratory. The properties of additional novel and widely used STRs were also investigated in this study. Loci were successfully sequenced and allele nomenclature was assigned to them according to the ISFG guidelines.
Effects of xhosa specific solute carrier family 22-member 2 haplotypes on the cellular uptake of metformin and cimetidine
(Elsevier B.V., 2025) Abrahams-October, Zainonesa; Kippie, Yunus; Pearce, Keenau; Benjeddou, Mongi
Background: Studies have shown that solute carrier transporters play an important role in the transport and distribution of metformin, and that genetic variation(s) in solute carrier genes have play a role in the variation of metformin efficacy and disposition observed in populations. This study aimed to determine the cellular uptake efficiency of metformin in SLC22A2 coding haplotypes of an indigenous South African population. Methods and results: To determine metformin and cimetidine cellular uptake in transfected HEK-293 cells, ultra high-performance liquid chromatography was used to quantitate substrate concentration(s). Haplotypes 3 and 4 showed decreased metformin uptake, and haplotypes 2 and 5 displayed increased metformin uptake in comparison to haplotype 1 (i.e. wildtype haplotype). Haplotypes 2–5 showed decreased uptake of cimetidine in comparison to haplotype 1, implying a reduced sensitivity to the inhibition of cimetidine. In all haplotypes, no significant transport was observed for metformin and cimetidine. Passive permeability of metformin was favoured in haplotypes 3 and 5, whilst the remaining haplotypes demonstrate higher passive permeability ratios in favour of cimetidine. Conclusion: Haplotype 4, which is characterised by the non-synonymous single nucleotide polymorphisms rs316019 and rs8177517, demonstrates potential impaired metformin transport.
Genetic diversity of the Organic Cation Transporter 1 gene within the Cape Coloured Population
(University of the Western Cape, 2012) Pearce, Brendon; Benjeddou, Mongi; Dept. of Biotechnology
The aim of this study was to investigate the genetic diversity of the SLC22A1 gene and to deduce its possible pharmacogenetic implications within the Cape Coloured population of South Africa; a uniquely admixed population of immigrant Europeans, Asians and the indigenous populations. Recent studies have reported an abundance of polymorphic variants within this solute carrier transporter gene encoding for the organic cation transporter 1, as well as evidence linking these variants to an effect on metformin uptake. This study included establishing baseline frequency distribution of previously reported alleles for 20 SNP variants within the SLC22A1 gene, as well as the development of SNaPshot® and Multiplex AS-PCR genotyping assays, and also exploring the possibility of using High-resolution melt (HRM) analysis as a costeffective alternative for SNP genotyping. Ethics clearance was obtained from the Ethics Committee of the University of the Western Cape. Biological samples in the form of buccal (oral) swabs were collected from 132 unrelated voluntary donors from the Cape Coloured population residing in the Cape Metropolitan area. Two SNaPshot® Multiplex Systems were specifically designed for the study,successfully optimized and used for genotyping. Hundred genetic profiles were then generated for a total of 20 SNP variants on SLC22A1 gene, using this primer extension-based genotyping method that enables multiplexing up 10 SNPs. Population genetics data obtained for the investigated SNPs were analysed using various statistical analysis software. Important population genetic parameters were calculated, and possible pharmacogenetics implications were then discussed. Among others, allelic and genotypic frequencies, as well as linkage disequilibrium were determined and compared with world populations. Minor deviation from Hardy- Weinberg equilibrium was observed in the Cape Coloured population. No significantLinkage Disequilibrium between the investigated SNPs was observed in this population. A Multiplex allele specific – PCR (MAS-PCR) genotyping system was successfully designed and optimized for the genotyping of 10 SNPs from the SLC22A1. This system, also developed specifically for this study, was made of 2 multiplexes each covering 5 SNPs. It is an inexpensive genotyping assay that allows for efficient discrimination of SNP polymorphisms in one reaction tube with standard PCR conditions. A pilot study was conducted to explore the possibility of using High-resolution melt (HRM) analysis as a cost-effective alternative for SNP genotyping. In addition to genotyping, HRM analysis can be used to scan large numbers of samples for novel genetic variations.
Genomic diversity and functional analysis of the solute carrier genes within indigenous African and Cape Admixed populations
(University of the Western Cape, 2016) Pearce, Brendon Clive; Benjeddou, Mongi
Solute carrier transporters belonging to the major facilitator family of membrane transporter are increasingly being recognized as a possible mechanism to explain inter-individual variation in drug efficacy and response. Genetic factors are estimated to be responsible for approximately 15-30% of inter-individual variation in drug disposition and response. The aims of this study were to determine the minor allele frequencies of 78 previously identified single nucleotide polymorphisms in the pharmacogenomically relevant SLC22A1-3 and SLCO1B1 genes in the Admixed population of South Africa. Thereafter, to determine whether allele and genotype frequencies for these SNP were different from that reported for other African, Caucasian, and Asian populations. The inferred haplotypes from the genetic information possessed the potential to subsequently be used in future to design and interpret results of pharmacogenomic association studies involving these genes and their substrate drugs. Furthermore, to determine whether the Cape Admixed population harbour novel SNPs in the proximal promoter regions of SLC22A1- 3 and SLCO1B1-3 genes, that encodes hOCT1-3 and hOATP1 and hOATP3, respectively. SNaPshot™ multiplex single base mini-sequencing systems were developed and optimized for each of SLC22A1, SLC22A2, SLC22A3, and SLCO1B1 genes covering the previously identified 78 SNPs. These systems were then used to genotype the alleles of 130 healthy Cape Admixed subjects residing in Cape Town, South Africa. In addition, the proximal promoter regions of the SLC22A1-3 and SLCO1B1-3 genes of 96 of the participants were screened for novel SNPs by direct sequencing. The Cape Admixed subjects investigated displayed a lack of variation and were monomorphic for 78% of the SNPs screened. None of the SLC22A3 SNPs investigated was observed in this study. Sequencing of the proximal promoter regions of the SLC22 and SLCO genes did not reveal any novel SNPs in the 96 Cape Admixed subjects that were screened. This study highlights the fact that African populations do not have the same allele frequencies for SNPs in harmacogenomically relevant genes. Furthermore, the Cape Admixed and other African populations do not share all reduced-function variants of the SLC22A1-3 and SLCO1B1-3 genes with Caucasian and Asian populations. In addition, previously identified novel regulatory variants in SLC22A2 did not exhibit a significant effect on the ability of the promoter to drive transcription. However, it must be noted that these results were observed at 95% confidence interval, and that a 99% confidence interval the significance may increase theoretically. Additionally, it should be noted that more intensive studies are required to determine the potential effect these novel variants may well cause. This study lays the foundation for the design and interpretation of future pharmacogenomic association studies between the variant alleles of the SLC22A and SLCO genes in the Cape Admixed population, as well as optimizations for future expression, and more importantly, drug transport assays with respect to drug disposition and efficacy.
Glucose-uptake activity and cytotoxicity of diterpenes and triterpenes isolated from lamiaceae plant species
(2020) Benjeddou, Mongi; Etsassala, Ninon G.E.R.; Ndjoubi, Kadidiatou O.
The prevalence of diabetes mellitus (DM), considered one of the most common metabolic disorders, has dramatically increased and resulted in higher rates of morbidity and mortality around the world in the past decade. It is well known that insulin resistance in target tissues and a deficiency in insulin secretion from pancreatic β-cells are the main characteristics of type 2 diabetes. The aim of this study was the bio-evaluation of compounds isolated from three selected plant species: namely, Salvia africana-lutea, Leonotis ocymifolia, and Plectranthus madagascariensis, for their glucose-uptake ability. Methanolic extracts were produced from the aerial parts of each plant. Compounds were identified using different spectroscopic techniques. The glucose-uptake ability of each compound was then evaluated in mammalian cells using 2-deoxyglucose-6-phosphate. The cytotoxicity of each compound was established via the MTT assay.
Identification of sub-clinical biomarkers that predict the risk of developing diabetic cardiomyopathy
(University of the Western Cape, 2022) Nxele, Xolisa; Benjeddou, Mongi
Cardiovascular disease (CVD) is the leading cause of death of people with obesity and type 2 diabetes (T2DM). According to a statistical report from the World Health Organization (WHO), approximately 17.9 million people die annually because of CVD and diabetic cardiomyopathy (DCM), a disease of the heart muscle occurring in the absence of coronary artery disease or hypertension. Although not fully elucidated, the pathophysiology of DCM includes myocardial left ventricular hypertrophy, impaired calcium handling, energy metabolism, inflammation, apoptosis and myocardial fibrosis.
In vitro evaluation of Leonotis leonurus to validate its potential as an alternative anti-diabetic drug
(University of the Western Cape, 2022) Sigodi, Yolanda; Benjeddou, Mongi
Africa is a rich source of medicinal plants with South Africa being known as a country with a strong history of traditional healing, which masses a variety of approximately 30 000 flowering plants and accounting for almost 10% of the world’s higher plant species. Leonotis leonurus, a member of the Lamiaceae family, has shown potential biomedical applications in a great diversity of ailments and has shown to have antidiabetic activity, with the most common herbal active ingredients used in treating diabetes being flavonoids, tannins, phenolics, and alkaloids (Hussein, 2018). In the present study, L. leonurus was screened for possible bioactive chemicals.
Inter-individual genetic variation and the development of hypertension in a Xhosa African population of Eastern Cape, South Africa
(University of the Western Cape, 2022) Mabhida, Sihle Ephraim; Benjeddou, Mongi
Cardiovascular diseases (CVD) are the leading cause of death globally, accounting for 18.6 million deaths. Hypertension (HTN) drives the global burden of CVD and is a leading cause of cardiovascular-related mortality with 1.4 billion affected adults and 10.4 million deaths globally. This public health condition has been escalating alarmingly in low and middle-income countries. In Sub-Saharan Africa, HTN is a major public health concern with South Africa having the highest prevalence between 27-58%. Accumulative evidence shows that HTN is driven by both modifiable and non-modifiable risk factors.
Intervertebral disc degenerative disease in South Africa: a case-control analysis of selected gene variants
(Springer Science and Business Media B.V., 2024) Pearce, Keenau; Less, Stephanie; Benjeddou, Mongi
Background: Intervertebral disc (IVD) degenerative disease is a multifactorial disease for which genetics plays an integral role. Several genes, and their variants, associated with the development and progression of IVD degenerative disease have been identified. While several studies have investigated these genes in Asian and European populations, no available evidence exists for the South African population. Therefore, this study aimed to investigate these parameters. Methods and results: Biological samples were collected in the form of buccal swabs from patients and DNA was extracted using a standard salt-lysis protocol. DNA purity and quantity was assessed by spectrophotometry, and subsequent genotyping was performed using the MassARRAY®System IPLEX extension reaction. For associations between variants and the presence of IVD degenerative disease, odds ratios (OR), confidence intervals (CI), chi-squared analysis and logistic regression was calculated. Age and sex were adjusted for, and Bonferroni’s correction was applied. This study found statistically significant associations for five of the evaluated single nucleotide polymorphisms (SNPs) with IVD degenerative disease, whereby IL-1α rs1304037 and rs1800587, ADAMTs-5 rs162509, and MMP-3 rs632478 demonstrated increased odds of a positive diagnosis for IVD degenerative disease, while decreased odds of IVD degenerative disease were seen for GDF-5 rs143383. Conclusion: To the best of our knowledge, this study represents the first of its kind to investigate the association of gene variants associated with IVD degenerative disease within the South African population. This study has shown that 5 of these gene variants were significantly associated with the presence of IVD degenerative disease, reflecting their integral roles in development and possible progression of the disease.
Intervertebral disc degenerative disease in South Africa: a case-control analysis of selected gene variants
(Springer Nature, 2024) Pearce, Keenau; Less, Stephanie; Benjeddou, Mongi
Intervertebral disc (IVD) degenerative disease is a multifactorial disease for which genetics plays an integral role. Several genes, and their variants, associated with the development and progression of IVD degenerative disease have been identified. While several studies have investigated these genes in Asian and European populations, no available evidence exists for the South African population. Therefore, this study aimed to investigate these parameters.
Investigation of socio-demographic, clinical and genetic factors associated with blood pressure and glycaemic control among indigenous South African adult patients
(University of the Western Cape, 2021) Masilela, Charity Mandisa; Benjeddou, Mongi
Achieving blood pressure and glycaemic treatment targets remain a major public health challenge in individuals with hypertension and diabetes mellitus (DM). This research project was, therefore, designed to investigate the socio-demographic, clinical and genetic factors associated with blood pressure and glycaemic control among indigenous South African adult patients. The main aims of the project were as follows: (1) To assess the prevalence and socio-demographic factors associated with uncontrolled hypertension, in individuals receiving chronic care in primary healthcare facilities, based in the rural areas of Mkhondo Municipality (Study 1). (2) To investigate the association of nineteen single nucleotide polymorphisms (SNPs) with blood pressure control among adult patients treated with hydrochlorothiazide (Study 2). (3) To assess the level of association between twelve SNPs with uncontrolled blood pressure for adult patients treated with amlodipine (Study 3). (4) To examine the association of five SNPs in selected genes (ABO, VEGFA, BDKRB2, NOS3 and ADRB2) with blood pressure response to enalapril treatment, and further assess interaction patterns that influence blood pressure response (Study 4). (5) To determine the prevalence of poor glycaemic control and its influencing factors among adult patients from Mkhondo Municipality attending chronic care for DM (Study 5). (6) To evaluate the level of association between polymorphisms found in the SLC22A1, SP1, PRPF31, NBEA, SCNN1B, CPA6 and CAPN10 genes, and glycaemic response to metformin and Sulphonylureas (SU) combination therapy among South African adults with DM. Also, to investigate interaction patterns that influence glycaemic control in response to metformin and SU combination therapy (Study 6).
Liposomal-naringenin radiosensitizes triple-negative breast cancer mda-mb-231 cells in vitro
(John Wiley and Sons Inc, 2024) Pearce, Keenau; Cairncross, Samantha; Benjeddou, Mongi
Naringenin has shown great promise in the realm of cancer therapeutics, demonstrating excellent cytotoxic action toward cancer cells and the enhanced effects of radiation therapy in vitro. However, the medicinal value of naringenin is severely limited clinically by poor bioavailability. Thus, multiple drug-delivery strategies for overcoming this limitation have been developed, of which liposomes are considered the most suitable due to their amphiphilic, modifiable, and biocompatible characteristics. In this study, we investigated the role of naringenin and liposomal-delivered naringenin as adjuncts to radiotherapy in the MDA-MB-231 triple-negative breast cancer cell line in vitro. Liposomal-naringenin was synthesized by thin-film hydration and extrusion and was characterized by spectrophotometry, dynamic light scattering, and zeta potential. The effects of free-from naringenin and liposomal-naringenin were evaluated toward MDA-MB-231 cell viability when combined with varying doses of radiation. Additionally, cell growth patterns, morphology, and colony formation were evaluated. The analysis demonstrated IC50 values of 387.5 and 546.6 µg/ml for naringenin and liposomal-naringenin, respectively. Naringenin and liposomal-naringenin significantly lowered cell viability, proliferation, and colony formation dose-dependently, as compared to radiation in isolation. The findings presented herein concur with previous accounts of the radiosensitizing potential of naringenin and further highlight the considerable biomedical application of liposomal-naringenin within the realm of radiotherapy.
Molecular detection and genetic manipulation of the Black Queen Cell Virus
(University of the Western Cape, 2002) Benjeddou, Mongi; Davison, Sean; Dept. of Biotechnology; Faculty of Science
The South African isolate of the Black Queen-Cell Virus (BQCV), a honeybee virus, was previously found to have an 8550 nucleotide genome excluding the poly(A) tail. Its genome contained two ORFs, a 5'-proximal ORF encoding a putative replicase protein and a 3'-proximal ORF encoding a capsid polyprotein.A reverse transcriptase PCR (RT -PCR) assay was developed for the detection of BQCV and acute bee-paralysis virus (ABPV). Complete genomes sequences w ere used to design unique PCR primers within a l-kb region from the 3' end of both genomes to amplify a fragment of 70.0 bp from BQCV and 900 bp from ABPV. The combined guanidinium thiocyanate and silica membrane method was used to extract total RNA from samples of healthy and laboratory-infected bee pupae. In a blind test, RT-PCR successfully identified the samples containing BQCV and ABPV. Sensitivities were of the order of 130 genome equivalents of purified BQCV and 1600 genome equivalents of ABPV.

Browsing by Author "Benjeddou, Mongi"

Results Per Page

Sort Options