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Item CHARACTERIZATION OF THE GUT MICROBIOME AND INFLAMMATORY MARKERS IN TREATMENT-NAIVE TRIPLE-NEGATIVE BREAST CANCER (TNBC) PATIENTS IN LAGOS, NIGERIA(Covenant University Ota, 2025-10) OGUNLEYE, Oluwanifemi Omodara; Covenant University DissertationTriple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen, progesterone, and HER2 receptors. Emerging studies suggest that gut microbial imbalance and chronic inflammation may contribute to breast cancer progression. This study investigated the gut microbiome profile and circulating inflammatory markers in treatment-naive TNBC patients compared with unknown subtypes and healthy controls to understand the microbiome–inflammation relationship in TNBC pathogenesis. Fecal DNA from TNBC, unknown subtype, and healthy control groups was extracted and analyzed using 16S rRNA sequencing through the Nephele QIIME2 pipeline. Alpha diversity was evaluated with the Shannon index, and group differences were tested using the Kruskal–Wallis and Mann–Whitney tests. Serum IL-6 and TNF-α levels were quantified using ELISA, and correlations were assessed using Pearson and Spearman analyses. Alpha diversity analysis revealed no statistically significant difference among groups (Kruskal–Wallis p = 0.298), though TNBC samples exhibited lower and more variable Shannon index values compared with controls. TNBC samples showed unstable high levels of Firmicutes, and Bacteriodota, and varying low levels of Proteobacteria and Actinobacteriota, indicating microbial imbalance. IL-6 and TNF-α levels did not differ significantly between TNBC and controls (p > 0.05), though TNBC patients displayed higher variability. A moderate positive correlation was found between IL-6 and TNF-α in TNBC (r = 0.5982), indicating co-regulated inflammatory activity. The PICRUSt functional prediction revealed altered microbial metabolic pathways in TNBC patients compared to controls, particularly a reduction in butyrate and propionate metabolism associated with short-chain fatty acid production. The findings suggest early gut dysbiosis and immune imbalance in TNBC despite the absence of significant statistical differences. Reduced microbial diversity, altered phylum-level composition, and cytokine co-regulation indicate biological perturbations in treatment-naive TNBC. These findings collectively support a potential link between microbial dysbiosis, altered short-chain fatty acid metabolism and elevated inflammatory activity in TNBC pathogenesis. It also highlights the need for larger, longitudinal studies to validate microbial and inflammatory biomarkers for early disease characterization.Item CHARACTERISATION OF THE GUT MICROBIOME AND FUNCTIONAL PROFILE IN ESTROGEN RECEPTOR-POSITIVE BREAST CANCER PATIENTS IN LAGOS, NIGERIA(Covenant University Ota, 2025-10) WILLIAMS, Moyosoreoluwa Mary; Covenant University DissertationEstrogen receptor-positive (ER+) breast cancer is the most prevalent molecular subtype globally, yet its association with gut microbial composition, functional potential and inflammatory drivers remains uncharacterised in sub-Saharan Africa. Employing the intersection of microbiology, oncology, and genomics, this study investigated the gut microbiome, predicted functional profiles, and systemic inflammatory markers in treatment-naïve ER+ breast cancer patients compared to healthy controls in Lagos, Nigeria. Faecal DNA samples from participants were extracted and analysed using 16S rRNA sequencing on the Illumina MiSeq platform using the QIIME2 pipeline. Microbial diversity was assessed through alpha (Shannon index) and beta diversity (NMDS, PCoA) metrics, and the group differences were tested using the Mann–Whitney test and Kruskal–Wallis, while PICRUSt2 predicted functional pathways with on focus on β-glucuronidase. Concurrently, systemic inflammation was evaluated through the quantification of Interleukin-6 (IL-6) and C-reactive protein (CRP) from blood serum. Analysis revealed no significant differences in alpha diversity between groups (p > 0.05). However, beta diversity demonstrated substantial compositional divergence (PERMANOVA R²=0.11, p=0.02), with cases showing an elevated Firmicutes/Bacteroidota ratio and depletion of Actinobacteriota, including Bifidobacterium and Collinsella. Functional prediction indicated heightened β-glucuronidase activity in ER+ cases, suggesting enhanced estrogen reactivation potential. Inflammatory markers displayed a complex profile, with significantly reduced IL-6 levels in patients despite stable CRP concentrations. These findings characterise distinct gut microbial dysbiosis and functional alterations in Nigerian ER+ breast cancer patients, revealing an estrobolome configuration potentially contributing to pathogenesis. The results underscore the necessity of population-specific microbiome studies and highlight potential biomarkers for early detection and targeted interventions in this understudied population.Item SINGLE NUCLEOTIDE POLYMORPHISMS OF Pfdhfr RESISTANCE GENE AMONG SYMPTOMATIC PATIENTS’ ISOLATES FROM SELECTED HOSPITALS IN IFO LGA, OGUN STATE(Covenant University Ota, 2025-10) SULE, Queen Elizabeth; Covenant University DissertationMalaria remains a primary universal health concern, particularly in endemic areas where drug resistance poses a serious threat to the effectiveness of key treatment and prevention strategies. Sulfadoxine-pyrimethamine (SP), commonly used for malaria prophylaxis, is increasingly compromised by resistance associated with mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) gene. This study aimed to assess the prevalence of P. falciparum infection and identify the single-nucleotide polymorphisms (SNPs) in the Pfdhfr resistance gene among symptomatic patients in Ifo Local Government Area, Ogun State, Nigeria. Five hundred patients with severe P. falciparum infection were recruited, and demographic data were recorded. Blood samples were analysed for P. falciparum stages and parasitemia levels using microscopy. DNA was extracted from samples with high parasitemia and genotyped for Pfdhfr mutations using PCR, followed by visualisation on 1% agarose gel electrophoresis. Microscopy confirmed P. falciparum malaria in 300 patients (60%). A significantly higher prevalence (71.05%) was recorded in the 0–4 years’ age group, while males accounted for 64.31% of cases (p < 0.05). Parasitemia levels (greater than 200 parasites/100 μL) were more pronounced in males than in females, and were highest among individuals aged 0–4 years. Among the 10.67% Pfdhfr genotypes identified, males exhibited a higher frequency (6.0%) than females. The overall prevalence of pfdhfr SNPs in N51I, C59R, S108, and I64L was (96%), (96%), (100%), and (0%), respectively. tripple mutant halotype (N51I+ C59R+S108), prevance was 92%. Males have a higher mutation rate (60%) than females (40%). The overall prevalence of pfdhfr SNPs in N51I, C59R, S108, and I164L was (96%), (96%), (100%), and (0%), respectively. tripple mutant halotype (N51I+ C59R+S108), prevance was 92%. Males have a higher mutation rate (60%) than females (40%). Also, individuals aged 0-4 years (20%) and 15-20 years (20%) show higher SNPs than the other age groups. The study highlights a high prevalence of P. falciparum and emerging Pfdhfr resistance mutations, emphasising the need for continuous surveillance and targeted interventions in malaria-endemic regions, such as Ifo LGA, Nigeria.Item FUNGAL-MEDIATED VANILLIC ACID PRODUCTION THROUGH BIOCONVERSION OF GALLIC ACID OBTAINED FROM RICE BRAN(Covenant University Ota, 2025-08) OGUNBAJO, Oluwafemi Omolade; Covenant University DissertationGallic and vanillic acids are naturally occurring phenolic compounds widely used in the pharmaceutical, food, and cosmetic industries due to their antioxidant properties. Rice bran is a nutrient-rich agro-industrial by-product. However, there are challenges of improper disposal and underutilization as a substrate for the production of valuable bioactive compounds. This study investigated the fungal-mediated bioconversion of rice bran into gallic acid under solid-state fermentation (SSF) and its subsequent transformation into vanillic acid through submerged fermentation (SMF) using Aspergillus niger. It was inoculated into a fermentation medium containing pre-treated rice bran and mineral salts and incubated for 5 days at 30 °C. Fermentation was monitored for pH, temperature, UV-Vis absorbance (276nm), and titration. The produced gallic acid was characterized using HPLC, GC-MS, and FTIR. Thereafter, 1% Methanol was introduced into a mineral salt medium containing the produced gallic acid as the substrate, and inoculated 1ml of the inoculum and incubated at 30 °C for 5 days. This was monitored and characterized as in the gallic acid production. During fermentation, the temperature ranged 28-33 °C, pH decreased from 6.5 to 5.2, the absorbance rose from 0.205 to 0.681 nm, and titration increased from 0.016 to 0.075 mol (p<0.05). HPLC quantified 6552.2 mg/L total phenolics, with gallic acid at 2569.8 mg/L. FTIR revealed gallic acid functional groups such as O–H, C=O, and C=C, while GC-MS identified volatile compounds including O-toluic acid, 2(1H)-naphthalene derivatives, and 3H-Cyclodeca[b]furan-2-one. For the vanillic acid production, fermentation filtrate temperature stayed at 29-30 oC, with the pH increasing in acidity from 6.5 to 4.3 through the 5-day period. This corresponded with the results of the titration, showing 0.016 to 0.079 mol results.The GC-MS showed volatile organic compounds present in vanillic acid, including protocatechuic, catechol, and syringic acids. HPLC quantified a total of 15,31203 mg/L of vanillic acid. FTIR revealed vanillic acid functional groups such as OCH₃, OH, and C=O. The results of this study provides strategic insights for sustainable bioprocess approaches in support of SDGs 3 and 12.Item EXPRESSION PROFILES OF CYTOCHROME P450 GENES ASSOCIATED WITH PERMETHRIN RESISTANCE IN Anopheles gambiae s.l. IN ADO-ODO OTA, OGUN STATE(Covenant University Ota, 2025-10) AINA, Motunrayo Oluwabunmi; Covenant University DissertationMalaria remains a significant tropical public health threat, where resistance to insecticides constitutes a severe hindrance to the efficacy of its primary vector control methods. Routinely applied pyrethroid insecticides are increasingly facing resistance associated with the overexpression of cytochrome P450 genes in the Anopheles gambiae sensu lato, underscoring the urgent search into these associated genes. This study assessed the expression profile of cytochrome P450 genes associated with permethrin resistance in Anopheles gambiae sensu lato collected from three localities in Ado-Odo, Ota. Ethical approval was obtained from the Covenant Health Research Ethics Committee (CHREC). Based on the WHO standard, female adult An. gambiae larvae (n=300) were collected using the dipping method and reared into adults in the Insectary Laboratory. These laboratory-reared mosquitoes were phenotypically identified using microscopy and genotypically characterised using polymerase chain reaction (PCR) based on species-specific primers. Thereafter, a WHO susceptibility bioassay was conducted in vivo for mosquitocidal activity against these adult mosquitoes in four replicates at a 0.75% permethrin concentration each on day 3 post-adult emergence. The relative expression of the cytochrome P450 genes (CYP6M2 and CYP6P3) was carried out using the quantitative real-time PCR (qRT-PCR). Higher occurrence rate of An. gambiae sensu lato. was recorded in Nestle (80%)), Chelsea (78%)) compared Gasline (30%) localities of Ado-Odo. In vivo insecticide susceptibility testing revealed consistently low mortality rates across all the replicates, ranging from 20% to 32% indicating increased resistance to permethrin. Results of relative expression of cytochrome P450 genes showed higher fold changes in CYP6M2 ranging from 0.63 to 122.4 than in CYP6P3 0.63 to 34.39 across the tested mosquito replicates. Thus, this study has further emphasized the prevalence of An. gambiae sensu lato members in Ado-Odo, Ota. Additionally, the results of higher permethrin resistant and upregulation of CYP6M2 and CYP6P3 genes inform the imminent need for integrated resistance surveillance with newer vector management for improved malaria control.Item ASSESSMENT OF THE QUALITY ATTRIBUTES OF BIOTRANSFORMED IPOMEA INVOLUCRATA LEAVES(Covenant University Ota, 2025-09) OLEKA-ARIWODO, Chiamaka Jennifer; Covenant University DissertationThe need for functional foods has found interest in underutilised leaves with potential health benefits. An underutilised plant, Ipomoea involucrata was used for this study while Amaranthus hybridus served as the control leaves for monitoring the edible status of the experimental leaves. The aim of this research is to assess the quality attributes of Ipomoea involucrata processed with a specific probiotic-aided fermentation into health-beneficial edible vegetable. I. involucrata leaves were collected, dried, and then submerged in LAB fermentation for 0, 24, 72, and 120 hours aseptically. Post fermentation test includes nutrition analyses (including mineral content), pH, antioxidant qualities, enzymatic tests, while vitamins and phytochemicals were determined by HPLC. According to the results, the pH of both plants decreased significantly (p < 0.05). Bacterial counts increased across all fermentation days in both plants. In I. involucrata, nutritional analysis showed a significant increase in carbohydrate and Ash, but a decrease in moisture and crude fiber. FRAP results were maintained, whereas DPPH scavenging capacity and protein content fluctuated across all fermentation days. LDH activity significantly reduced before increasing again, while α-amylase activity generally increased during the 5-day fermentation. In vitamin profiles, By Day 5, vitamin A, vitamin B2 reduced, while an increase in vitamin B9 were noticed. In I. involucrata, vitamin C increased on Day 3, whereas vitamin E initially dropped. According to the phytochemical analysis, rutin, catechin, resveratrol and kaempferol decreased, while the phenolic compounds like epicatechin and ellagic acid increased. Saponins revealed that stevioside increased and ginsenosides fluctuated. Mineral analysis significantly decreased in heavy elements including lead and cadmium. In this study, LAB fermentation improved the phytochemical and nutritional profile of I. involucrata, mainly by enriching bioactive substances, modifying vitamins and enzymes, and reducing toxic metals.Item TARGET-SITE MUTATION GENOTYPING OF INSECTICIDE-RESISTANT FEMALE Anopheles MOSQUITOES IN OTA(Covenant University Ota, 2025-10) TAIWO, Damilare Isaiah; Covenant University DissertationMalaria control techniques in sub-Saharan Africa significantly depend on insecticide-based measures such as insecticide-treated nets (ITNs) and indoor residual spraying (IRS). However, the resistance emergence in Anopheles mosquitoes, driven by target-site mutations, undermines their effectiveness and threatens elimination efforts. Key resistance markers include knockdown resistance mutations (Kdr) in the voltage-gated sodium channel (VGSC) gene and the G119S mutation in the Ace-1 gene, both of which reduce insecticide efficacy. This study investigated the morphological and molecular composition of Anopheles populations, their insecticide resistance status, prevalence of Kdr and Ace-1 mutations, and assessed the genetic diversity, gene flow, and population structure across breeding sites in Ota, Ogun State, Nigeria. Using Coetzee’s key, a total of 478 adult female mosquitoes were obtained and morphologically identified, with molecular assays confirming a uniform species composition of Anopheles gambiae (390 bp) across all sites. Susceptibility assays revealed strong pyrethroid resistance, with permethrin mortality rates of 15–25%, far below the WHO threshold of 90%. However, bendiocarb produced 98–100% mortality, indicating high susceptibility. Genotypic analysis showed predominance of the Kdr-W (L1014F) allele, especially in Nestle and Iju, where homozygous resistant individuals were frequent. The Kdr-E (L1014S) allele was rare and largely confined to homozygous susceptible genotypes, suggesting it is not yet established. Deviations from the Hardy-Weinberg equilibrium were detected in Nestle populations, while sequence alignment confirmed L1014F mutations in Atan, Iju, and Chelsea. Population genetic analyses showed no strong subdivision (χ² = 0.7885, Fst = -1.3586, Gst = -0.0395, Kst = -0.13760), but high haplotype diversity (Hd = 0.94–1.00), moderate nucleotide diversity (π = 0.27–0.31), and substantial gene flow (Nm ≈ 8.24), supported by PCA and phylogenetic clustering. This study reveals widespread pyrethroid resistance but sustained carbamate susceptibility, providing the first genetic dataset from Ota to guide surveillance and resistance management strategies.Item DEVELOPMENT OF A REGULARIZATION-BASED FAIRNESS-AWARE LOSS FUNCTION FOR MITIGATING POPULARITY BIAS IN MOVIE RECOMMENDER SYSTEMS(Covenant University Ota, 2025-08) IDOWU, Esther Oluwaseyi; Covenant University DissertationRecommender systems are a cornerstone of the movie entertainment industry, driving user engagement and personalizing content delivery to enhance customer experience. However, popularity bias where certain content is disproportionately recommended can limit the visibility of diverse contents, undermining innovation and customer satisfaction. This study proposed a regularization-based fairness-aware mechanism designed to mitigate popularity bias in recommender systems. The proposed mechanism integrates fairness-aware loss functions, such as exposure fairness loss, fairness-aware ranking loss and disparate Impact Loss, into the Neural Collaborative Filtering recommendation algorithm. The fairness-aware model was integrated into a movie recommendation system. The system was evaluated for technical effectiveness in terms of recommendation accuracy, fairness in exposure, and usability in real-world entertainment business contexts. All models achieved very high exposure fairness (≥0.9995). REBFAL matched the best baselines in long-tail coverage (0.2987) while showing a slightly higher exposure imbalance (0.7487), reflecting a trade-off between fairness and distribution.Item ASSOCIATION OF COMT AND CYP1B1 POLYMORPHISMS WITH PROSTATE CANCER RISK IN NIGERIAN MEN(Covenant University Ota, 2025-09) Pirisola, Ayomikun Joshua; Covenant University DissertationProstate cancer (PCa) disproportionately affects men of African descent, with Nigeria recording high mortality rates, yet genetic studies in this population remain sparse. This study investigated the association between COMT rs4680 Val158Met, rs9332377, and CYP1B1 rs1056836 genetic variants and PCa risk and severity in Nigerian men. This case-control study involved 65 histologically confirmed PCa patients aged (median) 65 years old and 59 healthy controls aged (median) 60 years old. Genomic DNA was extracted from whole blood. Genotyping was conducted via TaqMan real-time PCR. Chi-square tests were conducted to compare genotype/allele frequencies, and associations were estimated using unadjusted logistic regression odds ratios (ORs) with 95% confidence intervals. Kruskal-Wallis tests and Spearman correlations were used to examine correlations with Gleason scores. Findings showed that there is a significant genotype and allele difference in COMT rs4680, where low-activity AA is the genotype that presents high risk (OR=9.50, 95% CI: 3.08-36.42, p<0.001 vs. GG), under genotypic as well as dominant models. In the case of rs9332377, the effect of the TT genotype showed a trend towards a protective effect but did not reach statistical significance (OR=0.21, 95% CI: 0.03-0.94, p=0.062 vs. CC). There were significant differences in CYP1B1 rs1056836, with the C alleles higher in cases (83.7% vs. 13.6%), and the GG risk being borderline (OR=4.074, p=0.056). None of the variants were significantly correlated with Gleason scores (p>0.05), although there was a trend in the case of rs1056836 (Spearman rho=0.263, p=0.089). These results suggest that genetic variation in COMT and CYP1B1 may contribute to PCa susceptibility among Nigerian men, potentially through impaired oestrogen detoxification pathways. Further validation in larger cohorts, with adjustments for environmental factors and comparisons across populations, is needed to clarify these associations.Item EVALUATION OF SYNTHETIC FLAVONOID BASED COMPOUNDS AS INHIBITORS OF Plasmodium falciparum TRANSKETOLASE(Covenant University Ota, 2025-09) OROGUN, Yetunde Grace; Covenant University DissertationMalaria, primarily attributed to Plasmodium falciparum, remains a significant contributor to global mortality, with Africa experiencing the greatest burden, particularly in countries such as Nigeria, the Democratic Republic of Congo, and Mozambique. The rise in resistance to present therapies, including Artemisinin-based Combination Therapies (ACTs), underscores the urgent need for novel drug targets. Transketolase, a thiamine-dependent enzyme in the non-oxidative arm of the pentose phosphate pathway, is vital for parasite metabolism and structurally distinct from the human enzyme, making it a promising selective target. Twenty synthetic flavonoid-based compounds were evaluated as potential inhibitors of P. falciparum transketolase (PfTk). Molecular docking revealed strong binding affinities, while ADMET profiling showed that most compounds complied with Lipinski’s rule. Notably, Compounds 6, 7, 11, and 13 were predicted to be orally bioavailable with favorable pharmacokinetic and drug-likeness properties. The compounds were further tested in vitro against PfTk and human transketolase (hTk), with oxythiamine as the positive control, and cytotoxicity was assessed using hemolysis assays on human red blood cells. The results demonstrated that several compounds exhibited high potency and selective inhibition of PfTk with minimal activity on hTk. Among them, Compounds 6, 7, and 10 emerged as the most promising leads, combining high selectivity, oral bioavailability, and favorable safety margins. Additionally, Compounds 11 and 13, analogues of Compound 10, showed good drug-likeness and oral bioavailability, indicating potential for structural optimization. Hemolysis assays confirmed minimal red blood cell lysis across all compounds, supporting their safety. In conclusion, this study validates PfTk as a viable drug target and identifies Compounds 6, 7, and 10 as strong lead candidates, with Compounds 11 and 13 as promising analogues for further optimization and development of safe, effective antimalarial agents.