SACM - United Kingdom
Permanent URI for this collectionhttps://drepo.sdl.edu.sa/handle/20.500.14154/9667
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Item Restricted Biomarkers, Metagenomics, and Metabolomics in Grade C Molar Incisor Pattern Periodontitis: A Multidimensional Approach to Understand C/MIP Pathogenesis(King's College University, 2025) Alamri, Meaad Mohammed; Proctor, Gordon; Nibali, LuigiObjective: This project aimed to clarify grade C molar incisor pattern periodontitis (C/MIP) pathogenesis in young cases by comparing them to age-matched periodontitis-free controls in a multidimensional approach. Material and Methods: (1) The literature on saliva, GCF, serum, and blood biomarkers in systemically healthy and non-smoking young C/MIP (≤25 years old) was systematically searched for promising biomarkers. Six databases were searched, including PubMed, Embase, Web of Science, Scopus, Virtual Health Library and ProQuest, for cross-sectional, case-control, and cohort studies with more than 10 subjects in the cases group. Meta-analysis was done on biomarkers that were assessed using the same detection methods and sample type in at least two papers. (2) After that, a case series on 31 C/MIP young cases (≤25 years old) was compiled to evaluate grade C periodontitis through clinical data and radiographs. Following that, a series of four analyses were conducted on the same group of patients, the 31 C/MIP young cases in which (3) human total immunoglobulin G (IgG) levels were investigated in saliva, gingival crevicular fluid (GCF), and serum using an Enzyme-Linked Immunosorbent Assay (ELISA); (4) the saliva and serum metabolites profiles of C/MIP and controls were analysed using a combination of nuclear magnetic resonance (NMR) and mass spectrometry (MS) respectively; (5) DNA was extracted from plaque and saliva of the same group using Qigen PowerSoil kit. (6) metabolomics and metagenomics data were then integrated using R software and Cytoscape to identify significant microbe–metabolite interactions. Results: (1) Eighty-seven biomarkers were assessed, with the majority being higher in cases than in controls. Only the meta-analysis of total serum IgG with low heterogeneity value revealed a statistically significant increase in its levels in C/MIPs compared to controls (standardised mean difference: 1.08; 95% CI: 0.76, 1.40). (2) A considerable portion of MIPs were female, and almost half of the MIPs were Afro/Caribbean, with more than half reported having a family history of periodontitis with tooth loss in either siblings, parents, and/or grandparents at a young age. Most affected incisors and molars had grade 1 mobility and class I furcation involvement, with most cases having vertical bone loss in at least one molar. (3) After adjusting for covariates, cases had higher Immunoglobulin G levels in saliva (p=0.005) and gingival crevicular fluid (p<0.001) than controls; however, serum IgG levels did not reach the significance threshold (p=0.137) for differences between test and controls. Among other factors contributing to IgG levels, males had higher serum IgG than females (p=0.018), and serum IgG levels increased with age (p= 0.033). (4) Of the 42 salivary metabolites detected by NMR, dimethylamine, proline, and glycine were significantly lower in C/MIP than controls after adjusting for covariates. Conversely, the MS method detected 349 metabolites in serum, among which Bis(hydroxymethyl) propionic acid, 1-[(9Z)-octadecenoyl]-2-tetradecanoyl-sn-glycero-3-phosphocholine, decanoylcarnitine, 4-Picoline, tranexamic acid, 2-Hydroxy-5-vinylphenyl hydrogen sulfate, and L-Serine were lower in C/MIP compared to controls, whereas methyl indole-3-acetate, N-(3-acetamidopropyl) pyrrolidin-2-one, 4-Ethyl-2-hydroxy-6-methoxyphenyl hydrogen sulfate, and sulfosalicylic acid were higher in C/MIP than controls (5) C/MIP had a more diverse and distinct bacterial profile than controls in plaque and saliva. A novel unknown group of bacteria, labelled GGB, showed significant associations with C/MIP. The following bacteria were consistently identified in all analyses: C/MIP-associated taxa in plaque: Desulfobulbus oralis, Anaerolineaceae bacterium oral taxon 439, GGB4333 SGB5935, Treponema SGB3604, Campylobacter rectus, Treponema denticola, Eubacterium nodatum, Parvimonas micra, Eubacterium brachy, Slackia exigua, and Fretibacterium fastidiosum. Oral-health-associated taxa: Rothia mucilaginosa in saliva, and GGB10485 SGB49305 and Leptotrichia hongkongensis in plaque. Desulfobulbus oralis and GGB10485 SGB49305 showed considerable power as biomarkers in plaque. (6) Notable clusters of key periodontal pathogens were noticed including Porphyromonas gingivalis, Tannerella forsythia, Filifactor alocis and Abiotrophia defectiva and among metabolites, taurine, glutamine, N-Phenylacetylglutamine, and tetraacetylethylenediamine. Conclusion: This study identified for the first time the critical microbial and metabolic signatures associated with the pathogenesis of C/MIP in young cases using a combination of omics techniques. Integration of metagenomics and metabolomics revealed new insights into host-microbe interaction and metabolic pathways driving the disease, thus opening up new avenues for better diagnostic and therapeutic approaches.17 0Item Restricted Is Metabolomics a Useful Tool for the Evaluation of the Emerging Group of “Nitazene” 2-Benzylbenzimidazole Synthetic Opioids: Systematic Review(King's College London, 2024) Alsuamin, Ghada; Dowling, GeraldineNew psychoactive substances (NPS) can pose analytical challenges due to plenty of reasons, their chemical structures can have similarities with other NPS, limited knowledge of their pharmacokinetics and pharmacodynamics with their rapid appearance on the market and the instability of many NPS compounds. 2-Benzylbenzimidazole or nitazene have been the most reported opioids in early wakening system by EMCDDA in 2023. They are often adulterant with other opioids and can be up to 1000 times more than morphine leading to ingestion with micro doses. The findings based on searching the data bases PubMed and Scopus revealed that liquid chromatography-tandem mass spectrometry tandem with high- resolution mass spectrometry (LC-HRMS) have been employed to analyze nitazene and their metabolites in biological specimens as they undergo N-des-alkylation and O-des-alkylation, but metabolomics tool has not been employed diversly for nitazene. Metabolomics can be a valuable tool for nitazene as the findings of metabolomics tool have been promising when used on other NPS. Further research should be conducted to overcome the challenges associated with complicity and novelty of nitazene.18 0Item Restricted Evaluation of Acute Cardiorespiratory Disease: Integrating Metabolite-wide Analysis and Lung Mechanics Pathophysiology(Leicester University, 2024-01-30) Aljaroof, Masarrah Yousif; Greening, NeilChallenges in studying acute life-threatening events and a knowledge gap in biomarker exploration for overlapping cardio-respiratory conditions necessitate further investigation. This thesis aims to bridge the gap by identifying additional biomarkers using metabolomics and physiological measures in acute cardio-respiratory conditions. Our hypotheses aim to test the differentiation power of plasma metabolomic profiles, characterize ventilation heterogeneity, and identify of metabolic dysfunction in lipid mediators in acute cardiorespiratory conditions. Methods: We employed a multidimensional approach using LC-MS and GC-MS platforms to analyze plasma, breath, and sputum samples from the same population. The following studies were conducted: (1) Metabolite analysis in blood plasma samples of n = 54, in which n = 20 acquired from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients and n = 20 acquired from acute heart failure (AHF) patients, compared to n = 14 samples acquired from healthy volunteers. (2) Breath data analysis for ventilation heterogeneity involved 310 subjects using the FOT test, with a subgroup of 208 with published VOC measurements (1, 2), The analysis aimed to investigate the association between identified VOC metabolomics disturbances and respiratory impedance. (3) Prospective study using n = 141 sputum samples of AECOPD, acute asthma, pneumonia patients, and healthy control group targeting 13 metabolomic markers of inflammation resolution and comparing the results to a sub-cohort of n = 45 during stable status. Results: (I) Mass spectral analysis identified 2193 compounds in plasma samples of AECOPD, AHF, and healthy subjects. Biomarker scores of 19 metabolites (9 features associated with AECOPD and 10 with AHF) demonstrated ≥70% sensitivity and specificity in distinguishing between ACOPD, AHF, and health. (II) Resistance at 5 and 5-19 Hz as well as reactance at 5 Hz, area under the reactance AX, and resonant frequency were significantly different (p <0.000) between all groups; moreover, (p <0.05) indicated the significant impact of respiratory system compliance on the recovery of O, N, and S VOCs in exhaled breath. (III) Group comparisons revealed significant differences in lipid mediator PGE2 levels (p <0.01), with no significant differences observed in stable cohorts. Correlation analysis showed a negative association between eosinophil count and PGE2 levels (coefficient = -0.21, p <0.05) and a positive association between neutrophil count and PGE2 levels (coefficient = 0.24, p <0.05). Conclusion: This research highlights the potentials of metabolomics, both in targeted and untargeted approaches, along with the integration of bioinformatic statistical models in effectively differentiating between conditions with an overlapping pathology in an acute exacerbation’s events and healthy volunteers. Additionally, the study demonstrates the feasibility of utilizing handheld FOT as a valuable tool for assessing respiratory system mechanics in the acute care setting. Furthermore, examining the relationships between the analysed metabolites and other clinical observations adds to our understanding of acute cardio-respiratory conditions. These findings provide valuable insights that can contribute to the development of improved diagnostic strategies in the future.21 0