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1.
Heliyon ; 10(10): e31559, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38831830

RESUMO

Disturbances in the oral microbiota may be due to several mechanisms and factors, such as smoking. An imbalance in oral bacteria may result in changes to the innate immune system and the development of periodontal disease. This study aimed to investigate the distribution of oral microbiota in smokers and non-smokers in a South African population using subgingival plaque samples. From the 128 recruited participants, 57 were identified as smokers (serum cotinine: >15 ng/ml). Analysis of 16S rRNA gene sequencing demonstrated significant differences between the two groups with a reduced abundance of Actinobacteria in smokers. Fusobacterium and Campylobacter were found in higher abundance, while a lower abundance of Leptotrichia, Actinomyces, Corynebacterium, and Lautropia were observed. This study highlighted significant differences in the oral microbiota of smokers, indicating an abundance of anaerobic gram-negative bacteria. These findings suggest that smoking allows certain oral microorganisms to gain dominance, thereby predisposing individuals to periodontal disease development and progression.

2.
Transpl Immunol ; 84: 102045, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641148

RESUMO

BACKGROUND: Allogeneic stem cell transplantation (SCT) is a critical therapy for haematological malignancy but may lead to acute and chronic graft versus host disease (GvHD). T-cell depletion with alemtuzumab, either in vivo or ex vivo, reduces the incidence of GvHD but is a risk factor for disease relapse and poor immune reconstitution. Natural killer (NK) cells are the first lymphocytes to recover. Classical NK cells make up >90% of the normal circulating population and can directly kill neoplastic or virally infected cells while the regulatory subset makes up <10%, secretes cytokines and is not cytotoxic. The recovery and balance of these subsets post SCT remains controversial, with most studies analysing patients who received unmanipulated grafts and in vivo immunosuppression. OBJECTIVE: The aim was to assess the early recovery of NK cells in 18 consecutive patients receiving ex vivo T-cell depleted SCT and to compare the results to 25 individuals receiving haploidentical non-T cell depleted grafts. METHODS: All patients received myeloablative conditioning. After stem cell collection, the stem cells of the T cell depleted group were treated "in the bag" with alemtuzumab (CAMPATH 1H) at a concentration of 1mg/108 mononuclear cells and thereafter immediately infused. For those receiving non-T cell depleted grafts, GvHD prophylaxis was with post infusion therapeutic doses of cyclophosphamide. Blood samples were collected at days 21, 28 and 90. Complete blood counts were performed on an automated analyser while lymphocyte and NK subsets were examined using multiparameter flowcytometry. NK cells were defined as lymphocytes which were CD3-/CD56+. The classical subset was recognised as CD56dim/CD16+ while the regulatory population as CD56bright/CD16-. The results for both transplant types were compared at all time points using SPSS v8 statistical software. RESULTS: The recovery of lymphocytes was slow in both groups. Those receiving non-T cell depleted grafts had significantly higher T cell counts at day 21 and 28 when compared to the T cell depleted group (P < 0.05). In contrast, NK cells in the ex vivo T-cell depleted patients recovered rapidly and by day 21 was no different to normal (p > 0.05), while the non-T cell depleted group had significantly decreased numbers (p < 0.001), only recovering at day 90. Both groups had abnormal NK cell subset ratios with significantly elevated percentages of regulatory cells (p < 0.05). However, significant differences were observed between the two groups with those receiving T cell depleted grafts having lower percentages of regulatory cells as well as higher numbers of classical NK cells at day 21 and 28 (p < 0.01). CONCLUSION: This study of ex vivo T-cell depleted SCT's demonstrates that NK cells recover quicker when compared to those receiving unfractionated grafts. These results may have implications for GvHD and the GvL effect which warrants further study.


Assuntos
Alemtuzumab , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Células Matadoras Naturais , Depleção Linfocítica , Transplante Homólogo , Humanos , Alemtuzumab/uso terapêutico , Células Matadoras Naturais/imunologia , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Linfócitos T/imunologia , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/imunologia , Adulto Jovem , Idoso
3.
Sci Rep ; 12(1): 4107, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260775

RESUMO

The burden of chronic kidney disease (CKD) in Africa remains poorly characterized, due partly to the lack of appropriate diagnostic strategies. Although in recent years the diagnostic and prognostic utility of microRNAs (miRNAs) have gained prominence in the context of CKD, its value has not been evaluated in African populations. We investigated the expression of whole blood miRNAs (miR-126-3p, -30a-5p, -1299, -182-5p and -30e-3p) in a total sample of 1449 comprising of 13.3% individuals with CKD (stage 1-5) and 26.4% male participants, as well as the association of these miRNAs with prevalent CKD, in a community-based sample of South African adults. We used Reverse Transcription Quantitative Real-Time PCR (RT-qPCR) to analyze miRNA expression. There was an increased expression in whole blood miR-126-3p, -30a-5p, -1299 and -182-5p in individuals with CKD, compared to those without (all p ≤ 0.036), whereas miR-30e-3p showed no significant difference between the groups (p = 0.482). Only miR-126-3p, -182-5p and -30e-3p were independently associated with increased risk of CKD (all p ≤ 0.022). This study showed for the first time that there is a dysregulation of whole blood miR-126-3p, -30a-5p, -1299 and -182-5p in South Africans of mixed-ancestry with CKD. More research is needed to ascertain their role in CKD risk screening in African populations.


Assuntos
MicroRNAs , Insuficiência Renal Crônica , Adulto , Feminino , Humanos , Masculino , MicroRNAs/biossíntese , MicroRNAs/sangue , MicroRNAs/genética , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/genética , África do Sul/epidemiologia
4.
Biomedicines ; 11(1)2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36672511

RESUMO

The oral microbiota plays a crucial role in both systemic inflammation and metabolic syndrome (MetS), which is characterised by low-grade inflammation. Studies have analysed the gut microbiota using stool specimens from subjects with MetS; however, the etiological role of the oral microbiota in the development of MetS is still uncertain. We investigated the oral microbiota of 128 subgingival plaque samples from a South African cohort with and without MetS. After a comprehensive analysis of the oral microbiota, we observed a significant increase in Gram-positive aerobic and anaerobic microbiota in those with MetS. We observed an abundance of Actinomyces, Corynebacterium, and Fusobacterium genera in the MetS group, which differed significantly from previous studies, which found Granulicatella to be enriched in MetS. To further assess the impact of the metabolic parameters (FBG, Waist C, HDL, TGs, and BP) on the oral microbiota, we calculated the odds ratio (ORs) for significant oral microbiota identified between the MetS groups. We found that different species were associated with at least four MetS risk factors. This study has shown that the oral microbiota is disrupted in MetS and may promote inflammation providing a gateway to other systemic diseases, including diabetes and cardiovascular diseases.

5.
Front Genet ; 12: 710438, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594360

RESUMO

MicroRNAs are non-coding, post-transcriptional regulators of gene expression and their dysregulation has been associated with development of various diseases, including hypertension. Consequently, understanding their role in the pathogenesis and progression of disease is essential. Prior research focusing on microRNAs in disease has provided a basis for understanding disease prognosis and offered possible channels for therapeutic interventions. Herein, we aimed to investigate possible differences in the expression profiles of five microRNAs in the blood of participants grouped on the basis of their hypertension status. This was done to elucidate the possible roles played by these microRNAs in the development of hypertension. Using quantitative reverse transcription polymerase chain reaction, we evaluated the expression levels of miR-126-3p, 30a-5p, 182-5p, 30e-3p, and 1299 in the whole blood of 1456 participants, normotensive (n = 573), screen-detected hypertensive (n = 304) and known hypertensive (n = 579). The expression of miR-126-3p and 182-5p was significantly higher in known hypertensives relative to both screen-detected hypertensives and normotensives, and also in screen-detected hypertensives vs normotensives. A significant association between the expression of miR-126-3p, 182-5p, and 30a-5p and known hypertension was also evident. This study demonstrated dysregulated miR-126-3p, 182-5p, and 30a-5p expression in hypertension, highlighting the possible efficacy of these microRNAs as targets for the diagnosis of hypertension as well as the development of microRNA-based therapies.

6.
Front Genet ; 12: 702410, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567065

RESUMO

Aim: The influence of disease duration and anti-diabetic treatment on epigenetic processes has been described, with limited focus on interactions with microRNAs (miRNAs). miRNAs have been found to play key roles in the regulation of pathways associated with type 2 diabetes mellitus (T2DM), and expression patterns in response to treatment may further promote their use as therapeutic targets in T2DM and its associated complications. We therefore aimed to investigate the expressions of circulating miRNAs (miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p) in newly diagnosed and known diabetics on treatment, in South Africa. Methods: A total of 1254 participants with an average age of 53.8years were included in the study and classified according to glycaemic status (974 normotolerant, 92 screen-detected diabetes and 188 known diabetes). Whole blood levels of miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p were quantitated using RT-qPCR. Expression analysis was performed and compared across groups. Results: All miRNAs were significantly overexpressed in subjects with known diabetes when compared to normotolerant individuals, as well as known diabetics vs. screen-detected (p<0.001). Upon performing regression analysis, of all miRNAs, only miR-182-5p remained associated with the duration of the disease after adjustment for type of treatment (OR: 0.127, CI: 0.018-0.236, p=0.023). Conclusion: Our findings revealed important associations and altered expression patterns of miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p in known diabetics on anti-diabetic treatment compared to newly diagnosed individuals. Additionally, miR-182-5p expression decreased with increasing duration of T2DM. Further studies are, however, recommended to shed light on the involvement of the miRNA in insulin signalling and glucose homeostasis, to endorse its use as a therapeutic target in DM and its associated complications.

7.
Diagnostics (Basel) ; 11(6)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073154

RESUMO

This cross-sectional study investigated the association of miR-1299, -126-3p and -30e-3p with and their diagnostic capability for dysglycaemia in 1273 (men, n = 345) South Africans, aged >20 years. Glycaemic status was assessed by oral glucose tolerance test (OGTT). Whole blood microRNA (miRNA) expressions were assessed using TaqMan-based reverse transcription quantitative-PCR (RT-qPCR). Receiver operating characteristic (ROC) curves assessed the ability of each miRNA to discriminate dysglycaemia, while multivariable logistic regression analyses linked expression with dysglycaemia. In all, 207 (16.2%) and 94 (7.4%) participants had prediabetes and type 2 diabetes mellitus (T2DM), respectively. All three miRNAs were significantly highly expressed in individuals with prediabetes compared to normotolerant patients, p < 0.001. miR-30e-3p and miR-126-3p were also significantly more expressed in T2DM versus normotolerant patients, p < 0.001. In multivariable logistic regressions, the three miRNAs were consistently and continuously associated with prediabetes, while only miR-126-3p was associated with T2DM. The ROC analysis indicated all three miRNAs had a significant overall predictive ability to diagnose prediabetes, diabetes and the combination of both (dysglycaemia), with the area under the receiver operating characteristic curve (AUC) being significantly higher for miR-126-3p in prediabetes. For prediabetes diagnosis, miR-126-3p (AUC = 0.760) outperformed HbA1c (AUC = 0.695), p = 0.042. These results suggest that miR-1299, -126-3p and -30e-3p are associated with prediabetes, and measuring miR-126-3p could potentially contribute to diabetes risk screening strategies.

8.
Front Cardiovasc Med ; 8: 645541, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937359

RESUMO

Hypertension has a complex pathogenesis and symptoms appear in advanced disease. Dysregulation of gene expression regulatory factors like microRNAs has been reported in disease development. Identifying biomarkers which could help understand the pathogenesis and prognosis of hypertension is essential. The study's objective was to investigate microRNA expression profiles according to participant blood pressure status. Next generation sequencing was used to identify microRNAs in the whole blood of 48 body mass index-, smoking- and age-matched normotensive (n = 12), screen-detected hypertensive (n = 16) and known hypertensive (n = 20) female participants. Quantitative reverse transcription polymerase chain reaction was used to validate the next generation sequencing findings in a larger, independent sample of 84 men and 179 women. Using next generation sequencing, 30 dysregulated microRNAs were identified and miR-1299 and miR-30a-5p were the most significantly differentially expressed. Both microRNAs were upregulated in known hypertensives or screen-detected hypertensives compared to the normotensives. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated possible involvement of platelet activation, calcium signaling and aldosterone synthesis pathways. Further validation of miR-1299 and miR-30a-5p using quantitative reverse transcription polymerase chain reaction confirmed sequencing results while yielding new findings. These findings demonstrate microRNA dysregulation in hypertension and their expression may be related to genes and biological pathways essential for blood pressure homeostasis.

9.
Mol Biol Rep ; 48(3): 2553-2560, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33759050

RESUMO

MicroRNAs are important in development of disease, and description of novel microRNAs adds to the pool of microRNAs that can be targeted for diagnostic and therapeutic purposes in disease. Herein, we aimed to describe novel microRNAs in a normotensive and hypertensive African population and relate their expression to blood pressure parameters and hypertension status. Previous work using next-generation sequencing showed differential expression of two novel microRNAs in the blood of normotensives and hypertensives. Herein, we have investigated these novel microRNAs by quantitative reverse transcription polymerase chain reaction in a cohort of 881 participants in this study. The relationship between the novel microRNAs and systolic and diastolic blood pressure as well as mean arterial pressure was also investigated. Age and sex-adjusted Spearman's correlations were used to assess the relationship between microRNAs and cardiovascular risk profile variables whilst multivariable logistic regression models were used to assess the association of microRNAs with screen-detected and known hypertension. The novel microRNAs (miR-novel-chr1_36178 and miR-novel-chr15_18383) were significantly dysregulated by hypertension status. The expression of miR-novel-chr1_36178 differed according to sex, correlated with mean arterial pressure and systolic and diastolic blood pressure at higher levels of expression and was associated with screen-detected hypertension. The association of miR-novel-chr1_36178 expression with mean arterial pressure and systolic and diastolic blood pressure, as well as its dysregulation according to hypertension status suggests its possible utility as a biomarker target for hypertension diagnosis and/or therapeutics. Furthermore, its association with screen detected hypertension and dose-response relationship with blood pressure suggests it may be used to identify and monitor individuals at risk of hypertension.


Assuntos
Pressão Sanguínea/genética , MicroRNAs/genética , População Urbana , Adulto , Feminino , Regulação da Expressão Gênica , Humanos , Modelos Lineares , Masculino , MicroRNAs/metabolismo , Razão de Chances , África do Sul , Estatísticas não Paramétricas
10.
Appl Clin Genet ; 13: 209-219, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363396

RESUMO

BACKGROUND AND AIM: Maturity-onset diabetes of the young (MODY) is the result of single gene variants. To date, fourteen different MODY subtypes have been described. Variants in genes coding for glucokinase (GCK, MODY2) and hepatic nuclear factor 1 alpha (HNF1A, MODY3) are most frequently encountered. MODY patients are often misdiagnosed with type 1 or type 2 diabetes, resulting in incorrect treatment protocols. At the time of reporting, no data are available on MODY prevalence in populations from Africa. Our study aimed to investigate and report on the incidence of MODY-related variants, specifically HNF1A variants, in a population from the Western Cape. METHODS: Study participants were recruited (1643 in total, 407 males, 1236 females) and underwent anthropometric tests. Thereafter, blood was collected, and real-time PCR was used to screen for specific variants in HNF1A and GCK genes. RESULTS: Ninety-seven individuals (5.9%) were identified with a specific HNF1A gene polymorphism (rs1169288) and twelve (0.9%) with a GCK polymorphism (rs4607517). CONCLUSION: In total, 6.6% of the study population expressed MODY variants. To our knowledge, we are the first to report on MODY incidence in Africa. This research provides the basis for MODY incidence studies in South Africa, as well as data on non-Caucasian populations.

11.
Diabetes Metab Syndr Obes ; 13: 5037-5047, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376373

RESUMO

BACKGROUND: microRNAs (miRNAs) have been touted as potential diagnostic and prognostic biomarkers for various diseases. The aim of the present study was to evaluate the diagnostic value of miR-30a-5p and miR-182-5p for prediabetes and screen-detected type 2 diabetes mellitus (T2DM). METHODS: The study included 1270 participants (207 prediabetes, 94 screen-detected diabetes and 969 normotolerant) from the Vascular and Metabolic Health (VMH) study. Whole blood levels of miR-30a-5p and miR-182-5p were quantitated by RT-qPCR. Multivariable logistic regressions were used to relate miRNAs with prediabetes or T2DM and receiver operating characteristic (ROC) curves were used to evaluate the ability of each miRNA to diagnose these conditions. RESULTS: Both miRNAs were significantly highly expressed in individuals with prediabetes or T2DM (both ≥3.2-fold, and p<0.001). We also observed significant under-expression in T2DM relative to prediabetes for miR-182-5p (0.49-fold, p=0.001). Age, sex and BMI-adjusted partial correlation coefficient analysis revealed a significant correlation between the two miRNAs across glucose tolerance statuses (r≥0.932, p<0.001). In normotolerant individuals, both miRNAs showed a negative correlation with waist circumference and positive correlation with HDL-cholesterol whilst in T2DM they correlated positively with hip circumference, 2-hour insulin, HDL- and LDL-cholesterol. Multivariable logistic regressions revealed both miRNAs to be consistently and continuously associated with prediabetes or T2DM (OR≥1.18, 95% 95% CI: 1.10-1.28, p<0.001), while only miR-182-5p associated with a reduced prevalence of T2DM relative to prediabetes (OR: 0.89, 95% CI: 0.83-0.96, p=0.003). In ROC analyses, miR-182-5p almost outperformed HbA1c in diagnosing prediabetes; area under the curve 0.74 vs 0.69. CONCLUSION: Our findings demonstrate that miR-30a-5p and miR-182-5p are associated with dysglycaemia and could potentially predict prediabetes, particularly miR-182-5p.

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