Metagenomics datasets of water and sediments from eutrophication-impacted artificial lakes in South Africa.

We present metagenomes of 16 samples of water and sediment from two lakes, collected from eutrophic and non-eutrophic areas, including pooled samples enriched with phosphate and nitrate. Additionally, we assembled 167 bacterial metagenome-assembled genomes (MAGs). These MAGs were de-replicated into 83 unique genomes representing different species found in the lakes. All the MAGs exhibited >70% completeness and <10% contamination, with 79 MAGs being classified as 'nearly complete' (completeness >90%), while 54 falling within 80-90% range and 34 between 75-80% complete. The most abundant MAGs identified across all samples were Proteobacteria (n = 80), Firmicutes_A (n = 35), Firmicutes (n = 13), and Bacteriodota (n = 22). Other groups included Desulfobacteria_I (n = 2), Verrucomicrobiota (n = 4), Campylobacterota (n = 4) and Actinobacteriota (n = 6). Importantly, phylogenomic analysis identified that approximately 50.3% of the MAGs could not be classified to known species, suggesting the presence of potentially new and unknown bacteria in these lakes, warranting further in-depth investigation. This study provides valuable new dataset on the diverse and often unique microbial communities living in polluted lakes, useful in developing effective strategies to manage pollution.

Exosomal MicroRNAs in Pregnancy Provides Insight into a Possible Cure for Cancer.

The biological links between cancer and pregnancy are of recent interest due to parallel proliferative, immunosuppressive and invasive mechanisms between tumour and trophoblast development. Therefore, understanding "cancer-like" mechanisms in pregnancy could lead to the development of novel cancer therapeutics, however, little is understood on how tumour and trophoblast cells recapitulate similar molecular mechanisms. Based on our observations from a previous study, it was not only evident that exosomal miRNAs are involved in the pathophysiology of preeclampsia but also contained cancer-specific miRNAs, which suggested that "pseudo-malignant-like" exosomal-mediated mechanisms exist in pregnancy. The presented study therefore aimed to identify exosomal miRNAs (exomiR) in pregnancy which can be repurposed towards preventing tumour metastasis and immunosuppression. It was identified that exomiR-302d-3p, exomiR-223-3p and exomiR-451a, commonly associated with cancer metastasis, were found to be highly expressed in pregnancy. Furthermore, computational merging and meta-analytical pathway analysis (DIANA miRPath) of significantly expressed exomiRs between 38 ± 1.9 vs. 30 ± 1.11 weeks of gestation indicated controlled regulation of biological pathways associated with cancer metastasis and immunosuppression. Therefore, the observations made in this study provide the experimental framework for the repurposing of exosomal miRNA molecular mechanisms in pregnancy towards treating and preventing cancer.

Exosomal Th1/Th2 cytokines in preeclampsia and HIV-positive preeclamptic women on highly active anti-retroviral therapy.

Preeclampsia (PE) is a hypertensive disorder of pregnancy which is a leading cause of maternal and foetal morbidity and mortality. Furthermore, HIV/Highly Active Anti-Retroviral Treatment has been associated with the increased risk of preeclampsia due to maternal immune reconstitution, which complicates the clinical diagnosis of PE in these patients. It is therefore necessary to identify biomarkers involved in the pathology of both disorders with the intent to diagnose. Exosomal cytokines represent ideal biomarkers of PE and inflammatory conditions due to their immunomodulatory role in pregnancy. We therefore quantified exosomal Th1 (IL-2 and TNF-α) and Th2 cytokines (IL-10) in maternal circulation. A significant dysregulation in total exosomes, placental-derived exosomes and exosomal cytokines in PE and HIV-positive PE pregnant woman on Highly Active Antiretroviral Treatment (HAART) was observed (p < 0.01). Additionally, we observed a significant shift towards Th1 immunity in PE which becomes amplified in HIV-positive PE pregnant woman on HAART (p < 0.01). Moreover, we show the potential application of exosomal Tumor necrosis factor alpha (TNF-α) as a biomarker of PE and PE in HIV-positive pregnant women on HAART (CI: 95%, LHR > 10, sensitivity of 100% and specificity of 90%). These findings are in support of exosome release and exosome cytokine encapsulation as a tightly regulated process in favour of maintaining the immune microenvironment, which can orchestrate either normal pregnancy, or the pathogenesis of preeclampsia and preeclampsia in HIV/HAART pregnancies.

Exosomal microRNA profiling in early and late onset preeclamptic pregnant women reflects pathophysiology.

Background: Preeclampsia is the leading cause of maternal and fetal mortality due to the inability to diagnose and treat the disorder early in pregnancy. This is attributed to the complex pathophysiology and unknown etiology of the disorder, which is modulated by several known and unknown factors. Exosomes have recently been implicated as possible mediators of the pathogenesis of preeclampsia, with, however, no evidence linking these nanovesicles to the pathophysiology of preeclampsia and its subtypes. Methods: To better understand the pathophysiological role of exosomes in preeclampsia, we have analyzed the exosomal microRNA in early and late onset preeclamptic women in comparison to their gestationally matched normotensive controls using Digital Direct Detection (NanoString Technologies). Results: For the first time, distinct exosomal microRNA signatures in early and late onset preeclampsia have been identified. Moreover, these signatures indicate that exosomes are involved in key pathological features associated with preeclampsia and differentiate between the subtypes. Conclusion: This study forms the basis for the diagnostic and functional validation of the identified signatures as biomarkers of preeclampsia and its subtypes.

Placenta-derived exosomes: potential biomarkers of preeclampsia.

Preeclampsia remains a leading cause of maternal and fetal mortality, due to ineffective treatment and diagnostic strategies, compounded by the lack of clarity on the etiology of the disorder. Although several clinical and biological markers of preeclampsia have been evaluated, they have proven to be ineffective in providing a definitive diagnosis during the various stages of the disorder. Exosomes have emerged as ideal biomarkers of pathological states, such as cancer, and have more recently gained interest in pregnancy-related complications, due to their role in cellular communication in normal and complicated pregnancies. This occurs as a result of the specific placenta-derived exosomal molecular cargo, which may be involved in normal pregnancy-associated immunological events, such as the maintenance of maternal-fetal tolerance. This review provides perspectives on placenta-derived exosomes as possible biomarkers for the diagnosis/prognosis of preeclampsia. Using keywords, online databases were searched to identify relevant publications to review the potential use of placenta-derived exosomes as biomarkers of preeclampsia.

Placental exosomes and pre-eclampsia: Maternal circulating levels in normal pregnancies and, early and late onset pre-eclamptic pregnancies.

INTRODUCTION AND AIM: Exosomes are a subtype of extracellular vesicle (20-130 nm) released by biological cells under normal and pathological conditions. Although there have been reports of circulating exosomes in normal pregnancy, the relevance of placental-derived exosomes in normal and abnormal pregnancies still needs to be elucidated. The aim of this study was to quantify total and placental-derived exosomes in maternal plasma from normal (N), early onset- and late onset-preeclampsia (PE). METHOD: Plasma samples were obtained from pregnant women in the third trimester, for the isolation of exosomes by differential ultracentrifugation. Total exosomes were quantified using nanoparticle tracking analysis and immuno-reactive exosomal CD63 quantification. Placental-derived exosomes were quantified using placental alkaline phosphatase (PLAP) as a specific marker. The contribution of placental-derived exosomes to total exosomes in maternal plasma was determined by the ratio of PLAP+ exosomes to CD63+ exosomes. RESULTS: The concentration of total exosomes significantly increased in early onset-PE and late onset-PE compared to N (≤33 weeks) and N (≥34 weeks). The relative concentration of placental-derived exosomes significantly increased in early onset-PE but decreased in late onset-PE compared to N. The ratio of PLAP+ exosomes to total number of exosomes significantly decreased in early onset-PE and late onset-PE. A positive correlation between total and placental-derived exosomes were obtained in N (≤33 weeks: Pearson's r = 0.60, ≥34 weeks: Pearson's r = 0.67) and early onset-PE (Pearson's r = 0.51, p < 0.05) with the inverse in late onset-PE (Pearson's r = -0.62, p < 0.01). CONCLUSION: The differences in the contribution of placental-derived exosomes to total exosomes in maternal circulation suggests a possible pathophysiological role of placental-derived exosomes in pre-eclampsia.