Kangogo, M. | bioRxiv Science

bioRxiv2024

Placental malaria is associated with a TLR-Endothelin-3-oxidative damage response in human placenta tissues

Placental malaria, which is mainly caused by the sequestration of Plasmodium falciparum- infected erythrocytes in the placenta, is an important driver of poor pregnancy outcomes, including fetal growth restriction, preterm birth, and stillbirth. However, the mechanisms underlying its adverse outcomes are unclear. Mouse models have shown that placental malaria triggers a proinflammatory response in the placenta, which is accompanied by a fetal Toll-like receptor (TLR)4-mediated innate immune response associated with improved fetal outcomes. Here, we used hematoxylin and eosin staining to identify placental malaria positive and negative samples in our biobank of placentas donated by women living in a malaria-endemic region of Kenya and assessed the impact of placental malaria on the expression of TLRs, Endothelins, and oxidative damage. RT-qPCR analysis revealed that placental malaria was associated with an upregulation of TLR4, TLR7, and Endothelin-3. Moreover, immunohistochemistry showed that placental malaria was associated with elevated expression levels of the oxidative DNA damage marker, 8- hydroxy-2-deoxyguanosine, while RT-qPCR revealed that this was accompanied by an upregulation of p21, an inhibitor of cell cycle progression and marker of cellular response to DNA damage. These findings allude to a novel mechanism of placental malaria pathogenesis driven by a TLR-Endothelin-3-oxidative DNA damage signaling axis.

cell biology↗

bioRxiv2022

The Antimicrobial Activity of Pechuel-Loeschea leubnitziae Leaf Extract and its Effect on The Expression Level of Methicillin Resistant Staphylococcus Aureus and Candida albicans Virulence-Associated Genes

The complete halt in the synthesis of new effective antimicrobial compounds is a global concern. Pathogenic microorganisms virulence mechanisms seem to have a significant impact on their pathogenesis. The purpose of this study was to examine the antimicrobial activity of the ethanol and methanol fractions of Pechuel-Loeschea leubnitziae leaf extract, as well as its effect on the expression level of virulence-associated genes. The extracts fractions were evaluated for antimicrobial activity against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae (clinical), Methicillin-resistant Staphylococcus aureus, and Candida albicans ATCC 90029. The test organisms antibiogram pattern was determined. The extracts attenuation effect on the target genes of the susceptible organisms was investigated employing relative quantification using RT-qPCR. The test organisms antibiogram pattern revealed that it was drug-resistant, intermediate, and sensitive. The extracts tested positive for antimicrobial activity against Methicillin-resistant Staphylococcus aureus and Candida albicans ATCC 90029, with zones of inhibition varying from 20.33 to 29 mm. The lowest recorded MIC value was 4.688 mg/ml, while the highest was 37.5 mg/ml. In contrast to the methanol extract, the ethanol extract had a cidal action at a lower dose. The ethanol extracts Sub-MIC (18.25 mg/ml) merely reduced the expression of the hly gene in MRSA. The MRSA virulence genes were not suppressed by the sub-MIC of methanol extract (18.25 mg/ml). Notably, the expression of als1, pbl1, and sap1 in Candida albicans ATCC 90029 was significantly attenuated when exposed to sub-MICs of ethanol extract (2,344 mg/ml) and methanol extract (9.375 mg/ml). Per the findings of this research, the leaves of P. leubnitziae could be a source of an effective antimicrobial agent in the therapy of MRSA/Candida-related disorders.

molecular biology↗