Biology subjects

Oyerinde, O. R.

Publications and source records attributed to Oyerinde, O. R..

3 recordsLinked to original sources

bioRxiv2025

Innate immune responses to Plasmodium falciparum disrupt the blood-brain barrier

Plasmodium falciparum accumulation at the blood-brain barrier (BBB) is a hallmark of cerebral malaria, a life-threatening complication. Conversely, the contribution of the immune response to vascular injury has long been debated. Here, we studied the role of innate immune cells as potential effectors of vascular damage using a human in vitro 3D-BBB model. Parasite-stimulated immune cells from malaria-naive donors increased adhesion to microvessels, at least partly through LFA-1. This caused barrier disruption and inflammatory activation of BBB cells. Secretion of TNF-, IFN-{gamma}, and granzyme B by monocytes, NK and {gamma}{delta} T cells correlated with vascular injury, and accumulation of immune cells was required for local barrier damage. Our computational analysis disentangled pathogenic mechanisms driven specifically by either P. falciparum parasite or immune cells, as well as shared pathways. These findings demonstrate how vascular-immune interactions may contribute to vascular injury in cerebral malaria and point towards the potential of immunomodulatory therapeutics.

immunology↗

bioRxiv2025

Therapeutic Potential of Ocimum basilicum in Diabetes and Malaria Co-morbidity: Evidence from Parasitemia, Biochemical, and Coagulation Outcomes in Mice

Diabetes and malaria are major morbidities that impair hepatic and renal functions. This study investigated the effects of the hydromethanol extract of Ocimum basilicum (OCB) on parasitemia, biochemical markers, and coagulation parameters in diabetic BALB/C mice infected with Plasmodium berghei. Fifty-six male mice were divided into eight groups (n=7): normal control, diabetes only, malaria only, diabetes + malaria, malaria + OCB, diabetes + OCB, diabetes + malaria + OCB, and diabetes + malaria + metformin. Diabetes was induced by streptozotocin (40 mg/kg, i.p.) for 5 consecutive days, while Plasmodium berghei was inoculated in the malaria groups, and infection was confirmed by Giemsa-stained thin smears. Treatments consisted of OCB (100 mg/kg) or metformin (250 mg/kg) orally for 7 days; controls received phosphate-buffered saline. OCB significantly (p<0.05) reduced parasitemia in infected groups compared with untreated controls. In diabetic and malaria-induced mice, elevated fasting blood glucose, creatinine, and urea were markedly reduced by OCB, with decreases of 33.22%, 70.58%, and 26.32%, respectively, in the malaria + diabetes + OCB group relative to the untreated group. Serum alanine and aspartate aminotransferases were also lowered by OCB more effectively than metformin, indicating hepatoprotective activity. Coagulation profiles showed no significant differences in activated partial thromboplastin time and prothrombin time between OCB-treated and control groups, although prothrombin time decreased in the diabetes + OCB group. These findings demonstrate that O. basilicum possesses anti-plasmodial, antihyperglycemic, and organ-protective effects, highlighting its potential as a source of phytopharmaceutical agents for the treatment and management of malaria and diabetes.

pharmacology and toxicology↗

bioRxiv2025

Febrile temperature enhances Plasmodium falciparum cytoadhesion by disrupting the endothelial glycocalyx

Fever, a universal host defense response in infection and inflammation, paradoxically contributes to neurological complications in malaria. Febrile temperatures are known to enhance parasite virulence protein expression, but direct effects on the human endothelium remain unknown. We found that a 1-hour exposure to 40 {degrees}C, representative of fever in children with cerebral malaria, increased adhesion of Plasmodium falciparum-infected red blood cells and neutrophils to 3D brain microvascular models displaying a wide wall shear stress gradient. Mechanistically, this brief hyperthermia triggered rapid endothelial glycocalyx shedding, exposing endothelial receptors for binding. This response was more pronounced in brain than in pulmonary microvessels, revealing a greater vulnerability of the cerebral vasculature to fever. Pharmacological inhibition of matrix metalloproteinase activity preserved glycocalyx integrity and abolished the temperature-induced increase in adhesion. These findings identify fever as a host-specific amplifier of malaria-associated microvascular pathology, highlighting the importance of antipyretic strategies to mitigate disease severity.

microbiology↗