ABSTRACT Perillic acid (PA), a monocyclic monoterpene derived from limonene, was evaluated for its leishmanicidal activity alone and in combination with miltefosine, as well as in its microemulsion‐based formulation. PA demonstrated synergistic activity with miltefosine and was effective against both promastigote and amastigote forms of Leishmania amazonensis . Its anti‐amastigote effect was independent of nitric oxide production but was partially associated with reduced arginase activity in stimulated macrophages. In a murine model of cutaneous leishmaniasis, topical treatment with a PA‐loaded microemulsion resulted in a marked reduction in parasite burden, achieving a 99% reduction in L. amazonensis infections. PA also showed efficacy in vivo across different administration routes and showed significant skin permeation when formulated in a microemulsion. These findings highlight PA as a promising leishmanicidal agent and support its potential application in the treatment of cutaneous leishmaniasis.
ABSTRACT Strongyloidiasis is a neglected tropical disease caused by the soil‐transmitted helminth Strongyloides stercoralis . Immunological assays employing heterologous antigens from Strongyloides venezuelensis represent a valuable alternative to parasitological diagnosis. In this study, we evaluated the diagnostic performance of different antigenic preparations derived from S. venezuelensis infective larvae (L3) for the detection of anti‐ Strongyloides IgG antibodies in sera from Brazilian and Peruvian individuals. Total soluble (S‐L3), membrane (M‐L3), cuticular (C‐L3) and excretory/secretory (ES‐L3) antigenic extracts were assessed using enzyme‐linked immunosorbent assay (ELISA). Overall, Brazilian sera showed higher reactivity than Peruvian sera to all antigenic preparations. Both S‐iL3 and ES‐L3 demonstrated excellent diagnostic performance with samples from both countries, showing 100% sensitivity and specificities of 97.4% and 100%, respectively. When a single cut‐off value applicable to both populations was adopted, S‐L3 showed the best overall performance, achieving 100% sensitivity and 98.7% specificity at a cut‐off of 0.367, or 97.5% sensitivity and 100% specificity at a cut‐off of 0.416, followed by ES‐L3, C‐L3 and M‐L3. Heterologous antigenic extracts from S. venezuelensis , particularly S‐L3, may represent a useful alternative for the serological diagnosis of S. stercoralis infection in endemic settings such as Brazil and Peru.
ABSTRACT Innate immune receptors are central to host resistance against Trypanosoma cruzi infection, yet how parasite genetic diversity is associated with these responses remains poorly understood. Here, we characterized acute infection outcomes and myocardial innate immune transcriptional profiles in mice subjected to single and mixed infections with genetically distinct T. cruzi parasites (DTUs TcII, TcIII, and TcVI). Swiss mice were infected with RN2, RN23, Y, or CL‐Brener individually or in combination, and parasitemia, survival, and cardiac gene expression were assessed. The Y strain, CL‐Brener clone, and RN2 + RN23 + CL‐Brener condition exhibited a high‐severity profile, with marked parasitemia (8000–28,000 trypomastigotes/5 μL), mortality of 74%–100%, reduced myocardial transcription of Tlr2 , Tlr4 , Tlr9 , Trif , and Myd88 , and increased transcription of Nlrp3 , Casp1 , Il1β , and Tnfα . In contrast, RN2 and RN23 single infections exhibited low‐severity profiles and higher transcription of innate immune mediators associated with parasite control. Mixed‐infection groups displayed transcriptional and infection profiles differing from the corresponding single‐infection groups under a standardized total inoculum. Together, these findings identify distinct myocardial innate immune transcriptional profiles across single and mixed T. cruzi infection conditions and support further investigation of the contributions of parasite population composition and dose to acute infection outcomes.
Disseminated acanthamoebiasis is a rare but severe opportunistic infection that can involve multiple organs, including the liver, causing fatal outcomes. This study provides new insights into hepatic pathogenesis and possible relationship with angiogenesis activity and the therapeutic role of quercetin conjugated silver nanoparticles (Q-AgNPs). Sixty BALB/c mice were divided into four groups: uninfected control, uninfected treated with Q-AgNPs, infected group and infected treated with Q-AgNPs. The Q-AgNPs were synthesised and characterised by spectrophotometry, electron microscope, zeta potential and dynamic light scattering. Hepatic tissues were examined histopathologically for granulomas (classified as caseating/non-caseating and immature/mature) and vascular changes. Hypoglycaemia and expression of angiogenic markers (CD31, CD34 and MMP9) were assessed. Acanthamoeba polyphaga infection induced significant hepatic granulomatous inflammation, hypoglycaemia, vascular remodelling and upregulation of CD31, CD34 and MMP9, indicating active angiogenesis. Granulomas exhibited necrotic cores in some cases and progressed from immature to mature stages. Q-AgNPs treatment markedly attenuated granuloma numbers, suppressing angiogenic marker expression, mitigating inflammation, capillary permeability and liver lesions. This study provides novel evidence linking Acanthamoeba infection to hepatic granuloma formation and angiogenesis-driven pathology which may serve as useful biomarkers for extracerebral acanthamoebiasis. Further studies are needed to evaluate long-term outcomes and host-parasite interaction.
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) peptide accumulation and tau protein-mediated neurodegeneration, and neuroinflammation is increasingly recognized as a major process associated with tau pathology. Chronic Toxoplasma gondii infection reduces amyloid accumulation in AD models through immune modulation, but its stage-specific associations with tau-related pathology remain unclear. Here, we investigated how chronic T. gondii infection is associated with tau-related molecular and neuropathological changes in the 5XFAD AD mouse model. At 40 weeks post-infection, we profiled transcriptomic changes and evaluated Aβ-associated (21 genes), Aβ/tau-shared (22 genes), and tau-associated (21 genes) pathological programs together with p-tau immunoreactivity in brain sections. Chronic infection was associated with selective modulation of molecular networks linked to neuroimmune signalling and tau-related pathways rather than broad suppression of AD-related gene expression. Among tau-related pathological stages, the neuroinflammation-related amplification module linking Aβ and tau exhibited the most prominent transcriptomic change in T. gondii-infected AD mice, whereas upstream kinase-related initiation pathways and downstream toxin conversion or accumulation-related processes changed relatively minimally. These transcriptomic changes were accompanied by a marked reduction in phosphorylated tau load at the tissue level. Collectively, these findings suggest that chronic T. gondii infection is associated with selective modulation of tau-related pathogenic programs and reduced p-tau burden in the 5XFAD brain.
