Toxoplasma gondii is a worldwide prevalent parasite. The infection has been linked to variable inflammatory effects including neuroinflammation. Biochanin A (BCA) is an isoflavone, known for its anti-inflammatory and anti-oxidative properties. In this study, we examined the effect of BCA on the brain and liver inflammatory lesions in a murine model with chronic toxoplasmosis. Mice were divided in to six groups: non-infected control, non-infected BCA-treated, and four infected groups with Toxoplasmagondii Me49-type II cystogenic strain: infected control, BCA (50 mg/kg/day)-treated, combined BCA/cotrimoxazole-treated and cotrimoxazole (370 mg/kg/day) alone-treated. Gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) was evaluated by quantitative real-time PCR in the brain and liver tissues. In the infected control group, an upregulation of TNF-α and IL-1β mRNA expression levels was found. However, a downregulation of iNOS expression was detected in the brain of infected control mice. In both BCA- and combined-treated groups, the brain and liver tissues showed significantly reduced inflammatory lesions compared to the infected control mice with inhibited TNF-α and IL-1β mRNA levels. The iNOS expression levels in the brain tissues of BCA group were significantly higher than the levels of the infected control group. BCA alone or combined significantly reduced T. gondii cyst count in the brain tissues. In conclusion, the anti-inflammatory activity of BCA was demonstrated in the brain tissues of mice with chronic toxoplasmosis with decreased TNF-α and IL-1β expression levels and increased iNOS expression levels.

No abstract

Biochanin A (BCA) is a multifunctional natural compound that possesses anti-infective, anti-inflammatory, anti-oxidative and hepatoprotective effects. The aim of the study was to assess the therapeutic efficacy of BCA on Schistosoma mansoni-infected mice. Fifty mice were divided into six different groups as non-infected, non-infected BCA-treated, infected untreated, early infected BCA-treated (seven days post-infection (dpi)), late infected BCA-treated 60 dpi and infected praziquantel (PZQ)-treated groups. Parasitological, histopathological examination and immunohistochemical staining of transforming growth factor (TGF)-β, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) were investigated in liver sections. Cytochrome P450 (CYP450) gene expression of S. mansoni was evaluated by quantitative real-time polymerase chain reaction (RT-qPCR). A single dose of BCA significantly reduced worm burden in early (82.14%) and late infection (77.74%), mean tissue egg load in early (7.27 ± 0.495) and late BCA administration (7.63 ± 0.435) and decreased granuloma size. CYP450 mRNA expression was significantly reduced in early BCA treatment as compared to late treatment which emphasizes that early administration of BCA had more pronounced effects on worms than late administration. Both early and late BCA administration led to significant reduction in inflammatory cytokines as TGF and iNOS. Although the reduction of TGF and iNOS in BCA-treated mice was superior to PZQ, no statistically significant differences were noted. However, a significant downregulation of COX2 was noted in hepatocytes as compared to both infected control and PZQ-treated mice. BCA has schistosomicidal, anti-inflammatory, antioxidant and anti-fibrotic effects and could be regarded as a potential drug in schistosomiasis treatment.

Objectives: This tissue microarray (TMA) immunohistochemical (IHC) study elucidates the role of Wilms' tumor 1 protein (WT1) in diagnosis and prognostication of astrocytic tumors. Methods: IHC was applied to 75 astrocytic lesions (18 astrogliosis and 57 astrocytic tumors) using antibodies directed against WT1 clone 6F-H2, isocitrate dehydrogenase 1(IDH1), Bcl2 and Ki67. WT1 IHC staining was evaluated and scored blindly by 2 pathologists. Bcl2 and Ki67 scores and labelling indices were assessed and IDH1 status determined. Statistical analysis was performed using the appropriate methodology. Results: WT1 cytoplasmic expression was detected in 89.5% of astrocytic tumors but not in astrogliosis. Positive WT1 differentiated astrocytic tumors (92.6% accuracy) and grade II diffuse astrocytomas (93.5% accuracy) from astrogliosis with high sensitivity, specificity and positive predictive values (p<0.001). Increased WT1 score significantly associated higher Bcl2 and Ki67 labelling indices, increasing WHO tumor grade and tumor's histopathologic type (p<0.05) showing staining pattern variability by tumor entity and cell type. Glioblastomas, gliosarcomas and subependymal giant cell astrocytomas were the most frequently WT1 expressing tumors with frequent +3 WT1 score. About 21.4% of pilocytic astrocytomas had +3WT1 score in association with increased Bcl2 and Ki67 indices. Low WT1 scores in grade II and III diffuse astrocytomas were linked to the high frequency of IDH1 positivity, and were associated with low Bcl2 and Ki67 labelling indices. In glioblastomas, WT1 significantly associated poor prognostic variables: older age, negative-IDH1 status, high Bcl2 and Ki67 labelling indices (p=0.04, <0.001, =0.001 and <0.001 respectively). Conclusions: WT1 clone 6F-H2 is a highly accurate positive surrogate marker to differentiate astrocytic tumors notably the challenging grade II diffuse astrocytoma from astrogliosis. It significantly associates with poor prognostic variables including IDH1 negativity, high apoptotic and proliferative indices and depends on tumor's histopathologic entity more than its grade. Evaluation of WT1 expression seems essential to tailor patient's therapy.

No abstract