Vaccination with Toxoplasma lysate antigen or its encapsulated niosomes form immunomodulates adjuvant-induced arthritis through JAK3 downregulation.

BACKGROUND: Inflammatory autoimmune arthritis like that present in rheumatoid arthritis (RA) is treated by medications with many side effects. This study was a trial to benefit from Toxoplasma immune-modulatory effects on its host to treat arthritis in rat model resembling joints affection of RA. To avoid hazards of infection, Toxoplasma lysate antigen (TLA) was given instead of the whole infection, in addition to giving its encapsulated niosomes form, assuming that it would enhance the effect of TLA alone, to compare effects of both on disease activity with that of prednisolone. METHODS: Swiss albino rats were divided into 6 groups: normal control group and the remaining 5 groups were injected by CFA adjuvant to induce arthritis; one of those groups was the untreated model. Each of the other groups received one of the following (TLA, TLA-encapsulated niosomes, prednisolone or niosomes) for comparison of their results. Inflammatory markers measured at the end of the experiment were: interleukin 17 (IL-17), IL-10 and CRP by ELISA technique; histopathological assessment of the biopsied hind paw joints was done and also, Janus kinase 3 (JAK3) expression was assessed by immunohistochemistry. RESULTS: TLA and TLA-encapsulated niosomes both mitigated the signs of clinical and histopathological arthritis and were having anti-inflammatory effects (decreased CRP, IL-17 and JAK3 expressions, while increased IL-10 levels) with better effects in TLA-encapsulated niosomes-treated RA group, both groups' results were comparable to prednisolone. Niosomes also gave some anti-inflammatory effects but were mild in comparison to TLA and TLA-encapsulated niosomes. CONCLUSION: Vaccination with both TLA and TLA-encapsulated niosomes for the first time in adjuvant-induced arthritis ameliorated the disease through diversion of immune system and JAK3 downregulation. Both vaccinations should be further tested to evaluate the possibility of their introduction for disease treatment and in other autoimmune diseases.

Schistosomiasis mansoni: A new therapeutic target for ubiquinol, a natural inhibitor of neutral magnesium-dependent sphingomyelinase in murine model.

Constituting the host-parasite interface and playing a censorious role in host immune response modulation and parasite survival, tegument represents a crucial target for many antischistosomal drugs. Sphingomyelin forms a stable outer leaflet of tegumental membrane-lipid bilayer. Neutral magnesium -dependent sphingomyelinase (Mg2+-nSMase) is a key enzyme in sphingomyelin breakdown was identified in schistosomes. We investigated the in vivo efficacy of ubiquinol, a natural inhibitor of Mg2+-nSMase, in free and niosomes-encapsulated forms, through five-day and 15-day regimens on the early and late Schistosoma mansoni parasitic stages, respectively, compared to PZQ. Oral administration of 300 mg/kg/day ubiquinol-encapsulated niosomes (U-N) showed significant deterioration of the parasitic growth and development in the term of reduction of lung schistosomula burden (39.12%), adult worm burden (50.81%), hepatic and intestinal tissue-egg counts (80.89% and 75.54%, respectively). PZQ and free ubiquinol regimens reported reductions in lung schistosomula counts (45.36% and 22.90%, respectively) and total worm burdens of 86.28% and 24.58%, respectively. U-N therapy revealed worms de-pairing and remarkable diminution in female worms' perimeters and fecundity. Scanning electron microscope revealed disruption of tegumental ridges with excessive longitudinal corrugation. Transmission electron microscope showed testicular and ovarian parenchymal degeneration, signs of immaturity and cell apoptosis. Indirect immunofluorescence assay approved parasite's tegumental changes. Remarkable reduction of granulomas size with amelioration of hepatic pathology and fibrosis were assumed to be attributed to the anti-inflammatory and anti-oxidant properties of ubiquinol. These findings with the drug safety profile suggest that U-N could be a promising candidate for a new antischistosomal drug development.

Early diagnosis of experimental Trichinella spiralis infection by nano-based enzyme-linked immunosorbent assay (nano-based ELISA).

Trichinellosis is a serious foodborne zoonotic disease. It is an important threat to public health all over the world. Although anti-Trichinella IgG detection is the most widely used method for diagnosis of trichinellosis, but there is an obvious window between clinical symptoms and positive serology. Gold nanoparticles (AuNPs) can be conjugated with antibodies affording them promising applications for bio-chemical detection. Herein, AuNPs-based ELISA was evaluated for the first time in the detection of Trichinella spiralis circulating antigen (CAg) for its potential as a diagnostic tool of experimental infection. Swiss Albino mice were orally inoculated with 100 muscle larvae/mouse. Animals were sacrificed 6, 8, 10, 12, 14, 16, 22 and 28 day-post infection (dpi). Blood samples were tested for CAg by both standard ELISA and nano-based ELISA using anti-rabbit polyclonal IgG conjugated with AuNPs. CAg was only detected by nano-based ELISA 6, 8, 10 dpi and by both formats 12-28 dpi. Nano-based assay recorded a statistically significant high sensitivity (58.33%, 91.67%) and accuracy (72.22%, 94.44%) 8 and 10 dpi, respectively in comparison to standard ELISA. Both assays showed high sensitivity and accuracy 12-28 dpi. Thus, nano-based ELISA could be considered as an early sensitive diagnostic method for experimental trichinellosis.