MicroRNA mmu-miR-511-5p: A promising Diagnostic Biomarker in Experimental Toxoplasmosis Using Different Strains and Infective Doses in Mice with Different Immune States Before and After Treatment.

PURPOSE: Searching for a novel early diagnostic biomarker for toxoplasmosis, real-time-PCR was currently used to measure the serum mmu-miR-511-5p level in male Swiss-albino mice infected with either; ME49 or RH Toxoplasma gondii (T. gondii) strains. METHODS: Three mice groups were used; (GI) constituted the non-infected control group, while (GII) and (GIII) were experimentally infected with ME49 or RH strains, respectively. GII mice were orally infected using 10 or 20 ME49 cysts (ME-10 and ME-20), both were subdivided into; non-treated (ME-10-NT and ME-20-NT) and were further subdivided into; immunocompetent (ME-10-IC and ME-20-IC) [euthanized 3-days, 1, 2, 6 or 8-weeks post-infection (PI)], and immunosuppressed using two Endoxan® injections (ME-10-IS and ME-20-IS) [euthanized 6- or 8-weeks PI], and spiramycin-treated (ME-10-SP and ME-20-SP) that received daily spiramycin, for one-week before euthanasia. GIII mice individually received 2500 intraperitoneal RH strain tachyzoites, then, were subdivided into; non-treated (RH-NT) [euthanized 3 or 5-days PI], and spiramycin-treated (RH-SP) that were euthanized 5 or 10-days PI (refer to the graphical abstract). RESULTS: Revealed significant upregulation of mmu-miR-511-5p in GII, one-week PI, with gradually increased expression, reaching its maximum 8-weeks PI, especially in ME-20-NT group that received the higher infective dose. Immunosuppression increased the upregulation. Contrarily, treatment caused significant downregulation. GIII recorded significant upregulation 3-days PI, yet, treatment significantly decreased this expression. CONCLUSION: Serum mmu-miR-511-5p is a sensitive biomarker for early diagnosis of ME49 and RH infection (as early as one-week and 3-days, respectively), and its expression varies according to T. gondii infective dose, duration of infection, spiramycin-treatment and host immune status.

Trichinella spiralis: A new parasitic target for curcumin nanoformulas in mice models.

Trichinosis spiralis is a global disease with significant economic impact. Albendazole is the current-treatment. Yet, the world-widely emerging antimicrobial resistance necessitates search for therapeutic substitutes. Curcumin is a natural compound with abundant therapeutic benefits. This study aimed to evaluate the potential of crude-curcumin, chitosan and for the first time curcumin-nano-emulsion and curcumin-loaded-chitosan-nanoparticles against Trichinella spiralis adults and larvae in acute and chronic trichinosis models. Trichinosis spiralis was induced in 96 Swiss-albino mice. Infected mice were divided into 2 groups. Group I constituted the acute model, where treatment started 2 h after infection for 5 successive days. Group II constituted the chronic model, where treatment started at the 30th day-post-infection and continued for 10 successive days (Refer to graphical abstract). Each group contained 8 subgroups that were designated Ia-Ih and IIa-IIh and included; a; Untreated-control, b; Albendazole-treated (Alb-treated), c; Crude-curcumin-treated (Cur-treated), d; Curcumin-nanoemulsion-treated (Cur-NE-treated), e; Albendazole and crude-curcumin-treated (Alb-Cur-treated), f; Albendazole and curcumin-nanoemulsion-treated (Alb-Cur-NE-treated), g; Chitosan-nanoparticles-treated (CS-NPs-treated) and h; Curcumin-loaded-chitosan-nanoparticles-treated (Cur-CS-NPs-treated). Additionally, six mice constituted control-uninfected group III. The effects of the used compounds on the parasite tegument, in-vivo parasitic load-worm burden, local pathology and MDA concentration in small intestines of acutely-infected and skeletal muscle of chronically-infected mice were studied. Results showed that albendazole was effective, yet, its combination with Cur-NE showed significant potentiation against adult worms and muscle larvae and alleviated the pathology in both models. Cur-CS-NPs exhibited promising results in both models. Crude-curcumin showed encouraging results especially against muscle larvae on long-term use. Treatments effectively reduced parasite load, local MDA level and CD31 expression with anti-inflammatory effect in intestine and muscle sections.

Impact of the age of Biomphalaria alexandrina snails on Schistosoma mansoni transmission: modulation of the genetic outcome and the internal defence system of the snail

Of the approximately 34 identified Biomphalariaspecies,Biomphalaria alexandrinarepresents the intermediate host of Schistosoma mansoniin Egypt. Using parasitological and SOD1 enzyme assay, this study aimed to elucidate the impact of the age of B. alexandrinasnails on their genetic variability and internal defence against S. mansoniinfection. Susceptible and resistant snails were reared individually for self-reproduction; four subgroups of their progeny were used in experiment. The young susceptible subgroup showed the highest infection rate, the shortest pre-patent period, the highest total cercarial production, the highest mortality rate and the lowest SOD1 activity. Among the young and adult susceptible subgroups, 8% and 26% were found to be resistant, indicating the inheritance of resistance alleles from parents. The adult resistant subgroup, however, contained only resistant snails and showed the highest enzyme activity. The complex interaction between snail age, genetic background and internal defence resulted in great variability in compatibility patterns, with the highest significant difference between young susceptible and adult resistant snails. The results demonstrate that resistance alleles function to a greater degree in adults, with higher SOD1 activity and provide potential implications for Biomphalariacontrol. The identification of the most susceptible snail age enables determination of the best timing for applying molluscicides. Moreover, adult resistant snails could be beneficial in biological snail control.

Impact of the age of Biomphalaria alexandrina snails on Schistosoma mansoni transmission: modulation of the genetic outcome and the internal defence system of the snail.

Of the approximately 34 identified Biomphalariaspecies,Biomphalaria alexandrinarepresents the intermediate host of Schistosoma mansoniin Egypt. Using parasitological and SOD1 enzyme assay, this study aimed to elucidate the impact of the age of B. alexandrinasnails on their genetic variability and internal defence against S. mansoniinfection. Susceptible and resistant snails were reared individually for self-reproduction; four subgroups of their progeny were used in experiment. The young susceptible subgroup showed the highest infection rate, the shortest pre-patent period, the highest total cercarial production, the highest mortality rate and the lowest SOD1 activity. Among the young and adult susceptible subgroups, 8% and 26% were found to be resistant, indicating the inheritance of resistance alleles from parents. The adult resistant subgroup, however, contained only resistant snails and showed the highest enzyme activity. The complex interaction between snail age, genetic background and internal defence resulted in great variability in compatibility patterns, with the highest significant difference between young susceptible and adult resistant snails. The results demonstrate that resistance alleles function to a greater degree in adults, with higher SOD1 activity and provide potential implications for Biomphalariacontrol. The identification of the most susceptible snail age enables determination of the best timing for applying molluscicides. Moreover, adult resistant snails could be beneficial in biological snail control.