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Coccidiosis is a parasitic disease of wild and domestic animals caused by Eimeria spp. Currently, several drugs are available for the control of this disease but resistance has been confirmed for all them. There is an urgent need, therefore, for the identification of new compounds as alternative treatments to control coccidiosis. Astragalus membranaceus proven to have anti-inflammatory, anti-oxidant, immunomodulating and anticancer activities. The present study was therefore undertaken to assess the in vivo and the in vitro anticoccidial activity of Astragalus membranaceus root (AMR). Mice were divided into five groups, with the first left non-infected and the second, third, fourth and fifth groups being infected with 1 × 103 sporulated oocysts of E. papillata. The third, fourth and fifth groups also received, respectively, an oral dose of 10, 25 and 50 mg/kg AMR suspended in physiological saline daily for five consecutive days. 50 mg/kg, was the most effective dose, inducing a significant reduction in the number of oocysts output in mice faeces (by about 57%), accompanied by a significant decrease in the number of parasitic stages in jejunal sections. Moreover, the treatment with AMR increased the number of goblet cells and upregulated the expression of its specific gene, MUC2. In addition, our study proved that AMR reduced oxidative damage since levels of TBARS decreased (indicating reduced lipid peroxidation), levels of glutathione (GSH) and glutathione peroxidase (GPX) increased, and the mRNA level of iNOS was downregulated. Also, AMR treatment revealed anti-apoptotic activity as it was able to regulate the gene expression of Bcl-2 in the jejunum of E. papillata infected mice. Finally, the in vitro study revealed that AMR significantly inhabited the oocyst sporulation in a dose dependent manner. Overall, therefore, our results indicate that AMR exhibits significant in vivo and in vitro anticoccidial effects. Keywords: Coccidia, Astragalus membranaceus, Oxidative stress, MUC2, iNOs, Bcl2 sporulation

Ivermectin (Iv) is widely used to control Rhipicephalus annulatus infestations in cattle in Egypt. However, increasing resistance to ivermectin necessitates alternative approaches. This study aimed to address this resistance by investigating the interactions between ivermectin and essential oil components (EOCs)-carvacrol, cinnamaldehyde, D-limonene, trans-anethole, and thymol-against four R. annulatus tick isolates collected from Beni-Suef, El-Minia, and El-Fayoum. The larval immersion test was conducted using various ivermectin concentrations (3, 1.5, 0.75, 0.38, 0.19, 0.09, 0.045, 0.025, and 0.0125 mg/mL) prepared in EthTX1 %. Additionally, EOCs were tested at different concentrations (20, 10, 5, and 2.5 mg/mL) prepared by dilution in 5 % ethyl alcohol and EthTX 1 %. Ivermectin and each EOC were tested individually against the isolates. Subsequently, the LC50 of ivermectin was combined with the LC50 of each EOC in a 1:1 ratio to evaluate potential synergistic effects. All EOCs demonstrated significant toxicity against the isolates. The combination of carvacrol and thymol with ivermectin increased mortality, but the combination index (CI) exceeded one for all isolates, indicating no synergism. Similarly, while D-limonene, cinnamaldehyde, and trans-anethole also resulted in high mortality rates, including up to 100 %, no synergism was observed (CI > 1). However, these three EOCs exhibited CIs close to 1, suggesting an additive effect when combined with ivermectin. In conclusion, combining ivermectin with certain EOCs, particularly D-limonene, cinnamaldehyde, and trans-anethole, may offer an effective tool for controlling cattle ticks. Developing topical or pour-on formulations of ivermectin-EOC combinations could be an integral part of integrated management strategies to combat resistance to macrocyclic lactones like ivermectin. Further studies, including tests on adult ticks and field trials, are needed to evaluate the efficacy of these combinations., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The present study evaluated, in laboratory and field, the efficacy and safety of formulations of Pelargonium graveolens (geranium - G), Origanum majorana (oregano - O) commercial essential oils (EO) and thymol (T) to control of Rhipicephalus sanguineus sensu lato. In the laboratory, three formulas (A: 2% tween 80%, B: powder and C: nanoemulsion) by a mixture of these components (GOT) were prepared and evaluated, and the best one was used to assess its safety and field application against R. sanguineus s. l. on naturally infested dogs. Besides the major compounds of the EO used were identified. The results of the lab study showed that formula A (2.5 g of each G + O + T + 2% tween 80 to complete 100 mL) was significantly more effective than the other two formulas tested and exhibited highly effective adulticidal, larvicidal, and ovicidal activity against R. sanguineus s.l. Significant LC 50 and LC 90 values of GOT were evaluated (13.4 and 21.5 mg/mL, respectively) for the adulticidal activity, (2.81 and 4.46 mg/mL, respectively) for ovicidal activity and (2.44 and 4.45 mg/mL, respectively) for larvicidal activity. The safety of formula A has been proven by the absence of its cytotoxicity on a cell line of human epidermoid carcinoma. Citronella and carvacrol were the major compounds identified in the commercial essential oils of P. graveolens and O. majorana, respectively. Formula A was used in a field control trial for almost 8 months, during the tick infestation season (April to November, 2022). Fourteen naturally infested dogs were divided into two groups, each with seven dogs. One group received formula A spraying five times during an experiment that continued for 8 months, while the other group received treatment with commercially available malathion acaricide. The animals were sprayed on five occasions throughout the experiment (April, June, July, August, and September). The results showed a substantial percentage of effectiveness after the first application of formula A with a 99.3% reduction in tick count at day 28 post-application (PA). In the case of severe infestation 60 days after the first application of formula A (more than 180 ticks per dog), the second application was done, achieving an efficacy of 54.9% at day 3 PA, so an emergency spray was done at day 5 PA to combat the rest of the tick infestation, achieving efficacy of 99% after 3 days. Consequently, a regular spray (third, fourth, and fifth application) was done every 35 days. This regular spray revealed 100% effectiveness at 14 days PA. Biochemical parameters of treated dogs were evaluated to confirm the safety of formula A. Creatinine, ALT, and albumin of the dogs treated with formula A were within the normal range of dogs, while urea and AST were higher than the normal range. In conclusion, formula A can safely treat R. sanguineus s.l. infestations in dogs with regular application every 5 weeks., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Apicomplexan parasites, especially Eimeria sp., are the main intestinal murine pathogens, that lead to severe injuries to farm and domestic animals. Many anticoccidial drugs are available for coccidiosis, which, leads to the development of drug-resistant parasites. Recently, natural products are considered as an alternative agent to control coccidiosis. This study was designed to evaluate the anticoccidial activity of the Persea americana fruit extract (PAFE) in male C57BL/6 mice. A total of 35 male mice were divided into seven equal groups (1, 2, 3, 4, 5, 6, and 7). At day 0, all groups except the first group which served as uninfected-untreated control were infected orally with 1 × 10 3 E. papillata sporulated oocysts. Group 2 served as uninfected-treated control. Group 3 was considered an infected-untreated group. After 60 min of infection, groups 4, 5, and 6 were treated with oral doses of PAFE aqueous methanolic extract (100, 300, and 500 mg/kg of body weight, respectively). Group 7 was treated with amprolium (a reference drug for coccidiosis). PAFE with 500 mg/kg, was the most effective dose, inducing a significant reduction in the output of oocysts in mice feces (by about 85.41%), accompanied by a significant decrease in the number of the developmental parasite stages and a significant elevation of the goblet cells in the jejunal tissues. Upon treatment, a significant change in the oxidative status due to E. papillata infection was observed, where the levels of glutathione (GSH) increased, while, levels of malondialdehyde (MDA) and nitric oxide (NO) were decreased. In addition, the infection significantly upregulated the inflammatory cytokines of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ). This increase in mRNA expression of IL-1β, TNF-α, and IFN-γ was about 8.3, 10.6, and 4.5-fold, respectively, which significantly downregulated upon treatment. Collectively, P. americana is a promising medicinal plant with anticoccidial, antioxidant, and anti-inflammatory activities and could be used for the treatment of coccidiosis., Competing Interests: Declaration of Competing Interest The author(s) declare that they have no conflict of interest regarding the content of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glugea eda n. sp. is described from the mesenteries of the striated fusilier, Caesio striata, collected from the Red Sea coast off Yanbu' al Bahr, Saudi Arabia. Numerous blackish xenomas, ranged from 3 to 5 mm, were found in the body cavity associated with the mesenteries. Mature spores are monomorphic, ellipsoidal with an average size of 5(4-6) μm in length and 2.2 (2-3) μm in width. Observations of the ultrastructure revealed that the development was asynchronous and that the nuclei were isolated throughout the life cycle with uninucleate meronts. Sporoblasts were uninucleated and existed together with sporonts in a fully formed parasitophorous vacuole. The polar filament of the mature spore was isofilar with 24-28 coils, arranged in three rows. Phylogenetic analysis placed the current microsporidia within the clade grouping Glugea species and close to the species described from the Red Sea and Arabian Gulf. The morphometric and molecular comparison with other members of the genus Glugea evidenced the taxonomic novelty of the present form, suggesting that it should be considered as a new species. To the best of our knowledge, the parasite here described represents the first occurrence of microsporidian infection in the fish of the family Caesionidae., Competing Interests: Declaration of Competing Interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Trypanosomiasis is a neglected tropical disease, transmitted by blood-sucking insects and can affect humans and animals, depending on the species of Trypanosoma parasite. Trypanosoma has acquired resistance to the majority of drugs used; hence, alternative medicines are required. Indigofera oblongifolia leaf extract (IOE) has been shown to treat blood stage malaria. Here, IOE was used to demonstrate its effect on Trypanosoma evansi-infected mice., Methods: Analysis of IOE by gas chromatography-mass spectrometry showed the presence of many active components like flavonoids and phenolics. The mice were divided into three groups as follows: vehicle control, T. evansi-infected mice and T. evansi-infected-treated mice., Results: The findings demonstrate a significant effect of IOE treatment on T. evansi-infected mice. Parasitemia was decreased by 70%, weight loss was reduced, and splenomegaly was significantly decreased. Additionally, IOE improved the histological architecture of the spleen, as shown by the improved histological injury score post-treatment. Anemia was apparent during the course of infection in T. evansi-infected mice; this was reversed upon treatment with IOE to almost the normal level of hemoglobin and erythrocytes. Reduced glutathione and catalase were also ameliorated upon IOE treatment compared to T. evansi-infected mice., Conclusion: Overall, this study shows the ameliorative role of IOE against T. evansi-induced spleen injury in mice., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pigeons members of the order Columbiformes are a cosmopolitan group of birds with abundant and large populations associated with human activities. Therefore, the current study was conducted to determine the parasitic infections within the domestic pigeon Columba livia domestica. Eighteen pigeons were examined for the presence of gastrointestinal helminths, of which 77.78% were infected with a cyclophyllidean cestoda parasites. The morphology of this parasite based on light and scanning electron microscopic studies, revealed the presence of gravid worms, 2.00-4.52 cm long and 0.23-0.59 mm wide; a scolex had four suckers equipped by 5-6 rows of minute hooks and retractable rostellum with 230-250 hooks; genital pores unilateral; oval testes with 27-37 in number; bilobed ovary; post-ovarian vitelline gland; and 24-28 egg capsules present in uterus with 5-6 spherical eggs in each capsule. Molecular analysis based on sequences of ITS2 and ND1 gene regions was performed to confirm the taxonomy of this parasite based on its morphology. This revealed close identity of up to 92.0% and 72.0% for ITS2 and ND1 gene regions, respectively, with other cestoda species obtained from GenBank. Phylogenetic analysis supported the placement of this cycllophylid species within Davaineidae with close relationships to the previously described species of R. chiltoni, R. dromaius, and R. beveridgei based on the ITS2 gene region and R. coreensis and R. sonini based on the ND1 gene regions. Heavy metals accumulation in the recovered parasite and its host showed significantly higher concentrations in the parasite compared to its host tissues. Generally, concentrations of metals exceeded the permissible limits recommended by the US Environmental Protection Agency. Therefore, pigeon cestodes can be regarded as useful bio-indicators when evaluating the environmental pollution of terrestrial ecosystems by heavy metals., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Myxobolus absonusCellere et al., 2002 was originally described as having free cysts in the opercular cavity of the freshwater fish Pimelodus maculatus in Brazil. The present study provides a supplemental description of this parasite from the eye of its type host, with basis on morphological, ultrastructural, and molecular data of the SSU rRNA gene. The parasite formed spherical whitish cysts, which wall presented numerous microvilli that attached to the collagen layers of the corneal stroma. Myxospores were oval in valvular and sutural view, measuring 13.2 ± 0.4 μm in length, 8.5 ± 0.4 μm in width, and 6.6 ± 0.3 μm in thickness. Two asymmetric pyriform polar capsules were located at the anterior pole: the larger 6.2 ± 0.4 μm long and 3.6 ± 0.3 μm wide, containing a polar filament coiled in 6 turns; and the smaller 3.5 ± 0.3 μm long and 1.9 ± 0.1 μm wide, containing a polar filament coiled in 4 turns. At the posterior pole, the sporoplasm displayed two nuclei and numerous spherical sporoplasmosomes. Phylogenetic analysis using maximum likelihood, Bayesian inference and maximum parsimony revealed M. absonus clustering within a well-supported clade with poorly-resolved internal nodes, amongst the SSU rRNA sequences of other myxobolids that infect siluriform and characiform fish hosts, as well as the perciform-infecting species Myxobolus acanthogobii, Triangula percae and Cardimyxobolus japonensis. This clade appeared separated from the other clades comprising most of the species that infect siluriform and characiform hosts, showing that more than one myxobolid lineage evolved while parasitizing these taxonomic groups of fish., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply has been proposed to confer health benefits for patients suffering from some viral diseases, most notably with respect to HIV and influenza A virus (IAV) infections. In addition, selenium-containing multimicronutrient supplements improved several clinical and lifestyle variables in patients coinfected with HIV and Mycobacterium tuberculosis. Selenium status may affect the function of cells of both adaptive and innate immunity. Supranutritional selenium promotes proliferation and favors differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus supporting the acute cellular immune response, whereas excessive activation of the immune system and ensuing host tissue damage are counteracted through directing macrophages toward the M2 phenotype. This review provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M. tuberculosis, Helicobacter pylori). Data from epidemiologic studies and intervention trials, with selenium alone or in combination with other micronutrients, and animal experiments are discussed against the background of dietary selenium requirements to alter immune functions., (© 2015 American Society for Nutrition.)

The present study aimed to investigate oxidative stress, DNA damage, and histopathological alterations in hepatic tissues of Mongolian gerbils experimentally infected with Babesia divergens. It was found that parasitaemia reached approximately 77% at day 5 post-infection. The liver became dark-brown and extremely friable, and hepatic sinusoids were dilated and contained macrophages and parasite-containing erythrocytes. Infection also induced inflammation and injury of the liver. This was illustrated by (1) an increase in inflammatory cellular infiltrations, (2) a decrease in total antioxidant capacity, as indicated by lowered glutathione and catalase levels, (3) increased production of nitric oxide-derived products (nitrite/nitrate) and malondialdehyde, and (4) increased lactic acid dehydrogenase activity and protein carbonyl content in the liver. Infection also interfered with the normal cell cycle of the hepatic tissue, as indicated by a significant increase in the percentage of liver cells at G0/G1 from approximately 86.2% to 97.5% and in S phases from 0.28% to 2.2%. Collectively, the present data suggest that B. divergens infection could induce cell-cycle alteration following oxidative stress and DNA damage in hepatic tissue. Further work is required to investigate the mechanism by which this hepatic tissue damage takes place., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Testosterone (T) is known to induce persistent susceptibility to blood-stage malaria of Plasmodium chabaudi in otherwise resistant female C57BL/6 mice, which is associated with permanent changes in mRNA expression of the liver. Here, we investigate the spleen as the major effector against blood-stage malaria for any possible T-induced long-term effects on lincRNA and mRNA expression. Female C57BL/6 mice were treated with T for 3 weeks, then T was withdrawn for 12 weeks before challenging with P. chabaudi. LincRNA and mRNA expression was examined after 12 weeks of T-withdrawal and after subsequent infections using Agilent whole mouse genome oligo microarrays. Our data show for the first time long-term effects of T on lincRNA expression evidenced directly as persistent changes after T-withdrawal for 12 weeks and indirectly as altered responsiveness of expression to P. chabaudi infections. There are 3 lincRNA-species upregulated and 10 lincRNAs downregulated by more than 2-fold (p<0.01). In addition, 11 and 10 mRNAs are persistently up- and downregulated by T, respectively. These changes remain not sustained during infections at peak parasitemia, when 15 other lincRNAs and 9 other mRNAs exhibit an altered expression. The only exception is the Tnk1-mRNA encoding the non-receptor tyrosine kinase 1 that is persistently downregulated by 0.34-fold after T-withdrawal and that becomes upregulated by 5.9-fold upon infection at peak parasitemia, suggesting an involvement of tyrosine phosphorylation by Tnk1 in mediating long-term effects of T in the spleen. The T-induced changes in splenic mRNA expression are totally different to those previously observed in the liver. Collectively, our data support the view that T induces long-term organ-specific changes in both lincRNA and mRNA expression, that presumably contribute to organ-specific dysfunctions upon infection with blood-stage malaria of P. chabaudi., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Eimeria coecicola causes intestinal coccidiosis in rabbits and, thereby, enormous economic losses in rabbit farms. Here, we investigate the final target site of E. coecicola, the appendix of rabbits, at the level of gene expression. Rabbits, orally infected with E. coecicola, begin to shed parasitic oocysts with their feces on day 5 p.i., and approximately 1.1 million oocysts are maximally shedded on day 7 p.i. At maximal shedding, the appendix has increased in size by about 2-3-folds and reveals increased hemorrhage which is associated with increases in nitrite/nitrate, malondialdehyde and catalase activity and a decrease in glutathione. Agilent 2-color oligo whole rabbit genome microarray, in combination with quantitative real-time PCR, detects 45 and 36 genes whose expression is more than 2-fold up- and down-regulated, respectively, by E. coecicola infection on day 7 p.i. The most dramatic increase by approximately 50-fold reveals the mRNA of the pro- and anti-inflammatory pleiotropic cytokine interleukin 6 (IL-6), whereas the largest decrease by approximately 13-fold is detected for mRNAs encoding for DBP, SULT3A1, CRP and glutathione-S transferase. Also, there are up- and down-regulations in the expression of genes encoding diverse regions of antibodies. Our data suggest that IL-6 plays a central role in the infection of the appendix of rabbits by E. coecicola, presumably involved in both pathological injuries, host defences and healing processes., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Lead is a toxic metal inducing many destructive effects leading to a broad range of physiological, biochemical, and neurological dysfunctions in humans. Here, we investigated the effects of flaxseed oil (1000 mg/kg) on the outcome of renal cytotoxicity induced by lead acetate (20mg/kg) in male rats. Lead induced injury of the renal tissue. This was evidenced (i) as increases in lead concentration in the kidney, (ii) as increases in the histopathological damage of the renal tissue, (iii) as increases in uric acid, urea and creatinine, (iv) as increases in lipid peroxidation, nitric oxide and reactive oxygen species, and (v) as lowered glutathione levels and decreased activities of catalase and superoxide dismutase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase, respectively. All these lead-induced parameters were significantly altered during flaxseed oil treatment. Therefore, our study suggests the role of flaxseed oil in limiting renal cytotoxicity-induced by lead acetate as a model for lead toxicity., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Cysts of Sarcocystis capracanis obtained from infected goats were examined to clarify the effect of the parasite on the host. Muscle tissues from fresh oesophagus, tongue, diaphragm and skeletal muscles of 680 goats were slaughtered in the main abattoir of Cairo, Egypt and they were examined microscopically for Sarcocystis infection for the first time in Egypt. 540 out of 680 (79.4%) of examined goats were found to be infected with Sarcocystis sp. The infection was recorded firstly by light microscopy as spindle shaped cysts embedded in the muscle tissues. The validity of this species as S. capracanis was confirmed by means of ultrastructural characteristics of the primary cyst wall which revealed the presence of thick-radially striated wall with finger like projections, underlined by a thick layer of ground substance enclosing the developing metrocytes and merozoites that usually contain nearly all the structures of the apical complex and fill the interior cavity of the cyst. The cyst cavity is divided by many septa extending from the ground substance and producing large number of chambers. An experimental infection using the highly infected muscles was carried out to determine the final host, which is dog. Smears of intestinal epithelium were taken to examine the endogenous stages (gamogony and sporogony) by means of light microscopy. These stages were mainly observed as to infect the lamina propria of the posterior third of the small intestine. Gamogony and zygote formation (fertilization) occurred 2-8 days post infection, while sporulation took place within the final host 13-15 days and sporocysts were passed within faeces of the infected puppies at that time. The prepatent period of S. capracanis was 12-15 days, while the patent period was extended to 37 days. In goats, infection with S. capracanis led to the loss of weight, anaemia, abortion and even death in cases of heavy infection. While bleeding, watery faeces filled with mucous on 5th and 8th day p.i. as well as intestinal lesions are the pathogenic effects occurred in puppies after experimental infection., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Blood-stage malaria of Plasmodium chabaudi is characterized by its responsiveness to testosterone (T): T suppresses development of protective immunity, whereas once acquired immunity is T-unresponsive. Here, we have analyzed the liver, a T target and lymphoid organ with anti-malaria activity, for its T-responsiveness of gene expression in immune mice. Using Affymetrix microarray technology, in combination with quantitative RT-PCR, we have identified (i) T-unresponsive expression of newly acquired mRNAs encoding diverse sequences of IgG- and IgM-antibodies, (ii) 24 genes whose expression has become T-unresponsive including those encoding the T(H)2 response promoting EHMT2 and the erythrocyte membrane protein band 7.2 STOM, (iii) T-unresponsive expression of mRNAs for the cytokines IL-1β, IL-6, TNFα, and IFNγ, as well as iNOS, which are even not inducible by infection, and (iv) 35 genes retaining their T-responsiveness, which include those encoding the infection-inducible acute phase proteins SAA1, SAA2, and ORM2 as well as those of liver metabolism which encode the T-downregulated female-prevalent enzymes CYP2B9, CYP2B13, CYP3A41, CYP7A1, and SULT2A2 and the T-upregulated male-prevalent enzymes CYP2D9, CYP7B1, UGT2B1, HSD3B2, HSD3B5, respectively. The mRNA of the latter T-metabolizing enzyme is even 5-fold increased by T, suggesting a decrease in the effective T concentrations in the liver of immune mice. Collectively, our data suggest that the liver, which has acquired a selective T-unresponsiveness of gene expression, contributes to the acquired T-unresponsive, antibody-mediated protective immunity to blood-stage malaria of P. chabaudi., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Coccidiosis with the protozoan parasite Eimeria as the infectious agent causes enormous economic losses, particularly in poultry farms. Here, we investigated the effects of garlic on the outcome of coccidiosis caused by Eimeria papillata in male Balb/c mice. The data showed that mice infected with E. papillata revealed an output of 3260 ± 680 oocysts per gram faeces on day 4 p.i.. This output is significantly decreased to 1820 ± 415 oocysts in garlic-treated mice. Infection also induced inflammation and injury of the liver. This was evidenced (i) as increases in inflammatory cellular infiltrations, dilated sinusoids, and vacuolated hepatocytes, (ii) as increased mRNA levels of inducible nitric oxide synthase (iNOS) and of the cytokines interferon gamma (IFN-γ), and interleukin-6 (IL-6), (iii) as increased plasma levels of alanine and aspartate aminotransferases, alkaline phosphatase, γ-glutamyl transferase and total bilirubin, (iv) as increased production of nitric oxide derived products (nitrite/nitrate) and malondialdehyde, and (v) as lowered glutathione levels and decreased activities of catalase and superoxide dismutase, respectively. All these infection-induced parameters were significantly less altered during garlic treatment. In particular, garlic counteracted the E. papillata-induced loss of glutathione and the activities of catalase and superoxide dismutase. Our data indicated that garlic treatment significantly attenuated inflammation and injury of the liver induced by E. papillata infections., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Testosterone (T) regulates expression of protein-encoding genes directly through androgen receptor (AR) targeting androgen response element (ARE) in gene promoters or indirectly through non-genotropic mechanisms, but only limited information is available about T effects on expression of gene-regulatory non-coding miRNAs. Here, we investigate the effect of T on miRNA expression profiles in the female mouse liver using miRXplore microarrays and quantitative RT-PCR. T treatment for 3 weeks induced upregulation of the 6 miRNAs miR-22, miR-690, miR-122, let-7A, miR-30D and let-7D, reaching maximal expression at different time-points during T treatment. This upregulation was transient, i.e. it disappeared after T withdrawal for 12 weeks, and it was rather robust since it was not essentially affected by blood-stage infections with Plasmodium chabaudi malaria. In silico analysis revealed an ARE in the miR-122 promoter, while the other 5 miRNAs did not contain any ARE in their 2000bp promoters. The T-induced upregulation of the 6 miRNAs coincided with a downregulation of some of their target protein-encoding genes, the majority of which did incidentally not contain any ARE in their promoters. T treatment did not affect expression of AR and estrogen receptor beta (ERbeta), but significantly downregulated the miR-22 target genes ERalpha and aromatase. This downregulation is presumably not caused by T after its aromatase-mediated conversion to E(2) through ER, but rather by the T-induced upregulation of miR-22. Collectively, our data suggest that T can regulate expression of distinct miRNAs in vivo by both genotropic and non-genotropic mechanisms., (Copyright 2010 Elsevier Inc. All rights reserved.)