The Neuroprotective Effect Associated with Echinops spinosus in an Acute Seizure Model Induced by Pentylenetetrazole.

Echinops spinosus (ES) is a medicinal plant with a wide range of pharmacological and biological effects. It is a medicinal herb having a variety of therapeutic characteristics, including antioxidant, anti-inflammatory, and antibacterial capabilities. The primary goal of this research is to investigate the neuroprotective and anticonvulsant characteristics of E. spinosa extract (ESE) against pentylenetetrazole (PTZ)-induced acute seizures. Negative control rats, ESE treatment rats, PTZ acute seizure model rats, ESE + PTZ rats, and Diazepam + PTZ rats were used in the study. The rats were given a 7-day treatment. ESE pretreatment elevated the latency to seizure onset and lowered seizure duration after PTZ injection. By reducing Bax levels and enhancing antiapoptotic Bcl-2 production, ESE prevented the release of interleukin-1ß, tumor necrosis factor-α, and cyclooxygenase-2, as well as preventing hippocampal cell death after PTZ injection. ESE corrected the PTZ-induced imbalance in gamma-aminobutyric acid levels and increased the enzyme activity of Na+/K+-ATPase. Echinops spinosus is a potent neuromodulatory, antioxidant, antiinflammatory, and antiapoptotic plant that could be employed as a natural anticonvulsant in the future.

Silencing of heat shock protein 90 (hsp90): Effect on development and infectivity of Ichthyophthirius multifiliis.

BACKGROUND: Recently, an increasing number of ichthyophthiriasis outbreaks has been reported, leading to high economic losses in fisheries and aquaculture. Although several strategies, including chemotherapeutics and immunoprophylaxis, have been implemented to control the parasite, no effective method is available. Hence, it is crucial to discover novel drug targets and vaccine candidates against Ichthyophthirius multifiliis. For this reason, understanding the parasite stage biology, host-pathogen interactions, molecular factors, regulation of major aspects during the invasion, and signaling pathways of the parasite can promote further prospects for disease management. Unfortunately, functional studies have been hampered in this ciliate due to the lack of robust methods for efficient nucleic acid delivery and genetic manipulation. In the current study, we used antisense technology to investigate the effects of targeted gene knockdown on the development and infectivity of I. multifiliis. Antisense oligonucleotides (ASOs) and their gold nanoconjugates were used to silence the heat shock protein 90 (hsp90) of I. multifiliis. Parasite stages were monitored for motility and development. In addition, the ability of the treated parasites to infect fish and cause disease was evaluated. RESULTS: We demonstrated that ASOs were rapidly internalized by I. multifiliis and distributed diffusely throughout the cytosol. Knocking down of I. multifiliis hsp90 dramatically limited the growth and development of the parasite. In vivo exposure of common carp (Cyprinus carpio) showed reduced infectivity of ASO-treated theronts compared with the control group. No mortalities were recorded in the fish groups exposed to theronts pre-treated with ASOs compared with the 100% mortality observed in the non-treated control fish. CONCLUSION: This study presents a gene regulation approach for investigating gene function in I. multifiliis in vitro. In addition, we provide genetic evidence for the crucial role of hsp90 in the growth and development of the parasite, suggesting hsp90 as a novel therapeutic target for successful disease management. Further, this study introduces a useful tool and provides a significant contribution to the assessing and understanding of gene function in I. multifiliis.

Persea americana extract protects intestinal tissue from Eimeria papillata-induced murine Infection.

Coccidiosis is the most prevalent disease-causing widespread economic loss among farm and domestic animals. Currently, several drugs are available for the control of this disease but resistance has been confirmed for all of them. There is an urgent need, therefore, for the identification of new sources as alternative treatments to control coccidiosis. The present work aimed to study the effect of the Persea americana extract (PAE) as an anti-coccidial, anti-oxidant, and anti-apoptotic modulator during murine intestinal Eimeria papillata infection. A total of 25 male mice were divided into five groups, as follows: Group1: Non-infected-non-treated (negative control), Group2: Non-infected-treated group with PAE (500 mg/kg b.w). Group3: Infected-non-treated (positive control), Group4: Infected-treated group with PAE (500 mg/kg b.w.), and Group5: Infected-treated group with Amprolium (120 mg/kg b.w.). Groups (3-5) were orally inoculated with 1 × 103 sporulated E. papillata oocysts. After 60 min of infection, groups (4 and 5) were treated for 5 consecutive days with the recommended doses of PAE and amprolium. The fact that PAE has an anti-coccidial efficacy against intestinal E. papillata infection in mice has been clarified by the reduction of fecal oocyst output on the 5th day post-infection by about 85.41%. Moreover, there is a significant reduction in the size of each parasite stage in the jejunal tissues of the infected-treated group with PAE. PAE counteracted the E. papillata-induced loss of glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TCA). E. papillata infection also induced an increase in the apoptotic cells expressed by caspase-3 which modulated after PAE treatment. Moreover, the mRNA expression of the goblet cell response gene, mucin (MUC2), was upregulated from 0.50 to 1.20-fold after treatment with PAE. Based on our results, PAE is a promising medicinal plant with anti-coccidial, anti-oxidant, and anti-apoptotic activities and could be used as a food additive.

Blood Biomarkers of Neonatal Sepsis with Special Emphasis on the Monocyte Distribution Width Value as an Early Sepsis Index.

Background and Objectives: Early detection of neonatal sepsis is critical because it is potentially fatal. Therefore, sepsis biomarkers of sufficient sensitivity and specificity are needed. This study aimed to evaluate the utility of peripheral blood parameters as neonatal sepsis biomarkers and the diagnostic performance of the monocyte distribution width (MDW) in sepsis in a neonatal intensive care unit. Materials and Methods: A cross-sectional study was conducted from September 2019 to August 2020 at the King Saud University Medical City in Riyadh, Saudi Arabia. Samples were collected and organised as follows: 77 study cases were subdivided into two subgroups (other health complication (49) and sepsis (28)), and there were 70 controls. The causative microorganisms of neonatal sepsis were isolated. Peripheral blood samples were collected from each neonate in an ethylenediaminetetraacetic acid tube for a complete blood count and a leukocyte differential count. Moreover, the receiver operating characteristic (ROC) curve analysis was used to measure the diagnostic performance of the MDW. Results: The haematological parameters and neonatal sepsis cases had a considerable correlation. The MDW was the most significant haematological parameter. The ROC analysis of the MDW demonstrated that the area under the curve was 0.89 (95% confidence interval: 0.867 to 0.998) with a sensitivity of 89.3%, a specificity of 88.2%, and a negative predictive value of 97.2% at the cut-off point of 23. Conclusions: The use of haematological parameters is feasible and can be performed rapidly. Neonatal sepsis showed a strong correlation with leukopenia, anaemia, thrombocytopenia, and an elevated MDW value. Moreover, the ROC curve analysis confirmed the high diagnostic ability of the MDW in neonatal sepsis prediction.

Heteromicrocotyla polyorchis Unnithan, 1961 (Monogenea: Heteromicrocotylidae), a gill parasite of the yellow-spotted trevally, Carangoides fulvoguttatus (Carangidae) from Saudi Arabia: Morphology and phylogeny.

Little information for parasitic infections of Carangoides fulvoguttatus was recorded. The present study was intended to investigate the gill parasite Heteromicrocotyla polyorchis of this fish and to provide a full morphological description and clarify its taxonomic status through phylogenetic analysis of the 28S rRNA gene region. A total of sixty fish specimens have been collected from the studied area (the Red Sea in Jeddah Province, Saudi Arabia) and gills were isolated and examined for identification of parasites. Using light electron microscopy, the recovered monogenean parasite's morphology was exhaustively characterized and described. Microscope examinations found that this parasite species represent Heteromicrocotyla polyorchis, and it could be distinguished from congeners of the same genus by armed genital atrium and cirrus sac, follicular post-ovarian testes, unique shape and number of clamps on both haptor sides, and the dorsally curved tip of the male copulatory organ. Morphological features were combined with molecular analysis of the 28S rRNA gene region. The selected gene for the isolated Heteromicrocotyla species was analyzed using appropriate primers to assist in phylogeny with those in the GenBank database. The present monogenean species was characterized by unique genetic sequences that were analyzed and deposited in the GenBank for the first time under the accession number MW406473. Phylogenetic analyses reported that the maximum identity between the current Heteromicrocotyla species and taxa of Heteromicrocotylidae was between 91.42 and 92.09% and confirmed its taxonomic status in this family with a well-distinct clade. The present study supported the second report of H. polyorchis as carangid fish ectoparasites and investigates the first appearance in C. fulvoguttatus inhabiting Saudi Arabia.

Cucullanus bulbosus (Lane, 1916) Barreto, 1918 (Nematoda, Cucullanidae) from the common ponyfish Leiognathus equulus (Leiognathidae): Morphology and molecular study.

The common ponyfish Leiognathus equulus is a marine fish species with very high commercial value. Little information is available about its parasitic infections. Based on light and scanning electron microscopy, as well as sequencing and analysis of the partial regions of the ITS-1, 18S rRNA, COX1 genes, were employed for the systematic evaluation of a nematode parasite, which it first isolated from L. equulus in Jeddah Province, Red Sea, Saudi Arabia. Results revealed that this nematode parasite closely resembles the previously described Cucullanus bulbosus. Microscopic examination showed that it distinguished from congeners by the unique structure of hemispherical elevation at pseudobuccal capsule level, the ratio of esophagus/body length, spicules size, presence of pre-cloacal sucker, rod-shaped gubernaculum, and the arrangement of caudal papillae in males. Phylogenetic analyses based on ITS-1, 18S rRNA, and COX1 gene regions were constructed to investigate phylogenetic relationships between this parasite species and other related taxa. Results supported that Cucullanus bulbosus resembles a sister of Cucullanus genypteri, Cucullanus pulcherrimus, Cucullanus bourdini, Cucullanus extraneus, and Cucullanus hainanensis by using different genetic markers. This study provides more information about combining morphological and molecular data to identify Cucullanus species with the first natural occurrence in the common ponyfish inhabited in Saudi Arabia.

First record of third-stage Terranova larval type II (Nematoda, Anisakidae) in the common ponyfish Leiognathus equulus Forsskål.

The current study was carried out to investigate the natural occurrence of nematode parasites that infect the common ponyfish Leiognathus equulus from Jeddah, Saudi Arabia. Third-stage nematode larvae were found to be encysted in the peritoneum of the fish studied, with the prevalence of infection being 25%. Light microscopy revealed that this parasite belongs to the Anisakidae family within the genus Terranova by having all the generic characteristic features. Based on the intestinal caecum ratio to the length of the ventriculus being 2:1, the excretory pore with ventral location below the boring tooth, the body ended with a conical tail; the larvae found in the present study were identified as Terranova larval type. To validate its taxonomic position within Anisakidae, this Terranova species' morphological features were combined with the ITS-1 gene's molecular analysis. It demonstrated sequence similarities 94.38-76.57% with taxa of Anisakidae. A preliminary genetic comparison between the present parasite and other ascaridoids placed it as a putative sister taxon to the previously described Terranova species. The first record of the current anisakid larvae in the common ponyfish with a unique genetic sequence for the partial sequence of the ITS-1 gene was observed in this study. Its taxonomic position was confirmed in Anisakidae.

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria.

BACKGROUND: Vaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi. Blood-stage malaria induces extramedullary erythropoiesis in the liver. This study investigates how vaccination affects the course of malaria-induced expression of erythrocytic genes in the liver. METHODS: Female Balb/c mice were vaccinated at week 3 and week 1 before challenging with 106 P. chabaudi-parasitized erythrocytes. The non-infectious vaccine consisted of erythrocyte ghosts isolated from P. chabaudi-infected erythrocytes. Gene expression microarrays and quantitative real-time PCR were used to compare mRNA expression of different erythrocytic genes in the liver of vaccination-protected and non-protected mice during infections on days 0, 1, 4, 8, and 11 p.i. RESULTS: Global transcriptomics analyses reveal vaccination-induced modifications of malaria-induced increases in hepatic gene expression on days 4 and 11 p.i. On these days, vaccination also alters hepatic expression of the erythropoiesis-involved genes Ermap, Kel, Rhd, Rhag, Slc4a1, Gypa, Add2, Ank1, Epb4.1, Epb4.2, Epb4.9, Spta1, Sptb, Tmod1, Ahsp, Acyp1, Gata1, Gfi1b, Tal1, Klf1, Epor, and Cldn13. In vaccination-protected mice, expression of these genes, except Epb4.1, is significantly higher on day 4 p.i. than in un-protected non-vaccinated mice, reaches maximal expression at peak parasitaemia on day 8 p.i., and is slowed down or even decreased towards the end of crisis phase on day 11 p.i.. After day 1 p.i., Epor expression takes about the same course as that of the other erythroid genes. Hepatic expression of Epo, however, is delayed in both vaccinated and non-vaccinated mice for the first 4 days p.i. and is maximal at significantly higher levels in vaccinated mice on day 8 p.i., before declining towards the end of crisis phase on day 11 p.i. CONCLUSION: The present data indicate that vaccination accelerates malaria-induced erythroblastosis in the liver for 1-2 days. This may contribute to earlier replenishment of peripheral red blood cells by liver-derived reticulocytes, which may favour final survival of otherwise lethal blood-stage malaria, since reticulocytes are not preferred as host cells by P. chabaudi.

Chlorogenic acid prevents hepatotoxicity in arsenic-treated mice: role of oxidative stress and apoptosis.

Arsenic is a potent and toxic heavy metal found in the environment that causes health problems, including liver disease, in humans and animals. Chlorogenic acid (CA) is the most abundant caffeoylquinic acid isomer present in plants. This study aims to assess how CA protects the liver tissue following sodium arsenite (NaAsO2)-induced toxicity in mice. Male Swiss mice were allocated into 5 groups: Control, intragastrically administered CA (200 mg/kg), intragastrically administered NaAsO2 (5 mg/kg), and two groups administered with CA (100 and 200 mg/kg) and NaAsO2. CA was administered 30 min before NaAsO2 and all the mice were treated daily for 28 days. To investigate the biochemical, histopathological, immunohistochemical, and molecular changes, blood and liver samples were collected. NaAsO2 treatment increased the liver function biomarkers such as alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin. Lipid and nitric oxide production was elevated. Glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase decreased, indicating a disturbance in redox homeostasis. Histopathological examination revealed a granular degeneration of hepatocytes, infiltration of inflammatory cells, and centrilobular hepatocyte necrosis. Furthermore, tumor necrosis factor-α and interleukin-1ß were upregulated upon NaAsO2 treatment, suggesting the induction of inflammation. Moreover, NaAsO2 triggered apoptosis in the liver by upregulating Bax and caspase-3 and downregulating Bcl-2. However, CA abrogated the biochemical, molecular, and histological changes, reflecting its hepatoprotective role in response to NaAsO2 treatment. Our findings demonstrate that CA could be a potential therapeutic to minimize NaAsO2-induced hepatic injury.

Antioxidant and anti-apoptotic effects of selenium nanoparticles against murine eimeriosis.

Eimeriosis is caused by a protozoan parasite of the genus Eimeria and infection affecting most domestic animal species. The aim of this research was to comprehend the impact of selenium nanoparticles (SeNPs) on eimeriosis induced by Eimeria papillata in mouse jejunum, and how they work as antioxidants and anti-apoptotic agents against eimeriosis. The numbers of meronts, gamonts, and developing oocysts of E. papillata reduced after the infected mice were treated with the SeNPs. The levels of malondialdehyde (MDA), nitric oxide (NO), and other oxidative stress-related molecules, such as glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), were assayed. E. papillata was able to change the redox status of the jejunal cells; this was confirmed by the elevation of the MDA and NO levels, and the decrease of the GSH levels and the activities of the antioxidant enzymes CAT and SOD. SeNP treatment significantly reversed this disturbance of the redox status. The expression levels of the apoptotic markers Bax and caspase-3 in the jejunal samples were evaluated using qRT-PCR. The SeNPs decreased the Bax and caspase-3 expression after being administered to the E. papillata-infected mice. Collectively, the SeNPs demonstrated antioxidant and anti-apoptotic activities against murine eimeriosis.

Nephroprotective effect of Pleurotus ostreatus extract against cadmium chloride toxicity in rats.

Cadmium, present in the environment, accumulates in different organs of animals and humans, and has deleterious effects on the kidney. In this study, we investigated the protective effects of the methanolic extract of Pleurotus ostreatus in comparison with silymarin on renal function in cadmium-intoxicated rats for five days. Rats intraperitoneally injected with cadmium chloride (1 mg/kg). These rats were treated with either P. ostreatus extract (200 mg/kg) or silymarin to investigate the protective effects of the extract. Cadmium treatment induced significant histopathological impairments and increased cadmium levels, DNA fragmentation, and renal oxidative stress. However, treatment with P. ostreatus extract or silymarin improved the pathology, reduced the level of cadmium in renal tissue, and restored DNA fragmentation. In addition, a significant reduction in lipid peroxidation and reactive oxygen species levels, and a significant increase in the levels of glutathione and catalase activity were observed. Thus, protective effects of P. ostreatus extract to its components. Chromatographic analysis of the P. ostreatus confirmed the presence of five phenolics (gallic acid, chlorogenic acid, catechin, propyl gallate, and cinnamic acid) that exhibit strong antioxidant properties as free radical scavengers. Therefore, our findings demonstrate that treatment with P. ostreatus extract protects against cadmium-induced nephrotoxicity in female rats.

Quantitative proteomic profiling of immune responses to Ichthyophthirius multifiliis in common carp skin mucus.

Ichthyophthirius multifiliis, a ciliated protozoan parasite, causes ichthyophthiriasis and leads to considerable economic losses to the aquaculture industry. Understanding the fish immune response and host-parasite interactions could support developing novel strategies for better disease management and control. Fish skin mucus is the first line of defence against infections through the epidermis. Yet, the common carp, Cyprinus carpio, protein-based defence strategies against infection with I. multifiliis at this barrier remain elusive. The skin mucus proteome of common carp was investigated at 1 day and 9 days post-exposure with I. multifiliis. Using nano-LC ESI MS/MS and statistical analysis, the abundance of 19 immune related and signal transduction proteins was found to be differentially regulated in skin mucus of common carp in response to I. multifiliis. The analysis revealed increased abundance values of epithelial chloride channel protein, galactose-specific lectin nattection, high choriolytic enzyme 1 (nephrosin), lysozyme C, granulin and protein-glutamine gamma-glutamyltransferase 2 in I. multifiliis-exposed carp skin mucus. Multiple lectins and a diverse array of distinct serpins with protease inhibitor activity were identified likely implicated in lectin pathway activation and regulation of proteolysis, indicating that these proteins contribute to the carp innate immune system and the protective properties of skin mucus. The results obtained from this proteomic analysis enables a better understanding of fish host response to parasitic infection and gives insights into the key role skin mucus plays in protecting fish against deleterious effects of I. multifiliis.

Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway.

Paracetamol is responsible for acute liver failure in humans and experimental animals when taken at high doses and transformed into a reactive metabolite by the liver cytochrome P450. On the other hand, nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. Hence, the present experiment was aimed at studying the hepatoprotective effect of Myristica fragrans (nutmeg), kernel extract (MFKE) in respect to paracetamol (acetaminophen; N-acetyl-p-amino-phenol (APAP))-induced hepatotoxicity in rats, focusing on its antioxidant, anti-inflammatory, and anti-apoptotic activities. Liver toxicity was induced in rats by a single oral administration of APAP (2 g/kg). To evaluate the hepatoprotective effect of MFKE against this APAP-induced hepatotoxicity, rats were pre-treated with either oral administration of MFKE at 300 mg/kg daily for seven days or silymarin at 50 mg/kg as a standard hepatoprotective agent. APAP intoxication caused a drastic elevation in liver function markers (transaminases, alkaline phosphatase, and total bilirubin), oxidative stress indicators (lipid peroxidation and nitric oxide), inflammatory biomarkers (tumour necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and nuclear factor ĸB) and the pro-apoptotic BCL2 Associated X (Bax) and caspases-3 genes. Furthermore, analyses of rat liver tissue revealed that APAP significantly depleted glutathione and inhibited the activities of antioxidant enzymes in addition to downregulating two key anti-apoptotic genes: Cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein (c-FLIP) and B-cell lymphoma 2 (Bcl-2). Pre-treatment with MFKE, however, attenuated APAP-induced liver toxicity by reversing all of these toxicity biomarkers. This hepatoprotective effect of MFKE was further confirmed by improvement in histopathological findings. Interestingly, the hepatoprotective effect of MFKE was comparable to that offered by the reference hepatoprotector, silymarin. In conclusion, our results revealed that MFKE had antioxidant, anti-inflammatory, and anti-apoptotic properties, and it is suggested that this hepatoprotective effect could be linked to its ability to promote the nuclear factor erythroid 2⁻related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway.

Indigofera oblongifolia regulates the hepatic gene expression profile induced by blood stage malaria.

Malaria is still a major health problem worldwide. This study aimed to investigate the hepatoprotective role of Indigofera oblongifolia leaf extracts (ILE) against mice hepatic injury induced by Plasmodium chabaudi. Female C57BL/6 mice were treated with 100 mg/kg of ILE after infection with erythrocytes parasitized by P. chabaudi. On day 7 post-infection, the extract improved the histological alteration induced by the parasite. This was evidenced by the decreased histological index induced by ILE. Moreover, ILE was able to increase the hepatic antioxidant capacity and could significantly improve the decrease in erythrocyte count and hemoglobin content in mice blood plasma due to infection. ILE was also able to upregulate the expression of 24 genes related to metabolism and of 3 genes related to the immune response. Furthermore, the extract was able to downregulate the expression of 35 genes related to metabolism and of 82 genes related to immune response. Moreover, the microarray study showed that ILE regulated the change in gene expression induced by the parasite. Among these genes, we quantified the expression of cd209f, cyp7a1, Hsd3b5, Sult2a3, Lcn2, CcI8, Nos2, and saa3-mRNAs. These genes were regulated by ILE. Therefore, our results revealed the protective role of Indigofera oblongifolia against hepatic injury induced by blood stage malaria.

Vitamin D receptor regulates intestinal inflammatory response in mice infected with blood stage malaria.

Malaria is a harmful disease affecting both tropical and subtropical countries and causing sometimes fatal complications. The effects of malaria-related complications on the intestine have been relatively neglected, and the reasons for the intestinal damage caused by malaria infection are not yet clear. The present study aims to evaluate the influence of intestinal vitamin D receptor on host-pathogen interactions during malaria induced in mice by Plasmodium chabaudi. To induce the infection, animals were infected with 106P. chabaudi-parasitized erythrocytes. Mice were sacrificed on day 8 post-infection. The infected mice experienced a significant body weight loss and parasitaemia affecting about 46% of RBCs. Infection caused marked pathological changes in the intestinal tissue indicated by shortening of the intestine and villi. Moreover, the phagocytic activity of macrophages increased significantly (P < 0.01) in the infected villi compared to the non-infected ones. Infection by the parasite also induced marked upregulation of nuclear factor-kappa B, inducible nitric oxide synthase, Vitamin D Receptor, interleukin-1ß, tumour necrosis factor alpha and interferon gamma-mRNA. It can be implied from this that vitamin D receptor has a role in regulating malarial infection.

Gene expression of the liver of vaccination-protected mice in response to early patent infections of Plasmodium chabaudi blood-stage malaria.

BACKGROUND: The role of the liver for survival of blood-stage malaria is only poorly understood. In experimental blood-stage malaria with Plasmodium chabaudi, protective vaccination induces healing and, thus, survival of otherwise lethal infections. This model is appropriate to study the role of the liver in vaccination-induced survival of blood-stage malaria. METHODS: Female Balb/c mice were vaccinated with a non-infectious vaccine consisting of plasma membranes isolated in the form of erythrocyte ghosts from P. chabaudi-infected erythrocytes at week 3 and week 1 before infection with P. chabaudi blood-stage malaria. Gene expression microarrays and quantitative real-time PCR were used to investigate the response of the liver, in terms of expression of mRNA and long intergenic non-coding (linc)RNA, to vaccination-induced healing infections and lethal P. chabaudi malaria at early patency on day 4 post infection, when parasitized erythrocytes begin to appear in peripheral blood. RESULTS: In vaccination-induced healing infections, 23 genes were identified to be induced in the liver by > tenfold at p < 0.01. More than one-third were genes known to be involved in erythropoiesis, such as Kel, Rhag, Ahsp, Ermap, Slc4a1, Cldn13 Gata1, and Gfi1b. Another group of > tenfold expressed genes include genes involved in natural cytotoxicity, such as those encoding killer cell lectin-like receptors Klrb1a, Klrc3, Klrd1, the natural cytotoxicity-triggering receptor 1 Ncr1, as well as the granzyme B encoding Gzmb. Additionally, a series of genes involved in the control of cell cycle and mitosis were identified: Ccnb1, Cdc25c, Ckap2l were expressed > tenfold only in vaccination-protected mice, and the expression of 22 genes was at least 100% higher in vaccination-protected mice than in non-vaccinated mice. Furthermore, distinct lincRNA species were changed by > threefold in livers of vaccination-protected mice, whereas lethal malaria induced different lincRNAs. CONCLUSION: The present data suggest that protective vaccination accelerates the malaria-induced occurrence of extramedullary erythropoiesis, generation of liver-resident cytotoxic cells, and regeneration from malaria-induced injury in the liver at early patency, which may be critical for final survival of otherwise lethal blood-stage malaria of P. chabaudi.

Quantitative shotgun proteomics distinguishes wound-healing biomarker signatures in common carp skin mucus in response to Ichthyophthirius multifiliis.

Ichthyophthirius multifiliis is a ciliated protozoan parasite recognized as one of the most pathogenic diseases of wild and cultured freshwater fish. Fish skin mucus plays a significant role against invading pathogens. However, the protein-based modulation against infection with I. multifiliis, of host fish at this barrier is unknown. Thus, we investigated the skin mucus proteome of common carp using a shotgun proteomic approach at days 1 and 9 after I. multifiliis exposure. We identified 25 differentially expressed proteins in infected carp skin mucus. Upregulated proteins were mainly involved in metabolism, whereas downregulated proteins were mainly structural. This is the first proteomic analysis of infected common carp skin mucus, and it provides novel information about proteome alteration caused by I. multifiliis. Furthermore, we identified novel proteins with yet unknown function in common carp following penetrating injuries such as olfactomedin 4, lumican, dermatopontin, papilin and I cytoskeletal 18. This analysis, therefore, represents a key for the search for potential biomarkers, which can help in a better understanding and monitoring of interactions between carp and I. multifiliis. This proteomic study not only provides information on the protein-level pathways involved in fish-ciliate interactions but also could represent a complementary system for studying tissue repair.

Protective vaccination alters gene expression of the liver of Balb/c mice in response to early prepatent blood-stage malaria of Plasmodium chabaudi.

Current knowledge about liver responses to blood-stage malaria and their modulation by vaccination is still unclear. This study investigated effects of protective vaccination on liver gene and lincRNA expression of Balb/c mice at early prepatency of Plasmodium chabaudi blood-stage malaria. When a blood-stage vaccine was used to induce > 80% survival of otherwise lethal malaria, significant differences (p < 0.01) were detectable in global liver gene expression between vaccination-protected (potentially surviving) and non-protected non-vaccinated mice on day 1 p.i.. In the livers of protected mice, gene expression microarrays identified 224 and 419 genes, whose expression was up- and downregulated by > 3-fold, respectively. There were 24 genes upregulated by > 10-fold, including 10 IFN-inducible genes encompassing GTPases Irgm1, 2, and 3, and guanylate-binding protein Gbp11, the IL-1 decoy receptors Il1f9 and Il1ra1, the Il6 gene, and the gene for facilitated glucose transportation. Moreover, the IL-18 decoy receptor gene Il18bp, Gzmb, the genes Lif and Osmr encoding proteins of the IL-6 family, and the taurine transporter gene Slc6a6 were expressed > 3-fold in vaccinated mice. The genes Gbp10, 6, 4 were expressed by > 50% in vaccination-protected than in non-vaccinated mice. In addition, 43 lincRNA species were up- and 36 downregulated. Our data suggested novel regulatory elements of potential anti-malaria activity activated by protective vaccination in the liver, evidenced in response to early prepatent infections in vaccination-protected mice of otherwise lethal blood-stage malaria of P. chabaudi.

Ziziphus spina-christi leaf extract pretreatment inhibits liver and spleen injury in a mouse model of sepsis via anti-oxidant and anti-inflammatory effects.

Sepsis is a systemic response to infection that can result in acute hepatic and splenic damage. Ziziphus spina-christi (L.) is a wild tree used as a medicinal plant by ancient Egyptians. However, little is known about the mechanism underlying its effects on sepsis. The current study investigated the protective effects of a Z. spina-christi leaf extract (ZSCLE) on liver and spleen damage in a male C57BL/6 mouse model of sepsis, induced by cecal ligation and puncture (CLP). Prior to CLP, ZSCLE was administered daily for five consecutive days via oral gavage at doses of 100, 200, or 300 mg/kg. The mice were euthanized 9 h after CLP, and oxidative stress markers were measured (myeloperoxidase, lipid peroxidation, nitric oxide, and reduced glutathione). In addition, we investigated histological changes, anti-oxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), cytokine levels, protein expression of nuclear factor-κB and inducible nitric oxide synthase (iNOS), and mRNA levels of mitogen-activated protein kinase (8, 9, and 14), iNOS, tumor necrosis factor-α, and interleukin-1ß. Our results indicated that ZSCLE significantly and dose-dependently inhibited sepsis-induced liver and spleen injury. These results suggest that ZSCLE could provide a therapeutic agent for sepsis by inducing anti-inflammatory and anti-oxidant effects.

Profiling of jejunum inflammatory gene expression during murine eimeriosis.

To understand the host-parasite relationship during coccidiosis it is necessary to identify the transcriptional profile of the local host. In this study, gene profiling in the mouse jejunum due to infection with Eimeria papillata was investigated using Agilent microarray technology. On day 5 post-infection, the characterization of infected and non-infected mice jejunum transcriptional response was compared. There was an increase in the level of tumour necrosis factor-α, nitrite/nitrate and nitric oxide synthase activity was observed following infection. Also, the activity of glutathione peroxidase was reduced from 86.5 to 38.2 mU/g. In addition, E. papillata infection was associated with an increase in the activities of both the mice alkaline phosphatase and lactate dehydrogenase. Moreover, experimental E. papillata infection in mice induced a significant elevation in protein carbonyl content, by about 70%. Agilent genome microarray detected 11 genes whose expression was up-regulated by more than 10-fold, and 30 genes whose expression was down-regulated by a similar amount five days after infection with E. papillata. The expression profiles of the Fas apoptotic inhibitory molecule 3(FAIM3), chemokine (C-X-C motif) receptor 5 (Cxcr5), succinate receptor 1 (SUCNR1), hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 3 (Hsd3b3) and cytochrome P450, family 2, subfamily b, polypeptide 9 (Cyp2b9) genes, arbitrarily selected from the microarray analysis, closely resemble the expressions determined by quantitative PCR. The data indicate that, E. papillata is associated with the induction of inflammatory response and with gene regulation in mice jejunum.