The effects of low levels of aflatoxin B1 on health, growth performance and reproductivity in male rabbits

[EN] This study investigated the chronic effects of relatively low exposure to aflatoxin B1 (AFB1) on the growth performance, immune situation and reproduction in male rabbits. Bucks (n=32, 4.82±0.22 kg) were individually assigned to 4 treatments (8 replicates each) using a randomised complete block design. Four diets containing 0, 0.02, 0.05, and 0.1 mg AFB1/kg, were provided to bucks for 8 wk. Growth performance and semen quality were measured. Blood, organ and tissue samples were collected to measure haematological indices, liver function, organ weights and immune parameters. Compared to control, AFB1-contaminated diets reduced body weight and average daily gain (P<0.05), altered certain haematological indices and liver function with decreased monocytes percentage and mean corpuscular haemoglobin concentration, and increased plateletcrit and albumin (P<0.05), slightly impaired reproductive parameters with enhanced ratio of morphologically abnormal sperm cells at early stage and reduced post-stage acrosome integrity, testis weight and serum testosterone concentration (P<0.05), decreased immune function with reduced relative liver weight (%) and tumour necrosis factor-α levels in serum and liver tissue, and increased serum 8-hydroxy-2’-deoxyguanosine levels (P<0.05). Furthermore, bucks fed diets with relatively high AFB1 (0.05 and 0.1 mg AFB1/kg) had reduced red blood cell and haematocrit (P<0.05) in contrast with the low AFB1 group (0.02 mg AFB1/kg). In conclusion, diets containing 0.05 and 0.1 mg AFB1/kg had negative effects on bucks’ growth performance, haematology, reproductivity and immune function, whereas diet containing 0.02 mg AFB1/kg had only minor effects on the parameters measured.The study was funded by the Fundamental Research Funds for the Central Universities (XDJK2015C081).Sun, Y.; Dong, G.; E, G.; Liao, M.; Tao, L.; Lv, J. (2018). The effects of low levels of aflatoxin B1 on health, growth performance and reproductivity in male rabbits. World Rabbit Science. 26(2):123-133. https://doi.org/10.4995/wrs.2018.7433SWORD123133262Abdelaziz S.A., Hamada M.M. 2007. Phytic acid exposure alters AflatoxinB1-induced reproductive and oxidative toxicity in Albino Rats (Rattus norvegicus). eCAM, 6: 331-3471. https://doi.org/10.1093/ecam/nem137Abdel-Wahhab M.A., Nada S.A., Khalil F.A.2002. Physiological and toxicological responses in rats fed aflatoxin-contaminated diet with or without sorbent materials. Animal Feed Sci. 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Diet-induced bacterial immunogens in the gastrointestinal tract of dairy cows: Impacts on immunity and metabolism

Dairy cows are often fed high grain diets to meet the energy demand for high milk production or simply due to a lack of forages at times. As a result, ruminal acidosis, especially subacute ruminal acidosis (SARA), occurs frequently in practical dairy production. When SARA occurs, bacterial endotoxin (or lipopolysaccharide, LPS) is released in the rumen and the large intestine in a large amount. Many other bacterial immunogens may also be released in the digestive tract following feeding dairy cows diets containing high proportions of grain. LPS can be translocated into the bloodstream across the epithelium of the digestive tract, especially the lower tract, due to possible alterations of permeability and injuries of the epithelial tissue. As a result, the concentration of blood LPS increases. Immune responses are subsequently caused by circulating LPS, and the systemic effects include increases in concentrations of neutrophils and the acute phase proteins such as serum amyloid-A (SAA), haptoglobin (Hp), LPS binding protein (LBP), and C-reactive protein (CRP) in blood. Entry of LPS into blood can also result in metabolic alterations. Blood glucose and nonesterified fatty acid concentrations are enhanced accompanying an increase of blood LPS after increasing the amount of grain in the diet, which adversely affects feed intake of dairy cows. As the proportions of grain in the diet increase, patterns of plasma β-hydoxybutyric acid, cholesterol, and minerals (Ca, Fe, and Zn) are also perturbed. The bacterial immunogens can also lead to reduced supply of nutrients for synthesis of milk components and depressed functions of the epithelial cells in the mammary gland. The immune responses and metabolic alterations caused by circulating bacterial immunogens will exert an effect on milk production. It has been demonstrated that increases in concentrations of ruminal LPS and plasma acute phase proteins (CRP, SAA, and LBP) are associated with declines in milk fat content, milk fat yield, 3.5% fat-corrected milk yield, as well as milk energy efficiency

A Root-Knot Nematode Secretory Peptide Functions as a Ligand for a Plant Transcription Factor

Parasitism genes expressed in the esophageal gland cells of root-knot nematodes encode proteins that are secreted into host root cells to transform the recipient cells into enlarged multinucleate feeding cells called giant-cells. Expression of a root-knot nematode parasitism gene which encodes a novel 13-amino-acid secretory peptide in plant tissues stimulated root growth. Two SCARECROW-like transcription factors of the GRAS protein family were identified as the putative targets for this bioactive nematode peptide in yeast two-hybrid analyses and confirmed by in vitro and in vivo coimmunoprecipitations. This discovery is the first demonstration of a direct interaction of a nematode-secreted parasitism peptide with a plant-regulatory protein, which may represent an early signaling event in the root-knot nematode-host interaction

Discovering burst patterns of burst topic in Twitter

National Research Foundation (NRF) Singapore under International Research Centres in Singapore Funding Initiativ

Detecting community pacemakers of burst topic in Twitter

National Research Foundation (NRF) Singapore under International Research Centres in Singapore Funding Initiativ

Genetic testing and prognosis of sarcomatoid hepatocellular carcinoma patients

BackgroundSarcomatoid hepatocellular carcinoma (SHC) is a rare epithelial malignancy with high invasiveness and poor prognosis. However, the molecular characteristics and main driver genes for SHC have not been determined. The aim of this study is to explore the potentially actionable mutations of driver genes, which may provide more therapeutic options for SHC.MethodsIn this study, DNA extraction and library preparation were performed using tumor tissues from 28 SHC patients. Then we used Miseq platform (Illumina) to sequence the target-enriched library, and we aligned and processed the sequencing data. The gene groups were tested for SNVs/Indels/CNVs. Tumor mutation burden (TMB) was assessed by the 425-cancer-relevant gene panel. Multivariate analysis of COX’s model was used for survival analysis (OS) of patients’ clinical characteristics.ResultThe median overall survival (OS) of the patients was only 4.4 months. TP53, TERT, and KRAS were the top three frequently mutated genes, with frequencies of 89.3%, 64.3%, and 21.4%, respectively. A considerable number of patients carried mutations in genes involved in the TP53 pathway (96%) and DNA Damage Repair (DDR) pathway (21%). Multiple potentially actionable mutations, such as NTRK1 fusions and BRCA1/2 mutations, were identified in SHCs.ConclusionsThis study shows a landscape of gene mutations in SHC. SHC has high mutation rates in TP53 pathway and DDR pathway. The potentially actionable mutations of driver genes may provide more therapeutic options for SHC. Survival analysis found that age, smoking, drinking, and tumor diameter may be independent prognostic predictors of SHC

Proteomic Analysis of Rhesus Macaque Brain Explants Treated With Borrelia burgdorferi Identifies Host GAP-43 as a Potential Factor Associated With Lyme Neuroborreliosis

BackgroundLyme neuroborreliosis (LNB) is one of the most dangerous manifestations of Lyme disease, but the pathogenesis and inflammatory mechanisms are not fully understood.MethodsCultured explants from the frontal cortex of rhesus monkey brain (n=3) were treated with live Borrelia burgdorferi (Bb) or phosphate-buffered saline (PBS) for 6, 12, and 24 h. Total protein was collected for sequencing and bioinformatics analysis. In addition, changes in protein expression in the explants over time following Bb treatment were screened.ResultsWe identified 1237 differentially expressed proteins (DEPs; fold change ≥1.5 or ≤0.67, P-value ≤0.05). One of these, growth-associated protein 43 (GAP-43), was highly expressed at all time points in the explants. The results of the protein-protein interaction network analysis of DEPs suggested that GAP-43 plays a role in the neuroinflammation associated with LNB. In HMC3 cells incubated with live Bb or PBS for 6, 12, and 24 h, real-time PCR and western blot analyses confirmed the increase of GAP-43 mRNA and protein, respectively.ConclusionsElevated GAP-43 expression is a potential marker for LNB that may be useful for diagnosis or treatment

Ticagrelor vs Clopidogrel in CYP2C19 loss-of-function carriers with Stroke or TIA

BACKGROUNDComparisons between ticagrelor- aspirin and clopidogrel-aspirin in CYP2C19 loss-of-function carriers have not been well studied for secondary stroke prevention.METHODSWe conducted a randomized, double-blind, placebo-controlled trial of 6,412 patients with a minor ischemic stroke or TIA who carried CYP2C19 LOF alleles determined by point-of-care testing. Patients were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio to receive ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or clopidogrel (300 mg loading dose on day 1 followed by 75 mg per day for days 2 through 90), plus aspirin (75-300 mg loading dose followed by 75 mg daily for 21 days). The primary efficacy outcome was stroke and the primary safety outcome was severe or moderate bleeding, both within 90 days. RESULTSStroke occurred within 90 days in 191 (6.0%) versus 243 (7.6%), respectively (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P=0.008). Moderate or severe bleeding occurred in 9 patients (0.3%) in the ticagrelor-aspirin group and in 11 patients (0.3%) in the clopidogrel-aspirin group; any bleeding event occurred in 170 patients (5.3%) vs 80 (2.5%), respectively. CONCLUSIONSAmong Chinese patients with minor ischemic stroke or TIA within 24 hours after symptoms onset who were carriers of CYP2C19 loss-of-function alleles, ticagrelor- aspirin was modestly better than clopidogrel-aspirin for reducing the risk of stroke but was associated with more total bleeding events at 90 days. (CHANCE-2 ClinicalTrials.gov number, NCT04078737.

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival