Gene expression profiling within the spleen of Clostridium perfringens-challenged Broilers fed antibiotic-medicated and non-medicated diets

<p>Abstract</p> <p>Background</p> <p><it>Clostridium perfringens </it>(Cp) is a Gram-positive anaerobic bacterium that causes necrotic enteritis (NE) in poultry when it overgrows in the small intestine. NE disease has previously been controlled through the use of growth-promoting antibiotics. This practice was recently banned in European countries, leading to significantly increased incidence of NE threatening the poultry industry. Control strategies and technology as substitutes to dietary antibiotics are therefore urgently required. To develop the substitutes, it is important to understand host immune responses to Cp infection. However, the knowledge is still lacking. We therefore investigated gene expression profiles within immunologically-relevant tissue, the spleen, in order to identify factors that are involved in immunity to NE and have potential as therapeutic targets.</p> <p>Results</p> <p>Use of a 44 K Agilent chicken genome microarray revealed significant up-regulation of many immune-associated genes in Cp-challenged chickens, including <it>galectin 3</it>, <it>IFNAR1</it>, <it>IgY-receptor</it>, <it>TCRγ</it>, <it>granzyme A</it>, and <it>mannose-6-P-R</it>, which were subsequently validated by quantitative PCR assays. Functional annotation of differentially expressed genes was conducted using the High Throughput Gene Ontology Functional Annotation database. Medicated and Non-medicated chickens had similar annotation profiles with cell activities and regulation being the most dominant biological processes following Cp infection.</p> <p>Conclusion</p> <p>Broiler chickens demonstrated an intricate and holistic magnitude of host response to Cp challenge and the development of NE. Although the influence of dietary antibiotics appeared to be less significant than the disease process, both had a considerable impact on the host response. Markers previously identified in intestinal inflammatory diseases of other species, including humans, and indicators of enhanced antibody responses, appeared to be involved in the chicken response to Cp challenge. The significance in host immune responses of immune mediators identified from the present study warrants further studies to verify their functions during NE development and to determine their potential application to control NE disease.</p

Effect of immunized egg proteins on the performance and neonatal diarrhea incidence in newborn calves

Publication history: Accepted - 5 November 2020; Published online - 19 January 2021The aim of this study was to assess the effects of feeding immunized egg proteins (IEP) on the health and performance of newborn dairy calves. Sixty‐four Holstein calves, both male and female, were divided over two treatments. Calves either received IEP or a placebo (PCB) in their colostrum and calf milk replacer (CMR) for the first 14 days of their life. Until day 49, CMR was offered at 15% of birth weight (BW), at 10% on days 49–57 and at 5% on days 57–63. In addition, calves received starter concentrate, chopped straw and water from 3 days old until 70 days old at the end of study. Individual CMR and concentrate intake were measured daily whilst BW was recorded weekly. Visual faecal scoring and health observations were conducted daily. Faecal samples were collected weekly up to 4 weeks and during the first 4 days of scouring to screen for presence of Cryptosporidium parvum, rotavirus, coronavirus, E. coli and Salmonella. Results indicated that feeding IEP increased BW (p < .05) at 42 and 56 days old, and BW also tended (p = .06) to be higher after weaning at 63–70 days old compared to the PCB group. When analysed using a repeated measures model, compared to feeding PCB, feeding IEP increased total concentrate consumption (p = .001) by 3.6kg/calf. Over the entire study, daily water intake was higher (p = .002) for the IEP group when compared with the PCB group. In the IEP group, 12 calves were scored as scouring whereas there were 14 calves in the PCB group. There were no significant differences between treatments in faecal pathogen load of neither healthy nor scouring calves. In conclusion, supplementing IEP during the first 14 days of calf life improved the performance of newborn calves. Further work is warranted to understand the mode of action of IEP in calves

Neutral operator with variable parameter and third-order neutral differential equation

Additional file 1. The TRS sequences of structural genes in the HP-PRRSV/SD16 genome (GenBank: JX087437)

The Role of Alpha-Lipoic Acid in the Pathomechanism of Acute Ischemic Stroke

Background/Aims: Ischemic stroke results in increased cerebral infarction, neurological deficits and neuroinflammation. The underlying mechanisms involving the anti-inflammatory and neuroprotective properties of α-Lipoic acid (α-LA) remain poorly understood. Herein, we investigated the potential role of α-LA in a middle cerebral artery occlusion (MCAO) rat model and an in vitro lipopolysaccharide (LPS)-induced microglia inflammation model. Methods: In the in vivo study, infarct volume was examined by TTC staining and Garcia score was used to evaluate neurologic recovery. The cytokines were evaluated by enzyme-linked immunosorbent assay, and protein expression of microglia phenotype and NF-κB were measured using western blot. In the in vitro study, the expressions of microglia M1/M2 phenotype were evaluated using qRT-PCR, and immunofluorescence staining was used to assess the nuclear translocation of NF-κB. Results: Both 20 mg/kg and 40 mg/kg of α-LA alleviated infarct size, brain edema, and neurological deficits. Furthermore, α-LA induced the polarization of microglia to the M2 phenotype, modulated the expression of IL-1β, IL-6, TNF-α and IL-10, and attenuated the activation of NF-κB after MCAO. α-LA inhibited the expression of M1 markers, increased activation of the M2 markers, and suppressed the nuclear translocation of NF-κB in LPS-stimulated BV2 microglia. Conclusions: α-LA improved neurological outcome in experimental stroke via modulating microglia M1/M2 polarization. The potential mechanism of α-LA might be mediated by inhibition of NF-κB activation via regulating phosphorylation and nuclear translocation of p65

A comprehensive and high-resolution genome-wide response of p53 to stress

Tumor suppressor p53 regulates transcription of stress-response genes. Many p53 targets remain undiscovered because of uncertainty as to where p53 binds in the genome and the fact that few genes reside near p53-bound recognition elements (REs). Using chromatin immunoprecipitation followed by exonuclease treatment (ChIP-exo), we associated p53 with 2,183 unsplit REs. REs were positionally constrained with other REs and other regulatory elements, which may reflect structurally organized p53 interactions. Surprisingly, stress resulted in increased occupancy of transcription factor IIB (TFIIB) and RNA polymerase (Pol) II near REs, which was reduced when p53 was present. A subset associated with antisense RNA near stress-response genes. The combination of high-confidence locations for p53/REs, TFIIB/Pol II, and their changes in response to stress allowed us to identify 151 high-confidence p53-regulated genes, substantially increasing the number of p53 targets. These genes composed a large portion of a predefined DNA-damage stress-response network. Thus, p53 plays a comprehensive role in regulating the stress-response network, including regulating noncoding transcription

Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway

Background: Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents. Methods: The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels. Results: Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, we found that ivermectin markedly mediated mitochondrial dysfunction and induced apoptosis of ESCC cells, which indicated the anti-proliferative effect of ivermectin on ESCC cells was implicated in mitochondrial apoptotic pathway. Mechanistically, ivermectin significantly triggered ROS accumulation and inhibited the activation of NF-κB signaling pathway and increased the ratio of Bax/Bcl-2. Conclusions: These finding indicated that ivermectin has significant anti-tumour potential for ESSC and may be a potential therapeutic candidate against ESCC

Ultra-low-dose spectral-detector computed tomography for the accurate quantification of pulmonary nodules: an anthropomorphic chest phantom study

PURPOSETo assess the quantification accuracy of pulmonary nodules using virtual monoenergetic images (VMIs) derived from spectral-detector computed tomography (CT) under an ultra-low-dose scan protocol.METHODSA chest phantom consisting of 12 pulmonary nodules was scanned using spectral-detector CT at 100 kVp/10 mAs, 100 kVp/20 mAs, 120 kVp/10 mAs, and 120 kVp/30 mAs. Each scanning protocol was repeated three times. Each CT scan was reconstructed utilizing filtered back projection, hybrid iterative reconstruction, iterative model reconstruction (IMR), and VMIs of 40–100 keV. The signal-to-noise ratio and air noise of images, absolute differences, and absolute percentage measurement errors (APEs) of the diameter, density, and volume of the four scan protocols and ten reconstruction images were compared.RESULTSWith each fixed reconstruction image, the four scanning protocols exhibited no significant differences in APEs for diameter and density (all P > 0.05). Of the four scan protocols and ten reconstruction images, APEs for nodule volume had no significant differences (all P > 0.05). At 100 kVp/10 mAs, APEs for density using IMR were the lowest (APE-mean: 6.69), but no significant difference was detected between VMIs at 50 keV (APE-mean: 11.69) and IMR (P = 0.666). In the subgroup analysis, at 100 kVp/10 mAs, there were no significant differences between VMIs at 50 keV and IMR in diameter and density (all P > 0.05). The radiation dose at 100 kVp/10 mAs was reduced by 77.8% compared with that at 120 kVp/30 mAs.CONCLUSIONCompared with IMR, reconstruction at 100 kVp/10 mAs and 50 keV provides a more accurate quantification of pulmonary nodules, and the radiation dose is reduced by 77.8% compared with that at 120 kVp/30 mAs, demonstrating great potential for ultra-low-dose spectral-detector CT