3,3'-Diindolylmethane decreases VCAM-1 expression and alleviates experimental colitis via a BRCA1-dependent antioxidant pathway

Reactive oxygen species (ROS) exhibit a key role in the pathogenesis of inflammatory bowel disease (IBD). 3,3'-Diindolylmethane (DIM) can protect against oxidative stress in a breast cancer susceptibility gene 1 (BRCA1)-dependent manner. The aim of this study was to examine the therapeutic effects of DIM in experimental colitis and investigate the possible mechanisms underlying its effects on intestinal inflammation. The therapeutic effects of DIM were studied in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Pathological markers of colitis severity, antioxidant activity, and ROS generation in colonic tissue were measured. The impact of DIM on ROS-induced endothelial vascular cell adhesion molecule 1 (VCAM-1) expression and leukocyte-endothelial cell interaction was further investigated in cultures of endothelial cells and in the TNBS-induced colitis model. Administration of DIM was demonstrated to attenuate experimental colitis, as judged by pathological indices. DIM could effectively stimulate the expression of BRCA1 in vitro and in vivo and reduce ROS generation, leading to the inhibition of VCAM-1 expression and leukocyte-endothelial cell adhesion, and finally resulted in an alleviation of experimental colitis. DIM has shown anti-IBD activity in animal models by inhibiting ROS-induced VCAM-1 expression and leukocyte recruitment via a BRCA1-dependent antioxidant pathway and thus may offer potential treatments for IBD patients.     

A human antibody recognizing a conserved epitope of H5 hemagglutinin broadly neutralizes highly pathogenic avian influenza H5N1 viruses

Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are similar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from an H5N1-infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at positions 118, 121, 161, 164, and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains.     

两株高丁醇耐受细菌的分离鉴定及其丁醇耐受特性的研究

高浓度丁醇耐受菌株是丁醇异源重组生产的关键因素.本研究对不同环境中耐受丁醇的微生物进行筛选,从自然环境中分离得到两株能够耐受高浓度丁醇的菌株,分别命名为btpz-4-1和btpz-6-3,它们耐受丁醇的浓度达到了25 g/L.通过分子标记物16S rDNA的鉴定以及分子系统进化树的分析,btpz-4-1被鉴定为Lactobacillus mucosae,btpz-6-3被鉴定为Pediococcus pentosaceus.同时,对它们的生理特性进行研究,结果显示btpz-4-1和btpz-6-3的最适生长温度分别为45℃和42℃,最适生长pH分别为6.0和6.5.     

iDPF-PseRAAAC: A Web-Server for Identifying the Defensin Peptide Family and Subfamily Using Pseudo Reduced Amino Acid Alphabet Composition

Defensins as one of the most abundant classes of antimicrobial peptides are an essential part of the innate immunity that has evolved in most living organisms from lower organisms to humans. To identify specific defensins as interesting antifungal leads, in this study, we constructed a more rigorous benchmark dataset and the iDPF-PseRAAAC server was developed to predict the defensin family and subfamily. Using reduced dipeptide compositions were used, the overall accuracy of proposed method increased to 95.10% for the defensin family, and 98.39% for the vertebrate subfamily, which is higher than the accuracy from other methods. The jackknife test shows that more than 4% improvement was obtained comparing with the previous method. A free online server was further established for the convenience of most experimental scientists at http://wlxy.imu.edu.cn/college/biostation/fuwu/iDPF-PseRAAAC/index.asp. A friendly guide is provided to describe how to use the web server. We anticipate that iDPF-PseRAAAC may become a useful high-throughput tool for both basic research and drug design.     

Effects of Sodium Selenite on Aflatoxin B1-Induced Decrease of Ileac T cell and the mRNA Contents of IL-2, IL-6, and TNF-α in Broilers

The aim of this work was to assess the protective effect of sodium selenite on the ileum mucosal immunologic toxicity induced by aflatoxin B₁ (AFB₁). One hundred and eighty one-day-old healthy male avian broilers were divided into four groups of three replicates and 15 birds per replicate and fed with basal diet (control group), 0.3 mg/kg AFB₁ (AFB₁ group), 0.4 mg/kg Se (+Se group), and 0.3 mg/kg AFB₁?+?0.4 mg/kg Se (AFB₁+Se group), respectively. The ileac T-cell subsets were determined by the methods of flow cytometry (FCM), and the mRNA contents of interleukin-2 (IL-2), interleukin-6(IL-6), and tumor necrosis factor-alpha (TNF-α) by quantitative real-time PCR. Compared with those in control group, the percentages of CD₃ ⁺, CD₃ ⁺CD₄ ⁺, CD₃ ⁺CD₈ ⁺ intraepithelial lymphocytes (IELs) and LPLs, the CD4⁺/CD8⁺ ratio of IELs, and the mRNA contents of IL-2, IL-6, and TNF-α were decreased in AFB₁ group. However, compared with those in AFB₁ group, these parameters of AFB₁+Se group were increased to be close to those in control group. It was concluded that 0.3 mg/kg AFB₁ could reduce the cellular immune function of the ileum mucosa, but 0.4 mg/kg supplemented dietary selenium showed protective effects on AFB₁-induced immunologic injury.     

Bryostatin‐1 ameliorated experimental colitis in Il‐10−/− Mice by protecting the intestinal barrier and limiting immune dysfunction

Bryostatin‐1 (Bry‐1) has been proven to be effective and safe in clinical trials of a variety of immune‐related diseases. However, little is known about its effect on Crohn's disease (CD). We aimed to investigate the impact of Bry‐1 on CD‐like colitis and determine the mechanism underlying this effect. In the present study, 15‐week‐old male Il‐10^?/? mice with spontaneous colitis were divided into positive control and Bry‐1‐treated (Bry‐1, 30 μg/kg every other day, injected intraperitoneally for 4 weeks) groups. Age‐matched, male wild‐type (WT) mice were used as a negative control. The effects of Bry‐1 on colitis, intestinal barrier function and T cell responses as well as the potential regulatory mechanisms were evaluated. We found that the systemic delivery of Bry‐1 significantly ameliorated colitis in Il‐10^?/? mice, as demonstrated by decreases in the disease activity index (DAI), inflammatory score and proinflammatory mediator levels. The protective effects of Bry‐1 on CD‐like colitis included the maintenance of intestinal barrier integrity and the helper T cell (Th)/regulatory T cell (Treg) balance. These effects of Bry‐1 may act in part through nuclear factor erythroid 2‐related factor 2 (Nrf2) signalling activation and STAT3/4 signalling inhibition. The protective effect of Bry‐1 on CD‐like colitis suggests Bry‐1 has therapeutic potential in human CD, particularly given the established clinical safety of Bry‐1.     

Miscanthus sacchriflorus exhibits sustainable yields and ameliorates soil properties but potassium stocks without any input over a 12‐year period in China

The perennial C₄ Miscanthus spp. is used in China for bio‐fuel production and its ecological functions. However, questions arise as to its economic and environmental sustainability in abandoned farmland where the costs should be very low. Little is known about its yield performance and effects on soil properties when it was harvested annually without any inputs in China. To address these questions, an experiment was implemented for 12 years on annually harvested Miscanthus sacchariflorus planted in 2006 and managed without fertilization, irrigation, or any other inputs. We determined biomass yields each year, biomass allocation, and soil properties before and after its cultivation. Biomass yields of M. sacchariflorus reached a peak value (29.67 t/ha) 3 years after cultivation and was maintained at a stable level (averaged 22.22 t/ha) during 2012–2017. Its root shoot ratio increased due to more biomass allocated below‐ground with time. Long‐term cultivation of M. sacchariflorus increased organic carbon contents, pH (for the absence of fertilization), microbial carbon, nitrogen and phosphorus contents, and soil carbon nitrogen ratios (0–100 cm). Soil bulk density was decreased significantly (p < .05) independent of soil depths. Annual harvest did not reduce total nitrogen and phosphorus, available nitrogen, and potassium, but total the potassium content of soil (0–100 cm). Cultivation of M. sacchariflorus increased available phosphorus contents in 40–100 cm soil and reduced that value in 20–40 cm soil. Biological nitrogen fixation provided ~218.74 kg ha^?1 year^?1 (1 m depth) nitrogen for the system offsetting nitrogen export by biomass harvest and stabilizing nitrogen levels of soil. In conclusion, M. sacchriflorus exhibited sustainable biomass yields and ameliorated soil properties but the decrease of total potassium contents after 12 years’ cultivation without any input. These conclusions could provide important information timely for the government and encourage farmers to promote large‐scale utilization of M. sacchriflorus on the abandoned farmland in China.     

Overexpression of Axl reverses endothelial cells dysfunction in high glucose and hypoxia

The receptor tyrosine kinase Axl is involved in diabetic vascular disease. This study aims to investigate the effect of high glucose on endothelial cells injury and Axl expression in hypoxia condition in vitro, and we present details of the mechanism associated with overexpression of Axl rescue the high glucose injury. Our results showed that high glucose impaired both human umbilical vein endothelial cells (HUVECs) and EAhy926 cells angiogenesis in hypoxia condition. In addition, high glucose inhibits Axl and hypoxia-inducible factor 1-α (HIF-1α) protein expression in hypoxia condition. Axl overexpression significantly reversed endothelial cells dysfunction in high glucose/hypoxia. Furthermore, Axl overexpression in EAhy926 cells increases HIF-1α protein synthesis through PI3K/Akt/mTOR/p70 ^S6K signal pathway but not Mek/Erk in high glucose/hypoxia condition. This study demonstrates that high glucose can alter Axl signaling and HIF-1α in hypoxia condition. Overexpression of Axl may rescue endothelial cells dysfunction and HIF-1α expression through its downstream signals in high glucose/hypoxia.