Correlation of gut microbiota with leukopenia after chemotherapy in patients with colorectal cancer.

BACKGROUND: The most common toxic side effect after chemotherapy, one of the main treatments for colorectal cancer (CRC), is myelosuppression. OBJECTIVE: To analyze the correlation between gut microbiota and leukopenia after chemotherapy in CRC patients. METHODS: Stool samples were collected from 56 healthy individuals and 55 CRC patients. According to the leukocytes levels in peripheral blood, the CRC patients were divided into hypoleukocytes group (n = 13) and normal leukocytes group (n = 42). Shannon index, Simpson index, Ace index, Chao index and Coverage index were used to analyze the diversity of gut microbiota. LDA and Student's t-test(St test) were used for analysis of differences. Six machine learning algorithms, including logistic regression (LR) algorithm, random forest (RF) algorithm, neural network (NN) algorithm, support vector machine (SVM) algorithm, catboost algorithm and gradient boosting tree algorithm, were used to construct the prediction model of gut microbiota with leukopenia after chemotherapy for CRC. RESULTS: Compared with healthy group, the microbiota alpha diversity of CRC patients was significantly decreased (p < 0.05). After analyzing the gut microbiota differences of the two groups, 15 differential bacteria, such as Bacteroides, Faecalibacterium and Streptococcus, were screened. RF prediction model had the highest accuracy, and the gut microbiota with the highest predictive value were Peptostreptococcus, Faecalibacterium, and norank_f__Ruminococcaceae, respectively. Compared with normal leukocytes group, the microbiota alpha diversity of hypoleukocytes group was significantly decreased (p < 0.05). The proportion of Escherichia-Shigella was significantly decreased in the hypoleukocytes group. After analyzing the gut microbiota differences of the two groups, 9 differential bacteria, such as Escherichia-Shigella, Fusicatenibacter and Cetobacterium, were screened. RF prediction model had the highest accuracy, and the gut microbiota with the highest predictive value were Fusicatenibacte, Cetobacterium, and Paraeggerthella. CONCLUSION: Gut microbiota is related to leukopenia after chemotherapy. The gut microbiota may provide a novel method for predicting myelosuppression after chemotherapy in CRC patients.

Comparison of bacterial diversity in Bactrocera cucurbitae (Coquillett) ovaries and eggs based on 16S rRNA sequencing.

Next-generation sequencing allows for fine-scale studies of microbial communities. Herein, 16S ribosomal RNA high-throughput sequencing was used to identify, classify, and predict the functions of the bacterial communities in the eggs and ovaries of Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae), which is a pest that infests a variety of cucurbit fruits at different developmental stages. Taxonomic analyses indicate that bacteria associated with B. cucurbitae represent 19 phyla, which were spread across different developmental stages. Specifically, the egg microbiota had a higher alpha diversity than those of microbiota in the primary and mature ovaries. Significant differences were not observed between the primary and mature ovaries in terms of their microbiota's alpha diversities. Pseudomonadota, Deinococcota, Bacteroidota, Bacillota, and Actinomycetota were the dominant phyla in all three developmental stages of B. cucurbitae, and Pseudomonadaceae and Enterobacteriaceae were the most abundant families. Owing to the unique physiological environment of the ovaries, the diversity of their bacterial community was significantly lower than that in the eggs. This study provides new insights into the structure and abundance of the microbiota in B. cucurbitae at different developmental stages and contributes to forming management strategies for this pest.

Research on the Visual Imagery of Posters Based on the Culture Code Theory of Design.

According to the Culture Code Theory of Design, posters can be divided into strategy aspect, meaning aspect, and technical aspect. This study explored the impact of visual imagery on poster communication and effect focus on the meaning and technical aspects which directly related to the audiences. The visual imagery preference of ten public poster samples is collected from 40 participants by online questionnaire with the semantic differential method. The results show that the audience's visual imagery at the technical aspect is mainly related to the richness of colors, graphics, and texts. When receiving the information from the meaning aspect of the poster correctly, the visual imagery will be influenced by the type of theme. Most importantly, the same or similar visual imagery at the technical and meaning aspect encourages audiences to explore the deep information of posters. Poster works that keep visual imagery coherent and smooth at the two aspects can achieve a better effect.

DNase I improves blood-milk barrier integrity and alleviates inflammation induced by Staphylococcus aureus during mastitis.

Mastitis is an inflammation of mammary gland, which directly affects the milk production performance and causes huge economic losses in the dairy industry. During mastitis, the blood-milk barrier (BMB) loses its integrity and aggravates the severity of mastitis. Exogenous DNase I has been exerted protective effects in different model of tissue injury. Here, we designed a study to investigate the effects of DNase I on inflammation and BMB in a mice model of Staphylococcus aureus-induced mastitis. In the model, we found that DNase I treatment significantly alleviated the inflammatory response through decrease of inflammatory cells in mammary alveoli, MPO activity and cytokines in mammary gland. Furthermore, immunofluorescent staining and western blotting demonstrated that exogenous DNase I obviously reduced BMB permeability and changed the expression of tight junction proteins to support the re-establishment of the barrier integrity. Mechanismly, DNase I treatment inhibited NF-κB and enhanced AKT signaling pathways. Therefore, our results indicate that DNase I may be an effective treatment for attenuating mastitis.

Lysine-specific demethylase 1 (LSD1) serves as an potential epigenetic determinant to regulate inflammatory responses in mastitis.

It is well-established that lysine-specific demethylase 1 (LSD1) is the first identified histone demethylase. Based on its demethylase enzymatic activity, LSD1 plays a pivotal role in vast range of cellular processes and cancers, but the understanding of its effects on inflammation is relatively limited. Using in vivo models of lipopolysaccharide (LPS)-induced inflammation and in vitro assays in mouse mammary epithelial cells, we identified the novel regulatory roles and underlying mechanisms of LSD1 on LPS-induced mastitis. Mammary gland and cells were collected for the following experiments after treatment. Histological changes were determined by H&E. Western blot analysis was used to detect the protein expression. ELISA and real-time PCR were used to evaluate protein and mRNA expression of inflammatory genes. Our results showed that LPS treatment resulted in a significant increase in LSD1 protein expression. GSK-LSD1 is a selective inhibitor of LSD1 enzyme activity. Treatment of mice with GSK-LSD1 inhibited LSD1 activity, reduced inflammatory cells recruitment to tissues and attenuated LPS-induced damage in mammary gland. Mechanistic investigations suggested that LSD1 inhibition led to the increase of histone H3K4me2 and H3K9me2. Furthermore, GSK-LSD1 inhibition of LSD1 further inhibited nuclear factor κ-B (NF-κB) signaling cascades, and subsequently inhibited the production of cytokines (TNF-α, IL-6 and IL-1ß) in mammary gland. Taken together, our data reveal LSD1 as a potential regulator of inflammation and improve our understanding of epigenetic control on inflammation.

Characterization of fowl adenoviruses isolated between 2007 and 2014 in China.

Forty-three fowl adenovirus (FAdV) strains were isolated in China from 2007 to 2014 from poultry and ostriches with inclusion body hepatitis (IBH) and hydropericardium syndrome (HPS). Phylogenetic analysis showed that 28/43 strains clustered into Fowl aviadenovirus D (FAdV-D) and 9/43 strains clustered into FAdV-E. FAdV-C included three isolates of ostrich origin, one of goose origin and two of chicken origin. Based on hexon loop 1 gene sequencing analysis, these viruses were genetically related to FAdV-4, FAdV-8a, FAdV-8b and FAdV-11, of which FAdV-11 was dominant. The isolation in 2014 of three FAdV strains belonging to serotype 4 from ostrich flocks is to our knowledge the first finding of FAdV-4 infection and HPS cases in ostriches. Epidemiological analysis showed that FAdV has been circulating in northern and eastern China, where more than 50% of layers and broilers are raised. The hosts of this pathogen included broilers, layers, geese and ostriches. IBH and HPS cases had a sporadic or cluster distribution from 2007 to 2013; however, since 2014 the number of cases has increased sharply. To control FAdV, strict biosecurity protection measures are necessary and a multivalent vaccine may be needed.

Synergistic Anti-glioma Effects in Vitro and in Vivo of Enediyne Antibiotic Neocarzinostatin and Paclitaxel via Enhanced Growth Delay and Apoptosis-Induction.

Neocarzinostatin (NCS) is a member of enediyne antibiotics with high anticancer potential. Our study was performed to explore the synergistic anti-glioma effects of NCS and paclitaxel (PTX) in vitro and in vivo. By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicities of the drugs to human glioma cells U87MG and rat glioma cells C6 were evaluated. The results showed that the combinations of NCS and PTX can synergistically inhibit glioma cells survival. Cell apoptosis was detected by flow cytometry, and the results showed that the combinations of NCS and PTX synergistically enhanced apoptosis ratio of glioma cells. Western blot revealed that the cell signaling pathways of proliferation and apoptosis were synergistically regulated, in which Akt was synergistically inactivated, p53 was up-regulated with down-regulation of bcl-2. Meanwhile, with the subcutaneous model of U87MG cells and intracerebral implantation model of C6 cells, the combination strategy could synergistically delay the glioma growth and significantly prolong the survival of rats bearing orthotopic glioma. This study demonstrates that the combination of NCS and PTX can potentiate the effect on survival and apoptosis of glioma cells via suppression of Akt, bcl-2, and activations of p53; Meanwhile, the in vivo studies also confirmed that the combination of NCS and PTX synergistically inhibit the gliom growth. Our data about the combinational effects of NCS with PTX may provide an alternative strategy for glioma therapy.

Protective effect of SKLB010 against D-galactosamine/lipopolysaccharide-induced acute liver failure via nuclear factor-κB signaling pathway in macrophages.

Acute liver failure is characterized by the sudden loss of hepatic function and a high mortality. SKLB010, a derivative of thiazolidinediones, has been proved to be effective in protecting mice from acute liver failure caused by concanavalin A and carbon tetrachloride in our previous work. The purpose of the current study was to evaluate whether SKLB010 could prevent acute liver injury caused by d-galactosamine/lipopolysaccharide (LPS) in mice, and to investigate the underlying mechanisms. In the macrophage-mediated D-GalN/LPS model of acute liver injury, serum enzyme activity was suppressed and liver injury was attenuated by SKLB010. The serum levels of TNF-α and hepatic TNF-α mRNA expression were also markedly decreased after the treatment of SKLB010. In the liver of mice receiving injections of D-GalN/LPS, hepatocytes apoptosis and the infiltration of monocytes/macrophages were blocked by SKLB010. Furthermore, the survival rate of mice following D-GalN/LPS treatment was significantly improved by a single injection with SKLB010. In vivo, the luminescence intensity was suppressed by SKLB010 in NF-κB-luc mice after D-GalN/LPS treatment. In vitro, the production of tumor necrosis factor (TNF)-α and nitrite/nitrate in LPS-stimulated RAW264.7 macrophages was decreased by SKLB010 in a dose-dependent manner. Our further studies demonstrated that SKLB010 inhibited the phosphorylation of IκBα and p38MAPK, and the DNA binding activity of NF-κB in RAW264.7 cells. In conclusion, treatment with only a single injection of SKLB010 could significantly attenuate acute inflammation in mice induced by D-GalN/LPS, and these effects are likely associated with the inhibition of NF-κB activity.

PEGylated HM-3 presents anti-rheumatic bioactivity by inhibiting angiogenesis and inflammation.

PEGylation improves the pharmacokinetic and pharmacodynamic properties of polypeptide drugs. After PEGylation, the modified HM-3 (PEG-HM-3) exhibited a prolonged half-life in blood. In this paper, we evaluated the anti-rheumatic effect of PEG-HM-3, and investigated the target for angiogenesis and inflammation. The anti-rheumatic activity of PEG-HM-3 was documented in an adjuvant-induced arthritis (AIA) model. PEG-HM-3 significantly decreased the paw increase percentage and clinical scores, inhibited characteristic signs such as synovial hyperplasia, pannus formation, inflammatory infiltration and bone erosion in histological analysis, and reduced bone erosion with the X-ray analysis of the hint paws of rats. The target for angiogenesis and inflammation was assessed with in vivo and in vitro techniques. The in vivo experiments confirmed that PEG-HM-3 decreased the number of blood vessels in rheumatic synovium, reduced the level of serum anti-CII autoantibodies, and decreased the levels of synovial TNF-alpha and VEGF in a collagen-induced arthritis (CIA) model. The in vitro results confirmed that the anti-angiogenic effect of PEG-HM-3 was mainly achieved through the inhibition of HUVEC migration. PEG-HM-3 inhibited the mitotic effects in the T-cell population. PEG-HM-3 could significantly inhibit the TNF-alpha and VEGF levels in the LPS-stimulated macrophage and the latter effect was stronger than that seen with HM-3. Furthermore, the simulated molecule docking result showed that the RGD motif of PEG-HM-3 inserted into the pocket site of integrin αvß3, and PEG-HM-3 had a higher predicted affinity with integrin αvß3 compared to the predicted affinity of HM-3 and integrin αvß3. This study has uncovered that PEGylate HM-3 could present an anti-rheumatic bioactivity with a less frequent schedule, and PEG-HM-3 exhibited its anti-rheumatic effects by inhibiting angiogenesis and inflammation. Furthermore, the main targeting site has been confirmed, which explained the changes in the bioactivity of PEG-HM-3.