An integrated transcriptomics and network pharmacology approach to explore the mechanism of Wang-Bi tablet against SAPHO syndrome.

BACKGROUND: SAPHO syndrome is recognized as a rare entity with damage to skin and bones due to inflammation. Currently, the treatment for SAPHO syndrome is still a challenge in clinical practice. In this study, an integrated transcriptomics and network pharmacology approach was applied to explore the therapeutic effect and mechanism of Wang-Bi tablet (WBT) on SAPHO syndrome. METHODS: The main components of WBT and their targets, as well as the targets of SAPHO syndrome, were collected from databases. Network visualization was performed using Cytoscape software. The GO and KEGG enrichment analysis was executed by David dataset. Then, the molecular mechanism of WBT improving SAPHO syndrome was validated by transcriptomics of peripheral blood neutrophils in SAPHO syndrome. Finally, the above results were validated by molecular docking. RESULTS: The Network Pharmacology results showed there are 152 core targets for WBT treatment on SAPHO syndrome. RNA-seq data showed 442 differentially expressed genes (DEGs) in peripheral blood neutrophils of SAPHO patients. Intriguingly, NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway were included in the enrichment results of network pharmacology and RNA-seq. Moreover, we verified that the core components of WBT have good affinity with the core targets of NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway by molecular docking. CONCLUSIONS: This study illustrated that the possible mechanisms of WBT against SAPHO syndrome may be related to NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway, and further experiments are needed to prove these predictions.

Multiclass classification of motor imagery tasks based on multi-branch convolutional neural network and temporal convolutional network model.

Motor imagery (MI) is a cognitive process wherein an individual mentally rehearses a specific movement without physically executing it. Recently, MI-based brain-computer interface (BCI) has attracted widespread attention. However, accurate decoding of MI and understanding of neural mechanisms still face huge challenges. These seriously hinder the clinical application and development of BCI systems based on MI. Thus, it is very necessary to develop new methods to decode MI tasks. In this work, we propose a multi-branch convolutional neural network (MBCNN) with a temporal convolutional network (TCN), an end-to-end deep learning framework to decode multi-class MI tasks. We first used MBCNN to capture the MI electroencephalography signals information on temporal and spectral domains through different convolutional kernels. Then, we introduce TCN to extract more discriminative features. The within-subject cross-session strategy is used to validate the classification performance on the dataset of BCI Competition IV-2a. The results showed that we achieved 75.08% average accuracy for 4-class MI task classification, outperforming several state-of-the-art approaches. The proposed MBCNN-TCN-Net framework successfully captures discriminative features and decodes MI tasks effectively, improving the performance of MI-BCIs. Our findings could provide significant potential for improving the clinical application and development of MI-based BCI systems.

Evaluation of neoadjuvant immunotherapy and traditional neoadjuvant therapy for resectable esophageal cancer: a systematic review and single-arm and network meta-analysis.

Objective: This systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T]. Summary background data: NCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates. Results: We included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates. Conclusions: Among the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities. Systematic Review Registration: https://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.

Promotion of Egg Production Rate and Quality Using Limosilactobacillus oris BSLO 1801, a Potential Probiotic Screened from Feces of Laying Hens with Higher Egg Productive Performance.

In this experiment, laying hens were divided into a high productive group (group H) and a low productive group (group L). The purpose of this experiment was to screen and isolate a potential probiotic associated with the laying rate from group H by comparing the results via 16S rDNA high-throughput sequencing. The high-throughput sequencing analysis results showed that there were some differences in the composition of the gut microbiome between groups H and L on the Phylum and Genus levels. Through isolation and identification, we screened 16 lactobacilli strains. Among the 16 strains, S5 showed good acid tolerance, bile salt tolerance, and cholesterol degradation. Therefore, we chose strain S5 (identified as Limosilactobacillus oris, named Limosilactobacillus oris BSLO 1801) as a potential probiotic to promote the productivity of ordinary laying hens. During the animal experiment, 288 Hy-line white hens (30 weeks old) were divided into four groups, with six replications (n = 12) per group. The control group received the basic diet, and the treatment groups received the same basic diet supplemented with 107 CFU/kg, 108 CFU/kg, and 109 CFU/kg of BSLO 1801. The laying hens were acclimated to the environment for 1 week before the initiation of the experiment. Dietary supplementation with 107 CFU/kg and 109 CFU/kg of BSLO 1801 increased the laying rate significantly, and the potential probiotic improved the egg weight in all treatment groups. Additionally, the cholesterol content of the yolk dropped significantly in the 109 CFU/kg group, and the weight of egg yolk was significantly increased in all treatment groups. However, no significant differences in eggshell strength, eggshell thickness, protein height, and Haugh unit were observed among the four groups. These results revealed that lactobacilli spp. are important bacteria of the intestinal microbiome in highly productive laying hens, and BSLO 1801 was isolated as a potential probiotic. Through these animal experiments, we also found that adding BSLO 1801 to the basic diet of laying hens could effectively improve the laying rate, average egg weight, and yolk weight and reduce the cholesterol content in egg yolk.

Analysis of miRNA Expression in the Ileum of Broiler Chickens During Bacillus licheniformis H2 Supplementation Against Subclinical Necrotic Enteritis.

Subclinical necrotic enteritis (SNE) is one of the serious threats to the poultry industry. Probiotics have been proven to exert beneficial effects in controlling SNE. However, their exact mechanisms have not been fully elucidated. Moreover, few studies have focused on their impact on microRNAs (miRNAs). Therefore, the present study aimed to explore the miRNA expression profiles in the ileum of broiler chickens during probiotic supplementation for controlling SNE. A total of 180 newly hatched male broilers were randomly allocated into three groups, including a negative control group, an SNE infection group, and a Bacillus licheniformis H2 pretreatment group. Illumina high-throughput sequencing was conducted to identify the miRNA expression of the three groups. Results showed that 628 miRNAs, including 582 known miRNAs and 46 novel miRNAs, were detected in the miRNA libraries. The target genes of 57 significantly differentially expressed miRNAs were predicted and annotated. Moreover, they were found to be partly enriched in pathways related to immunity and inflammation such as tumor necrosis factor receptor binding, immune response-regulating signaling pathway, Toll-like receptor 2 signaling pathway, interleukin-15 production, activation of NF-κB-inducing kinase activity, and MAP kinase tyrosine/serine/threonine phosphatase activity. Some of the target genes of 57 miRNAs were related to the MAPK signaling pathway. Furthermore, the expression of several miRNAs, which may be involved in the MAPK signaling pathway, was significantly affected by SNE induction and showed no significant difference in the presence of H2. All these findings provide comprehensive miRNA expression profiles of three different treatment groups. They further suggest that H2 could exert beneficial effects in controlling SNE through immune and inflammatory response associated with altered miRNA expression, such as the MAPK signaling pathway.

The Mechanisms of Sijunzi Decoction in the Treatment of Chronic Gastritis Revealed by Network Pharmacology.

Chronic gastritis is characterized by inflammation in the gastric mucosa with a vicious circle in inflammatory cells and inflammatory mediators. Stomach adenocarcinoma would occur in the metaplastic gastric mucosa of chronic gastritis. Sijunzi decoction is a famous classical formula for the treatment of chronic gastritis. Although previous studies revealed some functions of Sijunzi decoction in treating chronic gastritis, the underlying mechanisms have not been illustrated clearly. In this study, we used network pharmacology to investigate the mechanism of Sijunzi decoction in treating chronic gastritis. Firstly, online datasets TCMSP, SWISS, and DisGeNET were used to investigate the functional mechanism of Sijunzi decoction against chronic gastritis and 18 genes were identified as targets of Sijunzi decoction in chronic gastritis. These 18 genes can be categorized into immunologically related genes and cancer-related genes. GO analysis showed that the 18 target genes were mainly enriched in angiogenesis, nitric oxide biosynthetic process, ERK1 and ERK2 cascade, cellular response to drug, and MAPK cascade. So, Sijunzi decoction alleviated chronic gastritis by inhibiting the local inflammatory response. Furthermore, we also investigated the impact of Sijunzi decoction on the peripheral blood leukocytes with our own RNA sequencing (RNA-seq) data of 11 chronic superficial gastritis patients. 102 differentially expressed genes (DEGs) were identified by comparing RNA-seq data of chronic superficial gastritis patients with healthy control groups. After performing a functional analysis on 102 DEGs and Sijunzi decoction potential targets and taking the intersection of these pathways, we found that platelet activation, angiogenesis, and pathways in cancer were candidate target pathways regulated by Sijunzi decoction. Thus, Sijunzi decoction also alleviates chronic gastritis by suppressing inflammatory response of peripheral blood leukocytes. Our results showed that Sijunzi decoction can ameliorate the local gastric inflammation and inflammations in peripheral blood leukocytes and might also reduce the incidence of stomach cancer in chronic gastritis.

Emodin ameliorates rheumatoid arthritis by promoting neutrophil apoptosis and inhibiting neutrophil extracellular trap formation.

Rheumatoid arthritis (RA) is a chronic, systemic, synovitis-based inflammatory disease with unknown etiology. Neutrophils play important roles in the pathogenesis of RA. Apoptosis and NETosis of neutrophils are two major mechanisms of programmed cell death that differ in their morphological characteristics and effects on the immune system. In rheumatoid arthritis, delayed neutrophil apoptosis amplifies the inflammatory response; and massive release of NETs and their components may cause tissue damage and provide self-antigens. Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs. In this study, we evaluated the effect of emodin on a murine adjuvant-induced arthritis (AA) model of RA in vivo and on neutrophil apoptosis and NETosis in vitro. Our results show that emodin alleviated AA by reducing neutrophil infiltration and proinflammatory cytokine (interleukin-6, interferon-gamma and tumor necrosis factor-α) release. Emodin promoted apoptosis and inhibited autophagy and NETosis in neutrophils. These findings indicate that emodin represents a potential therapeutic agent for RA.

Bacillus licheniformis normalize the ileum microbiota of chickens infected with necrotic enteritis.

Necrotic enteritis (NE) is a severe intestinal disease, which can change gut microbiota and result in a high cost for the poultry industry worldwide. However, little is known regarding how the gut microbiota of NE chicken ileum are changed by Bacillus licheniformis. This study was conducted to investigate how ileum microbiota structure was changed by B. licheniformis in broiler chickens challenged with Clostridium perfringens-induced NE through Illumina MiSeq sequencing. The broilers were randomly separated into four groups: the negative control group (NC), the positive control group (PC), the fishmeal and coccidia group (FC), and the PC group supplied with feed containing B. licheniformis (BL). Compared to the PC and FC, alpha diversity, beta diversity, and the bacterial taxa of the ileum microbiota were more similar in BL and NC. Some genera, which were related to the NE control, became insignificant in BL with NC, such as Lactobacillus, Lactococcus, Bacteroides, Ruminococcus and Helicobacter. The PICRUSt analysis revealed that a tumour suppressor gene, p53, which was negatively correlated with Helicobacter, was enriched in the BL group. Our findings showed that the ileum microbiota disorder caused by NE in chickens was normalized by dietary B. licheniformis supplementation.

Disruption in the cecal microbiota of chickens challenged with Clostridium perfringens and other factors was alleviated by Bacillus licheniformis supplementation.

Clostridium perfringens can induce necrotic enteritis of chickens, which causes large economic losses every year. Bacillus licheniformis, a probiotic, can inhibit the growth of pathogenic bacteria such as Clostridium perfringens, thereby improving the health status of chickens. However, from a microbial ecology perspective, the mechanisms by which alterations to the gut microbiota improve health remain unknown. In this study, we used Illumina MiSeq sequencing to investigate the cecal microbiota of a negative control group (NC), a C. perfringens and Eimeria challenge group with fishmeal supplementation (PC), a group supplemented with fishmeal and infected with coccidia (FC), and group PC with B. licheniformis supplementation (BL). We found that the health status of C. perfringens-challenged chickens was compromised, and that B. licheniformis improved the growth of the chickens challenged with pathogens. Microbial diversity analysis and taxonomic profiling of groups NC, PC, and FC revealed a disturbed cecal microflora of the birds with C. perfringens. We also characterized the microbiota of the chickens in the BL group using several methods. Principal coordinate analysis demonstrated that, compared with group PC, the bacterial community structure of group BL was more similar to that of group NC. Linear discriminant analysis with effect size revealed less differentially represented bacterial taxa between groups BL and NC than between groups PC and NC. In addition, groups BL and NC appeared to have similar overrepresented microbial taxa (such as Bacteroides, Helicobacter, Megamonas, and Akkermansia) compared with group PC. Finally, a phylogenetic investigation of communities by reconstruction of unobserved states analysis indicated that large differences existed between group PC and groups NC and BL. In conclusion, pre-treatment with B. licheniformis reduced the disturbance of the cecal microbiome induced by challenge with C. perfringens and other factors in broiler chickens.

Controlling of growth performance, lipid deposits and fatty acid composition of chicken meat through a probiotic, Lactobacillus johnsonii during subclinical Clostridium perfringens infection.

BACKGROUND: Meat is considered as a major source of polyunsaturated fatty acid (PUFA) which is essential for humans, therefore its lipid level and fatty acid composition have drawn great attention. As no clinical sign can be found in chicks subclinically infected by Clostridium perfringens (CP), the meat may be purchased and eaten. The objective of the present study was to determine whether Lactobacillus johnsonii (LJ) can control the CP-caused impact on growth, lipid levels, fatty acid composition and other flavor or nutritional quality in the meat. METHODS: 480 one-day-old chicks were divided into four groups and fed with basal diet (control and CP group). Supplemented with 1 × 105 (L-LJ) and 1 × 106 (H-LJ) colony-forming unit (cfu), CP diet was fed for 42 days. From day 19 to 22, birds of CP and LJ groups were administered with CP twice per day and the control was administered with liver broth. RESULTS: LJ-treated chickens were free from negative influences on growth performance and significant decrease of abdominal fat deposit., LJ inhibited CP-caused shearing force and drip loss increase and pH 40 min and 24 h decrease after sacrifice. In addition, LJ exhibited a positive effect on muscle lipid peroxidation by significantly increasing SOD, CAT and GSH-Px activity and decreasing MDA level. Besides, LJ attenuated the decrease of intramuscular fat, total cholesterol and triglyceride contents caused by CP infection. However, levels of total protein and most of amino acids were not changed. CP infection decreased C18:3n-3 (α-LA), C20:4n-6, C20:5n-3(EPA), C22:4n-6, C22:5n-3, C22:6n-3(DHA), total PUFA, n-3 PUFA and PUFA:SFA ratio and increased C14:0, total SFA and n-6:n-3 ratio. LJ was found to protect the muscle from these changes. Meanwhile, the 28-day gut permeability level was higher in CP group. CONCLUSIONS: These findings suggest that CP may affect the growth performance of chicks and negatively influence lipid content and fatty acid composition in chicken meat. Meanwhile, LJ treatment may be effective in controlling these changes by reducing the increased gut permeability caused by CP subclinical infection.

Bidirectional immunomodulating activity of fermented polysaccharides from Yupingfeng.

Accumulating evidence has proven the immunomodulating activity of Yupingfeng. This study compared the immunomodulatory activity in vitro of the unfermented Yupingfeng dreg polysaccharides (UYDP) with that of the fermented Yupingfeng dreg polysaccharides (FYDP) obtained using Rhizopus oligosporus SH. Results consistently elucidated the duality of the immunomodulatory roles of UYDP and FYDP in regulating proliferation, and cytokines expressions in murine lymphocytes and macrophages. Compared with UYDP, FYDP effectively enhanced the proliferation of lymphocytes and promoted mRNA expression of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, INF-γ, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and TLR-4 in lymphocytes and macrophages. Moreover, compared with UYDP, FYDP effectively normalized cell proliferation and downregulated mRNA expression levels of pro-inflammatory cytokines, NF-κB, TLR-4, and iNOs in lipopolysaccharide-induced chronic inflammation cells. The results revealed that the bidirectional immunomodulatory effects in vitro of UYDP and FYDP, and the bi-directional immunomodulatory activity of FYDP is superior over that of UYDP. Moreover, more studies in vivo that needs to be studied further.

Illumina Miseq platform analysis caecum bacterial communities of rex rabbits fed with different antibiotics.

Antibiotics have been widely used for the prevention and the treatment of diseases to humans and animals, and they have fed additives for agricultural animals to promote growth. However, there is a growing concern over the practice due to its side effects on intestinal microbial communities which plays a vital role in animals' health. To investigate the effect of antibiotics on the bacterial population of the caecum in rex rabbits, 80 rex rabbits were randomly divided into four groups: control group (B, basal diet), chlortetracycline group (C, 50 mg/kg), colistin sulfate group (S, 20 mg/kg) and zinc bacitracin group (Z, 40 mg/kg). Caecum microbial communities of rex rabbits from the four groups were analyzed through Illumina Miseq platform after being fed 28 days. The results showed that most obtained sequences belongs to Firmicutes followed by Bacteroidetes, and the ratio of Bacteroidetes/Firmicutes in C group (42.31 %) was higher than that in Z group (21.84 %). Zinc bacitracin supplementation caused a significant decreased of the Proteobacteria phylum and Lactobacillus spp. (P < 0.05), while the Lactobacillus spp. significantly increased in S group (P < 0.05). In addition, Ruminococcus spp., especially Ruminococcus albus were the predominant bacterial species found in both S and Z groups. The proportion of Coprococcus spp. significantly increased in Z group (P < 0.05). These findings suggested that the antibiotics used may cause significant changes in the caecum microbiota of rex rabbits, and we also found C group had a similarity caecum bacteria structure with B group which was probably due to the high levels of chlortetracycline resistance.

Fermented Yupingfeng polysaccharides enhance immunity by improving the foregut microflora and intestinal barrier in weaning rex rabbits.

Yupingfeng (YPF) is a kind of Astragali radix-based ancient Chinese herbal supplemented with Atractylodis Macrocephalae Rhizoma and Radix Saposhnikoviae. Increasing evidence has proven the beneficial immunomodulating activity of YPF. However, the action mechanism(s) of it is not known. Here, we explored the immunomodulatory activity of unfermented Yupingfeng polysaccharides (UYP) and fermented Yupingfeng polysaccharides (FYP) obtained using Rhizopus oligosporus SH in weaning Rex rabbits. The results showed that both UYP and FYP exhibited notable growth-promoting and immune-enhancing activities, improvement of the intestinal flora homeostasis, and maintenance of intestinal barrier integrity and functionality. Notably, compared with UYP, FYP effectively enhanced average daily gain, organ indices, interleukin-2 (IL-2), IL-4, IL-10, tumor necrosis factor-alpha (TNF-α), TLR2, and TLR4 mRNA levels in spleen, IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α, and IFN-γ protein concentrations in serum, and TLR2 and TLR4 mRNA expressions in the gastrointestinal tract (GIT). Moreover, FYP exhibited greater beneficial effects in improving the intestinal flora, including augment flora diversity and the abundance of cellulolytic bacteria, reduction the abundance of Streptococcus spp. and Enterococcus spp. in the GIT, particularly the foregut and maintaining the intestinal barrier integrity and functionality by upregulating zonula occludens 1, claudin, polymeric immunoglobulin receptor, trefoil factor, and epidermal growth factor mRNA levels in the jejunum and ileum. Our results indicated the immunoenhancement effect of FYP is superior over that of UYP, which is probably related with the amelioration of the intestinal microflora and intestinal barrier in the foregut.

Decreased IgA+ B cells population and IgA, IgG, IgM contents of the cecal tonsil induced by dietary high fluorine in broilers.

Fluoride is an environmental and industrial pollutant that affects various organs in humans and animals. The cecal tonsil is an important component of the mucosal immune system and performs important and unique immune functions. In the present study, we investigated the effects of dietary high fluorine on the quantities of IgA+ B cells in the cecal tonsil by immunohistochemistry, and the immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) contents in the cecal tonsil by ELISA. A total of 280 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg/kg) or the same diet supplemented with 400, 800 and 1,200 mg/kg fluorine (high fluorine groups I, II and III) in the form of sodium fluoride, respectively, throughout a 42-day experimental period. The results showed that the quantities of IgA+ B cells were lower (p < 0.05 or p < 0.01) and the IgA, IgG, and IgM contents were decreased (p < 0.05 or p < 0.01) in high fluorine groups II and III in comparison with those of control group. It was concluded that dietary fluorine, in the 800-1,200 mg/kg range, could reduce the numbers of the IgA+ B cells and immunoglobulin contents in the cecal tonsil, implying the local mucosal immune function was ultimately impacted in broilers.

Changes of the serum cytokine contents in broilers fed on diets supplemented with nickel chloride.

Cytokines are immunoregulatory proteins which play an important role in the immune system. The purpose of this study was to examine the serum cytokine contents including interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) induced by dietary nickel chloride in broilers by enzyme-linked immunospecific assay. A total of 240 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet or the same basal diet supplemented with 300, 600, and 900 mg/kg of nickel chloride. During the experimental period of 42 days, the results showed that the serum IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF-α contents were lower (p < 0.05 or p < 0.01) in the 300, 600, 900 mg/kg groups than those in the control group. It was concluded that dietary nickel chloride in the range of 300 to 900 mg/kg could reduce the serum cytokine contents, which could finally impact the immune function in broilers.