Background and roles: myosin in autoimmune diseases

The myosin superfamily is a group of molecular motors. Autoimmune diseases are characterized by dysregulation or deficiency of the immune tolerance mechanism, resulting in an immune response to the human body itself. The link between myosin and autoimmune diseases is much more complex than scientists had hoped. Myosin itself immunization can induce experimental autoimmune diseases of animals, and myosins were abnormally expressed in a number of autoimmune diseases. Additionally, myosin takes part in the pathological process of multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, autoimmune myocarditis, myositis, hemopathy, inclusion body diseases, etc. However, research on myosin and its involvement in the occurrence and development of diseases is still in its infancy, and the underlying pathological mechanisms are not well understood. We can reasonably predict that myosin might play a role in new treatments of autoimmune diseases

Developing neural network diagnostic models and potential drugs based on novel identified immune-related biomarkers for celiac disease

Abstract Background As one of the most common intestinal inflammatory diseases, celiac disease (CD) is typically characterized by an autoimmune disorder resulting from ingesting gluten proteins. Although the incidence and prevalence of CD have increased over time, the diagnostic methods and treatment options are still limited. Therefore, it is urgent to investigate the potential biomarkers and targeted drugs for CD. Methods Gene expression data was downloaded from GEO datasets. Differential gene expression analysis was performed to identify the dysregulated immune-related genes. Multiple machine algorithms, including randomForest, SVM-RFE, and LASSO, were used to select the hub immune-related genes (HIGs). The immune-related genes score (IG score) and artificial neural network (ANN) were constructed based on HIGs. Potential drugs targeting HIGs were identified by using the Enrichr platform and molecular docking method. Results We identified the dysregulated immune-related genes at a genome-wide level and demonstrated their roles in CD-related immune pathways. The hub genes (MR1, CCL25, and TNFSF13B) were further screened by integrating several machine algorithms. Meanwhile, the CD patients were divided into distinct subtypes with either high- or low-immunoactivity using single-sample gene set enrichment analysis (ssGSEA) and consensus clustering. By constructing IG score based on HIGs, we found that patients with high IG score were mainly attributed to high-immunoactivity subgroups, which suggested a strong link between HIGs and immunoactivity of CD patients. In addition, the novel constructed ANN model showed the sound diagnostic ability of HIGs. Mechanistically, we validated that the HIGs play pivotal roles in regulating CD's immune and inflammatory state. Through targeting the HIGs, we also found potential drugs for anti-CD treatment by using the Enrichr platform and molecular docking method. Conclusions This study unveils the HIGs and elucidates the networks regulated by these genes in the context of CD. It underscores the pivotal significance of HIGs in accurately predicting the presence or absence of CD in patients. Consequently, this research offers promising prospects for the development of diagnostic biomarkers and therapeutic targets for CD

Additional file 2 of Developing neural network diagnostic models and potential drugs based on novel identified immune-related biomarkers for celiac disease

Additional file 2: Fig. S1. GO and KEGG analysis of 58 differentially expressed immune-related genes. A GO enrichment results in differentially expressed immune-related genes. B KEGG enrichment results in differentially expressed immune-related genes. Fig. S2. Heatmap shows the overall landscape of CD patients' ssGSEA score of 28 immune gene sets. Fig. S3. Consensus matrix heatmap when K = 3–9. It is related to Fig. 3D. Fig. S4. The box plot shows the ssGSEA score of immune cells of the C1 and C2 groups. (ns, no significance, *P < 0.05, **P < 0.01, ***P < 0.001). Fig. S5. Validation of the IG score in the GSE164883 set. A The violin plot shows the IG score between the control and CD groups. B The ROC curve of the IG score in the GSE164883 validation set. Fig. S6. ROC analysis validated the diagnostic performance of HIGs. ROC curves of the indicated HIGs in the GSE11501 training set (A) and GSE164883 validation set (B). Fig. S7. Construction of artificial neural network (ANN) based on HIGs. A The construction of an artificial neural network (ANN) based on MR1, TNFSF13B, and CCL25. B The AUC of the training cohort with a value of 0.824. C The AUC of the test cohort with a value of 0.733. Fig. S8. 3D (left) and 2D (right) structure of complexes of HIGs and drugs. It is related to Fig. 7

Additional file 1 of Developing neural network diagnostic models and potential drugs based on novel identified immune-related biomarkers for celiac disease

Additional file 1: Table S1. 896 differentially expressed genes. Table S2. Results of three machine algorithms. Table S3. ssGSEA score of 28 immune gene sets in celiac disease patients. Table S4. IG score for GSE11501 training set based on HIGs. Table S5. IG score for GSE164883 validation set based on HIGs. Table S6. ANN diagnosis effect for the grouping of immune characteristics of celiac disease subtypes. Table S7. 2483 immune genes from the ImmPort database. Table S8. 28 immune gene sets from the TISIDB database

Study on screening potential allergenic proteins from infant milk powders based on human mast cell membrane chromatography and histamine release assays

Cow's milk allergy is mainly observed in infants and young children. Most allergic reactions affect the skin, followed by the gastrointestinal and respiratory systems. Conventional diagnosis is based on positive allergy studies and evaluation of parameters including IgE and IgG1 levels, acute allergic skin response and anaphylactic shock reactions. We developed a cell membrane chromatographic (CMC) method based on human mast cells (HMC-1) for screening potential allergens in infant formula milk powders (IFMP). HMC-1 cell membranes were extracted and mixed with silica to prepare cell membrane chromatography columns (10 mm × 2 mm i.d., 5 µm). Under the conditions of 0.2 mL/min flow rate and 214 nm detection wavelength, human breast milk showed no retention. However, IFMP showed clear retention. The retained fractions were collected and analyzed through matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Four major milk proteins, i.e., α-casein, β-casein, α-lactalbumin, and β-lactoglobulin A, were identified. Furthermore, these proteins and β-lactoglobulin B showed clear retention on HMC-1/CMC columns. To test the degranulation effects of the five proteins, histamine and β-hexosaminidase release assays were carried out. All five proteins induced HMC-1 cells to release histamine and β-hexosaminidase. Also, we established a reversed phase liquid chromatographic (RPLC) method for the determination of the five proteins in IFMP and the results showed that 90% proteins in IFMP were α-casein and β-casein. We concluded that cow's milk proteins may be potential allergens and caseins cause more β-casein allergic risk than other proteins. This conclusion was consistent with other studies. Keywords: Allergenic proteins, Cell membrane chromatography, Milk powder

Impacts of Intercropped Maize Ecological Shading on Tea Foliar and Functional Components, Insect Pest Diversity and Soil Microbes

Ecological shading fueled by maize intercropping in tea plantations can improve tea quality and flavor, and efficiently control the population occurrence of main insect pests. In this study, tea plants were intercropped with maize in two planting directions from east to west (i.e., south shading (SS)) and from north to south (i.e., east shading (ES) and west shading (WS)) to form ecological shading, and the effects on tea quality, and the population occurrence and community diversity of insect pests and soil microbes were studied. When compared with the non-shading control, the tea foliar nutrition contents of free fatty acids have been significantly affected by the ecological shading. SS, ES, and WS all significantly increased the foliar content of theanine and caffeine and the catechin quality index in the leaves of tea plants, simultaneously significantly reducing the foliar content of total polyphenols and the phenol/ammonia ratio. Moreover, ES and WS both significantly reduced the population occurrences of Empoasca onukii and Trialeurodes vaporariorum. Ecological shading significantly affected the composition of soil microbial communities in tea plantations, in which WS significantly reduced the diversity of soil microorganisms

Effect of the Chinese Medicine YangZheng XiaoJi on Reducing Fatigue in Mice with Orthotopic Transplantation of Colon Cancer

Background. Fatigue is a common, distressing, and persistent symptom for patients with malignant tumor including colorectal cancer (CRC). Although studies of cancer-related fatigue (CRF) have sprung out in recent years, the pathophysiological mechanisms that induce CRF remain unclear, and effective therapeutic interventions have yet to be established. Methods. To investigate the effect of the traditional Chinese medicine YangZheng XiaoJi (YZXJ) on CRF, we constructed orthotopic colon cancer mice, randomly divided into YZXJ group and control (NS) group. Physical or mental fatigue was respectively assessed by swimming exhaustion time or suspension tail resting time. At the end of the experiment, serum was collected to measure the expression level of inflammatory factors by ELISA and feces to microbiota changes by 16s rDNA, and hepatic glycogen content was detected via the anthrone method. Result. The nutritional status of the YZXJ group was better than that of the control group, and there was no statistical difference in tumor weight. The swimming exhaustion times of YZXJ group and control group were (162.80 ± 14.67) s and (117.60 ± 13.42, P < 0.05) s, respectively; the suspension tail resting time of YZXJ group was shorter than that of the control group (49.85 ± 4.56) s and (68.83 ± 7.26) s, P < 0.05)). Serum levels of IL-1β and IL-6 in YZXJ group were significantly lower than the control group (P < 0.05). Liver glycogen in YZXJ group was (5.18 ± 3.11) mg/g liver tissue, which was significantly higher than that in control group (2.95 ± 2.06) mg/g liver tissue (P < 0.05). At phylum level, increased abundance of Bacteroidetes, Verrucomicrobia, Actinobacteria, and Cyanobacteria and decreased Proteobacteria in YZXJ group emerged as the top differences between the two groups, and the Firmicutes/Bacteroidetes ratio was decreased in YZXJ group compared to the control group. At genus level, the abundance of Parabacteroides, unidentified Saprospiraceae, and Elizabethkingia which all belong to phylum Bacteroidetes were increased, while Arcobacter, Marinobacter, Alkanindiges, Sulfuricurvum, Haliangium, and Thiobacillus in phylum Proteobacteria were decreased after YZXJ intervention. YZXJ can also increase Pirellula, Microbacterium, and Alpinimonas and decrease Rubrobacter and Iamia. Conclusion. YZXJ may reduce the physical and mental fatigue caused by colorectal cancer by inhibiting inflammatory reaction, promoting hepatic glycogen synthesis, and changing the composition of intestinal microbiota