Expression profile and immunomodulatory roles of methionine-enkephalin and delta opioid receptor in Octopus ocellatus.

In this study, the expressions and distributions of methionine-enkephalin (Met-enk) and δ opioid receptor in the nervous system of Octopus ocellatus, and the immune regulatory mechanisms of Met-enk on O. ocellatus were explored. The distributions and expressions of Met-enk and δ opioid receptor were assessed by immunohistochemistry and enzyme-linked immunosorbent assay. UV-spectrophotometer, microplate reader, and flow cytometer were used to examine the effects of different concentrations of Met-enk on phagocytosis, antioxidant effects, and body surface mucus immunity of O. ocellatus hemocytes. The data were used to study the mechanisms of Met-enk immunity regulation in O. ocellatus. According to the results, the expression levels of Met-enk and δ opioid receptor in O. ocellatus lymphocytes were higher than those in hemocytes. The expression levels of Met-enk in the ganglia of O. ocellatus decreased in the following order: pedal ganglia > cerebral ganglia > visceral ganglia > optic ganglia > stellate ganglia. Moreover, the phagocytic activity of O. ocellatus hemocytes was enhanced with increasing Met-enk concentration. With increasing Met-enk concentration, the expressions of nitric oxide, total nitric oxide synthase, inducible nitric oxide synthase, catalase, hydrogen peroxide, myeloperoxidase, reduced glutathione, α-naphthy acetate esterase, and methionine aminopeptidases decreased in serums of O. ocellatus in the experimental group compared to the blank group. Similarly, the content of reduced glutathione in the hemocytes of O. ocellatus was also lower in the experimental group than in the blank group; however, the expressions of other substances were higher compared to the blank group. Furthermore, α-naphthy acetate esterase, myeloperoxidase, and hydrogen peroxide expressions in mucus immunity trials of the body surface were lower in the experimental group compared to the blank group. These results indicate that the distributions and expressions of Met-enk and δ opioid receptor in the nervous system of O. ocellatus were related to axoplasmic transport and immune regulation mechanisms. Met-enk participates in cellular immunity, humoral immunity, and mucus immunity in the form of neurotransmitters, thereby regulating the immune response of O. ocellatus.

Higher expression of PLEK and LY86 as the potential biomarker of carotid atherosclerosis.

Carotid atherosclerosis (AS) occurs in atherosclerotic lesions of the carotid artery, which can lead to transient ischemic attack and stroke in severe cases. However, the relationship between pleckstrin (PLEK) and lymphocyte antigen 86 (LY86) and carotid AS remains unclear. The carotid AS datasets GSE43292 and GSE125771 were downloaded from the gene expression omnibus database. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis was performed. Construction and analysis of protein-protein interaction network. Functional enrichment analysis, gene set enrichment analysis and comparative toxicogenomics database analysis were performed. TargetScan screened miRNAs that regulated central DEGs. A total of 305 DEGs were identified. According to gene ontology analysis, they were mainly enriched in immune system processes, extracellular regions and cytokine binding. Kyoto encyclopedia of genes and genomes analysis showed that the target cells were mainly enriched in Rap1 signal pathway, B cell receptor signal pathway and PPAR signal pathway. In the enrichment project of metascape, the reaction to bacteria, cell activation and chemotaxis can be seen in the enrichment project of gene ontology. Total 10 core genes (TYROBP, FCER1G, PLEK, LY86, IL10RA, ITGB2, LCP2, FCGR2B, CD86, CCR1) were obtained by protein-protein interaction network construction and analysis. Core genes (PLEK, LY86, IL10RA, ITGB2, and LCP2) were highly expressed in carotid AS samples and lowly expressed in normal samples. Comparative toxicogenomics database analysis showed that 5 genes were associated with pneumonia, inflammation, necrosis, and drug allergy. PLEK and LY86 genes are highly expressed in carotid AS. The higher the expression of PLEK and LY86, the worse the prognosis is.

Infection routes, invasion mechanisms, and drug inhibition pathways of human coronaviruses on the nervous system.

So far, numerous studies have reported on how coronaviruses affect the human nervous system. However, these studies mainly focused on the impact of a single coronavirus on the nervous system, and failed to fully report the invasion mechanisms and the rules of symptoms of the seven human coronaviruses. This research can assist medical professionals in identifying the regularity of coronavirus invasion into the nervous system by examining the impacts of human coronaviruses on the nervous system. Meanwhile, the discovery also helps humans to prevent the damage to the human nervous system caused by the more novel coronavirus in advance, thus reducing the rate of disease transmission and fatality caused by such viruses. In addition to describing the structures, routes of infection, and symptomatic manifestations of human coronaviruses, this review also finds that the structures of human coronaviruses correlate with virulence, pathways of infection, and blocking mechanisms of drugs. This review can provide a theoretical basis for the research and development of related drugs, promote the prevention and treatment of coronavirus infectious diseases, and contribute to global epidemic prevention.

FCGR2A as one novel potential target for poor survival prognosis of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma. Immunoglobulin FcγRIIa receptor (FCGR2A) has been implicated in various cancers, however, its role on ccRCC is not well studied. A total of 151 patients with ccRCC were recruited for the study. Cox proportional hazards regression analysis was performed to calculate the hazard radios of FCGR2A expression and tumor characteristics. Pathological changes associated with ccRCC in tumor tissue sections were analyzed by hematoxylin-eosin staining. Immunohistochemical and immunofluorescence staining were used to detect the protein expression of FCGR2A in the tissue sections. Correlation between the expression of FCGR2A and the overall survival (OS) of ccRCC patients was analyzed by biological process neural network and support vector machine. The expression of FCGR2A was significantly correlated with the TNM of tumor, family history of ccRCC and Fuhrman stage of ccRCC. Patients with high FCGR2A expression in the tumor tissue, had poorer OS than the patients with low and moderate FCGR2A expression. The Receiver operating characteristic curve showed that FCGR2A can be used as a sensitive and specific biomarker for the diagnosis of ccRCC. Western blotting revealed that the FCGR2A was expressed at higher levels in the ccRCC tissues. Biological process neural network and support vector machine fitting showed that the R2 between FCGR2A and survival time of ccRCC patients was 0.8429 and 0.7669, respectively. FCGR2A is highly expressed in ccRCC, higher expression of FCGR2A is associated with poorer OS of ccRCC.

Inhibition of apoptosis through AKT-mTOR pathway in ovarian cancer and renal cancer.

OBJECTIVE: Ovarian cancer and renal cancer are malignant tumors; however, the relationship between TTK Protein Kinase (TTK), AKT-mTOR pathway and ovarian cancer, renal cancer remains unclear. METHODS: Download GSE36668 and GSE69428 from Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed. Created protein-protein interaction (PPI) network. Used Gene Ontology analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional enrichment analysis. Gene Set Enrichment Analysis (GSEA) analysis and survival analysis were performed. Created animal model for western blot analysis. Gene Expression Profiling Interactive Analysis (GEPIA) was performed to explore the role of TTK on the overall survival of renal cancer. RESULTS: GO showed that DEGs were enriched in anion and small molecule binding, and DNA methylation. KEGG analysis presented that they mostly enriched in cholesterol metabolism, type 1 diabetes, sphingolipid metabolism, ABC transporters, etc., TTK, mTOR, p-mTOR, AKT, p-AKT, 4EBP1, p-4EBP1 and Bcl-2 are highly expressed in ovarian cancer, Bax, Caspase3 are lowly expressed in ovarian cancer, cell apoptosis is inhibited, leading to deterioration of ovarian cancer. Furthermore, the TTK was not only the hub biomarker of ovarian cancer, but also one significant hub gene of renal cancer, and its expression was up-regulated in the renal cancer. Compared with the renal cancer patients with low expression of TTK, the patients with high expression of TTK have the poor overall survival (P = 0.0021). CONCLUSION: TTK inhibits apoptosis through AKT-mTOR pathway, worsening ovarian cancer. And TTK was also one significant hub biomarker of renal cancer.

Dynamic Invariant-Specific Representation Fusion Network for Multimodal Sentiment Analysis.

Multimodal sentiment analysis (MSA) aims to infer emotions from linguistic, auditory, and visual sequences. Multimodal information representation method and fusion technology are keys to MSA. However, the problem of difficulty in fully obtaining heterogeneous data interactions in MSA usually exists. To solve these problems, a new framework, namely, dynamic invariant-specific representation fusion network (DISRFN), is put forward in this study. Firstly, in order to effectively utilize redundant information, the joint domain separation representations of all modes are obtained through the improved joint domain separation network. Then, the hierarchical graph fusion net (HGFN) is used for dynamically fusing each representation to obtain the interaction of multimodal data for guidance in the sentiment analysis. Moreover, comparative experiments are performed on popular MSA data sets MOSI and MOSEI, and the research on fusion strategy, loss function ablation, and similarity loss function analysis experiments is designed. The experimental results verify the effectiveness of the DISRFN framework and loss function.

miR-21 modification enhances the performance of adipose tissue-derived mesenchymal stem cells for counteracting urethral stricture formation.

The treatment of complicated long segment strictures remains to a challenge, and the substitution urethroplasty treatment is often accompanied by subsequent tissue fibrosis and secondary stricture formation. In situ injection of human adipose tissue-derived stem cells (hADSC) could potential be applied for prevention of urethral fibrosis, but the cells transplantation alone may be insufficient because of the complicated histopathological micro-environmental changes in the injury site. This study investigated whether miR-21 modification can improve the therapeutic efficacy of ADSCs against urethral fibrosis to limit urethral stricture recurrence. MiR-21-modified ADSCs (miR-21) were constructed via lentivirus-mediated transfer of pre-miR-21 and GFP reporter gene. In vitro results suggested that miR-21 modification can increase the angiogenesis genes expression of ADSCs and enhance its anti-oxidative effects against reactive oxygen species (ROS) damage. In vivo results showed that miR-21 modification contributes to increased urodynamic parameters and better formation of the epithelium and the muscle layer as compared to ADSCs transplantation alone groups. The results demonstrated that miR-21 modification in ADSCs could improve urethral wound healing microenvironment, enhance stem cell survival through ROS scavenging and promote the neovascularization via regulating angiogenic genes expression, which eventually increase the ADSCs' therapeutic potential for urethral wound healing.