Potential diagnostic markers and therapeutic targets for rheumatoid arthritis with comorbid depression based on bioinformatics analysis.

Background: Rheumatoid arthritis (RA) and depression are prevalent diseases that have a negative impact on the quality of life and place a significant economic burden on society. There is increasing evidence that the two diseases are closely related, which could make the disease outcomes worse. In this study, we aimed to identify diagnostic markers and analyzed the therapeutic potential of key genes. Methods: We assessed the differentially expressed genes (DEGs) specific for RA and Major depressive disorder (MDD) and used weighted gene co-expression network analysis (WGCNA) to identify co-expressed gene modules by obtaining the Gene expression profile data from Gene Expression Omnibus (GEO) database. By using the STRING database, a protein-protein interaction (PPI) network constructed and identified key genes. We also employed two types of machine learning techniques to derive diagnostic markers, which were assessed for their association with immune cells and potential therapeutic effects. Molecular docking and in vitro experiments were used to validate these analytical results. Results: In total, 48 DEGs were identified in RA with comorbid MDD. The PPI network was combined with WGCNA to identify 26 key genes of RA with comorbid MDD. Machine learning-based methods indicated that RA combined with MDD is likely related to six diagnostic markers: AURKA, BTN3A2, CXCL10, ERAP2, MARCO, and PLA2G7. CXCL10 and MARCO are closely associated with diverse immune cells in RA. However, apart from PLA2G7, the expression levels of the other five genes were associated with the composition of the majority of immune cells in MDD. Molecular docking and in vitro studies have revealed that Aucubin (AU) exerts the therapeutic effect through the downregulation of CXCL10 and BTN3A2 gene expression in PC12 cells. Conclusion: Our study indicates that six diagnostic markers were the basis of the comorbidity mechanism of RA and MDD and may also be potential therapeutic targets. Further mechanistic studies of the pathogenesis and treatment of RA and MDD may be able to identify new targets using these shared pathways.

Identification and characterization of lncRNAs and the interaction of lncRNA-mRNA in Epinephelus coioides induced with Singapore grouper iridovirus infection.

Singapore grouper iridovirus (SGIV) is a highly pathogenic double-stranded DNA virus, and the fatality rate of SGIV-infected grouper is more than 90%. Up to now, there is no effective methods to control the disease. Long non-coding RNAs (lncRNAs) might play an important role in individual growth and development, immune regulation and other life processes. In this study, lncRNAs were identified in Epinephelus coioides, an important economic aquaculture marine fish in China and Southeast Asia, and the regulatory relationships of lncRNAs and mRNA response to SGIV infection were analyzed. A total of 11,678 lncRNAs were identified and classified from the spleen and GS (grouper spleen) cells. 105 differentially expressed lncRNAs (DElncRNAs) were detected during SGIV infection. The lncRNAs and the regulated mRNAs were analyzed using co-expression network, lncRNA target gene annotation and GO enrichment. At 24 and 48 h after SGIV infection, 118 and 339 lncRNA-mRNA pairs in GS cells were detected, and 728 and 688 differentially expressed lncRNA-mRNA pairs in spleen were obtained, respectively. GO and KEGG were used to predict the DE lncRNAs' target genes, and deduce the DE lncRNAs-affected signaling pathways. In GS cells, lncRNAs might participate in cell part, binding and catalytic activity; and lncRNAs might be involved in immune system process and transcription factor activity in spleen. These data demonstrated that lncRNAs could regulate the expression of immune-related genes response to viral infection, and providing a new insight into understanding the complexity of immune regulatory networks mediated by lncRNAs during viral infection in teleost fish.

Mechanism of Sanhua Decoction in the Treatment of Ischemic Stroke Based on Network Pharmacology Methods and Experimental Verification.

OBJECTIVE: The mechanism of action of Sanhua Decoction (SHD) in the treatment of ischemic stroke (IS) was analyzed based on the network pharmacology technology, and the pharmacodynamics and key targets were verified using the rat middle cerebral artery occlusion (MCAO) model. METHODS: The GEO database was used to collect IS-related gene set S D , and DrugBank and TTD databases were used to obtain the therapeutic drug target set S T . IS disease gene set S I was collected from DisGeNET, GeneCards, and OMIM databases. These three different gene sets obtained from various sources were merged, duplicates were removed, and the resulting IS disease gene set S IS was imported into the STRING database to establish the protein-protein interaction (PPI) network. Two methods were used to screen the key targets of IS disease based on the PPI network analysis. The TCMSP database and PubChem were applied to retrieve the main chemical components of SHD, and the ACD/Labs software and the SwissADME online system were utilized for ADMET screening. HitPick, SEA, and SwissTarget Prediction online systems were used to predict the set of potential targets for SHD to treat IS. The predicted set of potential targets and the IS disease gene set were intersected. Subsequently, the set of potential targets for SHD treatment of IS was identified, the target information was confirmed through the UniProt database, and finally, the component-target data set for SHD treatment of IS was obtained. clusterProfiler was used for GO function annotation and KEGG pathway enrichment analysis on the target set of SHD active ingredients. A rat MCAO model was established to evaluate the pharmacodynamics of SHD in the treatment of IS, and Western blot analysis assessed the level of proteins in the related pathways. RESULTS: This study obtained 1,009 IS disease gene sets. PPI network analysis identified 12 key targets: AGT, SAA1, KNG1, APP, GNB3, C3, CXCR4, CXCL12, CXCL8, CXCL1, F2, and EDN1. Database analyses retrieved 40 active ingredients and 47 target genes in SHD. The network proximity algorithm was used to optimize the six key components in SHD. KEGG enrichment showed that the signaling pathways related to IS were endocrine resistance, estrogen, TNF signal pathway, and AGEs/RAGE. Compound-disease-target regulatory network analysis showed that AKT1, IL-6, TNF-α, TP53, VEGFA, and APP were related to the treatment of IS with SHD. Animal experiments demonstrated that SHD significantly reduces the neurological function of rat defect symptoms (P < 0.05), the area of cerebral avascular necrosis, and neuronal necrosis while increasing the levels of IL-6 and APP proteins (P < 0.05) and reducing the levels of AKT1 and VEGFA proteins (P < 0.05). CONCLUSION: The effective components of SHD may regulate multiple signaling pathways through IL-6, APP, AKT1, and VEGFA to reduce brain damage and inflammatory damage and exert a neuroprotective role in the treatment of IS diseases. Thus, this study provides a feasible method to study the pharmacological mechanism of traditional Chinese medicine compound prescriptions and a theoretical basis for the development of SHD into a new drug for IS treatment.

Evaluating the Therapeutic Mechanisms of Selected Active Compounds in Houttuynia cordata Thunb. in Pulmonary Fibrosis via Network Pharmacology Analysis.

Pulmonary fibrosis, a common outcome of pulmonary interstitial disease of various different etiologies, is one of the most important causes of respiratory failure. Houttuynia cordata Thunb. (family: Saururaceae) (H. cordata), as has been reported, is a Chinese herbal medicine commonly used to treat upper respiratory tract infection and bronchitis. Our previous study has proven that sodium houttuyfonate (an additional compound from sodium bisulfite and houttuynin) had beneficial effects in the prevention of pulmonary fibrosis (PF) induced by bleomycin (BLM) in mice. In the present study, network pharmacology was used to investigate the efficiency and potential mechanisms of H. cordata in PF treatment. Upon manual collection from the literature and databases such as TCMSP and TCM-ID, 10 known representative ingredients of H. cordata species were screened. Then, the prediction of the potential active ingredients, action targets, and signaling pathways were conducted through the Gene Ontology (GO), protein-protein interaction (PPI),and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The results of network pharmacology prediction suggested that H. cordata may act through multiple signaling pathways to alleviate PF, including the phosphatidylinositol 3-kinase-protein kinase B (PI3K/AKT) pathways, mitogen-activated protein kinase (MAPK) pathways, the tumor necrosis factor (TNF) pathways, and interleukin-17 (IL-17) signaling pathways. Molecular docking experiments showed that the chemical constituents of H. cordata had good affinity with TNF, MAPK1, and AKT1, and using lipopolysaccharide (LPS)-induced A549 cells, a model was established to verify the anti-pulmonary fibrosis effects and related mechanisms of H. cordata-relevant constituents. Finally, these evidences collectively suggest H. cordata may alleviate PF progression via PI3K/Akt, MAPK, and TNF signaling pathways and provide novel insights to verify the mechanism of H. cordata in the treatment of PF.

Research on the Mechanism of Qushi Huayu Decoction in the Intervention of Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Molecular Docking Technology.

OBJECTIVE: To use network pharmacology and molecular docking technology in predicting the main active ingredients and targets of Qushi Huayu Decoction (QHD) treatment in Nonalcoholic Fatty Liver Disease (NAFLD) and explore the potential mechanisms of its multi-component-multi-target-multi-pathway. MATERIALS AND METHODS: The main chemical components of QHD were searched using traditional Chinese medicine system pharmacology technology platform (TCMSP) and PubChem database. The main chemical components of the prescription were ADMET screened by the ACD/Labs software. The main active ingredient was screened by 60% oral bioavailability, and 60% of "bad" ingredients were removed from the drug-like group. Swiss Target Prediction, the SEA, and HitPick systems were sequentially used to search for the target of each active ingredient, and a network map of the QHD's target of the active ingredient was constructed. Genome annotation database platforms (GeneCards, OMIM, and DisGeNET) were used to predict action targets related to fatty liver disease. "Drug-Disease-Target" network diagram could be visualized with the help of Cytoscape (3.7.1) software. UniProt and STRING database platforms were used to build a protein interaction network. The KEGG signal pathway and DAVID platform were analyzed for biological process enrichment. RESULTS: A total of 128 active ingredients and 275 corresponding targets in QHD were discovered through screening. 55 key target targets and 27 important signaling pathways were screened, such as the cancer pathway, P13K-AKT signaling pathway, PPAR signaling pathway, and other related signaling pathways. CONCLUSIONS: The present study revealed the material basis of QHD and discussed the pharmacological mechanism of QHD in fatty liver, thus providing a scientific basis for the clinical application and experimental research of QHD in the future.

Stochastic determination of the spatial variation of potentially pathogenic bacteria communities in a large subtropical river.

Understanding the composition and assembly mechanism of waterborne pathogen is essential for preventing the pathogenic infection and protecting the human health. Here, based on 16S rRNA sequencing, we investigated the composition and spatial variation of potentially pathogenic bacteria from different sections of the Pearl River, the most important source of water for human in Southern China. The results showed that the potential pathogen communities consisted of 6 phyla and 64 genera, covering 11 categories of potential pathogens mainly involving animal parasites or symbionts (AniP), human pathogens all (HumPA), and intracellular parasites (IntCelP). Proteobacteria (75.87%) and Chlamydiae (20.56%) were dominant at the phylum level, and Acinetobacter (35.01%) and Roseomonas (8.24%) were dominant at the genus level. Multivariate analysis showed that the potential pathogenic bacterial community was significantly different among the four sections in the Pearl River. Both physicochemical factors (e.g., NO3-N, and suspended solids) and land use (e.g., urban land and forest) significantly shaped the pathogen community structure. However, spatial effects contributed more to the variation of pathogen community based on variation partitioning and path analysis. Null model based normalized stochasticity ratio analysis further indicated that the stochastic process rather than deterministic process dominated the assembly mechanisms by controlling the spatial patterns of potential pathogens. In conclusion, high-throughput sequencing shows great potential for monitoring the potential pathogens, and provided more comprehensive information on the potentially pathogenic community. Our study highlighted the importance of considering the influences of dispersal-related processes in future risk assessments for the prevention and control of pathogenic bacteria.

Transcriptome analysis revealed changes of multiple genes involved in muscle hardness in grass carp (Ctenopharyngodon idellus) fed with faba bean meal.

An 8-week feeding trial and transcriptome analysis were conducted to investigate the potential mechanism of muscle-hardening caused by faba bean in grass carp (Ctenopharyngodon idellus). Ordinary grass carp (fed with practical diet) and crisp grass carp (fed with faba bean meal) groups were designed. Lower water holding capacity and higher some texture parameters were observed in the muscle of crisp grass carp compared with another group. 19.62 GB clean reads were generated, and total 1354 genes exhibiting differentially expression were identified (FDR < 0.05). Genes function enrichment revealed up-regulated genes in crisp grass carp mainly in response to myofibroblast proliferation, while down-regulated genes in response to immune regulation. Consistent with this, the tight junction pathway and the NF-κB signaling pathway were likewise significantly enriched. In summary, this study identified several candidate genes and putative signaling pathways deserving further investigation to the mechanism of muscle-hardening in fish fed with faba bean.

Intestinal Microbiota of Grass Carp Fed Faba Beans: A Comparative Study.

Many reports of the intestinal microbiota of grass carp have addressed the microbial response to diet or starvation or the effect of microbes on metabolism; however, the intestinal microbiota of crisp grass carp has yet to be elucidated. Moreover, the specific bacteria that play a role in the crispiness of grass carp fed faba beans have not been elucidated. In the present study, 16S sequencing was carried out to compare the intestinal microbiota in the fore-, mid- and hind-intestine segments of grass carp following feeding with either faba beans or formula feed. Our results showed that (1) the hind-intestine presented significant differences in diversity relative to the fore- or midintestine and (2) faba beans significantly increased the diversity of intestinal microbiota, changed the intestinal microbiota structure (Fusobacteria was reduced from 64.26% to 18.24%, while Proteobacteria was significantly increased from 17.75% to 51.99%), and decreased the metabolism of energy, cofactors and vitamins in grass carp. Furthermore, at the genus and species levels, Acinetobacter accounted for 15.09% of the microbiota, and Acinetobacter johnsonii and Acinetobacter radioresistens constituted 3.41% and 2.99%, respectively, which indicated that Acinetobacter of the family Moraxellaceae contributed to changes in the intestinal microbiota structure and could be used as a potential biomarker. These results may provide clues at the intestinal microbiota level to understanding the mechanism underlying the crispiness of grass carp fed faba beans.

The mitochondrial genome of Sinibotia robusta of pearl river (Cypriniformes: Cobitidae).

We present the complete mitochondrial genome of Sinibotia robusta in this study. The mitochondrial genome is 16 575 bp in length and consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a control region. The nucleotide compositions of the light strand are 31.9% A, 25.7% T, 26.9% C and 15.5% G. Except ND6 and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. The genus most related to Botia Gray was Leptobotia Bleeker and Parabotia Sauvage, as revealed by phylogenetic relationships derived using a maximum likelihood tree. This mitogenome will help elucidate the morphological systematic complexity and phylogenetic structure of Cobitidae and related species.

The complete mitochondrial genome of Mastacembelus aculeatus (Cypriniformes, Mastacembelidae) from the Pearl River, China.

In this paper, the complete mitochondrial DNA (mtDNA) sequence of Mastacembelus aculeatus was determined. The mitochondrial genome is 16 543 bp in length, including 13 protein-coding genes, 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and a non-coding control region as those found in other vertebrates, with the gene identical to that of typical vertebrates. The overall base composition of the heavy strand is 30.0% A, 26.4% T, 14.8% C, and 28.7% G, with an AT bias of 56.49%. Phylogeny of M. aculeatus suggested more close relationship with Mastacembelus armatus and Mastacembelus favus. The complete mitogenome may add new information to existing mitogenome data for Mastacembelidae, providing further information that may contribute to their taxonomy, evolution, and phylogeny.

Therapeutic efficacy of fuzheng-huayu tablet based traditional chinese medicine syndrome differentiation on hepatitis-B-caused cirrhosis: a multicenter double-blind randomized controlled trail.

Aim. To evaluate and predict the therapeutic efficacy of Fuzheng-Huayu tablet (FZHY) based traditional Chinese Medicine (TCM) syndrome differentiation or TCM symptoms on chronic hepatitis B caused cirrhosis (HBC). Methods. The trial was designed according to CONSORT statement. It was a multi-center, double-blind, randomized, placebo-controlled trail. Several clinical parameters, Child-Pugh classification and TCM symptoms were detected and evaluated. The FZHY efficacy was predicted by an established Bayes forecasting method following the Bayes classification model. Results. The levels of HA and TCM syndrome score in FZHY group were significantly decreased (P < 0.05) compared to placebo group, respectively. The efficacy of FZHY on TCM syndrome score in HBC patients with some TCM syndromes was better. In TCM syndrome score evaluation, there were 53 effective and 22 invalid in FZHY group. TCM symptoms predicted FZHY efficacy on HBC were close to Child-Pugh score prediction. Conclusion. FZHY decreases the levels of HA and TCM syndrome scores, improves the life quality of HBC patients. Moreover, there were different therapeutic efficacies among different TCM syndromes, indicating that accurate TCM syndrome differentiation might guide the better TCM treatment. Furthermore, the FZHY efficacy was able to predict by Bayes forecasting method through the alteration of TCM symptoms.

Comparative sperm ultrastructure of three species in Siniperca (Teleostei: Perciformes: Sinipercidae).

Siniperca chuatsi, Siniperca kneri, and Siniperca scherzeri are three of the most economically important sinipercid species. The ultrastructure and morphology of the mature spermatozoa of them are examined using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The sperm consists of an acrosome-less head, a short midpiece and a long flagellum. Ultrastructurally, it has a homogeneously electron-dense nucleus in a granular pattern with nuclear lucent and a nuclear fossa excluding the centriolar complex. One to four mitochondria with lamellar cristae encircle the basal body of the flagellum in the midpiece. The cytoplasm surrounding the centrioles and the cylindric cytoplasmic channel contains glycogen granules and vesicles. Comprising the conventional 9+2 axoneme, vesicles and lateral fins, the sperm flagellum is inserted laterally on the nucleus, therefore the spermatozoon is asymmetrical. All of the spermatozoa of the three species are of the primitive or ect-aquasperm form and conform to the teleostean type II spermatozoa instead of the previously supposed type I. Variations in the shape of the heads, angles between the two centrioles, location of the cytoplasmic vesicles, mitochondrial number and structural characteristics of the lateral fins are notable among the three species. S. chuatsi is a sister-group of the other two species and is the most differentiated. The present study provides fresh insights to the comparative spermatology of Siniperca fishes and will be useful to the existing knowledge of the sinipercid fishes in systematic characters, biodiversity conservation and reproduction.

[An evaluation method for analysis of correlation between traditional Chinese medicine syndrome and seasonal changes of weather based on information entropy].

OBJECTIVE: A method based on dubious condition of information entropy was introduced and applied to discuss a complexity problem in the analysis of correlation between traditional Chinese medicine (TCM) syndrome and season. METHODS: Eight hundred and seventy one cases of chronic virus hepatitis B (hepatitis B) with TCM clinical data were analyzed by information entropy method. RESULTS: It was found that hepatitis B with Yin deficiency of liver and kidney happened more often in summer than in other seasons. CONCLUSION: It is inferred that the difference of seasons may influence the variation of TCM syndromes.