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DNA methylation plays a significant role in regulating transcription and exhibits a systematic change with age. These changes can be used to predict an individual's age. First, to identify methylation sites associated with biological age; second, to construct a biological age prediction model and preliminarily explore the biological significance of methylation-associated genes using machine learning. A biological age prediction model was constructed using human methylation data through data preprocessing, feature selection procedures, statistical analysis, and machine learning techniques. Subsequently, 15 methylation data sets were subjected to in-depth analysis using SHAP, GO enrichment, and KEGG analysis. XGBoost, LightGBM, and CatBoost identified 15 groups of methylation sites associated with biological age. The cg23995914 locus was identified as the most significant contributor to predicting biological age by calculating SHAP values. Furthermore, GO enrichment and KEGG analyses were employed to initially explore the methylated loci's biological significance. [ABSTRACT FROM AUTHOR]

The objective of this study is to analyze environmental genetic selection signals in large-scale sheep populations with conflicting environmental adaptations, aiming to identify and isolate genes associated with environmental adaptations in sheep populations. Kirghiz sheep, which inhabit high-altitude environments year-round, demonstrate the ability to adapt to extreme conditions. In this study, 42 Kirghiz sheep, 24 Tien-Shan in Kyrgyzstan sheep, 189 Qira black sheep, and 160 Chinese Merino sheep were genotyped using Illumina Ovine SNP50K chip. Regions exhibiting a selection signal threshold of 5%, as well as PI analysis and haplotype statistical scanning gene data were annotated, and intersecting genes were identified as candidate genes. Through Fst and haplotype statistical analysis revealed the key gene PDGFD and its vicinity's impact on fat deposition in sheep tails. Additionally, Fst and PI analysis uncovered genes related to high-altitude adaptation as well as those linked to animal growth and reproduction. Further GO and KEGG enrichment pathway analyses unveiled pathways associated with high-altitude adaptation such as negative regulation of peptidyl-tyrosine phosphorylation and xenobiotic metabolism processes.This investigation into the adaptability of Kirghiz sheep provides theoretical support and practical guidance for the conservation and genetic enhancement of Kirghiz sheep germplasm resources. [ABSTRACT FROM AUTHOR]

Abstract DNA methylation plays a significant role in regulating transcription and exhibits a systematic change with age. These changes can be used to predict an individual’s age. First, to identify methylation sites associated with biological age; second, to construct a biological age prediction model and preliminarily explore the biological significance of methylation-associated genes using machine learning. A biological age prediction model was constructed using human methylation data through data preprocessing, feature selection procedures, statistical analysis, and machine learning techniques. Subsequently, 15 methylation data sets were subjected to in-depth analysis using SHAP, GO enrichment, and KEGG analysis. XGBoost, LightGBM, and CatBoost identified 15 groups of methylation sites associated with biological age. The cg23995914 locus was identified as the most significant contributor to predicting biological age by calculating SHAP values. Furthermore, GO enrichment and KEGG analyses were employed to initially explore the methylated loci’s biological significance.

[Objective] SRO gene family is a class of plant-specific transcription factors, which plays an important role in plant growth and development and stress response. The study of the SRO gene family in Brassica juncea L. provides a theoretical basis for analyzing the function of SRO genes in B. juncea L. and its genetic improvement. [Method] Bioinformatics was used to identify members of the SRO gene family in the genomes of two types of oilseed mustard and vegetable mustard, the software and database such as TBtools, MEGA, Cytoscape, NCBI, STRING, EggNOG were used for the analysis of physicochemical properties, sequence characterization, evolutionary relationships, regulatory networks, etc., as well as RT-qPCR to analyze the expression patterns under salt stress. [Result] There were differences in the number of members of the SRO gene family between the two types of B. juncea L., and they belonged to two major classes. Among them, class A SRO proteins contained WWE, PARP and RST structural domains, whereas class B proteins were lack of WWE domains. The promoter region of the SRO genes contained a variety of cis-acting elements for abiotic stress response and hormone response. The microRNA-BjuSRO-target genes constructed a complex regulatory network, which was involved in apoptosis, root morphogenesis, immune response, cellular response to heterologous stimuli, and response to reactive oxygen species, and other biological processes. The RT-qPCR results showed that BjuVA1a, BjuVA1e, BjuVA2a, BjuVA3a, BjuVB1b, and BjuVA2a were significantly upregulated under salt stress. [Conclusion] The SRO gene family in the mustard has functional diversity, and BjuVA1a, BjuVA1e, BjuVA2a, BjuVA3a, BjuVB1b, and BjuVA2a are closely related to the response to salt stress, which can be used as candidate genes for breeding new salt-tolerant varieties of B. juncea L. [ABSTRACT FROM AUTHOR]

【Objective】The transparent traits in Pterophyllum scalare has high economic and scientific value. This article aims to explore the differential expression genes (DEG) between transparent gill cover (TGC) and opaque gill cover (OGC) tissues of P. scalare, and explore the relevant signaling pathways affecting the transparent gill cover traits of P. scalare, so as to provide a theoretical basis for the subsequent screening of key genes regulating the transparent gill cover trait of P. scalare and related mechanism studies.【Method】The gill cover tissue of P. scalare (strain: red-topped tri-color) was selected as the research material, and 6 samples were selected from each group of OGC and TGC. Transcriptomic sequencing was carried out based on the Illumina Novaseq 6000 sequencing platform with using Fastp to perform quality control on raw sequencing data. The transcript and the corresponding single gene (Unigene) were obtained by de novo assembling of quality control data by Trinity software, and the initial assembly sequence was deredundancy analysis and result evaluation by CD-HIT software and BUSCO software, respectively. After redundancy, unigene were functionally annotated based on sequence homology. RSEM software was used to calculate the expression of unigene in each sample. DEGs between OGC and TGC were calculated using DESeq2 software. GO and KEGG pathway enrichment analysis was performed on DEGs using Goatools software and KOBAS software, respectively.【Result】(1) After quality control of sequencing data, the average error rate of each sample sequencing base was less than 0.1%, Q20 was higher than 97.78%, and Q30 was higher than 93.58%, and the sequencing quality was reliable. After de novo assembling, 200 303 transcripts were obtained, corresponding to 123 178 unigenes. After deredundancy analysis, a total of 147 932 transcripts are obtained, corresponding to 108 070 unigenes, with an average length of 991.85 bp and N50 is 2 430 bp. (2) A total of 40 180 unigenes were annotated in the NR, KEGG, eggNOG, GO, Pfam, and Swiss-Prot databases, accounting for 37.98% of the total, of which 10 747 genes were annotated simultaneously in 6 databases, accounting for 26.75% of the total. (3) TGC relative to OGC has a total of 432 DEGs, of which TGC significantly up-regulated 267 genes and down-regulated 165 genes relative to OGC. (4) GO enrichment results showed that 432 DEGs were mainly enriched in 5 biological pathways: IMP biosynthesis, IMP metabolism, "de novo" IMP biosynthesis, amino acid binding, and modified amino acid binding. (5) KEGG enrichment results showed that 432 DEGs were mainly enriched in 7 biological pathways: neuroactive ligand-receptor interaction, tyrosine metabolism, purine metabolism, a carbon pool of folate, phenylalanine metabolism, nucleotide metabolism, ubiquinone and other terpene-quinone biosynthesis.【Conclusion】432 genes related to the transparent gill cover trait of P. scalare were obtained by transcriptomic sequencing, which were mainly involved in 12 signaling pathways. The results will provide reference for the mining and functional study of genes related to transparent gill cover trait in P. scalare.

【Objective】The transparent traits in Pterophyllum scalare has high economic and scientific value. This article aims to explore the differential expression genes (DEG) between transparent gill cover (TGC) and opaque gill cover (OGC) tissues of P. scalare, and explore the relevant signaling pathways affecting the transparent gill cover traits of P. scalare, so as to provide a theoretical basis for the subsequent screening of key genes regulating the transparent gill cover trait of P. scalare and related mechanism studies.【Method】The gill cover tissue of P. scalare (strain: red-topped tri-color) was selected as the research material, and 6 samples were selected from each group of OGC and TGC. Transcriptomic sequencing was carried out based on the Illumina Novaseq 6000 sequencing platform with using Fastp to perform quality control on raw sequencing data. The transcript and the corresponding single gene (Unigene) were obtained by de novo assembling of quality control data by Trinity software, and the initial assembly sequence was deredundancy analysis and result evaluation by CD-HIT software and BUSCO software, respectively. After redundancy, unigene were functionally annotated based on sequence homology. RSEM software was used to calculate the expression of unigene in each sample. DEGs between OGC and TGC were calculated using DESeq2 software. GO and KEGG pathway enrichment analysis was performed on DEGs using Goatools software and KOBAS software, respectively. 【Result】(1) After quality control of sequencing data, the average error rate of each sample sequencing base was less than 0.1%, Q20 was higher than 97.78%, and Q30 was higher than 93.58%, and the sequencing quality was reliable. After de novo assembling, 200 303 transcripts were obtained, corresponding to 123 178 unigenes. After deredundancy analysis, a total of 147 932 transcripts are obtained, corresponding to 108 070 unigenes, with an average length of 991.85 bp and N50 is 2 430 bp. (2) A total of 40 180 unigenes were annotated in the NR, KEGG, eggNOG, GO, Pfam, and Swiss-Prot databases, accounting for 37.98% of the total, of which 10 747 genes were annotated simultaneously in 6 databases, accounting for 26.75% of the total. (3) TGC relative to OGC has a total of 432 DEGs, of which TGC significantly up-regulated 267 genes and down-regulated 165 genes relative to OGC. (4) GO enrichment results showed that 432 DEGs were mainly enriched in 5 biological pathways: IMP biosynthesis, IMP metabolism, “de novo” IMP biosynthesis, amino acid binding, and modified amino acid binding. (5) KEGG enrichment results showed that 432 DEGs were mainly enriched in 7 biological pathways: neuroactive ligand-receptor interaction, tyrosine metabolism, purine metabolism, a carbon pool of folate, phenylalanine metabolism, nucleotide metabolism, ubiquinone and other terpene-quinone biosynthesis. 【Conclusion】432 genes related to the transparent gill cover trait of P. scalare were obtained by transcriptomic sequencing, which were mainly involved in 12 signaling pathways. The results will provide reference for the mining and functional study of genes related to transparent gill cover trait in P. scalare. [ABSTRACT FROM AUTHOR]

The study aims to analyze genetic mutation and clinical characteristics and study their correlation with survival prognosis of patients with myelodysplastic syndromes (MDS). Moreover, the differential DNA methylation profiles between TET2 mutated (Mut)/ASXL1 wild-type (WT) and TET2-Mut/ASXL1-Mut MDS samples were investigated to explore the mechanism of MDS patients with TET2/ASXL1 mutations. The clinical data of 195 patients diagnosed with MDS were selected and statistically analyzed. The DNA methylation sequencing data set was obtained from the GEO and bioinformatics analyzed. Of the 195 MDS patients, 42 (21.5%) carried TET2 mutations. 81% of TET2-Mut patients could detect comutated genes. The most commonly comutated gene in MDS patients with TET2-Mut was ASXL1, which had a tendency towards poorer prognosis (P = 0.08). GO analysis showed that highly methylated differentially methylated genes (DMGs) was mainly enriched in biological processes such as cell surface receptor signal pathway and cell secretion. Hypomethylated DMGs was mainly enriched in cell differentiation and cell development. KEGG analysis showed that hypermethylated DMGs was mainly enriched in Ras signal pathway and MAPK signal pathway. Hypomethylated DMGs was mainly enriched in extracellular matrix receptor interaction and focal adhesion. PPI network analysis identified 10 hub genes of hypermethylated and hypomethylated DMGs that may be associated with patients with TET2-Mut/ASXL1-Mut respectively. Our results illustrate the interrelationships between genetic mutations and clinical phenotypes and disease outcomes, with substantial potential for clinical application. Differentially methylated hub genes might represent potential biomarkers and provide novel insights and possible targets for MDS with double TET2/ASXL1 mutations. [ABSTRACT FROM AUTHOR]

Broiler skeletal muscle growth is significantly influenced by miRNAs. Our earlier research demonstrated that miR-24-3p significantly suppressed the proliferation of chicken myoblasts while promoting their differentiation. The purpose of this study is to investigate miR-24-3p potential target genes in chickens. We collected myoblasts of Jinghai yellow chicken and transfected four samples with mimics of miR-24-3p and another four samples with mimic NC (negative control) for RNA-seq. We obtained 54.34 Gb of raw data in total and 50.79 Gb of clean data remained after filtering. Moreover, 11,635 genes were found to be co-expressed in these two groups. The mimic vs. NC comparison group contained 189 DEGs in total, 119 of which were significantly up-regulated and 70 of which were significantly down-regulated. Important biological process (BP) terminology such as nuclear chromosomal segregation, reproduction, and nuclear division were discovered by GO enrichment analysis for DEGs in the mimic vs. NC comparison group. KEGG pathway analysis showed that focal adhesion, cytokine–cytokine receptor interaction, the TGF-β signaling pathway, and the MAPK signaling pathway were enriched in the top 20. Variation site analysis illustrated the SNP (single nucleotide polymorphisms) and INDEL (insertion–deletion) in the tested samples. By comparing the target genes predicted by miRDB (MicroRNA target prediction database) and TargetScan with the 189 DEGs found by the transcriptome sequencing, we discovered two up-regulated DEGs (NEURL1 and IQSEC3) and two down-regulated DEGs (REEP1 and ST6GAL1). Finally, we carried out qPCR experiments on eight DEGs and discovered that the qPCR results matched the sequencing outcomes. These findings will aid in identifying potential miR-24-3p target genes in chicken skeletal muscle and offer some new directions for upcoming research on broiler breeding. [ABSTRACT FROM AUTHOR]

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs, deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, the mixture of three herbs had a combinational effect. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFA-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

The Wenshenyang recipe (WSYR) has the effect of treating infertility, but the mechanisms underlying this activity have not been fully elucidated. In this study, network pharmacology and RNA sequencing were combined, with databasebased "dry" experiments and transcriptome analysis-based "wet" experiments used conjointly to analyse the mechanism of WSYR in the treatment of infertility. In the dry analysis, 43 active compounds in WSYR and 44 therapeutic targets were obtained through a database search, 15 infertility pathways were significantly enriched, and key targets, such as ESR1, TP53, AKT1, IL-6, and IL-10 were identified. Then the wet experiments were performed to detect the expression changes of the 412 genes from 15 infertility pathways identified by dry analysis. HK-2 cells were treated with the three herbs of WSYR and subjected to targeted RNA sequencing. Based on the results, 92 of the 412 genes in 15 infertility pathways were identified as DEGs. Additionally, key targets, such as ESR2, STAT1, STAT3, and IL6, were also identified in the wet experiments. RT-qPCR experiments further verified that WSYR played an antiinflammatory role by upregulating IL-4 and IL-10 and Epimedium brevicornu Maxim (Yinyanghuo) showed broader effect than Drynaria fortunei (Kunze) J. Sm (Gusuibu) and Cistanche deserticola Y.C.Ma (Roucongrong). By screening compounds of WSYR using molecular docking models of ESR1 and ESR2, it was further found that xanthogalenol in Gusuibu, arachidonate in Roucongrong, and anhydroicaritin in Yinyanghuo had good affinity for estrogen receptors. These findings provide evidence for an estrogenregulating role of the three herbs in WSYR. [ABSTRACT FROM AUTHOR]

Objective: To investigate the differential gene expression and function of peripheral blood monocytes in patients with coronary heart disease and acute myocardial infarction. Methods: Patients receiving coronary angiography in Kunming First People’s Hospital from September 2020 to September 2021 were collected and total RNA of peripheral blood monocytes was extracted. DNBSEQ platform was used for second-generation highthroughput sequencing. We tested and screened differentially expressed genes, and made KEGG and GO enrichment analysis. Results: There were 89 differentially expressed genes,67 up-regulated genes and 22 downregulated genes in acute myocardial infarction group compared with normal coronary artery group. Among them, there were 14 differential lncRNAs, 72 differential mRNAs, and 3 differential circRNAs. KEGG pathway enrichment analysis, KEGG disease enrichment analysis and KEGG molecular enrichment analysis were completed. GO cell composition enrichment analysis, GO cell function enrichment analysis and GO biological process molecular enrichment analysis were completed. Conclusions: 10 mRNAs,6 lncRNAs,and 2 circRNAs with significant differences were screened. The enrichment analysis involves infection,transcriptional disorder,PI3K Akt signaling pathway, lipid synthesis, phagocytic vesicle cavity, extracellular matrix, lipopolysaccharide binding, etc., which may be related to the occurrence and development of coronary atherosclerosis and the occurrence of acute thrombotic events. [ABSTRACT FROM AUTHOR]

The objective of this study is to analyze environmental genetic selection signals in large-scale sheep populations with conflicting environmental adaptations, aiming to identify and isolate genes associated with environmental adaptations in sheep populations. Kirghiz sheep, which inhabit high-altitude environments year-round, demonstrate the ability to adapt to extreme conditions. In this study, 42 Kirghiz sheep, 24 Tien-Shan in Kyrgyzstan sheep, 189 Qira black sheep, and 160 Chinese Merino sheep were genotyped using Illumina Ovine SNP50K chip. Regions exhibiting a selection signal threshold of 5%, as well as PI analysis and haplotype statistical scanning gene data were annotated, and intersecting genes were identified as candidate genes. Through Fst and haplotype statistical analysis revealed the key gene PDGFD and its vicinity's impact on fat deposition in sheep tails. Additionally, Fst and PI analysis uncovered genes related to high-altitude adaptation as well as those linked to animal growth and reproduction.Further GO and KEGG enrichment pathway analyses unveiled pathways associated with high-altitude adaptation such as negative regulation of peptidyl-tyrosine phosphorylation and xenobiotic metabolism processes.This investigation into the adaptability of Kirghiz sheep provides theoretical support and practical guidance for the conservation and genetic enhancement of Kirghiz sheep germplasm resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Zhu, Zhang, Wang, Li, Zhou, Han, Yang, Peng, Han, Zhang, Zheng and Liu.)

Critical in revealing cell heterogeneity and identifying new cell subtypes, cell clustering based on single-cell RNA sequencing (scRNA-seq) is challenging. Due to the high noise, sparsity, and poor annotation of scRNA-seq data, existing state-of-the-art cell clustering methods usually ignore gene functions and gene interactions. In this study, we propose a feature extraction method, named FEGFS, to analyze scRNA-seq data, taking advantage of known gene functions. Specifically, we first derive the functional gene sets based on Gene Ontology (GO) terms and reduce their redundancy by semantic similarity analysis and gene repetitive rate reduction. Then, we apply the kernel principal component analysis to select features on each non-redundant functional gene set, and we combine the selected features (for each functional gene set) together for subsequent clustering analysis. To test the performance of FEGFS, we apply agglomerative hierarchical clustering based on FEGFS and compared it with seven state-of-the-art clustering methods on six real scRNA-seq datasets. For small datasets like Pollen and Goolam, FEGFS outperforms all methods on all four evaluation metrics including adjusted Rand index (ARI), normalized mutual information (NMI), homogeneity score (HOM), and completeness score (COM). For example, the ARIs of FEGFS are 0.955 and 0.910, respectively, on Pollen and Goolam; and those of the second-best method are only 0.938 and 0.910, respectively. For large datasets, FEGFS also outperforms most methods. For example, the ARIs of FEGFS are 0.781 on both Klein and Zeisel, which are higher than those of all other methods but slight lower than those of SC3 (0.798 and 0.807, respectively). Moreover, we demonstrate that CMF-Impute is powerful in reconstructing cell-to-cell and gene-to-gene correlation and in inferring cell lineage trajectories. As for application, take glioma as an example; we demonstrated that our clustering methods could identify important cell clusters related to glioma and also inferred key marker genes related to these cell clusters. [ABSTRACT FROM AUTHOR]

Critical in revealing cell heterogeneity and identifying new cell subtypes, cell clustering based on single-cell RNA sequencing (scRNA-seq) is challenging. Due to the high noise, sparsity, and poor annotation of scRNA-seq data, existing state-of-the-art cell clustering methods usually ignore gene functions and gene interactions. In this study, we propose a feature extraction method, named FEGFS, to analyze scRNA-seq data, taking advantage of known gene functions. Specifically, we first derive the functional gene sets based on Gene Ontology (GO) terms and reduce their redundancy by semantic similarity analysis and gene repetitive rate reduction. Then, we apply the kernel principal component analysis to select features on each non-redundant functional gene set, and we combine the selected features (for each functional gene set) together for subsequent clustering analysis. To test the performance of FEGFS, we apply agglomerative hierarchical clustering based on FEGFS and compared it with seven state-of-the-art clustering methods on six real scRNA-seq datasets. For small datasets like Pollen and Goolam, FEGFS outperforms all methods on all four evaluation metrics including adjusted Rand index (ARI), normalized mutual information (NMI), homogeneity score (HOM), and completeness score (COM). For example, the ARIs of FEGFS are 0.955 and 0.910, respectively, on Pollen and Goolam; and those of the second-best method are only 0.938 and 0.910, respectively. For large datasets, FEGFS also outperforms most methods. For example, the ARIs of FEGFS are 0.781 on both Klein and Zeisel, which are higher than those of all other methods but slight lower than those of SC3 (0.798 and 0.807, respectively). Moreover, we demonstrate that CMF-Impute is powerful in reconstructing cell-to-cell and gene-to-gene correlation and in inferring cell lineage trajectories. As for application, take glioma as an example; we demonstrated that our clustering methods could identify important cell clusters related to glioma and also inferred key marker genes related to these cell clusters.

Abstract Background Tail-anchored membrane proteins (TAMPs) differ from other integral membrane proteins, because they contain a single transmembrane domain at the extreme carboxyl-terminus and are therefore obliged to target to membranes post-translationally. Although 3–5% of all transmembrane proteins are predicted to be TAMPs only a small number are well characterized. Results To identify novel putative TAMPs across different species, we used TAMPfinder software to identify 859, 657 and 119 putative TAMPs in human (Homo sapiens), plant (Arabidopsis thaliana), and yeast (Saccharomyces cerevisiae), respectively. Bioinformatics analyses of these putative TAMP sequences suggest that the list is highly enriched for authentic TAMPs. To experimentally validate the software predictions several human and plant proteins identified by TAMPfinder that were previously uncharacterized were expressed in cells and visualized at subcellular membranes by fluorescence microscopy and further analyzed by carbonate extraction or by bimolecular fluorescence complementation. With the exception of the pro-apoptotic protein harakiri, which is, peripherally bound to the membrane this subset of novel proteins behave like genuine TAMPs. Comprehensive bioinformatics analysis of the generated TAMP datasets revealed previously unappreciated common and species-specific features such as the unusual size distribution of and the propensity of TAMP proteins to be part of larger complexes. Additionally, novel features of the amino acid sequences that anchor TAMPs to membranes were also revealed. Conclusions The findings in this study more than double the number of predicted annotated TAMPs and provide new insights into the common and species-specific features of TAMPs. Furthermore, the list of TAMPs and annotations provide a resource for further investigation.

Abstract Background MiRNAs can regulate gene expression directly or indirectly, and long noncoding RNAs as competing endogenous RNA (ceRNAs) can bind to miRNAs competitively and affect mRNA expression. The ceRNA network is still unclear in breast cancer. In this study, a ceRNA network was constructed, and new treatment and prognosis targets and biomarkers for breast cancer were explored. Methods A total of 1 096 cancer tissues and 112 adjacent normal tissues to cancer from the TCGA database were used to screen out significant differentially expressed mRNAs (DEMs), lncRNAs (DELs), and miRNAs (DEMis) to construct a ceRNA network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict potential functions. Survival analysis was performed to predict which functions were significant for prognosis. Results From the analysis, 2 139 DEMs, 1 059 DELs, and 84 DEMis were obtained. Targeting predictions for DEMis‐DELs and DEMis‐DEMs can yield 26 DEMs, 90 DELs, and 18 DEMis. We performed GO enrichment analysis, and the results showed that the upregulated DEMs were involved in nucleosomes, extracellular regions, and nucleosome assembly, while the downregulated DEMs were mainly involved in Z disk, muscle contraction, and structural constituents of muscle. KEGG pathway analysis was performed on all DEMs, and the pathways were enriched in retinol metabolism, steroid hormone biosynthesis, and tyrosine metabolism. Through survival analysis of the ceRNA network, we identified four DEMs, two DELs, and two DEMis that were significant for poor prognosis. Conclusions This study suggested that constructing a ceRNA network and performing survival analysis on the network could screen out new significant treatment and prognosis targets and biomarkers.

The purpose of the study is to identify and analyze patterns of the diurnal dynamics of the expression of genes that differ in the shape of the curve. It can be expected that the similarity of the patterns of daily expression (shape of the curve) of genes is a reflection of the synchronization of gene expression by common external and internal signals or participation in similar biological processes. Different signals that have daily dynamics (light, activity, nutrition, stress, temperature, etc.) can affect different levels of expression regulation, which can be manifested in various forms of patterns of daily gene expression. In our research, we used experimental data on gene expression at the level of translation (ribosome profling) in the liver and kidney of a mouse (GSE67305 and GSE81283). To identify genes with a daily rhythm of expression, we used a oneway analysis of variance. To identify similar­in­shape curves of the daily dynamics of gene expression, we propose an approach based on cluster analysis. The distance between the genes was calculated by aligning the phases and fnding the maximum cross­correlation between the patterns of the daily expression of these genes by the cyclic shift. This approach allowed us to identify genes that have not only expression patterns with a single maximum (sinusoidal, asymmetrical, shifted to the left or right, pulsed), but also complex composite signals with several extremes. As a result, the groups of genes united by the similarity of the shape of the daily expression curve without regard to their phase characteristics were identifed. GO enrichment analysis of groups of genes with sharply different patterns of daily expression (sinusoidal and pulsed) in the mouse kidneys and liver showed that the group of genes with a sinusoidal pattern was more associated with regulation of circadian rhythm and metabolism. The group of genes with a pulsed pattern is largely associated with the protective functions of the organism, which require the quick response. Thus, our studies have confrmed the effectiveness of the proposed approach to the analysis of the diurnal dynamics of gene expression. The identifed dynamic patterns of diurnal expression are important for the further study of complex circadian regulation, synchronization and interaction of biological processes with diurnal dynamics in mammals.

Purpose: To develop a comprehensive differential expression gene profile as well as a prediction model based on the expression analysis of pediatric sepsis specimens.Methods: In this study, compared with control specimens, a total of 708 differentially expressed genes in pediatric sepsis (case–control at a ratio of 1:3) were identified, including 507 up-regulated and 201 down-regulated ones. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes indicated the close interaction between neutrophil activation, neutrophil degranulation, hematopoietic cell lineage, Staphylococcus aureus infection, and periodontitis. Meanwhile, the results also suggested a significant difference for 16 kinds of immune cell compositions between two sample sets. The two potential selected biomarkers (MMP and MPO) had been validated in septic children patients by the ELISA method.Conclusion: This study identified two potential hub gene biomarkers and established a differentially expressed genes-based prediction model for pediatric sepsis, which provided a valuable reference for future clinical research.

A number of methods are being developed and used for analysis of gene expression data such as RNA-Seq data. Most of these tools focus on finding genes that are responsible for the disease conditions. Methods such as co-expression network generation, module detection and differential co-expression analysis are used to look into specific changes in the gene expression data among different conditions. In this paper, a comparative study of four differential co-expression analysis tools are presented, namely, WGCNA, DiffCorr, MODA and CEMiTool, for RNA-Seq data. The different methods used by these tools are studied and tested on schizophrenia and bipolar disorder datasets and their effectiveness in finding the related differentially co-expressed genes and pathways are being discussed. The relevancy of the resultant genes and pathways are decided on the basis of whether the genes and pathways are associated with the given disease conditions.

Abstract Background The aim of this research was to investigate the retinal transcriptome changes in long‐term streptozotocin (STZ)‐induced rats' retinas using RNA sequencing (RNA‐seq), to explore the molecular mechanisms of diabetic retinopathy (DR), and to identify novel targets for the treatment of DR by comparing the gene expression profile we obtained. Methods In this study, 6 healthy male SD rats were randomly divided into wild‐type (WT) group and streptozotocin (STZ)‐induced group, 3 rats each group. After 6 months, 3 normal retina samples and 3 DM retina samples (2 retinas from the same rat were considered as 1 sample) were tested and differentially expressed genes (DEGs) were measured by RNA‐seq technology. Then, we did Gene Ontology (GO) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and validated the results of RNA‐seq through qRT–PCR. Results A total of 118 DEGs were identified, of which 72 were up‐regulated and 46 were down‐regulated. The enriched GO terms showed that 3 most significant enrichment terms were binding (molecular function), cell part (cellular component), and biological regulation (biological process). The results of the KEGG pathway analysis revealed a significant enrichment in cell adhesion molecules, PI3K‐Akt signaling pathway, and allograft rejection, etc. Conclusion Our research has identified specific DEGs and also speculated their potential functions, which will provide novel targets to explore the molecular mechanisms of DR.

The paper presents the results of a study of the tissue­specificity of the circadian phase characteristics of biological processes in the mouse liver and kidneys. We performed a comparative analysis of the translatomes in these two organs based on experimental data on the daily dynamics of the level of translation of mouse genes from the GEO database (GSE67305 and GSE81283) obtained by ribosome profiling. Genes with a pronounced daily dynamics of translation were revealed (3 358 genes in the liver and 2 938 in the kidneys). Further, for each of the 12 time points (ZT0–ZT22), for each tissue (liver, kidneys), groups of genes that were in a phase with an increased level of translation were identified. It was assumed that the gene is in a phase with an increased level of translation if at a given time point its ribosome profiling rate for both replicas exceeded the daily average value for this gene. The greatest number of rhythmic genes in the liver has an increased level of translation at the beginning of the dark phase of the day corresponding to increased animal activity. In the kidneys, the differences in the distribution of the number of genes in the phase of an elevated translation level by the time of day were less pronounced, and the maximum number of such genes was observed from the middle of the light phase of the day to the middle of the dark one. A statistical analysis of enrichment of Gene Ontology terms in these twelve gene groups in the liver and kidneys was perform ed. Analyzing the processes, the rhythmicity of which is typical of both liver and kidneys, we have identified the processes, the circadian phase characteristics of which in these tissues coincide and the processes having essentially different temporal phase patterns for these tissues. Processes with strict tissue­specific rhythmic translation have also been identified. The approach used in our work allows us to analyze the organo/tissue­specificity of the phase characteristics of biological processes, and the results emphasize the need to take into account the phase circadian characteristics when comparing the features of the course of biological processes in various organs.

Background: The aim of this research was to investigate the retinal transcriptome changes in long‐term streptozotocin (STZ)‐induced rats' retinas using RNA sequencing (RNA‐seq), to explore the molecular mechanisms of diabetic retinopathy (DR), and to identify novel targets for the treatment of DR by comparing the gene expression profile we obtained. Methods: In this study, 6 healthy male SD rats were randomly divided into wild‐type (WT) group and streptozotocin (STZ)‐induced group, 3 rats each group. After 6 months, 3 normal retina samples and 3 DM retina samples (2 retinas from the same rat were considered as 1 sample) were tested and differentially expressed genes (DEGs) were measured by RNA‐seq technology. Then, we did Gene Ontology (GO) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and validated the results of RNA‐seq through qRT–PCR. Results: A total of 118 DEGs were identified, of which 72 were up‐regulated and 46 were down‐regulated. The enriched GO terms showed that 3 most significant enrichment terms were binding (molecular function), cell part (cellular component), and biological regulation (biological process). The results of the KEGG pathway analysis revealed a significant enrichment in cell adhesion molecules, PI3K‐Akt signaling pathway, and allograft rejection, etc. Conclusion: Our research has identified specific DEGs and also speculated their potential functions, which will provide novel targets to explore the molecular mechanisms of DR. [ABSTRACT FROM AUTHOR]

Objective · To explore the mechanism of esophageal squamous cell carcinoma (ESCC) and its potential targeted drugs, and to provide the theoretical basis for diagnosis and treatment of ESCC. Methods · Two GEO sets GSE38129 and GSE20347 were selected, and differentially expressed genes (DEGs) were screenedR language. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were conducted for DEGs. The most significant module genes and key genes were analyzedprotein-protein interaction (PPI) network for DEGs. Targeted drug prediction was made for phosphorylase B kinase (PBK). Results · A total of 670 DEGs were identified, consisting of 342 down-regulated genes and 328 up-regulated genes. The enriched functions and pathways of DEGs included extracellular structure organization, extracellular matrix organization, p53 signaling pathway, IL-17 signaling pathway and cell cycle. Twenty key genes were identifiedanalyzing DEGs' PPI network. The key gene PBK was related to the cell cycle, and the of PBK was up-regulated in the two data sets. The potential drug Compound 1 of PBK was predictedallosteric site detection and compound library virtual screening. Conclusion · The key genes of ESCC can be effectively analyzedbioinformatics. The prediction results of targeted drugs of key gene PBK may provide reference for the targeted therapy of ESCC. [ABSTRACT FROM AUTHOR]

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Lung cancer remains a formidable global health challenge, necessitating the exploration of novel therapeutic approaches. This study investigates the potential of Cuscuta reflexa Roxb. stem extract as an anticancer agent against human lung cancer, focusing on its antioxidative and ROS-dependent apoptotic effects. Utilizing a combination of network pharmacology and in-vitro experimental validation, we delineate the multifaceted molecular mechanisms underlying the observed effects. The antioxidant potential of C. reflexa stem extract was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH • ), 2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS •+ ) and ferric reducing/antioxidant power (FRAP), hydroxyl free radical scavenging, reactive nitrogen oxide scavenging and super oxide anion radical scavenging assays. Furthermore, the antiproliferative and proapoptotic effect of C. reflexa stem extract was evaluated against A549 lung adenocarcinoma cell line using the consecrated sulforhodamine B (SBR) and Annexin V-PI assays. Additionally, the mitochondrial membrane potential (MMP) and the total reactive oxygen species (ROS) estimation assays were performed. As a result, network pharmacology analysis revealed a complex interaction network between the bioactive constituents of C. reflexa and key proteins implicated in lung cancer progression. The C. reflexa stem extract showed dose-dependent antioxidant activity against DPPH • (IC 50 - 87.38 µg/mL), reactive nitrogen oxide (IC 50 - 318.34 µg/mL), FRAP (IC 50 - 359.96 µg/mL), hydroxy free radicals (IC 50 - 526.12 µg/mL) than ABTS ●+ (IC 50 - 698.45 µg/mL) and super oxide anion (IC 50 - 892.71 µg/mL) as well as cytotoxic activity against A549 cells (IC 50 - 436.80 µg/mL). Observations of morphological features in treated cells have revealed hallmark of apoptosis properties. Furthermore, as a result of treatment with C. reflexa stem extract, ROS generation and mitochondrial depolarization were increased in A549 cells, suggesting that this treatment has significant apoptotic properties. . These findings highlight the potential utility of this natural extract as an innovative therapeutic strategy for lung cancer treatment. The integration of network pharmacology and experimental validation enhances our understanding of the underlying mechanisms and provide the way for further translational research.Communicated by Ramaswamy H. Sarma.

Background: Tail-anchored membrane proteins (TAMPs) differ from other integral membrane proteins, because they contain a single transmembrane domain at the extreme carboxyl-terminus and are therefore obliged to target to membranes post-translationally. Although 3–5% of all transmembrane proteins are predicted to be TAMPs only a small number are well characterized. Results: To identify novel putative TAMPs across different species, we used TAMPfinder software to identify 859, 657 and 119 putative TAMPs in human (Homo sapiens), plant (Arabidopsis thaliana), and yeast (Saccharomyces cerevisiae), respectively. Bioinformatics analyses of these putative TAMP sequences suggest that the list is highly enriched for authentic TAMPs. To experimentally validate the software predictions several human and plant proteins identified by TAMPfinder that were previously uncharacterized were expressed in cells and visualized at subcellular membranes by fluorescence microscopy and further analyzed by carbonate extraction or by bimolecular fluorescence complementation. With the exception of the pro-apoptotic protein harakiri, which is, peripherally bound to the membrane this subset of novel proteins behave like genuine TAMPs. Comprehensive bioinformatics analysis of the generated TAMP datasets revealed previously unappreciated common and species-specific features such as the unusual size distribution of and the propensity of TAMP proteins to be part of larger complexes. Additionally, novel features of the amino acid sequences that anchor TAMPs to membranes were also revealed. Conclusions: The findings in this study more than double the number of predicted annotated TAMPs and provide new insights into the common and species-specific features of TAMPs. Furthermore, the list of TAMPs and annotations provide a resource for further investigation. [ABSTRACT FROM AUTHOR]

Monocytic myeloid‐derived suppressor cells (MO‐MDSCs) play an important role in maintaining normal pregnancy. However, it is still not clear what kind of changes in MO‐MDSCs may lead to miscarriage, and which gene expression changes take place when MO‐MDSCs migrate to the uterus as bone marrow‐derived cells. Methods: We used flow sorting technology to obtain MO‐MDSCs from the maternal–fetal interface and bone marrow, respectively. Affymetrix 3′IVT expression profiling chip technology was used to detect the differential gene expression profiles in MO‐MDSCs at the maternal–fetal interface in a mouse model of spontaneous abortion compared with the normal fertility control mice. We also compared the differential gene expression of MO‐MDSCs at the maternal–fetal interface compared with bone marrow in the normal fertility control mice. Results: We found that 3,409 genes in MO‐MDSCs were upregulated and 1,539 genes were downregulated at the maternal–fetal interface in the spontaneous abortion mice compared with the normal fertility mice. These genes are enriched in cellular components, biological processes, molecular functions, and protein binding, tumor signaling pathway, the PI3K–Akt signaling pathway, intratumoral proteoglycans, and extracellular matrix receptor interactions. Furthermore, we found that 270 genes in MO‐MDSCs were upregulated and 383 genes were downregulated at the maternal–fetal interface in the normal fertility mice compared with those in the bone marrow. These genes are enriched in cellular components, biological processes, molecular functions, cell cycle, tumor transcriptional disorder, and cell adhesion molecules. Conclusion: Differential gene expression in MO‐MDSCs likely contributes to a successful pregnancy in fetal–maternal immunotolerance. The goal of this study was to find the changes in monocytic myeloid‐derived suppressor cells (MO‐MDSCs) that lead to miscarriage, with the identification of underlying changes at the gene level. We list the upregulated and downregulated genes and the major pathways affected, and report that differential gene expression in MO‐MDSCs contributes to the successful pregnancy in fetal–maternal immunotolerance. [ABSTRACT FROM AUTHOR]

Background: MiRNAs can regulate gene expression directly or indirectly, and long noncoding RNAs as competing endogenous RNA (ceRNAs) can bind to miRNAs competitively and affect mRNA expression. The ceRNA network is still unclear in breast cancer. In this study, a ceRNA network was constructed, and new treatment and prognosis targets and biomarkers for breast cancer were explored. Methods: A total of 1 096 cancer tissues and 112 adjacent normal tissues to cancer from the TCGA database were used to screen out significant differentially expressed mRNAs (DEMs), lncRNAs (DELs), and miRNAs (DEMis) to construct a ceRNA network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict potential functions. Survival analysis was performed to predict which functions were significant for prognosis. Results: From the analysis, 2 139 DEMs, 1 059 DELs, and 84 DEMis were obtained. Targeting predictions for DEMis‐DELs and DEMis‐DEMs can yield 26 DEMs, 90 DELs, and 18 DEMis. We performed GO enrichment analysis, and the results showed that the upregulated DEMs were involved in nucleosomes, extracellular regions, and nucleosome assembly, while the downregulated DEMs were mainly involved in Z disk, muscle contraction, and structural constituents of muscle. KEGG pathway analysis was performed on all DEMs, and the pathways were enriched in retinol metabolism, steroid hormone biosynthesis, and tyrosine metabolism. Through survival analysis of the ceRNA network, we identified four DEMs, two DELs, and two DEMis that were significant for poor prognosis. Conclusions: This study suggested that constructing a ceRNA network and performing survival analysis on the network could screen out new significant treatment and prognosis targets and biomarkers.Identification of differentially expressed lncRNAs (DELs), mRNAs (DEMs), and miRNAs (DEMis) in breast cancer. Construction of competing endogenous RNA (ceRNA) regulatory network and screening new treatment and prognosis targets and biomarkers for breast cancer. [ABSTRACT FROM AUTHOR]

Abstract The GASA (GA- stimulated Arabidopsis) gene family is highly specific to plants, signifying a crucial role in plant growth and development. Herein, we retrieved 119 GASA genes in 10 different plant species in two major lineages (monocots and eudicots). Further, in the phylogenetic tree we classified these genes into four well-conserved subgroups. All the proteins contain a conserved GASA domain with similar characteristics and a highly specific 12-cysteine residue of the C-terminus position. According to the global microarray data and qRT-PCR based analysis, the OsGASA gene family was dominantly expressed in the seedling and transition phase of floral stages. Despite this, OsGASA genes profoundly contribute to rice grain size and length, whereas the highest abundance of transcript level was noticed in stage-2 (Inf 6, 3.0-cm-long spikelet) and stage-3 (Inf 7, 5.0-cm-long spikelet) under GA treatment during panicle formation. Additionally, the maximum expression level of these genes was recorded in response to GA and ABA in young seedlings. Further, in response to abiotic stresses, OsGASA1/8/10 was up- regulated by salt, OsGASA2/5/7 by drought, OsGASA3/6 by cold, and OsGASA4/9 by heat stress. With the exception of OsGASA4 , the higher transcription levels of all the other GASA genes were induced by Cd and Cr metal stresses (8–10 fold changes) at various time points. Finally, the GO ontology analysis of GASAs revealed the biological involvement in the GA-mediated signaling pathway and abiotic stresses. Prominently, most of these proteins are localized in cellular components such as the cell wall and extracellular region, where the molecular functions such as ATP binding and protein binding were observed. These results imply that GASAs are significantly involved in rice panicle developmental stages, responses to external stimuli, and hormones. [ABSTRACT FROM AUTHOR]

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein-protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs, deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, the mixture of three herbs had a combinational effect. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFA-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

Tanshinone IIA (Tan IIA) is one of the major fat-soluble ingredients in Salvia miltiorrhiza which has been widely used for various inflammatory conditions associated with cardiovascular and cerebrovascular disorders. However, the underlying anti-inflammatory mechanisms of Tan IIA are incompletely understood. The purpose of this study was to illuminate the anti-inflammatory mechanism of Tan IIA based on the protein interaction network (PIN) analysis. A PIN of Tan IIA was constructed with 281 nodes and 814 interactions and analyzed by gene ontology (GO) enrichment analysis based on Markov Cluster algorithm (MCL). Three modules were associated with anti-inflammatory actions. The most interesting finding of this study was that the anti-inflammatory effect of Tan IIA may be partly attributable to the mediate activation of TRAF2, TRAF3 and TRAF6, to inhibit the toll-like receptor signaling pathway and combine with AGER. Therefore, the module-based network analysis approach will be a new method for better understanding the anti-inflammatory mechanism of Tan IIA. [ABSTRACT FROM AUTHOR]

The aim of this study was to screen target genes and gene functions of androgen receptor (AR) in LNCaP cell line by ChIP-seq data analysis. We downloaded the gene expression profile GSE14092 from Gene Expression Omnibus database and selected ChIP-seq data (GSM353644) of AR stimulated by androgen R1881 (R1881 stimulation group) and the ChIP-seq data (GSM353643) of AR without R1881 stimulation (control group). MACS peak calling software was used to identify the AR binding cites. After target genes selection and function analysis, motif finding analysis was utilized to predict the AR co-located transcription regulation factors, and we analyzed their functions through GO enrichment analysis. Total 27202 and 2730 AR binding sites were detected in the R1881 stimulation group and the control group, respectively and 398 and 58 target genes were identified in R1881 stimulation group and control group, respectively. Based on GO enrichment analysis, 20 biological processes which AR regulated in the LNCaP cells were enriched, including xenobiotic metabolic process, positive regulation of interleukin-2 production and cellular response to sterol etc. We finally identified 99 transcription factors with high motif enrichment significant levels, and the enrichment of AR co-located transcription factors was significantly enriched in the biological process of regulation of cell proliferation in which 13 transcription factors were involved (FOXJ1, FOXM1, NF1, SOX2, HOXD13, FOXO1, FOXP3, FOXO4, SOX9, PGR, DBP, JUN and TLX1). The analysis of AR target genes and gene functions help us to elucidate the mechanism of the prostate cancer on a molecular level. In addition, it will pave the way to effective therapies for prostatic cancer. However, further experiments are still needed to confirm our results. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Severe sepsis after trauma still associated with a high mortality rate in intensive care units (ICU). In this study we aimed to identify genes related to multiple trauma complicated by severe sepsis. MATERIALS AND METHODS: The gene expression profile dataset GSE12624 including 36 samples of traumatic patients not complicated by sepsis and 34 traumatic patients complicated by sepsis was downloaded from GEO (Gene Expression Omnibus) database. The limma package in R was applied to identify differentially expressed genes (DEGs) between these two groups of samples. All the DEGs were divided into up- and down-regulation groups according to the changes of their expression value, which were then subjected to GO enrichment analysis. Two genes with largest changes among the up- and down-regulation groups were selected. Interaction networks based on these two genes were constructed using Hit- Predict software and then pathway enrichment analysis for the networks were performed by WebGestalt software. RESULTS: A total of 21 up-regulated genes and 37 down-regulated genes were obtained, which were mainly related to GO terms "endopeptidase inhibitor activity" and "response to wounding", respectively. The IlogFCI of genes PLAU (urokinase-type plasminogen activator) and MMP8 (matrix metalloproteinase-8) ranked first in down-regulated or up-regulated list. There were 18 genes which can interact with PLAU at a high degree of confidence while there were 5 genes with MMP8. Further analysis showed that PLAU was closely associated with the pathway "complement and coagulation cascades". CONCLUSIONS: PLAU and MMP8 may act as potential targets for diagnosis and therapy of trauma complicated by sepsis. [ABSTRACT FROM AUTHOR]

Salvianolic Acid B (Sal B) is one of the main medicinal ingredients of Radix Salvia miltiorrhiza (Danshen) and possesses a variety of pharmacological effects. The purpose of this study was to discover the new mechanism of action of Sal B based on the protein interaction network (PIN) analysis. A PIN of Sal B was constructed with 852 nodes and 8,626 interactions. By fast agglomerate algorithm based on the edge clustering coefficients (FAG-EC), 11 modules were detected from the network. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of Sal B played in cardiovascular disease were related to multiple biological processes, which could represent the characteristics of Chinese Material Medica (CMM) as a whole to regulate the disease. The most interesting finding of this work was that the anti-inflammatory effect of Sal B was due to the immune response of T lymphocytes by regulating IL-2 family, CD3E, CD79A, MAP3K7 and PRKCQ. Therefore, the module-based network analysis will be an effective method for better understanding CMM. [ABSTRACT FROM AUTHOR]

BACKGROUND: Abdominal aortic aneurysm (AAA) is a relatively common disease in elderly. Currently, only surgical treatment has been available for ruptured AAA. Thus, it is impressing to elucidate the molecular cellular mechanisms of AAA in order to develop the effective medications. AIM: This study is to explore the significant pathways and crosstalk between them in response to AAA. METHODS: The crosstalk of pathways was analyzed based on PPI datasets and expression profiles. RESULTS: It was showed that significant pathways included Cytokine-cytokine receptor interaction (hsa04060), B cell receptor signaling pathway, Chemokine signaling pathway (hsa04062), Cell adhesion molecules (CAMs) (hsa04514), and Hematopoietic cell lineage (hsa04640), which were in accordance with Lenk's results. Further analysis indicated that Chemokine signaling pathway (Hsa04062) and Cytokine-cytokine receptor interaction (Hsa04060) were both connected with the Cell adhesion molecules (CAMs) (Hsa04514) through the signal transduction (GO:0007165). B cell receptor signaling pathway (Hsa04662) and Cytokine-cytokine receptor interaction (Hsa04060) were both connected with the Natural killer cell mediated cytotoxicity (Hsa04650) through the apoptosis (GO:0006915) and signal transduction (GO:0007165), respectively. These crosstalks seemed to exit according to previous reports. We hope our study could provide insights for abdominal aortic aneurysm mechanism to some extent. CONCLUSIONS: We analyzed the significant pathways related with AAA through Sp and DAVID method. The results were in accordance with previous reports. [ABSTRACT FROM AUTHOR]

Salvianolic Acid B (Sal B) is one of the main medicinal ingredients of Radix Salvia miltiorrhiza (Danshen) and possesses a variety of pharmacological effects. The purpose of this study was to discover the new mechanism of action of Sal B based on the protein interaction network (PIN) analysis. A PIN of Sal B was constructed with 852 nodes and 8,626 interactions. By fast agglomerate algorithm based on the edge clustering coefficients (FAG-EC), 11 modules were detected from the network. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of Sal B played in cardiovascular disease were related to multiple biological processes, which could represent the characteristics of Chinese Material Medica (CMM) as a whole to regulate the disease. The most interesting finding of this work was that the anti-inflammatory effect of Sal B was due to the immune response of T lymphocytes by regulating IL-2 family, CD3E, CD79A, MAP3K7 and PRKCQ. Therefore, the module-based network analysis will be an effective method for better understanding CMM. [ABSTRACT FROM AUTHOR]

The Wenshenyang recipe (WSYR) has the effect of treating infertility, but the mechanisms underlying this activity have not been fully elucidated. In this study, network pharmacology and RNA sequencing were combined, with database-based "dry" experiments and transcriptome analysis-based "wet" experiments used conjointly to analyse the mechanism of WSYR in the treatment of infertility. In the dry analysis, 43 active compounds in WSYR and 44 therapeutic targets were obtained through a database search, 15 infertility pathways were significantly enriched, and key targets, such as ESR1, TP53, AKT1, IL-6, and IL-10 were identified. Then the wet experiments were performed to detect the expression changes of the 412 genes from 15 infertility pathways identified by dry analysis. HK-2 cells were treated with the three herbs of WSYR and subjected to targeted RNA sequencing. Based on the results, 92 of the 412 genes in 15 infertility pathways were identified as DEGs. Additionally, key targets, such as ESR2, STAT1, STAT3, and IL6, were also identified in the wet experiments. RT-qPCR experiments further verified that WSYR played an anti-inflammatory role by upregulating IL-4 and IL-10 and Epimedium brevicornu Maxim (Yinyanghuo) showed broader effect than Drynaria fortunei (Kunze) J. Sm (Gusuibu) and Cistanche deserticola Y.C.Ma (Roucongrong). By screening compounds of WSYR using molecular docking models of ESR1 and ESR2, it was further found that xanthogalenol in Gusuibu, arachidonate in Roucongrong, and anhydroicaritin in Yinyanghuo had good affinity for estrogen receptors. These findings provide evidence for an estrogen-regulating role of the three herbs in WSYR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Zhao, Zhang, Huang, Qiao, Zhan, Ma, Gong, Dang and Lu.)

• Gene expression profiles of three Daphnia magna strains were determined by RNA-seq. • GO enrichment analysis revealed the chitin metabolism differed in two strains. • As with the mRNA levels, the chitin content was significantly different in two strains. • The strain with higher amount of chitin was more tolerant to a chitin synthesis inhibitor, diflubenzuron. • 48h-EC50 values for diflubenzuron differed by 14-fold among strains. Ecotoxicity testing of crustaceans using Daphnia magna has been implemented in the chemical management systems of various countries. While the chemical sensitivity of D. magna varies depending on genetically different clonal lineages, the strain used in ecotoxicity tests, including the acute immobilization test (OECD TG202), has not been specified. We hypothesized that comprehensive gene expression profiles could provide useful information on phenotypic differences among strains, including chemical sensitivity. To test this hypothesis, we performed mRNA sequencing on three different strains (NIES, England, and Clone 5) of D. magna under culture conditions. The resulting expression profile of the NIES strain was clearly different compared to the profiles of the other two strains. Gene ontology (GO) enrichment analysis suggested that chitin metabolism was significantly enriched in the NIES strain compared to that in the England strain. Consistent with the GO analysis, evidence of high levels of chitin metabolism in the NIES strain were observed across multiple levels of biological organization, such as expression of chitin synthase genes, chitin content, and chitinase activity, which suggested that the different strains would exhibit different sensitivities to chemicals used to inhibit chitin synthesis. We found that among all strains, the NIES strain was more tolerant to diflubenzuron, a chitin synthesis inhibitor, with a 14-fold difference in the 48 h-EC 50 value for the acute immobilization test compared to the England strain. The present study demonstrates that the differences among strains in chitin metabolism may lead to sensitivity difference to diflubenzuron, and serves as a case study of the usefulness of comprehensive gene expression profiles in finding sensitivity differences. [Display omitted] [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation (HSCT) is an effective treatment method used in many neoplastic and non-neoplastic diseases that affect the bone marrow, blood cells, and immune system. The procedure is associated with a risk of adverse events, mostly related to the immune response after transplantation. The aim of our research was to identify genes, processes and cellular entities involved in the variety of changes occurring after allogeneic HSCT in children by performing a whole genome expression assessment together with pathway enrichment analysis. We conducted a prospective study of 27 patients (aged 1.5–18 years) qualified for allogenic HSCT. Blood samples were obtained before HSCT and 6 months after the procedure. Microarrays were used to analyze gene expressions in peripheral blood mononuclear cells. This was followed by Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein–protein interaction (PPI) analysis using bioinformatic tools. We found 139 differentially expressed genes (DEGs) of which 91 were upregulated and 48 were downregulated. "Blood microparticle", "extracellular exosome", "B-cell receptor signaling pathway", "complement activation" and "antigen binding" were among GO terms found to be significantly enriched. The PPI analysis identified 16 hub genes. Our results provide insight into a broad spectrum of epigenetic changes that occur after HSCT. In particular, they further highlight the importance of extracellular vesicles (exosomes and microparticles) in the post-HSCT immune response. [ABSTRACT FROM AUTHOR]

Network pharmacology (NP) is a useful, emerging means of understanding the complex pharmacological mechanisms of traditional herbal medicines. Sochehwan (SCH) is a candidate herbal prescription for drug repurposing as it has been suggested to have beneficial effects on metabolic syndrome. In this study, NP was adopted to complement the shortcomings of literature-based drug repurposing strategies in traditional herbal medicine. We conducted in vitro studies to confirm the effects of SCH on potential pharmacological targets identified by NP analysis. Herbal compounds and molecular targets of SCH were explored and screened from a traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and an oriental medicine advanced searching integrated system (OASIS). Forty-seven key targets selected from a protein-protein interaction (PPI) network were analyzed with gene ontology (GO) term enrichment and KEGG pathway enrichment analysis to identify relevant categories. The tumor necrosis factor (TNF) and mitogen-activated protein kinase (MAPK) signaling pathways were presented as significant signaling pathways with lowest p-values by NP analysis, which were downregulated by SCH treatment. The signal transducer and activator of transcription 3 (STAT3) was identified as a core key target by NP analysis, and its phosphorylation ratio was confirmed to be significantly suppressed by SCH. In conclusion, the NP-based approach used for target prediction and experimental data obtained from Raw 264.7 cells strongly suggested that SCH can attenuate inflammatory status by modulating the phosphorylation status of STAT3. [ABSTRACT FROM AUTHOR]