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This study aims to identify the differences in metabolites between Fructus Chebulae (FC) and Fructus Terminaliae Billericae (FTB). Untargeted metabolomics was used to analyze differentially expressed metabolites (DEMs) with ultra-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC-ESI-MS/MS). A grand total of 558 metabolites were detected, with 155 in positive ion mode and 403 in negative ion mode. Further differential analysis yielded 110 and 87 significantly different metabolites, which were mainly polyphenols, flavonoids, terpenoids, and alkaloids. Analysis of KEGG data showed that differentially expressed metabolites (DEMs) in both positive and negative ion modes were found to be enriched in 5 and 18 metabolic pathways, respectively, with metabolic pathways being the most enriched among them. In sum, this study reveals the differential metabolic profiles of FC and FTB and provides support for their further applications in traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

This study was aimed at investigating the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by smoking—based on bioinformatics analysis and in vitro experimental evidence. The GEO, GEO2R, TargetScan, miRDB, miRWalk, DAVID, and STRING databases were used for bioinformatics analysis. The mRNA expression and the protein levels were determined by real-time PCR and ELISA. After taking the intersection of the diversified results of the databases, four differentially expressed miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) were screened out. Subsequently, a total of 57 target genes of the selected miRNAs were obtained. The results of DAVID analysis showed that the selected miRNAs participated in COPD pathogenesis through long-term potentiation, the TGF-β signaling pathway, the PI3K-Akt signaling pathway, etc. The results of STRING prediction showed that TP53, EP300, and MAPK1 were the key nodes of the PPI network. The results of the confirmatory experiment showed that, compared with the control group, the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated, while the expression of MYB was down-regulated and the protein levels of ZEB1, MAPK1, and EP300 were increased. Taken together, miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) and their regulated target genes and downstream protein molecules (ZEB1, EP300, and MAPK1) may be closely related to the pathological process of COPD. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to investigate the differences in the proteomic expression between uncomplicated parapneumonic pleural effusion (UPPE) and complicated parapneumonic pleural effusion (CPPE). Material and methods: There were 10 patients with UPPE and 10 patients with CPPE. These patients were combined due to the complication of pleural effusion and further divided into group A and group B. An LC-MS analysis was conducted with the extraction of high-abundance proteins, and proteins with 1.5-fold or higher difference multiples were identified as differential proteins. Then, gene ontology (GO) and KEGG analyses were conducted on the differential proteins between the groups. Results: Compared with the UPPE group, there were 38 upregulated proteins and 29 downregulated proteins in the CPPE group. The GO analysis revealed that the CPPE group had enhanced expressions in monosaccharide biosynthesis, glucose catabolism, fructose-6-phosphate glycolysis, glucose-6-phosphate glycolysis, and NADH regeneration as well as reduced expressions in fibrinogen complexes, protein polymerization, and coagulation. Moreover, the KEGG analysis showed that the CPPE group had enhanced expressions in amino acid synthesis, the HIF-1 signalling pathway, and glycolysis/glyco-isogenesis and decreased expressions in platelet activation and complement activation. Conclusions: In pleural effusion in patients with CPPE, there are enhanced expressions of proteins concerning glucose and amino acid metabolism, NADH regeneration, and HIF-1 signalling pathways together with decreased expressions of proteins concerning protein polymerization, blood coagulation, platelet activation, and complement activation. [ABSTRACT FROM AUTHOR]

This study aims to identify the differences in metabolites between Fructus Chebulae (FC) and Fructus Terminaliae Billericae (FTB). Untargeted metabolomics was used to analyze differentially expressed metabolites (DEMs) with ultra-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC-ESI-MS/MS). A grand total of 558 metabolites were detected, with 155 in positive ion mode and 403 in negative ion mode. Further differential analysis yielded 110 and 87 significantly different metabolites, which were mainly polyphenols, flavonoids, terpenoids, and alkaloids. Analysis of KEGG data showed that differentially expressed metabolites (DEMs) in both positive and negative ion modes were found to be enriched in 5 and 18 metabolic pathways, respectively, with metabolic pathways being the most enriched among them. In sum, this study reveals the differential metabolic profiles of FC and FTB and provides support for their further applications in traditional Chinese medicine.

Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women that induces reproductive and metabolic derangements. Women with PCOS seem to have disturbances in lipid metabolism in the adipose tissue. Nevertheless, gene expression in adipose tissue of PCOS women and its relation to other disturbances have been fragmentarily investigated. We utilized microarray data to identify the most important up- and down-regulated candidate genes in adipose tissue of PCOS women in contrast to healthy women using the meta-analysis technique. Microarray data produced from three independent experiments (n = 3) conducted on adipose tissue in women with PCOS were retrieved from ArrayExpress. Then, the datasets were merged using the metaSeq package in Rstudio and differentially expressed genes (DEGs) were selected in the studies. The integrative bioinformatics analyses of candidate genes were performed by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein–protein interaction (PPI) network construction. Of these, 12 up-regulated genes and 12 down-regulated genes were identified and assessed as the most highly up-regulated and down-regulated genes in adipose tissue of women with PCOS. These DEGs that were annotated by KEGG analysis were mainly involved in PI3K-Akt, MAPK, Rap1, and Ras signaling pathways, and pathways in cancer such as hepatocellular carcinoma and gastric cancer, as well as metabolic pathways, and brain disorder pathways such as Alzheimer's disease and Huntington disease pathways. In the PPI networks, PRDM10, FGFR2, IGF1R, and FLT1 were the key nodes in the up-regulated networks, while the NDUFAB1 and NME2 proteins were key in the down-regulated networks. Overall, these findings provide insight into the gene expression in adipose tissue of PCOS women and its relation to other disturbances. [ABSTRACT FROM AUTHOR]

The main features of a giant cell tumor of bone (GCTB) are frequent recurrence and aggressive osteolysis, which leads to a poor prognosis in patients. Although the treatment methods for a GCTB, such as scraping and resection, effectively inhibit the disease, the tendency toward malignant transformation remains. Therefore, it is important to identify new treatment methods for a GCTB. In this study, we first found high Siglec-15 expression in GCTB tissues, which was significantly associated with Campanacci staging and tumor recurrence. In Spearman’s analysis, Siglec-15 expression was significantly correlated with Ki-67 levels in tumor tissues. In vitro, the mRNA and protein levels of Siglec-15 were high in GCTB stromal cells (Hs737. T), and Siglec-15 knockdown inhibited the biological characteristics of GCTB stromal cells. The RNA sequencing results enabled a prediction of the downstream genes by using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and MCODE analyses, and the findings showed that CXCL8 was significantly regulated by Siglec-15 and might be a promising downstream target gene of Siglec-15. Therefore, Siglec-15 may be a potential immunotherapy target for a GCTB.

Tea (Camellia sinensis L.) is an important perennial cash crop and a typical subtropical plant. It is widely concerned because of its unique flavor and health benefits. In recent years, low temperatures have severely restricted the growth of tea plants and quality of tea products, especially in spring. As a common precursor for all porphyrin compounds, 5-aminolevulinic acid (ALA) is involved in photosynthesis and respiration and plays an active role in improving salt, drought and low-temperature tolerance in plants. However, it is not yet clear what affect exogenous ALA has on tea plants' tolerance under low temperature. In the present study, we collected and deciphered the transcriptome profiles from Shaancha No. 1 leaf tissues under low temperature (−4 °C) treatment (T-4), exogenous ALA application (T-A), pretreated ALA before low temperature (T-A-4) and untreated control (T-CK). Results showed that 4990 (2375 up- and 2615 down-regulated), 223 (103 up- and 120 down-regulated) and 92 (13 up- and 79 down-regulated) differentially expression genes (DEGs) were identified at T-CK vs. T-4, T-CK vs. T-A and T-4 vs. T-A-4, respectively. Both T-4 and T-A treatments triggered a myriad of stress resistance genes up-regulated related to multiple signaling pathways by means of Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. This included MAPK, a toll-like receptor that signals pathways involved in cold resistance. However, gene ontology (GO) analysis showed that the DEGs in T-4 treatment were mainly enriched in the phenylpropanoid metabolic and redox processes that were relevant to membrane structure damage response. In contrast, the DEGs in T-A treatment were mainly enriched in cell recognition and amylase activity. Furthermore, in pairwise comparison of T-A-4 vs. T-4, the DEGs were enriched in ascorbate and aldarate, retionol, taurine and hypotaurine, glutathione metabolic pathways and two biosynthesis process including zeatin, diterpenoid biosynthesis, which might contribute to mitigating the damage caused by low temperature. Overall, these results indicated that exogenous ALA application may improve the biochemical attributes and enhance the tolerance to low temperature, which provides a valuable strategy to improve tea quality and cold stress. [ABSTRACT FROM AUTHOR]

This study was aimed at investigating the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by smoking—based on bioinformatics analysis and in vitro experimental evidence. The GEO, GEO2R, TargetScan, miRDB, miRWalk, DAVID, and STRING databases were used for bioinformatics analysis. The mRNA expression and the protein levels were determined by real-time PCR and ELISA. After taking the intersection of the diversified results of the databases, four differentially expressed miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) were screened out. Subsequently, a total of 57 target genes of the selected miRNAs were obtained. The results of DAVID analysis showed that the selected miRNAs participated in COPD pathogenesis through long-term potentiation, the TGF-β signaling pathway, the PI3K-Akt signaling pathway, etc. The results of STRING prediction showed that TP53, EP300, and MAPK1 were the key nodes of the PPI network. The results of the confirmatory experiment showed that, compared with the control group, the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated, while the expression of MYB was down-regulated and the protein levels of ZEB1, MAPK1, and EP300 were increased. Taken together, miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) and their regulated target genes and downstream protein molecules (ZEB1, EP300, and MAPK1) may be closely related to the pathological process of COPD.

Vitiligo is a disease characterized by acquired depigmentation, white macules, and patches on the skin due to the dysfunction of epidermal melanocytes. In this study, we attempt to profile the microRNA (miRNA) expression patterns and predict the potential targets, assessing the biological functions of differentially expressed miRNAs in the blood of generalized vitiligo patients. Peripheral blood samples were taken from all participants, and the expression levels of 89 identified miRNAs were analyzed with real-time quantitative polymerase chain reaction (PCR). The results indicated significant upregulation of six miRNAs and downregulation of 19 miRNAs in the plasma of vitiligo patients. The top three upregulated miRNAs were hsa-miR-451a, hsa-miR-25-3p, and hsa-miR-19a-3p, and the top three downregulated miRNAs were hsa-miR-146a-5p, hsa-miR-940, and hsa-miR-142-3p. Moreover, the miRNA expression profiles of patients with Type 3 and Type 4 phototypes were substantially different in such a way that the patients with Type 3 phototype would be more prone to the emergence of melanoma and cancer. While significant variations in the expression patterns of miRNAs in male and female vitiligo patients were demonstrated, miR-let-7i-5p, miR-19a-3p, miR-25-3p, and miR-451a were commonly upregulated, and miR-142-3p and miR-146a-5p were commonly repressed in both sexes. This study may shed light on the roles of differentially expressed miRNAs in vitiligo patients by examining the miRNA expression patterns and the combined effects of miRNA and their predicted targets. [ABSTRACT FROM AUTHOR]

Camellia saponins are important by-products of Camellia Oleifer Abel. processing. In this study, an eco-friendly method based on natural deep eutectic solvents (NaDESs, proline and glycerol at a molar ratio of 2:5) was established to extract saponin s from C.oleifera cakes. The content of saponin (702.22 ± 1.28 mg/g) obtained using NaDES was higher than those extracted using water or methanol. UPLC-Q-TOF MS analysis of chemical structure showed that the difference in the extraction technique alter individual saponins. A widely targeted metabolomic approach and KEGG metabolic pathway analysis showed that the upregulated metabolites in the NaDES-based extract mainly included flavonoids, alkaloids, and phenolic acids; and they were involved in arginine and proline metabolism, metabolic pathways, phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, and flavonoid biosynthesis. The present study proposes a selective substitute for use in the extraction of camellia saponins with composition analysis. [Display omitted] • A Pro-Gly combination was optimized to extract saponins from Camellia oleifera cake. • Five compounds were identified only in methanol- and NaDES-based extracts. • Seven marker compounds with higher content in NE annotated in five pathways. [ABSTRACT FROM AUTHOR]

Host–virus protein interactions are critical for intracellular viral propagation. Understanding the interactions between cellular and viral proteins may help us develop new antiviral strategies. Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe damage to the global swine industry. Here, we employed co-immunoprecipitation and liquid chromatography-mass spectrometry to characterize 426 unique PEDV nucleocapsid (N) protein-binding proteins in infected Vero cells. A protein–protein interaction network (PPI) was created, and gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses revealed that the PEDV N-bound proteins belong to different cellular pathways, such as nucleic acid binding, ribonucleoprotein complex binding, RNA methyltransferase, and polymerase activities. Interactions of the PEDV N protein with 11 putative proteins: tripartite motif containing 21, DEAD-box RNA helicase 24, G3BP stress granule assembly factor 1, heat shock protein family A member 8, heat shock protein 90 alpha family class B member 1, YTH domain containing 1, nucleolin, Y-box binding protein 1, vimentin, heterogeneous nuclear ribonucleoprotein A2/B1, and karyopherin subunit alpha 1, were further confirmed by in vitro co-immunoprecipitation assay. In summary, studying an interaction network can facilitate the identification of antiviral therapeutic strategies and novel targets for PEDV infection. [ABSTRACT FROM AUTHOR]

The main features of a giant cell tumor of bone (GCTB) are frequent recurrence and aggressive osteolysis, which leads to a poor prognosis in patients. Although the treatment methods for a GCTB, such as scraping and resection, effectively inhibit the disease, the tendency toward malignant transformation remains. Therefore, it is important to identify new treatment methods for a GCTB. In this study, we first found high Siglec-15 expression in GCTB tissues, which was significantly associated with Campanacci staging and tumor recurrence. In Spearman's analysis, Siglec-15 expression was significantly correlated with Ki-67 levels in tumor tissues. In vitro, the mRNA and protein levels of Siglec-15 were high in GCTB stromal cells (Hs737. T), and Siglec-15 knockdown inhibited the biological characteristics of GCTB stromal cells. The RNA sequencing results enabled a prediction of the downstream genes by using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and MCODE analyses, and the findings showed that CXCL8 was significantly regulated by Siglec-15 and might be a promising downstream target gene of Siglec-15. Therefore, Siglec-15 may be a potential immunotherapy target for a GCTB. [ABSTRACT FROM AUTHOR]

Labor pain has an important impact on maternal labor experience, mood, and postpartum depression. It is of great emotional significance to pay attention to the pain stress response of pregnant women and take necessary intervention measures in the labor process to weaken the sense of delivery experience and reduce the risk of complications. To better understand the molecular alteration of pain and stress changes during the delivery, we analyzed the metabolomic and proteomic of the plasma collected during the labor process at different stages, revealing the significant changes in metabolites and proteins and the key regulatory pathways. The KEGG enrichment analysis showed the differentially expressed metabolites and differentially expressed proteins were mainly enriched in glutamate metabolism, glutathione metabolism, oxidative phosphorylation, glycolysis/gluconeogenesis, and citrate cycle (TCA cycle). In particular, the glutathione metabolism played a major role in the metabolic pathway of the whole labor process. The result demonstrated the potential significance of the glutathione metabolic pathway in pain regulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

During the operational phase of offshore wind farms, the generation of low-frequency underwater noise has received widespread attention due to its potential adverse impact on fish health. This study conducted a field survey of underwater noise at offshore wind farms located in Shandong province, China. Subsequently, a small-scale experiment was conducted to study the stress on black rockfish (Sebastes schlegelii). The fish were exposed to noise with dominant frequency of 80 Hz, 125 Hz and 250 Hz. These frequencies are same with the frequencies from wind power noise (wpn) at the actual site. After a 40-day experimental period, transcriptome sequencing was conducted on brain, liver, and kidney tissues of black rockfish to elucidate the underlying molecular mechanisms involved in the response to noise stress originating from offshore wind farms. The results revealed that the 125 Hz group exhibited the highest number of differentially expressed genes (DEGs) between the noise-exposed and control check group (CK group), with a total of 797 in the brain, 1076 in the liver, and 2468 in the kidney. Gene Ontology (GO) analysis showed that DEGs were significantly enriched in entries related to cellular processes, membrane components, binding, and metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were enriched mainly in metabolism, immunity, apoptosis, signal transduction, and diseases. The findings indicate that prolonged exposure to underwater noise from offshore wind farms may induce metabolic imbalance, immune dysfunction, and an increased risk of myocardial diseases in black rockfish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that can cause diarrhea in pigs of all ages with varying severity. Host-virus protein interactions are critical for intracellular viral replication. Elucidating the interactions between cellular and viral proteins can help us to design antiviral strategies. PDCoV N protein is the most abundant and vital regulator in virus replication. In this study, 604 host proteins were identified to interact with PDCoV N protein by Co-IP combined with LC-MS, of which 243 proteins were specifically bound to N protein. PPI analysis revealed that the N-interacting host proteins are categorized into three groups: ribonucleoprotein complex biogenesis modulation, cellular nitrogen compound metabolism, and nucleic acid binding. GO and KEGG analyses showed that the host proteins are primarily involved in mRNA splicing, stress granule assembly, spliceosomal snRNP assembly. Additionally, four host proteins-TRIM25, HNRNPUL1, RPS27A, and SLC3A2-were selected to validate the interactome data through Co-IP and Confocal assays. This study can help in designing anti-PDCoV strategies and understanding the replication mechanism of PDCoV., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abstract Background Atherosclerosis is the leading cause of cardiovascular disease with a high mortality worldwide. Understanding the atherosclerosis pathogenesis and identification of efficient diagnostic signatures remain major problems of modern medicine. This study aims to screen the potential diagnostic genes for atherosclerosis. Methods We downloaded the gene chip data of 135 peripheral blood samples, including 57 samples with atherosclerosis and 78 healthy subjects from GEO database (Accession Number: GSE20129). The weighted gene co-expression network analysis was applied to identify atherosclerosis-related genes. Functional enrichment analysis was conducted by using the clusterProfiler R package. The interaction pairs of proteins encoded by atherosclerosis-related genes were screened using STRING database, and the interaction network was further optimized with the cytoHubba plug-in of Cytoscape software. Results The logistic regression diagnostic model was constructed to predict normal and atherosclerosis samples. A gene module which included 532 genes related to the occurrence of atherosclerosis were screened. Functional enrichment analysis basing on the 532 genes identified 235 significantly enriched GO terms and 44 significantly enriched KEGG pathways. The top 50 hub genes of the protein–protein interaction network were identified. The final logistic regression diagnostic model was established by the optimal 10 key genes, which could distinguish atherosclerosis samples from normal samples. Conclusions A predictive model based on 10 potential atherosclerosis-related genes was obtained, which should shed light on the diagnostic research of atherosclerosis.

Background: Globally, esophageal cancer ranks as the seventh most common cancer. Esophageal squamous cell carcinoma (ESCC) is one of its major histological types. ESCC accounts for the vast majority of cases in China, and the mortality rate is high. Cisplatin, the standard adjuvant chemotherapy drug for ESCC, has a modest response rate due to the development of drug resistance. Hinokiflavone (HF) is a natural biflavonoid compound with anti-melanoma activity. However, its anti-tumor effect on ESCC and the underlying mechanisms remain largely unknown. Methods: The ESCC cell lines KYSE150 and TE14 were used. The cell counting kit-8 assay and flow cytometry analysis, along with colony formation, EdU, wound healing, and Transwell migration assays, were performed to assess cell characteristics (viability, migration, invasion, and apoptosis) following treatment with HF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), western blotting, and molecular docking were used to investigate the pathways potentially modulated by HF. In vivo antitumor effects of HF were also investigated using a mouse xenograft model. Results: Our findings revealed that HF inhibited ESCC cell proliferation. Hoechst 33342 staining, annexin V-FITC/PI staining, and western blotting confirmed that HF causes caspase-dependent apoptosis. KEGG pathway enrichment analysis and western blotting indicated that the PI3K/AKT/mTOR pathway played an important role in the process of HF-induced apoptosis. Furthermore, HF effectively impaired the migration and invasion abilities of KYSE150 cells and downregulated the expression of the matrix metalloproteinases (MMP) MMP2 and MMP9. HF inhibited tumor growth and exhibited minimal toxicity in the organs of the KYSE150 xenograft model. Conclusion: This is the first study to demonstrate the inhibition of ESCC growth and progression by HF. The underlying mechanism is through blocking the PI3K/AKT/mTOR signaling pathway, thereby inhibiting cell proliferation and inducing apoptosis. HF can be used as a complementary/alternative agent for ESCC therapy. [ABSTRACT FROM AUTHOR]

Background. Primary dental caries is the most prevalent oral disease among preschool children, which can cause severe damage to teeth and even affect the mental well-being of children. Various studies have demonstrated that the oral microbiome plays a pivotal role in the onset and development of dental caries. However, it remains uncertain about the key microbial markers associated with caries, owing to the limited evidence. Methods. Fifteen S-ECC children and fifteen healthy controls were selected from three-year-old children in this study. Their clinical data and oral saliva samples were collected. Shotgun sequencing was conducted to investigate the microbial differences and the relevant functions between the two groups. Results. We observed no apparent difference in oral microbial community diversity between the two groups. Still, at the genus/species levels, several characteristic genera/species such as Propionibacterium, Propionibacterium acidifaciens, Prevotella denticola, Streptococcus mutans and Actinomyces sp. oral taxon 448/414 increased significantly in S-ECC children, compared with the oral health group. Furthermore, we found that functional pathways involving glycolysis and acid production, such as starch and sucrose metabolism, fructose and mannose metabolism, glycolysis/gluconeogenesis, were prominently up-regulated in the high-caries group. Conclusions. Our study showed that dental caries in children were associated with the alterations in the oral microbiota at the composition and functional levels, which may potentially inspire the exploration of microbial diagnosis or therapeutic treatments. [ABSTRACT FROM AUTHOR]

Hypertension is a cardiovascular disease that causes great harm to health and life, affecting the function of important organs and accompanied by a variety of secondary diseases, which need to be treated with drugs for a long time. P. ternata alone or combination with western medicine has played an important role in traditional Chinese medicine. Although P. ternata is used clinically to treat hypertension, its functional molecular mechanism and pharmacological mechanism have not been elucidated. Therefore, in this study, the potentially effective components, and targets of P. ternata in the treatment of hypertension were screened by the method of network pharmacology, and the mechanism of P. ternata in the treatment of hypertension was analyzed by constructing a component-target relationship network, PPI interaction network, targets’ function analysis, and molecular docking. In the study, 12 potentially effective components and 88 targets were screened, and 3 potential protein modules were found and analyzed after constructing a PPI network using targets. In addition, 10 targets were selected as core targets of the PPI network. After that, the targets were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, the molecular docking method is used to study the interaction between the targets and the active components. The above evidence shows that the mechanism of P. ternata in the treatment of hypertension is complicated, as it acts in many ways, mainly by affecting nerve signal transmission, cell proliferation, and apoptosis, calcium channels, and so on. The binding between targets and active components mainly depends on Pi bonds and hydrogen bonds. Using the method of network pharmacology and molecular docking to analyze the mechanism of P. ternata in the treatment of hypertension will help to provide a better scientific basis for the combined use of traditional Chinese medicine and western medicine, and will better help to improve the quality of P. ternata and point out its direction.

• Metabolic patterns and regulatory pathways during pumpkin seeds germination were illuminated. • Significant metabolic fluctuations at different timepoint of sprouting were pinpointed. • Fatty acids, phospholipids and lignans experienced notable accumulation during germination. • Biosynthesis of unsaturated fatty acids and phenylpropanoid biosynthesis were principle metabolic pathways. • Day 7 sprouted samples exerted noteworthy inhibitory potential against AChE enzyme. • Docosahexaenoic acid, lirioresinol A and tocotrienols were possibly efficacy constituents. While pumpkin seeds (Cucurbita maxima) are regarded as agro-industrial waste, they serve as powerhouses packed with a plethora of valuable compounds with potential nutraceutical significance. The present work offers an integrated view of metabolites dynamics and their regulatory pathways over the course of pumpkin seeds germination and their potential entanglements on Alzheimerʼs disease (AD) mitigation through Ultra Performance Liquid Chromatography-mass spectrometry (UPLC-MS/MS) analysis and chemometrics. A total of 76 compounds spanning amino acids, phenolic acid, flavonoids, lignans, vitamins, fatty acids, phospholipids and phytosterols were annotated revealing changing trends during germination process. Coincidentally, orthogonal projection to latent structures-discriminant analysis (OPLS-DA) demonstrated a clear separation trend among the five pumpkin samples assuring their chemical heterogeneity. Complementarily, OPLS-DA models were constructed in different timepoint comparisons to pick out the significant metabolic features which were subsequently imported into MetaboAnalyst 5.0 (https://www.metaboanalyst.ca/) software for metabolic pathway enrichment analysis. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed biosynthesis of unsaturated fatty acids, phenylpropanoid biosynthesis, glycerophospholipid metabolism and phenylalanine, tyrosine and tryptophan biosynthesis as the top predictive metabolic pathways associated with significant phytochemical shifts during germination process. Importantly, our efficacy experimental results dissected that 5 d and 7 d sprouted samples exerted noteworthy inhibitory potentials against acetylcholine esterase (AChE) and monoamine oxidase (MAO-B) enzymes. OPLS-derived coefficients plots portrayed that docosahexaenoic acid, oleic acid, lirioresinol A and tocotrienols dramatically augmented during germination were probably ascribed to promising AChE and MAO-B inhibitory activities. These findings offer a turning point for using pumpkin sprouts with an appreciable biochemical content to pursue the concept of nutritional therapy and accelerate perpetual influx of novel bioproducts to rectify AD. [Display omitted] [ABSTRACT FROM AUTHOR]

The genomic and carbohydrate metabolic features of Pseudoalteromonas agarivorans Hao 2018 (P. agarivorans Hao 2018) were investigated through pan-genomic and transcriptomic analyses, and key enzyme genes that may encode the process involved in its extracellular polysaccharide synthesis were screened. The pan-genome of the P. agarivorans strains consists of a core-genome containing 2331 genes, an accessory-genome containing 956 genes, and a unique-genome containing 1519 genes. Clusters of Orthologous Groups analyses showed that P. agarivorans harbors strain-specifically diverse metabolisms, probably representing high evolutionary genome changes. The Kyoto Encyclopedia of Genes and Genomes and reconstructed carbohydrate metabolic pathways displayed that P. agarivorans strains can utilize a variety of carbohydrates, such as d-glucose, d-fructose, and d-lactose. Analyses of differentially expressed genes showed that compared with the stationary phase (24 h), strain P. agarivorans Hao 2018 had upregulated expression of genes related to the synthesis of extracellular polysaccharides in the logarithmic growth phase (2 h), and that the expression of these genes affected extracellular polysaccharide transport, nucleotide sugar synthesis, and glycosyltransferase synthesis. This is the first investigation of the genomic and metabolic features of P. agarivorans through pan-genomic and transcriptomic analyses, and these intriguing discoveries provide the possibility to produce novel marine drug lead compounds with high biological activity. [ABSTRACT FROM AUTHOR]

Background: Globally, esophageal cancer ranks as the seventh most common cancer. Esophageal squamous cell carcinoma (ESCC) is one of its major histological types. ESCC accounts for the vast majority of cases in China, and the mortality rate is high. Cisplatin, the standard adjuvant chemotherapy drug for ESCC, has a modest response rate due to the development of drug resistance. Hinokiflavone (HF) is a natural biflavonoid compound with anti-melanoma activity. However, its anti-tumor effect on ESCC and the underlying mechanisms remain largely unknown. Methods: The ESCC cell lines KYSE150 and TE14 were used. The cell counting kit-8 assay and flow cytometry analysis, along with colony formation, EdU, wound healing, and Transwell migration assays, were performed to assess cell characteristics (viability, migration, invasion, and apoptosis) following treatment with HF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), western blotting, and molecular docking were used to investigate the pathways potentially modulated by HF. In vivo anti-tumor effects of HF were also investigated using a mouse xenograft model. Results: Our findings revealed that HF inhibited ESCC cell proliferation. Hoechst 33342 staining, annexin V-FITC/PI staining, and western blotting confirmed that HF causes caspase-dependent apoptosis. KEGG pathway enrichment analysis and western blotting indicated that the PI3K/AKT/mTOR pathway played an important role in the process of HF-induced apoptosis. Furthermore, HF effectively impaired the migration and invasion abilities of KYSE150 cells and downregulated the expression of the matrix metalloproteinases (MMP) MMP2 and MMP9. HF inhibited tumor growth and exhibited minimal toxicity in the organs of the KYSE150 xenograft model. Conclusion: This is the first study to demonstrate the inhibition of ESCC growth and progression by HF. The underlying mechanism is through blocking the PI3K/AKT/mTOR signaling pathway, thereby inhibiting cell proliferation and inducing apoptosis. HF can be used as a complementary/alternative agent for ESCC therapy. [ABSTRACT FROM AUTHOR]

The stellate ganglion (SG) of the autonomic nervous system plays important role in cardiovascular diseases (CDs). Myocardial infarction (MI) is associated with sustained increasing cardiac sympathetic nerve activity. Expressions and functions of proteins in SG tissue after MI are remaining unclear. This study is to explore the expression characteristics of proteins in SGs associated with MI. Japanese big-ear white rabbits (n = 22) were randomly assigned to the control group and MI group. The MI model was established by left anterior descending coronary artery ligation and confirmed by serum myocardial enzymes increasing 2,3,5-triphenyltetrazolium (TTC) staining and echocardiography. The expressions of proteins in rabbit SGs after MI were detected using tandem mass tags (TMT) quantitative proteomic sequencing. There were 3,043 credible proteins were predicted in rabbit SG tissues and 383 differentially expressed proteins (DEPs) including 143 upregulated and 240 downregulated proteins. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEPs involved in adrenergic signaling in cardiomyocytes, positive regulation of ERK1 and ERK2 cascade, and other biological processes. Three kinds of proteins directly correlated to CDs were selected to be validated by the subsequent western blot experiment. This study first identified the characterization of proteins in rabbit SG after MI, which laid a solid foundation for revealing the mechanism of roles of SG on the MI process. [ABSTRACT FROM AUTHOR]

Tea (Camellia sinensis L.) is an important perennial cash crop and a typical subtropical plant. It is widely concerned because of its unique flavor and health benefits. In recent years, low temperatures have severely restricted the growth of tea plants and quality of tea products, especially in spring. As a common precursor for all porphyrin compounds, 5-aminolevulinic acid (ALA) is involved in photosynthesis and respiration and plays an active role in improving salt, drought and low-temperature tolerance in plants. However, it is not yet clear what affect exogenous ALA has on tea plants’ tolerance under low temperature. In the present study, we collected and deciphered the transcriptome profiles from Shaancha No. 1 leaf tissues under low temperature (−4 °C) treatment (T-4), exogenous ALA application (T-A), pretreated ALA before low temperature (T-A-4) and untreated control (T-CK). Results showed that 4990 (2375 up- and 2615 down-regulated), 223 (103 up- and 120 down-regulated) and 92 (13 up- and 79 down-regulated) differentially expression genes (DEGs) were identified at T-CK vs. T-4, T-CK vs. T-A and T-4 vs. T-A-4, respectively. Both T-4 and T-A treatments triggered a myriad of stress resistance genes up-regulated related to multiple signaling pathways by means of Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. This included MAPK, a toll-like receptor that signals pathways involved in cold resistance. However, gene ontology (GO) analysis showed that the DEGs in T-4 treatment were mainly enriched in the phenylpropanoid metabolic and redox processes that were relevant to membrane structure damage response. In contrast, the DEGs in T-A treatment were mainly enriched in cell recognition and amylase activity. Furthermore, in pairwise comparison of T-A-4 vs. T-4, the DEGs were enriched in ascorbate and aldarate, retionol, taurine and hypotaurine, glutathione metabolic pathways and two biosynthesis process including zeatin, diterpenoid biosynthesis, which might contribute to mitigating the damage caused by low temperature. Overall, these results indicated that exogenous ALA application may improve the biochemical attributes and enhance the tolerance to low temperature, which provides a valuable strategy to improve tea quality and cold stress.

The stellate ganglion (SG) of the autonomic nervous system plays important role in cardiovascular diseases (CDs). Myocardial infarction (MI) is associated with sustained increasing cardiac sympathetic nerve activity. Expressions and functions of proteins in SG tissue after MI are remaining unclear. This study is to explore the expression characteristics of proteins in SGs associated with MI. Japanese big-ear white rabbits (n = 22) were randomly assigned to the control group and MI group. The MI model was established by left anterior descending coronary artery ligation and confirmed by serum myocardial enzymes increasing 2,3,5-triphenyltetrazolium (TTC) staining and echocardiography. The expressions of proteins in rabbit SGs after MI were detected using tandem mass tags (TMT) quantitative proteomic sequencing. There were 3,043 credible proteins were predicted in rabbit SG tissues and 383 differentially expressed proteins (DEPs) including 143 upregulated and 240 downregulated proteins. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEPs involved in adrenergic signaling in cardiomyocytes, positive regulation of ERK1 and ERK2 cascade, and other biological processes. Three kinds of proteins directly correlated to CDs were selected to be validated by the subsequent western blot experiment. This study first identified the characterization of proteins in rabbit SG after MI, which laid a solid foundation for revealing the mechanism of roles of SG on the MI process.

Background: Atherosclerosis is the leading cause of cardiovascular disease with a high mortality worldwide. Understanding the atherosclerosis pathogenesis and identification of efficient diagnostic signatures remain major problems of modern medicine. This study aims to screen the potential diagnostic genes for atherosclerosis.Methods: We downloaded the gene chip data of 135 peripheral blood samples, including 57 samples with atherosclerosis and 78 healthy subjects from GEO database (Accession Number: GSE20129). The weighted gene co-expression network analysis was applied to identify atherosclerosis-related genes. Functional enrichment analysis was conducted by using the clusterProfiler R package. The interaction pairs of proteins encoded by atherosclerosis-related genes were screened using STRING database, and the interaction network was further optimized with the cytoHubba plug-in of Cytoscape software.Results: The logistic regression diagnostic model was constructed to predict normal and atherosclerosis samples. A gene module which included 532 genes related to the occurrence of atherosclerosis were screened. Functional enrichment analysis basing on the 532 genes identified 235 significantly enriched GO terms and 44 significantly enriched KEGG pathways. The top 50 hub genes of the protein-protein interaction network were identified. The final logistic regression diagnostic model was established by the optimal 10 key genes, which could distinguish atherosclerosis samples from normal samples.Conclusions: A predictive model based on 10 potential atherosclerosis-related genes was obtained, which should shed light on the diagnostic research of atherosclerosis. [ABSTRACT FROM AUTHOR]

Host–virus protein interactions are critical for intracellular viral propagation. Understanding the interactions between cellular and viral proteins may help us develop new antiviral strategies. Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe damage to the global swine industry. Here, we employed co-immunoprecipitation and liquid chromatography-mass spectrometry to characterize 426 unique PEDV nucleocapsid (N) protein-binding proteins in infected Vero cells. A protein–protein interaction network (PPI) was created, and gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses revealed that the PEDV N-bound proteins belong to different cellular pathways, such as nucleic acid binding, ribonucleoprotein complex binding, RNA methyltransferase, and polymerase activities. Interactions of the PEDV N protein with 11 putative proteins: tripartite motif containing 21, DEAD-box RNA helicase 24, G3BP stress granule assembly factor 1, heat shock protein family A member 8, heat shock protein 90 alpha family class B member 1, YTH domain containing 1, nucleolin, Y-box binding protein 1, vimentin, heterogeneous nuclear ribonucleoprotein A2/B1, and karyopherin subunit alpha 1, were further confirmed by in vitro co-immunoprecipitation assay. In summary, studying an interaction network can facilitate the identification of antiviral therapeutic strategies and novel targets for PEDV infection.

Renal cell carcinoma (RCC), with high morbidity and mortality, is one of the top ten serious cancers. Due to limited therapies and little knowledge about the mechanism underlying RCC, overall survival of RCC patients is poor. UBE2C is a member of ubiquitin modification system and promotes carcinogenesis in cancer, but its role in RCC is unknown. Based on the TCGA (The Cancer Genome Atlas) data, UBE2C was over-expressed in a total of 525 RCC tissues and displayed higher expression in advanced tissues (stage IV vs stage I, p

Objective: To explore the mechanism of Radix Astragali-Lithospermum Erythrorhizon on the treatment of diabetic ulcer through the method of network pharmacology. Methods: This study included 32 compounds and 81 key targets. 100 GO functional items and 116 KEGG signal pathways were obtained by enrichment analysis. Quercetin, kaempferol, isorhamnetin, mononetin, sitosterol, ivy sapogenin and other components of astragalus-purple herb play a key role in the targets of interleukin-6, cystatin 3, vascular endothelial growth factor, epidermal growth factor receptor and mitogen-activated protein kinase 8 in diabetic ulcer, and are mainly concentrated in AGE-RAGE, TNF and other signal pathways. Results: There were 32 compounds and 81 key targets. 100 GO functional items and 116 KEGG signal pathways were obtained by enrichment analysis. Quercetin, kaempferol, isorhamnetin, mononetin, sitosterol, ivy sapogenin and other components of astragalus-purple herb play a key role in the targets of interleukin-6, cystatin 3, vascular endothelial growth factor, epidermal growth factor receptor and mitogen-activated protein kinase 8 in diabetic ulcer, and are mainly concentrated in AGE-RAGE, TNF and other signal pathways. Conclusion: Radix Astragali-Lithospermum Erythrorhizon may play the role of inhibiting inflammation, anti-apoptosis, promoting cell proliferation, angiogenesis and immune regulation through multi-components and multitargets, and play a role in the treatment of diabetic ulcer. [ABSTRACT FROM AUTHOR]

The genomic and carbohydrate metabolic features of Pseudoalteromonas agarivorans Hao 2018 (P. agarivorans Hao 2018) were investigated through pan-genomic and transcriptomic analyses, and key enzyme genes that may encode the process involved in its extracellular polysaccharide synthesis were screened. The pan-genome of the P. agarivorans strains consists of a core-genome containing 2331 genes, an accessory-genome containing 956 genes, and a unique-genome containing 1519 genes. Clusters of Orthologous Groups analyses showed that P. agarivorans harbors strain-specifically diverse metabolisms, probably representing high evolutionary genome changes. The Kyoto Encyclopedia of Genes and Genomes and reconstructed carbohydrate metabolic pathways displayed that P. agarivorans strains can utilize a variety of carbohydrates, such as d-glucose, d-fructose, and d-lactose. Analyses of differentially expressed genes showed that compared with the stationary phase (24 h), strain P. agarivorans Hao 2018 had upregulated expression of genes related to the synthesis of extracellular polysaccharides in the logarithmic growth phase (2 h), and that the expression of these genes affected extracellular polysaccharide transport, nucleotide sugar synthesis, and glycosyltransferase synthesis. This is the first investigation of the genomic and metabolic features of P. agarivorans through pan-genomic and transcriptomic analyses, and these intriguing discoveries provide the possibility to produce novel marine drug lead compounds with high biological activity.

Environmental changes in intensive aquaculture commonly lead to hypoxic stress for cultured largemouth bass (Micropterus salmoides). To better to understand the hypoxic stress response mechanisms, the miRNA expression profiles of the livers of largemouth bass exposed for 24 h to three different dissolved oxygen levels (7.0 ± 0.2 mg/L as control, 3.0 ± 0.2 mg/L and 1.2 ± 0.2 mg/L) were compared. In this study, a total of 266 known miRNAs were identified, 84 of which were differentially expressed compared with the control group. Thirteen of the differentially expressed miRNAs (miR-15b-5p, miR-30a-3p, miR-133a-3p, miR-19d-5p, miR-1288-3p, miR456, miR-96-5p, miR-23a-3p, miR-23b-5p, miR-214, miR-24, miR-20a-3p, and miR-2188-5p) were significantly enriched in VEGF signaling pathway, MAPK signaling pathway, and phosphatidylinositol signaling system. These miRNAs were significantly downregulated during stress, especially after a 4-h exposure to hypoxia. In contrast, their target genes (vegfa, pla2g4a, raf1a, pik3c2a, clam2a, inpp1, pi4k2b, mtmr14, ip6k, itpkca, map3k7, and Jun) were significant upregulated after 4 h of hypoxic stress. Moreover, two potential hypoxia-tolerance signal transduction pathways (MAPK signaling pathway and phosphatidylinositol signaling system) were revealed, both of which may play important roles in responding to acute hypoxic stress. We see that miRNAs played an important role in regulating gene expression related to physiological responses to hypoxia. [ABSTRACT FROM AUTHOR]

Exopolysaccharides (EPSs) are carbohydrate polymers produced and secreted by microorganisms. In a changing marine environment, EPS secretion can reduce damage from external environmental disturbances to microorganisms. Meanwhile, EPSs have promising application prospects in the fields of food, cosmetics, and pharmaceuticals. Changes in external environmental pH have been shown to affect the synthesis of EPSs in microorganisms. In this study, we analyzed the effects of different initial fermentation pHs on the production, monosaccharide composition, and antioxidant activity of the EPSs of Pseudoalteromonas agarivorans Hao 2018. In addition, the transcriptome sequence of P. agarivorans Hao 2018 under different initial fermentation pH levels was determined. GO and KEGG analyses showed that the differentially expressed genes were concentrated in the two-component regulatory system and bacterial chemotaxis pathways. We further identified the expression of key genes involved in EPS synthesis during pH changes. In particular, the expression of genes encoding the glucose/galactose MFS transporter, phosphomannomutase, and mannose-1-phosphate guanylyltransferase was upregulated when the environmental pH increased, thus promoting EPS synthesis. This study not only contributes to elucidating the environmental adaptation mechanisms of P. agarivorans, but also provides important theoretical guidance for the directed development of new products using biologically active polysaccharides.

Background: Dexmedetomidine is widely used for perioperative and ICU patients. microRNAs (miRNAs) function as regulators of gene expression. The aim of the study was to assay expression profiling of microRNA in rat hearts following administration of dexmedetomidine. Methods: In this study 6 rats were randomly divided into two groups (n = 3): dexmedetomidine group and control group. The rats of dexmedetomidine group were intraperitoneally given dexmedetomidine in a dose of 100 μg/kg whereas the rats in control group were administered normal saline intraperitoneally. The hearts were excised 30 min after the administration of dexmedetomidine or normal saline under anesthesia. The samples were analyzed for differentially expressed microRNAs with Exiqon miRNA Array. The differentially expressed microRNAs were confirmed by using qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to find the target genes and signaling pathways of the aberrantly expressed miRNAs. Results: Six microRNAs were identified to be significantly expressed, among of which, five microRNAs (miRNA-434-3p, miRNA-3596d, miRNA-496-5p, miRNA-7a-2-3p and miRNA-702-3p) were up-regulated and 1 microRNA (miRNA-208b-3p) down-regulated compared to those of control group. The aberrantly expressed microRNAs were further validated by Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). GO and KEGG analyses were used to identify target genes and the signaling pathways. Conclusions: The use of dexmedetomidine is associated with differentially expressed microRNAs which may be involved in cardioprotection following administration of dexmedetomidine.

Abstract Background Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet. Methods In this study, we investigated the metabolite profiling of He plasma treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF) mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO and KEGG analysis we try to figure out the metabolism pathway that was significantly affected by gas plasma treatment. Results By GC-TOF mass-spectrometry, 573 signals were detected and evaluated using PCA and OPLS-DA. By KEGG analysis we listed all the differential metabolites and further classified into different metabolic pathways. The results showed that beta-alanine metabolism pathway was the most significant change after He gas plasma treatment in myeloma cells. Besides, propanoate metabolism and linoleic acid metabolism should also be concerned during gas plasma treatment of cancer cells. Conclusions Cold atmospheric plasma treatment could significantly alter the metabolite profiling of myeloma tumor cells, among which, the beta-alanine metabolism pathway is the most susceptible to He gas plasma treatment.

Abstract Background Since the first evidence suggesting existence of stem-like cancer cells, the process of cells reprogramming to the stem cell state remains as an attractive tool for cancer stemness research. Current knowledge in the field of cancer stemness, indicates that the microenvironment is a fundamental regulator of cell behavior. With regard to this, we investigated the changes of genome wide gene expression in reprogrammed human colon normal epithelial CRL-1831 and colon carcinoma DLD1 cell lines grown under more physiologically relevant three-dimensional (3D) cell culture microenvironment compared to 2D monolayer. Methods Whole genome gene expression changes were evaluated in both cell lines cultured under 3D conditions over a 2D monolayer by gene expression microarray analysis. To evaluate the biological significance of gene expression changes, we performed pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Gene network analysis was used to study relationships between differentially expressed genes (DEGs) in functional categories by the GeneMANIA Cytoscape toolkit. Results In total, we identified 3228 and 2654 differentially expressed genes (DEGs) for colon normal and cancer reprogrammed cell lines, respectively. Furthermore, the expression of 1097 genes was commonly regulated in both cell lines. KEGG enrichment analysis revealed that in total 129 and 101 pathways for iPSC-CRL-1831 and for CSC-DLD1, respectively, were enriched. Next, we grouped these pathways into three functional categories: cancer transformation/metastasis, cell interaction, and stemness. β-catenin (CTNNB1) was confirmed as a hub gene of all three functional categories. Conclusions Our present findings suggest common pathways between reprogrammed human colon normal epithelium (iPSC-CRL-1831) and adenocarcinoma (CSC-DLD1) cells grown under 3D microenvironment. In addition, we demonstrated that pathways important for cancer transformation and tumor metastatic activity are altered both in normal and cancer stem-like cells during the transfer from 2D to 3D culture conditions. Thus, we indicate the potential of cell culture models enriched in normal and cancer stem-like cells for the identification of new therapeutic targets in cancer treatment.

Key message: MiRNA transcriptome analysis of different tissues in poplar and larch suggests variant roles of miRNAs in regulating wood formation between two kinds of phyla. Poplar and larch belong to two different phyla. Both are ecological woody species and major resources for wood-related industrial applications. However, wood properties are different between these two species and the molecular basis is largely unknown. In this study, we performed high-throughput sequencing of microRNAs (miRNAs) in the three tissues, xylem, phloem and leaf of Populus alba × Populus glandulosa and Larix kaempferi. Differentially expressed miRNA (DEmiRNA) analysis identified 85 xylem-specific miRNAs in P. alba × P. glandulosa and 158 xylem-specific miRNAs in L. kaempferi. Among 36 common miRNAs, 12 were conserved between the two species. GO and KEGG analyses of the miRNA target genes showed similar metabolism in two species. Through KEGG and BLASTN, we predicted target genes of xylem differentially expressed (DEmiRNA) in the wood formation-related pathways and located DEmiRNAs in these pathways. A network was built for wood formation-related DEmiRNAs, their target genes and orthologous genes in Arabidopsis thaliana. Comparison of DEmiRNA and target gene annotation between P. alba × P. glandulosa and L. kaempferi suggested the different functions of DEmiRNAs and divergent mechanism in wood formation between two species, providing knowledge to understand wood formation mechanism in gymnosperm and angiosperm woody plants. [ABSTRACT FROM AUTHOR]

In plants, cytochrome P450 monooxygenase (CYP) plays an important role in detoxifying xenobiotic chemicals and coordinating abiotic stresses. Agilent 44 K rice microarray has been used to focus on the transcriptional profile of osCYP genes in rice seedling exposed to Cr solution containing K2CrO4 or Cr(NO3)3. Our study showed that expression profiles of 264 osCYP genes identified were tissue, dose and stimulus specific in rice seedlings. Comparative genomics analysis revealed that more differentially expressed osCYP genes were discovered in roots than in shoots under both Cr exposures. Results from Venn diagram analysis of differentially expressed osCYP genes demonstrated that there were common osCYP genes and unique osCYP genes present in different rice tissue as well as in different Cr treatments, which may control and/or regulate involvement of different CYP isoenzymes under Cr exposure individually or combinedly. KEGG analysis indicated that significant up- and down-regulated osCYP genes in rice tissues were chiefly related to "biosynthesis of secondary metabolites". However, involvements of osCYP genes mapped in the "biosynthesis of secondary metabolites" were tissue and dose specific, implying their distinctly responsive and adaptive mechanisms during Cr exposure. Overall, our findings are evident to describe and clarify their individual roles of specific osCYP genes in regulating involvement of CYP isoforms in Cr detoxification by rice seedlings. [ABSTRACT FROM AUTHOR]

Andrographis paniculata plantlets were elicited with 50 µM jasmonic acid (JA) in vitro for 1 week and proteome analysis was carried out. HPLC analysis revealed enhanced andrographolide content in JA treated plantlets. Isolated protein samples from both JA treated and untreated control plantlets were analysed by Q-TOF–LC–MS/MS. JA elicitation influenced expression of 22 proteins involved in the isoprenoid pathway in treated and three with untreated plantlets. 3308 proteins in control and 3994 from JA elicited were identified with 1393 found common in both. The differential expression study of proteins revealed a pattern with 621 decreased and 201 enhanced. About 40 metabolic processes identified by functional annotation of proteins and highly elevated (5.7%) post-translational modifications were observed in JA treated. KEGG analysis unveiled appearance of additional secondary metabolism related proteins; primarily phenylpropanoids, isoprenoids and flavonoids from both elicited and untreated. Various transcription factors such as DREB's, MYC's, WRKY, and MED which uniquely influenced terpenoid biosynthesis were identified through differential expression study following JA elicitation. The total proteome and differential expression of proteins in JA elicited and untreated in vitro grown A. paniculata plantlets are reported for the first time. These finding will be of significance in understanding elicitation mechanism, gene regulation, metabolic network changes in post elicitation scenario, search of new/novel compounds and developing strategies for manipulating yield enhancement of plant-derived bioactive molecules in general and diterpene lactones in particular. Key message: Andrographis paniculata proteome showed 3308 control proteins, 3994 in JA elicited tissue. Differential expression study indicated 621 downregulated, 201 upregulated proteins. KEGG revealed terpenoid biosynthesis upregulation attributed to enhanced andrographolide. [ABSTRACT FROM AUTHOR]

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To investigate the association between DD, ID and II genotypes of ACE gene and carotid stenosis, and to construct a network of ACE-related genes regulating carotid stenosis. Meta-analysis was used to study the association between three genotypes DD, ID and II of carotid stenosis susceptibility gene ACE; functional annotation of ACE gene was conducted by GO analysis; and a network of ACE-related genes that regulate the mechanisms of carotid stenosis was established. Meta-analysis showed that DD and II genotypes of ACE gene were associated with carotid stenosis. GO analysis showed that the main biological processes involved in ACE include: the process of transforming angiotensinogen into mature angiotensin; angiotensin's mediation of the brain's response to alcohol consumption and thirst control; any chemical reaction involving the regulation of angiotensin; and the process of catalyzing the release of a C-terminal dipeptide from a polypeptide chain. A network of ACE gene regulation of carotid stenosis was constructed in combination with KEGG analysis. The ACE gene is a susceptibility gene for carotid stenosis. Through the functional annotation and pathway analysis of ACE gene, an ACE gene-involved carotid stenosis regulatory mechanisms network was constructed. [ABSTRACT FROM AUTHOR]

Organic acid production including lactate and acetate is an economically attractive technology that has gained momentum worldwide over the past years. These series of action need to be performed by an esoteric and complex microbial community, in which different members have distinct roles in the establishment of a collective organization. In this study, we analyzed the bioma from bioreactors with various pH conditions of 4.0, 5.0 and 6.0 (R1, R2 and R3), respectively, involved in acidogenic digestion for stable production of various organic acids by means of high-throughput Illumina sequencing, disclosing thousands of genes and extracting more than 53 microbial genomes. At pH 5.0, the hydrolysis reaction was enhanced and thus the lactic acid fermentation was stably improved to 45.96 mm/L and acetic acid to 73.77 mm/L. R2 was found with the most suitable pH condition for stable organic acids production as Lactobacilli and Bifidobacteria were the major members. Both the members have the key roles in heterofermentation and produce higher transcripts of key encoding enzymes involved in the dominant heterofermentation pathways. [ABSTRACT FROM AUTHOR]

The red-eared slider (Trachemys scripta elegans), identified as one of the 100 most invasive species in the world, is a freshwater turtle originally from the eastern United States and northeastern Mexico. Field investigations have shown that T. s. elegans can survive and lay eggs in saline habitats. In order to understand the molecular mechanisms of salinity adaptation, high-throughput RNA-Seq was utilized to identify the changes in gene expression profiles in the liver of T. s. elegans in response to elevated salinity. We exposed individuals to 0, 5, or 15 psu (practical salinity units) for 30 days. A total of 157.21 million reads were obtained and assembled into 205138 unigenes with an average length of 620 bp and N50 of 964 bp. Of these, 1019 DEGs (differentially expressed genes) were found in the comparison of 0 vs. 5 psu, 1194 DEGs in 0 vs. 15 psu and 1180 DEGs in 5 vs. 15 psu, which are mainly related to macromolecule metabolic process, ion transport, oxidoreductase activity and generation of precursor metabolites and energy by GO (Gene Ontology) enrichment analyses. T. s. elegans can adapt itself into salinity by balancing the entry of sodium and chloride ions via the up-regulation expression genes of ion transport (potassium voltage-gated channel subfamily H member 5, KCNH5; erine/threonine-protein kinase 32, STK32; salt-inducible kinase 1, SIK1; adiponectin, ACDC), and by accumulating plasma urea and free amino acid via the up-regulation expression genes of amino acid metabolism (ornithine decarboxylase antizyme 3, OAZ3; glutamine synthetase, GLUL; asparaginase-like protein 1b, ASRGL; L-amino-acid oxidase-like, LAAO; sodium-dependent neutral amino acid transporter B, SLC6A15s; amino acid permease, SLC7A9) in response to osmotic regulation. An investment of energy to maintain their homeostatic balance is required to salinity adaptation, therefore, the genes related to energy production and conversion (F-ATPase protein 6, ATP6; cytochrome c oxidase subunit I, COX1; cytochrome c oxidase subunit III, COX3; cytochrome b, CYTb; cytochrome P450 17A1, CYP17A1) were up-regulated with the increase of gene expression associated with lipid metabolism (apolipoprotein E precursor, APoE; coenzyme Q-binding protein, CoQ10; high-density lipoprotein particle, SAA) and carbohydrate metabolism (HK, MIP). These findings improve our understanding of the underlying molecular mechanisms involved in salinity adaptation and provide general guidance to illuminate the invasion potential of T. s. elegans into saline environments.

MicroRNAs (miRNAs) are a kind of small non-coding RNAs that have been reported to play a vital role in mediating host-pathogen interactions. High-throughput sequencing technology was applied to identify and illuminate mRNAs and miRNAs from grouper infected with Vibrio alginolyticus. The KEGG pathway enrichment analysis showed that the most significate DEGs are associated with Toll-like receptor signaling pathway and NOD-like receptor signaling pathway. We obtained 374 known miRNAs and 116 novel miRNAs. During them, there are 31 up-regulated miRNAs and 93 down-regulated miRNAs. miRNA-mRNA GO and KEGG analysis show that there are 90 miRNAs associated with the immune system. The target genes of immune-related miRNAs (miR-142, miR-146, miR-150, miR-155, miR-203, miR-205, miR-24, miR-31) and genes (CD80, IL-2, AMPK, PI3K) in Epinephelus coioddes were predicted and validated. This study provides an opportunity to further understanding the molecular mechanisms especially the immune system of miRNA regulation in Epinephelus coioddes host-pathogen interactions. • A comprehensive miRNA database was constructed for Epinephelus coioddes liver under Vibrio alginolyticus infection. • miR-142, miR-146, miR-150, miR-155, miR-203, miR-205, miR-24 and miR-31 were response to Vibrio alginolyticus infection • Key biological processes related to Epinephelus coioddes liver under Vibrio alginolyticus infection were identified. • The liver can also be an immune organ to protect groupers from viral infection. [ABSTRACT FROM AUTHOR]

Highly efficient somatic embryogenesis (SE) initiation systems are crucial for the clonal propagation and genetic transformation of Lilium Oriental × Trumpet hybrid. To elucidate the underlying mechanism of SE induction, we conducted de novo transcriptome sequencing of the roots at four different times in relation to SE initiation (0 days, control; 20 days, embryogenic callus induction (ECI) 1; 40 days, ECI2; 55 days, ECI3). A total of 4621, 7582, and 7427 differentially expressed genes (DEGs) were identified from the ECI1 vs. control, ECI2 vs. control, and ECI3 vs. control comparisons, respectively. The gene-enrichment analysis revealed 54 significant DEGs. Further analysis showed that the transcript levels of the auxin-related genes ARF9/15/16, the abscisic acid-related (ABA-related) genes PYL4/9, and stress-related transcription factors, including WRKY26, MYB36, NAC100, bHLH2/5/18/112, and HSP90, were increased at the ECI1 stage. ABI5 can influence the expression of stress-responsive genes as an ABA signalling regulator. The upregulated ABI5 could be caused by the increased ARF9/15/16, PYL4/9, WRKY26, MYB36, NAC100, bHLH2/5/18/112, and HSP90 at the ECI2 and ECI3 stages to regulate the ECI. These genes had the most abundant transcripts among the DEGs, indicating that auxin and stress-related signalling pathways are involved in SE initiation of Lilium spp. [ABSTRACT FROM AUTHOR]

Objective: This study is to obtain the gene expression profiles of human umbilical vein endothelial cells(hUVECs) under different shear stress by RNA-Sequencing(RNA-Seq), and provide evidence for further exploring the mechanism on morphological and functional changes in endothelial cells affected by flow shear stress. Methods: A 6-channel streamer system was used to establish the hydrodynamic cell model with adjustable shear stress in hUVECs. Laminar shear stress(15 dynes/cm2) was used as control group and low shear stress(0.1 dynes/cm2) was used as experimental group. All cells were loaded for 18 h respectively; total RNA was extracted and synthesized by reverse transcription. The library was constructed and sequenced using Illumina Hi Seq. Results: Sequence alignment showed that there were 19986 gene alignments, and the number of new transcripts in each group was about 50% of the total transcripts.Differential expression analysis of genes showed that, compared with control group, there were 983 up-regulated genes and 701 down-regulated genes in low shear stress group. 18499 genes were classified and annotated, GO analysis showed that most of the genes were enriched into biological process. KEGG analysis showed that Top20 enrichment signal pathway is related to cell cycle, DNA replication, cell division, cell stress and apoptosis. Conclusion: Low shear stress not only activates proliferation-related genes in endothelial cells, but also involves DNA damage repair and apoptosis-related genes. [ABSTRACT FROM AUTHOR]

Water temperature affects the survival, growth, immunity, reproduction, and productivity of farmed fish. The temperature beyond suitable range will disrupt the normal physiological activity. Common carp (Cyprinus carpio L.) is a representative eurythermic fish; they are able to sense and respond to changes in water temperature by adjusting their physiology. To investigate the miRNAs in common carp at different temperatures, nine liver small-RNA libraries (5 °C, 17 °C, and 30 °C, each group have three biological repetitions) were constructed and sequenced using high-throughput sequencing. A total of 110 known miRNAs were identified. Twenty-nine known miRNAs were differentially expressed compared with in control group. GO and KEGG analysis indicated that the miRNAs may play important roles in metabolism and environment information processing. Specifically, we considered the insulin-signaling and glycerophospholipid metabolism pathway, and the results show that in 30 °C, miR-301a, miR-203b-5p, and miR-210-3p were upregulated; their target genes which are the mechanistic targets of the rapamycin kinase (mtor) gene and the protein kinase AMP-activated catalytic subunit alpha 1 (prkaa1) gene in the insulin-signaling pathway were downregulated. And miR-9-5p, miR-27d, miR-92b-3p, and miR-155 were upregulated; their target genes, 1-acylglycerol-3-phosphate O-acyltransferase 3 (agpat3), CDP-diacylglycerol-inositol 3-phosphatidyltransferase (cdipt), glycerol-3-phosphate acyltransferase mitochondrial (gpam), and phosphatidylglycerophosphate synthase 1 (pgs1), in glycerophospholipid metabolism pathway were downregulated. But in 5 °C, the situation was opposite. These findings suggest that significant changes occur in energy metabolism and metabolic processes with components of the cell membrane in different temperatures, which significantly advance our understanding of the regulatory mechanisms underlying the physiological change of temperature stress-induced in liver, specifically with regard to miRNAs. These data provide a foundation for further studies of the role of miRNAs in environmental adaptation in fish. [ABSTRACT FROM AUTHOR]

Abstract Nitrite helps meat products retain colour and prevents decay, but excessive intake can be carcinogenic. To investigate the mechanism of nitrite degradation by lactic acid bacteria, Lactobacillus fermentum RC4 were grown in broth containing NaNO 2 at 0, 100, 300, or 500 mg/L, and 8-plex iTRAQ proteomics and bioinformatics analysis were employed to explore protein expression patterns during nitrite degradation. Real-time PCR was used to confirm mRNA expression levels of selected genes. In the 100, 300, and 500 mg/L sodium nitrite groups, 31, 87, and 190 differentially expressed proteins (DEPs) were identified, of which 24, 57, and 109 were up-regulated and 7, 30, and 81 were down-regulated. Gene ontology (GO) and Kyoto Encyclopaedia of genes and genomes (KEGG) analyses of DEPs indicated that adh E and lpd A involved in carbohydrate metabolism, cys K linked to amino acid metabolism, nir B related to nitrogen metabolism, fab I and acc D associated with lipid metabolism, and gsk involved in nucleotide metabolism were dramatically differentially expressed. Nitrogen metabolism is essential for maintaining nitrogen balance, and the above genes appear to be involved in L. fermentum RC4 growth and development during nitrite reduction. These novel proteomics results provide new insight into the potential mechanism nitrite degradation by L. fermentum. Biological significance Nitrite helps meat products retain colour and prevents decay, but excessive intake can be carcinogenic. The probiotic L. fermentum RC4 can degrade nitrite but the mechanism is poorly understood. Herein, we performed quantitative proteomic profiling of L. fermentum RC4 using the iTRAQ approach, and identified various mechanisms potentially involved in nitrite degradation, including carbohydrate, amino acid, lipid, nucleotide, and nitrogen metabolic pathways. This is the first iTRAQ proteomic analysis of nitrite degradation by L. fermentum RC4, and the results provide novel insight. Graphical abstract Unlabelled Image Highlights • Nitrite inhibits Lactobacillus fermentum RC4 growth and alters gene expression. • 100, 300, and 500 mg/L sodium nitrite up-regulated 24, 57, and 109 DEPs. • 100, 300, and 500 mg/L sodium nitrite down-regulated 7, 30, and 81 DEPs. • Nitrite degradation involves multiple pathways and nitrogen metabolism is crucial. • A dh E , lpd A , cys K , fab I , acc D, gsk and nir B are particularly strongly affected. [ABSTRACT FROM AUTHOR]

Spiroplasma eriocheiris is a novel pathogen similar to the Spiroplasma mirum and also had an ability to infect the newborn mice and caused cataract. Our study was designed to study how S. eriocheiris infects mouse 3T6-Swiss albino cells and to elucidate the cellular molecular pathogenesis of Spiroplasma . FCM analysis and MTT analysis clearly shown that S. eriocheiris could induce 3T6 cell apoptosis and cause cell viability decreased seriously. Immunofluorescence experiments and TEM analysis shown that S. eriocheiris can invade 3T6 cells and form typical inclusion bodies and exhibit vacuolization in vitro . S. eriocheiris -oxytetracycline protection assay show that the infective bacteria already were detected at 1 h post infection, and sharply increased at 12 h after the bacteria infection. To further study the infection mechanism of S. eriocheiris , global mRNA and microRNA (miRNA) expression profiling were analyzed after the cells infected with the bacteria. A total of 619 non-redundant annotated transcripts (183 up-regulated and 436 down-regulated) and 22 miRNAs (8 up-regulated and 14 down-regulated) were differential expression after 6 h S. eriocheiris infection compared to control group. Integrated analysis shown that homologous genes from differential expression miRNA targets and the differential expression genes of the mRNA microarray were major focused on two important pathways focal adhesion and MAPK signaling pathway. To validate the results of microarray, eight focal adhesion (β-Catenin, Parvin, Grb2 and ERK) and MAPK signaling pathway (FGFR, Grb2, ERK, MKK3, p38 and JNK) genes and the housekeeping gene GAPDH were assayed by qPCR and Western blot to confirm the results. Eight miRNAs (miR-143-3p, miR-214-5p, miR-322-3p, miR-328-5p, miR-351-5p, miR-466h-5p, miR-503-5p and miR-30c-1-3p) and the housekeeping gene U6 miRNA were assayed by qPCR to confirm the results of microarray. All the results help us better understand the infection mechanism of S. eriocheiris . [ABSTRACT FROM AUTHOR]