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Seventeen compounds were isolated and identified from the ethyl acetate part of Zanthoxylum bungeanum Maxim., including one new compound 18-acetyloxyneocryptotanshinone (1) and 16 known compounds (2–17). Their structures were elucidated by extensive spectroscopy. The absolute configuration of 1 was confirmed by electronic circular dichroism (ECD). All compounds were evaluated for the inhibition of LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, of which 1 and 10 exhibited the most significant inhibitory effect, with IC50 of 17.29 and 10.27 μM, respectively. [ABSTRACT FROM AUTHOR]

Introduction: Allergic rhinitis (AR) is identified as a multifactorial disease caused by the interaction of genes and surroundings, which is difficult to cure. MicroRNAs were reported to be engaged in AR development. Here, we aimed to seek the anti-inflammatory effects and regulatory mechanism of miR-193b-3p in AR. Methods: Mucosal tissues from AR patients and healthy volunteers were collected, and human nasal epithelial cells (HNECs) were treated with IL-13 to establish a cell model of AR. The gene expression of miR-193b-3p, ETS1, TLR4, GM-CSF, eotaxin, and MUC5AC was determined by RT-qPCR. The protein levels of ETS1 and TLR4 were examined using Western blot. Enzyme-linked immunosorbent assay was performed to measure protein concentration of GM-CSF, eotaxin, and MUC5AC in cell supernatant. Dual luciferase assay was applied to verify the interaction among miR-193b-3p, ETS1, and TLR4. Results: The expression of miR-193b-3p was declined in clinical samples from AR patients and in IL-13-induced HNECs, while the mRNA and protein levels of ETS1 and TLR4 were elevated. MiR-193b-3p overexpression or ETS1 silencing notably decreased the mRNA and protein levels of GM-CSF, eotaxin, and MUC5AC in IL-13-treated HNECs. Mechanistically, miR-193b-3p directly combined with ETS1 to silence ETS1 expression. ETS1 promoted the transcriptional activity of TLR4 through interacting with TLR4 promoter. Furthermore, rescue experiments revealed that ETS1 overexpression abolished miR-193b-3p sufficiency-mediated suppression of the mRNA and protein levels of GM-CSF, eotaxin, and MUC5AC in IL-13-treated HNECs. Similarly, TLR4 overexpression compromised the inhibitory impacts of ETS1 downregulation on the mRNA and protein levels of GM-CSF, eotaxin, and MUC5AC in IL-13-induced HNECs. Discussion:MiR-193b-3p repressed IL-13-induced inflammatory response in HNECs by suppressing ETS1/TLR4 axis, which indicated that miR-193b-3p might be a therapeutic target for AR treatment. [ABSTRACT FROM AUTHOR]

For migratory fish, passing through the cold, fast flowing water of a dam causes stress, leading to disease and even death. To determine the immune response to cold stress in a dam-lake after swimming fatigue in Chinese sucker (Myxocyprinus asiaticus), the spleen mRNA expression profiles in response to cold stress (CS) after fatigue stress (FS) were compared with that of the control (SS). We identified 40,952 differentially expressed genes (DEGs) in the spleen for at least one comparison among 211,397 unigenes. We identified 11,869 DEGs (4,968 upregulated and 6,901 downregulated), 17,803 DEGs (10,610 upregulated and 7,193 downregulated), and 30,579 DEGs (20,652 upregulated and 9,927 downregulated) in the SS vs. FS, SS vs. CS, and FS vs. CS comparisons, respectively. Enrichment analysis indicated the involvement of the immune system and infectious diseases, including the toll-like receptor pathway, the complement and coagulation cascade, and the natural killer cell-mediated cytotoxicity pathway. There were 2,991 DEGs (271 upregulated and 2,720 downregulated), and 2,878 DEGs (873 upregulated and 2,005 downregulated) associated with these pathways in the SS vs. FS and SS vs. CS comparisons, respectively. In the cold stress after fatigue group, the expression levels of heat shock protein (HSP) 70 and HSP90 genes were significantly upregulated; however, more immune response genes showed significantly downregulated expression in SS vs. CS compared with that in SS vs. FS, including those encoding tumor necrosis factor, C–C motif chemokines (3, 8, and 13), complement components (C3, C4, C6, and C7), immunoglobulin, and cathepsins. Overall, cold stress combined with swimming fatigue from passing the dam resulted in the downregulation of many immune genes, suggesting that the Chinese sucker might have experienced serious immune suppression. • 40,952 spleen unigenes were identified from cold-stressed, fatigued Chinese sucker. • The unigenes were associated with 21 immune system-related pathways. • Differentially expressed genes were identified in the cold stress and fatigue groups. • Cold stress after fatigue downregulated immune genes in the Chinese sucker spleen. [ABSTRACT FROM AUTHOR]

Identifying essential genes in comparison states (EGS) is vital to understanding cell differentiation, performing drug discovery, and identifying disease causes. Here, we present a machine learning method termed Prediction of Essential Genes in Comparison States (PreEGS). To capture the alteration of the network in comparison states, PreEGS extracts topological and gene expression features of each gene in a five-dimensional vector. PreEGS also recruits a positive sample expansion method to address the problem of unbalanced positive and negative samples, which is often encountered in practical applications. Different classifiers are applied to the simulated datasets, and the PreEGS based on the random forests model (PreEGSRF) was chosen for optimal performance. PreEGSRF was then compared with six other methods, including three machine learning methods, to predict EGS in a specific state. On real datasets with four gene regulatory networks, PreEGSRF predicted five essential genes related to leukemia and five enriched KEGG pathways. Four of the predicted essential genes and all predicted pathways were consistent with previous studies and highly correlated with leukemia. With high prediction accuracy and generalization ability, PreEGSRF is broadly applicable for the discovery of disease-causing genes, driver genes for cell fate decisions, and complex biomarkers of biological systems. [ABSTRACT FROM AUTHOR]

The light–dark cycle is the primarily environmental stimulus responsible for entraining the major circadian clock located within the suprachiasmatic nucleus (SCN), which in turn coordinates various physiological processes in fish, including those in non‐SCN regions of the brain. To better understand differences in gene expression due to the light–dark cycle, we compared the transcriptomes of Pelteobagrus vachellii in non‐SCN regions of the brain in the daytime (12:00) and nighttime (24:00). The two cDNA libraries yielded 217,575,058 and 350,784,004 paired‐end clean reads, and 311,143 unique transcript fragments (unigenes) averaging 600.94 base pairs were assembled. It was possible to annotate ~7,426 (2.39%) unigenes based on homology with all database sequences. Gene expression analysis revealed that 2,406 and 1,665 annotated unigenes were up‐ and downregulated, respectively, with ≥twofold differences between daytime and nighttime. Enrichment analysis of differentially expressed genes predicted the pathways in which they operate, including development, endocrine function, adaptation to environmental changes and immunity. In summary, characterization of daytime and nighttime gene expression patterns in P. vachellii showed that the light–dark cycle coordinates gene expression in non‐SCN regions of the brain. [ABSTRACT FROM AUTHOR]

Understanding the molecular mechanisms underlying cell migration, which plays an important role in tumor growth and progression, is critical for the development of novel tumor therapeutics. Overexpression of transmembrane protein 30A (TMEM30A) has been shown to initiate tumor cell migration, however, the molecular mechanisms through which this takes place have not yet been reported. Thus, we propose the integration of computational and experimental approaches by first predicting potential signaling networks regulated by TMEM30A using a) computational biology methods, b) our previous mass spectrometry results of the TMEM30A complex in mouse tissue, and c) a number of migration-related genes manually collected from the literature, and subsequently performing molecular biology experiments including the in vitro scratch assay and real-time quantitative polymerase chain reaction (qPCR) to validate the reliability of the predicted network. The results verify that the genes identified in the computational signaling network are indeed regulated by TMEM30A during cell migration, indicating the effectiveness of our proposed method and shedding light on the regulatory mechanisms underlying tumor migration, which facilitates the understanding of the molecular basis of tumor invasion. [ABSTRACT FROM AUTHOR]

Drought is the one of the most important environment stresses that restricts crop yield worldwide. Cassava (Manihot esculenta Crantz) is an important food and energy crop that has many desirable traits such as drought, heat and low nutrients tolerance. However, the mechanisms underlying drought tolerance in cassava are unclear. Ethylene signaling pathway, from the upstream receptors to the downstream transcription factors, plays important roles in environmental stress responses during plant growth and development. In this study, we used bioinformatics approaches to identify and characterize candidate Manihot esculenta ethylene receptor genes and transcription factor genes. Using computational methods, we localized these genes on cassava chromosomes, constructed phylogenetic trees and identified stress-responsive cis-elements within their 5’ upstream regions. Additionally, we measured the trehalose and proline contents in cassava fresh leaves after drought, osmotic, and salt stress treatments, and then it was found that the regulation patterns of contents of proline and trehalose in response to various dehydration stresses were differential, or even the opposite, which shows that plant may take different coping strategies to deal with different stresses, when stresses come. Furthermore, expression profiles of these genes in different organs and tissues under non-stress and abiotic stress were investigated through quantitative real-time PCR (qRT-PCR) analyses in cassava. Expression profiles exhibited clear differences among different tissues under non-stress and various dehydration stress conditions. We found that the leaf and tuberous root tissues had the greatest and least responses, respectively, to drought stress through the ethylene signaling pathway in cassava. Moreover, tuber and root tissues had the greatest and least reponses to osmotic and salt stresses through ethylene signaling in cassava, respectively. These results show that these plant tissues had differential expression levels of genes involved in ethylene signaling in response to the stresses tested. Moreover, after several gene duplication events, the spatiotemporally differential expression pattern of homologous genes in response to abiotic and biotic stresses may imply their functional diversity as a mechanism for adapting to the environment. Our data provide a framework for further research on the molecular mechanisms of cassava resistance to drought stress and provide a foundation for breeding drought-resistant new cultivars. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4+ CD25+ Foxp3+ regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets and have the opposite effects on autoimmunity. Clinical observation has revealed that the Th17/Treg imbalance exists in patients with acute coronary syndrome. We investigated whether the Th17/Treg functional imbalance existed during atherogenesis in ApoE−/− mice. Methods and results: Th17/Treg functions at different levels including cell frequencies, related cytokine secretion and key transcription factors were investigated comparatively between ApoE−/− mice and their age-matched C57BL/6J mice. The results demonstrated that ApoE−/− mice revealed significantly increased secretion of Th17 related cytokines (IL-17 and IL-6) and expression of transcription factor (RORγt) levels and obviously decreased number in Treg cells, secretion of Treg related cytokines (TGF-β1) and expression of transcription factor (Foxp3) levels as compared with age-matched C57BL/6J mice. Th17 related mediators reached their maximum expression values at the early stage (8–16weeks of age) in ApoE−/− mice, and then followed by continuous depression of their expression levels. Meanwhile, the expression of Treg related mediators was much lower in ApoE−/− mice than in their age-matched wild-type littermates. Conclusions: Th17/Treg functional imbalance exists during atherogenesis in ApoE−/− mice, suggesting a potential role of Th17/Treg imbalance in the formation and progression of atherosclerosis. [Copyright &y& Elsevier]

Cherimoya, a typical climacteric fruit, is very susceptible to postharvest losses, due to rapid softening. It has been reported that xyloglucan endotransglycosylases (XET) and expansins (EXP) contribute to fruit softening while 1-methylcyclopropene (1-MCP) is used to delay softening in many fruit. However, the effects of 1-MCP on cherimoya fruit softening and in relation to the expression of XET and EXP genes remain unclear. In this study, three different full length XET cDNAs, termed AcXET1, AcXET2 and AcXET3, were isolated and characterized. Delay in cherimoya fruit softening by 1-MCP in relation to the expression of XET and EXP genes was investigated. Cherimoya fruit stored at 20°C softened rapidly within 5d and displayed a typical climacteric pattern of ethylene production. Application of 1-MCP greatly delayed and inhibited ethylene production and softening of fruit during storage at 20°C. Northern blot analysis showed that three AcXETs or AcEXPs exhibited different expression patterns during fruit softening while mRNAs of AcXET2, AcEXP1 and AcEXP3 significantly accumulated on day 3 and mRNAs of AcXET1 or AcEXP2 accumulated on day 5 or day 6. 1-MCP treatment not only delayed the accumulation of AcXET1, AcEXP1 and AcEXP3 for 1, 3 and 2d, respectively, but also reduced the mRNA levels of AcXET1, AcXET2, AcXET3, AcEXP1, AcEXP2 and AcEXP3. These data suggest that differential expression of AcXETs and AcEXPs is associated with fruit softening of cherimoya and application of 1-MCP retarded or suppressed the expression of AcXETs or AcEXPs, which may be attributed at least or partially to 1-MCP delayed fruit softening. [Copyright &y& Elsevier]