Intestinal inflammation frequently occurs alongside dysmotility, which is characterized by altered myosin light chain phosphorylation levels. Curcumin, an active component from the ginger family, is reported to confer anti-inflammatory effects. However, the effects of curcumin on both diarrhea and constipation associated inflammation remains to be elucidated. The present study was designed to investigate the effects of curcumin on diarrhea and constipation and to determine the related mechanisms. Sprague-Dawley rats were used to establish diarrhea and constipation models via intracolonic acetic acid (4%) instillation or cold water gavage for 2 weeks, respectively. Blood samples were collected to measure the serum levels of the cytokines TNF-α and IL-1β using ELISA kits. Western blotting was performed to measure NF-κB, RhoA, Rho-related kinase 2, phosphorylated MLC 20 , phosphorylated myosin phosphorylated target subunit 1, 130k Da-MLC kinase (MLCK), c-kit tyrosine kinase protein expression, and reverse transcription-quantitative PCR was conducted to measure MLCK expression levels. The results indicated that curcumin reversed the elevations in the pro-inflammatory cytokines IL-1β and TNF-α by inhibiting the NF-κB pathway in rats with diarrhea and constipation. The results also indicated that myosin light chain (MLC) phosphorylation in intestinal smooth muscle was positively and negatively associated with the motility of inflammation-related diarrhea and constipation in rats, respectively. Curcumin significantly reversed the increased MLC phosphorylation in the jejunum of the rats with diarrhea, significantly enhanced the reductions in inflammatory mediators, including TNF-α and IL-1β, of rats with constipation and significantly ameliorated the related hyper-motility and hypo-motility in rats with both diarrhea and constipation. In conclusion, the potential roles of the MLC kinase, c-kit tyrosine and Rho A/Rho-associated kinase 2 pathways, which are involved in curcumin-induced amelioration of inflammation-related diarrhea and constipation, were explored in the present study. Results from the present study suggested that curcumin has potential therapeutic value for treating intestinal inflammation and inflammation-related motility disorders.
Mineral nutrition plays an important role in crop growth, yield and quality. MiR156 is a regulatory hub for growth and development. To date, the understanding of miR156-mediated mineral homeostasis is limited. In this study, we overexpressed Nta-miR156a in the tobacco cultivar TN90 and analyzed the effects of miR156 on mineral element homeostasis in tobacco by comparative transcriptome analysis. The results showed that the overexpression of miR156a caused significant morphological changes in transgenic tobacco. Chlorophyll and three anti-resistance markers, proline, total phenolics, and total flavonoids, were altered due to increased miR156 expression levels. Interestingly, the distribution of Cu, Mn, Zn, and Fe in different tissues of transgenic tobacco was disordered compared with that of the wild type. Comparative transcriptome analysis showed that the overexpression of miR156 resulted in 2656 significantly differentially expressed genes. The expression levels of several metal-transport-related genes, such as NtABC, NtZIP, NtHMA, and NtCAX, were significantly increased or decreased in transgenic tobacco. These results suggest that miR156 plays an essential role in regulating mineral homeostasis. Our study provides a new perspective for the further study of mineral nutrient homeostasis in plants.
We aimed to characterize the stomach adenocarcinoma (STAD) microbiota and its clinical value using an integrated analysis of the microbiome and transcriptome. Microbiome and transcriptome data were downloaded from the Cancer Microbiome Atlas and the Cancer Genome Atlas databases. We identified nine differentially abundant microbial genera, including Helicobacter, Mycobacterium, and Streptococcus, which clustered patients into three subtypes with different survival rates. In total, 74 prognostic genes were screened from 925 feature genes of the subtypes, among which five genes were identified for prognostic model construction, including NTN5, MPV17L, MPLKIP, SIGLEC5, and SPAG16. The prognostic model could stratify patients into different risk groups. The high-risk group was associated with poor overall survival. A nomogram established using the prognostic risk score could accurately predict the 1, 3, and 5 year overall survival probabilities. The high-risk group had a higher proportion of histological grade 3 and recurrence samples. Immune infiltration analysis showed that samples in the high-risk group had a higher abundance of infiltrating neutrophils. The Notch signaling pathway activity showed a significant difference between the high- and low-risk groups. In conclusion, a prognostic model based on five feature genes of microbial subtypes could predict the overall survival for patients with STAD.
This study aimed to explore the temperature-related pathogenic mechanism of Ralstonia solanacearum infection in tomato (Lycopersicon esculentum Mill.). Based on bioinformatics analysis of microarray dataset (GSE33657), the co-differentially expressed genes (co-DEGs) ribonucleic acids were identified in R. solanacearum GMI1000-infected L. esculentum Mill., which was cultured at 20°C and 28°C, in rich medium containing casamino acids, peptone, and glucose (CPG) and planta. In total, 63 upregulated co-DEGs and 57 downregulated co-DEGs were identified between 20°C and 28°C in the CPG and planta groups. Protein–protein interaction network revealed 70 protein interaction pairs and 59 nodes. Notably, iolG, iolE, ioll and RSc1248 played critical roles in the network. The subcellular localization and functional annotation showed that the increased expressed proteins were mainly localized in the inner cell membrane, while those with decreased expression were localized in the cytoplasm. Furthermore, these proteins were mainly enriched in regulation of DNA-templated transcription. RSc1154 and RhlE were predicted to be temperature-related pathogenic genes for R. solanacearum in tomato. Furthermore, phosphorelay signal transduction system function might play an important role in R. solanacearum infection. The candidate genes were verified by quantitative real-time PCR, and the results were consistent with gene expression profile.
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