Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disorder in the colon and rectum leading to low life-quality and high societal costs. Ursolic acid (UA) is a natural product with pharmacological and biological activities. The studies are aimed at investigating the protective and treatment effects of UA against the dextran sulfate sodium- (DSS-) induced UC mouse model and its underlying mechanism. UA was orally administered at different time points before and after the DSS-induced model. Mice body weight, colon length, and histological analysis were used to evaluate colon tissue damage and therapeutic evaluation. Intestinal transcriptome and microbe 16 s sequencing was used to analyze the mechanisms of UA in the prevention and treatment of UC. The early prevention effect of UA could effectively delay mouse weight loss and colon length shorten. UA alleviated UC inflammation and lowered serum and colon IL-6 levels. Three classical inflammatory pathways: MAPKs, IL-6/STAT3, and PI3K were downregulated by UA treatment. The proportion of macrophages and neutrophils in inflammatory cell infiltration was reduced in UA treatment groups. UA could significantly reduce the richness of intestinal flora to avoid the inflammatory response due to the destruction of the intestinal epithelial barrier. The function of UA against UC was through reducing intestinal flora abundance and regulating inflammatory and fatty acid metabolism signaling pathways to affect immune cell infiltration and cytokine expression.
Clear cell renal cell carcinoma (ccRCC) was the most aggressive histological type of renal cell carcinoma (RCC) and accounted for 70–80% of cases of all RCC. The aim of this study was to identify the potential biomarker in ccRCC and explore their underlying mechanisms. Four profile datasets were downloaded from the GEO database to identify DEGs. GO and KEGG analysis of DEGs were performed by DAVID. A protein–protein interaction (PPI) network was constructed to predict hub genes. The hub gene expression within ccRCC across multiple datasets and the overall survival analysis were investigated utilizing the Oncomine Platform and UALCAN dataset, separately. A meta-analysis was performed to explore the relationship between the hub genes: EGFR and ccRCC. 127 DEGs (55 upregulated genes and 72 downregulated genes) were identified from four profile datasets. Integrating the result from PPI network, Oncomine Platform, and survival analysis, EGFR, FLT1, and EDN1 were screened as key factors in the prognosis of ccRCC. GO and KEGG analysis revealed that 127 DEGs were mainly enriched in 21 terms and 4 pathways. The meta-analysis showed that there was a significant difference of EGFR expression between ccRCC tissues and normal tissues, and the expression of EGFR in patients with metastasis was higher. This study identified 3 importance genes (EGFR, FLT1, and EDN1) in ccRCC, and EGFR may be a potential prognostic biomarker and novel therapeutic target for ccRCC, especially patients with metastasis.
9 January 2024 in Clinical and Translational Oncology
Clear cell renal cell carcinoma (ccRCC) is the most common and invasive histological subtype of all kidney malignancies, with high levels of incidence and mortality. In the present study, long non-coding (lnc)RNA expression profiles of patients with ccRCC from The Cancer Genome Atlas database were comprehensively analyzed to identify differentially expressed lncRNAs (DElncRNAs). The patients with ccRCC were then divided into training and validation cohorts. Univariate and LASSO regression analyses were performed to select the most significant survival-associated candidate DElncRNAs in the training cohort. Multivariate Cox regression analysis was then performed to develop a risk score formula and a prognostic nomogram for predicting 3- and 5-year overall survival (OS). The accuracies of the nomogram predictions were evaluated by determining the area under the receiver operating characteristic curve (AUC) and a calibration plot. Finally, functional enrichment analysis and protein-protein interaction network prediction were implemented to predict the functions and molecular mechanisms of the candidate DElncRNAs in ccRCC. A total of 1,553 DElncRNAs were identified, and 5 candidate DElncRNAs (AC026992.2, AC245041.2, LINC00524, LINC01956 and LINC02080) were included in the nomogram. The AUC values for 3- and 5-year overall survival in the training cohort were 0.768 and 0.814, respectively, which were increased compared with that based on the clinical index (0.760 and 0.694, respectively). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the 521 mRNAs highly associated with 5 DElncRNAs were primarily involved in 17 terms and 25 pathways, respectively. Based on the 5 DElncRNAs, a novel and convenient prognostic nomogram for predicting 3- and 5-year OS for patients with ccRCC was developed. The results of the present study may be conducive to the development of a precise predictive tool for the prognosis of ccRCC and may provide information regarding the molecular mechanisms of ccRCC. However, additional experimental in vitro and in vivo studies investigating lncRNAs may be required.
29 June 2021 in Evidence-Based Complementary and Alternative Medicine
Silkworm droppings are the product of mulberry leaves digested by silkworm intestines, which are an important medicinal resource in traditional Chinese medicine (TCM). The contents of total fat, fat acids, crude protein, amino acids, and secondary metabolites of obtained mulberry leaves and silkworm droppings were analyzed by HPLC, GC-MS, and UHPLC-Q-TOF MS. The target genes and enriched pathways related to significantly changed compositions between mulberry leaves and silkworm droppings were analyzed by network pharmacology. High unsaturated C18 : 3 fatty acids were transformed to low unsaturated C18 : 1 from mulberry leaves to silkworm droppings. Only lysine and 17 mini-peptides had significantly higher content in silkworm droppings than in mulberry leaves. There were 36 common target genes or the different compounds between mulberry leaves and silkworm droppings. The main pathways of mulberry leaf were enriched in antivirus and anticancer properties, while the pathways of silkworm droppings were enriched in hormone regulation and signal transduction.
This study is aimed at exploring whether Xiaotan Sanjie decoction (XTSJ) inhibits gastric cancer (GC) proliferation and metastasis by regulating lncRNA‐ATB expression. qRT‐PCR and Western blot were used to analyze lncRNA‐ATB and downstream‐regulated genes/proteins in human GC cells. CCK8, Edu, and flow cytometry assays were used to detect the inhibitory effect of XTSJ on cell proliferation and apoptosis. Moreover, transwell and wound healing assays were used to detect the inhibitory effect of XTSJ on migration and invasion. qRT‐PCR and Western blot were used to detect regulated genes and proteins levels. The HGC‐27 cell line was used for follow‐up analysis due to the high level of lncRNA‐ATB and cell characteristics. XTSJ inhibited the proliferation and metastasis of HGC‐27 in a dose‐dependent manner. Further research found that XTSJ downregulated lncRNA‐ATB, Vimentin, and N‐cadherin, while it upregulated miR‐200a and E‐cadherin in a dose‐dependent manner. XTSJ also upregulated Caspase 3, Caspase 9, Bax, and downregulated Bcl‐2. Furthermore, XTSJ inhibited tumor growth in vivo and downregulated EMT signaling pathways. These results indicate that XTSJ may affect EMT and Bcl‐2 signaling pathways by regulating lncRNA‐ATB and miR‐200a, thus inhibiting proliferation, migration, and invasion of HGC‐27 cells. Therefore, XTSJ may be an effective treatment for the high levels of lncRNA‐ATB in GC.