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This study aimed to investigate the relationship and potential mechanisms of miR‐200c‐5p in colorectal cancer (CRC) progression. Differentially expressed miRNAs were screened using the TCGA database. Subsequently, univariate analysis was performed to identify CRC survival‐related miRNAs. Survival and receiver operator characteristic curves were generated. The target genes of miR‐200c‐5p and the relevant signaling pathways or biological processes were predicted by the miRNet database and enrichment analyses. The miR‐200c‐5p expression was detected using quantitative reverse‐transcription polymerase chain reaction, Cell Counting Kit‐8, Transwell, and cell apoptosis experiments were performed to determine miR‐200c‐5p's impact on CRC cell viability, invasiveness, and apoptosis. Finally, we constructed a CRC mouse model with inhibited miR‐200c‐5p to evaluate its impact on tumors. miR‐200c‐5p was upregulated in CRC, implying a favorable prognosis. Gene set enrichment analysis revealed that miR‐200c‐5p may participate in signaling pathways such as the TGF‐β signaling pathway, RIG‐I‐like receptor signaling pathway, renin‐angiotensin system, and DNA replication. miR‐200c‐5p potentially targeted mRNAs, including KCNE4 and CYP1B1, exhibiting a negative correlation with their expression. Furthermore, these mRNAs may participate in biological processes like the regulation of intracellular transport, cAMP‐dependent protein kinase regulatory activity, ubiquitin protein ligase binding, MHC class II protein complex binding, and regulation of apoptotic signaling pathway. Lastly, miR‐200c‐5p overexpression repressed the viability and invasiveness of CRC cells but promoted apoptosis. The tumor size, weight, and volume were significantly increased by inhibiting miR‐200c‐5p (p < 0.05). miR‐200c‐5p is upregulated in CRC, serving as a promising biomarker for predicting CRC prognosis. [ABSTRACT FROM AUTHOR]

Background. Notwithstanding the mounting evidence to suggest that systemic lupus erythematosus (SLE) accelerates the progression of atherosclerosis, the mechanisms underlying this phenomenon are yet to be completely understood. This research examined the molecular mechanism behind this vascular complication. Methods. The Gene Expression Omnibus database was retrieved to acquire the gene expression datasets for SLE (GSE109248) and atherosclerosis (GSE100927). The shared differentially expressed genes (DEGs) of SLE and atherosclerosis were screened with the help of the "limma" package in R software, followed by function enrichment analysis, protein–protein interaction (PPI) network construction, key module analysis, hub gene selection, and coexpression analysis. Results. In GSE109248 and GSE100927, 1195 and 418 DEGs in totals were identified, respectively. Subsequently, we acquired 78 common DEGs (70 upregulated genes and eight downregulated genes) with the same expression trends by using the Venn diagram. Finally, 12 hub genes, including PTPRC, TYROBP, FCGR3A, ITGAX, LCP2, IL1B, IRF8, LILRB2, CD68, C1QB, CCR7, and C1QA were identified by using seven different algorithms in Cytohubba. The functional analysis illustrates that these genes were predominantly enriched in immune and inflammation response, lipid and atherosclerosis, and osteoporosis. These results indicate an important role of SLE in inducing excessive inflammation, which may be medicate by these hub genes and can induce osteoporosis and imbalance of the normal mineral balance in the body as well as lipid abnormalities, which eventually leads to premature onset of atherosclerosis. In total, nine transcription factors (TFs) that may participate in regulating the function of these genes were identified. All hub genes and four TFs were validated successfully. Conclusion. The results of our research show that SLE and atherosclerosis have common DEGs, pathophysiology, and hub genes. These findings can provide fresh evidence and insights into a further investigation into the mechanisms at play. [ABSTRACT FROM AUTHOR]

This study is aimed at screening prognostic biomarkers in cholangiocarcinoma (CHOL) based on competitive endogenous RNA (ceRNA) regulatory network analysis. Microarray data for lncRNAs, mRNA, and miRNAs were downloaded from the GEO and TCGA databases. Differentially expressed RNAs (DERs) were identified in CHOL and normal liver tissue samples. WGCNA was used to identify disease-related gene modules. By integrating the information from the starBase and DIANA-LncBasev2 databases, we constructed a ceRNA network. Survival analysis was performed, and a prognostic gene-based prognostic score (PS) model was generated. The correlation between gene expression and immune cell infiltration or immune-related feature genes was analyzed using TIMER. Finally, real-time quantitative PCR (RT-qPCR) was used to verify the expression of the 10 DERs with independent prognosis. A large cohort of DERs was identified in the CHOL and control samples. The ceRNA network consisted of 6 lncRNAs, 2 miRNAs, 90 mRNAs, and 98 nodes. Ten genes were identified as prognosis-related genes, and a ten-gene signature PS model was constructed, which exhibited a good prognosis predictive ability for risk assessment of CHOL patients (AUC value = 0.975). Four genes, ELF4, AGXT, ABCG2, and LDHD, were associated with immune cell infiltration and closely correlated with immune-related feature genes (CD14, CD163, CD33, etc.) in CHOL. Additionally, the consistency rate of the RT-qPCR results and bioinformatics analysis was 80%, implying a relatively high reliability of the bioinformatic analysis results. Our findings suggest that the ten-signature gene PS model has significant prognostic predictive value for patients with CHOL. These four immune-related DERs are involved in the progression of CHOL and may be useful prognostic biomarkers for CHOLs. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) can affect the immune system of geese by inducing liver injury. The polysaccharide of Atractylodes macrocephala Koidz (PAMK) have obvious immune-enhancing effects. Accordingly, this experiment investigated the effect of PAMK on LPS-induced liver injury in goslings. Two hundred 1-day-old goslings were randomly divided into the control group, LPS group, PAMK group, and PAMK+ LPS group, and the PAMK and PAMK+ LPS groups were fed the basal diet with 400 mg/kg PAMK, while the control and LPS groups were fed the basal diet. On D 21, 23, and 25 of the formal trial, the goslings in the LPS and PAMK+LPS groups were injected intraperitoneally with 2 mg/kg LPS, and goslings in the control and PAMK groups were injected intraperitoneally with the same amount of saline. Livers were collected on D 25. HE-stained sections showed that PAMK could effectively alleviate the LPS-induced indistinct hepatic cord structure, loss of cytoplasmic contents of hepatocytes, and dilatation of hepatic sinusoids. The biochemical parameters of liver tissues showed that PAMK could alleviate the LPS-induced upregulation of alanine aminotransferase and aspartate aminotransferase. To further investigate the mechanism of the mitigating effect of PAMK on LPS-induced injury, livers from the LPS and PAMK+LPS groups were selected for transcriptome sequencing. The sequencing results showed that there were 406 differentially expressed genes (DEGs) in the livers of LPS and PAMK+LPS goslings, of which 242 upregulated and 164 downregulated. The Kyoto Encyclopedia of Genes and Genome (KEGG) analysis showed that DEGs were significantly enriched in immune signal transduction, cell cycle, and cell metabolism. Besides, protein‒protein interaction analysis showed that 129 DEGs were associated with each other, including 7 DEGs enriched in the p53 and FOXO signaling pathway. In conclusion, PAMK may alleviate LPS-induced liver injury in gosling through the p53 and FOXO signaling pathway. These results provide a basis for further development of PAMK as an immunomodulator. [ABSTRACT FROM AUTHOR]

Background & Aims Hallmarks of non-alcoholic fatty liver disease (NAFLD) are increased triglyceride accumulation within hepatocytes. The prevalence of NAFLD increases steadily with increasing thyrotropin (TSH) levels. However, the underlying mechanisms are largely unknown. Here, we focused on exploring the effect and mechanism of TSH on the hepatic triglyceride content. Methods As the function of TSH is mediated through the TSH receptor (TSHR), Tshr −/− mice (supplemented with thyroxine) were used. Liver steatosis and triglyceride content were analysed in Tshr −/− and Tshr +/+ mice fed a high-fat or normal chow diet, as well as in Srebp-1c −/− and Tshr −/− Srebp-1c −/− mice. The expression levels of proteins and genes involved in liver triglyceride metabolism was measured. Results Compared with control littermates, the high-fat diet induced a relatively low degree of liver steatosis in Tshr −/− mice. Even under chow diet, hepatic triglyceride content was decreased in Tshr −/− mice. TSH caused concentration- and time-dependent effects on intracellular triglyceride contents in hepatocytes in vitro . The activity of SREBP-1c, a key regulator involved in triglyceride metabolism and in the pathogenesis of NAFLD, was significantly lower in Tshr −/− mice. In Tshr −/− Srebp-1c −/− mice, the liver triglyceride content showed no significant difference compared with Tshr +/+ Srebp-1c −/− mice. When mice were injected with forskolin (cAMP activator), H89 (inhibitor of PKA) or AICAR (AMPK activator), or HeG2 cells received MK886 (PPARα inhibitor), triglyceride contents presented in a manner dependent on SREBP-1c activity. The mechanism, underlying TSH-induced liver triglyceride accumulation, involved that TSH, through its receptor TSHR, triggered hepatic SREBP-1c activity via the cAMP/PKA/PPARα pathway associated with decreased AMPK, which further increased the expression of genes associated with lipogenesis. Conclusions TSH increased the hepatic triglyceride content, indicating an essential role for TSH in the pathogenesis of NAFLD. [ABSTRACT FROM AUTHOR]

Ferroptosis is a newly discovered form of cell death due to iron-dependent lipid peroxidation. In animal breeding, many environmental factors could lead to oxidative stress, which in turn reduce animal immunity and production performance. Polysaccharide of Atractylodes macrocephala Koidz (PAMK) has antioxidation, immunomodulatory, and inflammatory modulating effects. For investigating the effect of PAMK on splenic ferroptosis in gosling caused by lipopolysaccharide (LPS), 40 one-day-old Magang goslings were randomly divided into 4 groups (CON group, LPS group, PAMK group, and LPS+PAMK group). The protein expression of the ferroptosis marker Glutathione Peroxidase 4 (GPX4), the relative mRNA expression of ferroptosis-related genes and cytokines, and the oxidative stress and iron content of spleen tissues were examined. The correlation between ferroptosis and inflammatory factors was further analyzed by principal component analysis. The results showed that, compared with CON group, LPS caused alterations in the expression of the ferroptosis pathway genes and cytokines, which could upregulate levels of ferroptosis and inflammation. However, after treated with PAMK, the inflammation and ferroptosis was alleviated. Meanwhile, PAMK restored the expression and distribution of GPX4. In addition, PAMK alleviated the oxidative stress caused by LPS and reduced the iron content in spleen. Principal component analysis showed that cytokines were more closely related to antioxidant indexes. The CON, PAMK and LPS+PAMK groups had similar effects on the four components, with the LPS and PAMK groups showing the furthest difference in results. The result indicated that PAMK could reduce the level of oxidative stress and inflammatory cytokines in spleen of gosling caused by LPS, and jointly alleviate ferroptosis by regulating genes related to the ferroptosis pathway. [ABSTRACT FROM AUTHOR]

Polysaccharide Of Atractylodes Macrocephala Koidz (PAMK) has been proved to have anti-cancer, antitumor, anti-inflammation function and improve the immune level of the organism. The miRNA plays a very important role in regulating the immune function by negatively regulate the expression of target genes. To explore the molecular mechanism of PAMK active the lymphocytes, thirty 61-d-old geese were randomly divided into 4 groups (C, CTX, PAMK, PAMK+CTX). The thymus morphology, the level of serum granulocyte-macrophage colony-stimulating factor (GMC-SF), IL-1β, IL-3, IL-5, the relative mRNA expression of CD25, novel_mir2, CTLA4 and CD28 signal pathway were measured. Further more, the lymphocytes was extracted from thymus to measure the relative mRNA expression of CD28 signal pathway. The results showed that PAMK could significantly maintain normal cell morphology of thymus, alleviate the decrease level of GMC-SF, IL-1β, IL-5, IL-6, TGF-β, the increase level of IL-4, IL-10, and the decrease relative mRNA expression of novel_mir2, CD25 and CD28 signal pathway in thymus and lymphocytes induced by cyclophosphamide (CTX). In conclusion, PAMK alleviated the decreased T lymphocytes activation levels induced by CTX through novel_mir2/CTLA4/CD28/AP-1 signal pathway. [ABSTRACT FROM AUTHOR]