miRNAs are critical post-transcriptional regulators of gene expression and key mediators of tumourigenesis. miR-501-5p is newly identified to be involved in the tumor progression, but its biological ...role and mechanism remain largely unknown. This study is aimed to study the role of miR-501-5p in the progression of gastric cancer.
Real-time PCR analysis was used to determine miR-501-5p expression in gastric cancer cell lines, clinical tissues and 112 clinicopathologically characterized gastric cancer specimens. The role of miR-501-5p in maintaining gastric cancer stem cell like phenotype was examined by tumor-sphere formation assay and expression of stem cell markers. Luciferase reporter assay, cellular fractionation and western blot analysis were used to determined that miR-501-5p activated the wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β.
Herein, our results revealed that miR-501-5p was markedly upregulated in gastric cancer cell lines and clinical tissues. High miR-501-5p levels predicted poor overall survival in gastric cancer patients. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-501-5p enhanced the cancer stem cell-like phenotype in gastric cancer cells. Notably,wnt/β-catenin signaling was hyperactivated in gastric cancer cells that overexpress miR-501-5p, and mediated miR-501-5p-induced cancer stem cell-like phenotype. Furthermore, miR-501-5p directly targeted and suppressed multiple repressors of the wnt/β-catenin signaling cascade, including DKK1, NKD1 and GSK3β. These results demonstrate that miR-501-5p maintains constitutively activated wnt/β-catenin signaling by directly targeting DKK1, NKD1 and GSK3β, which promotes gastric cancer stem cell like phenotype.
Taken together, our findings reveal a new regulatory mechanism of miR-501-5p and suggest that miR-501-5p might be a potential target in gastric cancer therapy.
The main objective of this study was to explore the effects of broiler embryonic injection of Lactobacillus Plantarum on the growth performance, lipid metabolism of serum and liver, microbial ...diversity, and short-chain fatty acids of broiler intestines after hatching. On d 14 of incubation, 720 eggs of Arbor Acres were randomly divided into 4 experimental groups: no treatment control (C), Treatments injected with stroke-physiological saline solution (S), Supernatant of MRS medium culture of lactobacillus (Q) and Lactobacillus Plantarum spp. (J). The Hatch rate for each replicate was counted at 1 d of age. After hatching, each group were divided into six replicates of 10 broilers, and chicken from groups C, Q and J were reared until 14 d of age. The production performance of the three groups of chicks from 1 to 14 days was recorded and statistically analyzed separately. Serum and liver tissue were collected at 7 and 14 days of age for the detection of lipid metabolism index. 16S rDNA sequencing and Short-Chain Fatty Acids measurement of cecum contents were performed at 14 days of age. Overall, Lactobacillus injection significantly reduced feed conversion ratio (FCR) at 1–7 and 1–14 days of age, compared to the other 2 groups (P < 0.05). 16S rRNA sequencing results showed that the Roseburia and coprobacillus had a significantly positive correlation with body weight (P < 0.05). The Roseburia and lachnospira were significantly correlated with FCR (P < 0.05), and the absolute abundance of g_Anaerostipes as a biomarker in the J group was higher than in the C group (P < 0.05). The Q and J group increased the content of acetic, propionic, butyric, and total acid in the cecum contents (P < 0.05). In the jejunum, the J group increased the content of acetic, propionic, butyric, and total acids compared to the C and Q groups (P < 0.05). The J group increased the blood of total cholesterol (TC) content at 1 day of age and the triglyceride (TG) content of 7- and 14-day-old broilers (P < 0.05). and the J group raised the TG, TC, and high-density lipoprotein (HDL) level in the liver of 14-day-old broilers (P < 0.05). The J group reduced the liver's low-density lipoprotein (LDL) at 14 days of age (P < 0.05). In conclusion, the lactobacillus Plantarum injection at the embryonic stage alters lipid metabolism by short-chain fatty acids especially butyric produced by the specific bacteria of Roseburia and Anaerostipes.
Fatty liver syndrome (FLS) is a kind of nutritional metabolic disease in laying hens. Revealing FLS pathogenesis during the early period is what really makes sense for the prevention or nutritional ...regulation strategies. In the study, 9 healthy or naturally occurring early FLS birds were screened based on visual inspection, liver index and morphologic analysis. Liver and fresh cecal content samples were collected. Then transcriptomic and 16S rRNA technologies are applied to investigate hepatic transcriptome and cecum microbiota composition. Unpaired Student t test and some omics methods were used for statistical analysis. Results showed higher liver weight and index were found in FLS group; morphologic analysis indicated that there existed more lipid droplets in the liver of birds with FLS. Based on DESeq2 analysis, there were 229 up- and 487 down-regulated genes in the FLS group, among which most genes related to de novo fatty acid synthesis were up-regulated such as acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase, and ELOVL fatty acid elongase 6 (ELOVL6). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that pathways associated with lipid metabolism and liver damage were affected. 16S rRNA sequencing analysis of cecum microbiota showed that there was a significant difference between the Con and FLS groups. LEfSe analysis revealed that the relative abundance of Coprococcus, Odoribacter, Collinsella, Turicibacter, YRC22, Enterococcus, Shigella, and Bifidobacterium were down-regulated in the FLS group, whereas the abundance of Bacteroides, Mucispirillum, Butyricicoccus, Campylobacter, Akkermansia, and Clostridium were up-regulated. The KEGG enrichment from differential microbiota suggested that some metabolism-related functions were altered to some extent. Taken together, during the developmental of early fatty liver of laying hens, lipogenesis was enhanced, whereas abnormal metabolism occurs not only in lipid transportation but also in hydrolysis, which caused structural damage to the liver organ. Moreover, the dysbiosis of the cecum microbiota occurred. All of these serve as targets or provide theoretical references for the development of probiotics for fatty liver prevention in laying hens.
Previous studies have emphasized the effect of parent marital conflict on youth's Internet addiction. However, few researchers have examined the mediating role of parent-child attachment and peer ...attachment between marital conflict and Internet addiction. To fill in this gap, this study aims to examine whether father-child, mother-child, and peer attachment play a mediating role between parent marital conflict and Internet addiction. This cross-sectional study included 450 college students in two Universities in China. Structural equation modeling (SEM) was conducted to examine research questions. Results showed that Internet addiction was positively associated with marital conflict and negatively associated with peer attachment. Moreover, both mother-child and father-child attachment mediated the relationship between marital conflict and Internet addiction through peer attachment. To our knowledge, this was the first study examining the mediating role of parent-child and peer attachment between parent marital conflict and youth's Internet addiction. Our findings suggested that educational workers should pay more attention on the development of youth's parent-child and their peer attachment, because youth's attachment played an important role in youth's Internet addiction. Moreover, our findings emphasized that father and mother both important people on the development of youth's peer attachment, which may in turn influence youth's Internet addition.
•Parent marital conflict has a direct effect on youths' Internet addiction.•Father-child, mother-child and peer attachment were all important mediators.•Clinicians should pay more attention on youth's attachment development.•Both father and mother were important people in youth attachment development.
Gastric cancer (GC) is one of the most common malignant tumors with high mortality and metastasis rate. Previous studies elucidated that Long non-coding RNA (LncRNA) MEG3 was down-regulated in ...various tumors and participated in tumor progression. The aim of our study was to investigate the regulating role of MEG3 in cell proliferation and metastasis of GC cells. Our data showed that down-regulated MEG3 was observed in GC tissues and cell lines (MKN74, MKN45, SGC7901, AGS). Overexpressed MEG3 by pcDNA3.1-MEG3 transfection suppressed cell proliferation, migration and invasion of GC cells remarkably. Besides that, the targeting relationship between MEG3 and miR-21 was firstly revealed by bioinformatics prediction. Overexpressed miR-21 was observed in GC tissues and cell lines. Results from luciferase report assay indicated that miR-21 was a target of MEG3 and results from qRT-PCR indicated that the expression of miR-21 was negatively regulated by MEG3. Moreover, overexpressed miR-21 promoted cell proliferation and metastasis. However, pcDNA3.1-MEG3 transfection could counteract the promoting role of miR-21 mimic on GC cell proliferation and metastasis, indicating that MEG3 suppressed proliferation and metastasis of GC cells through inhibiting miR-21 expression. Finally, the mice tumor model experiments showed that overexpressed MEG3 could also inhibit tumor growth and metastasis in vivo through inhibiting miR-21 expression. In summary, our study revealed the regulating role of MEG3/miR-21 axis in GC progression and provided a new potential therapeutic strategy for GC treatment.
With global warming and ban on antibiotics, it occurs occasionally that deoxynivalenol (DON) together with Clostridium perfringens impairs the gut health of broiler chickens. However, the interactive ...effect of DON and C. perfringens on intestinal health is still unknown. A total of 120 one-day-old Arbor Acres broilers were randomly distributed to 4 groups. Birds were gavaged with C. perfringens (8 × 108 CFU/d per bird) or sterile medium and fed a DON diet (0 or 5 mg of DON per kg diet) to investigate the interactive effects. The main effect analysis showed that DON diet significantly downregulated (P < 0.05) the mRNA expression of mucin-2, B-cell lymphoma-2–associated X, and cysteinyl aspartate–specific proteinase-3 of jejunal mucosa; decreased (P < 0.05) the indexes of ACE, Chao1, Shannon, and Simpson; and also decreased the relative abundance of the phylum Bacteroidete and the genera Lactococcus in jejunal contents of broilers chickens. Meanwhile, C. perfringens significantly increased (P < 0.05) crypt depth; decreased (P < 0.05) the ratio of villi height to crypt depth, the activity of jejunal diamine oxidase, and the relative abundance of Lactococcus; and upregulated (P < 0.05) the relative expression of B-cell lymphoma-2 and cysteinyl aspartate–specific proteinase-8. Furthermore, the interactions between DON and C. perfringens were most significant (P < 0.05) in the mRNA expression of lipopolysaccharide-induced TNF factor (LITAF) and TLR-4, the abundance of the genera Lactococcus in jejunal contents, and butyric acid concentrations in cecal contents of birds. Finally, Spearman correlation analysis suggested that the most negative correlations (P < 0.05) with the abundance of the genera except Lactobacillus were observed within the mRNA expression of LITAF. The abundance of Lactococcus had a positive correlation (P < 0.05) with the expression of Caspase-3. Most genera except Lactobacillus negatively correlated (P < 0.05) with acetic acid, butyric acid, and total short-chain fatty acids. In conclusion, dietary deoxynivalenol and C. perfringens challenge had a harmful effect on the jejunal health and should be carefully monitored in broiler production.
Palladium (Pd) has been acknowledged to be a rare inner transition metal, which plays a pivotal role in many fields. This article focuses on developing a safe and effective near-infrared fluorescent ...probe, MW-PD, which would make a great contribution to the detection of palladium residue in drugs, especially trace residues. The fluorescent probe was rationally designed by combining the dicyanoisophorone fluorophore with an allyloxycarbonyl group. Based on the Tsuji–Trost reaction, the probe exhibited high selectivity and sensitivity toward Pd (0) over other common metal ions with a low detection limit (8.0 nM). Moreover, MW-PD showed biocompatibility and was successfully applied to imaging Pd (0) in Hela cells.
The gene cell division cycle associated 5 (CDCA5), also called sororin, has oncogenic characteristics and is upregulated in various carcinomas. Nevertheless, the involvement of CDCA5 in ovarian ...cancer (OC), a highly aggressive form of cancer, and the underlying mechanism of metastasis remain inadequately investigated.
The bioinformatics data revealed a negative correlation between the patient's survival and CDCA5 expression, which was overexpressed in OC. Functional assays also confirmed high expression levels of CDCA5 in OC tissues and cells. This suggests that CDCA5 may potentially enhance the motility, migration, and proliferation of OC cells invitro. It impedes DNA damage and apoptosis in OC cells, inhibiting xenograft development in nude mice. The RNA sequencing results suggest CDCA5 is majorly associated with biological functions related to the extracellular matrix (ECM) and influences the transforming growth factor (TGF) signaling pathway. Moreover, subsequent functional investigations elucidated that CDCA5 facilitated the migration and invasion of OC cells viathe TGF-β1/Smad2/3 signaling pathway activation.
CDCA5 may be a strong potential therapeutic target for the treatment and management of OC.
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