Ellagic acid induces apoptosis and autophagy in colon cancer through the AMPK/mTOR pathway.

Ellagic acid (EA), found in fruits and foods, has been shown to be effective in the treatment of breast, colon and bladder cancer. However, due to the complexity of colon cancer, the therapeutic mechanism of EA for colon cancer is still unclear. Cell Counting Kit-8 (CCK-8) assay were employed to investigate the cell proliferation. Western blotting and flow cytometry assays were utilized to investigate apoptosis and autophagy in CRC cells (HCT116), respectively. Moreover, western blotting and luciferase reporter assays were evaluated the effect of EA on AMPK/mTOR pathway. Through flow cytometry analysis, EA could promote the apoptosis of HCT116 cells. In addition, EA can reduce the phosphorylation of mTOR, promoted phosphorylation of AMPK, and induced autophagy in HCT116 cells. Also, Dorsomorphin pretreatment can reduce the expression of autophagy protein, which indicates that EA induces autophagy through AMPK/mTOR pathway. These results suggest that EA inhibits the growth of colon cancer through AMPK/mTOR pathway and induces apoptosis and protective autophagy.

Long Non-Coding RNA CKMT2-AS1 Reduces the Viability of Colorectal Cancer Cells by Targeting AKT/mTOR Signaling Pathway.

Background: Colorectal cancer (CRC) has not only seriously affected people's lives, but also burdened the government healthcare system. Long non-coding RNAs (lncRNA) have attracted more and more attention in the cancer study field. Methods: Experiments were completed in the Medical Research and Innovation Center of Shanghai Pudong Hospital, China from 2019 to 2020. Cell cycle was detected by western blot analyzing and flow cytometry. Apoptosis analysis were determined using flow cytometry or western blot analysis. LncRNA CKMT2-AS1 was knocked down by shRNA transfection. Results: We found CKMT2-AS1 was the most significant=0.0105 for SW480 and P=0.0071 for HCT116) difference lncRNA between colorectal cancer treated with autophagy inducer and colorectal cancer without any treatment. Effective shRNA-CKMT2-AS1 was also designed. Following, we found the treatment of autophagy inducer and autophagy inducer + shRNA-NC were able to suppress the proliferation of both SW480 and HCT116 cells. In addition, the treatment of autophagy inducer + shRNA-CKMT2-AS1 significantly reduced the apoptosis of SW480 and HCT116 cells induced by autophagy. Furthermore, we found the phosphorylation of mTOR, AKT was enhanced in SW480, and HCT116 cells treated with autophagy inducer + shRNA-CKMT2-AS1 compared to the cells treated with autophagy inducer of autophagy inducer + shRNA-NC. Conclusion: Enhancing the expression of CKMT2-AS1 will become a promising strategy to prevent the progress of colorectal cancer.

Polymorphism, expression and structure analysis of key genes in the ovarian steroidogenesis pathway in sheep (Ovis aries).

BACKGROUND: Litter size is an important factor that significantly affects the development of the sheep industry. Our previous TMT proteomics analysis found that three key proteins in the ovarian steroidogenesis pathway, STAR, HSD3B1, and CYP11A1, may affect the litter size trait of Small Tail Han sheep. OBJECTIVE: The purpose of this study was to better understand the relationship between polymorphisms of these three genes and litter size. MATERIAL AND METHOD: Sequenom MassARRAY detected genetic variance of the three genes in 768 sheep. Real-time qPCR of the three genes was used to compare their expression in monotocous and polytocous sheep in relevant tissues. Finally, bioinformatics analysis predicted the protein sequences of the different SNP variants. RESULT: Association analysis showed that there was a significant difference in litter size among the genotypes at two loci of the CYP11A1 gene (p < 0.05), but no significant difference was observed in litter size among all genotypes at all loci of the STAR and HSD3B1 genes (p > 0.05). However, STAR expression was significantly different in polytocous and monotocous sheep in the pituitary (p < 0.01). Tissue-specific expression in the ovary was observed for HSD3B1 (p < 0.05), but its expression was not different between polytocous and monotocous sheep. Bioinformatics analysis showed that the g.33217408C > T mutation of CYP11A1 resulted in major changes to the secondary and tertiary structures. In contrast, gene polymorphisms in STAR and HSD3B1 had minimal impacts on their protein structures. DISCUSSION: This may explain why the CYP11A1 variant impacted litter size while the others did not. The single nucleotide polymorphism of the CYP11A1 gene would serve as a good molecular marker when breeding to increase litter size in sheep. Our study provides a basis for further revealing the function of the ovarian steroidogenesis pathway in sheep reproduction and sheep breeding.

Smoke suppression properties of Si-Al mesoporous structure on medium density fiberboard.

In this article, smoke suppression of Si-Al mesoporous structure on medium density fiberboard (MDF) was investigated by cone calorimeter test (CCT), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and fourier transform infrared spectrometry (FTIR). The CCT results show that the Si-Al mesoporous structure can effectively decrease heat release rate (HRR), total heat release (THR), smoke production rate (SPR), total smoke production (TSP), smoke rate (SR), CO and CO2 concentration, etc. Particularly, the SR curves of MDF present that Si-Al mesoporous structure are considered to be a filter, which can net the solid particles and volatile flammable components in the smoke and fix onto wood fiber. Remarkably, the CO and CO2 concentration curves of MDF indicate that the Si-Al mesoporous structure has an excellent adsorption property, which can rapidly absorb CO and CO2 that generated in wood combustion process. On the other hand, the FTIR and TGA results reveal that the Si-Al mesoporous structure can significantly improve the structure of char residue.

Comparison of laparoscopic versus open gastrectomy for advanced gastric cancer: an updated meta-analysis.

BACKGROUND: Laparoscopic gastrectomy (LG) has been used as an alternative to open gastrectomy (OG) to treat early gastric cancer. However, the use of LG for advanced gastric cancer (AGC) has been in debate. METHODS: Literature retrieval was performed by searching PubMed, EMBASE, and the Cochrane library up to July 2014. Potential studies comparing the surgical effects between LG with OG were evaluated and data were extracted accordingly. Meta-analysis was carried out using RevMan. The pooled risk ratio and weighted mean difference (WMD) with 95 % confidence interval (95 % CI) were calculated. RESULTS: Overall, 26 studies were included in this meta-analysis. LG had some advantages over OG, including shorter hospitalization (WMD, -3.63, 95 % CI, -4.66 to -2.60; P < 0.01), less blood loss (WMD, -161.37, 95 % CI, -192.55 to -130.18; P < 0.01), faster bowel recovery (WMD, -0.78, 95 % CI, -1.05 to -0.50; P < 0.01), and earlier ambulation (WMD, -0.95, 95 % CI, -1.47 to -0.44; P < 0.01). In terms of surgical and oncological safety, LG could achieve similar lymph nodes (WMD, -0.49, 95 % CI, -1.78 to 0.81; P = 0.46), a lower complication rate [odds ratio (OR), 0.71, 95 % CI, 0.59 to 0.87; P < 0.01], and overall survival (OS) and disease-free survival (DFS) comparable to OG. CONCLUSIONS: For AGCs, LG appeared comparable with OG in short- and long-term results. Although more time was needed to perform LG, it had some advantages over OG in achieving faster postoperative recovery. Ongoing trials and future studies could help to clarify this controversial issue.

Efficacy of Laparoscopic Mini Gastric Bypass for Obesity and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background. Controversies on the utility of laparoscopic mini gastric bypass (LMGB) in weight loss and type 2 diabetes mellitus (T2DM) control still exist. Methods. We conducted a comprehensive literature search of PubMed, EMBASE, and Cochrane Library. Review Manager was used to perform the meta-analysis and the weighted mean difference (WMD) and/or odds ratio with 95% confidence interval (95% CI) were used to evaluate the overall size effect. Results. The literature search identified 16 studies for systematic review and 15 articles for meta-analysis. Compared with LAGB, LSG, and LRYGB, LMGB showed significant weight loss [WMD, -6.58 (95% CI, -9.37, -3.79), P < 0.01 (LAGB); 2.86 (95% CI, 1.40, 5.83), P = 0.004 (LSG); 10.33 (95% CI, 4.30, 16.36), P < 0.01 (LRYGB)] and comparable/higher T2DM remission results [86.2% versus 55.6%, P = 0.06 (LAGB); 89.1% versus 76.3%, P = 0.004 (LAGB); 93.4% versus 77.6%, P = 0.006 (LAGB)]; LMGB also had shorter learning curve and less operation time than LRYGB [WMD, -35.2 (95% CI, -46.94, -23.46)]. Conclusions. LMGB appeared to be effective in weight loss and T2DM remission and noninferior to other bariatric surgeries. However, clinical utility of LMGB needs to be further validated by future prospective randomized controlled trials.

Grainyhead-like 2 Promotes Tumor Growth and is Associated with Poor Prognosis in Colorectal Cancer.

GRHL2 was implicated in regulating cancer development. Our previous study demonstrated that knockdown GRHL2 in colorectal cancer (CRC) cells inhibited cell proliferation by targeting ZEB1. It is unclear whether GRHL2 expression may have diagnostic or prognostic value in colorectal carcinoma. Additionally, how GRHL2 is associated with the clinical features of colorectal carcinoma is not known. In current study, immunohistochemistry stains were performed to examine GRHL2 in 171 colorectal cancers and paired normal colon mucosa. The prognostic value of GRHL2 was investigated in a retrospective cohort study with a five-year follow-up. The effects of GRHL2 on cell growth in vitro and in vivo were explored by GRHL2 over-expressing in HT29 and SW620 CRC cells. Further, the regulation of cell cycle and proliferation proteins by GRHL2 were assessed by flow cytometry and western blot. We found that GRHL2 was over-expressed in CRC tissues, and played an important role in CRC tumorigenesis. GRHL2 expression positively correlated with tumor size and TNM stage. Kaplan-Meier analysis showed that GRHL2 was an independent prognostic factor for both overall survival and recurrence-free survival. Ectopic over-expression of GRHL2 in CRC cell line HT29 and SW620 induced an increase of cellular proliferation in vitro and promoting tumor growth in vivo. The acquisition of GRHL2 regulated cell cycle and modulates the expression of proliferation proteins p21, p27, cyclin A and cyclin D1. Together, our findings reveal GRHL2 can be used as a novel predictive biomarker and represent a potential therapeutic target against CRC.

[Expression and clinical significance of GRHL2 in colorectal cancer].

OBJECTIVE: The purpose of this study was to detect the expression of GRHL2 in colorectal cancer (CRC) tissues, and to assess the relationship between GRHL2 expression and clinicopathological features. METHODS: Immunohistochemistry was used to examine GRHL2 in 75 CRC tissues. GRHL2 mRNA and protein levels in the CRC tissues were also analyzed by qRT-PCR and Western blot. The relationship between GRHL2 and clinicopathological features was assessed by Pearson's chi-square (χ(2)) test. RESULTS: Positive immunoreactivity for GRHL2 was detected in the nuclei of CRC cells. GRHL2 expression was increased in CRC tissues compared withthat in the paired non-tumor tissues (61.3% vs. 44.0%, P<0.01). Moreover, qRT-PCR results showed that the relative expression level of GRHL2 mRNA in the colorectal cancer tissue was (2.64±0.35), significantly higher than that of normal mucosa tissue (1.19±0.23, P<0.001). The expression level of GRHL2 mRNA was higher in stage III-IV patients (2.84±0.36) than that of stage I-II cases (2.31±0.32, P<0.05). Western blot results also showed that the expression level of GRHL2 protein in the colorectal carcinoma tissue was significantly higher than that in the normal mucosa (P<0.05). GRHL2 expression was positively correlated with tumor size, TNM stage and Ki-67 (P<0.05, respectively). CONCLUSION: Taking together, our findings demonstrate that GRHL2 is overexpressed in CRC, and plays an important role in the progression of CRC.