Heat shock factor 1 (HSF1) is a powerful multifaceted oncogenic modifier that plays a role in maintaining the protein balance of cancer cells under various stresses. In recent studies, there have been reports of increased expression of HSF1 in colorectal cancer (CRC) cells, and the depletion of the HSF1 gene knockdown has inhibited colon cancer growth both in vivo and in vitro. Therefore, HSF1 is a promising target for colon cancer treatment and chemoprevention. In the present study, we found that Schizandrin A (Sch A) significantly inhibited the growth of CRC cell lines by inducing cell cycle arrest, apoptosis and death. Through HSE luciferase reporter assay and quantitative PCR (qPCR), we identified Sch A as a novel HSF1 inhibitor. In addition, Sch A could effectively inhibit the induction of HSF1 target proteins such as heat-shock protein (HSP) 70 (HSP70) and HSP27, whether in heat shock or normal temperature culture. In the Surface Plasmon Resonance (SPR) experiment, Sch A showed moderate affinity with HSF1, further confirming that Sch A might be a direct HSF1 inhibitor. The molecular docking and molecular dynamic simulation results of HSF1/Sch A suggested that Sch A formed key hydrogen bond and hydrophobic interactions with HSF1, which may contribute to its potent HSF1 inhibition. These findings provide clues for the design of novel HSF1 inhibitors and drug candidates for colon cancer treatment.

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Purpose. The aim of this study was to investigate the role of Visinin Like 1 (VSNL1) in the proliferation and migration of gastric cancer (GC) cells as well as its clinical prognostic significance. Methods. To this end, we evaluated VSNL1 expression in GC tissues and cell lines by real-time PCR and immunohistochemistry. To further explore the effects of VSNL1, a lentiviral vector expressing a short hairpin RNA (shRNA) against VSNL1 was constructed and transduced into the GC cell lines BGC-823 and SGC-7901. The interference efficiency of VSNL1-shRNA was determined by western blot. The effects of VSNL1 on the migration and invasion of GC cells as well as the expression of P2X3/P2Y2 were explored using MTS, colony formation, migration, and western blot assays. Results. VSNL1 mRNA and protein levels were increased in GC tissues and cell lines. Furthermore, VSNL1 expression was positively correlated with Lauren’s classification, lymph node metastasis, distant metastasis, TNM stage, and prognosis. VSNL1 expression was inversely correlated with the 5-year survival rate of GC patients. VSNL1 expression was markedly reduced in cells transduced with lentivirus expressing shRNA against VSNL1, and inhibiting VSNL1 expression significantly suppressed cell growth, migration, and colony formation and reduced the expression of P2X3/P2Y2. Conclusion. VSNL1 may promote the proliferation and migration of GC cells by regulating P2X3 and P2Y2 expression. VSNL1 plays important roles in GC development and metastasis and may be correlated with patient prognosis.

Background: Complete mesocolic excision (CME) emphasizes sharp dissection along the mesocolon plane and ligation of the supplying vessels at their origin. Although laparoscopic CME is reported to be feasible and safe, the benefit of laparoscopic CME over noncomplete mesocolic excision (NCME) remains unclear. This meta-analysis aimed to compare the safety, quality, and effect of laparoscopic CME with NCME. Materials and Methods:A systematic literature search with no limits was performed in PubMed, Embase, and Web of Science on March 27, 2020. Studies comparing laparoscopic CME with NCME were enrolled. Outcomes of interests included intraoperative, pathologic, postoperative, and survival outcomes.Results: Seven studies (5 articles and 2 conference abstracts) published between 2015 and 2020 with a total of 1595 patients (742 by CME and 853 by NCME) were enrolled. Compared with NCME, laparoscopic CME was associated with less intraoperative blood loss [P < 0.001, weighted mean difference (WMD) = −12.01, 95% confidence interval (CI): −13.56 to −10.45, I 2 = 44%], more harvested lymph nodes (P < 0.001, WMD = 6.50, 95% CI: 3.57-9.42, I 2 = 89%), longer length of specimens (P = 0.004, WMD = 3.57, 95% CI: 1.12-6.03, I 2 = 93%), longer distance from tumor to high tie (P < 0.001, WMD = 1.36, 95% CI: 0.87-1.85, I 2 = 76%), and longer distance from nearest bowel wall to high tie (P < 0.001, WMD = 1.36, 95% CI: 0.87-1.85, I 2 = 85%). No differences were observed in terms of operative time, postoperative complications, wound infection, ileus, proximal, and distal resection margin or disease-free survival between 2 groups. Conclusions:The currently limited evidences suggest that laparoscopic CME can slightly decrease intraoperative blood loss and improve specimen quality, but its safety and survival benefits need to be further studied. High-quality evidences are needed before laparoscopic CME can be recommended as the standard procedure for colon cancer surgery.

Background N6‐methyladenosine (m6A) is the most prevalent methylation modification of eukaryotic RNA, and methyltransferase‐like 3 (METTL3) plays a vital role in multiple cell functions. This study aimed to investigate the role of m6A methylase METTL3 in slow transit constipation (STC). Material and Method The expression of METTL3 and DGCR8 was measured in STC tissues and glutamic acid‐induced interstitial cells of Cajal (ICCs). The effects of METTL3, miR‐30b‐5p, and DGCR8 on the biological characteristics of ICCs were investigated on the basis of loss‐of‐function analyses. Luciferase reporter assay was used to identify the direct binding sites of miR‐30b‐5p with PIK3R2. Results The results showed that the METTL3, DGCR8, miR‐30b‐5p, and the methylation level of m6A were significantly increased in STC tissues and glutamic acid‐induced ICCs. Silencing of METTL3 and miR‐30b‐5p inhibited apoptosis, autophagy, and pyroptosis of glutamic acid‐induced ICCs. Moreover, overexpression of miR‐30b‐5p reversed the cytoprotection of METTL3 knockdown in glutamic acid‐induced ICCs. Besides, DGCR8 knockdown could facilitate cell growth and decrease apoptotic glutamic acid‐induced ICCs. Mechanically, we illustrated that METTL3 in glutamic acid‐induced ICCs significantly accelerated the maturation of pri‐miR‐30b‐5p by m6A methylation modification, resulting in the reduction of PIK3R2, which results in the inhibition of PI3K/Akt/mTOR pathway and ultimately leads to the cell death of STC. Conclusions Collectively, these data demonstrated that METTL3 promoted the apoptosis, autophagy, and pyroptosis of glutamic acid‐induced ICCs by interacting with the DGCR8 and successively modulating the miR‐30b‐5p/PIK3R2 axis in an m6A‐dependent manner, and METTL3 may be a potential therapeutic target for STC.

Hypoxia-mediated tumor progression is a major problem in colorectal cancer (CRC). MicroRNA (miR)-200b-3p can attenuate tumorigenesis in CRC, while exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) can promote cancer progression. Nevertheless, the function of exosomal miR-200b-3p derived from CAFs in CRC remains unclear. In this study, CAFs and normal fibroblasts (NFs) were isolated from CRC and adjacent normal tissues. Next, exosomes were isolated from the supernatants of CAFs cultured under normoxia and hypoxia. Cell viability was tested using the cell counting kit-8 assay, and flow cytometry was used to assess cell apoptosis. Cell invasion and migration were evaluated using the transwell assay. Dual-luciferase was used to investigate the relationship between miR-200b-3p and high-mobility group box 3 (HMBG3). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the miR-200b-3p and HMBG3 level. Our results found that the miR-200b-3p level was sharply reduced in CRC tissues compared to adjacent normal tissues. Additionally, the miR-200b-3p level was reduced in exosomes derived from hypoxic CAFs compared to exosomes derived from CAFs under normoxia. Exosomes derived from hypoxic CAFs weakened the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. However, hypoxic CAFs-derived exosomes with upregulated miR-200b-3p increased the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. In addition, HMBG3 was identified as the downstream target of miR-200b-3p in CRC cells, and its overexpression partially reversed the anti-tumor effect of the miR-200b-3p agomir on CRC via the mediation of the β-catenin/c-Myc axis. Furthermore, compared to exosomes derived from normoxia CAFs, exosomes derived from hypoxic CAFs weakened the therapeutic effects of 5-FU on CRC in vivo via the upregulation of HMGB3 levels. Collectively, the loss of exosomal miR-200b-3p in hypoxia CAFs reduced the sensitivity to 5-FU in CRC by targeting HMGB3. Thus, our research outlines a novel method for the treatment of CRC.

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In this paper, a facile aqueous route to water-soluble CdSe/CdS quantum dots (QDs) under mild conditions has been developed. The samples were characterized by means of transmission electron microscopy, energy-dispersive X-ray spectroscopy, and photoluminescence (PL) spectroscopy. The PL property of the QDs can be controlled by adjusting the reaction time. The CdSe/CdS QDs after 48-h reaction with size of 5 nm have the strongest PL intensity located at 553 nm, and the highest quantum yield of 19.9 %. The obtained QDs were applied for the colorectal cancer screening. The QDs could be conjugated with antibody of aldo-keto reductase family 1, member B10 (AKR1B10) for the detection of AKR1B10. The AKR1B10 in PBS/5 % serum solution with concentration of 1 ng/mL could be well calibrated, and the limit of detection could be lower than 0.05 ng/mL.Keywords CdSe/CdS quantum dots Á Water soluble Á Colorectal cancer Á Aldo-keto reductase family 1, member B10 (AKR1B10) Á Nanomedicine Á Health effects