Background: MethylatedSDC2andTFPI2are widely used for colorectal cancer (CRC) detection. However, they often miss some CRCs, which directly diminishes the sensitivity. Further investigations of the underlying mechanisms leading to the missed samples will facilitate developing more eligible methylation markers.Methods: CRC samples from TCGA and GEO datasets were divided into three groups, High-methylation/ High-methylation (HH), High-methylation/Low-methylation (HL), and Low-methylation/Low-methylation (LL) according to the methylation status ofSDC2andTFPI2promoters. Variations in age, tumor location and microsatellite instable were then assessed between the three groups and verified in our custom cohort.Results: Samples of HL group preferred to derive from left-sided CRCs (P < 0.05). HH samples showed the highest microsatellite instability and mutation load (mean nonsynonymous mutations for HH/HL/LL: 10.55/3.91/7.02,P = 0.0055). Almost all mutations ofBRAF, one of the five typical CpG island methylator phenotype (CIMP) related genes, were observed in HH group (HH/HL/LL: 51/0/1,P = 0.018). Besides, older patients were frequently found in HH group. Expression analysis identified 37, 84, and 22 group-specific differentially expressed genes (DEGs) for HH, HL, and LL, respectively. Functional enrichment analysis revealed that HH-specific DEGs were mainly related to transcription regulation, while LL-specific DEGs were enriched in the biological processes of extracellular matrix interaction and cell migration.Conclusions: The current study revealed that the performance of methylation-based markers might be affected by tumor location, patient age, mutation load and MSI, and these respective sides should be considered when developing new methylation markers for CRC detection.

MicroRNAs play critical roles in the occurrence and progression in various cancers including colorectal cancer. Here, we found that microRNA-30a expression was significantly downregulated in colorectal cancer tissues compared to adjacent noncancerous tissues, and the suppression levels of microRNA-30a were significantly associated with tumor differentiation and lymph node metastasis. We also discovered that the expression level of microRNA-30a was inversely proportional to the invasive potential of several colorectal cancer cell lines. Moreover, overexpression of microRNA-30a in colorectal cancer cells inhibited activity of cell migration and invasion. Luciferase reporter assay confirmed metadherin could be a direct target of microRNA-30a, as the overexpression of microRNA-30a decreased metadherin expression at both the protein and messenger RNA levels. Furthermore, the knockdown of metadherin expression in SW620 significantly decreased cell metastasis and invasion. The upregulation of metadherin at the protein level negatively correlated with the expression of microRNA-30a in colorectal cancer tissues, and this upregulation could partially attenuate the effect induced by microRNA-30a. These findings indicate that microRNA-30a may act as a tumor suppressor in colorectal cancer and that microRNA-30a represses cell migration and invasion by decreasing metadherin, highlighting the therapeutic potential of microRNA-30a and metadherin in colorectal cancer treatment.

MicroRNAs (miRNAs) are dysregulated in the context of many cancer types, making them potentially ideal diagnostic or therapeutic targets in patients in which they are aberrantly expressed. In the present study, we found miR-7 to be downregulated in gastric cancer (GC), and we further determined its expression to be closely linked to GC sensitivity to the chemotherapeutic compound cisplatin. This effect appears to be at least partially attributable to the regulation of LDH-A, which is a miR-7 target gene and expression of LDH-A is negatively correlated with miR-7 expression in primary GC tumor samples. When upregulated, we also determined that miR-7 was able to inhibit the proliferation, colony formation, and glycolysis of GC cells owing to its regulation of LDH-A. Moreover, overexpression of miR-7 render cells more sensitive to cisplatin. Our results thus provide novel evidence that miR-7 is a key mediator of GC growth and chemosensitivity through its regulation of LDH-A, thus potentially highlighting this pathway as a therapeutic target for treating affected patients.

High strength polyvinyl alcohol (PVA)/soy protein isolate (SPI) composite hydrogels (EPSG) were constructed by the introduction of PVA into SPI through the crosslinking with epichlorohydrin (ECH) and a freezing-thawing process. The EPSG hydrogels were characterized by scanning electron microscopy, FTIR, X-ray diffraction and compressive test. The results revealed that chemical crosslinking interactions occurred for SPI and PVA during the fabrication process. The composite hydrogels exhibited a homogenous porous structure, indicating certain miscibility between PVA and SPI. The introduction of PVA increased the compressive strength of SPI hydrogels greatly, which could reach as high as 5.38 MPa with the water content ratio of 89.5%. Moreover, the water uptake ratio of completely dried SPI hydrogel (namely xerogel) decreased gradually from 327.4% to 148.1% with the incorporation of PVA, showing a better potential as implants. The cytocompatibility and hemocompatibility of the EPSG hydrogels were evaluated by a series of in vitro experiments. The results showed that the EPSG hydrogels had no cytotoxicity (cell viability values were above 86.7%), good biocompatibility and hemocompatibility, showing potential applications as a direct blood contact material in the field of tissue engineering.

Background: Numerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease. Methods: The current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC. Results: We obtained 438,558 DMCs, 15,462 DMRs, and 1568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC. The HOXL-score estimated by HOXC10 and HOXD1 methylation, whose methylation status were then confirmed by sanger sequencing in our custom ESCC samples, showed good ability in discriminating ESCC from normal samples. Conclusions: We observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of esophageal squamous cell carcinoma.

In the present study, we have in situ synthesized polypyrrole (PPy) on the hydroxyethyl cellulose/soy protein isolate (HEC/SPI) sponges to construct electro-conductive HEC/SPI/PPy composite sponges (EHSS-Pn, n > 0). The composite sponges were characterized by Fourier transform infrared spectroscopy X-ray diffraction, scanning electron microscopy, conductivity and mechanical tests. The results indicated that EHSS-Pn still exhibit homogenous inter-connected macroporous structure for cell adhesion, proliferation and metabolism, indicating that the incorporation of PPy didn’t break the original HEC/SPI sponge structure. The electrical conductivity and mechanical properties of the HEC/SPI sponge were improved significantly by the incorporation of PPy. Cytocompatibility and hemocompatibility of all the sponges were evaluated by a series of in vitro experiments. The results of MTT assay and cell direct contact tests showed that the introduction of PPy didn’t cause any cytotoxicity and EHSS-Pn had good biocompatibility. Moreover, EHSS-Pn had good hemocompatibility and no obvious side effects on the as-prepared anticoagulant whole blood after the introduction of PPy. Therefore, the electro-conductive EHSS-Pn showed potential application in the tissue engineering field that requires electrical conductivity for stimulation or sensing such as neural tissue restoration.