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Background: Metastasis of colorectal cancer (CRC) extremely affects the prognosis of CRC patients. Recently, the genetic methylation has been shown to associate with tumor metastasis. This research aimed to explore the Syk gene, which is frequently hypermethylated in different cancers, and its impact on the metastasis of CRC cells. Methods: We employed the UALCAN database for the detection of the methylation levels of Syk in different cancers. CIBERSORT, TIMER and TISIDB tools were employed to analyze the association of Syk expression with immune features of CRC. Treatment with decitabine has been noted to restore the expression of Syk in CRC cells. The invasion and migration abilities of CRC cell lines were determined using transwell and wound healing assays. The correlation between Syk and c‐Myc was established using the GEPIA2 database and Western blot assays. ​Results: Our results, based on UALCAN, revealed that the methylation level of Syk was altered in diverse cancers including colon adenocarcinoma. We found that expression profile and methylation level of Syk was correlated with immune features of colon adenocarcinoma. Decitabine can restore the expression of Syk in HCT116 and SW480 cells, hence affecting their migration and invasion. Results from GEPIA2 showed that Syk expression was correlated with c‐Myc, while Western blotting analysis revealed a negative association between the expression level of Syk and c‐Myc. ​Conclusions:​ ​This study demonstrates that the expression of Syk could be restored by decitabine in colorectal cancer, thus affecting the migration and invasion abilities of CRC cells., In our study, we aimed to research the correlation of methylation level of Syk and metastasis of colorectal cancer (CRC). We further used Decitabine to restore the expression of Syk in CRC cells. The results revealed that Decitabine could restore the expression of Syk and therefore prohibited the migration and invasion of CRC cells.

The hypoxic tumor microenvironment promotes tumor survival by inducing the expression of genes involved in angiogenesis and metastasis. As a direct target of hypoxia‐inducible factor, lysine demethylase 4B (KDM4B) is overexpressed in multiple cancers, suggesting that a general KDM4B regulatory mechanism may exist in these cancer types. In this study, we sought to further investigate the general and unique roles of KDM4B in ovarian, colon, and renal cancer cells. We first identified a set of potential KDM4B targets shared by SKOV3ip.1, HCT116, and RCC4 cell lines, as well as numerous genes specifically regulated in each cell line. Through Gene Ontology, KEGG, and Oncobox pathway analyses, we found that KDM4B primarily regulated biosynthetic and cell cycle pathways in normoxia, whereas in hypoxia, it regulated pathways associated with inflammatory response and migration. TCGA data analyses reveal high expression of KDM4B in multiple cancer types and differential expression across cancer stages. Kaplan–Meier plots suggest that elevated KDM4B expression may contribute to a better or worse prognosis in a manner specific to each cancer type. Overall, our findings suggest that KDM4B plays complex roles in regulating multiple cancer processes, providing a useful resource for the future development of cancer therapies that target KDM4B expression., KDM4B regulates 26 common genes shared by HCT116, SKOV3ip.1, and RCC4 cell lines. KDM4B regulates numerous genes that are specific for each cell line. KDM4B regulates cell cycle‐related targets in normoxia and inflammatory response and migration‐related genes in hypoxia. KDM4B is highly expressed in multiple cancers and is differentially expressed across cancer stages.

Weight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

Aligned hydrogels have received increasing attention in tissue engineering and electrochemical fields due to their favorable structure. In this work, xanthan gum-based hydrogels (XGH) with aligned pores were prepared via photoinitiated free radical irradiation that used sodium acetate crystals as template. The microstructure, compressive strength, porosity, and absorption capacity of the hydrogel were studied and compared with the non-aligned hydrogels. Scanning electron microscope analysis confirmed the aligned porous structure of the hydrogel. The maximum compressive strength for the aligned hydrogel prepared with 12% acrylamide and 1.5% xanthan gum reached 0.439 MPa at a strain of 95%. Furthermore, aligned XGH exhibited better flexibility than non-aligned hydrogels, as indicated by the Young’s compressive modulus. The porosity of the aligned hydrogels ranged from 94.9% to 88.8% as the acrylamide concentration increased from 12% to 20%. Simulated body fluid absorption showed that hydrogels with aligned pores could attain absorption equilibrium within 5 min, and the maximum absorption capacity reached 33.6 g/g for the sample made with 0.5% xanthan gum and 12% acrylamide. In addition, exhibited preferable biocompatibility, as demonstrated by the cytotoxicity test.

Liver metastasis of colorectal cancer (LMCRC) severely damages patient health, causing poor prognosis and tumor relapse. Marker genes associated with LMCRC identified by previous study did not meet therapeutic demand. Therefore, it is necessary to identify new biomarkers regulating the metastasis network and screen potential drugs for future treatment. Here, we identified that cell adhesion molecules and peroxisome proliferator-activated receptor (PPAR) signaling pathway were significantly enriched by analyzing the integrated-multiple expression profiles. Moreover, analysis with robust rank aggregation approach revealed a total of 138 differentially expressed genes (DEGs), including 108 upexpressed and 30 downexpressed genes. With establishing protein–protein interaction network, we also identified the subnetwork significantly enriching the metastasis-associated hub genes including ALB, APOE, CDH2, and ORM1. ESR2, FOXO3, and SRY were determined as key transcription factors regulating hub genes. In addition, ADH-1, epigallocatechin, CHEMBL1945287, and cochinchinenin C were predicted as potential therapeutic drugs. Moreover, the antimigration capacity of ADH-1 and epigallocatechin were confirmed in CRC cell lines. In conclusion, our findings not only offer opportunities to understand metastasis mechanism but also identify potential therapeutic targets for CRC.

The present study was conducted to evaluate the efficacy and tolerability of using an immune checkpoint inhibitor (ICI; programmed cell death protein 1/ligand 1 [PD-1/PD-L1] inhibitor or cytotoxic T-lymphocyte antigen [CTLA]-4 inhibitor) combined with chemotherapy in the first-line treatment of small cell lung cancer.Potential articles and studies were identified using Web of Science, Cochrane Library, and ClinicalTrials.gov. The end points included overall survival, progression-free survival, objective response rate, and adverse events. Significant heterogeneity was represented by a P value (PFive eligible articles were included. Both overall survival (hazard ratio [HR] = 0.83; 95% CI, 0.75-0.91; P 0.001) and progression-free survival (HR = 0.80; 95% CI, 0.73-0.86; P 0.001) were significantly prolonged by joint ICI + chemotherapy treatment. Additionally, the rates of tolerable grade ≥3 adverse events were similar between the ICI combination regimens and conventional chemotherapy (relative risk = 1.05; 95% CI, 0.98-1.12; P = 0.17). Subanalysis demonstrated that patient survival and objective response rate were more efficiently improved with a combination of anti-PD-1/PD-L1, but not anti-CTLA-4, + chemotherapy.Based on data from the available literature, clinical efficacy (as measured by patient survival and objective response rate) was improved with a combination of anti-PD-1/PD-L1 + chemotherapy as first-line treatment compared with chemotherapy alone in patients with small cell lung cancer.

XRCC4 and DNA Ligase IV (LIG4) cooperate to join two DNA ends at the final step of DNA double-strand break (DSB) repair through non-homologous end-joining (NHEJ). However, it is not fully understood how these proteins are localized to the nucleus. Here we created XRCC4{sup K271R} mutant, as Lys271 lies within the putative nuclear localization signal (NLS), and XRCC4{sup K210R} mutant, as Lys210 was reported to undergo SUMOylation, implicated in the nuclear localization of XRCC4. Wild-type and mutated XRCC4 with EGFP tag were introduced into HeLa cell, in which endogenous XRCC4 had been knocked down using siRNA directed to 3′-untranslated region, and tested for the nuclear localization function by fluorescence microscopy. XRCC4{sup K271R} was defective in the nuclear localization of itself and LIG4, whereas XRCC4{sup K210R} was competent for the nuclear localization with LIG4. To examine DSB repair function, wild-type and mutated XRCC4 were introduced into XRCC4-deficient M10. M10-XRCC4{sup K271R}, but not M10-XRCC4{sup K210R}, showed significantly reduced surviving fraction after 2 Gy γ-ray irradiation as compared to M10-XRCC4{sup WT}. The number of γ-H2AX foci remaining 2 h after 2 Gy γ-ray irradiation was significantly greater in M10-XRCC4{sup K271R} than in M10-XRCC4{sup WT}, whereas it was only marginally increased in M10-XRCC4{sup K210R} as compared tomore » M10-XRCC4{sup WT}. The present results collectively indicated that Lys271, but not Lys210, of XRCC4 is required for the nuclear localization of XRCC4 and LIG4 and that the nuclear localizing ability is essential for DSB repair function of XRCC4. - Highlights: • XRCC4{sup K271R} is defective in the nuclear localization of itself and LIG4. • XRCC4{sup K210R} is competent for the nuclear localization of itself and LIG4. • XRCC4{sup K271R} is deficient in DSB repair function. • XRCC4{sup K210R} is mostly normal in DSB repair function.« less

The potential of adult human adipose tissue stem cells (hASCs) to differentiate into hepatocytes has generated much excitement over the possible use of hASCs in therapeutic applications. An understanding of the molecular mechanisms that underlie the plasticity of hASCs toward hepatocytes will help to make this possibility a reality. Herein, we show that a homogenous population of hASCs characterized by a high level of CD73, CD90, and CD105 express the pluripotent transcription factors OCT4, SOX2, NANOG, and SALL4 under proliferation conditions. A high level of activin A allows for hASCs acquiring the fate of definitive endoderm (DE) cells and expressing the specific transcription factors HEX, FOXA2, SOX17, and GATA4 synchronously. Using a reproducible three-stage method by mimicking liver embryogenesis, hASCs were directed to differentiate into functional hepatocytes. In the first stage, hASCs were induced to become DE cells by 2 days cultured in serum-free medium and 3 days of activin A treatment. Next, the presence of fibroblast growth factor (FGF) 4 and bone morphogenetic protein (BMP) 2 in the medium for 5 days induced efficient hepatic differentiation from DE cells. After 10 days of further maturated by the sequential exposure to hepatocyte growth factor (HGF), oncostatin M (OSM), and dexamethasone (DEX), the hASC-derived hepatocytes expressed mature hepatocytes marker and exhibited functional characterization, including albumin secretion, glycogen storage, urea production, activity of drug transporters, and cytochrome P450 activity. These findings will be useful for the implementation of hASC-derived hepatocytes in therapeutic purposes, metabolic analyses, drug toxicity screening, and studies of hepatocyte function.

In this study, effects of different pretreatment methods on the enzymatic digestibility of Pennisetum alopecuroides, a ubiquitous wild grass in China, were investigated to evaluate its potential as a feedstock for biofuel production. The stalk samples were separately pretreated with H2SO4, NaOH and FeCl3 solutions of different concentrations at 120 &deg, C for 30 min, after which enzymatic hydrolysis was conducted to measure the digestibility of pretreated samples. Results demonstrated that different pretreatments were effective at removing hemicellulose, among which ferric chloride pretreatment (FCP) gave the highest soluble sugar recovery (200.2 mg/g raw stalk) from the pretreatment stage. In comparison with FCP and dilute acid pretreatment (DAP), dilute alkaline pretreatment (DALP) induced much higher delignification and stronger morphological changes of the biomass, making it more accessible to hydrolysis enzymes. As a result, DALP using 1.2% NaOH showed the highest total soluble sugar yield through the whole process from pretreatment to enzymatic hydrolysis (508.5 mg/g raw stalk). The present work indicates that DALP and FCP have the potential to enhance the effective bioconversion of lignocellulosic biomass like P. alopecuroides, hence making this material a valuable and promising energy plant.