Low serum level of 25-OH vitamin D relates to Th17 and treg changes in colorectal cancer patients.

BACKGROUND: Serum 25-hydroxyvitamin D [25(OH)D] level alters in colorectal cancer (CRC) development. Regulatory T (Treg) cells and T- helper type 17 (Th17) cells are involved in immune response. Th17-mediated proinflammatory responses contribute to tumorigenesis, and Treg plays different roles in different periods of CRC. Vitamin D deficiency is associated with significant variations in peripheral immune cells. This study investigated the relationship between Th17 and Treg cells and 25(OH)D level in CRC. METHODS: Ninety-five CRC patients were included, as well as 80 healthy controls during the same period at the Affiliated Hospital of Jiangnan University. 25(OH)D level was analyzed through electrochemiluminescence (ECLIA). Th17 and Treg levels were evaluated through flow cytometry. Serum levels of interleukin (IL)-10, IL-17, IL-23, and transforming growth factor-ß (TGF-ß), were analyzed through commercial enzyme-linked immunoassay (ELISA) kits. RESULTS: 25(OH)D levels were downregulated in the serum of CRC patients. Decreased 25(OH)D level contributed to CRC pathogenesis. Decreased 25(OH)D level in CRC correlated with increased Treg and Th17 cell ratios and TGF-ß1, IL-10, IL-17, and IL-23 levels in peripheral blood. CONCLUSION: Decreased 25(OH)D level in the serum of CRC patients had negative correlation with Treg and Th17 ratios and relative cytokines levels.

Deletion 101 residue at caveolin-1 scaffolding domain peptides impairs the ability of increasing heme oxygenase-1 activity.

OBJECTIVE: Resident alveolar macrophages (AMs) are activated and release proinflammatory mediators and chemokines during acute lung injury. We have previous reported that caveolin-1 (Cav-1) scaffolding domain (CSD) peptide inhibited the proinflammatory cytokines expression by up-regulating heme oxygenase-1 (HO-1) activity. In this study, we aimed to investigate the effect of residue R101 in CSD peptide on the activity of HO-1 in AMs. METHODS: The binding mode between HO-1 and CSD peptides (WT CSD and Δ101 CSD truncation peptides) was analyzed and the free energy was calculated. The inflammatory genes and M1/M2macrophage polarization-associated genes expression were measured by real-time PCR. The activities of HO-1 were determined by the spectrophotometical method. Western blot analyzed the content of Cav-1, HO-1, IκB and MAPK signals (phosphorylated ERK, JNK and p38 MAPK). RESULTS: Δ101CSD peptide could bind to HO-1 protein and to disrupt the interaction of HO-1 and Cav-1. However, Δ101CSD peptide had lower activity of HO-1 in LPS-treated AMs compared with WT CSD. The expression of IL-1ß and MCP-1 and NO content were decreased by WT CSD peptide in LPS treated AMs. However, only MCP-1 expression and NO content were downregulated byΔ101CSD peptide. Meanwhile, compared with those in LPS + hemin + WT CSD group, the mRNA expression of TNF-α, Cd86, IL-12b and NOS2 significantly increased while expression of IL10, Arg1 and CD163 significantly decreased in LPS + hemin + Δ101CSD group. The effect of WT CSD peptide on the inhibition of MAPK signaling pathway were stronger than Δ101 CSD peptide evidenced by the level of phosphorylated ERK, JNK and p38 MAPK. CONCLUSION: Deletion of residue R101 impairs the ability of CSD peptide to increase HO-1 activity and to dampen inflammatory response in LPS-challenged rat AMs.

A 65­gene signature for prognostic prediction in colon adenocarcinoma.

The aim of the present study was to examine the molecular factors associated with the prognosis of colon cancer. Gene expression datasets were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases to screen differentially expressed genes (DEGs) between colon cancer samples and normal samples. Survival­related genes were selected from the DEGs using the Cox regression method. A co­expression network of survival­related genes was then constructed, and functional clusters were extracted from this network. The significantly enriched functions and pathways of the genes in the network were identified. Using Bayesian discriminant analysis, a prognostic prediction system was established to distinguish the positive from negative prognostic samples. The discrimination efficacy of the system was validated in the GSE17538 dataset using Kaplan­Meier survival analysis. A total of 636 and 1,892 DEGs between the colon cancer samples and normal samples were screened from the TCGA and GSE44861 dataset, respectively. There were 155 survival­related genes selected. The co­expression network of survival­related genes included 138 genes, 534 lines (connections) and five functional clusters, including the signaling pathway, cellular response to cAMP, and immune system process functional clusters. The molecular function, cellular components and biological processes were the significantly enriched functions. The peroxisome proliferator­activated receptor signaling pathway, Wnt signaling pathway, B cell receptor signaling pathway, and cytokine­cytokine receptor interactions were the significant pathways. A prognostic prediction system based on a 65­gene signature was established using this co­expression network. Its discriminatory effect was validated in the TCGA dataset (P=3.56e­12) and the GSE17538 dataset (P=1.67e­6). The 65­gene signature included kallikrein­related peptidase 6 (KLK6), collagen type XI α1 (COL11A1), cartilage oligomeric matrix protein, wingless­type MMTV integration site family member 2 (WNT2) and keratin 6B. In conclusion, a 65­gene signature was screened in the present study, which showed a prognostic prediction effect in colon adenocarcinoma. KLK6, COL11A1, and WNT2 may be suitable prognostic predictors for colon adenocarcinoma.

LncRNA-UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p.

Recent preliminary studies reported the in vitro tumor-promoting effects of long non-coding RNA urothelial carcinoma associated 1 (UCA1) in colorectal cancer (CRC). However, the in vivo functions and molecular mechanism of UCA1 in CRC remain unclear. Therefore, we investigated the detailed role and mechanism of UCA1 in CRC. We found that UCA1 was up-regulated in CRCs and negatively correlated with survival time in two CRC cohorts. Functional assays revealed the in vitro and in vivo growth-promoting function of UCA1 and revealed that UCA1 can decrease the sensitivity of CRC cells to 5-FU by attenuating apoptosis. Further mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The protein levels of CREB1 were significantly up-regulated in CRCs, negatively associated with survival time and positively correlated with the UCA1 expression. The present work provides the first evidence of a UCA1-miR-204-5p-CREB1/BCL2/RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.

Caffeic acid phenethyl ester attenuates ionize radiation-induced intestinal injury through modulation of oxidative stress, apoptosis and p38MAPK in rats.

Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. This study aimed to investigate the radioprotective effects of CAPE on X-ray irradiation induced intestinal injury in rats. Rats were intragastrically administered with 10 µmol/kg/d CAPE for 7 consecutive days before exposing them to a single dose of X-ray irradiation (9Gy) to abdomen. Rats were sacrificed 72 h after exposure to radiation. We found that pretreatment with CAPE effectively attenuated intestinal pathology changes, apoptosis, oxidative stress, bacterial translocation, the content of nitric oxide and myeloperoxidase as well as the concentration of plasma tumor necrosis factor-α. Pretreatment with CAPE also reversed the activation of p38MAPK and the increased expression of intercellular cell adhesion molecule-1 induced by radiation in intestinal mucosa. Taken together, these results suggest that pretreatment with CAPE could be a promising candidate for treating radiation-induced intestinal injury.

Protective effects of caffeic acid phenethyl ester against acute radiation-induced hepatic injury in rats.

Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. The current study was intended to evaluate the protective effect of CAPE against the acute radiation-induced liver damage in rats. Male Sprague-Dawley rats were intraperitoneally administered with CAPE (30 mg/kg) for 3 consecutive days before exposing them to a single dose of 30 Gy of ß-ray irradiation to upper abdomen. We found that pretreatment with CAPE significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase and increased the activity of superoxide dismutase and glutathione. Histological evaluation further confirmed the protection of CAPE against radiation-induced hepatotoxicity. TUNEL assay showed that CAPE pretreatment inhibited hepatocyte apoptosis. Moreover, CAPE inhibited the nuclear transport of NF-κB p65 subunit, decreased the level of tumor necrosis factor-α, nitric oxide and inducible nitric oxide synthase. Taken together, these results suggest that pretreatment with CAPE offers protection against radiation-induced hepatic injury.

[Application of preoperative nutritional risk screening in perioperative nutrition support for colorectal cancer patients].

OBJECTIVE: To investigate the guidance role of preoperative nutritional risk screening in perioperative nutrition support for colorectal cancer patients in order to provide evidence for the rational clinical application of nutrition support. METHODS: Nutritional risk screening was carried out in 290 hospitalized colorectal cancer patients from The Fourth People's Hospital of Wuxi City, Tongji Hospital of Tongji University and The Second Hospital of Soochow University with the nutritional risk screening(NSR) 2002 score summary table. Postoperative bowel function recovery and associated nutritional indices were compared between patients who received preoperative nutrition support according to the risk screening results and those who did not. RESULTS: Among 110 patients at nutritional risk, 65 received perioperative nutrition support and had faster recovery of intestinal function [time to first flatus (2.3±0.5) d vs. (3.3±0.5) d, time to first defecation (3.5±0.5) d vs. (4.6±0.6) d, semi-fluid intake (10.1±1.2) d vs. (12.4±2.2) d], shorter postoperative stay [(15.7±1.1) d vs. (18.8±1.4) d], and higher albumin, prealbumin and transferrin [(33.2±4.5) g/L vs. (26.0±4.0) g/L, (0.28±0.05) g/L vs. (0.16±0.04) g/L, (1.92±0.33) g/L vs. (1.75±0.45) g/L] at 7-day postoperatively (all P<0.05) as compared to those without perioperative nutrition support(n=45). While among 180 cases without nutritional risk, there were no significant differences in the above indices between patients who received preoperative nutrition support and those who did not (all P>0.05). CONCLUSION: It is important to evaluate the nutritional risk in hospitalized patients with colorectal cancer, and to carry out nutrition support actively for those at nutritional risk.