The aim of this study is to explore the differentially expressed lncRNAs, which may have potential biological function and diagnostic value in colorectal cancer (CRC). Through integrated data mining, we finally identified nine differentially expressed lncRNAs and their potential mRNA targets. After a series of bioinformatics analyses, we screened significant pathways and GO terms that are related to the up-regulated and down-regulated transcripts respectively. Meanwhile, the nine lncRNAs were validated in 30 paired tissues and cell lines by qRT-PCR and the results were basically consistent with the microarray data. We also tested the nine lncRNAs in the serum of 30 CRC patients matched with the CRC tissue, 30 non-cancer patients and 30 health controls. Finally, we found that BLACAT1 was significant for the diagnosis of CRC. The area under the curve (AUC), sensitivity and specificity were 0.858 (95% CI: 0.765–0.951), 83.3% and 76.7% respectively between CRC patients and health controls. Moreover, BLACAT1 also had distinct value to discriminate CRC from other non-cancer diseases. The results indicated that the differentially expressed lncRNAs and their potential target transcripts could be considered as potential therapeutic targets for CRC patients. Meanwhile, lncRNA BLACAT1 might represent a new supplementary biomarker for the diagnosis of CRC.

Tumor associated neutrophils (TANs) play important roles in the progress of CRC. Since tumor microenvironments could influence the phenotypes of TANs, altering the tumor microenvironment to polarize the phenotype of TANs may be a new strategy for tumor treatment. This study aims to investigate the effect of anti-TGF-β on the polarization of TANs from a pro-tumor phenotype towards an anti-tumor phenotype in CRC. In this work, CRC patients had more infiltration of TANs and higher expression of TGF-β in CRC tissue when compared with the controls. In vitro, SW480 cells were co-cultured with primed neutrophils, which simulated the TANs in the tumor microenvironment, and TGF-β was blocked by anti-TGF-β (1D11) in order to polarize TANs. Anti-TGF-β treatment increased the cytotoxicity of TANs and decreased the metastatic chemoattractants secreted by TANs, and ultimately increased the apoptosis of CRC cells significantly while remarkably suppressing the migration of tumor cells. The changes of signaling pathways in the TANs and tumor cells were explored. The results showed that anti-TGF-β attenuated CRC may be partly mediated by suppression of PI3K/AKT signaling pathways in TANs and partly mediated by suppression of TGF-β/Smad signaling pathways in tumor cells. Furthermore, the tumor in the mice treated with 1D11 was obviously smaller and had reverse tumorigenesis compared with the controls, while neutrophil depletion reduced the anti-tumor effect of 1D11. Our data suggest that anti-TGF-β attenuates tumor growth via the polarization of TANs to an anti-tumor phenotype in CRC, which provides new strategies for CRC treatment.

Streptococcal Species is increasingly recognized as a potentially preventable emerging infection in human’s brain with high prevalence around the world. Streptococcus constellatus is one of the most common pathogens. Meanwhile, anaerobic bacteria are the rare causes for intracranial infection. To date, intracranial mixed infection caused by Prevotella intermedia and Streptococcus constellatus has not been reported. We reported a Chinese case to raise the global awareness of severity of the intracranial mixed infection. Here, we illustrated the epidemiological risk factors, clinical manifestations and outcomes of the patient. For patients who suffer from exacerbated brain infection with fetid cerebrospinal fluid, early repeated imaging is urgently needed and empiric antibiotic therapy should consider anaerobic and aerobic bacteria in these situations.

Background. Vitamin C (Vc) deficiency is frequently observed in cancer sites and has been proposed to have an antitumor effect. However, the mechanism of Vc’s killing effect is not clear. Besides, epigenetic alterations exhibit significant effects on colorectal cancer (CRC). This study aimed to explore the mechanism of Vc’s killing effect and its association to epigenetic alterations in CRC. Methods. Cell morphology, apoptosis, proliferation, and cycle were assayed to test Vc’s suppressive function in CRC cell lines. Xenograft and peritoneal implantation metastasis models were performed to evaluate the high-dose Vc’s inhibitory effect on tumor growth and metastasis. Immunohistochemistry was used to measure CD31 expression in solid tumors. A literature summary was applied for screening differently expressed long noncoding RNAs (lncRNAs) in CRC tissues and was closely associated with CRC progression. The qPCR was used to detect the expression of these lncRNAs. The association between Vc and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was evaluated in MALAT1-transfected CRC cells and a xenograft model. Results. Vc was confirmed to function in proliferation suppression, apoptosis induction, and S phase arresting in CRC cell lines. High-dose Vc, but not physiologically low-dose Vc, was identified as a suppressive function on tumor growth in xenograft models and an inhibitory effect on implantation metastasis in peritoneal implantation metastasis mice. Furthermore, a consistent downregulation of MALAT1 induced by Vc was verified among CRC cell lines and tumor tissues from both mouse models. Finally, experiments on MALAT1-knockdown CRC cells and its xenograft model suggested that Vc had a tendency in killing CRC with high MALAT1 expression. Conclusions. Our findings demonstrate that high-dose Vc has more efficiency in suppressing CRC with higher MALAT1 expression. It gives high-dose Vc the possibility of a better curative effect on CRC with overexpressed MALAT1. Further clinical studies are still needed.

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