This study aimed to investigate the effects of triggering receptor expressed on myeloid cell-2 (TREM2) on the production of pro-inflammatory mediators and cytokines induced by lipopolysaccharide (LPS) in BV2 microglia. TREM2 expression or TREM2-specific siRNA were used to induce TREM2 overexpression or silencing. The BV2 cells were pre-treated with the PI3 K inhibitor of LY294002 for 1 h and stimulated with LPS for 24 h. Then, the cell viability, apoptosis, phagocytosis, nitric oxide (NO), lactate dehydrogenase (LDH), and cytokine production, as well as the activation of AKT and NF-kB were determined, respectively. We found LPS stimulation significantly reduced BV2 cell viability, enhanced BV2 cell phagocytosis and apoptosis compared to the control groups. In addition, LPS stimulation significantly increased the production of NO, LDH, TNF-α, IL-1β, and the activation of AKT and NF-kB, while decreased the levels of IL-10 and TGF-β1. However, these pro-inflammatory effects were significantly attenuated by TREM2 overexpression or pre-treatment with LY294002, while enhanced by TREM2 silencing. Thus, we concluded that TREM2 inhibited neuroinflammation by down-regulating PI3 K/AKT and NF-kB signaling in BV2 microglia. Above all, therapeutic enhanced TREM2 expression may be a new strategy for intervention of neuroinflammatory diseases.

Human guts harbor abundant microbes that regulate many aspects of host physiology. However, bacterial imbalance or dysbiosis in the gut due to the dietary or environmental changes may cause colorectal cancer (CRC). Increasing studies show that gut microbiota plays an important role in the occurrence and development of CRC, as a result of virulence factors, bacterial metabolites, or inflammatory pathways. In the future, probiotics or targeting the microbiota will probably be a powerful weapon in the battle against CRC. This review seeks to outline the relationship between gut microbiota and the development of CRC as well as the potential mechanisms of microbiota involved in treatment of CRC, so as to provide some references for research on the development, prevention, and treatment of this disease.

Background: The leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) is considered a cancer stem cell marker, and is often overexpressed in tumors. The interaction between Lgr5 and the immune-related tumor microenvironment is not completely understood. The aim of this study was to examine the role of Lgr5 in the microenvironment of gastric cancer (GC), and to explore possible immunological mechanisms influencing Lgr5 expression that are governed by regulatory T cells. Methods: Lgr5 expression was examined in 180 GC tumors by immunohistochemistry, and in 80 pairs of GC tumors for analysis of Th1/Th2 cytokines by ELISA. In addition, SGC7901 cells were co-cultured with patient-derived Tregs, varying concentrations of TGF-β1, TGF-β1 neutralizing antibody, or TGF-β receptor inhibitor SB431542, and Lgr5 and β-catenin expression were examined by qRT-PCR and western blot. Results: In this study, an immunosuppressive microenvironment was associated with high Lgr5 expression in GC. Furthermore, Lgr5 expression was up-regulated in GC cells co-cultured with Tregs or treated with exogenous TGF-β1. This up-regulation was partially inhibited by the TGF-β1 neutralizing antibody, or TGF-β1 receptor antagonist SB431542. β-catenin was up-regulated with high Lgr5 expression induced by exogenous TGF-β1, and this up-regulation was inhibited by SB431542. An increased number of Tregs and high Lgr5 expression in GC tissues were significantly associated with low overall survival. Conclusion: Tregs promoted increased Lgr5 expression in GC cells via TGF-β1 and TGF-β1 signaling pathway, which may involve activation of the Wnt signaling pathway. High Lgr5 expression via TGF-β confer poor prognosis in gastric cancer.

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Background: Regulatory T cells (Tregs) and plasmacytoid dendritic cells (pDCs) are the main immunosuppressive cells in tumor microenvironment of gastric cancer (GC). In this prospective study, the association of prognosis with Tregs subsets and pDCs were further analyzed.Methods: pDCs, Tregs population and its expression of inducible costimulator (ICOS) were analyzed in peripheral blood from 41 GC patients by multicolor flow cytometry. These cell populations in carcinoma tissue, peritumor tissue and normal gastric mucosa from 87 GC patients were also detected by immunohistochemistry and double immunofluorescence.Results: Both ICOS+Foxp3+Treg cells (P=0.0341 and P=0.0298, respectively) and pDC (P=0.0237 and P=0.0083, respectively) in peripheral blood and tumor tissue could predict poor clinical outcome in GC patients. However, the total Foxp3+Tregs in the GC tissue didn't correlated with the outcome (P=0.4299). No correlation of CD4+ T cell or CD8+ T cell frequency could be found with clinical outcome neither in peripheral blood nor in tumor tissue.Conclusions: ICOS+Tregs and pDCs could predict poor prognosis of GC, targeting ICOS-L/ICOS costimulation axis may be a potential treatment for GC.

It has previously been reported that cardamonin is able to regulate glycometabolism and vasodilation whilst also exhibiting anti-inflammatory and antitumor properties. The antitumor effect of cardamonin is multifaceted, and so it is necessary to investigate the antitumor mechanisms of cardamonin at the molecular level. Cardamonin alters chemotherapy-resistant colon cancer cell growth; however, the underlying mechanism is unknown. The present study was conducted to investigate the effect of cardamonin on chemotherapy-resistant colon cancer cells and the possible mechanisms of action. Cardamonin significantly suppressed the growth of chemotherapy-resistant colon cancer cells, induced apoptosis and promoted caspase-3/9 activity and Bax protein expression in 5-fluorouracil (5-FU)-resistant HCT-116 cells. Cardamonin significantly suppressed c-MYC, octamer-binding transcription factor 4, cyclin E, testes-specific protease 50 and nuclear factor-κB protein expression in 5-FU-resistant HCT-116 cells. The findings of the present study demonstrate that cardamonin suppresses chemotherapy-colon cancer cell via the NF-κB pathway in vitro.

The results from the present study demonstrate that the HALC is a valid surgical approach for cancer of the right hemicolon that retains the benefits of minimally invasive surgery. We believe that this technique is a safe, useful, and feasible method for patients with right-sided colonic cancer. If practiced more, it might be advocated as a "bridge" between traditional laparoscopic surgery and conventional open procedures.

BackgroundThe relative rarity and anatomical position of retrorectal tumors may lead to difficulty in diagnosis and surgical management.MethodsThis was a retrospective review of 62 patients who had resection of retrorectal tumors between 2002 and 2010.ResultsAll patients in this study were treated by excision of the retrorectal tumors. Surgical approach included transsacral approach (52 cases), transabdominal approach (eight cases), and combined approach (two cases). A total of 48 benign lesions (77.4%) and 14 malignant lesions (22.6%) were confirmed by histological examination. The 48 benign cases included dermoid cysts (17 cases), simple cysts (eight cases), teratomas (eight cases), neurofibromas (eight cases), fibrolipomas (four cases), neurilemmomas (two cases), and synovioma (one case). The 14 malignant cases included lymphomas (four cases), malignant teratomas (three cases), fibrosarcomas (two cases), interstitialomas (four cases) and malignant mesothelioma (one case). Complications occurred in 14.5% of patients and included intraoperative bleeding (three cases), rectal injury (three cases), and presacral infection (three cases).ConclusionPrimary retrorectal tumors are very rare. Successful treatment of these tumors requires extensive knowledge of pelvic anatomy and expertise in pelvic surgery.