The aim of the study was to investigate the effects of lactic acid on the phenotypic polarization and immune function of macrophages. The human monocyte/macrophage cell line, THP-1, was selected and treated with lactic acid. Immunofluorescence staining, laser confocal microscopy, reverse-transcription polymerase chain reaction (RT-PCR), western blot, siRNA, and ELISA analyses were used to observe changes in the levels of cluster of differentiation (CD)68, CD163, hypoxia inducible factor (HIF)-1α, and programmed death ligand-1 (PD-L1) as well as those of cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12, and IL-10. THP-1 macrophages and T cells were co-cultured in vitro to observe the changes in proliferation and apoptosis of T cells. The results showed that, lactic acid (15 mmol/l) significantly upregulated the expression of the macrophage M 2 marker CD163 (P<0.05), cytokines, IFN-γ and IL-10, secreted by M 2-tumor-associated macrophages (TAM, P<0.05), and HIF-1α and PD-L1 (P<0.05), and downregulated the expression of cytokines, TNF-α and IL-12, secreted by M 1-TAM (P<0.05). Redistribution of M 2-TAM subsets and PD-L1 expression was reversed after further transfection of THP-1 cells with HIF-1α siRNA (P<0.05). After co-culturing, T-cell proliferation was inhibited and apoptosis was promoted. In summary, modulation of lactic acid level can redistribute M 2-TAM subsets and upregulate PD-L1 to assist tumor immune escape. The HIF-1α signaling pathway may participate in this process, revealing that macrophages, as 'checkpoints' in organisms, are links that connect the immune status and tumor evolution, and can be used as a target in tumor treatment.
Long non‐coding RNAs (lncRNAs) have recently emerged as key regulators of the occurrence and progression of various human cancers, including colorectal cancer. However, the regulatory mechanism of lncRNAs in the tumorigenesis of colorectal cancer remains poorly understood. In this study, we aimed to elucidate the potential role of lncRNA HCG18 in colorectal cancer. Herein, we found that HCG18 expression was significantly upregulated in colorectal cancer tissues and cell lines. Knockdown of HCG18 significantly inhibited the growth and invasion of colorectal cancer cells, while its overexpression had the opposite effect. Moreover, HCG18 was identified as a sponge of miR‐1271. Our results showed that knockdown of HCG18 markedly upregulated miR‐1271 expression in colorectal cancer cells. Notably, HCG18 expression was inversely correlated with miR‐1271 expression in colorectal cancer specimens. Further investigation revealed that HCG18 contributed to the enhancement of MTDH/Wnt/β‐catenin signalling in colorectal cancer cells. The antitumour effect of HCG18 inhibition was significantly reversed by miR‐1271 inhibition or MTDH overexpression. Overall, the results of our study demonstrate that HCG18 exerts a potential oncogenic function in colorectal cancer by enhancing MTDH/Wnt/β‐catenin signalling via sponging of miR‐1271, highlighting the importance of HCG18/miR‐1271/ MTDH/Wnt/β‐catenin signalling in the progression of colorectal cancer.
One of the most frequent and serious complications of endoscopic retrograde cholangiopancreatography (ERCP) is acute pancreatitis. The aim of this study was to evaluate the preventive effect of low-dose heparin (unfractionated or low-molecular-weight heparin) on post-ERCP pancreatitis (PEP) and its side-effects by a systematic review and meta-analysis of clinical trials. Searching PubMed and EMBASE, up to August 2011, two independent reviewers systematically identified prospective clinical trials detecting the effect of prophylactic low-dose heparin on the incidence of PEP, severe PEP, and post-ERCP hemorrhage complications. Four clinical trials fulfilled our selection criteria, with three prospective randomized and one nonrandomized. A meta-analysis of these clinical trials was then performed. A total of 1438 patients were included. Meta-analysis of these trials indicated that there was no significant association between the use of heparin and the reduction of PEP [relative risk (RR) 0.67, 95% confidence interval (CI): 0.44-1.03, P=0.07] and severe PEP (RR 0.62, 95% CI: 0.15-2.60, P=0.51). However, low-dose heparin did not increase the incidence of post-ERCP hemorrhage complications (RR 0.84, 95% CI: 0.34-2.03, P=0.69). This meta-analysis did not demonstrate a statistically significant benefit of prophylactic heparin use for the prevention of post-ERCP pancreatitis. More multicenter trials involving a larger number of patients are needed to show a possible prevention effect of PEP from heparin and its related compounds.
AIM:To observe the effect of proteasome inhibitor MG-132 on severe acute pancreatitis (SAP) and associated lung injury of rats. METHODS: Male adult SD rats were randomly divided into SAP group, sham-operation group, and MG-132 treatment group. A model of SAP was established by injection of 5% sodium taurocholate into the biliarypancreatic duct of rats. The MG-132 group was pretreated with 10 mg/kg MG-132 intraperitoneally (ip) 30 min before the induction of pancreatitis. The changes in serum amylase, myeloperoxidase (MPO) activity of pancreatic and pulmonary tissue were measured. The TNF-α level in pancreatic cytosolic f ra c t i o n s wa s a s s aye d w i t h a n e n z y m e -l i n ke d immunosorbent assay (ELISA) kit. Meanwhile, the pathological changes in both pancreatic and pulmonary tissues were also observed. RESULTS: MG-132 significantly decreased serum amylase, pancreatic weight/body ratio, pancreatic TNF-α level, pancreatic and pulmonary MPO activity (P < 0.05). Histopathological examinations revealed that pancreatic and pulmonary samples from rats pretreated with MG-132 demonstrated milder edema, cellular damage, and inflammatory activity (P < 0.05). CONCLUSION:The proteasome inhibitor MG-132 shows a protective effect on severe acute pancreatitis and associated lung injury of rats.© 2008 The WJG Press. All rights reserved. Chen X, Li SL, Wu T, Liu JD. Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats.
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