Decreased expression levels of DAL-1 and TOB1 are associated with clinicopathological features and poor prognosis in gastric cancer

PurposeWe previously demonstrated that the functional inactivation of DAL-1 and TOB1 promotes an aggressive phenotype in gastric cancer cells, but the links between both genes and the survival of patients with gastric cancer are unknown. Here, we investigated the correlations of the expression levels of DAL-1 and TOB1 with the progression of gastric cancer.MethodsA total of 270 patients who underwent resectable gastrectomy were included. The expression of DAL-1 and TOB1 was detected by immunohistochemistry.ResultsLow expression of DAL-1 in cancer tissue was significantly associated with tumor site (p < 0.05), histological grade (p < 0.01), depth of invasion (p < 0.05), lymph node metastasis status (p < 0.05), Lauren classification (p < 0.001), and clinical stage (p < 0.01). A lower level of TOB1 was observed in gastric cancer patients with diffuse type disease compared to patients with either intestinal or mixed type disease (p < 0.001). Additionally, Spearman’s correlation analysis revealed that decreased expression of DAL-1 was positively correlated with low TOB1 expression (r=0.304, p < 0.001). The survival analysis showed that low levels of DAL-1 and TOB1 were significantly associated with poor survival of gastric cancer patients (p <0.001 and p < 0.05, respectively).ConclusionThe downregulation of DAL-1 and TOB1 expression is associated with shorter survival of gastric cancer patients. Hence, DAL-1 and TOB1 may be considered potential novel markers for predicting the outcomes of patients with gastric cancer.     

Suppression of puerarin on polymethylmethacrylate-induced lesion of peri-implant by inhibiting NF-κB activation in vitro and in vivo

Puerarin (PR), a natural isoflavone isolated from Chinese traditional plant pueraria lobata, has attracted considerable attention due to its important biological and pharmacological activities. However, its effects on lesion of peri-implant and related mechanism of action are still not clear, which require further investigation. In this study, we evaluated the effects of PR on polymethylmethacrylate (PMMA)-induced lesion of peri-implant in vitro and in vivo, and explored its possible mechanism of action. Our results indicated that PR could inhibit PMMA-induced osteoclastogenesis in RAW264.7 cells with a dose-dependent manner in vitro and effectively down-regulate mRNA and protein expressions of matrix metalloprotein 9 (MMP-9), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and receptor activator of nuclear factor (NF)-κB (RANK), primarily via the suppression of NF-κB signaling. Furthermore, we found that PMMA induction could directly cause the phosphorylation of IκB and significantly promote the nuclear translocation of p65 in RAW264.7 cells. In other words, PR was able to dose-dependently attenuate the PMMA-induced nuclear translocation of p65 in RAW264.7 cells. In vivo, PR was observed to attenuate PMMA-induced osteoclastogenesis, osteolysis, mRNA expressions of receptor activator of nuclear factor (NF)-κB ligand (RANKL) and RANK, as well as protein levels of MMP-9, TNF-α, IL-6, and p65 in a murine calvarial osteolysis model. These findings suggested that PR might be a potential therapeutic drug to lesion of peri-implant, and provided new insights for understanding its possible mechanism.     

The oncogenic impact of RNF2 on cell proliferation,invasion and migration through EMT on mammary carcinoma

Mammary carcinoma (MC) is one of most common malignancy in women, and ring finger protein 2 (RNF2) possesses various roles in vast human tumors. In MC tissues as well as in cell lines RNF2 exhibited high expression, had significant association with tumor size, lymph node status, TNM stage, patients’ poor survival, and promoted cell proliferation, colony formation, cell migration and invasion of MC cell lines which was mediated by downregulation of E-cadherin protein. These data reveal that RNF2 protein plays a vital role in the development of MC and may be a potential therapy target of MC.     

Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.     

Expression and prognostic value of FOXP1 in esophageal squamous cell carcinoma

BackgroundForkhead box protein P1 (FOXP1) has been suggested as a prognostic marker in several malignant tumors. However, the significance of FOXP1 in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression pattern of FOXP1 in normal esophageal tissue and ESCC and to analyze the clinicopathological significance and prognostic value of FOXP1 in ESCC.MethodsFOXP1 was detected by immunohistochemistry using tissue microarrays containing tumor tissues and adjacent normal tissues from 270 ESCC patients with oncological follow-up data.ResultsNormal esophageal tissues predominantly showed an exclusive nuclear FOXP1 (n-FOXP1) expression pattern, and no exclusive cytoplasmic FOXP1 (c-FOXP1) staining was found. In ESCC, the expression rates of exclusive n-FOXP1-positive, exclusive c-FOXP1-positive, both nuclear and cytoplasmic positive and complete negative were 14.4%, 28.9%, 10.4% and 46.3%, respectively. High n-FOXP1 expression was significantly correlated with decreased postoperative recurrence and distant metastasis (P < 0.05). Furthermore, elevated c-FOXP1 expression was significantly associated with regional lymph node metastasis and distant metastasis (P < 0.05). High c-FOXP1 expression had an effect on shorter overall survival (OS) time, but the difference was not statistically significant (P > 0.05). Kaplan–Meier analysis showed that ESCC patients with high n-FOXP1 expression survived significantly longer than patients with low n-FOXP1 expression. Multivariate analysis confirmed that patients with high n-FOXP1 staining exhibit good prognosis and n-FOXP1 was an independent factor for ESCC prognosis.ConclusionsOur results suggest that FOXP1 plays an essential role in ESCC progression and prognosis and may be a useful biomarker for predicting survival.     

MicroRNA-301b-3p accelerates the growth of gastric cancer cells by targeting zinc finger and BTB domain containing 4

MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment.     

The Chinese National Twin Registry: a ‘gold mine’ for scientific research

The Chinese National Twin Registry (CNTR) currently includes data from 61 566 twin pair from 11 provinces or cities in China. Of these, 31 705, 15 060 and 13 531 pairs are monozygotic, same‐sex dizygotic and opposite‐sex dizygotic pairs, respectively, determined by opposite sex or intrapair similarity. Since its establishment in 2001, the CNTR has provided an important resource for analysing genetic and environmental influences on chronic diseases especially cardiovascular diseases. Recently, the CNTR has focused on collecting biologic specimens from disease‐concordant or disease‐discordant twin pairs or from twin pairs reared apart. More than 8000 pairs of these twins have been registered, and blood samples have been collected from more than 1500 pairs. In this review, we summarize the main findings from univariate and multivariate genetic effects analyses, gene–environment interaction studies, omics studies exploring DNA methylation and metabolomic markers associated with phenotypes. There remains further scope for CNTR research and data mining. The plan for future development of the CNTR is described. The CNTR welcomes worldwide collaboration.     

“中国科技期刊卓越行动计划”资助期刊特征分析

【目的】 对“中国科技期刊卓越行动计划”资助期刊的特征进行分析,可以了解这些具有较高国际影响力的国内科技期刊的特点,为其他有潜力的科技期刊发展提供参考。【方法】 利用文献调研、网站调研、统计分析等方法对入选科技期刊的主办及主管单位、学科类别、国内外学术影响力等方面进行系统剖析,同时通过SCI收录情况与JCR分区指标对顶层的领军期刊和重点期刊进行重点分析。【结果】 领军期刊和重点期刊项目重点支持英文期刊;以域选刊,重点关注优先建设领域;所有期刊均被SCI收录,主要引证指标表现优秀。梯队期刊兼顾中、英文期刊;资助数量最多,覆盖学科领域较广;整体国际学术影响力不高,但其中的中文期刊具有较高的国内影响力。高起点新刊项目主要支持英文期刊,关注优先建设领域。【结论】 “中国科技期刊卓越行动计划”资助期刊在国际影响力、主要引证指标、出版体系等方面呈现出尖兵引领、梯次跟进的态势,同层次期刊可以逐步探索良性的竞争与合作模式,冲击更优、更强的国际一流期刊;未受到资助的期刊可参照相应的指标不断追跑,从而促进我国科技期刊体系的持续健康发展。