IL-10 contributes to gemcitabine resistance in extranodal NK/T-cell lymphoma cells via ABCC4

Investigational New Drugs - Background Chemotherapy resistance is a main reason for treatment failure in extranodal NK/T-cell lymphoma (ENKTL). Interleukin-10 (IL-10) is closely related to...     

滋肾育胎丸加减方预防ACA阳性者不良妊娠结局的效果及机制研究＊

目的 探讨滋肾育胎丸加减方预防抗磷脂抗体（ACA）阳性者不良妊娠结局的效果及机制研究。方法 选取2016年2月至2019年2月我院收治的89例ACA阳性，先兆性流产或有习惯性流产（RSA）史患者，将采用西医治疗的40例作为对照组，将采用西医联合滋肾育胎丸加减方治疗的49例作为观察组，比较两组中医证候疗效、中医证候积分、ACA-IgA、ACA-IgM、ACA-IgG、凝血指标［血小板聚集功能（PAF）、活化蛋白C（PC）、抗凝血酶（AT）、纤溶酶原激活抑制物-1（PAI-1）］、Th1/Th2细胞因子［干扰素γ（IFN-γ）、白介素-2（IL-2）、白介素-4（IL-4）、白介素-10（IL-10）］、妊娠结局、安全性。结果 治疗2周后检测ACA，观察组2例未降低，对照组11例未降低，观察组未降低患者占比低于对照组（P<0.05）；观察组总有效率100.00%高于对照组85.00%（P<0.05）；观察组治疗4周、7周后中医证候积分低于对照组（P<0.05）；观察组治疗4周、7周后ACA-IgA、ACA-IgM、ACA-IgG低于对照组（P<0.05）；观察组治疗4周、7周后PAF、PAI-1低于对照组，PC、AT高于对照组（P<0.05）；观察组治疗4周、7周后IFN-γ、IL-2低于对照组，IL-4、IL-10高于对照组（P<0.05）；观察组活产率95.92%高于对照组80.00%（P<0.05）；组间不良反应总发生率比较，差异无统计学意义（P>0.05）。结论 动态监测ACA对滋肾育胎丸加减方精准应用具有指导意义，指导滋肾育胎丸加减方通过调理脏腑、气血、经络功能，改善先兆性流产或有RSA史患者临床症状及凝血因子指标，降低ACA水平，并可改善患者免疫耐受功能，提高胎儿活产率，且安全性高。     

甲状腺未分化癌发生肺转移的危险因素分析

目的:探讨甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)发生肺转移的危险因素。方法:回顾性分析2010年至2015年SEER数据库中被确诊为ATC的405例患者临床病理资料。通过对年龄、种族、性别、原发灶最大径、原发灶数量、甲状腺外组织侵犯、食管侵犯、气管侵犯、中央区淋巴结转移、颈侧区淋巴结转移10个因素进行单因素分析,进而对单因素分析中有统计学差异的指标行多因素Logistic回归分析,寻找ATC患者发生肺转移的危险因素。结果:405例ATC患者中,发生肺转移107例,未发生肺转移298例。单因素分析显示:原发灶最大径>4 cm、甲状腺外组织侵犯、颈侧区淋巴结转移是预测发生肺转移的显著性因素(均P<0.05)。多因素Logistic回归分析显示:原发灶最大径>4 cm及颈侧区淋巴结转移是ATC患者发生肺转移的独立危险因素(均P<0.05)。结论:原发灶最大径>4 cm、颈侧区淋巴结转移的ATC患者极易发生肺转移,因此,一定要认真参考病理结果,若发现存在以上肺转移危险因素,则积极采取多模式治疗方案,并缩短随访时间,行相关检查(如胸部CT扫描、PET-CT等)。     

Characterization of viral genomic mutations in novel influenza A (H7N9)-infected patients: the association between oseltamivir-resistant variants and viral shedding duration

Since February 2013, human infections with the novel influenza A H7N9 virus have occurred in eastern China. It is important to detect mutations in viral genes and analyze the clinical features of patients and viral shedding duration related to neuraminidase inhibitor (NAI) resistance. We collected clinical specimens from 31 hospitalized H7N9 patients and sequenced NA, PB2, HA, and M gene fragments. Of the 31 identified patients, 7 (22.6%) carried the R292K substitution in NA, 30 (96.8%), 3 (9.7%), and 5 (16.1%) carried E627K, Q591K, and D701N mutations in PB2, respectively, and 2 (6.5%) carried both E627K and D701N mutations in PB2. All 26 identified patients harbored Q226L mutations and possessed only a single arginine (R) at cleavage sites in the HA and a S31N mutation in M2. Among 7 NA-R292K mutated patients, 3 died and 4 were discharged. There was no significant difference in the days that patients started oseltamivir treatment after symptom onset between NA-R292K mutant and NA-R292 wild-type patients (median days, 7 vs 6, P?=?0.374). NA-R292K mutant patients had a significantly longer duration of viral shedding than NA-R292 wild-type patients after oseltamivir treatment (median days, 10 vs 5, P?=?0.022). The mutation of R292K in NA conferring the potential ability of oseltamivir resistance resulted in prolonged viral duration and poor outcome and should be taken into consideration in the clinical management of infected patients.

     

LncRNA XIST acts as a MicroRNA-520 sponge to regulate the Cisplatin resistance in NSCLC cells by mediating BAX through CeRNA network

Background: In recent years, LncRNA acts as a member of competing endogenous RNA (ceRNA), playing an important role in drug resistance of lung cancer. The aim of this study was to identify potential biomarkers about cisplatin resistant lung cancer cells using a comprehensive ceRNA network.Methods: {"type":"entrez-geo","attrs":{"text":"GSE6410","term_id":"6410"}}GSE6410 (GPL-201) analyzed gene expression changes about cisplatin resistance in A549 NSCLC cells. {"type":"entrez-geo","attrs":{"text":"GSE43249","term_id":"43249"}}GSE43249 (GPL-14613) included noncoding RNA expression profiling derived from the cisplatin resistant A549 lung cells. GEO2R, an online analysis tool, analyzed the differentially expressed mRNAs and miRNAs (DEmRNAs and DEmiRNAs). To explore the functional enrichment implication of differentially expressed mRNAs, we used the GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Through miRDB, Targetscan, Starbase and miRWalk, we found targeted miRNAs. The Kaplan-Meier curve method was used to show clinical survival analysis of targeted RNAs (P<0.05). The Starbase database predicted potential lncRNAs mediated targeted miRNAs. Eventually, the novel ceRNA network of lncRNAs, miRNAs, mRNA was constructed by cytoscape3.7.2.Results: 118 differentially expressed mRNAs were the basis of the mediated ceRNA network. DAVID and Kaplan-Meier picked out BAX, an apoptosis regulator. Venn diagram demonstrated 8 miRNAs commonly regulating BAX. Starbase predicted lncRNA XIST mediated miRNAs. Finally, lncRNA XIST may be a useful biomarker regulating cisplatin resistance in lung cancer cells and further, we explored the BAX may effect tumor-infiltrating immune cells.Conclusions: LncRNA XIST competitively bound to miRNA 520 in the regulation of cisplatin resistance by BAX, participating apoptosis in the p53 signaling pathway.     

Plastin 1 drives metastasis of colorectal cancer through the IQGAP1/Rac1/ERK pathway

Tumor metastasis is the dominant cause of death in colorectal cancer (CRC) patients, and it often involves dysregulation of various cytoskeletal proteins. Plastin 1 (PLS1) is an actin‐bundling protein that has been implicated in the structure of intestinal epithelial microvilli; however, its role in CRC metastasis has not yet been determined. In this study, we demonstrated that PLS1 is highly expressed in 33.3% (45/135) of CRC patients and is correlated with lymph node metastasis and poor survival. In in vitro and in vivo experiments, PLS1 induced the migration and invasion of CRC cells and the metastases to the liver and lung in mice. Moreover, the expressions of key factors for CRC metastases, matrix metalloproteinase (MMP) 9 and 2, were enhanced by PLS1, which was dependent on phosphorylating ERK1/2 activated by IQGAP1/Rac1 signaling. The connection between these signals and PLS1 was further confirmed in CRC tissues of patients and the metastatic nodules from a mouse model. These findings suggest that PLS1 promotes CRC metastasis through the IQGAP1/Rac1/ERK pathway. Targeting PLS1 may provide a potential approach to inhibit the metastasis of CRC cells.     

Scutellarin,a modulator of mTOR,attenuates hepatic insulin resistance by regulating hepatocyte lipid metabolism via SREBP‐1c suppression

High levels of consumption of saturated lipids have been largely associated with the increasing prevalence of metabolic diseases. In particular, saturated fatty acids such as palmitic acid (PA) have been implicated in the development of insulin resistance (IR). Scutellarin (Scu) is one of the effective traditional Chinese medicines considered beneficial for liver diseases and diabetes. In this study, we investigated the effect of Scu on IR and lipid metabolism disorders in vitro and in high fat diet (HFD)‐fed mice. In vitro, we found that Scu decreased insulin‐dependent lipid accumulation and the mRNA expression of CD36, Fasn, and ACC in PA‐treated HepG2 cells. Additionally, Scu upregulated Akt phosphorylation and improved the insulin signalling pathway. Moreover, Scu downregulated mammalian target of rapamycin (mTOR) phosphorylation and the n‐SREBP‐1c protein level and also reduced lipid accumulation via the mTOR‐dependent pathway, as confirmed by the molecular docking of Scu to mTOR. In HFD‐fed C57BL/6 mice, Scu improved oral glucose tolerance, pyruvate tolerance and the IR index and also increased the Akt phosphorylation level. Moreover, Scu reduced hepatocyte steatosis, decreased lipid accumulation and triglyceride levels, inhibited mTOR phosphorylation, and decreased the SREBP‐1c level in the liver. Taken together, these findings suggest that Scu ameliorates hepatic IR by regulating hepatocyte lipid metabolism via the mTOR‐dependent pathway through SREBP‐1c suppression.     

Development and Validation of a Metabolic-related Prognostic Model for Hepatocellular Carcinoma

Background and AimsGrowing evidence suggests that metabolic-related genes have a significant impact on the occurrence and development of hepatocellular carcinoma (HCC). However, the prognostic value of metabolic-related genes for HCC has not been fully revealed.MethodsmRNA sequencing and clinical data were obtained from The Cancer Genome Atlas and the GTEx Genotype-Tissue Expression comprehensive database. Differentially expressed metabolic-related genes in tumor tissues (n=374) and normal tissues (n=160) were identified by the Wilcoxon test. Time-dependent receiver operating characteristic curve analysis, univariate multivariate Cox regression analysis and Kaplan-Meier survival analysis were used to evaluate the predictive effectiveness and independence of the prognostic model. Two independent cohorts (International Cancer Genome Consortiums and {"type":"entrez-geo","attrs":{"text":"GSE14520","term_id":"14520"}}GSE14520) were applied to verify the prognostic model.ResultsOur study included a total of 793 patients with HCC. We constructed a risk score consisting of five metabolic-genes (BDH1, RRM2, CYP2C9, PLA2G7, and TXNRD1). For the overall survival rate, the low-risk group had a considerably higher rate than the high-risk group. Univariate and multivariate Cox regression analyses indicated that the risk score was an independent predictor for the prognosis of HCC.ConclusionsWe constructed and validated a novel prognostic model, which may provide support for the precise treatment of HCC.