Correlation between magnetic resonance imaging characteristics and BRAF alteration status in individuals with optic pathway/hypothalamic pilocytic astrocytomas

Background and purposeMost individuals with optic pathway/hypothalamic pilocytic astrocytoma (OPHPA) harbor either the BRAF V600E mutation or KIAA1549-BRAF fusion (K-B). This study aimed to investigate the imaging characteristics of OPHPA in relation to BRAF alteration status.Materials and methodsSeven cases of OPHPA harboring either the BRAF V600E mutation or K-B fusion were included in the study. Preoperative magnetic resonance imaging (MRI) was assessed for degree of T2 hyperintensity on T2-weighted images (T2WI) and the ratio of nonenhancing T2 or fluid-attenuated inversion recovery (FLAIR) hyperintense area to the contrast enhanced area (CE) on gadolinium-enhanced-T1 weighted images (T2/FLAIR-CE mismatch). The T2 signal intensity was normalized to cerebrospinal fluid (T2/CSF) for both the V600E and K-B group and compared. T2/FLAIR-CE mismatch was assessed by calculating the proportion of the tumor volume of nonenhancing high T2 signal intensity to the whole lesion (nonenhancing and enhancing components).ResultsFour and three cases of OPHPA harboring the BRAF V600E mutation and K-B, respectively, were analyzed. The T2/CSF value was higher in the K-B group than in the V600E group. Moreover, the V600E group had a larger T2/FLAIR-CE mismatch than the K-B group.ConclusionsThe BRAF alteration status in individuals with OPHPA was associated with preoperative MRI by focusing on T2 signal intensity and T2/FLAIR-CE mismatch. The BRAF V600E mutation was associated with a lower T2/CSF value and larger T2/FLAIR-CE mismatch, whereas K-B fusion was associated with a higher T2/CSF value and smaller T2/FLAIR-CE mismatch.     

PARP1: A potential biomarker for gastric cancer

Gastric cancer (GC) is the third leading cause of cancer mortality worldwide, with an overall 5-y survival rate of 25%. The majority of GCs are caused by infectious agents, including the bacterium Helicobacter pylori (H. pylori) and Epstein–Barr virus (EBV). Furthermore, inappropriate repair of DNA damage can also result in genomic instability, which has shown to be a key factor in carcinogenesis of different regions including gastric region. Present study was designed to explore the association between base excision repair pathway genes, PARP1 and APEX1 and gastric pathology and H. pylori infection. Two hundred gastric cancer tissue samples (114 H. pylori positive and 86 H. pylori negative) and adjacent uninvolved area taken as controls was used for expression analysis of BER pathway genes at mRNA level and protein levels using quantitative PCR (qPCR) and immunohistochemistry (IHC) respectively. Oxidative stress and DNA damage was also determined by measuring the level of antioxidant enzymes and comet assay respectively. Significant upregulation in PARP1 (p < 0.001) and APEX1 (p < 0.02) was observed in GC tissue samples compared to controls and this upregulation was more pronounced in H. pylori positive cases (HPGC) (PARP1, p < 0.02: APEX1, p < 0.04) than H. pylori negative cases (HNGC). Upregulation of BER pathway genes in HPGC was found correlated with smoking status (p < 0.0001), T stage (p < 0.01) and lymph node metastasis (p < 0.03). Moreover, immunohistochemical staining of BER pathway genes was found correlated with a number of clinicopathological characteristics such as tumor type (p < 0.03), tumor size (p < 0.01) and lymph node metastasis (p < 0.01). Expression levels of APEX1 and PARP1 gene also correlated with increased oxidative burden (p < 0.0001) and DNA damage (p < 0.001) in GC patients. Survival analysis showed that upregulation of PARP1 gene was associated with poor overall survival outcome of gastric cancer patients (HR = 2.04 (95% CI = 1.10–3.76; p < 0.02). Univariate and multivariate cox regression analysis showed the upregulated PARP1 gene (HR = 5.03; 95%CI (2.22–11.35); p = 0.0001), positive smoking status (HR = 3.58; 95%CI (1.67–7.65); p = 0.001), positive status for H pylori infection (HR = 4.38; 95%CI (1.82–10.56); p = 0.001) and advance N-stage (HR = 5.29; 95%CI (2.28–12.24); p = 0.0001) were independent prognostic factors for gastric cancer and may serve as a valuable biomarker for the diagnosis and progression of GC and can be helpful in developing individualized treatment strategies for treating GC.     

Hippo/YAP信号通路在眼部作用的研究进展

Hippo-YAP通路在机体发育和疾病发生中均具有重要作用。Hippo-YAP通路的调节紊乱可能导致病理组织过度生长和肿瘤的进展；近年来研究发现，Hippo-YAP信号通路的异常调节可能与眼部疾病相关，如圆锥角膜、Sveinsson 脉络膜视网膜萎缩和视网膜变性等，本文就Hippo/YAP 在眼部作用的研究进展进行系统综述，为眼部疾病的治疗提供理论基础。     

基于网络药理学和分子对接技术探讨生脉注射液抗新型冠状病毒肺炎的作用机制

目的采用网络药理学与分子对接技术探讨生脉注射液的活性成分和治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法利用TCMSP及BATMAN-TCM数据库筛选生脉注射液的活性化合物,通过TCMSP及Targetnet在线数据库预测作用靶点,通过Cytoscape3.7.1构建活性成分-作用靶点网络图;在GeneCards及OMIM数据库中以"coronavirus pneumonia"为关键词搜索冠状病毒肺炎相关疾病靶点,与生脉注射液化合物靶点进行交集筛选出共同靶点作为研究靶点,将共同靶点导入STRING数据库获取数据后在Cytoscape 3.7.1软件中构建蛋白质-蛋白质相互作用网络图;利用R语言进行GO(gene ontology)功能、KEGG(Kyoto encyclopedia of genes and genomes)通路富集分析,预测其作用机制,并构建"成分-靶点-通路"网络图;通过DiscoveryStudio 2.5软件对关键靶点进行分子对接分析。结果生脉注射液筛选得到22个活性化合物,分别为邻苯二甲酸二辛酯、β-谷甾醇、当归酰基戈米辛O、戈米辛A、戈米辛R、五味子丙素、内南五味子酯乙、长南酸、南五味子内酯、香蒲木脂素B、新杜松烷酸A、新杜松烷酸B、新杜松烷酸C、新南五味子木脂宁、五味子内酯A、五味子内酯E、五味子酸、尿苷、薯蓣皂苷元、鸟嘌呤核苷、N-反式阿魏酰酪胺、豆甾醇。相应作用靶点224个,与COVID-19的共同靶点16个,分别为CASP3、CASP8、PTGS2、BCL2、BAX、PRKCA、PTGS1、PIK3CG、F10、NOS3、DPP4、NOS2、TLR9、ACE、ICAM1、PRKCE,关键靶点涉及CASP3、PTGS2、NOS2、NOS3、ICAM1。GO功能富集分析得到生物过程(BP)条目771个,细胞组成(CC)条目11个,分子功能(MF)条目79个。KEGG通路富集分析筛选得到67条(P0.05)信号通路,主要涉及糖尿病并发症AGE-RAGE信号通路、凋亡通路、P53信号通路、小细胞肺癌通路等。分子对接结果显示与关键靶点对接较好的成分有五味子内酯E、豆甾醇、N-反式阿魏酰酪胺。结论生脉注射液中的活性化合物五味子内酯E、豆甾醇、N-反式阿魏酰酪胺等能作用于CASP3、PTGS2、NOS2、NOS3等靶点调节多条信号通路发挥抗炎、免疫调节、抗休克、增加血氧饱和度等作用,从而可能发挥对COVID-19的治疗作用。     

右归丸经IL-6/STAT3信号通路对膝骨关节炎模型大鼠软骨组织退变的调控机制

目的:观察右归丸对膝骨关节炎(KOA)模型鼠软骨组织信号转导和转录激活因子3(STAT3)和白细胞介素-6(IL-6)表达水平的影响。方法:将大鼠随机分为假手术组、模型组、硫酸氨基葡萄糖组、右归丸高、中、低剂量组,每组10只。采用改良Hulth法制备大鼠KOA模型,假手术组和模型组给予等体积生理盐水灌胃,右归丸高、中、低剂量组分别给予右归丸4.8,2.4,1.2 g·kg^-1灌胃,硫酸氨基葡萄糖组给予硫酸氨基葡萄糖0.17 g·kg^-1灌胃,连续给药8周。干预结束24 h后股动脉采血处死各组大鼠,取鼠膝关节软骨,采用苏木素-伊红(HE)染色法观察各组软骨的病理改变,并进行Mankin评分;免疫组化法检测各组关节软骨组织中STAT3,超氧化物歧化酶3(SOD3)和Wnt抑制因子1(WIF1)的表达;实时荧光定量聚合酶链式反应(Real-time PCR)检测软骨组织中IL-6 mRNA的表达;蛋白免疫印迹法(Western blot)检测各组关节软骨组中WIF1蛋白的表达。结果:与假手术组比较,模型组大鼠软骨组织Makin评分明显升高,软骨组织STAT3在蛋白水平上的表达明显增加和IL-6 mRNA水平上的表达显著增加,WIF1在蛋白水平上的表达显著降低(P<0.01);模型组关节软骨边缘严重破坏,软骨细胞排列紊乱。与模型组比较,右归丸高剂量干预组大鼠软骨组织Makin评分,STAT3的在蛋白水平上的表达明显降低,右归丸各干预组IL-6 mRNA水平上的表达显著降低,WIF1在蛋白水平上的表达显著增加(P<0.05,P<0.01),软骨结构趋于正常,软骨细胞分布仅偶见不均,关节软骨表面欠光滑。结论:右归丸能显著改善KOA大鼠的关节软骨退变,抑制KOA中软骨组织的炎症反应,这可能与其抑制STAT3和IL-6的表达有关。     

<i>Sinomenium</i> Inhibits the Viability of Hepatoma Carcinoma Cells through Activating IFNA2

Hepatocellular carcinoma (HCC) ranks the sixth place of most common cancers. Meanwhile, it is the tertiary mortality cause of cancer. There is no effective therapeutic method to prevent and treat the liver cancer. Sinomenine is a kind of Chinese traditional medicine herbal, it is reported that it can inhibit the viability of several cancer cells. The study is to explore whether sinomenine is also able to inhibit the cell viability of HCC and its potential mechanism. The IC50 of sinomenine in BEL-7402 cells was 5.351 mmol/L, and the IC50 of sinomenine in SMMC-7721 cells was 6.204 mmol/L. The gene expression results showed the relative expression of FGF2, CCND2, DCN, F3, MMP7, NRG1, HMGB1, TRIM29, HAS2, EHF, CTGF, PLK2 were down-regulated, and the relative expression of VEGF A, CITED2, NUPR1, DDX58, IRF9, NAMPT, MMP1, NDRG1, HMGA2, PPARGC1A, IFIT2, PARP9, HEY1, LOX, ETV1, ISG15, BACH, CYLD were up-regulated. Moreover, the IPA analysis results suggested that IFIT3, IFIT1, OAS1, MX1, IRF9, IFI6, IFITM1, ISG15 were up-regulated in BEL-7402 cells treated with sinomenine by activating IFNA2. The findings presented in this study may provide a promising method for the prevention and treatment of liver cancer.     

基于JAK2/STAT3信号通路探讨大黄素保护AR42J胰腺腺泡细胞损伤的作用机制

目的基于JAK2/STAT3信号通路探讨大黄素保护AR42J胰腺腺泡细胞损伤的作用机制。方法将AR42J细胞以1×10~5/mL铺于6孔板,分为对照组、雨蛙素组(雨蛙素10~(-8) mol/L)、大黄素组(终浓度0.25、0.5、1.0mg/L),通过碘-淀粉比色法淀粉酶(AMS)试剂盒测定细胞上清淀粉酶活力水平,确定雨蛙素刺激AR42J胰腺腺泡细胞损伤的收样时间;ELISA法检测TNF-α活力;Western blot法分析JAK2/STAT3通路相关蛋白的表达情况。结果①与对照组比较,雨蛙素组中的AMS、TNF-α、JAK2/STAT3通路相关蛋白表达量显著提高,差异有统计学意义(P0.05)。②与雨蛙素组比较,大黄素各干预组可显著降低雨蛙素诱导的胰腺腺泡细胞损伤的淀粉酶活力、TNF-α含量、JAK2和STAT3的mRNA相对表达量,差异有统计学意义(P0.01)。③大黄素0.5、1.0 mg/L干预组的作用优于0.25 mg/L干预组,差异有统计学意义(P0.001)。结论大黄素能够减轻雨蛙素诱导的胰腺腺泡细胞损伤,其作用机制可能与调控JAK2/STAT3信号通路有关。