小剂量异维A酸联合2%超分子水杨酸治疗中重度痤疮疗效观察

目的:探讨口服小剂量异维A酸联合外用2%超分子水杨酸治疗中重度痤疮的临床疗效。方法:共选取74例中重度痤疮患者作为研究对象,口服小剂量异维A酸10mg,1次/d。治疗组:37例,联合外用2%新型超分子水杨酸治疗;对照组:37例,联合外用夫西地酸乳膏及阿达帕林凝胶治疗。对两组患者治疗前后的皮损数量变化及治疗效果进行对比分析。结果:经过8周的治疗,两组研究对象的总皮损数量较治疗前均显著减少(P<0.05),且治疗组与对照组比较,无明显差异(P>0.05)。针对不同类型的皮损,治疗组对粉刺的疗效比对照组更具优势,对丘疹与结节的疗效无明显差异。结论:治疗中重度痤疮,小剂量异维A酸联合外用2%超分子水杨酸临床疗效较好,副作用小,可作为痤疮治疗的新选择。     

Hemagglutinin from multiple divergent influenza A and B viruses bind to a distinct branched,sialylated poly-LacNAc glycan by surface plasmon resonance

Influenza viruses initiate infection via specific interactions of hemagglutinin (HA) with host cell surface sialic acid-containing glycans. Antigenic drift has resulted in HA amino acid sequence changes that affect binding properties for sialic acids. Further, viral propagation in eggs and cell culture for vaccine production can yield variants with mutations that affect the conformation and affinity of HA for sialic acids. Therefore, influenza vaccine researchers and manufacturers need robust analytical methods to assess directly the ability of vaccine candidates to bind to their specific sialic acid ligand. We developed a surface plasmon resonance method that uses an extended, biantennary glycan terminating with α-2,6 linked sialic acids to bind influenza HA and assess this interaction. Recombinant HA (rHA) from both influenza A and B viruses isolated from 1999 to 2017 strongly and specifically bind this sialic acid ligand, suggesting the binding ability of divergent HA for this ligand is resistant to antigenic drift. Importantly, the method can differentiate between wild type and mutant rHA for which binding to this sialylated glycan and red blood cells in hemagglutination assays is compromised. We believe this method can be a powerful tool to screen influenza A and B vaccine candidates and final vaccine preparations for their functional ability to bind sialic acids, which allows manufacturers to identify preparations in which mutations that affect sialic acid binding have arisen during propagation. Evaluation of vaccine rHA antigen integrity by confirmation of the receptor binding site functionality is a prudent cautionary step to assure the antigenic quality of seasonal influenza vaccines.     

Inhibition of fatty acid synthase (FASN) affects the proliferation and apoptosis of HepG2 hepatoma carcinoma cells via the β-catenin/C-myc signaling pathway

Introduction and objectivesResearch in the last few years has proven that inhibition of fatty acid synthase (FASN) suppresses the migration and invasion of hepatoma carcinoma cells. This study aims to explore the effect of fatty acid synthase knockdown on the apoptosis and proliferation of HepG2 cells.Materials and methodsThe human liver cancer cell line HepG2 was cultured and then transfected with FASN-specific siRNA and negative control RNAi. After 48 h, cells and protein lysates were used for western blotting, CCK-8 (cell counting kit-8) assays, flow cytometry and other tests. To assess cell apoptosis, Bax, Bcl-2 and caspase-3 were detected; to assess proliferation, CDK4 (cyclin-dependent kinases 4) and P21 were detected; and to determine the signaling pathway involved, β-catenin and C-myc were also detected.ResultsInhibition of FASN in HepG2 cells can decrease proliferation and promote apoptosis. Flow cytometry and CCK-8 assays demonstrated that the apoptosis rate of FASN-specific siRNA-transfected cells was significantly increased compared to that of the control cells (p < 0.01). In addition, the cell cycle analysis revealed that FASN-specific siRNA-transfected cells induced G1 phase arrest (p < 0.05), but an increasing trend in G2 (p < 0.05).Compared with expression in negative RNAi-transfected cells, the expression of Bcl-2 and CDK-4 was reduced and the expression of Bax, caspase-3 and P21 was increased in FASN-specific siRNA-transfected cells (p < 0.05). Regarding the signaling pathway, the expression of β-catenin and C-myc was significantly reduced when compared to that in negative control cells (p < 0.05).ConclusionsInhibition of FASN suppressed the cell survival of HepG2 cells by inhibiting the β-catenin/C-myc pathway. This result suggests the potential treatment value of FASN for hepatoma carcinoma (HCC).     

Dysregulation in nucleic acid‐sensing pathway genes is associated with cancer patients’ prognosis

The innate immune system, the first line of defense against pathogens, is activated by nucleic acids from microbial invaders that are recognized by nucleic acid‐sensing receptors. Recent evidence affirms the ability of these receptors to respond to nucleic acids released by damaged cancer cells. The innate immune system is also involved in cancer immunosurveillance, and could be modulated for devising effective antitumor therapies by targeting nucleic acid‐sensing pathways. A systematic, comprehensive analysis of dysregulation in nucleic acid‐sensing pathways in cancer is required to fully understand its role. Based on multidimensional data of The Cancer Genome Atlas pan‐cancer cohort, we revealed that upregulation of cytosolic DNA‐sensing genes like AIM2 and CGAS was common in tumor tissues. We used 15 genes in the nucleic acid‐sensing pathway to cluster all tumor patients into 2 subgroups and found that the subgroup with higher expression of nucleic acid‐sensing pathway genes was associated with poorer prognosis across cancer types. However, in homologous recombination deficient patients, the nucleic acid recognition activated subgroup was associated with better prognosis, which confirms the therapeutic effect of nucleic acid recognition. This study contributes to a better understanding of the functions and mechanisms of nucleic acid recognition in cancer, lays the foundation for new therapeutic strategies, and enlarges the scope of development of new drugs.     

丝穗金粟兰化学成分研究

目的对丝穗金粟兰Chloranthus fortunei的化学成分进行研究。方法利用多种色谱分离方法和波谱学鉴定方法对丝穗金粟兰中的化学成分进行了分离鉴定,并借助MTT法对其中得到的部分化合物进行了抗肿瘤活性的初步筛选。结果从丝穗金粟兰95%乙醇提取物中分离得到16个化合物,分别鉴定为迷迭香酸(1)、2′-羟基-4,3′,4′,6′-四甲氧基查耳酮(2)、卡瓦胡椒素A(3)、cycloshizukaol A(4)、白术内酯III(5)、4β-hydroxy-8,12-epoxyeudesma-7,11-diene-1,6-dione(6)、(8α)-6,8-dihydroxycadina-7(11),10(15)-dien-12-oic acidγ-lactone(7)、curcolonol(8)、11-hydroxyldrim-8,12-en-14-oic acid(9)、木栓酮(10)、异香草酸(11)、6β-hydroxystigmast-4-en-3-one(12)、3,4-二羟基苯甲酸(13)、莽草酸(14)、东莨菪苷(15)以及N-acetyltyramine 1-O-β-D-glucoside(16)。化合物4和5表现出微弱的细胞毒作用,半数抑制浓度(IC50)值在46～85μmol/L。结论化合物2、10、11、13～15为首次从金粟兰属植物中获得,化合物1～3、6～16为首次从丝穗金粟兰中分离得到。丝穗金粟兰中部分倍半萜显示出弱的抗肿瘤活性。