益气化瘀解毒方对MRP、GST-π和Topo Ⅱ基因在Sorafenib获得性耐药人肝癌QGY7702细胞表达的干预研究

目的探讨益气化瘀解毒方干预后对Sorafenib获得性耐药人肝癌QGY7702细胞(QGY7702/Sora)增殖及MRP、GST-π和Topo Ⅱ基因表达的影响。方法培养QGY7702/Sora细胞和QGY7702细胞,利用Cell Counting Kit-8(CCK-8)法检测Sorafenib对细胞的半数抑制率浓度(IC50值),计算耐药指数RI;观察益气化瘀解毒方对耐药细胞的增殖影响;采用荧光定量PCR检测药物干预前后2种细胞中MRP、GST-π和Topo Ⅱ基因表达水平。结果亲本细胞和耐药细胞Sorafenib的IC50值分别为(7.993±0.522)μmol/L和(19.651±1.216)μmol/L,RI约为2.5。益气化瘀解毒方可抑制耐药细胞的增殖活性。2种细胞的MRP、GST-π、Topo Ⅱ表达量无明显差异(P>0.05)。Sorafenib组可促进耐药细胞MRP 、GST-π基因的过表达(P<0.05),益气化瘀解毒方组可抑制GST-π基因的过表达(P<0.01),且联合Sorafenib可显著提高Topo Ⅱ基因的表达量(P<0.01)。结论 QGY7702/Sora细胞MRP、GST-π和Topo Ⅱ的表达水平与亲本细胞无显著差异。耐药细胞对Sorafenib敏感性降低与MRP、GST-π过表达相关,而益气化瘀解毒方拮抗Sorafenib耐药与抑制GST-π过表达相关。     

Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms

Ischemic stroke is a global disease with high disability and mortality rates. Cognitive impairment is one of the major clinical features of ischemic stroke, and microglia‐mediated inflammation has been shown to be an important contributor to the pathogenesis of ischemic stroke. Kellerin, extracted from Ferula sinkiangensis, was previously shown to inhibit microglial activation and exert a strong anti‐neuroinflammatory effect. However, there is no report of the potential therapeutic effect of kellerin on ischemic stroke by targeting microglial cells. In this study, we wanted to examine the effects of kellerin on ischemic stroke in the bilateral common carotid artery occlusion (BCCAO) model and the lipopolysaccharide (LPS)‐activated microglia model. We found that kellerin alleviated cognitive impairment, decreased neuronal loss, suppressed microglial activation, and transformed microglia from the pro‐inflammatory M1 phenotype to the anti‐inflammatory M2 phenotype in BCCAO mice. Moreover, in in vitro studies, we found that kellerin regulated microglial polarization and inhibited the NLRP3 and MAPK signaling pathways after LPS treatment. These findings provide a new understanding of the function of kellerin in ischemic stroke, and suggest that kellerin could be a potential therapeutic agent for the treatment of ischemic stroke.     

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.     

益肾养血通窍汤联合西药治疗神经性耳鸣临床研究

目的：观察益肾养血通窍汤联合西药治疗神经性耳鸣的临床效果。方法：将 78 例神经性耳鸣患者按随机数字表法分成 2 组，对照组 39 例采用甲钴胺注射液治疗；观察组 39 例采用甲钴胺注射液联合益肾养血通窍汤治疗。对比 2 组治疗前后血液流变学指标、中医证候积分、耳鸣致残量表（THI）评分及耳鸣严重程度积分。结果：2 组治疗前各血液流变学指标比较，差异无统计学意义（P＞0.05）。治疗后，2 组血液流变学指标均较前改善（P＜0.05），观察组治疗后血液流变学指标与对照组相比降低，差异有统计学意义 （P＜0.05）。2 组治疗前各中医证候积分比较，差异无统计学意义 （P＞0.05）。治疗后，2 组中医证候积分较前改善，观察组治疗后中医证候积分与对照组相比明显降低，差异有统计学意义（P＜0.05）。2 组治疗前 THI 量表评分、耳鸣严重程度积分比较，差异无统计学意义（P＞0.05）。2 组治疗后 THI 量表评分、耳鸣严重程度积分均较前改善，观察组治疗后THI 量表评分、耳鸣严重程度积分与对照组相比降低，差异有统计学意义（P＜0.05）。结论：益肾养血通窍汤联合西药治疗神经性耳鸣的临床效果明显，可有效改善血流速度，缓解耳鸣症状，提高患者听力。