来氟米特是一种用于治疗免疫系统疾病的免疫调节剂,但由于存在药物不良反应,超过50%的患者在用药1年后停用该药。目前,药物遗传学研究表明单核苷酸多态性（SNPs）对来氟米特血药浓度有一定的影响,与类风湿性关节炎（RA）患者的有效性和耐受性存在潜在相关。体外研究表明,细胞色素P450酶CYP1A2、CYP2C19和CYP3A4参与来氟米特在机体内的代谢,CYP1A2*1F等位基因可能与RA患者的来氟米特不良反应相关。此外,二氢乳清酸脱氢酶（DHODH）基因rs3213422（19C＞A）的C等位基因和雌激素受体（ESR1/2）的基因多态性可能与来氟米特的不良反应和治疗效果相关。本文总结了参与来氟米特体内过程相关代谢酶及转运体的基因多态性与来氟米特及其活性代谢物特立氟胺血药浓度、临床疗效以及药物不良反应的相关性,为深入研究来氟米特临床合理用药提供参考信息。

葡萄糖醛酸基转移酶（UDP-glucuronosyltransferase,UGT）2B17丰要参与雄激素包括睾酮、双氢睾酮和雄甾酮代谢,是雄激素的主要代谢酶。与雄激素的另一个重要代谢酶UGT2B15氨基酸序列有很高的同源性（约95%）,而且基因座位相邻。近年来,人们发现UGT2B17基因存在普遍的遗传缺失现象,这种遗传差异对疾病造成的影响已经引起了众多研究者的关注。UGT2B17基因拷贝数变异（copy number variants,CNV）源自4号染色体上一段约120kb的DNA序列缺失和插入,该基因多态性发生频率高,种族差异明显,与器官移植,骨质疏松症,肿瘤发生,乃至兴奋剂检查密切相关。UGT2B17的CNV研究方法及功能意义具有重大遗传学及药物基因组学意义。下面我将从UGT2B17基因缺失与个体种族差异、移植排斥反应、肿瘤发生发展等几个方面进行探讨。

Oat containing rich beta-glucan, polyphenols, flavonoids, saponins, alkaloids, and other substances shows good biological activities. Therefore, the present study aimed to uncover the possible mechanism and therapeutic effect of Avenanthramide C in lessening inflammatory responses in pediatric pneumonia. Pediatric pneumonia was induced by liposaccharide (LPS) for vivo model and vitro model. Macrophage was performed to determine the mechanism and effects of Avenanthramide C in pediatric pneumonia. NLRP3 activity participated in the effects of Avenanthramide C in pediatric pneumonia. Avenanthramide C induced p-PI3K and p-Akt expressions and reduced ubiquitination of PI3K expression in pediatric pneumonia. On the other hand, Avenanthramide C integrated serine at 821 sites of the PI3K protein function. Avenanthramide C reduced ROS (reactive oxygen species)-induced mitochondrial damage by PI3K/AKT function in a model of pediatric pneumonia. Avenanthramide C protects pyroptosis in a model of pediatric pneumonia by PI3K/AKT/Nrf2/ROS signaling. Taken together, our results demonstrated that Avenanthramide C protects pyroptosis through dependent ROS-induced mitochondrial damage by PI3K ubiquitination and phosphorylation in a model of pediatric pneumonia, suggesting its potential use for the treatment of pediatric pneumonia and other inflammatory diseases.

目的基于网络药理学及细胞实验验证的方法探讨环黄芪醇治疗酒精性肝损伤的作用靶点及机制。方法运用SwissTargetPrediction数据库预测环黄芪醇的潜在作用靶点。于各疾病数据库中检索酒精性肝损伤疾病的相关靶点,提取共同靶点,利用蛋白

Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence in many countries. The purpose of this study is to explore the function of Schisandrin B and its underlying molecular mechanisms in colitis.In this study, mice with colitis were induced by giving 2.0% dextran sulfate sodium (DSS, MP) in the drinking water for seven days. Furthermore, TCMSP server and GEO DataSets were used to analyze the mechanism of Schisandrin B in colitis.It was found that Schisandrin B presented colitis in mice model. At the same time, Schisandrin B not only reduced inflammation in vivo and vitro model of colitis, but also suppressed the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome in vivo and vitro model of colitis. In addition, Schisandrin B induced AMP-activated protein kinase (AMPK) / Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in model of colitis, and regulated AMPK protein at 316 sites. The inhibition of AMPK reduced the anti-inflammation effects of Schisandrin B on NLRP3 inflammasome. Apart from that, Schisandrin B decreased reactive oxygen species (ROS)-induced mitochondrial damage and reduced epithelial cells damage of colitis through regulating pyroptosis.Collectively, our novel findings for first time showed that, Schisandrin B suppressed NLRP3 inflammasome activation-mediated interleukin-1beta (IL-1 beta) level and pyroptosis in intestinal epithelial cells of colitis model through the activation of AMPK/Nrf2 dependent signaling-ROS-induced mitochondrial damage, which may be a significant therapeutic approach in the treatment of acute colitis.

Sepsis is a common critical illness in ICU and always a great difficulty in clinical treatment. GPR43 (G protein-coupled receptor 43) participates in regulating appetite and gastrointestinal peptide secretion to modulate fat decomposition and formation. However, the biological contribution of GPR43 on inflammation of sepsis has not been previously investigated. We investigated the mechanisms of GPR43 gene, which plays a possible role in distinguishing sepsis and contributes to the pathogenesis of sepsis-induced inflammatory reaction. Furthermore, we performed studies with mice induced to sepsis by Cecal Ligation and Puncture (CLP), Knockout GPR43 (GPR43-/-) mice, and Wild Type (WT) mice induced with CLP. In addition, lung tissues and cell samples were analyzed by histology, Quantitative Polymerase Chain Reaction (Q-PCR), Enzyme-linked Immunosorbent (ELISA) Assay, and western blot. GPR43 agonist could significantly reduce inflammation reactions and trigger lung injury in mice with sepsis. As for GPR43-/- mice, the risks of sepsis-induced inflammatory reactions and corresponding lung injury were promoted. On the one hand, the up-regulation of GPR43 gene reduced ROS mitochondrial damage to inhibit inflammatory reactions via the inactivation of NLRP3 Inflammasome by PPAR gamma/ Nox1/EBP50/ p47phox signal channel. On the other hand, the down-regulation of GPR43 promoted inflammatory reactions in vitro model through the acceleration of ROS-dependently mitochondrial damage by PPAR gamma/ Nox1/EBP50/ p47phox/ NLRP3 signal channel. These findings indicate that the inhibition of GPR43 as a possible important factor of sepsis may shed lights on the mechanism of sepsis-induced inflammation reaction.

Colon cancer, a common type of malignant tumor, seriously endangers human health. However, due to the relatively slow progress in diagnosis and treatment, the clinical therapeutic technology of colon cancer has not been substantially improved in the past three decades. The present study was designed to investigate the effects and involved mechanisms of schisandrin B in cell growth and metastasis of colon cancer. C57BL/6 mice received AOM and dextran sulfate sodium. Mice in treatment groups were gavaged with 3.75-30 mg/kg/day of schisandrin B. Transwell chamber migration, enzyme-linked immunosorbent assay (ELISA), Western blot analysis, immunoprecipitation (IP) and immunofluorescence were conducted, and HCT116 cell line was employed in this study. Data showed that schisandrin B inhibited tumor number and tumor size in the AOD+DSS-induced colon cancer mouse model. Schisandrin B also inhibited cell proliferation and metastasis of colon cancer cells. We observed that schisandrin B induced SMURF2 protein expression and affected SIRT1 in vitro and in vivo. SMURF2 interacted with SIRT1 protein, and there was a negative correlation between SIRT1 and SMURF2 expressions in human colorectal cancer. The regulation of SMURF2 was involved in the anticancer effects of schisandrin B in both in vitro and in vivo models. In conclusion, the present study revealed that schisandrin B suppressed SIRT1 protein expression, and SIRT1 is negatively correlated with the induction of SMURF2, which inhibited cell growth and metastasis of colon cancer. Schisandrin B could be a leading compound, which will contribute to finding novel potential agents and therapeutic targets for colon cancer.

The Warburg effect is a significant hallmark of gastric cancer (GC), and increasing evidence emphasizes the crucial role of circular RNAs (circRNAs) in GC tumorigenesis. However, the precise molecular mechanisms by which circRNAs drive the GC Warburg effect are still elusive. The present study was designed to unveil the roles of circRNAs and the corresponding potential mechanism. High-regulated expression of circCUL3 was observed in both GC tissues and cell lines. Clinically, the high expression of circCUL3 was closely correlated with advanced clinical stage and overall survival in GC patients. Functionally, cellular experimental investigations demonstrated that circCUL3 promoted the proliferation, glucose consumption, lactate production, ATP quantity, and extracellular acidification rate (ECAR) of GC cells. In vivo, circCUL3 knockdown repressed tumor growth. Mechanistic analysis demonstrated that circCUL3 promoted signal transducer and activator of transcription (STAT)3 expression through sponging miR-515-5p; moreover, transcription factor STAT3 accelerated the transcriptional level of hexokinase 2 (HK2). In summary, the present findings provide mechanistic insights into circCUL3/miR-515-5p/STAT3/HK2 axis regulation on the GC Warburg effect, providing a novel possibility for an understanding of GC pathogenesis.