Upregulation of miR-489-3p and miR-630 inhibits oxaliplatin uptake in renal cell carcinoma by targeting OCT2

Renal cell carcinoma (RCC) is one of the most common malignant tumors affecting the urogenital system, accounting for 90% of renal malignancies. Traditional chemotherapy options are often the front-line choice of regimen in the treatment of patients with RCC, but responses may be modest or limited due to resistance of the tumor to anticarcinogen. Downregulated expression of organic cation transporter OCT2 is a possible mechanism underlying oxaliplatin resistance in RCC treatment. In this study, we observed that miR-489-3p and miR-630 suppress OCT2 expression by directly binding to the OCT2 3′-UTR. Meanwhile, via 786-O-OCT2-miRNAs stable expression cell models, we found that miRNAs could repress the classic substrate 1-methyl-4-phenylpyridinium (MPP⁺), fluorogenic substrate N,N-dimethyl-4-(2-pyridin-4-ylethenyl) aniline (ASP⁺), and oxaliplatin uptake by OCT2 both in vitro and in xenografts. In 33 clinical samples, miR-489-3p and miR-630 were significantly upregulated in RCC, negatively correlating with the OCT2 expression level compared to that in adjacent normal tissues, using tissue microarray analysis and qPCR validation. The increased binding of c-Myc to the promoter of pri-miR-630, responsible for the upregulation of miR-630 in RCC, was further evidenced by chromatin immunoprecipitation and dual-luciferase reporter assay. Overall, this study indicated that miR-489-3p and miR-630 function as oncotherapy-obstructing microRNAs by directly targeting OCT2 in RCC.     

基于“证治代谢组学”假说探讨中药（单体/复方）药效物质基础的研究思路与实践＊

中药(单体/复方)药效物质基础研究是中医药现代研究的关键问题之一。然而,目前运用的生化和分子生物学方法很难诠释其多靶点、整体性和动态性的整合调节作用。课题组提出的"证治代谢组学"假说理论指出,不同的证候存在"证相关代谢谱群"和"证相关生物标志物",这可能是中药药效物质基础所在,辨证论治后偏离的代谢网络功能呈现回归趋势。基于"证治代谢组学"假说开展中药(单体/复方)药效物质基础研究,这将为阐释中药(单体/复方)防病治病和养生保健的科学内涵及其对疾病个体的整合调节作用提供新的思路。本文以冠心病为研究载体、气阴虚血瘀证为切入点、活血保心丸为干预措施,就该研究思路的内涵与总体模式、提出的背景与依据、实践的方式与可行性、创新与特色及其研究意义等进行了简要介绍。     

Enhancing positive perceptions of aging by savoring life lessons

Objectives: This study examined the effects of savoring valuable life lessons on perceptions of aging and on well-being among older adults.

Method: A total of 303 adults (mean age = 68.12 years) were randomly assigned to one of three experimental conditions: savoring life lessons (n = 95), reflecting on negative aspects of aging (n = 129), or untreated-control condition (n = 79). Participants in the savoring condition wrote about a valuable lesson they had learned in growing older, whereas participants in the negative-aging condition wrote about physical losses they had experienced in aging.

Results: After controlling for baseline happiness, health, gender, and age, participants who savored valuable life lessons reported greater positive perceptions of aging and life satisfaction, compared to participants in the negative-aging and untreated-control conditions. There were no differences across conditions in negative perceptions of aging or in anxiety.

Conclusion: These findings suggest that savoring valuable life lessons could be an effective addition to psychoeducational programs designed to improve perceptions of aging.     

Mindfulness to regulate emotions: The Mindfulness and Emotional Intelligence Program (PINEP) and its adaptation to a virtual learning platform

The present study examines the effect of the Mindfulness and Emotional Intelligence Program (PINEP), adapted to the virtual learning platform Moodle where participants receive Mindfulness training in 12 sessions lasting an hour and a half. The sample consists of 89 people, assigned randomly to a control group on the waiting list and to an experimental group that undertakes the training. The results indicate that the participants who completed PINEP showed improvement in the variables of health, empathy and mindfulness, in comparison with the participants of the group on the waiting list.     

Structural brain differences in emotional processing and regulation areas between male batterers and other criminals: A preliminary study

Poor emotion processing is thought to influence violent behaviors among male batterers in abusive relationships. Nevertheless, little is known about the neural mechanisms of emotion processing in this population. With the objective of better understanding brain structure and its relation to emotion processing in male batterers, the present study compares the cortical grey matter thickness of male batterers to that of other criminals in brain areas related to emotion. Differences among these brain areas were also compared to an emotional perception task. An MRI study and an emotional perception assessment was conducted with 21 male batterers and 20 men convicted of crimes other than Intimate Partner Violence (IPV). Results demonstrated that batterers’ had significantly thinner cortices in prefrontal (orbitofrontal), midline (anterior and posterior cingulate) and limbic (insula, parahipocampal) brain regions. The thickness of the dorsal posterior cingulate cortex in the batterer group correlated with scores on the emotional perception task. These findings shed light on a neuroscientific approach to analyzing violent behavior perpetrated by male batterers, leading to a better understanding of the underlying mechanisms involved in IPV.     

“药妆品”全球监管情况以及对我国的启示

目的：梳理全球范围内"药妆品"监管情况，并对我国政府监管和行业发展提出建议。方法：选取化妆品生产和消费的主要国家或地区作为研究对象，如欧盟、美国、日本、韩国、加拿大等。通过对我国以及上述国家或地区的化妆品定义、相关产品分类、是否承认"药妆品"等情况进行研究比对，对其中容易造成错误理解的概念进行阐释，结合近年来相关问题的监管手段及监管趋势进行分析，总结出适合我国国情的监管建议。结果：通过研究比对，"药妆品"概念不符合大多数国家或地区关于"化妆品"的定义及相关法规要求，监管部门对此持相对谨慎态度，并采取了多种监管手段。结论："药妆品"在全球范围内基本不具有合法地位，我国监管部门应继续保持打击力度，加强上市后监督检查；同时，进一步规范产品分类和功效宣称，积极引导整个行业长期健康发展。     

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。     

Can a pragmatic responsive feeding scale be developed and applied globally?

Responsive feeding (RF) has been recognized as necessary to prevent all forms of malnutrition including stunting and childhood obesity. Specific RF guidelines have been developed, but it is unclear how RF behaviours can be monitored systematically. Therefore, developing valid and reliable abbreviated and pragmatic RF scales is an important global priority. This is challenging, as RF is a construct with multiple dimensions including recognizing and responding to hunger and satiety cues, providing a nurturing environment during feeding episodes, and understanding how feeding needs evolve as a function of the developmental stage of the young child. Further, RF is embedded within the responsive parenting framework that in addition to RF includes sleep, soothing and play routines and the interconnections between them. A recent pioneer study conducted in a rural area of Cambodia validated an 8‐item RF scale through direct feeding observations of 6‐ to 23‐month‐old infants at home, as part of two cross‐sectional surveys conducted before and after a complementary feeding intervention. It is important for similar research to be conducted elsewhere to find out if it is possible or not to develop a core RF scale that is valid and reliable and that has adequate specificity and sensitivity for application in community studies and population surveys globally. As highlighted in this article, different definitions of RF have been used in the field; thus, it is important to reach consensus on a single definition to help move this research area forward.     

胡蜂毒提取物对胶原诱导性类风湿性关节炎大鼠的作用研究

目的建立胶原诱导性类风湿关节炎(collagen-induced arthritis,CIA)大鼠模型来探讨胡蜂毒提取物对大鼠类风湿性关节炎(rheumatoid arthritis,RA)的治疗作用。方法将SD大鼠随机分为正常组、模型组、阳性对照组(注射用蜂毒冻干粉,1.25 mg·kg^-1)和胡蜂毒提取物低、中、高剂量(0.125、0.25、0.5 mg·kg^-1)组,除正常组外,其余各组采用多点注射鸡Ⅱ型胶原加完全弗氏佐剂的方法来诱导大鼠RA模型,每7 d一次,共14 d。造模结束后,各给药组于足趾皮下注射对应剂量的药物,连续给药14 d。分别于造模前、造模第14天和给药第14天测量大鼠踝关节直径和周长,并进行AI评分;观察大鼠脏器指数和踝关节组织HE染色的变化;采用酶联免疫吸附测定(ELISA)检测大鼠血清中相关炎症因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、IL-8、前列腺素(PG)E-2、环氧化酶(COX)-2和类风湿因子免疫球蛋白(Ig)G、Ig A、Ig M的含量变化;利用流式细胞术检测大鼠脾脏T细胞亚群的变化。结果与模型组比较,胡蜂毒提取物对CIΑ大鼠的关节肿胀(直径及周长)抑制效果显著(P<0.01),能明显降低其AI评分(P<0.01或P<0.05),能不同程度恢复大鼠的脏器指数(P<0.01或P<0.05),改善踝关节组织病理学结构病变,降低大鼠血清中各炎症因子和类风湿因子的表达(P<0.01或P<0.05),调节和改善T细胞亚群比例的紊乱(P<0.01或P<0.05)。结论胡蜂毒提取物对CIA大鼠具有较好的治疗作用,这与其对炎症细胞因子网络的调控和对免疫的调节有关系。     

调衡方对Lewis肺癌荷瘤体巨噬细胞吞噬功能的影响＊

目的 研究调衡方对Lewis肺癌荷瘤小鼠巨噬细胞形态、 数量及活性的影响，探讨调衡方对荷瘤体巨噬细胞作用的免疫调节机制。方法 将传代培养的Lewis肺癌细胞接种于小鼠右腋皮下建转移肺癌模型；灌胃给药8 d后，从小鼠腹腔分离抽取巨噬细胞并培养；调衡方各组巨噬细胞培养48 h后，在显微镜下观察活细胞的形态，墨汁吞噬试验以及金葡菌吞噬试验观察巨噬细胞的吞噬能力，细胞酶化学染色观察巨噬细胞胞内酸性磷酸酶的变化，用酶联免疫吸附法（ELISA）检测各培养组M?上清中IL-1、IL-6、TNF-α表达水平。结果 调衡方小、中、大剂量各组巨噬细胞培养48 h后，与对照组比较，巨噬细胞体积显著增大，对墨汁和金葡菌的吞噬能力均显著提升，酸性磷酸酶的活性也明显增强，且能抑制炎性因子IL-1、IL-6、TNF-α分泌，这均与给药浓度呈正相关。结论 调衡方能增强巨噬细胞的吞噬功能，进而提高胞内酸性磷酸酶等的活性，通过抑制巨噬细胞分泌炎性因子（IL-1、IL-6、TNF-α）有控制巨噬细胞向M2型极化的可能，并减轻肿瘤浸润程度，降低肿瘤发展及转移，而发挥抗肿瘤免疫调节的作用。