Cyanidin-3-glucoside protects against high glucose-induced injury in human nucleus pulposus cells by regulating the Nrf2/HO-1 signaling

Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin with antioxidant and anti-inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)-induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK-8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl-caspase-3, caspase-3, Bax, Bim, collagen II, aggrecan, MMP-3, MMP-13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si-Nrf2 or pcDNA3.0-Nrf2. C3G treatment (12.5, 25, and 50 μM) improved cell viability of HNPCs under HG condition. HG-induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl-caspase-3/caspase-3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP-3, MMP-13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N-acetylcysteine (NAC) reversed HG-induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO-1 in HG-induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS-mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO-1 signaling pathway.     

《欧洲内分泌学会临床实践指南：妊娠期功能性和无功能性垂体腺瘤》指南解读

垂体腺瘤（PA）通常引起性腺轴的损害，导致女性患者的生育能力下降。妊娠可使垂体增大，而性腺轴的激素分泌也随之发生相应改变。因此，对患有PA的妊娠妇女的规范化管理显得尤为重要。2021年8月，欧洲内分泌学会（ESE）发布了关于妊娠期功能性和无功能性PA的临床指南，该指南从腺瘤的大小、位置和有无内分泌功能方面，描述了从妊娠前到分娩后诊断、治疗的时机和选择。本文在ESE指南的基础上，对该指南进行了解读，总结了该指南的要点，以期结合中国的临床经验及患者特点，为临床医师管理此类患者提供具有实践意义的指导意见。     

Validation of the Knowledge of Genome Sequencing (KOGS) scale in cancer patients

IntroductionThe Knowledge of Genome Sequencing (KOGS) questionnaire was recently developed to measure knowledge of genomic sequencing (GS), with preliminary psychometric data supporting its reliability and validity. The aim of this study was to test the reliability and validity of the KOGS in a larger sample, and to confirm its utility in a cancer setting.MethodsThe Genetic Cancer Risk in the Young (RisC) study recruits participants with a personal history of cancer, to investigate heritable cancer causes and future cancer risk using germline GS. Participants (n = 261) in a psychosocial substudy of RisC completed a questionnaire after consent to RisC but before GS, including the KOGS, the Intolerance of Uncertainty Scale, the Chew health literacy scale and items assessing demographic and disease variables. Confirmatory factor analysis (CFA), Cronbach alpha and correlational analyses were undertaken.ResultsThe CFA testing a single-factor model yielded a good model fit, χ2/df = 2.43, comparative fit index (CFI) = 0.97, root mean square error of approximation (RMSEA) = 0.07 and weighted mean root square (WRMR) = 1.03. Factor loadings of all items were above 0.60 and ranged between.66 and.93. The single factor score demonstrated excellent internal consistency (α = 0.82). KOGS scores were significantly associated with health literacy (r = 0.23, p < .001), having a university education [t(258) = ?4.53, p < .001] and having a medical or science background [t(259) = ?3.52, p < .001] but not with speaking a language other than English at home, time since diagnosis, previous genetic counselling/testing or intolerance of uncertainty.DiscussionThis study confirmed a single-factor structure for the KOGS, and its reliability and validity in a cancer population. Associations with measures of health literacy and education were significant and positive as expected, supporting the KOG’s construct validity. Previous genetic counselling may not be sufficient to provide specific knowledge of GS.     

Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions

Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.     

Short-Term Left Ventricular Reverse Remodeling after Transcatheter Aortic Valve Replacement in Children

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