DNA损伤在衰老相关疾病中的研究进展

DNA损伤是衰老相关疾病领域的研究热点, 可引起细胞周期停滞、凋亡, 加快个体衰老速度、增加衰老相关疾病的患病风险。本文将从细胞衰老和个体衰老两个层面阐述其与衰老之间的研究进展, 并综述其与衰老常见相关疾病(肿瘤、心血管疾病、阿尔茨海默病)及早衰综合征的关系, 为抗衰老研究和临床干预衰老相关疾病提供理论依据。     

慢性疼痛中枢调控网络的研究现状与思考＊

慢性疼痛是一种复杂的身心疾病，包括躯体痛觉异常、认知障碍、负性情绪等多个方面的改变，同时伴随着神经系统的功能以及结构的改变。本文将对慢性疼痛与下行疼痛调节通路、疼痛情感-认知调控网络以及中脑边缘奖赏网络的相关性，以及针刺镇痛的中枢机制相关研究文献进行综述，旨在探讨下行疼痛调节通路、疼痛情感-认知调控网络以及中脑边缘奖赏网络在慢痛发生机制中的作用，为临床治疗慢性疼痛类疾病提供更优势的治疗方案。     

Go-Ichi-Ni-San 2: A potential biomarker and therapeutic target in human cancers

Cancer incidence and mortality are increasing globally, leading to its rising status as a leading cause of death. The Go-Ichi-Ni-San (GINS) complex plays a crucial role in DNA replication and the cell cycle. The GINS complex consists of four subunits encoded by the GINS1, GINS2, GINS3, and GINS4 genes. Recent findings have shown that GINS2 expression is upregulated in many diseases, particularly tumors. For example, increased GINS2 expression has been found in cervical cancer, gastric adenocarcinoma, glioma, non-small cell lung cancer, and pancreatic cancer. It correlates with the clinicopathological characteristics of the tumors. In addition, high GINS2 expression plays a pro-carcinogenic role in tumor development by promoting tumor cell proliferation and migration, inhibiting tumor cell apoptosis, and blocking the cell cycle. This review describes the upregulation of GINS2 expression in most human tumors and the pathway of GINS2 in tumor development. GINS2 may serve as a new marker for tumor diagnosis and a new biological target for therapy.     

Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

金黄色葡萄球菌异质性耐药机制及实验室检测技术

 异质性耐药是一种特殊的细菌耐药类型，常表现为同一克隆来源的不同细菌亚群对某种抗菌药物表现出不一致的耐药特征，大多数亚群对某种抗菌药物敏感，而少部分亚群对其耐药或高度耐药。异质性耐药分离株常会导致特定抗菌药物抗感染治疗失败。针对异质性耐药菌较为深入的研究主要集中于革兰阴性菌，革兰阳性球菌的相关报道较少。近年有研究报道万古霉素、利奈唑胺、苯唑西林等多种类型抗菌药物异质性耐药金黄色葡萄球菌分离株出现，但其实际临床意义尚待进一步评估。此文对金黄色葡萄球菌异质性耐药机制和检测技术最新进展进行综述，为细菌异质性耐药机制研究和新型检测技术研发提供新的思路。     

Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression

Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.     

Vaccine innovation model: A technology transfer perspective in pandemic contexts

This work identifies the innovations that made it possible for the Bio-Manguinhos/Fiocruz Immunobiological Technology Institute to engage in the entire production of the Oxford/AstraZeneca vaccine (ChAdOx1 nCov-19) in Brazil, just 1.8 years after the COVID-19 pandemic was declared. The results were summarized in a case-based innovation model composed of 11 workstreams, 32 stages, 22 gates, 11 innovations, and 38 events. In terms of research contributions, three were found: (i) the identification of firm and government-level innovations allowing the substantial reduction in the COVID-19 vaccine time-to-market in Brazil; (ii) the presentation of empirical evidence supporting the new Outbreak Paradigm for vaccine research, development, and production; and (iii) the proposition of a conceptual model for describing innovations through the vaccine value chain in pandemic contexts, particularly when technology transfer is involved.     

Innovating medication reviews through a technology-enabled process

Medication reviews are effective in improving the quality of medication use among older people. However, they are conducted to various standards resulting in a wide range of outcomes which limit generalisability of findings arising from research studies. There also appear to be funding and time constraints, lack of data storage for quality improvement purposes, and non-standardised reporting of outcomes, especially clinically relevant outcomes. Furthermore, the coronavirus disease-19 (COVID-19) pandemic has restricted many face-to-face activities, including medication reviews. This article introduces a technology-enabled approach to medication reviews that may overcome some limitations with current medication review processes, and also make it possible to conduct medication reviews during the COVID-19 pandemic by providing an alternate platform. The possible advantages of this technology-enabled approach, legislative considerations and possible implementation in practice are discussed.