The methyltransferase SETD3-mediated histidine methylation: Biological functions and potential implications in cancers

SETD3 belongs to a family of SET-domain containing proteins. Recently, SETD3 was found as the first and so-far the only known metazoan histidine methyltransferase that catalyzes actin histidine 73 (His73) methylation, a pervasive modification which was discovered more than 50 years ago. In this review, we summarize some recent advances in SETD3 research, focusing on structural properties, substrate-recognition features, and physiological functions. We particularly highlight potential pathological relevance of SETD3 in human cancers and raise some questions to promote discussion about this novel histidine methyltransferase.     

中药玄参的化学成分

从中药玄参（ＳｃｒｏｐｈｕｌａｒｉａｎｉｎｇｐｏｅｎｓｉｓＨｅｍｓｌ．）中分离得到１个新化合物：４－Ｏ－（对甲氧基肉桂酰基）－α－Ｌ－鼠李糖［４－Ｏ－（ｐ－ｍｅｔｈｏｘｙｃｉｎｎａｍｏｙｌ）－α－Ｌ－ｒｈａｍｎｏｐｙｒａｎｏｓｅ］;同时还分离到４个已知的环烯醚萜甙：爪钧草甙（ｈａｒｐａｇｉｄｅ）,爪钩草酯甙（ｈａｒｐａｇｏｓｉｄｅ）,Ｏ－甲基梓醇（Ｏ－ｍｅｔｈｙｌｃａｔａｌｐｏｌ）,士可玄参甙Ａ（ｓｃｒｏｐｏｌｉｏｓｉｄｅＡ）和１个已知的苯丙素甙：安格洛甙Ｃ（ａｎｇｏｒｏｓｉｄｅＣ）。新化合物的结构通过化学降解和光谱分析得到证明。     

黄曲霉毒素生物合成的遗传调控研究进展

黄曲霉毒素是一类具有较强毒性和致癌力的次级代谢产物,在小麦、水稻、玉米和花生等多种粮食、油料、饲料和食品中检出率均比较高。因此,黄曲霉毒素不仅给人和动物的健康造成极其严重的威胁,而且也给食品和饲料等行业造成了巨大的经济损失。黄曲霉毒素主要由黄曲霉和寄生曲霉产生。自上个世纪60年代首次发现黄曲霉毒素以来,研究者在黄曲霉毒素合成途径、降解、合成机制和致病机理等方面做了大量研究。本文主要综述近年来国内外以黄曲霉为对象的黄曲霉毒素合成的遗传调控机制研究进展。从转录调控、蛋白翻译后修饰、信号转导途径、参与生长发育和形态建成的蛋白和其他酶等方面对黄曲霉毒素合成机制展开综述,为今后进一步深入系统研究黄曲霉毒素合成机制奠定基础,同时为制定防治黄曲霉及其毒素的策略提供理论基础。     

海南岛海岸带木麻黄和厚藤叶片碳、氮、磷含量及其化学计量特征

海岸带植物叶片的化学计量学特征及其影响因素可以为改善海岸带的生态环境提供理论依据。选取海南岛沿岸12个市（县）海岸带木麻黄防护林的木麻黄和周边沙滩上的藤本植物厚藤为研究对象,通过测定木麻黄与厚藤叶片中的碳（C）、氮（N）和磷（P）含量,分析两种植物叶片C、N和P的化学计量学特征及其差异,探究不同环境因子对两种植物叶片C、N、P含量、C：N、C：P和N：P的影响,以期寻找影响海岸带植被生长的主要限制因素。结果表明：海南岛木麻黄叶片C、N和P的平均含量分别是399.06±20.29、12.56±1.04、1.04±0.35 g·kg^-1,C：N、C：P和N：P分别为32.04±2.82、420.65±121.27和12.92±3.21;厚藤叶片C、N和P的平均含量分别是364.31±30.20、12.84±1.96和2.06±0.64 g·kg^-1,C：N、C：P和N：P分别为29.13±4.95、185.85±63.14和6.47±2.12。相关性分析结果表明：木麻黄叶片的N含量与年平均气温和年平均降水量呈显著正相关关系,P含量与年平均降水量呈极显著正相关关系,C：P和N：P与年平均降水量呈显著负相关关系;厚藤叶片C含量与年平均气温呈显著正相关,C：N与年平均降水量呈显著负相关。木麻黄叶片的N含量与10~20 cm土层的SOC呈显著负相关关系,C：N与10~20 cm土层的SOC呈显著正相关,C：P与0~10 cm土层的C：N呈显著正相关关系;厚藤叶片的C含量与10~20 cm土层的SOC呈显著负相关关系,P含量与0~10 cm土层的TN含量,N：P和10~20 cm的SOC含量呈正相关关系,C：N与0~10 cm土层的C：N呈显著正相关关系,C：P与0~10 cm的TN含量呈显著负相关关系而与0~10 cm土层的C：N呈极显著正相关关系,N：P与0~10 cm土层的TN含量呈显著负相关关系。研究结果表明海南岛海岸带植被叶片的碳氮含量较低,N可能是影响该区域植物生长的主要因子,同时,植被生长受到年平均气温、年平均降水量的共同影响,受土壤养分含量影响低,环境因子对不同类型的植物的影响并不相同。     

Ghrelin Affects Gastric Cancer Progression by Activating AMPK Signaling Pathway

Biochemical Genetics - As the endogenous ligand for the GH secretagogue receptor (GHSR), Ghrelin is aberrant expressed in multiple malignant carcinoma, and involved in regulating a number of...     

Construction of a robust prognostic model for adult adrenocortical carcinoma: Results from bioinformatics and real-world data

This study aims to construct a robust prognostic model for adult adrenocortical carcinoma (ACC) by large-scale multiomics analysis and real-world data. The RPPA data, gene expression profiles and clinical information of adult ACC patients were obtained from The Cancer Proteome Atlas (TCPA), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Integrated prognosis-related proteins (IPRPs) model was constructed. Immunohistochemistry was used to validate the prognostic value of the IPRPs model in Fudan University Shanghai Cancer Center (FUSCC) cohort. 76 ACC cases from TCGA and 22 ACC cases from GSE10927 in NCBI’s GEO database with full data for clinical information and gene expression were utilized to validate the effectiveness of the IPRPs model. Higher FASN (P = .039), FIBRONECTIN (P < .001), TFRC (P < .001), TSC1 (P < .001) expression indicated significantly worse overall survival for adult ACC patients. Risk assessment suggested significantly a strong predictive capacity of IPRPs model for poor overall survival (P < .05). IPRPs model showed a little stronger ability for predicting prognosis than Ki-67 protein in FUSCC cohort (P = .003, HR = 3.947; P = .005, HR = 3.787). In external validation of IPRPs model using gene expression data, IPRPs model showed strong ability for predicting prognosis in TCGA cohort (P = .005, HR = 3.061) and it exhibited best ability for predicting prognosis in GSE10927 cohort (P = .0898, HR = 2.318). This research constructed IPRPs model for predicting adult ACC patients’ prognosis using proteomic data, gene expression data and real-world data and this prognostic model showed stronger predictive value than other biomarkers (Ki-67, Beta-catenin, etc) in multi-cohorts.     

无关供者脐带血干细胞移植概况

脐带血作为造血干细胞的一大来源,已逐渐获得医学界的认可,随着临床实践的不断展开,对脐带血的使用也趋于标准化。我们通过移植物抗宿主病和治愈情况对骨髓移植与脐带血移植进行了比较,提供了移植用脐带血的择优选取办法及移植的最低细胞剂量,对双份脐带血的选择给出建议,同时对非亲缘脐血与骨髓共输注临床使用情况和嵌合体检测做了介绍与评价。可以看出,在治疗恶性血液病时,脐带血移植是一个可靠的方法。     

Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments

Background

Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR) has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis.

Methodology/Principal Findings

We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C^hi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation.

Conclusions/Significance

The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.     

钢渣组分特征及其用于土壤改良的可行性初步研究

通过测定钢渣的化学组成分析得出其组分特征,进一步通过在有降解碱剂HPMA参与的重（轻）度盐碱土壤及钢渣中栽种不同植物种子（玉米、茄子、水稻和长春花）,观察植物的长势,探究钢渣是否可以用于土壤改良。结果发现钢渣的化学成分与土壤基本相同,但部分成分如CaO、Fe₂O₃、MgO、MnO₂等显著高于土壤,而另外一些组分TiO₂、K₂O、Na₂O、P₂O₅在钢渣中未检测出来。对比重（轻）度盐碱土壤,钢渣与HPMA共同作用时,玉米、茄子、水稻和长春花等发芽率及生长速率明显提高;与常用的蛭石、珍珠岩改良剂对比实验中,不同植物存在类似的发芽率和生长速率,说明钢渣可以作为温室土壤结构改良剂;与钢渣产地丰富的树皮土资源配比形成复方改良剂,发现其具有类似花土（泥炭土）的生长速率和发芽率。初步研究表明,钢渣可以用于盐碱地改良,而且对于设施农业的土壤结构改良具有功效,与当地树皮土资源结合,具有形成复方土壤改良剂的潜力。     

Retracted: Kinesin family member 2C aggravates the progression of hepatocellular carcinoma and interacts with competing endogenous RNA

Kinesin family member 2C (KIF2C), a substantial mitotic regulator, has been verified to exert a malignant function in several cancers. However, its function in hepatocellular carcinoma (HCC) remains unclear. In this study, the expression profile of KIF2C in HCC was characterized through the dataset from the TCGA and clinical tissue microarrays containing 220 pairs of resected HCC tissues and adjacent nontumor tissues in our hospital. The results indicated that KIF2C was substantially higher expression in tumor tissues than adjacent nontumor tissues. High expression of KIF2C significantly correlated with large tumor (>5.0 cm) (P = .001) and implied a dismal postoperative overall survival (OS) (hazard ratio [HR] = 1.729; P = .002) in our cohort of patients. Gain and loss of function assays displayed that KIF2C promoted HCC cell proliferation, accelerated cell cycle progression, and impeded apoptosis. By bioinformatic tools and mechanistic investigation, we found that KIF2C interacted with various cell-cycle-related proteins and was significantly involved in growth-promoting pathways. KIF2C upregulated PCNA and CDC20 expression. Subsequently, we investigated the regulation of KIF2C by competing endogenous RNA and elucidated that has-miR-6715a-3p was directly bond to the 3′-untranslated region of KIF2C through dual luciferase assays, thereby inhibiting KIF2C expression. Furthermore, the long noncoding RNA GS1-358P8.4 was found to be a candidate of KIF2C for has-miR-6715a-3p binding. HCC patients with high lncRNA-GS1-358P8.4 expression had shorter OS and relapse-free survival compared to those with low expression, which was accordance with the KIF2C. Taken together, KIC2C aggravated HCC progression, it could serve as a prognostic indicator and confer a novel target for clinical treatment.