An MRI study of the superior temporal subregions in patients with current and past major depression

The superior temporal gyrus (STG), especially its lateral portion, and temporal pole (TP) both play a central role in emotional processing, but it remains largely unknown whether patients with major depressive disorder (MDD) exhibit morphologic changes in these regions. We delineated the STG subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), rostral STG, and caudal STG] and TP using magnetic resonance imaging in 29 currently depressed patients (mean age = 32.5 years, 7 males), 27 remitted depressed patients (mean age = 35.1 years, 9 males), and 33 age- and gender-matched healthy control subjects (mean age = 34.0 years, 12 males). Both current and remitted MDD patients showed a significant volume reduction of the left PT and bilateral caudal STG as compared with healthy controls. The TP volume did not differ between the groups. The right PT volume was negatively correlated with total score on the Beck Depression Inventory in the MDD patients as a whole. Medication, presence of melancholia, and comorbidity with anxiety disorders did not affect the TP and STG volumes. These findings suggest that the volume reduction of the STG, but not the TP, may represent enduring brain changes in MDD even after recovery from depression, but right STG volume may also be related to the severity of depressive symptoms.     

Deregulation of FGFR1 and CDK6 oncogenic pathways in acute lymphoblastic leukaemia harbouring epigenetic modifications of the MIR9 family

The role of epigenetic mechanisms in the regulation of microRNAs (miRNAs) with a tumour‐suppressor function in human neoplasms has recently been established. Several miRNAs have been found to be inappropriately regulated by DNA methylation in patients with acute lymphoblastic leukaemia (ALL). We analysed the methylation status of the three members of the MIR9 family (MIR9‐1, MIR9‐2 and MIR9‐3) in a uniformly treated cohort of 200 newly diagnosed ALLs. MIR9 was methylated in 54% of the patients and was associated with downregulation of MIR9 (P < 0·01). Hypermethylation of MIR9 was an independent prognostic factor for disease‐free survival, overall survival and event‐free survival in a multivariate analysis (P < 0·01). Epigenetic downregulation of MIR9 induced upregulation of its targets, FGFR1 and CDK6, while treatment of ALL cells with FGFR1 (PD‐173074) and CDK6 (PD‐0332991) inhibitors induced a decrease in cell proliferation and an increase in apoptosis of ALL cells. Our results indicate that the MIR9 family is involved in the pathogenesis and clinical behaviour of ALL and provide the basis for new therapeutic strategies in the treatment of ALL, targeting the epigenetic regulation of miRNAs and/or the FGFR1 or CDK6‐RB pathway directly.     

MIR29B regulates expression of MLLT11 (AF1Q), an MLL fusion partner, and low MIR29B expression associates with adverse cytogenetics and poor overall survival in AML

MLLT11, an MLL fusion partner, is a poor prognostic biomarker for paediatric acute myeloid leukaemia (AML), adult normal cytogenetics AML, and adult myelodysplastic syndrome. MLLT11 is highly regulated during haematopoietic progenitor differentiation and development but its regulatory mechanisms have not been defined. In this study, we demonstrate by transfection experiments that MIR29B directly regulates MLLT11 expression in vitro. MIR29B expression level was also inversely related to MLLT11 expression in a cohort of 56 AML patients (P<0·05). AML patients with low MIR29B/elevated MLLT11 expression had poor overall survival (P=0·038). Therefore, MIR29B may be a potential prognostic biomarker for AML patients.     

A novel virus-like particle based on hepatitis B core antigen and substrate-binding domain of bacterial molecular chaperone DnaK

Hepatitis B virus core (HBc) protein has been proved to be an attractive carrier for foreign epitopes, and can display green fluorescent protein (GFP) on its surface. The structure of substrate-binding domain of DnaK [DnaK (394-504 aa), DnaK SBD] is similar to GFP, we therefore reasoned that DnaK SBD might also be tolerated. Electron microscopic observations suggested that the chimeric proteins containing the truncated HBc (HBcΔ) and DnaK SBD could self-assemble into virus-like particle (VLP). Then the accessibility of DnaK SBD and the adjuvanticity of VLP HBcΔ-SBD were demonstrated by two recombinant peptide vaccines against gonadotropin-releasing hormone (GnRH), GhM and GhMNR. The latter carries in addition the peptide motif NRLLLTG which is known to bind to DnaK and DnaK SBD. The combination of VLP HBcΔ-SBD and GhMNR elicited stronger humoral responses and caused further testicular atrophy than the combinations of VLP HBcΔ and GhMNR or VLP HBcΔ-SBD and GhM in Balb/c mice. These findings indicate VLP HBcΔ-SBD might serve as an excellent carrier for GhMNR and some other peptide vaccines.     

Association between the rs3802201 polymorphism of the lncRNA MIR2052HG gene and the risk of recurrent miscarriage in a Southern Chinese population

BackgroundPlenty of studies have indicated that some genetic polymorphisms of the breast cancer which associated with its susceptibility may also be related to the susceptibility of abortion. MIR2052HG plays an important role in the onset and progression of breast cancer by maintaining the level of ERα, but to the best of our knowledge, the correlation between risk of recurrent abortion and MIR2052HG rs3802201 C>G polymorphism is still unclear. Therefore, we conducted this case‐control study to investigate whether MIR2052HG rs3802201 C>G polymorphism is associated with susceptibility of recurrent miscarriage (RM).MethodsWe recruited 392 healthy controls and 248 patients with RM to process this research, the participants were all from southern China, and genotyping was performed by TaqMan method.ResultsOur results showed that there was no evidence indicates the MIR2052HG rs3802201 C>G is related to RM (CG and CC: adjusted OR = 0.970, 95% CI = 0.694–1.355, p = 0.8577; GG and CC: adjusted OR = 0.743, 95% CI = 0.416–1.330, p = 0.3174; dominant model: adjusted OR = 0.925, 95% CI = 0.672–1.272, p = 0.6298; recessive model: adjusted OR = 0.751, 95% CI = 0.430–1.321, p = 0.3233).ConclusionWe verified that the MIR2052HG rs3802201 C>G allele might be uncorrelated to the RM risk, but these findings require further validation in multicenter studies with larger sample size and different ethnicities.     

Long non‐coding RNA MIR31HG as a prognostic predictor for malignant cancers: A meta‐ and bioinformatics analysis

BackgroundThe possible regulatory mechanism of MIR31HG in human cancers remains unclear, and reported results of the prognostic significance of MIR31HG expression are inconsistent.MethodsThe meta‐analysis and related bioinformatics analysis were conducted to evaluate the role of MIR31HG in tumor progression.ResultsThe result showed that high MIR31HG expression was not related to prognosis. However, in the stratified analysis, we found that the overexpression of MIR31HG resulted in worse OS, advanced TNM stage, and tumor differentiation in respiratory system cancers. Moreover, our results also found that MIR31HG overexpression was related to shorter OS in cervical cancer patients and head and neck tumors. In contrast, the MIR31HG was lower in digestive system tumors which contributed to shorter overall survival, advanced TNM stage, and distant metastasis. Furthermore, the bioinformatics analysis showed that MIR31HG was highly expressed in normal urinary bladder, small intestine, esophagus, stomach, and duodenum and low in colon, lung, and ovary. The results obtained from FireBrowse indicated that MIR31HG was highly expressed in LUSC, CESC, HNSC, and LUAD and low in STAD and BLCA. Gene Ontology analysis showed that the co‐expressed genes of MIR31HG were most enriched in the biological processes of peptide metabolism and KEGG pathways were most enriched in Ras, Rap1, and PI3K‐Akt signaling pathway.ConclusionMIR31HG may serve as a potential biomarker in human cancers.     

犬经皮插管肾动脉注射人HGF基因的实验研究

目的:运用介入插管技术,经犬肾动脉快速注射含人肝细胞生长因子(HGF)重组基因的质粒(pCMV鄄HGF)。检测不同时间犬肾脏组织中外源性人HGF蛋白的水平,了解外源性HGF基因在犬肾脏组织内的表达情况。方法:健康成年犬6只,在麻醉和无菌条件下均经左肾动脉介入插管。其中4只注射pCMV鄄HGF质粒,1只注射空质粒(pcDNA3)对照,1只为注射等渗盐水空白对照。注射后不同时间留取犬静脉血以及部分肾组织,采用ELISA方法,分别检测血清及肾组织中人HGF蛋白的水平。结果:①该实验建立的检测人重组HGF的ELISA敏感性高(15～1000ng/ml),重复性强;②接受3种不同处理的犬静脉血中均未检测到人重组HGF蛋白的存在;③注射pCMV鄄HGF质粒的犬肾组织中能够检测到人重组HGF蛋白的存在。72h肾组织中HGF的水平范围在27～667ng/mg蛋白之间。注射空质粒和等渗盐水的犬(即2号和5号犬)肾组织则无表达。结论:运用介入插管技术,经犬肾动脉快速注射pCMV鄄HGF可以在肾脏内产生基因高转染表达。     

The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.