Resolving the lineage relationship between malignant cells and vascular cells in glioblastomas

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.

Case-control study of female breast cancer and occupational risk factors based on lasso logistic regression in Beijing / 中华劳动卫生职业病杂志

Objective: To understand the relationship between female breast cancer and occupational risk factors in Beijing, and provide scientific basis for the formulation of prevention strategies and measures. Methods: From June to December 2019, A 1: 1 case-control study was adopted, eight medical institutions in Beijing were selected as the research objects. Patients with breast cancer diagnosed by medical institutions were selected as case group and non breast cancer patients in the same medical institution as control group. A total of 973 subjects were included, including 495 in the case group and 478 in the control group. A one-to-one survey was conducted using a questionnaire uniformly compiled by the Beijing Centers for Disease Control and Prevention. The survey content mainly includes basic demographic characteristics and occupational risk factors. The Trait Coping Style Questionnaire (TCSQ) was used to investigate the corresponding methods, including two aspects: positive coping and negative coping. First, chi square test or Wilcoxon rank sum test were used for univariate analysis. Then Lasso regression was used to screen the risk factors of breast cancer. Finally, the risk factors were screened by multivariate logistic regression analysis. Results: Education lovel was 49.64%, body mass index (BMI) was 18.4~23.9 kg/m(2), accounting for 48.82%, marital status ws 84.48%. Compared with no night shift history, there was a significant increase in risk of breast cancer at night shift history (OR=1.70, 95% CI: 1.25~2.30, P<0.05) . Compared with most of the sitting posture and sometimes standing, the risk of breast cancer was increased, and the difference was statistically significant (OR=2.01, 95%CI: 1.40~2.90, P<0.05) . Conclusion: In the occupation risk factors, night shift work and working posture are related to the incidence of breast cancer in women, establishing a good schedule and avoiding long standing can effectively prevent and reduce the occurrence of breast cancer.

Transcriptome Analysis Identifies SenZfp536, a Sense LncRNA that Suppresses Self-renewal of Cortical Neural Progenitors / 神经科学通报·英文版

Long non-coding RNAs (lncRNAs) regulate transcription to control development and homeostasis in a variety of tissues and organs. However, their roles in the development of the cerebral cortex have not been well elucidated. Here, a bioinformatics pipeline was applied to delineate the dynamic expression and potential cis-regulating effects of mouse lncRNAs using transcriptome data from 8 embryonic time points and sub-regions of the developing cerebral cortex. We further characterized a sense lncRNA, SenZfp536, which is transcribed downstream of and partially overlaps with the protein-coding gene Zfp536. Both SenZfp536 and Zfp536 were predominantly expressed in the proliferative zone of the developing cortex. Zfp536 was cis-regulated by SenZfp536, which facilitates looping between the promoter of Zfp536 and the genomic region that transcribes SenZfp536. Surprisingly, knocking down or activating the expression of SenZfp536 increased or compromised the proliferation of cortical neural progenitor cells (NPCs), respectively. Finally, overexpressing Zfp536 in cortical NPCs reversed the enhanced proliferation of cortical NPCs caused by SenZfp536 knockdown. The study deepens our understanding of how lncRNAs regulate the propagation of cortical NPCs through cis-regulatory mechanisms.

Relationship between depression-like behavior and expression of aquaporin 4 in brain of urea transporter B null mice / 解剖学报

[Abstract] Objective To investigate the ultrastructural changes of hippocampus in urea transporter B (UT-B) null mice and the alterations of distribution and expression level of aquaporin 4 (AQP4) in brain, and to discuss the relationship between AQP4 expression changes and depression-like behaviors in UT-B null mice. Methods Behavior differences of wild-type and UT-B null mice(10 in each group) were detected with sucrose preference and forced swimming test. The ultrastructural changes of hippocampus were observed by transmission electron microscopy (TEM). Immunohistochemistry and Western blotting were performed to detect the distribution and expression level of AQP4 in both genotypes. Results The sucrose preference index of wild-type mice and UT-B null mice were (84. 67 ± 1. 62)% and (65. 67±2. 66)%, respectively (P<0. 001). The immobility time of forced swimming was (209. 1±7. 00) seconds and (128. 6±3. 75) seconds respectively (P<0. 001). The two behavioral test results showed that UT-B null mice exhibited depression-like behavior. TEM results displayed the abnormal neurons with swelling of myelinated and unmyelinated fibers and degenerative changes, and perivascular astrocyte end-feet swelling. Immunohistochemistry results showed AQP4-immunoreactive (IR) cells were significantly reduced in cortex, hippocampus and thalamus. AQP4-IR cells were distributed in the pia matter, ependymal and cerebrovascular, but the perivascular immunostaining decreased. Western blotting analysis showed that the expression level of AQP4 in hippocampus was down-regulated by 27. 1% (P< 0. 05). Conclusion Reduced expression of AQP4 in the cerebral cortex and hippocampus of UT-B null mice might induce depressive behaviors by inference neurogenesis and cerebral metabolism.

Analysis on diuretic effect of a phenylphthalazines compound PU1424 / 中国药理学通报

Aim To study on the diuretic effect of a phenylphthalazines compound PU1424 and its influence on electrolyte balance, glucose and lipid metabolism, hepatic and renal functions.Methods Male Sprague Dawley rats were randomly divided into solvent control group,PU1424 treated group and HCTZ treated group.Urine was collected per 6 h and blood samples were collected at the end of drug administration.Urinary osmolality was measured by Freezing Point Osmometer;urea concentration was measured by Urea Detection Kit;ion level, blood glucose level, blood lipid level, hepatic and renal function were analyzed by Automatic Biochemical Analyzer.Results Compared to the solvent control group, and urine output of rats treated with PU1424 and HCTZ was increased as 1.52 times and 1.78 times and water intake increased as 1.42 times and 1.56 times respectively.Urine osmolalities were decreased as 61.5% and 50.4% of the control group, and urine urea concentration was decreased as 57.1% and 56.8% of the control group.Urinary electrolytes were decreased by administration of PU1424 and HCTZ compared to the intact plasma electrolytes.The blood glucose levels and blood lipid levels of rats treated with PU1424 had no changes, while the blood glucose and total cholesterol were increased by administration of HCTZ.The urea nitrogen, creatinine, alkaline phosphatase and total protein were intact by administration of PU1424 and HCTZ except the alanine/straw ration increased by HCTZ.Conclusion New diuretic candidate compound PU1424 displays significant diuretic effect with electrolyte balance, blood glucose level, blood lipid level, hepatic and renal function intact.