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Abstract Abnormal lipid metabolism is an essential hallmark of glioblastoma. Hormone sensitive lipase (HSL), an important rate-limiting enzyme contributed to lipolysis, which was involved in aberrant lipolysis of glioblastoma, however, its definite roles and the relevant regulatory pathway have not been fully elucidated. Our investigations disclosed high expression of HSL in glioblastoma. Knock-down of HSL restrained proliferation, migration, and invasion of glioblastoma cells while adding to FAs could significantly rescue the inhibitory effect of si-HSL on tumor cells. Overexpression of HSL further promoted tumor cell proliferation and invasion. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the regulatory role of ncRNAs on HSL. Mechanistically, hsa_circ_0021205 regulated HSL expression by sponging miR-195-5p, which further promoted lipolysis and drove the malignant progression of glioblastoma. Besides, hsa_circ_0021205/miR-195-5p/HSL axis activated the epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggested that hsa_circ_0021205 promoted tumorigenesis of glioblastoma through regulation of HSL, and targeting hsa_circ_0021205/miR-195-5p/HSL axis can serve as a promising new strategy against glioblastoma.

Summary: Glioblastoma stem cells (GSCs) reside in hypoxic periarteriolar niches of glioblastoma micro-environment, however, the crosstalk of GSCs with macrophages on regulating tumor angiogenesis and progression are not fully elucidated. GSCs-derived exosomes (GSCs-exos) are essential mediators during tumor immune-microenvironment remodeling initiated by GSCs, resulting in M2 polarization of tumor-associated macrophages (TAMs) as we reported previously. Our data disclosed aberrant upregulation of miR-374b-3p in both clinical glioblastoma specimens and human cell lines of GSCs. MiR-374b-3p level was high in GSCs-exos and can be internalized by macrophages. Mechanistically, GSCs exosomal miR-374b-3p induced M2 polarization of macrophages by downregulating phosphatase and tensin expression, thereby promoting migration and tube formation of vascular endothelial cells after coculture with M2 macrophages. Cumulatively, these data indicated that GSCs exosomal miR-374b-3p can enhance tumor angiogenesis by inducing M2 polarization of macrophages, as well as promote malignant progression of glioblastoma. Targeting exosomal miR-374b-3p may serve as a potential target against glioblastoma.

Summary: T-box transcription factor 15 (TBX15) plays important role in various cancers; however, its expression and role in glioma is still unclear. In this study, our findings indicated that TBX15 was increased in gliomas compared to normal brain tissues, and high levels of TBX15 were related to poor survival. Furthermore, TBX15 silencing in glioma cells not only inhibited their proliferation, migration, and invasion in vitro, but also weakened their ability to recruit macrophages and polarize the latter to the M2 subtype. Mechanism study indicated that thioredoxin domain containing 5 (TXNDC5) lies downstream of TBX15. Furthermore, rescue assays verified that the role of TBX15 in glioma cells is dependent on TXNDC5. Moreover, sh-TBX15 loaded into DNA origami nanocarrier suppressed the malignant phenotype of glioma in vitro and in vivo. Taken together, the TBX15/TXNDC5 axis is involved in the genesis and progression of glioma, and is a potential therapeutic target.

Metabolism remodelling of macrophages in the glioblastoma microenvironment contributes to immunotherapeutic resistance. However, glioma stem cell (GSC)-initiated lipid metabolism remodelling of transformed macrophages (tMΦs) and its effect on the glioblastoma microenvironment have not been fully elucidated. Total cholesterol (TC) levels and lipid metabolism enzyme expression in macrophages in the GSC microenvironment were evaluated and found that the TC levels of tMΦs were increased, and the expression of the lipid metabolism enzymes calmodulin (CaM), apolipoprotein E (ApoE), and liver X receptor (LXR) was upregulated. Knockdown of HOXC-AS3 led to a decrease in the proliferation, colony formation, invasiveness, and tumorigenicity of tMΦs. Downregulation of CaM resulted in a decline in TC levels. HOXC-AS3 overexpression led to increases in both CaM expression levels and TC levels in tMΦs. RNA pull down and mass spectrometry experiments were conducted and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was screened as the HOXC-AS3 binding proteins related to lipid metabolism. RIP and RNA pull down assays verified that HOXC-AS3 can form a complex with hnRNPA1. Knockdown of hnRNPA1 downregulated CaM expression; however, downregulation of HOXC-AS3 did not affect hnRNPA1 expression.TMΦs underwent lipid metabolism remodelling induced by GSC via the HOXC-AS3/hnRNPA1/CaM pathway, which enhanced the protumor activities of tMΦs, and may serve as a potential metabolic intervening target to improve glioblastoma immunotherapy.

Many organizations are willing to increase human capital investment through various employee training programs. This study empirically examines a proposed model that explains the relationship between the different types of employee training, including general and firm-specific training and employee turnover in Korean firms. This study used a survey sample of 10,069 employees in 467 publicly traded firms in South Korea. 78% of participating companies provided training programs to the employees. This study conducted quantitative cross-sectional regression analyses to test the hypotheses. The study suggests empirical evidence that general training and firm-specific training reduce employee turnover intention. Moreover, the magnitude of firm-specific training on turnover intention is much higher than general training. Furthermore, employee organizational identification has a partial mediating effect on training and turnover intention. However, the study found no substantial evidence of the moderating effect of employees’ justice perception of receiving training opportunities. Based on the human capital theory and social exchange perspective, the results indicate that both types of training programs help employee retention, and cultivating employee organizational identification can be critical in the training-turnover process.

Background: Glioma is the most common malignant tumor of the central nervous system, with high heterogeneity, strong invasiveness, high therapeutic resistance, and poor prognosis, comprehending a serious challenge in neuro-oncology. Until now, the mechanisms underlying glioma progression have not been fully elucidated. Methods: The expression of DExH-box helicase 9 (DHX9) in tissues and cells was detected by qRT-PCR and western blot. EdU and transwell assays were conducted to assess the effect of DHX9 on proliferation, migration and invasion of glioma cells. Cocultured model was used to evaluate the role of DHX9 on macrophages recruitment and polarization. Animal study was performed to explore the role of DHX9 on macrophages recruitment and polarization in vivo. Bioinformatics analysis, dualluciferase reporter assay and chromatin immunoprecipitation (ChIP)-qPCR assay was used to explore the relation between DHX9 and TCF12/CSF1. Results: DHX9 was elevated in gliomas, especially in glioblastoma multiforme (GBM). Besides promoting the proliferation, migration, and invasion of glioma cells, DHX9 facilitated the infiltration of macrophages into glioma tissues and polarization to M2-like macrophages, known as tumor-associated macrophages (TAMs). DHX9 silencing decreased the expression of colony-stimulating factor 1 (CSF1), which partially restored the inhibitory effect on malignant progress of glioma and infiltration of TAMs caused by DHX9 knockdown by targeting the transcription factor 12 (TCF12). Moreover, TCF12 could directly bind to the promoter region of CSF1. Conclusion: DHX9/TCF12/CSF1 axis regulated the increases in the infiltration of TAMs to promote glioma progression and might be a novel potential target for future immune therapies against gliomas. [ABSTRACT FROM AUTHOR]

Objective: To investigate evidence supporting whether ultrasonic irrigation as a supplement is more effective than syringe irrigation in root canal cleaning., Methods: An electronic search was conducted in PubMed, Embase, Web of Science, Cochrane Library, ProQuest Dissertation and Theses, Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature Database. Studies were retrieved from January 1, 1985 to March 1, 2014. The Chinese journals on stomatology and the bibliography of all relevant articles were manually searched. Relevant clinical randomized controlled trial (RCT) and clinical controlled trial (CCT) were selected. Two investigators evaluated the risk of bias of the included trials in accordance with Cochrane risk of bias assessment tools and collected data of included studies. Meta-analysis was then performed in RevMan 5.2., Results: Nine articles that satisfied the eligibility criteria were included in this Meta-analysis. Seven studies showed low bias risk, and the remaining studies exhibited moderate bias risk. Histological results showed that ultrasonic irrigation supplement could significantly improve canal and isthmus debridement at the apical area (P < 0.01). Antibacterial efficacy was evaluated by bacterial culture (P = 0.26) and polymerase chain reaction (P = 0.99) methods, no significant differences in antibacterial efficacy were observed., Conclusion: Ultrasonic irrigation supplement is more effective than syringe irrigation in root canal debridement at the apical area. However, antibacterial efficacy is not statistically significant.