Edited by Laszlo NagyKeywords: MicroRNA MiR-26 LXR Cholesterol efflux ABCA1 ARL7 a b s t r a c t Cellular cholesterol levels are tightly regulated and represent a balance of cholesterol uptake, endogenous synthesis and efflux. Although the classic transcriptional regulations of cholesterol metabolism by liver X receptors (LXRs) have been well studied, the potential effects of LXRresponsive microRNAs (miRNAs) still need to be unveiled. Here, we describe that miR-26, an LXR-suppressed miRNA, inhibits the expression of the ATP-binding cassette transporter A1 (ABCA1) and ADP-ribosylation factor-like 7 (ARL7), two LXR target genes which play critical roles in cholesterol efflux. These findings have not only figured out an alternative mechanism for LXR regulation, but also provided a potential therapeutic target for cholesterol metabolic disorders.

BackgroundGlioblastoma is refractory to conventional treatment, which is combined of surgery, chemotherapy and radiotherapy. Recent studies have shown that glioma initiating cells (GICs) contribute to tumorigenesis and radioresistance. Recently, other studies showed that the GICs use the autophagy as the major pathway to survive. Chloroquine, an anti-malarial chemical, is an autophagic inhibitor which blocks autophagosome fusion with lysosome and slows down lysosomal acidification. The aim of this study was to explore the mechanisms of chloroquine on the radiosensitivity of GICs.MethodsHuman glioblastoma cell lines U87 were investigated. MTT and clonogenic survival assay were used to evaluate the cell viability and survival from radiation. The formation of autophagosomes were evaluated by immunofluorescence. Annexin V-FITC/PI staining and flow cytometry were used to quantify the apoptotic cells. The expression levels of proteins were analyzed by Western blot. Cell cycle status was analyzed by checking DNA content after staining with PI. A comet assay was used to assess the DNA repair in the cells. Tumorsphere assay was used for evaluating GICs’ renewal ability.ResultsTreatment of U87 GICs with chloroquine (10–80 nmol/L) alone inhibited the cell growth in a dose-dependent manner. A dose of chloroquine (20 nmol/L) obviously enhanced the radiation sensitivity of U87 GICs., we found more punctate patterns of microtubule-associated protein LC3 immunoreactivity in radiation-treated U87 GICs, and the level of membrane-bound LC3-II was obviously enhanced. A combination of radiation and chloroquine obviously enhanced the U87 GICs’ apoptosis, as demonstrated by the enhanced levels of caspase-3, and reduced level of Bcl-2. In additon, combination of radiation and chloroquine cause G1/G0 cell cycle arrest. what’s more, Chloroquine obviously weakened the repair of radiation-induced DNA damage as reflected by the tail length of the comet. Combination treatment of irradiation and chloroquine has synergistic effects on decreasing the GICs’ tumorsphere number and diameter.ConclusionChloroquine enhances the radiosensitivity of GICs in vitro, suggesting the feasibility of joint treatment with chloroquine with radiation for GBM.

Heat shock proteins belong to a conserved protein family and are involved in multiple cellular processes. Heat shock protein 27 (Hsp27), also known as heat HSPB1, participates in cellular responses to not only heat shock, but also oxidative or chemical stresses. However, the contribution of HSPB1 to anti-oxidative response remains unclear. Here, we show that HSPB1 activates G6PD in response to oxidative stress or DNA damage. HSPB1 enhances the binding between G6PD and SIRT2, leading to deacetylation and activation of G6PD. Besides, HSPB1 activates G6PD to sustain cellular NADPH and pentose production in glioma cells. High expression of HSPB1 correlates with poor survivalrate of glioma patients. Together, our study uncovers the molecular mechanism by which HSPB1 activates G6PD to protect cells from oxidative and DNA damage stress.

PurposeMany epidemiological studies have investigated environmental risk factors for the development of acoustic neuroma. However, these results are controversial. We conducted a meta-analysis of case-control studies to identify any potential relationship between history of noise exposure, smoking, allergic diseases, and risk of acoustic neuroma.Materials and MethodsWe searched PubMed to identify relevant articles. Two researchers evaluated the eligibility and extracted the data independently.ResultsEleven case-control studies were included in our meta-analysis. Acoustic neuroma was found to be associated with leisure noise exposure [odds ratio (OR)=1.33, 95% confidence interval (CI): 1.05–1.68], but not with occupational noise exposure and ever noise exposure (OR=1.20, 95% CI: 0.84–1.72 and OR=1.15, 95% CI: 0.80–1.65). The OR of acoustic neuroma for ever (versus never) smoking was 0.53 (95% CI: 0.30–0.94), while the subgroup analysis indicated ORs of 0.95 (95% CI: 0.81–1.10) and 0.49 (95% CI: 0.41–0.59) for ex-smoker and current smoker respectively. The ORs for asthma, eczema, and seasonal rhinitis were 0.98 (95% CI: 0.80–1.18), 0.91 (95% CI: 0.76–1.09), and 1.52 (95% CI: 0.90–2.54), respectively.ConclusionOur meta-analysis is suggestive of an elevated risk of acoustic neuroma among individuals who were ever exposed to leisure noise, but not to occupational noise. Our study also indicated a lower acoustic neuroma risk among ever and current cigarette smokers than never smokers, while there was no significant relationship for ex-smokers. No significant associations were found between acoustic neuroma and history of any allergic diseases, such as asthma, eczema, and seasonal rhinitis.

Candida meningitis in neurosurgical patients is relatively unusual but is associated with a high mortality rate. We present our experience with this infection and discuss the clinical characteristics, treatment options and outcomes. We retrospectively reviewed neurosurgical patients with multiple positive cerebrospinal fluid (CSF) culture results in our hospital from January 2013 to December 2019. Nine patients were available for review according to our inclusion and exclusion criteria. Four species of Candida were isolated from the CSF samples and Candida albicans accounted for half of all infections. Eight infections were associated with ventricle peritoneal shunt, lumbar cistern peritoneal shunt or external ventricular drain. All of these foreign intracranial materials were removed or changed and all the patients received antifungal treatment, including fluconazole and/or voriconazole. It is associated with severe long-term outcomes in survivors and a mortality rate that reaches 11.1%. Prior treatments with broad-spectrum and high-grade antibiotics and anaemia are possible risk factors for Candida meningitis. We advise that foreign intracranial material should be removed or changed as early as possible and the timing of re-shunt operation can be 1 month after control of Candida meningitis has been achieved, with several negative CSF culture results.