TSPO exacerbates acute cerebral ischemia/reperfusion injury by inducing autophagy dysfunction.

Autophagy is considered a double-edged sword, with a role in the regulation of the pathophysiological processes of the central nervous system (CNS) after cerebral ischemia-reperfusion injury (CIRI). The 18-kDa translocator protein (TSPO) is a highly conserved protein, with its expression level in the nervous system closely associated with the regulation of pathophysiological processes. In addition, the ligand of TSPO reduces neuroinflammation in brain diseases, but the potential role of TSPO in CIRI is largely undiscovered. On this basis, we investigated whether TSPO regulates neuroinflammatory response by affecting autophagy in microglia. In our study, increased expression of TSPO was detected in rat brain tissues with transient middle cerebral artery occlusion (tMCAO) and in BV2 microglial cells exposed to oxygen-glucose deprivation or reoxygenation (OGD/R) treatment, respectively. In addition, we confirmed that autophagy was over-activated during CIRI by increased expression of autophagy activation related proteins with Beclin-1 and LC3B, while the expression of p62 was decreased. The degradation process of autophagy was inhibited, while the expression levels of LAMP-1 and Cathepsin-D were significantly reduced. Results of confocal laser microscopy and transmission electron microscopy (TEM) indicated that autophagy flux was disordered. In contrast, inhibition of TSPO prevented autophagy over-activation both in vivo and in vitro. Interestingly, suppression of TSPO alleviated nerve cell damage by reducing reactive oxygen species (ROS) and pro-inflammatory factors, including TNF-α and IL-6 in microglia cells. In summary, these results indicated that TSPO might affect CIRI by mediating autophagy dysfunction and thus might serve as a potential target for ischemic stroke treatment.

Identification of VASH1 as a Potential Prognostic Biomarker of Lower-Grade Glioma by Quantitative Proteomics and Experimental Verification.

Background: VASH1 is a novel angiogenic regulatory factor, that participates in the process of carcinogenesis and the development of diverse tumors. Our study aimed to investigate the expression and prognostic value of the VASH1 in Lower-Grade Glioma (LGG), to explore its functional network in LGG and its effects on biological behaviors. Methods: LGG transcriptome data, somatic mutation profiles and clinical features analyzed in the present study were obtained from the TCGA, GTEx, CCLE, CGGA, UALCAN, and GEPIA2 databases, as well as clinical data and tissue sections of 83 LGG patients in our hospital. The expression characteristics of VASH1 in LGG were investigated by univariate, multivariate, immunohistochemistry, qRT-PCR, and western-blot. Subsequently, we analyzed the prognostic significance of VASH1 in LGG patients by survival analysis, subject operation characteristic curve, correlation analysis, external validation, independent prognostic significance analysis, and clinical stratification, and confirmed its biological effect on glioma cell lines in vitro. Finally, we performed GO, KEGG, and GSEA to clarify biological functions and related pathways. CIBERSORT and ESTIMATE algorithms were used to calculate the proportion of immune cells and immune microenvironment fraction in LGG. Result: We found that VASH1 is highly expressed in LGG tissues and is associated with poor prognosis, WHO grade, IDH1 wild-type, and progressive disease (P < 0.05). Multivariate and the Nomogram model showed that high VASH1 expression was an independent risk factor for glioma prognosis and had better prognostic prediction efficacy in different LGG Patient cohorts (HR = 4.753 and P=0.002). In vitro experiments showed that knockdown of VASH1 expression in glioma cell lines caused increased glioma cell proliferation, invasion, and migration capacity. The mechanism may be related to VASH1 promoting microtubule formation and remodeling of immune microenvironment. Conclusion: Our study firstly found that high VASH1 expression was associated with poor prognosis. In addition, We identified the possible mechanism by which VASH1 functioned in LGG. VASH1 inhibits the invasion and migration of tumor cells by affecting microtubule formation and immune infiltration in the tumor microenvironment. May be an important endogenous anti-tumor factor for LGG and provide a potential biomarker for individualized treatment of LGG.

An innovative prognostic model based on autophagy-related long noncoding RNA signature for low-grade glioma.

Autophagy is a highly conserved lysosomal degradation process essential in tumorigenesis. However, the involvement of autophagy-related long noncoding RNAs (lncRNAs) in low-grade glioma (LGG) remains unclear. In this study, we established an autophagy-related lncRNA prognostic signature for patients with LGG and assess its underlying functions. We used univariate Cox, least absolute shrinkage and selection operator and multivariate Cox regression models to establish an autophagy-related lncRNA prognostic signature. Kaplan-Meier survival analysis, receiver operating characteristic curve, nomogram, C-index, calibration curve and clinical decision-making curve were used to assess the predictive capability of the identified signature. A signature comprising nine autophagy-related lncRNAs (AL136964.1, ARHGEF26-AS1, PCED1B-AS1, AS104072.1, PRKCQ-AS1, LINC00957, AS125616.1, PSMB8-AS1 and AC087741.1) was identified as a prognostic model. Patients with LGG were divided into the high- and low-risk cohorts based on the median model-based risk score. The survival analysis revealed a 10-year survival rate of 9.3% (95% CI 1.91-45.3%) and 13.48% (95% CI 4.52-40.2%) in high-risk patients in the training and validation sets, respectively, and 48.4% (95% CI 24.7-95.0%) and 48.4% (95% CI 28.04-83.4%) in low-risk patients in the training and validation sets, respectively. This finding suggested a relatively low survival in high-risk patients. In addition, the lncRNA signature was independently prognostic and potentially associated with the progression of LGG. Therefore, the 9-autophagy-related-lncRNA signature may play a crucial role in the diagnosis and treatment of LGG, which may offer new avenues for tumour-targeted therapy.

The Role of Exosomal miRNAs in Glioma: Biological Function and Clinical Application.

Gliomas are complex and heterogeneous central nervous system tumors with poor prognosis. Despite the increasing development of aggressive combination therapies, the prognosis of glioma is generally unsatisfactory. Exosomal microRNA (miRNA) has been successfully used in other diseases as a reliable biomarker and even therapeutic target. Recent studies show that exosomal miRNA plays an important role in glioma occurrence, development, invasion, metastasis, and treatment resistance. However, the association of exosomal miRNA between glioma has not been systemically characterized. This will provide a theoretical basis for us to further explore the relationship between exosomal miRNAs and glioma and also has a positive clinical significance in the innovative diagnosis and treatment of glioma.

Endovascular recanalization for symptomatic chronic internal carotid artery occlusion: a study of 19 cases / 国际脑血管病杂志

Objective:To investigate the efficacy and safety of endovascular recanalization in the treatment of chronically occluded internal carotid artery (COICA).Methods:From January 2014 to January 2019, patients over 50 years of age with symptomatic COICA underwent endovascular recanalization in the Department of Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University were enrolled retrospectively. The modified Rankin Scale (mRS) was used to evaluate the improvement of neurological function.Results:A total of 19 patients with symptomatic COICA were enrolled, of which 16 (84.21%) were successfully recanalized. None of the patients had severe neurological deficits during the periprocedural period and after procedure. The neurological function of patients with successful recanalization gradually improved over time. The neurological function improved in 4 patients (25.0%) at 24 h after endovascular treatment and 9 (56.3%) at 18 months postprocedural follow-up. The follow-up of CT angiography showed that the internal carotid artery in patients with successful recanalization was unobstructed, and there was no obvious in-stent stenosis.Conclusion:Endovascular recanalization is feasible, safe and effective in patients with symptomatic COICA.

Liquid biopsy in central nervous system tumors: the potential roles of circulating miRNA and exosomes.

The Central nervous system (CNS) tumor still remains the most lethal cancer, and It is hard to diagnose at an earlier stage on most occasions. It is found that recurrent disease is finally observed in patients who occurred chemo-resistance after completely primary treatment. It is a challenge that monitoring treatment efficacy and tumor recurrence of CNS tumors are full of risks and difficulties by brain biopsies. However, the brain biopsies are considered as an invasive technique with low specificity and low sensitivity. In contrast, the liquid biopsy is based on blood and cerebrospinal fluid (CSF) test, which is going to acceptable among the patients through it's minimally invasive and serial bodily fluids. The advantages of liquid biopsy are to follow the development of tumors, provide new insights in real time, and accurate medical care. The major analytical constituents of liquid biopsy contain the Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating cell-free microRNAs (cfmiRNAs), and circulating exosomes. Liquid biopsy has been widely utilized in CNS tumors in recent years, and the CTCs and ctDNA have become the hot topics for researching. In this review, we are going to explain the clinical potential of liquid biopsy biomarkers in CNS tumor by testing circulating miRNAs and exosomes to evaluate diagnose, prognosis, and response to treatment.

Excessive fluoride increases the expression of osteocalcin in the mouse testis / 中华男科学杂志

Objective@#To observe the influence of excessive fluoride on the levels of osteocalcin and testosterone in the testis of the male mouse.@*METHODS@#Twenty-four C57BL/6J male mice were equally randomized into a normal control and a fluorosis model group, the former fed on distilled water while the latter on a solution of sodium fluoride (100 mg/L) in distilled water, both for 12 weeks. Then, the level of osteocalcin in the testis tissue was measured with the immunohistochemical streptavidin-peroxidase (SP) method and those of osteocalcin and testosterone in the serum determined by ELISA.@*RESULTS@#After 12 weeks of fluoride intervention, the level of serum osteocalcin was significantly higher in the fluorosis models than in the normal controls (［68.05 ± 5.32］ vs ［47.50 ± 5.73］ pg/mL, F = 11.901, P = 0.008), while that of testosterone markedly lower in the former than the latter group (［8.07 ± 1.35］ vs ［12.94 ± 3.09］ ng/mL, F = 2.313, P = 0.006). The results of immunohistochemical SP showed the expression of osteocalcin in the cell membrane and cytoplasm of the fluorosis models, which was evidently higher than in the normal controls.@*CONCLUSIONS@#Twelve-week intake of 100 mg/L fluoride solution can decrease the level of testosterone and increase the expression of osteocalcin in the testis of the male mouse.