Considering the protective effect of exendin-4 against oxidative stress in spiral ganglion neurons.

Objectives: The protection of spiral ganglion neurons (SGNs) is crucial for hearing loss. Exendin-4 has been shown to have neuroprotective effects in several neurological disorders. Therefore, this study aimed to investigate the effect of the glucagon-like protein-1 receptor (GLP-1R) agonist exendin-4 on kanamycin-induced injury in mouse SGNs in vitro. Materials and Methods: In this study, GLP-1R expression in SGNs was verified by immunofluorescence and immunohistochemical staining. In vitro-cultured SGNs and the organ of Corti were exposed to kanamycin with or without exendin-4 treatment. The cell survival rate was measured using the cell counting kit-8 assay, and the damage to auditory nerve fibers (ANF) projecting radially from the SGNs was evaluated using immunofluorescence staining. Reactive oxygen species (ROS) content was determined by flow cytometry, and glutathione peroxidase (GSH-Px) content, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content were determined by spectrophotometry. Protein expression of nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) was detected using western blotting. Results: GLP-1R was expressed in SGNs. Treatment with 1 mM kanamycin for 24 hr induced SGN damage. Exendin-4 (100 nM) had a protective effect against kanamycin-induced SGN cell injury, improved cell survival rate, reduced nerve fiber injury, increased SOD activity and GSH-Px level, and reduced MDA and ROS contents. The Nrf2/HO-1 pathway was activated. Conclusion: Exendin-4 alleviates oxidative damage and exerts neuroprotective effects in kanamycin-induced SGN injury through the Nrf2/HO-1 signaling pathway. Exendin-4 has the potential to prevent or treat hearing loss due to SGN damage.

Mastoid obliteration and external auditory canal reconstruction using 3D printed bioactive glass S53P4 /polycaprolactone scaffold loaded with bone morphogenetic protein-2: A simulation clinical study in rabbits.

Introduction: The lack of good prosthetic materials and objective standards has limited the promotion of mastoid obliteration and external auditory canal reconstruction, and the quality of the surgery varies. In this study, bioactive glass S53P4 (S53P4), the most popular artificial prosthetic material, was modified and combined with polycaprolactone (PCL) and bone morphogenetic protein-2 (BMP-2) to produce an individualized biological scaffold using 3D printing technology to explore a better material and method for mastoid obliteration and external auditory canal reconstruction. Methods: 3D-printed S53P4/PCL scaffolds were fabricated from 3D reconstruction data of bone defect areas in New Zealand rabbits simulating "Canal Wall Down Mastoidectomy". The water absorption, swelling rate, porosity, and Young's modulus of the scaffold were measured, and the morphology and pore size of the scaffold were observed using scanning electron microscopy. The cytotoxicity of the S53P4/PCL scaffolds was detected using the CCK8 assay, and the in vitro antibacterial activity of the S53P4/PCL scaffolds was detected using the inhibition circle method. The BMP-2-loaded S53P4/PCL scaffolds were prepared using the drop-in lyophilization method and implanted into animal models. The biocompatibility, osteogenic activity, and external auditory canal repair of the scaffolds were observed using endoscopy, micro-CT, and histological examination. Results: The S53P4/PCL scaffold was highly compatible with the defective area of the animal model, and its physicochemical properties met the requirements of bone tissue engineering. In vitro experiments showed that the S53P4/PCL scaffold was non-cytotoxic and exhibited better antibacterial activity than the same volume of the S53P4 powder. In vivo experiments showed that the S53P4/PCL scaffold had good biocompatibility and osteogenic activity, and could effectively repair bone defects and reconstruct the normal morphology of the external auditory canal in animal models. Furthermore, its osteogenic activity and repair ability were significantly improved after loading with BMP-2. Conclusions: The 3D printed S53P4/PCL scaffold has great potential for clinical mastoid obliteration and external auditory canal reconstruction.

Single-nucleotide polymorphisms influence the promoter activities of systemic lupus erythematosus-associated genes.

Systemic lupus erythematosus (SLE) is a protypical autoimmune disease and genetic factors play important roles in its pathogenesis. Since present SLE susceptibility loci are mainly studied through meta-analysis of genome-wide association study, we performed promoter activity analysis to examine the biological functions of SLE-associated single-nucleotide polymorphisms (SNPs). We found at SNP positions rs1341239, rs1800795, rs1800796, rs1800872, rs1800871, rs187238, rs360719, rs8178822, rs3761549, different alleles influenced respective promoter activities in different manners, and the effects also appeared under glucocorticoid treatment. In addition, some SNPs showed strong correlations with levels of respective serum factors, but in most cases the associations were only demonstrated in SLE individuals. Our study has further disclose the functional roles of SLE-associate SNPs in SLE pathogenesis.

Prognostic value of Flotillin-1 expression in patients with solid tumors.

BACKGROUND: In numerous studies, Flotillin-1 was reported to be involved in tumor progression, indicating prognosis in various types of cancer. However, the results were inconsistent. RESULTS: A total of 2473 patients from 13 articles were included. The results indicated that: (1) Patients detected with high expression level of Flotillin-1 protein had a significantly shorter OS (HR =1.64; 95%CI: 1.39-1.88), statistical significance was also observed in subgroup meta-analyses stratified by the cancer type, nationality, detecting method, cutoff value, analysis type, sample size and publication date. (2) Patients with high Flotillin-1 protein expression level had a poorer DFS (HR = 2.49; 95%CI: 1.64-3.35), a worse RFS(HR = 3.26; 95%CI: 1.10-5.43) and a potential shorter PFS(HR = 1.84; 95%CI: 0.81-2.87). (3) The pooled odds ratios (ORs) showed that increased Flotillin-1 level was also related to lymph node metastasis (OR =6.30; 95% CI: 3.15-12.59), distant metastasis (OR =6.02; 95% CI: 1.50-24.06) and more advanced TNM stage (OR =4.69; 95% CI: 2.74-8.03). MATERIALS AND METHODS: A comprehensive retrieval was performed in multiple databases, including PubMed, Embase, Web of Science and CNKI. The relevant articles were screened for investigating the association between increased Flotillin-1 expression level and prognosis. Additionally, clinicopathological features data was also extracted from these studies. CONCLUSIONS: High expression level of Flotillin-1 protein was correlated with poorer clinical outcome. It might serve as a prognostic biomarker and a potential predictive factor of clinicopathology in various tumors. Further well-designed clinical studies should be performed to verify the clinical utility of Flotillin-1 in human solid tumors.

HOXB7 as a promising molecular marker for metastasis in cancers: a meta-analysis.

Numerous studies on carcinoma have revealed that the expression level of HOXB7 in cancerous tissues was significantly higher than that in noncancerous tissues. Elevated expression of HOXB7 is associated with the susceptibility to lymph node metastasis and distant metastasis in various tumors. In this study, a meta-analysis was performed to involve majority of relevant articles and explore the association of HOXB7 expression level with metastasis in cancer patients. Literature retrieval was conducted by searching in a number of electronic databases (up to December 1, 2015). The meta-analysis was conducted with RevMan 5.3 software and Stata SE12.0. A total of 1,532 patients with carcinoma from 14 studies were included in analysis. The results of meta-analysis demonstrated that lymph node metastasis was observed more frequently in the patients group with high expression level of HOXB7 than in the patients group with low expression level of HOXB7 (odds ratio =2.17, 95% CI: 1.74-2.71, P<0.00001, fixed-effects model). In addition, a similar result was observed in the association between HOXB7 expression and distant metastasis; the odds ratio was 1.77 (95% CI: 1.09-2.88, P=0.02, fixed-effects model). This meta-analysis demonstrated that the overexpression of HOXB7 was significantly associated with metastasis in cancer patients, which may be served as a common molecular marker for indicating cancer metastasis.

Long non-coding RNA-LET can indicate metastasis and a poor prognosis: a meta-analysis.

INTRODUCTION: Recent studies have reported that long non-coding RNA low expression in tumor (lncRNA-LET) was down-regulated in several cancers. The current meta-analysis aims to determine whether lncRNA-LET can be used as a potential biomarker for metastasis and prognosis. EVIDENCE ACQUISITION: We collected all relevant papers by searching multiple electronic databases (PubMed, EMBASE, Google Scholar, CNKI, Wanfang Database) and explored the association between the expression levels of lncRNA-LET and lymph node metastasis (LNM), distant metastasis (DM) and overall survival (OS). EVIDENCE SYNTHESIS: A total of 383 patients from four studies were finally included. The meta-analysis results showed that LNM occurred more frequently in patients from the lncRNA-LET low expression group than in patients from the lncRNA-LET overexpression group (OR=4.56, 95% CI 2.92-7.12, P<0.00001), and a similar result was observed between lncRNA-LET expression and DM (OR=4.77, 95% CI 2.29-9.94, P<0.0001). Additionally, we found that patients with low expression of lncRNA-LET had a poorer OS than those with lncRNA-LET overexpression (HR=2.39, 95% CI 1.57-3.21, P=0.000). CONCLUSIONS: lncRNA-LET may serve as a common molecular marker for metastasis and prognosis in human cancers.

Positive association between IL-16 rs1131445 polymorphism and cancer risk: a meta-analysis.

INTRODUCTION: The association between IL-16 rs1131445 polymorphism and cancer risk is not consistent or even contradictory, this meta-analysis aims to investigate the role of IL-16 gene rs1131445 polymorphisms in the risk of cancer. EVIDENCE ACQUISITION: A comprehensive online search was conducted in PubMed, EMBASE and CNKI databases to identify eligible studies. The case-control studies related IL-16 rs1131445 C/T polymorphism with the cancer susceptibility were selected according to the inclusion and exclusion criteria. After extracting the basic data information and quality of literature evaluation, the meta-analysis was performed by using STATA 12.0 software, with calculating odds ratio and 95% confidence interval, and further subgroup analysis, literature publication bias test and sensitivity analysis. EVIDENCE SYNTHESIS: There are totally 1677 cases and 1989 non-tumor controls finally involved. Meta-analysis showed that there are statistical correlations between the IL-16 rs1131445 C/T polymorphism and the cancer risk in Asian populations (TS vs. C, OR=0.80, 95%CI: 0.73-0.88; TT vs. TC, OR=0.75, 95%CI: 0.65-0.87; TT vs. CC, OR=0.69, 95% CI: 0.56-0.84; CC+TC vs. TT, OR=1.36, 95%CI: 1.19-1.55; CC vs. TC+TT, OR=1.27, 95%CI: 1.05-1.53) (all P<0.05). CONCLUSIONS: IL-16 rs1131445 C/T polymorphism is related to the susceptibility to cancer in Asians, suggesting that the C allelic gene of rs1131445 is significantly associated with an increasing cancer risk.

Low expression of long non-coding RNA-LET can indicate metastasis and a poor prognosis: a meta-analysis.

BACKGROUND: Recent studies have reported that the lncRNA-LET was down-regulated in several cancers.The current meta-analysis aims to determine whether lncRNA-LET can be used as a potential biomarker for metastasis and prognosis. METHODS: We collected all relevant papers by searching multiple electronic databases(Pubmed,EMBASE,Google Scholar,CNKI,Wanfang database) and explored the association between the expression levels of lncRNA-LETand lymph node metastasis (LNM),distant metastasis (DM) and overall survival (OS). RESULTS: A total of 383 patients from four studies were finally included.The meta-analysis results showed that LNM occurred more frequently in patients with low lncRNA-LET expression group than in patients with high lncRNA-LET expression group(OR=4.56,95%CI:2.92-7.12,p<0.00001),and a similar result was observed between lncRNA-LET expression and DM,the OR was 4.77(95%CI:2.29-9.94, p<0.0001).Additionally,we found that patient with low lncRNA-LET expression had a poorer OS than those high lncRNA-LET expression (HR=2.39,95 %CI:1.57-3.21,p = 0.000). CONCLUSION: LncRNA-LETmay serve as a common molecular marker for metastasis and prognosis in human cancers.

[PET/CT-based classification of delayed radiation encephalopathy following radiotherapy for nasopharyngeal carcinoma].

OBJECTIVE: To investigate positron-emission tomography-computed tomography (PET/CT) findings of radiation encephalopathy (RE) following radiotherapy for nasopharyngeal carcinoma (NPC), observe the metabolic changes of the compromised brain tissues, and postulate the clinical classification of RE to provide reference for its diagnosis. METHODS: This study included 53 pathologically confirmed NPC patients who received previous radical radiotherapy, and the diagnosis of RE was established according to the clinical manifestations and CT/PET findings. All the patients underwent PET/CT whole-body and head scans, and the image data were evaluated along with the clinical data of the patients. RESULTS: RE most frequently involved the lateral or bilateral inferior temporal lobes. PET identified hypometabolic changes in the bilateral temporal lobes of 35 patients (70 lobes) and in the lateral temporal lobe of 18 patients (18 lobes). According to the PET/CT findings, the lesions were classified into 3 types, namely the oedema type (56 temporal lobes), liquefactive necrosis type (10 temporal lobes), and atrophic calcification type (22 temporal lobes). One patient with oedema type lesion received neurotrophic treatment and recovered completely with normal brain tissue density and metabolism, but the oedema type lesions in 2 patients progressed into to atrophic calcification type; the liquefactive necrotic lesions in another 2 patients also progressed into atrophic calcification type. CONCLUSION: RE patients exhibit significant hypometabolic changes in the inferior temporal lobe on PET. According to the findings by PET/CT, RE can be classified into the oedema type, liquefactive necrosis type, and atrophic calcification type, and lesions of the former two types may progress into the third type.