Background: Y-box-binding protein-1 (YB-1) is aberrantly expressed in a variety of cancers. However, the biological functional role of YB-1 in glioma is not yet clear. Methods: The expression of MDM2 and YB-1 was analyzed by real time PCR. Overexpression and knockdown of YB-1 in glioma cells were created by transfection of pcDNA-YB-1 and siRNA against YB-1, respectively. Cell viability was performed by CCK8 assay. Results: Our findings showed that glioma tissues had higher expressions of YB-1 than that in cancer-free tissues in 54 glioma patients, which were also positively correlated with Murine MDM2 expression. Overexpression of YB-1 or MDM2 renders a drug resistance feature in glioma cell exposed to temozolomide (TMZ), by directly targeting p53. Genetic or chemical inhibition of MDM2 significantly blocked YB-1-modulated response of glioma cells to TMZ. Moreover, inhibition of YB-1 or MDM2 reduced glioma cells metastasis and mortality in mice. Conclusion: YB-1 facilitates the resistance of glioma cells to TMZ by direct activation of MDM2/p53 signaling and represents a promising molecular target for glioma treatment.

Glioma has been a major healthcare burden; however, the specific molecular regulatory mechanism underlying its initiation and progression remains to be elucidated. Although it is known that many miRNAs are involved in the regulation of malignant phenotypes of glioma, the role of miR-4476 has not been reported yet. In the present study, we identify miR-4476 as an upregulated microRNA, which promotes cell proliferation, migration, and invasion in glioma. Further mechanistic analyses indicate that the adenomatous polyposis coli (APC), a negative regulator of the Wnt/β-catenin signaling pathway, is a direct target of miR-4476 and mediates the oncogenic effects of miR-4476 in glioma. C-Jun, a downstream effector of the Wnt/β-catenin signaling, is upregulated by miR-4476 overexpression. In turn, c-Jun could positively regulate miR-4476 expression by binding to the upstream of its transcription start site (TSS). Furthermore, in our clinical samples, increased miR-4476 is an unfavorable prognostic factor, and its expression positively correlates with c-Jun expression but negatively correlates with that of APC. In conclusion, our study demonstrates that miR-4476 acts as a tumor enhancer, directly targeting APC to stimulate its own expression and promoting the malignant phenotypes of glioma.

Background: Gliomas are highly lethal brain tumors. Despite multimodality therapy with surgery, radiotherapy, chemotherapy, and immunotherapy, glioma prognosis remains poor. Ferroptosis is a crucial tumor suppressor mechanism that has been proven to be effective in anticancer therapy. However, the implications of ferroptosis on the clinical prognosis, chemotherapy, and immune checkpoint inhibitor (ICI) therapy for patients with glioma still need elucidation.Methods: Consensus clustering revealed two distinct ferroptosis-related subtypes based on the Cancer Genome Atlas (TCGA) glioma dataset (n = 663). Subsequently, the ferroptosis-related gene prognostic index (FRGPI) was constructed by weighted gene co-expression network analysis (WGCNA) and “stepAIC” algorithms and validated with the Chinese Glioma Genome Atlas (CGGA) dataset (n = 404). Subsequently, the correlation among clinical, molecular, and immune features and FRGPI was analyzed. Next, the temozolomide sensitivity and ICI response for glioma were predicted using the “pRRophetic” and “TIDE” algorithms, respectively. Finally, candidate small molecular drugs were defined using the connectivity map database based on FRGPI.Results: The FRGPI was established based on the HMOX1, TFRC, JUN, and SOCS1 genes. The distribution of FRGPI varied significantly among the different ferroptosis-related subtypes. Patients with high FRGPI had a worse overall prognosis than patients with low FRGPI, consistent with the results in the CGGA dataset. The final results showed that high FRGPI was characterized by more aggressive phenotypes, high PD-L1 expression, high tumor mutational burden score, and enhanced temozolomide sensitivity; low FRGPI was associated with less aggressive phenotypes, high microsatellite instability score, and stronger response to immune checkpoint blockade. In addition, the infiltration of memory resting CD4⁺ T cells, regulatory T cells, M1 macrophages, M2 macrophages, and neutrophils was positively correlated with FRGPI. In contrast, plasma B cells and naïve CD4⁺ T cells were negatively correlated. A total of 15 potential small molecule compounds (such as depactin, physostigmine, and phenacetin) were identified.Conclusion: FRGPI is a promising gene panel for predicting the prognosis, immune characteristics, temozolomide sensitivity, and ICI response in patients with glioma.

Background: This study aims to systematically assess the effectiveness and safety of acupuncture on hearing loss (HL) after traumatic brain injury (TBI). Methods: In this study, the following databases will be retrieved from inception up to the May 1, 2019: PUBMED, EMBASE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database. All databases will be retrieved without any language restrictions. Two reviewers will independently carry out article selection, data collection, and risk of bias evaluation. Any disagreements will be solved by a third reviewer through discussion. Results: This study will systematically investigate the effectiveness and safety of acupuncture for treating HL after TBI through evaluating HL assessment, hearing threshold, quality of life, and adverse events. Conclusion: The expected findings of this study will provide latest evidence for assessing the effectiveness and safety of acupuncture for HL after TBI. Ethics and dissemination: This study is supposed to be published in a peer-reviewed journal. No ethical approval is needed because this study will based on the literature analysis, but not the individual patient. PROSPERO registration number: PROSPERO CRD42019133417.

Diabetic cutaneous wounds represent a major clinical challenge due to persistent inflammation, oxidative stress, infection, and impaired angiogenesis. Here