TBC1D1 represses glioma progression by altering the integrity of the cytoskeleton.

BACKGROUND: Glioma is one of the most aggressive malignant brain tumors and is characterized by invasive growth and poor prognosis. TBC1D1, a member of the TBC family, is associated with the development of various malignancies. However, the role of TBC1D1 in glioma-genesis remains unclear. METHODS: The effect of TBC1D1 on the prognosis of glioma patients and related influencing factors were analyzed in the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. Expression of TBC1D1 in glioma cell lines was detected by western blotting. Cell viability and proliferation were measured by EdU and Colony formation assays, respectively. Transwell and wound healing assays were performed to determine the cell migration and invasion capacities. Immunofluorescence was used to observe actin morphology in the cytoskeleton. RESULTS: We discovered that high TBC1D1 expression in gliomas led to poor prognosis. Downregulation of TBC1D1 in glioma cells significantly inhibited multiple important functions, such as proliferation, migration, and invasion. We further demonstrated that the tumor-inhibitory effect of TBC1D1 might occur through the P-LIMK/cofilin pathway, destroying the cytoskeletal structure and affecting the depolymerization of F-actin, thereby inhibiting glioma migration. CONCLUSION: TBC1D1 affects the balance and integrity of the actin cytoskeleton via cofilin, thereby altering the morphology and aggressiveness of glioma cells. This study provides a new perspective on its role in tumorigenesis, thereby identifying a potential therapeutic target for the treatment of gliomas.

SLC1A5 is a novel biomarker associated with ferroptosis and the tumor microenvironment: a pancancer analysis.

Solute carrier family 1 member 5 (SLC1A5) is a member of the solute carrier (SLC) superfamily of transporters and plays an important role in tumors as a key transporter of glutamine into cells. However, the relationship between SLC1A5, which is involved in immune regulation, and immune cell infiltration in the tumor microenvironment has not been elucidated, and the relationship between SLC1A5 and ferroptosis is rarely reported. Therefore, we comprehensively analyzed the expression level of SLC1A5 across cancers and compared it with that in normal tissues. Then, the relationship between SLC1A5 expression and the tumor immune microenvironment was analyzed by single-cell analysis, gene set enrichment analysis (GSEA), and Tumor Immune Estimation Resource (TIMER). Next, the correlations of the SLC1A5 expression level with immunotherapy response, immunomodulator expression, tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. Finally, in vitro experiments verified that SLC1A5 participates in ferroptosis of glioma cells to regulate tumor progression. Our results indicated that SLC1A5 is aberrantly expressed in most cancer types and closely associated with prognosis. The GSEA results showed that SLC1A5 is involved in immune activation processes and closely related to the infiltration levels of different immune cells in different cancer types. Upon further investigation, we found that SLC1A5 is a suppressor of ferroptosis in glioma, and SLC1A5 knockdown inhibited the proliferation and migration of glioma cells in vitro. In conclusion, we conducted a pancancer analysis of SLC1A5, demonstrated its role as a prognostic biomarker in cancer patients and explored its potential biological functions.

Surveillance, Epidemiology, and End Results database and propensity score matching analysis of postoperative radiotherapy for non-malignant meningioma: A retrospective cohort study.

BACKGROUND: The clinical effect of postoperative radiotherapy (PORT) in non-malignant meningioma (NMM) has not been well explored. METHODS: A total of 8629 patients with NMM (surgery alone group: n = 7716, postoperative radiotherapy group: n = 913) were obtained from the Surveillance, Epidemiology, and End Results database. Patient profiles were matched by 1:1 propensity score matching (PSM). Logistic regression analysis was performed to identify factors associated with PORT versus surgery alone (SA). Univariate and multivariate Cox regression analyses determined prognostic variables with overall survival (OS) in NMM. Subgroup analyses were performed with Cox proportional hazards regression models. RESULTS: All the SA (n = 7716) and PORT (n = 913) groups were included. Women with PORT (66.3%) and SA (70.9%) were almost twice as likely as men, and tumors with benign behaviors in the SA group were almost seven times more frequent than those with malignant characteristics. We explored the demographic, clinical characteristics, and prognostic factors in NMM. Laterality, surgery, tumor size, diagnosis year, age, and tumor behavior were associated with PORT versus SA. Patients treated with PORT had better OS than those treated with SA (p = 0.03). After PSM, PORT remained comparable to SA (hazard ratio 0.56, 95% confidence interval 0.35-0.88, p = 0.013). In the subgroup analysis of PORT treatment, borderline malignant behavior increased the death risk by 23%, while other variables did not have a significant clinical benefit (p > 0.05). CONCLUSIONS: Borderline malignant behavior should be considered seriously, and the PORT regimen should be actively implemented for patients with benign meningiomas.

Prediction of prognosis in patients with nontraumatic intracranial hemorrhage using blood urea nitrogen-to-creatinine ratio on admission: a retrospective cohort study based on data from the medical information Mart for intensive care-IV database.

Background: The blood urea nitrogen-to-creatinine ratio (BUNCR) has been proposed as a potential biomarker for critical illness-induced catabolism. However, its specific relevance and significance in the context of non-traumatic intracranial hemorrhage (NTIH) remains unclear. As such, the primary objective of this study was to determine the role of BUNCR in the prognosis of patients with NTIH. Materials and methods: All data were sourced from the Medical Information Mart for Intensive Care-IV 2.0 (MIMIC-IV) database. Study outcomes included 30-day and 1-year mortality rates. Univariate and multivariate logistic regression analyses were used to calculate adjusted odds ratio with corresponding 95% confidence interval, and generalized additive model were used to identify both linear and non-linear relationships between BUNCR and mortality rates. A two-piecewise regression model was performed to calculate the saturation effect. Subgroup analyses were performed to evaluate outcome stability in various groups. Results: A retrospective study of 3,069 patients with NTIH revealed a U-shaped relationship between BUNCR levels and 30-day/1-year mortality. The two-piecewise regression model showed that the inflection points for 30-day and 1-year mortality were 10.455 and 16.25, respectively. On the left side of the inflection point, the 30-day and 1-year mortality rate decreased by 17.7% (OR = 0.823, 95%CI: 0.705-0.960; p = 0.013) and 5.3% (OR = 0.947, 95%CI: 0.899-0.999; p = 0.046), respectively, per 1 unit increment of BUNCR. On the right side of the inflection point, the 30-day and 1-year mortality rate increased by 1.6% (OR = 1.016, 95%CI: 1.000-1.031; p = 0.046) and 3.6% (OR = 1.036, 95%CI:1.019-1.054; p < 0.001) per 1 unit decrement of BUNCR. Subgroup analyses revealed consistent results across different strata. Conclusion: This study identified a nonlinear relationship between BUNCR and mortality in patients with NTIH, indicating that BUNCR may be valuable prognostic marker for early identification and proactive management.

Effects of shuxuetong injection for cerebral infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: Cerebral infarction (CI) is a common disease with high morbidity and disability. Shuxuetong (SXT) injection is a Chinese Materia Medica standardized product used in the treatment of CI. Currently, there is a lack of high-quality evidence to support the effectiveness and safety of SXT on patients with CI. This systematic review protocol aims at describing a meta-analysis to evaluate the efficacy of SXT for the treatment of CI. METHODS: We will search the databases of PubMed, MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, China national knowledge infrastructure database (CNKI), Wan fang database, Chongqing VIP information, and SinoMed from their inception to Jun 2020. Two reviewers will independently screen Randomized controlled trials of SXT for the treatment of CI. The meta-analysis will be conducted using RevMan V.5.3 software. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether SXT is an effective intervention for patients with CI. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/3F6ZH.

Overexpressed miR-183 promoted glioblastoma radioresistance via down-regulating LRIG1.

BACKGROUND: Glioma is the most common cause of cancer-related death. Therapy based on radiation seemed to effectively, while the radioresistance of several glioblastoma cells abolished the therapy. Thus, to employ the potential mechanism underlying the radioresistance is essential for glioma treatment. METHODS: Radioresistant cells were constructed using the X-ray radiation. Cell viability and apoptosis were detect using CCK-8 and Annexin-V/propidium iodide (PI), respectively. Real-time PCR and western blot were performed to determine gene expression. Luciferase reporter assay was carried out to detect the relationship between miR-183 and LRIG1. Mice xenotransplant model of glioma was established to detect the role of miR-183 in vivo. RESULTS: The expression of miR-183 was increased, while LRIG1 was decreased in resistant tissues rather than in sensitive tissues. The expression of LRIG1 was lower in radioresistant gliblastoma cell line U251R rather than in normal glioblastoma cell line U251. Overexpressed miR-183 suppressed cell apoptosis in radioresistance U251R cells (U251R). MiR-183 targets LRIG1 to regulate its expression. U251R cells transfected miR-183 inhibitor promoted the expression of LRIG1, and decreased the expression of EFGR and p-Akt, while U251R cells co-transfected with shRNA-LRIG1 abolished the effects of miR-183 knockdown. U251 cells transfected with miR-183 mimic decreased the expression of LRIG1, and promoted the expression of EFGR and p-Akt, while cells co-transfected with pcDNA-LRIG1 abolished the effects of miR-183 overexpression. In vivo experiments demonstrated that miR-183 inhibitor suppressed tumor growth, while miR-183 mimic promoted tumor growth. CONCLUSION: MiR-183 overexpression promoted radioresistance of glioblastoma via down-regulating LRIG1 and increasing the activity of EFGR/Akt.

Silymarin prevents NLRP3 inflammasome activation and protects against intracerebral hemorrhage.

Inflammatory response mediates secondary injury during intracerebral hemorrhage (ICH). In the present study, we determined oxidative stress and involvement of NLRP3 in ICH injury and analyzed whether silymarin might offer protective effect against ICH injury. Post 24h after ICH injury there was increased oxidative stress markers (reactive oxygen species (ROS) and lipid peroxides) compared to sham group. Silymarin (200mg/kg) treatment 30 mins post ICH injury prevented increase in oxidative stress markers and up-regulated antioxidant status. Further, there was significant increase in nuclear levels of NF-κB-p65 and pro-inflammatory cytokine expressions post ICH injury. NLRP3 inflammasome activation and downstream targets such as caspase-1 and IL-1ß expressions were significantly up regulated in ICH injury. Silymarin treatment significantly down regulated the inflammatory responses by suppressing NF-κB-p65 levels and inflammasome-mediated caspase-1/IL-1ß expressions. Further, treatment with silymarin post ICH injury increased Nrf-2/HO-1 and thereby improved overall cytoprotection. These findings together show that silymarin acts as neuroprotective compound by preventing inflammatory activation and up regulating Nrf-2/HO-1 signaling post ICH injury.