3D Porous VOx/N-Doped Carbon Nanosheet Hybrids Derived from Cross-Linked Dicyandiamide-Chitosan Hydrogels for Superior Supercapacitor Electrode Materials.

Three-dimensional porous carbon materials with moderate heteroatom-doping have been extensively investigated as promising electrode materials for energy storage. In this study, we fabricated a 3D cross-linked chitosan-dicyandiamide-VOSO4 hydrogel using a polymerization process. After pyrolysis at high temperature, 3D porous VOx/N-doped carbon nanosheet hybrids (3D VNCN) were obtained. The unique 3D porous skeleton, abundant doping elements, and presence of VOx 3D VNCN pyrolyzed at 800 °C (3D VNCN-800) ensured excellent electrochemical performance. The 3D VNCN-800 electrode exhibits a maximum specific capacitance of 408.1 F·g-1 at 1 A·g-1 current density and an admirable cycling stability with 96.8% capacitance retention after 5000 cycles. Moreover, an assembled symmetrical supercapacitor based on the 3D VNCN-800 electrode delivers a maximum energy density of 15.6 Wh·Kg-1 at a power density of 600 W·Kg-1. Our study demonstrates a potential guideline for the fabrication of porous carbon materials with 3D structure and abundant heteroatom-doping.

Facile Electrochemical Synthesis of Bifunctional Needle-like Co-P Nanoarray for Efficient Overall Water Splitting.

The development of low-cost and high-performance bifunctional electrocatalysts for overall water splitting is still challenging. Herein, we employed a facile electrodeposition method to prepare bifunctional cobalt phosphide for overall water splitting. The needle-like cobalt phosphide (Co-P-1) nanoarray is uniformly distributed on nickel foam. Co-P-1 exhibits excellent electrocatalytic activity for hydrogen evolution reaction (HER, 85 mV at 10 mA/cm2, 60 mV/dec) and oxygen evolution reaction (OER, 294 mV at 50 mA/cm2, 60 mV/dec). The cell-voltage of 1.60 V is found to achieve the current density of 10 mA/cm2 for overall water splitting in the two-electrode system, comparable to that of previously reported Pt/C/NF||RuO2/NF. The excellent electrocatalytic performance can be attributed to the needle-like structure with more active sites, accelerated charge transfer and evolved bubbles' release. This work can provide new approach to the development of a bifunctional electrocatalyst for overall water splitting.

Claudin-3 facilitates the progression and mediates the tumorigenic effects of TGF-ß in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a significantly malignant and lethal brain tumor with an average survival time of less than 12 months. Several researches had shown that Claudin-3 (CLDN3) is overexpressed in various cancers and might be important in their growth and spread. In this study, we used qRT-PCR, western blotting, immunohistochemistry, and immunofluorescence staining assays to investigate the expression levels of various proteins. To explore the proliferation abilities of GBM cells, we conducted the CCK-8 and EdU-DNA formation assays. Wound healing and transwell assays were used to investigate the capacities of invasion and migration of GBM cells. Additionally, we constructed an intracranial xenograft model of GBM to study the in vivo role of CLDN3. Our study devoted to investigate the function of CLDN3 in the pathogenesis and progression of GBM. Our study revealed that CLDN3 was upregulated in GBM and could stimulate tumor cell growth and epithelial-mesenchymal transition (EMT) in both laboratory and animal models. We also discovered that CLDN3 expression could be triggered by transforming growth factor-ß (TGF-ß) and reduced by specific inhibitors of the TGF-ß signaling pathway, such as ITD-1. Further analysis revealed that increased CLDN3 levels enhanced TGF-ß-induced growth and EMT in GBM cells, while reducing CLDN3 levels weakened these effects. Our study demonstrated the function of CLDN3 in facilitating GBM growth and metastasis and indicated its involvement in the tumorigenic effects of TGF-ß. Developing specific inhibitors of CLDN3 might, therefore, represent a promising new approach for treating this devastating disease.

TMEM2 induces epithelial-mesenchymal transition and promotes resistance to temozolomide in GBM cells.

Glioblastoma multiforme (GBM) is the most common intracranial malignant tumor and is notorious for its poor prognosis. An important element in the short overall survival of GBM patients is the lack of understanding the pathogenesis and progression of tumor and deficiency biomarkers that can be used for early diagnosis and therapeutic sensitivity monitoring. Studies have shown that transmembrane protein 2 (TMEM2) is participated in tumorigenesis of various human tumors, including rectal and breast cancers. Although Qiuyi Jiang et al. have reported that TMEM2 combined with IDH1/2 and 1p19q can predict the survival time of glioma patients based on bioinformatics, its expression and biological role of glioma remain unclear. In our study, we investigated the effect of TMEM2 expression level on glioma malignancy in public datasets and an independent internal dataset. We revealed TEMM2 expression was higher in GBM tissues than in non-tumor brain tissues (NBT). Moreover, the increase in TMEM2 expression level was closely related to tumor malignancy. The survival analysis showed that TMEM2 high expression reduces survival time in all glioma patients, including GBM and LGG patients. Subsequent experiments demonstrated that knockdown TMEM2 inhibited proliferation of GBM cells. In addition, we analyzed TMEM2 mRNA levels in different GBM subtypes, and demonstrated that TMEM2 expression was upregulated in mesenchymal subtype. Meanwhile, bioinformatics analysis and transwell assay indicated that knockdown TMEM2 suppressed epithelial-mesenchymal transition (EMT) in GBM. Importantly, Kaplan-Meier analysis demonstrated that TMEM2 high expression reduced the treatment response to TMZ in GBM patients. Knockdown of TMEM2 alone did not reduce apoptosis GBM cells, but significant apoptotic cells were observed in the group treated with additional TMZ. These studies may contribute to improving the accuracy of early diagnosis and evaluating the effectiveness of TMZ treatment in GBM patients.

Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma.

Glioblastoma multiforme (GBM) is the most common and fatal primary malignant central nervous system tumor in adults. Although there are multiple treatments, the median survival of GBM patients is unsatisfactory, which has prompted us to continuously investigate new therapeutic strategies, including new drugs and drug delivery approaches. Ferroptosis, a kind of regulated cell death (RCD), has been shown to be dysregulated in various tumors, including GBM. Fatostatin, a specific inhibitor of sterol regulatory element binding proteins (SREBPs), is involved in lipid and cholesterol synthesis and has antitumor effects in a variety of tumors. However, the effect of fatostatin has not been explored in the field of ferroptosis or GBM. In our study, through transcriptome sequencing, in vivo experiments, and in vitro experiments, we found that fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. We also designed a p28-functionalized PLGA nanoparticle loaded with fatostatin, which could better cross the blood-brain barrier (BBB) and be targeted to GBM. Our research identified the unprecedented effects of fatostatin in GBM and presented a novel drug-targeted delivery vehicle capable of penetrating the BBB in GBM.

Identification and validation of a novel prognostic signature based on mitochondria and oxidative stress related genes for glioblastoma.

BACKGROUND: Mitochondria represent a major source of reactive oxygen species (ROS) in cells, and the direct increase in ROS content is the primary cause of oxidative stress, which plays an important role in tumor proliferation, invasion, angiogenesis, and treatment. However, the relationship between mitochondrial oxidative stress-related genes and glioblastoma (GBM) remains unclear. This study aimed to investigate the value of mitochondria and oxidative stress-related genes in the prognosis and therapeutic targets of GBM. METHODS: We retrieved mitochondria and oxidative stress-related genes from several public databases. The LASSO regression and Cox analyses were utilized to build a risk model and the ROC curve was used to assess its performance. Then, we analyzed the correlation between the model and immunity and mutation. Furthermore, CCK8 and EdU assays were utilized to verify the proliferative capacity of GBM cells and flow cytometry was used to analyze apoptosis rates. Finally, the JC-1 assay and ATP levels were utilized to detect mitochondrial function, and the intracellular ROS levels were determined using MitoSOX and BODIPY 581/591 C11. RESULTS: 5 mitochondrial oxidative stress-related genes (CTSL, TXNRD2, NUDT1, STOX1, CYP2E1) were screened by differential expression analysis and Cox analysis and incorporated in a risk model which yielded a strong prediction accuracy (AUC value = 0.967). Furthermore, this model was strongly related to immune cell infiltration and mutation status and could identify potential targeted therapeutic drugs for GBM. Finally, we selected NUDT1 for further validation in vitro. The results showed that NUDT1 was elevated in GBM, and knockdown of NUDT1 inhibited the proliferation and induced apoptosis of GBM cells, while knockdown of NUDT1 damaged mitochondrial homeostasis and induced oxidative stress in GBM cells. CONCLUSION: Our study was the first to propose a prognostic model of mitochondria and oxidative stress-related genes, which provided potential therapeutic strategies for GBM patients.

TFR2 regulates ferroptosis and enhances temozolomide chemo-sensitization in gliomas.

Glioma is a common type of brain tumor with high incidence and mortality rates. Iron plays an important role in various physiological and pathological processes. Iron entry into the cell is promoted by binding the transferrin receptor 2 (TFR2) to the iron-transferrin complex. This study was designed to assess the association between TFR2 and ferroptosis in glioma. Lipid peroxidation levels in glioma cells were assessed by determination of lipid reactive oxygen species (ROS), glutathione content, and mitochondrial membrane potential. The effect of TFR2 on TMZ sensitivity was examined by cell viability assays, flow cytometry, and colony formation assays. We found that Low TFR2 expression predicted a better prognosis for glioma patients. And overexpression of TFR2 promoted the production of reactive oxygen species and lipid peroxidation in glioma cells, thereby further promoting ferroptosis. This could be reversed by the ferroptosis inhibitors Fer-1 and DFO (both inhibitors of ferroptosis). Moreover, TFR2 potentiated the cytotoxic effect of TMZ (temozolomide) via activating ferroptosis. In conclusion, we found that TFR2 induced ferroptosis and enhanced TMZ sensitivity in gliomas. Our findings might provide a new treatment strategy for glioma patients and improve their prognosis.

Development and validation of immunogenic cell death-related signature for predicting the prognosis and immune landscape of uveal melanoma.

Introduction: Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, and the main treatment for UM is currently surgery and plaque brachytherapy. UM is highly susceptible to metastasis, which eventually occurs in nearly half of all patients; once metastasis occurs, patients have a poor prognosis and the condition is difficult to treat. Therefore, the identification of new and effective UM biomarkers is vital for the application of therapeutic strategies. Immunogenic cell death (ICD) is a type of regulatory cell death that activates adaptive immune responses and generates long-term immunological memory. ICD can promote antitumor immunity, which may be a potential immunotherapeutic strategy for UM. Methods: The data of UM from the Cancer Genome Atlas (TCGA) was used as a training set and the data from Gene Expression Omnibus (GEO) was used as a validation set. To determine the expression pattern of ICD-related genes in UM, survival analysis and difference analysis was conducted. The ICD-related risk signature was constructed by employing the least absolute shrinkage and selection operator (LASSO) Cox regression. Subsequently, immune profile and somatic mutation analysis were performed. In addition, cell experiments were performed to verify the role of immunogenic cell death-related genes in UM. Results: In this study, we analyzed the relationship between ICD-related gene expression and UM patient prognosis, somatic mutations, and the tumor immune microenvironment. Importantly, we constructed a 5-gene ICD-related risk signature and confirmed it as a novel prognostic biomarker in UM patients. We found that the high-risk group had more immune cell infiltration and a worse prognosis than the low-risk group. In cellular experiments, we confirmed the high expression of FOXP3 inMUM2B andOCM-1A cell lines and that knockdown of FOXP3 markedly inhibited the proliferation of UM tumor cells. Discussion: ICD-related genes play a critical role in the tumor immune microenvironment. Our results may contribute to the development of effective immunotherapies.

Immunogenic cell death-related risk signature predicts prognosis and characterizes the tumour microenvironment in lower-grade glioma.

Lower-grade glioma (LGG) is a common malignant primary tumour in the central nervous system, and most patients eventually develop highly aggressive gliomas despite comprehensive traditional treatment. Tumour molecular subtypes and prognostic biomarkers play a crucial role in LGG diagnosis and treatment. Therefore, the identification of novel biomarkers in LGG patients is crucial for predicting the prognosis of glioma. Immunogenic cell death (ICD) is defined as regulated cell death that is sufficient to activate the adaptive immune response of immunocompetent hosts. The combination of ICD and immunotherapy might exert a greater and more persistent antitumour effect in gliomas. In our study, we explored the expression, function, and genetic alterations of 34 ICD-related genes. Using 12 ICD-related genes, including IL17RA, IL1R1, EIF2AK3, CD4, PRF1, CXCR3, CD8A, BAX, PDIA3, CASP8, MYD88, and CASP1, we constructed and validated an ICD-related risk signature via least absolute shrinkage and selection operator (LASSO) Cox regression analysis. All the information was obtained from public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and the Chinese Glioma Genome Atlas (CGGA) databases. Our results revealed that ICD-high risk groups have a poor prognosis and might be more sensitive to immune checkpoint blockade (ICB) immunotherapy. In addition, ICD-high risk groups were associated with 1p19q noncodeletion, higher WHO grade, wild type IDH, and an immunosuppressive tumour microenvironment. We verified the prognostic value of 12 ICD-related genes in TCGA and CGGA databases. Immunohistochemistry was performed to verify the expression of several ICD-related genes at the protein level. Our study provides a novel and comprehensive perspective to elucidate the underlying mechanisms of LGG prognosis and direction for future individualized cancer immunotherapy.

Identification and validation of a 17-gene signature to improve the survival prediction of gliomas.

Gliomas are one of the most frequent types of nervous system tumours and have significant morbidity and mortality rates. As a result, it is critical to fully comprehend the molecular mechanism of glioma to predict prognosis and target gene therapy. The goal of this research was to discover the hub genes of glioma and investigate their prognostic and diagnostic usefulness. In this study, we collected mRNA expression profiles and clinical information from glioma patients in the TCGA, GTEx, GSE68848, and GSE4920 databases. WGCNA and differential expression analysis identified 170 DEGs in the collected datasets. GO and KEGG pathway analyses revealed that DEGs were mainly enriched in gliogenesis and extracellular matrix. LASSO was performed to construct prognostic signatures in the TCGA cohort, and 17 genes were used to build risk models and were validated in the CGGA database. The ROC curve confirmed the accuracy of the prognostic signature. Univariate and multivariate Cox regression analyses showed that all independent risk factors for glioma except gender. Next, we performed ssGSEA to demonstrate a high correlation between risk score and immunity. Subsequently, 7 hub genes were identified by the PPI network and found to have great drug targeting potential. Finally, RPL39, as one of the hub genes, was found to be closely related to the prognosis of glioma patients. Knockdown of RPL39 in vitro significantly inhibited the proliferation and migration of glioma cells, whereas overexpression of RPL39 had the opposite effect. And we found that knockdown of RPL39 inhibited the polarization and infiltration of M2 phenotype macrophages. In conclusion, our new prognosis-related model provides more potential therapeutic strategies for glioma patients.

FAIM2 is a potential pan-cancer biomarker for prognosis and immune infiltration.

Fas apoptosis inhibitory molecule 2 (FAIM2) is an important member of the transmembrane BAX inhibitor motif containing (TMBIM) family. However, the role of FAIM2 in tumor prognosis and immune infiltration has rarely been studied. Here, we conducted a pan-cancer analysis to explore the role of FAIM2 in various tumors and further verified the results in glioma through molecular biology experiment. FAIM2 expression and clinical stages in tumor samples and para-cancerous samples were analyzed by TIMER2 database, GEPIA database, and the TISIDB database. The role of FAIM2 on prognosis was analyzed via GEPIA2. We utilized the ESTIMATE algorithm to evaluate the ImmuneScore and StromalScore of various tumors. In addition, we explored the correlation between FAIM2 expression and tumor immune cell infiltration by the TIMER2 database. The immune checkpoint genes, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and DNA methylation related to FAIM2 were analyzed based on the TCGA database. The correlation between FAIM2 expression with Copy number variations (CNV) and methylation is explored by GSCA database. Protein-Protein Interaction (PPI) analysis was obtained from the STRING database and the CellMiner database was used to explore the association between FAIM2 expression and drug response. FAIM2 co-expression genes were studied by the LinkedOmics database. Immunohistochemistry, Western Blotting Analysis, Cell Viability Assay, Colony Formation Assay, and Edu staining assay were used in the molecular biology experiments section. The FAIM2 expression was down-regulated in most tumors and highly expressed FAIM2 was associated with a better prognosis in several cancers. FAIM2 plays an essential role in the tumor microenvironment and is closely associated with immune Infiltration in various tumors. The expression of FAIM2 was closely correlated to TMB, MSI, MMR, CNV, and DNA methylation. Furthermore, FAIM2 related genes in the PPI network and its co-expression genes in glioma are involved in a large number of immune-related pathways. Molecular biology experiments verified a cancer suppressor role for FAIM2 in glioma. FAIM2 may serve as a potential pan-cancer biomarker for prognosis and immune infiltration, especially in glioma. Moreover, this study might provide a potential target for tumor immunotherapy.

Development and validation of cuproptosis-associated prognostic signatures in WHO 2/3 glioma.

WHO 2/3 glioma is a common intracranial tumor that seriously affects the quality of life and survival time of patients. Previous studies have shown that the tricarboxylic acid (TCA) cycle is closely related to the occurrence and development of glioma, while recent studies have shown that cuproptosis, a novel programmed death pathway, is closely related to the inhibition of the TCA cycle. In our study, eight of ten cuproptosis-related genes (CRGs) were found to be differentially expressed between normal and WHO 2/3 glioma tissues. Through the LASSO algorithm, the cuproptosis-associated risk signatures (CARSs) were constructed, which can effectively predict the prognosis of WHO 2/3 glioma patients and are closely related to clinicopathological features. We analyzed the relationship between risk score and immune cell infiltration through Xcell, ssGSEA, TIMER database, and immune checkpoint molecules. In addition, the relationship between risk score and chemotherapeutic drug sensitivity was also investigated. The prognosis-related independent risk factors FDX1 and CDKN2A identified from CARSs are considered potential prognostic biomarkers for WHO 2/3 glioma. The clinical prognosis model based on cuproptosis is expected to provide an effective reference for the diagnosis and treatment of clinical WHO 2/3 glioma patients.

Exploring the inverse association of glioblastoma multiforme and Alzheimer's disease via bioinformatics analysis.

Glioblastoma multiforme (GBM) and Alzheimer's disease (AD) are two major diseases in the nervous system with a similar peak age of onset, which has the typical characteristics of high cost, difficult treatment, and poor prognosis. Epidemiological studies and a few molecular biological studies have hinted at an opposite relationship between AD and GBM. However, there are few studies on their reverse relationship, and the regulatory mechanism is still unclear, indicating that further systematic research is urgently needed. Our study firstly employs advanced bioinformatics methods to explore the inverse relationship between them and find various target drugs. We obtained the gene expression dataset from public databases (GEO, TCGA, and GTEx). Then, we identified 122 differentially expressed genes (DEGs) of AD and GBM. Four significant gene modules were identified through protein-protein interaction (PPI) and module construction, and 13 hub genes were found using cytoHubba. We constructed co-expression networks and found various target drugs through these hub genes. Functional enrichment analysis revealed that the AMPK pathway, cell cycle, and cellular senescence play important roles in AD and GBM. Our study may provide a potential direction for studying the opposite molecular mechanism of AD and GBM in the future.

IRF2-ferroptosis related gene is associated with prognosis and EMT in gliomas.

Ferroptosis is a new type of programmed cell death that has excellent anti-tumor potential in different tumors. However, the research on ferroptosis in glioma is still incomplete. In this study, we aimed to revealed the relationship between ferroptosis-related genes (FRGs) and glioma. We collected gene expression profiles of glioma patients from the TCGA and CGGA databases. All glioma samples were classified into five subtypes using the R software ConsensusClusterPlus. Subsequently, we performed single sample gene set enrichment analysis (ssGSEA) to explore the correlation between different subtypes and immune status and ferroptosis. Then co-expression modules were constructed via weighted gene co-expression network analysis (WGCNA). A Gene Ontology (GO) analysis was conducted to analyze the potential biological functions of the genes in the modules. Finally, we identified 10 hub genes using the PPI network. The in vitro experiments were used to validate our predictions. We found that the expression level of IRF2 is positively correlated with the grade of glioma. The overexpression of IRF2 could protect glioma cells from ferroptosis and enhance the invasive and migratory abilities. Silence of IRF2 had the opposite effect. In conclusion, we demonstrated a novel ferroptosis-related signature for predicting prognosis, and IRF2 could be a potential biomarker for diagnosis and treatment in glioma.

High-Performance Optical PET Analysis via Non-Isothermal Crystallization Kinetics.

The optical properties of PET have always been a problem that related research has been trying to break through. In the previous work, we modified PET by adding PSLDH (phosphate antioxidant) to obtain a PET film with excellent optical properties. Through non-isothermal crystallization kinetic analysis of modified PET, we hope to verify the conclusion of optical properties by the effect of PSLDH addition on the crystallization properties of PET. PET and PSLDH modified PET were tested by DSC at different cooling rates. The non-isothermal crystallization kinetic process was calculated and analyzed by Jeziorny and Mo methods and the non-isothermal crystallization activation energy was analyzed by Kissinger and Friedman methods by analyzing the DSC curves. The results show that the addition of PSLDH at 0.05 wt% can make the crystallization of PET smaller and slower, which is the same as the case required for excellent optical properties. At the same time, the results can also guide the processing of the optical PET film.

Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment.

Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood-brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice.

TMCO1 expression promotes cell proliferation and induces epithelial-mesenchymal transformation in human gliomas.

Transmembrane and coiled-coil domains 1 (TMCO1) is a recently discovered transmembrane protein of endoplasmic reticulum (ER), which plays a critical role in maintaining calcium homeostasis. TMCO1 dysfunction has been proved to be closely related to a variety of human diseases, including glaucoma, deformities, mental retardation and tumorigenesis. However, the role of TMCO1 in gliomas remains unclear. The purpose of this study was to detect the role of TMCO1 in the pathogenesis and progression of gliomas. This study demonstrated that TMCO1 was upregulated in gliomas and its overexpression predicted poor prognosis. We also revealed that the expression of TMCO1 was associated with the World Health Organization (WHO) grade of gliomas. Knockdown of TMCO1 inhibited the proliferation and induced apoptosis of U87 and U251 cells. In addition, TMCO1 induced GBM cell migration and invasion by promoting epithelial-mesenchymal transition (EMT). These date collectively proved the crucial role of TMCO1 as a novel prognostic factor and underlying therapeutic target for glioma patients.

TMBIM1 promotes proliferation and attenuates apoptosis in glioblastoma cells by targeting the p38 MAPK signalling pathway.

Glioblastoma multiforme (GBM) is the most common and most fatal primary malignant brain tumour in adults. The average survival time of patients after diagnosis is only 12-15 months. And its characteristics of excessive proliferation and apoptosis evasion play a crucial role in the poor prognosis of patients. Therefore, it is worth investigating the molecular mechanism of GBM to find an effective therapeutic target to overcome the dilemma. In the current study, Transmembrane BAX inhibitor motif containing 1 (TMBIM1) was highly expressed in GBM tissues and high TMBIM1 expression in GBM cell lines (U87 and U251) could promote cell proliferation and inhibit cell cycle arrest. In addition, TMBIM1 could significantly attenuate GBM cell apoptosis and decrease the sensitivity of GBM cells to temozolomide (TMZ). In terms of the molecular mechanism, we revealed that TMBIM1 interferes with the p38/MAPK pathway by inhibiting p38 phosphorylation to promote cell proliferation and attenuate cell apoptosis. In vivo experiments showed that the survival time of mice in TMBIM1 knockdown group was significantly prolonged. Our discovery provided an important basis for future intensive molecular mechanism research in GBM and presented a potential target for the treatment of GBM.

Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common and fatal primary tumor in the central nervous system (CNS). Due to the existence of blood-brain barrier (BBB), most therapeutics cannot efficiently reach tumors in the brain, and as a result, they are unable to be used for effective GBM treatment. Accumulating evidence shows that delivery of therapeutics in form of nanoparticles (NPs) may allow crossing the BBB for effective GBM treatment. METHODS: Betulinic acid NPs (BA NPs) were synthesized by the standard emulsion approach and characterized by electron microscopy and dynamic light scattering analysis. The resulting NPs were characterized for their anti-tumor effects by cell viability assay, EdU-DNA synthesis assay, cell cycle assay, mitochondrial membrane potential, and PI-FITC apoptosis assay. Further mechanistic studies were carried out through Western Blot and immunostaining analyses. Finally, we evaluated BA NPs in vivo for their pharmacokinetics and antitumor effects in intracranial xenograft GBM mouse models. RESULTS: BA NPs were successfully prepared and formed into rod shape. BA NPs could significantly suppress glioma cell proliferation, induce apoptosis, and arrest the cell cycle in the G0/G1 phase in vitro. Furthermore, BA NPs downregulated the Akt/NFκB-p65 signaling pathway in a concentration dependent manner. We found that the observed anti-tumor effect of BA NPs was dependent on the function of CB1/CB2 receptors. Moreover, in the intracranial GBM xenograft mouse models, BA NPs could effectively cross the BBB and greatly prolong the survival time of the mice. CONCLUSIONS: We successfully synthesized BA NPs, which could cross the BBB and demonstrated a strong anti-tumor effect. Therefore, BA NPs may potentially be used for effective treatment of GBM.

Identification of immunogenic cell death-related gene classification patterns and immune infiltration characterization in ischemic stroke based on machine learning.

Ischemic stroke (IS) accounts for more than 80% of strokes and is one of the leading causes of death and disability in the world. Due to the narrow time window for treatment and the frequent occurrence of severe bleeding, patients benefit less from early intravenous thrombolytic drug therapy. Therefore, there is an urgent need to explore the molecular mechanisms poststroke to drive the development of new therapeutic approaches. Immunogenic cell death (ICD) is a type of regulatory cell death (RCD) that is sufficient to activate the adaptive immune response of immunocompetent hosts. Although there is growing evidence that ICD regulation of immune responses and immune responses plays an important role in the development of IS, the role of ICD in the pathogenesis of IS has rarely been explored. In this study, we systematically evaluated ICD-related genes in IS. The expression profiles of ICD-related genes in IS and normal control samples were systematically explored. We conducted consensus clustering, immune infiltration analysis, and functional enrichment analysis of IS samples using ICD differentially expressed genes. The results showed that IS patients could be classified into two clusters and that the immune infiltration profile was altered in different clusters. In addition, we performed machine learning to screen nine signature genes that can be used to predict the occurrence of disease. We also constructed nomogram models based on the nine risk genes (CASP1, CASP8, ENTPD1, FOXP3, HSP90AA1, IFNA1, IL1R1, MYD88, and NT5E) and explored the immune infiltration correlation, gene-miRNA, and gene-TF regulatory network of the nine risk genes. Our study may provide a valuable reference for further elucidation of the pathogenesis of IS and provide directions for drug screening, personalized therapy, and immunotherapy for IS.