Multi-scale brain attributes contribute to the distribution of diffuse glioma subtypes.

Gliomas are primary brain tumors and are among the most malignant types. Adult-type diffuse gliomas can be classified based on their histological and molecular signatures as IDH-wildtype glioblastoma, IDH-mutant astrocytoma, and IDH-mutant and 1p/19q-codeleted oligodendroglioma. Recent studies have shown that each subtype of glioma has its own specific distribution pattern. However, the mechanisms underlying the specific distributions of glioma subtypes are not entirely clear despite partial explanations such as cell origin. To investigate the impact of multi-scale brain attributes on glioma distribution, we constructed cumulative frequency maps for diffuse glioma subtypes based on T1w structural images and evaluated the spatial correlation between tumor frequency and diverse brain attributes, including postmortem gene expression, functional connectivity metrics, cerebral perfusion, glucose metabolism, and neurotransmitter signaling. Regression models were constructed to evaluate the contribution of these factors to the anatomic distribution of different glioma subtypes. Our findings revealed that the three different subtypes of gliomas had distinct distribution patterns, showing spatial preferences toward different brain environmental attributes. Glioblastomas were especially likely to occur in regions enriched with synapse-related pathways and diverse neurotransmitter receptors. Astrocytomas and oligodendrogliomas preferentially occurred in areas enriched with genes associated with neutrophil-mediated immune responses. The functional network characteristics and neurotransmitter distribution also contributed to oligodendroglioma distribution. Our results suggest that different brain transcriptomic, neurotransmitter, and connectomic attributes are the factors that determine the specific distributions of glioma subtypes. These findings highlight the importance of bridging diverse scales of biological organization when studying neurological dysfunction.

KDM1A, a potent and selective target, for the treatment of DNMT3A-deficient non-small cell lung cancer.

BACKGROUND: DNMT3A is a crucial epigenetic regulation enzyme. However, due to its heterogeneous nature and frequent mutation in various cancers, the role of DNMT3A remains controversial. Here, we determine the role of DNMT3A in non-small cell lung cancer (NSCLC) to identify potential treatment strategies. METHODS: To investigate the role of loss-of-function mutations of DNMT3A in NSCLC, CRISPR/Cas9 was used to induce DNMT3A-inactivating mutations. Epigenetic inhibitor library was screened to find the synthetic lethal partner of DNMT3A. Both pharmacological inhibitors and gene manipulation were used to evaluate the synthetic lethal efficacy of DNMT3A/KDM1A in vitro and in vivo. Lastly, MS-PCR, ChIP-qPCR, dual luciferase reporter gene assay and clinical sample analysis were applied to elucidate the regulation mechanism of synthetic lethal interaction. RESULTS: We identified DNMT3A is a tumour suppressor gene in NSCLC and KDM1A as a synthetic lethal partner of DNMT3A deletion. Both chemical KDM1A inhibitors and gene manipulation can selectively reduce the viability of DNMT3A-KO cells through inducing cell apoptosis in vitro and in vivo. We clarified that the synthetic lethality is not only limited to the death mode, but also involved into tumour metastasis. Mechanistically, DNMT3A deficiency induces KDM1A upregulation through reducing the methylation status of the KDM1A promoter and analysis of clinical samples indicated that DNMT3A expression was negatively correlated with KDM1A level. CONCLUSION: Our results provide new insight into the role of DNMT3A in NSCLC and elucidate the mechanism of synthetic lethal interaction between KDM1A and DNMT3A, which might represent a promising approach for treating patients with DNMT3A-deficient tumours.

Berberine inhibits glioma cell migration and invasion by suppressing TGF-ß1/COL11A1 pathway.

Glioma is a clinically heterogeneous disease with a poor prognosis. Berberine (BBR), as a multi-target anti-tumor alkaloid, has the ability to penetrate the blood-brain barrier and shows cytotoxicity to glioma cells. In previous studies, we demonstrated that berberine inhibits glioma cell proliferation by inhibiting mutant p53 protein and promoting mitochondrial damage. In addition, berberine has been shown to reduce collagen accumulation in pulmonary fibrosis, diabetic nephropathy and arthritis. However, its effect on collagen in cancer needs to be further elucidated. In this study, we proved that the collagen XI alpha 1 chain (COL11A1) is highly expressed in glioma cell lines and associated with migration and invasion of glioma cells. Knocking down COL11A1 caused decreased expression of MMPs. Berberine could inhibit the migration and invasion of glioma cells by suppressing the TGF-ß1/COL11A1 pathway and changes actin cytoskeleton arrangement. Nude mouse subcutaneous xenografts model also showed that berberine inhibited the expression of COL11A1 in vivo. Collectively, berberine that targets COL11A1 to inhibit glioma migration and invasion, may serve as a promising candidate for the development of anti-glioma drugs in the future.

Collagen XI alpha 1 chain, a potential therapeutic target for cancer.

Extracellular matrix (ECM) plays an important role in the progression of cancer. Collagen is the most abundant component in ECM, and it is involved in the biological formation of cancer. Although type XI collagen is a minor fibrillar collagen, collagen XI alpha 1 chain (COL11A1) has been found to be upregulated in a variety of cancers including ovarian cancer, breast cancer, thyroid cancer, pancreatic cancer, non-small-cell lung cancer, and transitional cell carcinoma of the bladder. High levels of COL11A1 usually predict poor prognosis, while COL11A1 is related to angiogenesis, invasion, and drug resistance of cancer. However, little is known about the specific mechanism by which COL11A1 regulates tumor progression. Here, we have organized and summarized the recent developments regarding elucidation of the relationship between COL11A1 and various cancers, as well as the interaction between COL11A1 and intracellular signaling pathways. In addition, we have selected therapeutic agents targeting COL11A1. All these indicate the possibility of using COL11A1 as a target for cancer treatment.

Mechanisms involved in the anti-tumor effects of Toosendanin in glioma cells.

BACKGROUND: Toosendanin (TSN) is a triterpenoid compound mainly used as an ascaris repellant. Recent studies have shown that it possesses antitumor effects in many types of tumor cells. However, the effects of TSN on glioma cells have rarely been reported. METHODS: Different assays were performed to investigate the effects of TSN on the different glioma cell lines including U87MG and LN18. The assays included colony formation, wound healing, and transwell assays. Furthermore, Hoechst 33342 staining, flow cytometry, and western blotting analysis were performed to investigate the apoptotic activities of TSN. Finally, the results were confirmed using a xenograft tumor model that comprised of nude mice. RESULTS: In vitro, the CCK-8 and colony formation assays showed that TSN effectively inhibited glioma cell proliferation. Moreover, the inhibitory effects on glioma cell migration and invasion were demonstrated through the wound healing and transwell assays, respectively. Hoechst 33342 staining, flow cytometry, and western blotting assays demonstrated the significant effect of TSN in the apoptosis induction of glioma cells. Furthermore, the anti-glioma effect of TSN was exerted through the inhibition of the PI3K/Akt/mTOR signaling pathways as demonstrated by western blotting analysis. In addition, the effects of TSN on glioma cell viability, apoptosis, cell cycle arrest, migration, and invasion were reversed by 740Y-P, a PI3K activator. Finally, the mouse xenograft model confirmed the suppressive effect of TSN on tumor growth in vivo. CONCLUSION: Our results suggest that TSN is a promising chemotherapeutic drug for patients with glioma.

Non-invasive skin cholesterol testing: a potential proxy for LDL-C and apoB serum measurements.

BACKGROUND: Lipid management is the first line of treatment for decreasing the incidence of cardiovascular events in patients with coronary heart disease (CHD), and a variety of indicators are used to evaluate lipid management. This work analyses the differences in LDL-C and apoB for lipid management evaluation, as well as explores the feasibility of skin cholesterol as a marker that can be measured non-invasively for lipid management. METHODS: The prospective study enrolled 121 patients who had been diagnosed with acute coronary syndrome (ACS) at the department of emergency medicine of the First Affiliated Hospital of the USTC from May 2020 to January 2021, and the patients were grouped into Group I (n=53) and Group II (n=68) according to whether they had comorbid hyperlipidemia and/or diabetes mellitus. All patients were administered 10 mg/day of rosuvastatin and observed for 12 weeks. Lipid management was assessed on the basis of LDL-C and apoB, and linear correlation models were employed to assess the relationship between changes in these well accepted markers to that of changes in skin cholesterol. RESULTS: Out of 121 patients with ACS, 53 patients (43.80 %) had combined hyperlipidemia and/or diabetes mellitus (Group I), while 68 patients (56.20 %) did not (Group II). Cardiovascular events occur at earlier ages in patients with CHD who are comorbid for hyperlipidemia and/or diabetes (P<0.05). LDL-C attainment rate is lower than apoB attainment rate with rosuvastatin therapy (P<0.05), which is mainly attributable to patients with low initial LDL-C. Skin cholesterol reduction correlated with LDL-C reduction. (r=0.501, P<0.001) and apoB reduction (r=0.538, P<0.001). Skin cholesterol reduction continued over all time points measured. CONCLUSIONS: Examination of changes in apoB levels give patients with low initial LDL-C more informative data on lipid management than LDL-C readings. In addition, non-invasive skin cholesterol measurements may have the potential to be used independently for lipid management evaluation.

Sustaining Circulating Regulatory T Cell Subset Contributes to the Therapeutic Effect of Paroxetine on Mice With Diabetic Cardiomyopathy.

BACKGROUND: G protein coupled receptor kinase 2 (GRK2) inhibitor, paroxetine, has been approved to ameliorate diabetic cardiomyopathy (DCM). GRK2 is also involved in regulating T cell functions; the potential modifications of paroxetine on the immune response to DCM is unclear.Methods and Results:DCM mouse was induced by high-fat diet (HFD) feeding. A remarkable reduction in the regulatory T (Treg) cell subset in DCM mouse was found by flow cytometry, with impaired cardiac function evaluated by echocardiography. The inhibited Treg differentiation was attributable to insulin chronic stimulation in a GRK2-PI3K-Akt signaling-dependent manner. The selective GRK2 inhibitor, paroxetine, rescued Treg differentiation in vitro and in vivo. Furthermore, heart function, as well as the activation of excitation-contraction coupling proteins such as phospholamban (PLB) and troponin I (TnI) was effectively promoted in paroxetine-treated DCM mice compared with vehicle-treated DCM mice. Blockade of FoxP3 expression sufficiently inhibited the proportion of Treg cells, abolished the protective effect of paroxetine on heart function as well as PLB and TnI activation in HFD-fed mice. Neither paroxetine nor carvedilol could effectively ameliorate the metabolic disorder of HFD mice. CONCLUSIONS: The impaired systolic heart function of DCM mice was effectively improved by paroxetine therapy, partially through restoring the population of circulating Treg cells by targeting the GRK2-PI3K-Akt pathway.

Soluble ST2 as a possible biomarker for inflammation in patients with acute heart failure.

AIM: The aim of this study was to explore the relationship between peripheral circulating serum soluble suppression of tumorigenicity-2 (sST2) levels and inflammatory biomarkers in patients with acute heart failure (AHF). METHODS: One hundred and eleven consecutive AHF patients with NYHA class II-IV were enrolled, and peripheral blood was collected within 24 h of admission for the detection of NT-ProBNP, sST2, hypersensitive troponin I, cytokines, precalcitoninogen, C-reactive protein, in addition to routine standard of care blood tests. RESULTS: The median sST2 of 111 patients was 47.50 ng/ml (24.25-86.15 IQR), of whom 43 patients (38.7%) had sST2 35 ng/ml or less; linear correlation analysis showed that serum sST2 correlated with NT-ProBNP ( r2  = 0.32), NEU% ( r2  = 0.41), NLR ( r2  = 0.36), CRP ( r2  = 0.50), IL-18 ( r2  = 0.43) ( P  < 0.001), and correlated with Hs-cTnI ( r2  = 0.19), NUE ( r2  = 0.25), LYM ( r2  = -0.23), IL-2RA ( r2  = 0.29) ( P  < 0.05). Multiple linear regression analysis depicted that CRP (ß = 0.318), IL-18 (ß = 0.368), NEU% (ß = 0.346), NLR (ß = -0.304), and NT-ProBNP (ß = 0.324) significantly correlated with sST2 values, respectively ( P  < 0.05). ST2 levels have a linear association with length of hospitalization. CONCLUSION: Peripheral blood inflammatory markers (CRP, IL-18, NEU%, NLR) in patients with AHF had a close relationship with sST2 levels, and the mechanism of action of sST2 may be related to the inflammatory response.

PD-L2 drives resistance to EGFR-TKIs: dynamic changes of the tumor immune environment and targeted therapy.

There is a lack of effective treatments to overcome resistance to EGFR-TKIs in EGFR mutant tumors. A deeper understanding of resistance mechanisms can provide insights into reducing or eliminating resistance, and can potentially deliver targeted treatment measures to overcome resistance. Here, we identified that the dynamic changes of the tumor immune environment were important extrinsic factors driving tumor resistance to EGFR-TKIs in EGFR mutant cell lines and syngeneic tumor-bearing mice. Our results demonstrate that the acquired resistance to EGFR-TKIs is accompanied by aberrant expression of PD-L2, leading a dynamic shift from an initially favorable tumor immune environment to an immunosuppressive phenotype. PD-L2 expression significantly affected EGFR mutant cell apoptosis that depended on the proportion and function of CD8+ T cells in the tumor immune environment. Combined with single-cell sequencing and experimental results, we demonstrated that PD-L2 specifically inhibited the proliferation of CD8+ T cells and the secretion of granzyme B and perforin, leading to reduced apoptosis mediated by CD8+ T cells and enhanced immune escape of tumor cells, which drives EGFR-TKIs resistance. Importantly, we have identified a potent natural small-molecule inhibitor of PD-L2, zinc undecylenate. In vitro, it selectively and potently blocks the PD-L2/PD-1 interaction. In vivo, it abolishes the suppressive effect of the PD-L2-overexpressing tumor immune microenvironment by blocking PD-L2/PD-1 signaling. Moreover, the combination of zinc undecylenate and EGFR-TKIs can synergistically reverse tumor resistance, which is dependent on CD8+ T cells mediating apoptosis. Our study uncovers the PD-L2/PD-1 signaling pathway as a driving factor to mediate EGFR-TKIs resistance, and identifies a new naturally-derived agent to reverse EGFR-TKIs resistance.

Intraoperative radiotherapy in recurrent IDH-wildtype glioblastoma with gross total resection: A single-center retrospective study.

BACKGROUND: Isocitrate dehydrogenase-wildtype (IDHwt) glioblastoma (GBM) is one of the most aggressive primary brain tumors. The recurrence of GBM is almost inevitable. As an adjuvant option to surgery, intraoperative radiotherapy (IORT) is gaining increasing attention in the treatment of glioma. This study is aimed to evaluate the therapeutic efficacy of IORT on recurrent IDHwt GBM. METHODS: In total, 34 recurrent IDHwt GBM patients who received a second surgery were included in the analysis (17 in the surgery group and 17 in the surgery + IORT group). RESULTS: The progression-free survival and overall survival after the second surgery were defined as PFS2 and OS2, respectively. The median PFS2 was 7.3 months (95% CI: 6.3-10.5) and 10.6 months (95% CI: 9.3-14.6) for those patients who received surgery and surgery + IORT, respectively. Patients in the surgery + IORT group also had a longer OS2 (12.8 months, 95% CI: 11.4-17.2) than those in the surgery group (9.3 months, 95% CI: 8.9-12.9). The Kaplan-Meier survival curves, analyzed by log-rank test, revealed a statistically significant difference in PFS2 and OS2 between both groups, suggesting that IORT plays an active role in the observed benefits for PFS2 and OS2. The effects of IORT on PFS2 and OS2 were further confirmed by multivariate Cox hazards regression analysis. Two patients in the surgery group developed distant glioma metastases, and no radiation-related complications were observed in the IORT group. CONCLUSIONS: This study suggests that low-dose IORT may improve the prognosis of recurrent IDHwt GBM patients. Future prospective large-scale studies are needed to validate the efficacy and safety of IORT.

D-Mannitol/Graphene Phase-Change Composites with Structured Conformation and Thermal Pathways Allow Durable Solar-Thermal-Electric Conversion and Electricity Output.

Durable electricity generation from a phase-change material (PCM)-assisted solar thermoelectric generator (STEG) through photo-thermal-electric conversion is a promising way to take advantage of the clean solar energy. However, due to the deficient and mismatched thermal charging and discharging rates in the PCMs, the previous PCM-supported STEGs usually exhibit inefficient solar-thermal-electric conversion (<1%) and limited electricity output. In this work, we report a structured D-mannitol/graphene phase-change composite fabricated by a radial ice-template assembly and infiltration strategy, in which radially aligned graphene nanoplates are bridged by graphitized polyimide that offers multidirectional and interlaced thermal highways for rapid thermal charging, while the sample conformation is further regulated by the ice-template mold, promising the optimal charging and discharging balance in the PCM. After being integrated with a solar concentrator and a thermoelectric device, this powerful STEG outputs tremendous power density, with the solar-thermal-electric conversion approaching 2.40%. The plenteous electricity supply is demonstrated to reliably charge a mobile phone under normal sunlight. This elaborate STEG design opens up opportunities for providing sufficient power guarantees for the self-powering of electronic devices in the wild.

Anticancer effects of OSW-1 on glioma cells via regulation of the PI3K/AKT signal pathway: A network pharmacology approach and experimental validation in vitro and in vivo.

Background: Gliomas are the most common primary intracranial malignant tumors with poor prognosis, despite the remarkable advances in medical technology that have been made. OSW-1, isolated from Ornithogalum saundersiae, possesses anticancer activity against various malignant cancer cells. However, the effects of OSW-1 on gliomas and its potential mechanisms remain unclear. Methods: Network pharmacology was employed for predicting potential key targets and mechanisms of the anticancer effects of OSW-1 on glioma. Experiments, including the Cell Counting Kit-8, colony formation, and flow cytometry, were performed to investigate how OSW-1 affects the biological behavior of glioma cells in vitro. Western blotting was used to detect changes in related proteins, such as those involved in the cell cycle, apoptosis, and signaling pathways. The nude mouse xenograft model was used to detect the effect of OSW-1 on inhibiting the proliferation of glioma cells in vivo. Results: An "OSW-1-Targets-Glioma" intersection network consisting of 151 intersecting genes was acquired to construct a "Protein-Protein Interaction network" and predict the top 10 core targets. According to the Kyoto Encyclopedia of Genes and Genomes pathway analysis, the PI3K/AKT signaling pathway was the top 3-ranked pathway, with 38 enriched intersecting genes. The glioma T98G and LN18 cell lines were used to verify the predictions. OSW-1 significantly inhibited the viability and proliferation of glioma cells in a dose- and time-dependent manner. Flow cytometry showed that OSW-1 arrested the cell cycle at the G2/M phase, and the apoptotic ratio of glioma cells increased significantly with increasing concentrations. Western blotting revealed that the expression levels of p-PI3K and p-AKT1 in glioma cells treated with OSW-1 were significantly lower than those in the controls; however, 740Y-P, a PI3K activator, significantly reversed the inactivation of the PI3K/AKT signaling pathway caused by OSW-1. Furthermore, the mouse xenograft model confirmed the suppressive effect of OSW-1 on tumor growth in vivo. Conclusion: OSW-1 is a promising anti-glioma chemotherapeutic drug owing to its anticancer effects via downregulation of the PI3K/AKT signaling pathway. However, OSW-1 still has a long way to go to become a real anti-glioma drug.

Anticancer Effects of I-BET151, an Inhibitor of Bromodomain and Extra-Terminal Domain Proteins.

I-BET151 is an inhibitor of bromodomain and extra-terminal domain (BET) proteins that selectively inhibits BET family members (BRD2, BRD3, BRD4, and BRDT). Over the past ten years, many studies have demonstrated the potential of I-BET151 in cancer treatment. Specifically, I-BET151 causes cell cycle arrest and inhibits tumor cell proliferation in some hematological malignancies and solid tumors, such as breast cancer, glioma, melanoma, neuroblastoma, and ovarian cancer. The anticancer activity of I-BET151 is related to its effects on NF-κB, Notch, and Hedgehog signal transduction pathway, tumor microenvironment (TME) and telomere elongation. Remarkably, the combination of I-BET151 with select anticancer drugs can partially alleviate the occurrence of drug resistance in chemotherapy. Especially, the combination of forskolin, ISX9, CHIR99021, I-BET151 and DAPT allows GBM cells to be reprogrammed into neurons, and this process does not experience an intermediate pluripotent state. The research on the anticancer mechanism of I-BET151 will lead to new treatment strategies for clinical cancer.

Anticancer Effects and Mechanisms of OSW-1 Isolated From Ornithogalum saundersiae: A Review.

For centuries, cancer has been a lingering dark cloud floating on people's heads. With rapid population growth and aging worldwide, cancer incidence and mortality are growing rapidly. Despite major advances in oncotherapy including surgery, radiation and chemical therapy, as well as immunotherapy and targeted therapy, cancer is expected be the leading cause of premature death in this century. Nowadays, natural compounds with potential anticancer effects have become an indispensable natural treasure for discovering clinically useful agents and made remarkable achievements in cancer chemotherapy. In this regards, OSW-1, which was isolated from the bulbs of Ornithogalum saundersiae in 1992, has exhibited powerful anticancer activities in various cancers. However, after almost three decades, OSW-1 is still far from becoming a real anticancer agent for its anticancer mechanisms remain unclear. Therefore, in this review we summarize the available evidence on the anticancer effects and mechanisms of OSW-1 in vitro and in vivo, and some insights for researchers who are interested in OSW-1 as a potential anticancer drug. We conclude that OSW-1 is a potential candidate for anticancer drugs and deserves further study.

Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells.

Glioma is the most general primary and lethal intracranial malignant tumor. Pterostilbene (PTE), an analog of stilbene and resveratrol, has attracted attention in recent years due to its significant antitumor activity in multiple solid tumors; however, its effect on drug-resistant glioma cells and the underlying mechanism have not yet been reported. In this study, we found that pterostilbene inhibited proliferation, induced intrinsic mitochondria-mediated apoptosis and caused S phase arrest, inhibited migration and excessive invasion in glioma cells. Pretreatment with the pan-caspase-inhibitor Z-VAD-FMK attenuated the PTE-induced apoptosis of glioma cells. Moreover, PTE significantly increased the production of reactive oxygen species (ROS) and reduce the mitochondrial membrane potential (MMP). Inhibition of ROS with N-acetyl-L-cysteine not only rescued PTE-induced reduction of cellular viability but also prevented glioma cell apoptosis. We also discovered ERK 1/2 and JNK signaling pathways were activated by PTE and contributed to induce glioma cell apoptosis. In addition, specific inhibitors of ERK 1/2 and JNK attenuated PTE-induced apoptosis. Besides, PTE significantly reduced tumor volume and prolonged median survival of tumor-bearing rats in vivo. In summary, the results of this study indicate that the anti-tumor effect of PTE on glioma cells may provide a new treatment option for glioma patients.

Berberine Inhibits Cell Proliferation by Interfering with Wild-Type and Mutant P53 in Human Glioma Cells.

INTRODUCTION: Glioma is the most common malignant brain tumor. TP53 is the most common mutant gene in human cancer. Wild-type p53 (wtp53) is a tumor suppressor protein whereas mutant p53 (mutp53) is an oncoprotein that promotes tumor cell proliferation. Our aim was to examine the inhibitory effects of berberine on the proliferation of human glioma cells via regulation of wtp53, mutp53, and their downstream molecules. METHODS: We selected wtp53 cells (U87 cells) and mutp53 cells (U251 cells termed p53 R273H) to examine the inhibitory effects of berberine on human glioma cells. We used the CCK-8 kit to detect the toxic effect of berberine. Flow cytometry was used to detect the effect of berberine. Clone formation test was used to test the inhibitory effect of berberine on the proliferation of glioma cells. Western blot was used to detect the changes of related proteins such as p53, p-p53, p21 and cyclin D1. Lentivirus transduction was used to transduce wild-type p53 into U251 cells to further examine the effect of berberine. The nude mouse subcutaneous tumor model was used to detect the effect of berberine on inhibiting the proliferation of glioma cells in vivo. RESULTS: Berberine promoted the phosphorylation of wtp53, increased the expression of p21 protein, reduced cyclin D1 content, and caused G1 phase arrest in U87 cells. Berberine also reduced mutp53 content and caused G2 phase arrest in U251 cells with a concurrent decrease in p21, cyclin D1, and cyclin B1 content. Transduction with wtp53 enhanced the effects on cell cycle arrest. Further, berberine significantly inhibited glioma growth in vivo mouse tumor model. DISCUSSION: Glioma is a group of heterogeneous brain tumors with unique biological and clinical characteristics. Berberine can inhibit glioma cells through a variety of ways. Our research indicated that berberine inhibited the proliferation of glioma cells by interfering with wtp53 and mutp53. This indicates that berberine could be used as a potential drug to treat wild-type and mutant p53 glioma.