TTD: Therapeutic Target Database describing target druggability information.

Target discovery is one of the essential steps in modern drug development, and the identification of promising targets is fundamental for developing first-in-class drug. A variety of methods have emerged for target assessment based on druggability analysis, which refers to the likelihood of a target being effectively modulated by drug-like agents. In the therapeutic target database (TTD), nine categories of established druggability characteristics were thus collected for 426 successful, 1014 clinical trial, 212 preclinical/patented, and 1479 literature-reported targets via systematic review. These characteristic categories were classified into three distinct perspectives: molecular interaction/regulation, human system profile and cell-based expression variation. With the rapid progression of technology and concerted effort in drug discovery, TTD and other databases were highly expected to facilitate the explorations of druggability characteristics for the discovery and validation of innovative drug target. TTD is now freely accessible at: https://idrblab.org/ttd/.

Molecular genetic mechanisms of teratozoospermia.

In recent years, the incidence of teratospermia has been increasing, and it has become a very important factor leading to male infertility. The research on the molecular mechanism of teratospermia is also progressing rapidly. This article briefly summarizes the clinical incidence of teratozoospermia, and makes a retrospective summary of related studies reported in recent years. Specifically discussing the relationship between gene status and spermatozoa, the review aims to provide the basis for the genetic diagnosis and gene therapy of teratozoospermia.

Dihydrotriazine derivatives display high anticancer activity and inducing apoptosis, ROS, and autophagy.

A series of dihydrotriazine derivatives bearing 5-aryloxypyrazole moieties were designed, and their anticancer activities against three human cancer cell lines (SGC-7901, HepG-2 and MCF-7) and one non-cancer cell line (LO2) were explored using the MTT assay in vitro. Most of the compounds exhibited potent antiproliferative activities against the three cancer cell lines, with compound 10e (IC50 = 2.12 µM) exhibiting the most potent antiproliferative activity against HepG-2 cells. Interestingly, autophagy was observed in the 10e-treated HepG-2 cells. Compound 10e also increased reactive oxygen species (ROS) levels and resulted in marked HepG-2 cells apoptosis. Further studies revealed that compound 10e could enhance the expression of Cl-PARP, Cl-caspase-3, and Cl-caspase-9. In addition, 10e triggered the formation of autophagosomes by promoting LC3-II and Beclin-1 expression. These results might be useful for exploring and developing dihydrotriazine derivatives as novel anticancer agents.

New ursolic acid derivatives bearing 1,2,3-triazole moieties: design, synthesis and anti-inflammatory activity in vitro and in vivo.

In order to discover novel anti-inflammatory agents, three series of compounds obtained by appending 1,2,3-triazole moieties on ursolic acid were designed and synthesized. All compounds have been screened for their anti-inflammatory activity by using an ear edema model. The potent anti-inflammatory compound was subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assays. In general, the derivatives were found to be potent anti-inflammatory activity. Especially, the compound 11b exhibited the strongest activity of all of the compounds prepared, with 82.81% inhibition after intraperitoneal administration, which was better than celecoxib as a positive control. Molecular docking results unclose the rationale for the interaction of the compound 11b with COX-2 enzyme. Further studies revealed that compound 11b exhibited effective COX-2 inhibitory activity, with half-maximal inhibitor concentration (IC50) value of 1.16 µM and selectivity index (SI = 64.66) value close to that of celecoxib (IC50 = 0.93 µM, SI = 65.47). Taken together, these results could suggest a promising chemotype for development of new COX-2-targeting anti-inflammatory agent.

Synthesis, Characterization and Biological Evaluation of Benzothiazole-Isoquinoline Derivative.

Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi-target-directed ligands (MTDLs), we synthesized a series of (R)-N-(benzo[d]thiazol-2-yl)-2-(1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl) acetamides with substituted benzothiazoles and (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. All compounds were tested for their inhibitory potency against monoamine oxidase (MAO) and cholinesterase (ChE) by in vitro enzyme activity assays, and further tested for their specific inhibitory potency against monoamine oxidase B (MAO-B) and butyrylcholinesterase (BuChE). Among them, six compounds (4b-4d, 4f, 4g and 4i) displayed excellent activity. The classical antidepressant forced swim test (FST) was used to verify the in vitro results, revealing that six compounds reduced the immobility time significantly, especially compound 4g. The cytotoxicity of the compounds was assessed by the MTT method and Acridine Orange (AO) staining, with cell viability found to be above 90% at effective compound concentrations, and not toxic to L929 cells reversibility, kinetics and molecular docking studies were also performed using compound 4g, which showed the highest MAO-B and BuChE inhibitory activities. The results of these studies showed that compound 4g binds to the primary interaction sites of both enzymes and has good blood-brain barrier (BBB) penetration. This study provides new strategies for future research on neurodegenerative diseases complicated by depression.

Fsk and IBMX inhibit proliferation and proapoptotic of glioma stem cells via activation of cAMP signaling pathway.

OBJECTIVE: We aimed to find out the underlying mechanism of forskolin (Fsk) and 3-isobutyl-1-methylxanthine (IBMX) on glioma stem cells (GSCs). METHODS: The expression of cAMP-related protein CREB and pCREB as well as apoptosis-related proteins were detected through Western blot analysis. The level of proliferation and growth rate of human GSCs was measured through thiazolyl blue tetrazolium bromide assay and stem cells forming sphere assay. The apoptosis-related gene expression was measured through reverse transcription-polymerase chain reaction. RESULTS: cAMP signaling pathway was activated in GSCs with Fsk-IBMX administration. Fsk-IBMX could inhibit the proliferation as well as invasion and promote the apoptosis of U87 cells. Besides, U0126 could inhibit MAPK signaling pathway to increase the sensitivity of GSCs to cAMP signaling pathway. As a result, Fsk-IBMX combined with U0126 had more negative effect on GSCs. CONCLUSIONS: The relationship of cAMP and MAPK signaling pathway in GSCs may provide a potential therapeutic strategy in glioma.

Simultaneous determination of ferulic acid and gastrodin of Tianshu Capsule in rat plasma by ultra-fast liquid chromatography with tandem mass spectrometry and its application to a comparative pharmacokinetic study in normal and migraine rats.

Tianshu Capsule, consisting of Ligusticum chuanxiong Hort and Gastrodia elata Blume, is a widely used Traditional Chinese Medicine preparation for the treatment of migraine. Ferulic acid and gastrodin are main active constituents in Ligusticum chuanxiong Hort and Gastrodia elata Blume, and have been used as marker components for quality control of Tianshu Capsule. In this study, a selective, sensitive, and reliable ultra-fast liquid chromatography with tandem mass spectrometry method was developed for simultaneous determination of ferulic acid and gastrodin in rat plasma using geniposide as internal standard. The plasma samples were extracted by protein precipitation with methanol after acidification and separated on a Shim-Pack XR-ODS C18 column (75 × 3.0 mm, 2.2 µm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.6 mL/min. Detection was performed on 3200 QTRAP mass spectrometry equipped with turbo ion spray source in negative ionization mode. Validation parameters were within acceptable ranges. The validated method was applied to compare the pharmacokinetic profiles of ferulic acid and gastrodin in normal and migraine rats. Our results showed that there were remarkable differences in the pharmacokinetic properties of the analytes between the normal and migraine groups.

Tanshinone IIA Affects Autophagy and Apoptosis of Glioma Cells by Inhibiting Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway.

OBJECTIVE: To test the effects of Tanshinone IIA (Tan IIA) on cell viability, cycle, apoptosis, and autophagy of human glioma cell U251 by regulating phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signal pathway. METHODS: Tan IIA and PI3K agonist (740 Y-P) were used to treat glioma cells U251. MTT assay was used to assess cell viability and flow cytometry was used to detect cell apoptosis and cell cycle. The expressions of apoptosis-related proteins (Bcl-2 and Bax), autophagy-related proteins (LC3B and Beclin 1) and PI3K/Akt/mTOR signal pathway-associated proteins (p-PI3K, p-Akt and p-mTOR) were evaluated by Western blotting. RESULTS: Tan IIA decreased the expression of p-PI3K and p-Akt proteins, inhibited cell viability and promoted apoptosis. Meanwhile, the expression of Bax increased, while the expression of Bcl-2 decreased. In addition, Tan IIA promoted autophagy in U251 glioma cells and raised the expression of LC3B and Beclin 1. However, 740 Y-P played a reversed role of Tan IIA in cell viability, cycle, apoptosis, and autophagy of U251 cells. CONCLUSION: Tan IIA could suppress the viability of U251 cells and induce cell apoptosis and autophagy, which might be related to the inhibition of the PI3K/Akt/mTOR signal pathway.

Structural Features and Potent Antidepressant Effects of Total Sterols and ß-sitosterol Extracted from Sargassum horneri.

The purified total sterols and ß-sitosterol extracted from Sargassum horneri were evaluated for their antidepressant-like activity using the forced swim test (FST) and tail suspension test (TST) in mice. Total sterols and ß-sitosterol significantly reduced the immobility time in the FST and TST. Total sterols were administered orally for 7 days at doses of 50, 100, and 200 mg/kg, and ß-sitosterol was administered intraperitoneally at doses of 10, 20, and 30 mg/kg. ß-sitosterol had no effect on locomotor activity in the open field test. In addition, total sterols and ß-sitosterol significantly increased NE, 5-HT, and the metabolite 5-HIAA in the mouse brain, suggesting that the antidepressant-like activity may be mediated through these neurotransmitters.

Long Noncoding RNA lncCAMTA1 Promotes Proliferation and Cancer Stem Cell-Like Properties of Liver Cancer by Inhibiting CAMTA1.

Hepatocellular carcinoma (HCC) is the most common subtype of liver malignancy, and it is characterized by poor prognosis because of cancer stem cell (CSC)-mediated high postsurgical recurrence rates. Thus, targeting CSCs, or HCC cells with CSC-like properties, is an effective strategy for HCC therapy. Here, using long noncoding RNA (lncRNA) microarray analysis, we identified a novel lncRNA termed lncCAMTA1 that is increased in both liver CSCs and HCC. High lncCAMTA1 expression in HCC indicates poor clinical outcome. In vitro and in vivo functional experiments showed that overexpression of lncCAMTA1 promotes HCC cell proliferation, CSC-like properties, and tumorigenesis. Conversely, depletion of lncCAMTA1 inhibits HCC cell proliferation, CSC-like properties, and tumorigenesis. Mechanistically, we demonstrated that lncCAMTA1 physically associates with the calmodulin binding transcription activator 1 (CAMTA1) promoter, induces a repressive chromatin structure, and inhibits CAMTA1 transcription. Furthermore, CAMTA1 is required for the effects of lncCAMTA1 on HCC cell proliferation and CSC-like properties, and the expression of lncCAMTA1 and CAMTA1 is significantly negatively correlated in HCC tissues. Collectively, our study revealed the important roles and underlying molecular mechanisms of lncCAMTA1 on HCC, and suggested that lncCAMTA1 could be an effective prognostic factor and a potential therapeutic target for HCC.

Limited sampling strategy for predicting area under the concentration-time curve for mycophenolic Acid in Chinese adults receiving mycophenolate mofetil and tacrolimus early after renal transplantation.

BACKGROUND: The objective of the study was to investigate the pharmacokinetics of mycophenolate mofetil (MMF) in Chinese adults early after renal transplantation by an enzyme multiplied immunoassay technique and to establish a limited sampling strategy to predict the area under the concentration-time curve for plasma levels of mycophenolic acid (MPA-AUC). METHODS: Fifty-eight recipients who underwent renal transplantation with an organ donated after cardiac death used a triple immunosuppressant strategy of MMF, tacrolimus, and prednisone. On the seventh day posttransplantation, plasma samples were collected at 0 hours (pre-dose) and at 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours postdose (C0h, C0.5h, C1h, C1.5h, C2h, C4h, C6h, C8h, C10h, and C12h, respectively). Enzyme multiplied immunoassay technique was used to measure mycophenolic acid concentration, and model equations were generated by multiple stepwise regression analysis to determine MPA-AUC0-12h. RESULTS: The 3-point equation obtained by multiple linear regression analysis was MPA-AUC = 7.951 + 4.04C6h + 1.893C2h + 4.542C10h (adjusted r = 0.863); the 4-point equation was MPA-AUC = 4.272 + 4.074C6h + 1.896C2h + 4.680C10h + 0.859C0.5h (adjusted r = 0.918). The % mean prediction error, % mean absolute error, and % root mean squared prediction error for the best-fit formula using C6h, C2h, C10h, and C0.5h were -0.2%, 8.7%, and 14.2%, respectively. CONCLUSIONS: In Chinese adults receiving MMF and tacrolimus early after renal transplantation, the best equation for predicting MPA-AUC0-12h is 4.272 + 4.074C6h + 1.896C2h + 4.680C10h + 0.859C0.5h.

Pulmonary hypertension risk in patients with hemoglobin h disease: low incidence and absence of correlation with splenectomy.

Pulmonary hypertension (PHT) is a common complication for patients with ß thalassemia intermediate (TI), especially splenectomized patients. However, the frequency and risk factors of PHT in patients with hemoglobin H (HbH) disease is unknown. The purpose of this study was to identify the prevalence of PHT risk manifested as tricuspid regurgitant jet velocity (TRV) ≥2.5 m/s in patients with HbH disease and its correlation with splenectomy. One hundred and ninety-eight patients with HbH disease who visited the 303rd Hospital of the People's Liberation Army (Nanning, China) were investigated. Thirteen subjects (6.5%) were diagnosed as having a risk of PHT. Regression analyses showed that the prevalence of PHT risk was correlated only with age (r = 0.195, p = 0.006) and not with splenectomy. The risk of PHT in patients older than 35 years was 5.7 times (range 1.8-18.6) greater than that for patients younger than 35 years. For splenectomized patients compared to those with HbH disease, patients with TI had a higher frequency of PHT risk, higher nucleated red blood cell counts (46.03 ± 41.11 × 10(9)/l vs. 0.18 ± 1.19 × 10(9)/l, p < 0.001) and a higher platelet counts (837.6 ± 178.9 × 10(9)/l vs. 506.7 ± 146.2 × 10(9)/l, p < 0.001). PHT risk is low in patients with HbH disease and does not correlate with splenectomy. Patients older than 35 years should be monitored regularly.

[Efficacy of Schizandra chinesis polysaccharide on cyclophosphamide induced dyszoospermia of rats and its effects on reproductive hormones].

OBJECTIVE: To explore the efficacy of Schizandra Chinensis polysaccharide (SCP) on cyclophosphamide (CTX) induced dyszoospermia of rats and its effects on reproductive hormones. METHODS: SCP was extracted by ethanol-alkali solution. Fifty male Wistar rats were randomly divided into 5 groups, i.e., the normal control group, the model group, the low dose SCP group (100 mg/kg), the middle dose SCP group (200 mg/kg), and the high dose SCP group (400 mg/kg). Except the normal control group, the dyezoospermia rat model was established by peritoneal injection of CTX at the daily dose of 80 mg/kg, once daily for 5 successive days. After modeling, SCP was intragastrically administered at corresponding dose to the three SCP groups. Equal volume of normal saline was given to rats in the normal control group and the model group by gastrogavage. All the medication was performed once daily for 60 successive days. The blood serum and testis were withdrawal 24 h after the last intragastric administration. The levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) in the testis homogenate were determined by enzyme linked immunosorbent assay. The sperm count, the motility rate, and the teratospermia rate were compared. The morphology of the testis was observed using HE staining. RESULTS: Compared with the normal control group, the sperm count and the motility rate decreased, the teratospermia rate increased, the serum levels of FSH and LH increased, the T content in the testis homogenate decreased in the model group, showing statistical difference (P <0.01). Compared with the model group, the sperm count and the motility rate increased, the teratospermia rate decreased, the serum levels of FSH and LH decreased, the T content in the testis homogenate increased in the model group, showing statistical difference (P <0.01, P <0.05). All the indices showed dose-dependent manner in the SCP groups. The histological results showed the pathological injury in the testicular tissue was improved in all SCP groups. CONCLUSION: SCP showed obvious therapeutical effects on CTX induced dyszoospermia in rats, and its mechanisms might be correlate with recovering the regulation function of hypothalamus-hypophysis-gonad axis.

Echinacoside Protects Against Dysfunction of Spermatogenesis Through the MAPK Signaling Pathway.

Dysfunction at various levels of spermatogenesis (SD) is one of the important causes of infertility in men of reproductive age and requires advanced treatment strategies. Increasing evidence suggests that the therapeutic effects of echinacoside (ECH) mainly depend on their capacity to inhibit cell death. This study aimed to explore the therapeutic potential of ECH in SD rat models. Treatment with ECH reverted the morphological changes observed in testes with spermatogenesis dysfunction. It improved total sperm number, decreased the sperm deformity rate, and increased the sperm forward motility rate. The level of glutathione (GSH) was significantly higher in ECH-treated mice, whereas the lactate dehydrogenase (LDH) and SOD activities were improved compared with those in the spermatogenesis dysfunction model. Moreover, the increased expression of p38 and JNK was partially reversed by ECH. The number of normal TM3 cells increased gradually in an Echinacea dosage-dependent manner, suggesting that ECH promoted the proliferation of TM3 cells. In addition, treatment with ECH partially reversed the increased expression of p38 and JNK in TM3 cells. ECH protects against oxidative stress damage by activating antioxidant enzymes and MAPK signaling-related factors (p38 and JNK). It suggested that treatment with ECH alleviated spermatogenetic dysfunction of testes in male mice and it could be a promising strategy for patients suffering severe SD.

Thermo- and Light-Responsive Polymer-Coated Magnetic Nanoparticles as Potential Drug Carriers.

A series of thermo- and light-responsive copolymers of poly (N-isopropylacrylamide) (PNIPAM) and 6-[4-(4-methoxy phenyl azo)-phenoxyl-hexyl methacrylate) (AzoMA) (PNIPAM-b-PAzoMA) were synthesized via reversible addition-fragmentation chain transfer (RAFT) radical polymerization. The resulting copolymers had a narrow molecular weight distribution range of 1.06-1.24, in which M n changed regularly with the monomer concentration. Subsequently, the diblock copolymers were successfully modified on the surface of iron oxide nanoparticles through the interaction between the chemical bonds to prepare Fe3O4@(PNIPAM-b-PAzoMA) nanoparticles. The size of fabricated nanoparticles with excellent thermo-sensitivity and photo-sensitivity was controlled at about 40-50 nm. Cell viability assays suggested that the nanoparticles showed no significant cytotoxicity and potential drug delivery in the tumor microenvironment.

Stem Cell-Based Therapy for Asherman Syndrome: Promises and Challenges.

Asherman syndrome (AS) has an adverse effect on reproductive health and fertility by affecting endometrial regeneration. Stem cell-based therapies hold promise for future use in activating non-functional endometrium and reconstructing the endometrium in vivo. It has been postulated that various endometrial stem cells (EnSCs) are responsible for endometrial regeneration. Numerous studies have focused on bone marrow-derived stem cells (BMDSCs), which may provide new ideas for repairing endometrial lesions and reconstructing the endometrium. Other sources of stem cells, such as menstrual blood, umbilical cord, and amniotic membrane, have also attracted much attention as candidates for transplantation in AS. This review discusses the features and specific biomarkers among four types of resident endometrial stem cells, applications of four different sources of exogenous stem cells in AS, and development of stem cell therapy using biomaterials and exosomes.

The Role of Immune Cells in Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion affects approximately 1-2% of women of childbearing, and describes a condition in which women suffer from three or more continuous spontaneous miscarriages. However, the origin of recurrent spontaneous abortion (RSA) remains unknown, preventing effective treatment and placing stress upon patients. It has been acknowledged that successful pregnancy necessitates balanced immune responses. Therefore, immunological aberrancy may be considered a root cause of poor pregnancy outcomes. Considerable published studies have investigated the relationship between various immune cells and RSA. Here, we review current knowledge on this area, and discuss the five main categories of immune cells involved in RSA; these include innate lymphocytes (ILC), macrophages, decidual dendritic cells (DCs), and T cells. Furthermore, we sought to summarize the impact of the multiple interactions of various immune cells on the emergence of RSA. A good understanding of pregnancy-induced immunological alterations could reveal new therapeutic strategies for favorable pregnancy outcomes.

Circular RNA circitga7 accelerates glioma progression via miR-34a-5p/VEGFA axis.

Circular RNAs (circRNAs) are a group of noncoding RNAs derived from back-splicing events. CircRNA is reported to be involved in various tumor progressions, including glioma. Although there are a few reports of circular RNAs participating in gliomas, it is still unclear whether circular RNAs regulate the occurrence of gliomas. In our research, we found that the expression of circITGA7 in glioma tissues and glioma cells increased significantly. Knocking down circITGA7 can significantly inhibit the proliferation of glioma cells and reduce cell metastasis. Through analysis and dual-luciferase report assay, we found that circITGA7 acts as a sponge for miR-34a-5p targeting VEGFA in glioma. Our study showed that circITGA7 regulates the proliferation and metastasis of glioma cell lines (SW1783&U373) by regulating the miR-34a-5p/VEGFA pathway. In conclusion, our study revealed a regulatory loop for the circITGA7/miR-34a-5p/VEGFA axis to regulate glioma development.

Circular RNA circCCDC66 promotes glioma proliferation by acting as a ceRNA for miR-320a to regulate FOXM1 expression.

BACKGROUND: In this study, we determine the potential roles and uncover the regulatory mechanisms of circCCDC66 in regulating cell growth and cell metastasis of glioma. METHODS: qRT-PCR was used to detect the expressions of circCCDC66 in gliomas and tissues. The biological function of circCCDC66 in glioma cell lines was elucidated by functional experiments. Cell counting kit-8 and transwell were used to detect the effect of circCCDC66 on the proliferation, migration and invasion of glioma cells. Bioinformatics analysis was applied to reveal the targets of circCCDC66. RESULTS: The results showed circCCDC66 was overexpressed in glioma and acted as an oncogene. CircCCDC66 knockdown suppressed the proliferation, migration, and invasion of glioma cells. We constructed a circCCDC66 regulating miRNA network and revealed miR-320a was a potential target of circCCDC66, which was down-regulated in high-grade gliomas compared to low-grade gliomas. Bioinformatics analysis showed circCCDC66-miR-320a/b axis was involved in regulating multiple cancer-related pathways. Furthermore, we identified FOXM1 as a key target of circCCDC66, which was involved in regulating DNA damage response pathways. In mechanism study, circCCDC66 could sponge miR-320a, thereby increasing the expression of FOXM1. CONCLUSIONS: CircCCDC66 could facilitate glioma cells proliferation, invasion and migration by down-regulating miR-320a and up-regulating FOXM1.

Identification of an N6-methyladenosine (m6A)-related signature associated with clinical prognosis, immune response, and chemotherapy in primary glioblastomas.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation regulators play crucial role in tumorigenicity and progression. However, their biological significance in primary glioblastomas (GBM) has not been fully elucidated. METHODS: In the present study, we evaluated the 22 m6A RNA regulators using the integrated data of primary GBM samples from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. The different m6A modification patterns and m6A-related gene signature in primary GBM were distinguished by using principal component analysis. Single-sample gene set enrichment analysis was introduced to assess the relative level of immune infiltration. Gene set variation analysis was performed to calculate the enrichment score of the signaling pathways for different clusters. An m6A scoring scheme was established to evaluate the m6A modification pattern in individual tumors in order to predict prognosis and evaluate tumor microenvironment (TME) cell infiltration, immune response, and chemotherapy effect in primary GBM. RESULTS: Two distinct m6A modification subgroups associated with different clinical features and biological pathways were identified among the 371 primary GBM. Based on 132 prognostic m6A phenotype-related differentially expressed genes (DEGs) between 2 m6A cluster subgroups, an m6A scoring model was constructed to assess the m6A modification pattern in individual tumors. The high-m6A score group was associated with better prognosis and immune response and worse chemotherapy effect. CONCLUSIONS: The findings of the present study indicate the potential role of m6A modification in primary GBM, which will help enhance our understanding of TME characteristics, predict clinical prognosis, and provide important insight into effective immunotherapy and chemotherapy.