Double pituitary adenomas: report of two cases and systematic review of the literature.

Objective: Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure. Methods: Two cases of DPA patients with Cushing's disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission. Results: Among 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing's syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (<1cm) were the most frequent in terms of tumor size (62/92, 67.39%). The detection rate for double lesions on 3.0T MRI was 50.00% (14/28), which significantly higher than 1.5T MRI (P = 0.034). Univariate analysis revealed that female, Cushing's syndrome and only single lesion detected by surgical exploration were associated with significantly worse prognosis (P<0.05). Multivariate analysis identified double lesion detected by surgical exploration (OR = 0.08, P = 0.003) and contiguous type tumor (OR = 0.06, P = 0.017) as independent protective factors for DPA patients. Conclusions: The double lesion detected by surgical exploration is independently associated with a better prognosis for DPA patients. Comprehensive intraoperative exploration are crucial measures to avoid missing causative lesions.

IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis.

Cytosolic double-stranded DNA surveillance by cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) signaling triggers cellular senescence, autophagy, biased mRNA translation, and interferon-mediated immune responses. However, detailed mechanisms and physiological relevance of STING-induced senescence are not fully understood. Here, we unexpectedly found that interferon regulatory factor 3 (IRF3), activated during innate DNA sensing, forms substantial endogenous complexes in the nucleus with retinoblastoma (RB), a key cell cycle regulator. The IRF3-RB interaction attenuates cyclin-dependent kinase 4/6 (CDK4/6)-mediated RB hyperphosphorylation that mobilizes RB to deactivate E2 family (E2F) transcription factors, thereby driving cells into senescence. STING-IRF3-RB signaling plays a notable role in hepatic stellate cells (HSCs) within various murine models, pushing activated HSCs toward senescence. Accordingly, IRF3 global knockout or conditional deletion in HSCs aggravated liver fibrosis, a process mitigated by the CDK4/6 inhibitor. These findings underscore a straightforward yet vital mechanism of cGAS-STING signaling in inducing cellular senescence and unveil its unexpected biology in limiting liver fibrosis.

Analysis of visual acuity status and difference in children of the same age from different areas of Xi'an City / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To understand the current status and differences in visual acuity of children of the same age from different regions of Xi'an, and to take an effective basis for the prevention of children's myopia.METHODS: Random stratified sampling was used to select the uncorrected distance visual acuity and computed dioptric data of 41 285 children aged 6-12 from 6 towns, 10 urban and rural areas and 112 country schools screened by Xi'an Central Hospital in December 2022.RESULTS: The myopia detection rate in different regions of Xi'an is 47.16% in towns, 38.59% in urban and rural areas, and 32.29% in the country, and the total myopia rate is 37.50%. The myopia rate of 6-12 years old in towns is higher than that in urban and rural areas, and that of urban and rural areas is higher than that of country; the myopia rate of girls is higher than that of boys; myopia rate increases with age; mild myopia: the myopia rate in towns is significantly higher than that of the urban and rural areas and the country; high myopia: the myopia rate in the country is significantly higher than that of the towns and the urban and rural areas. The total rate of deficient hyperopia reserves in different regions of Xi'an is 92.08% in towns, 93.67% in urban and rural areas, and 90.92% in the country, and the total rate of deficient hyperopia reserves is 92.09%. The rate of deficient hyperopia reserves at the age of 6-12 is higher in the urban and rural areas than in the towns, and higher in the towns than in the country; the total rate of deficient hyperopia reserve is higher in girls than in boys; it is the peak period of the development of hyperopia reserve rate before the age of 8.CONCLUSION: The total myopia rate and the total vision reserve deficiency rate of 6-12 years old in different regions of Xi'an are different, and 8-9 years old is the accelerated period of myopia development, and the peak of deficient hyperopia reserve is before the age of 8 years old. With the growth of age, the myopia rate shows a certain growth trend, and the rate of deficient hyperopia reserve shows a decreasing trend after reaching the peak. The total myopia rate and insufficient acuity reserve rate of girls are higher than those of boys.

The regulatory effect of morphine postconditioning in left stellate ganglion on remodeling after myocardial infarction / 中国药理学通报

Aim To investigate the regulatory effect of morphine postconditioning in the LSG on remodeling after myocardial infarction. Methods SD rats were randomly divided into four groups: sham operation group (Sham), myocardial infarction group (MI), myocardial infarction + saline group (Control) and myocardial infarction + morphine postconditioning group (MI + Morphine) . The rat MI model was constructed by ligating the left anterior descending coronary artery, and then morphine was given to the LSG by percutaneous posterior approach. After four weeks, the changes of cardiac function in rats were detected by ultrasound. Masson staining was used to detect fibrosis changes; the expression of Collagen I and Collagen III protein was detected by Western blot. The mRNA expression of ANP and BNP was detected by RT-qPCR. The expression of JJLOR in LSG was detected by immunofluorescence. The concentration of catecholamine in plasma and myocardial tissue was detected by ELISA. Results Compared with the sham group, the cardiac function of the MI group was significantly impaired, the myocardial tissue showed significant fibrosis changes, and the concentration of catecholamine in plasma and myocardial tissue significantly increased. Compared with the control group, the MI + Morphine group reduced myocardial fibrosis collagen deposition in rats after MI, inhibited the expression of ANP and BNP in myocardial tissue, reduced the concentration of catecholamine, and improved the cardiac function of MI rats. Immunofluorescence results showed that JJLOR was expressed in LSG after MI and increased after morphine postconditioning. Conclusions This study shows that morphine postconditioning in the LSG has a protective effect on myocardial remodeling after myocardial infarction. The mechanism may be related to the activation of JJLOR in the LSG by morphine and the reduction of catecholamine release from sympathetic nerve endings.

Expression of GDNF and AR in Testicular Peritubular Cells of Surgery-induced Cryptorchidism Mice / 中山大学学报(医学科学版)

ObjectiveTo investigate the expression of glial cell line-derived neurotrophic factor （GDNF） and androgen receptor （AR） in testicular peritubular cells （TPCs） of cryptorchidism mouse models and explore the theoretical significance of cryptorchidism-induced spermatogenesis dysfunction. MethodsA total of 30 five-week-old male ICR rats were divided randomly by using random number table method into 6 groups. Cryptorchidism was surgically induced in 3 randomly selected groups and the other 3 groups underwent sham surgery as the control groups. On days 4， 7 and 14 after surgery， we harvested the mice testes of the 3 groups and their corresponding control groups， then measured the testicular volumes， analyzed the testicular histopathology and detected the mRNA and protein expression levels of AR and GDNF in TPCs by immunofluorescence， real-time PCR and Western blot. ResultsIn normal control groups， on days 4， 7 and 14 after surgery， the testicular volumes were （125.58±19.22） mm3，（123.45±20.12） mm3， （140.09±13.62） mm3 ， respectively. Clear layers of spermatogenic cells were well arranged and abundant sperm cells were found. Peritubular cells were morphologically homogeneous， with slim-spindle appearance and normal cell thickness. The mRNA expression levels of AR were 1.00±0.05， 1.06±0.07 and 1.19±0.13； GDNF mRNA 1.00±0.04， 1.09±0.05， and 1.10±0.07. The protein expression levels of AR were 1.01±0.01， 0.79±0.02 and 1.01±0.04； GDNF protein （18.68±0.43） pg/mL， （14.39±0.36） pg/mL and （16.88±0.37） pg/mL. In cryptorchidism groups， on days 4， 7 and 14 after surgery， the testicular volumes were （115.64±3.91） mm3， （69.51±14.97） mm3 and （44.86±5.56） mm3， respectively. Spermatogenic cells were disorganized， seminiferous tubules were disrupted， peritubular cells shrank， bent and fractured. The mRNA expression levels of AR were 0.76±0.06， 0.53±0.04， and 0.29±0.02； GDNF mRNA 0.72±0.05， 0.42±0.02 and 0.30±0.03. The protein expression levels of AR were 0.54±0.02， 0.98±0.04 and 0.31±0.01； GDNF protein （8.50±0.34） pg/mL， （17.44±0.32） pg/mL and （6.83±0.34） pg/mL. Statistically significant differences （P < 0.05） were found in 7-day and 14-day testicular volumes between control and cryptorchidism groups but not in the 4-day testicular volume （P > 0.05）. Testicular volumes， AR and GDNF mRNA and protein expression in control groups had no statistically significant difference （P > 0.05）， while those in cryptorchidism groups showed a trend of gradual decline in the amount and the differences between groups were statistically significant （P < 0.05）. ConclusionsIn surgery-induced cryptorchidism mice， after the induction， the expression of AR and GDNF in TPCs showed a gradual decrease over time. AR and GDNF play a major role in mediating the TPCs damage in cryptorchidism. This study provides a theoretical basis for mechanism researches of cryptorchidism-induced spermatogenesis dysfunction.

Anoikis regulator GLI2 promotes NC cell immunity escape by TGF-ß-mediated non-classic hedgehog signaling in colorectal cancer: based on artificial intelligence and big data analysis.

BACKGROUND: Anoikis is a speed-limited procedure to inhibit tumor metastasis during epithelial-mesenchymal transition (EMT). Previous studies have explored anoikis-related genes (ARG) in predicting prognosis and distinguishing tumoral immunity in many types of cancer. However, the role of ARGs in regulating NK cell exhaustion (NKE) and in predicting chemotherapy sensitivity is not clear. Therefore, it is necessary to work on it. METHODS: Gene expression profiles and clinical features are collected from TCGA and GEO, and data analysis is performed in R4.2.0. RESULTS: The ARGs-based no-supervised learning algorithm identifies three ARG subgroups, amongst which the prognosis is different. WCGNA and Artificial intelligence (AI) are applied to construct an NKE-related drug sensitivity stratification and prognosis identification model in digestive system cancer. Pathways association analysis screens out GLI2 is a key gene in regulating NKE by non-classic Hedgehog signaling (GLI2/TGF-ß/IL6). In vitro experiments show that down-regulation of GLI2 enhances the CAPE-mediated cell toxicity and accompanies with down-regulation of PD-L1, tumor-derive IL6, and snial1 whereas the expression of cleaved caspas3, cleaved caspase4, cleaved PARP, and E-cadherin are up-regulated in colorectal cancer. Co-culture experiments show that GLI2- decreased colorectal tumor cells lead to down-regulation of TIM-3 and PD1 in NK cells, which are restored by TGF-bate active protein powder. Besides, the Elisa assay shows that GLI2-decreased colorectal tumor cells lead to up-regulation of IFN-gamma in NK cells.

Thrombotic events and prophylactic anticoagulation in pediatric patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) can occur in children with COVID-19, and the efficacy and safety of prophylactic anticoagulant therapy are uncertain. This study aimed to assess the incidence of VTE in pediatric patients with COVID-19, the association of D-dimer with thrombus formation, and the effectiveness and safety of prophylactic anticoagulation treatment. METHODS: We systematically searched databases from January 2020 to February 2023. A systematic review and meta-analysis were conducted to determine the incidence of VTE in children and evaluate the efficacy and safety of prophylactic anticoagulant therapy. RESULTS: Thirteen cohort studies and one clinical trial were included. The pooled incidence rate of VTE in affected children was 1.5% (95% CI 0.4-2.9%). Children with D-dimer levels five times higher than normal had a higher risk of VTE (OR 4.92, 95% CI 1.60-15.11). Prophylactic anticoagulant therapy did not significantly reduce the risk of VTE (OR 1.35, 95% CI 0.74-2.49). The safety of prophylactic anticoagulant therapy was relatively high, with major bleeding and all-cause mortality rates below 0.1% (95% CI 0.0-0.2%). CONCLUSIONS: The incidence of VTE in children with COVID-19 is low, and prophylaxis based on ISTH standards is reasonable. Low-molecular-weight heparin (LMWH) for VTE prevention has a high level of safety. However, more high-quality studies are needed to understand the impact of anticoagulant therapy on VTE incidence in pediatric patients with COVID-19.

Advances in genetic abnormalities, epigenetic reprogramming, and immune landscape of intracranial germ cell tumors.

Intracranial germ cell tumors (IGCTs) are a rare subtype of central nervous system neoplasms that predominantly affect young individuals and exhibit a higher incidence in East Asia. IGCTs can be pathologically divided into two main categories: germinomas and non-germinomatous germ cell tumors (NGGCTs). Despite the scarcity of this disease, recent advancements in molecular biology techniques have facilitated the discovery of the inherent genetic and molecular characteristics of IGCTs. Somatic mutations that result in the activation of the KIT/RAS/MAPK and PI3K/AKT/mTOR pathways, chromosomal instability leading to characteristic changes in chromosomal fragments (notably 12p gain), and potentially diagnostic miRNAs (such as miR-371a-3p) may provide valuable insights for the efficient diagnosis, targeted therapy, and prognosis evaluation of IGCTs. Additionally, transcriptomic and methylomic analyses have provided new perspectives on the intrinsic development of IGCTs, further elucidating their equivalence with GCTs at other sites. The evaluation of the tumor immune landscape may guide prognosis prediction and immunotherapy for IGCT patients. Nevertheless, current research still faces challenges such as the absence of basic laboratory research systems, a single source of large sample research data, and a limited overall volume of research. The incorporation of larger sample sizes, the implementation of more innovative evaluation systems, and the employment of novel experimental methods are urgently required to become the focus of future research.

BCL2A1 is associated with tumor-associated macrophages and unfavorable prognosis in human gliomas.

B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family. Previous studies have shown that BCL2A1 is closely related to the tumorigenesis and resistance to chemotherapy of multiple solid tumors, such as breast cancer. However, the expression pattern and potential biological function of BCL2A1 in glioma remain unknown. For the first time, we found that the expression of BCL2A1 was higher in human glioma tissues than in normal brain tissues (NBTs) in both public datasets and an in-house cohort. High BCL2A1 expression was associated with advanced WHO grade, IDH 1/2 wild type and the mesenchymal (ME) subtype, and its overexpression in glioma predicted resistance to temozolomide (TMZ) chemotherapy and unfavorable prognosis. In addition, Gene set enrichment analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that BCL2A1 was significantly correlated with the immune response and immune-related pathways, and BCL2A1 expression was positively correlated with microenvironmental parameters (immune, stromal, and ESTIMATE scores) and macrophage infiltration. Interestingly, bioinformatic prediction and immunohistochemical/immunofluorescence staining analysis revealed that BCL2A1 expression was obviously associated with the tumor-associated macrophages (TAMs) markers CD68 and CCL2. Notably, knockdown of BCL2A1 significantly inhibited cell proliferation of U87 and U251 in vitro, induced smaller tumor size and prolonged survival time of mice in vivo. Co-culture experiments of macrophages and GBM cells showed that BCL2A1 knockdown inhibited macrophage migration. Meanwhile, knockdown of BCL2A1 was associated with low expression of CD68 and CCL2 in intracranial xenograft model. This may suggest that BCL2A1 promotes the progression of glioma and influences the prognosis of patients by participating in TAMs infiltration. In conclusion, these findings suggest that BCL2A1 could serve as a promising prognostic indicator and immunotherapy target in gliomas.

Advances in the role of gut microbiota in the regulation of the tumor microenvironment (Review).

As a protector of human health, the gut microbiota plays an important role in the development of the immune system during childhood, and the regulation of dietary habits, metabolism and immune system during adulthood. Dysregulated gut flora is not pathogenic, but it can weaken the protective effect of the immune system and cause various diseases. The tumor microenvironment is a physiological environment formed during tumor growth, which provides nutrients and growth factors necessary for tumor growth. As an important factor affecting the tumor microenvironment, the intestinal microflora affects the development of tumors through the mechanisms of gut and microflora metabolites, gene toxins and signaling pathways. The present article aimed to review the components and mechanisms of action, clinical applications, and biological targets of gut microbiota in the regulation of the tumor microenvironment. The present review provides novel insights for the future use of intestinal flora, to regulate the tumor microenvironment, to intervene in the occurrence, development, treatment and prognosis of tumors.

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.

Apalutamide for metastatic castration-sensitive prostate cancer: final analysis of the Asian subpopulation in the TITAN trial.

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.

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.

Recent Progress in Emerging Novel MXenes Based Materials and their Fascinating Sensing Applications.

Early transition metals based 2D carbides, nitrides and carbonitrides nanomaterials are known as MXenes, a novel and extensive new class of 2D materials family. Since the first accidently synthesis based discovery of Ti3 C2 in 2011, more than 50 additional compositions have been experimentally reported, including at least eight distinct synthesis methods and also more than 100 stoichiometries are theoretically studied. Due to its distinctive surface chemistry, graphene like shape, metallic conductivity, high hydrophilicity, outstanding mechanical and thermal properties, redox capacity and affordable with mass-produced nature, this diverse MXenes are of tremendous scientific and technological significance. In this review, first we'll come across the MXene based nanomaterials possible synthesis methods, their advantages, limitations and future suggestions, new chemistry related to their selected properties and potential sensing applications, which will help us to explain why this family is growing very fast as compared to other 2D families. Secondly, problems that help to further improve commercialization of the MXene nanomaterials based sensors are examined, and many advances in the commercializing of the MXene nanomaterials based sensors are proposed. At the end, we'll go through the current challenges, limitations and future suggestions.

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.

The RNA-binding protein CSTF2 regulates BAD to inhibit apoptosis in glioblastoma.

RNA-binding proteins (RBP) regulate several aspects of co- and post-transcriptional gene expression in cancer cells. CSTF2 is involved in the expression of many cellular mRNAs and involved in the 3'-end cleavage and polyadenylation of pre-mRNAs to terminate transcription. However, the role of CSTF2 in human glioblastoma (GBM) and the underlying mechanisms remain unclear. In the present study, CSTF2 was found to be upregulated in GBM, and its high expression predicted poor prognosis. Knockdown CSTF2 induced GBM cell apoptosis both in vitro and in vivo. Specific mechanism studies showed that CSTF2 unstabilized the mRNA of the BAD protein by shortening its 3' UTR. Additionally, an increase in the expression level of CSTF2 decreased the expression level of BAD. In conclusion, CSTF2 binds to the mRNA of the BAD protein to shorten its 3'UTR, which negatively affects the BAD mediated apoptosis and promotes GBM cell survival.

Overexpressing SIRT6 can Attenuate the Injury of Intracerebral Hemorrhage by Down-Regulating NF-kB.

Sirtuin-6 (SIRT6), a member of the sirtuins family of NAD ( +) dependent deacetylases, has been shown to have beneficial effects in ischemic stroke. However, the role of SIRT6 in intracerebral haemorrhage (ICH) has not reported. We observed that SIRT6 expression was down-regulated in human ICH patients and down-regulated in ICH-induced rat cortical neurons. We subsequently found that SIRT6 overexpression reduced brain tissue damage and increased neuronal survival in the ICH model of rats and hemin-induced cortical neurons. Our further study found that overexpression of SIRT6 can reduce inflammatory response by down-regulating the expression of NF-kB and thus promote the recovery of neurological function in ICH animals. In conclusion, SIRT6 can inhibit the expression of NF-kB and plays a neuroprotective role in ICH by inhibiting the NF-kB-mediated inflammatory response.SIRT6 could be a novel therapeutic target for ICH.