SIRPB1 regulates inflammatory factor expression in the glioma microenvironment via SYK: functional and bioinformatics insights.

BACKGROUND: SIRPB1 expression is upregulated in various tumor types, including gliomas, and is known to contribute to tumor progression; nevertheless, its function in the immune milieu of gliomas is still mainly unknown. METHODS: This study, we analyzed 1152 normal samples from the GTEx database and 670 glioma samples from the TCGA database to investigate the relationship between the expression of SIRPB1 and clinicopathological features. Moreover, SIRPB1 gene knockout THP-1 cell lines were constructed using CRISPR/Cas9 and were induced into a co-culture of macrophages and glioma cells in vitro to learn more about the role of SIRPB1 in the glioma immune milieu. Lastly, we established a prognostic model to predict the effect of SIRPB1 on prognosis. RESULTS: Significantly higher levels of SIRPB1 expression were found in gliomas, which had an adverse effect on the immune milieu and correlated poorly with patient survival. SIRPB1 activation with certain antibodies results in SYK phosphorylation and the subsequent activation of calcium, MAPK, and NF-κB signaling pathways. This phenomenon is primarily observed in myeloid-derived cells as opposed to glioma cells. In vitro co-culture demonstrated that macrophages with SIRPB1 knockout showed decreased IL1RA, CCL2, and IL-8, which were recovered upon ectopic expression of SIRPB1 but reduced again following treatment with SYK inhibitor GS9973. Critically, a lower overall survival rate was linked to increased SIRPB1 expression. Making use of SIRPB1 expression along with additional clinicopathological variables, we established a nomogram that showed a high degree of prediction accuracy. CONCLUSIONS: Our study demonstrates that glioma cells can be activated by macrophages via SIRPB1, subsequently reprogramming the TME, suggesting that SIRPB1 could serve as a promising therapeutic target for gliomas.

CHRNA9 as a New Prognostic Marker and Potential Therapeutic Target in Glioma.

Background: The nicotinic acetylcholine receptor (nAChR) subunit alpha-9 (CHRNA9) is a unique cholinergic receptor, which is involved in tumor proliferation, apoptosis, metastasis and chemotherapy resistance. However, the correlation between the expression level of CHRNA9 in glioma and the clinical features and prognosis of glioma patients has not been clarified. The aim of this study was to verify the expression level of CHRNA9 in glioma and its effect on prognosis by bioinformatics methods. Methods: The RNA-seq data of glioma and normal samples were obtained from the TCGA and GTEx databases. Bioinformatics methods were utilized to analyze the differential expression of CHRNA9 between tumor samples and normal samples. The potential association between CHRNA9 and the clinicopathological features of glioma patients was also investigated. The Kaplan-Meier method and Cox regression were utilized to analyze the relationship between CHRNA9 expression level and survival time and prognostic value of glioma patients. Enrichment analysis was applied to predict gene function and signaling pathways associated with CHRNA9. Experimental verification was performed using tumor tissues and paracancerous tissues from glioma patients. Results: The results of bioinformatics analysis showed that the expression of CHRNA9 was increased in glioma tissues, correlating with poor prognosis and reduced patient survival time. Enrichment analysis suggested that CHRNA9 may interact with the JAK/STAT pathway. CHRNA9 was also found to be abnormally expressed in various other tumors and associated with the expression levels of numerous immune checkpoints in glioma. The findings from the analysis of clinical samples revealed that the expression levels of both mRNA and protein of CHRNA9 in glioma tissues were higher than those in paracancerous tissues. Similarly, the mRNA expression levels of STAT3, IL-6, and TNF-α, which are crucial factors in the STAT3 pathway, were elevated in glioma tissues compared to paracancerous tissues. Conclusion: CHRNA9 is a potential prognostic marker and immunotherapy target for glioma, with its mechanism of action potentially linked to the STAT3 pathway.

Differentiation route determines the functional outputs of adult megakaryopoiesis.

Emerging evidence has revealed a direct differentiation route from hematopoietic stem cells to megakaryocytes (direct route), in addition to the classical differentiation route through a series of restricted hematopoietic progenitors (stepwise route). This raises the question of the importance of two alternative routes for megakaryopoiesis. Here, we developed fate-mapping systems to distinguish the two routes, comparing their quantitative and functional outputs. We found that megakaryocytes were produced through the two routes with comparable kinetics and quantity under homeostasis. Single-cell RNA sequencing of the fate-mapped megakaryocytes revealed that the direct and stepwise routes contributed to the niche-supporting and immune megakaryocytes, respectively, but contributed to the platelet-producing megakaryocytes together. Megakaryocytes derived from the two routes displayed different activities and were differentially regulated by chemotherapy and inflammation. Our work links differentiation route to the heterogeneity of megakaryocytes. Alternative differentiation routes result in variable combinations of functionally distinct megakaryocyte subpopulations poised for different physiological demands.

Epidemiology, Characteristics, and Prognostic Factors of Primary Atypical Teratoid/Rhabdoid Tumors in the Spinal Canal: A Systematic Review.

Primary atypical teratoid/rhabdoid tumors (AT/RTs) in the spinal canal are rare central nervous system (CNS) neoplasms that are challenging to diagnose and treat. To date, there has been no standard treatment regimen for these challenging malignant tumors. Thus, we conducted this research to explore potential prognostic factors and feasible treatment modalities for improving the prognosis of these tumors. Articles were retrieved from the PubMed, MEDLINE, and Embase databases, using the keywords "atypical teratoid/rhabdoid tumor," "rhabdoid tumor," "spine," "spinal," "spinal neoplasm", and "spinal cord neoplasm." All eligible cases demonstrated SMARCB1-deficient expression validated by pathological examination. We collected and analyzed data related to clinical presentation, radiological features, pathological characteristics, treatment modalities and prognosis via Kaplan-Meier and Cox regression analyses. Thirty-six articles comprising 58 spinal AT/RT patients were included in the study. The median progression-free survival (PFS) and overall survival (OS) were 18 and 22 months, respectively. Kaplan-Meier analysis demonstrated significant survival improvements for OS in the nonmetastasis, male, radiotherapy and intrathecal chemotherapy groups as well as for PFS in the chemotherapy and radiotherapy groups. Multivariate analysis revealed that chemotherapy and radiotherapy were prognostic factors for improved PFS, and that intrathecal chemotherapy reduced the risk of mortality. Spinal AT/RTs are uncommon malignant entities with a dismal survival rate. Although our review is limited by variability between cases, there is some evidence revealing potential risk factors and the importance of systematic chemotherapy, intrathecal chemotherapy and radiotherapy in spinal AT/RT treatment modalities.

P129, a pyrazole ring-containing isolongifolanone-derivate: synthesis and investigation of anti-glioma action mechanism.

BACKGROUND: Cyclin-dependent kinase-2 (CDK-2) is an important regulatory factor in the G1/S phase transition. CDK-2 targeting has been shown to suppress the viability of multiple cancers. However, the exploration and application of a CDK-2 inhibitor in the treatment of glioblastoma are sparse. METHODS: We synthesized P129 based on isolongifolanone, a natural product with anti-tumor activity. Network pharmacology analysis was conducted to predict the structural stability, affinity, and pharmacological and toxicological properties of P129. Binding analysis and CETSA verified the ability of P129 to target CDK-2. The effect of P129 on the biological behavior of glioma cells was analyzed by the cell counting kit-8, colony formation, flow cytometry, and other experiments. Western blotting was used to detect the expression changes of proteins involved in the cell cycle, cell apoptosis, and epithelial-mesenchymal transition. RESULTS: Bioinformatics analysis and CETSA showed that P129 exhibited good intestinal absorption and blood-brain barrier penetrability together with high stability and affinity with CDK-2, with no developmental toxicity. The viability, proliferation, and migration of human glioma cells were significantly inhibited by P129 in a dose- and time-dependent manner. Flow cytometry and western blotting analyses showed G0/G1 arrest and lower CDK-2 expression in cells treated with P129 than in the controls. The apoptotic ratio of glioma cells increased significantly with increasing concentrations of P129 combined with karyopyknosis and karyorrhexis. Apoptosis occurred via the mitochondrial pathway. CONCLUSION: The pyrazole ring-containing isolongifolanone derivate P129 exhibited promising anti-glioma activity by targeting CDK-2 and promoting apoptosis, indicating its potential importance as a new chemotherapeutic option for glioma.

Ube2L6 Promotes M1 Macrophage Polarization in High-Fat Diet-Fed Obese Mice via ISGylation of STAT1 to Trigger STAT1 Activation.

INTRODUCTION: In obesity-related type 2 diabetes mellitus (T2DM), M1 macrophages aggravate chronic inflammation and insulin resistance. ISG15-conjugation enzyme E2L6 (Ube2L6) has been demonstrated as a promoter of obesity and insulin resistance. This study investigated the function and mechanism of Ube2L6 in M1 macrophage polarization in obesity. METHODS: Obesity was induced in Ube2L6AKO mice and age-matched Ube2L6flox/flox control mice by high-fat diet (HFD). Stromal vascular cells were isolated from the epididymal white adipose tissue of mice. Polarization induction was performed in mouse bone marrow-derived macrophages (BMDMs) by exposure to IFN-γ, lipopolysaccharide, or IL-4. F4/80 expression was assessed by immunohistochemistry staining. Expressions of M1/M2 macrophage markers and target molecules were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. Protein interaction was validated by co-immunoprecipitation (Co-IP) assay. The release of TNF-α and IL-10 was detected by ELISA. RESULTS: The polarization of pro-inflammatory M1 macrophages together with an increase in macrophage infiltration was observed in HFD-fed mice, which could be restrained by Ube2L6 knockdown. Additionally, Ube2L6 deficiency triggered the repolarization of BMDMs from M1 to M2 phenotypes. Mechanistically, Ube2L6 promoted the expression and activation of signal transducer and activator of transcription 1 (STAT1) through interferon-stimulated gene 15 (ISG15)-mediated ISGlylation, resulting in M1 macrophage polarization. CONCLUSION: Ube2L6 exerts as an activator of STAT1 via post-translational modification of STAT1 by ISG15, thereby triggering M1 macrophage polarization in HFD-fed obese mice. Overall, targeting Ube2L6 may represent an effective therapeutic strategy for ameliorating obesity-related T2DM.

Gain-of-Function KIDINS220 Variants Disrupt Neuronal Development and Cause Cerebral Palsy.

BACKGROUND: Kinase D-interacting substrate of 220 kDa (KIDINS220) is a multifunctional scaffolding protein essential for neuronal development. It has been implicated in neurological diseases with either autosomal dominant (AD) or autosomal recessive (AR) inheritance patterns. The molecular mechanisms underlying the AR/AD dual nature of KIDINS220 remain elusive, posing challenges to genetic interpretation and clinical interventions. Moreover, increased KIDINS220 exhibited neurotoxicity, but its role in neurodevelopment remains unclear. OBJECTIVE: The aim was to investigate the genotype-phenotype correlations of KIDINS220 and elucidate its pathophysiological role in neuronal development. METHODS: Whole-exome sequencing was performed in a four-generation family with cerebral palsy. CRISPR/Cas9 was used to generate KIDINS220 mutant cell lines. In utero electroporation was employed to investigate the effect of KIDINS220 variants on neurogenesis in vivo. RESULTS: We identified in KIDINS220 a pathogenic nonsense variant (c.4177C > T, p.Q1393*) that associated with AD cerebral palsy. We demonstrated that the nonsense variants located in the terminal exon of KIDINS220 are gain-of-function (GoF) variants, which enable the mRNA to escape nonsense-mediated decay and produce a truncated yet functional KIDINS220 protein. The truncated protein exhibited significant resistance to calpain and consequently accumulated within cells, resulting in the hyperactivation of Rac1 and defects in neuronal development. CONCLUSIONS: Our findings demonstrate that the location of variants within KIDINS220 plays a crucial role in determining inheritance patterns and corresponding clinical outcomes. The proposed interaction between Rac1 and KIDINS220 provides new insights into the pathogenesis of cerebral palsy, implying potential therapeutic perspectives. © 2023 International Parkinson and Movement Disorder Society.

Association between viral infections and glioma risk: a two-sample bidirectional Mendelian randomization analysis.

BACKGROUND: Glioma is one of the leading types of brain tumor, but few etiologic factors of primary glioma have been identified. Previous observational research has shown an association between viral infection and glioma risk. In this study, we used Mendelian randomization (MR) analysis to explore the direction and magnitude of the causal relationship between viral infection and glioma. METHODS: We conducted a two-sample bidirectional MR analysis using genome-wide association study (GWAS) data. Summary statistics data of glioma were collected from the largest meta-analysis GWAS, involving 12,488 cases and 18,169 controls. Single-nucleotide polymorphisms (SNPs) associated with exposures were used as instrumental variables to estimate the causal relationship between glioma and twelve types of viral infections from corresponding GWAS data. In addition, sensitivity analyses were performed. RESULTS: After correcting for multiple tests and sensitivity analysis, we detected that genetically predicted herpes zoster (caused by Varicella zoster virus (VZV) infection) significantly decreased risk of low-grade glioma (LGG) development (OR = 0.85, 95% CI: 0.76-0.96, P = 0.01, FDR = 0.04). No causal effects of the other eleven viral infections on glioma and reverse causality were detected. CONCLUSIONS: This is one of the first and largest studies in this field. We show robust evidence supporting that genetically predicted herpes zoster caused by VZV infection reduces risk of LGG. The findings of our research advance understanding of the etiology of glioma.

Atypical teratoid/rhabdoid tumour with CDK6 amplification in a child: a case report and literature review.

Atypical teratoid/rhabdoid tumours (AT/RTs) are rare central nervous system neoplasms that frequently occur in infants and children and have a very poor prognosis. In recent years, molecular analysis of AT/RTs has shown that biallelic inactivation of SMARCB1 (INI1, SNF5, BAF47) or SMARCA4 (BRG1) frequently occurs. Here, we present a case of basal ganglia AT/RT with SMARCB1 gene deficiency and CDK6 gene amplification in a 5-year-old child. A 5-year-old boy was hospitalized due to a 1-week history of frontal and parietal headache. Magnetic resonance imaging (MRI) demonstrated a 3 cm × 2 cm × 1.5 cm heterogeneous enhanced mass located at the right basal ganglia that partially protruded into the right lateral ventricle. The lesion was successfully resected under electrophysiological monitoring and neuronavigation. The postoperative pathological examination implied an AT/RT diagnosis, with loss of SMARCB1 protein, SMARCB1 gene deficiency and CDK6 gene amplification. Unfortunately, the patient died due to respiratory and circulatory failure at 5 weeks after the operation. To date, standard regimens have not yet been established due to the lack of large-scale prospective studies for AT/RT. The p16-RB signalling pathway should be considered as a potential target for AT/RT treatment modalities. Apart from traditional regimens, targeted therapies, especially CDK4/6 inhibitors, are likely a promising therapeutic option for AT/RT treatment.

National Brain Tumour Registry of China (NBTRC) statistical report of primary brain tumours diagnosed in China in years 2019-2020.

Background: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed. Methods: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). The cases were tabulated by histology and anatomical site. Categorical variables were reported as numbers (percentages). The distribution of tumours by age (0-14, 15-19, 20-39, 40-64, and 65+ years) was analysed. Findings: There were a total of 25,537 brain tumours, foremost among them meningioma (23.63%), followed by tumours of the pituitary (23.42%), and nerve sheath tumours (9.09%). Glioblastoma, the most common and lethal form of primary brain cancer in adults, represented 8.56% of all cases. Of note, 6.48% of the malignant tumours were located in the brain stem. The percentage of malignant brain tumours decreased with increasing age, 24.08% in adults (40+ years), 30.25% in young adults (20-39 years), 35.27% in adolescents (15-19 years), and 49.83% in children (0-14 years). Among the 2107 paediatric patients, the most common sites were ventricle (17.19%), brainstem (14.03%), pituitary and craniopharyngeal duct (13.4%), and cerebellum (12.3%), a distribution that differed from that of the entire cohort. The histology distribution was also unique in children, with glioblastoma much less incident compared to the whole cohort (3% vs. 8.47%, p < 0.01). 58.80% of all patients chose higher-level neurosurgical hospitals outside of their province of residence. The median in-hospital length of stay (LOS) for the various pathologies ranged from 11 to 19 days. Interpretation: The histological and anatomical site distribution of brain tumours in the NBTRC was statistically different in the subgroup of children (0-14 years). Patient choice of pursuing trans-provincial treatment was common and the in-hospital LOS was longer compared to that reported in similar European and American patient populations, which merits further attention. Funding: The National Key Research and Development Program of China (2015BAI12B04, 2013BAI09B03, 2014BAI04B01, and 2021YFF1201104) and Chinese National Natural Science Foundation of China (81971668).

The risk of intracranial hemorrhage in glioma patients receiving anticoagulant treatment for venous thromboembolism: a bayesian network meta-analysis.

PURPOSE: We aimed to perform a Bayesian network meta-analysis to assess the risk of intracranial hemorrhage (ICH) in patients with glioma receiving anticoagulant treatment for venous thromboembolism. METHODS: The PubMed, Embase and Web of Science databases were searched for relevant publications until September 2022. All studies evaluating the risk of ICH in patients with glioma receiving anticoagulant treatment were included. Bayesian network meta-analysis and pairwise meta-analysis were performed to compare the ICH risk between the anticoagulant treatments. The Cochrane's Risk of Bias Tool and the Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of studies. RESULTS: A total of 11 studies with 1301 patients were included. Pairwise comparisons showed no significant differences excepted with LMWH vs. DOACs (OR: 7.28, 95% CI: 2.11-25.17) and LMWH vs. Placebo (OR: 3.66, 95% CI: 2.15-6.24). For network meta-analysis, significant difference was found between patients treated with LMWH vs. Placebo (OR: 4.16, 95% CI: 2.00-10.14) and LMWH vs. DOACs (OR: 10.13, 95% CI: 2.70-70.19). CONCLUSIONS: It seems that LMWH has the highest risk of ICH in glioma patients, while no evidence indicates that DOACs increase the risk of ICH. The use of DOACs may perhaps be a better choice. Further larger studies focusing on the benefit-to-risk ratio are warranted.

Interaction of reproductive tract infections with estrogen exposure on breast cancer risk and prognosis.

BACKGROUND: Reproductive tract infections influenced a series of inflammatory processes which involved in the development of breast cancer, while the processes were largely affected by estrogen. The present study aimed to explore the associations of breast cancer risk and prognosis with reproductive tract infections and the modification effects of estrogen exposure. METHODS: We collected history of reproductive tract infections, menstruation and reproduction from 1003 cases and 1107 controls and a cohort of 4264 breast cancer patients during 2008-2018 in Guangzhou, China. We used logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for risk; Cox model was applied to estimate the hazard ratios (HRs) and 95% CIs for progression-free survival (PFS) and overall survival (OS). RESULTS: It was found that previous reproductive tract infections were negatively associated with breast cancer risk (OR = 0.80, 95%CI, 0.65-0.98), particularly for patients with more menstrual cycles (OR = 0.74, 95%CI, 0.57-0.96). Patients with previous reproductive tract infections experienced better OS (HR = 0.61; 95% CI, 0.40-0.94) and PFS (HR = 0.84; 95% CI, 0.65-1.09). This protective effect on PFS was only found in patients with more menstrual cycles (HR = 0.52, 95% CI:0.34-0.79, Pinteraction = 0.015). CONCLUSIONS: The findings suggested that reproductive tract infections may be protective for the initiation and development of breast cancer, particularly for women with a longer interval of lifetime estrogen exposure.

Angiopep-2-conjugated FeTi@Au core-shell nanoparticles for tumor targeted dual-mode magnetic resonance imaging and hyperthermic glioma therapy.

Herein, we fabricated gold surface-coated iron titanium core-shell (FeTi@Au) nanoparticles (NPs) with conjugation of angiopep-2 (ANG) (FeTi@Au-ANG) NPs for targeted delivery and improved NPs penetration by receptor-mediated endocytosis to achieve hyperthermic treatment of gliomas. The synthesized "core-shell" FeTi@Au-ANG NPs exhibited spherical in shape with around 16 nm particle size and increased temperature upon alternating magnetic field (AMF) stimulation, rendering them effective for localized hyperthermic therapy of cancer cells. Effective targeted delivery of FeTi@Au-ANG NPs was demonstrated in vitro by improved transport and cellular uptake, and increased apoptosis in glioma cells (C6) compared with normal fibroblast cells (L929). FeTi@Au-ANG NPs exhibited higher deposition in brain tissues and a superior therapeutic effect in an orthotopic intracranial xenograft mouse model. Taken together, our data indicate that FeTi@Au-ANG NPs hold significant promise as a targeted delivery strategy for glioma treatment using hyperthermia.

Association between Elderly Sarcopenia and Inflammatory Cytokine Interleukin-17: A Cross-Sectional Study.

Aging slows down the mechanisms behind skeletal muscle weakening and mobility. Increases in inflammation brought on by aging may contribute to some characteristics of sarcopenia. As a result of population aging worldwide, sarcopenia, an age-related disease, has become a huge burden on both individuals and society as a whole. The study of the morbidity mechanism and available sarcopenia treatments has received more attention. The inflammatory response may be one of the most important methods behind the pathophysiology of sarcopenia in the aged, according to the background of the study. This anti-inflammatory cytokine inhibits the ability of human monocytes and macrophages to induce inflammation as well as the production of cytokines like IL-6. Here, we investigate the association between sarcopenia and interleukin-17 (IL-17), an inflammatory cytokine in the aged. There were 262 subjects aged 61-90 years who were screened for sarcopenia in Hainan General Hospital. The subjects were divided into 45 males and 60 females aged 65-79 years (average age: 72.00 ± 4.31 years). 105 patients without sarcopenia were randomly selected among 157 participants. It included 50 males and 55 females, aged 61-76 years (mean age: 69.10 ± 4.55 years) as per the standard definition of the Asian Working Group for Sarcopenia (AWGS). The "skeletal muscle index" (SMI), "hand grip strength" (HGS), "gait speed" (GS), "biochemical indexes," "serum IL-17 level," nutritional status, and past medical history of the two groups were evaluated and compared. Compared with the participants without sarcopenia, sarcopenia patients had higher average age; less physical exercise; lower total scores of BMI, pre-ALB, IL-17, and SPPB; and a higher proportion of malnutrition risk (all P < 0.05). By "ROC curve analysis," the best critical point was IL-17 in the growth of sarcopenia. The area that comes under ROC (AUROC) value was 0.627 (95% CI = 0.552, 0.702, P = 0.002). The ideal threshold value for IL-17 to estimate sarcopenia was 18.5 pg/mL. In the unadjusted model, IL-17 was considerably linked to sarcopenia (OR = 1.123, 95% CI = 1.037-1.215, P = 0.004). After the covariate adjustment observed in the complete adjustment model (OR = 1.111, 95% CI = 1.004-1.229, P = 0.002), this significance still exists. The results of this study suggest a strong relationship between sarcopenia and IL-17. This study will look at IL-17's potential to serve as a key sarcopenia indicator. This trial is registered with ChiCTR2200022590.

Statins and risk of venous thromboembolic diseases: A two-sample mendelian randomization study.

BACKGROUND AND AIMS: In observational studies, statins have been suggested to have protective effects on venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). To this aim, we performed a two-sample mendelian randomization (MR) analysis to determine whether these associations were causal. METHODS AND RESULTS: Data on the single nucleotide polymorphisms (SNPs) related to statin medication were obtained from the FinnGen study, and data for VTE, PE and DVT of lower extremities (LEDVT) were from the UK Biobank study, respectively. Inverse variance weighted (IVW) method was used as the principal analysis of MR, and sensitivity analysis was performed to detect horizontal pleiotropy and heterogeneity. MR estimates showed an inverse causal association between statin medication and the risk of VTE (odds ratio [OR]: 0.999, 95% CI: 0.998-1.000, P = 0.004), PE (OR: 0.999, 95% CI: 0.999-1.000, P = 0.011) and LEDVT (OR: 0.999, 95% CI: 0.999-1.000, P = 0.008). CONCLUSION: Our findings provide direct evidence that statins might decrease the risk of VTE, PE and LEDVT in agreement with observational studies. The specific mechanism of statin therapy for venous thromboembolism needs to be further studied.

Paramecium bursaria as a Potential Tool for Evaluation of Microplastics Toxicity

Microplastics (MPs) are normally defined as small plastic wastes with a size of 1 µm to 5 mm in diameter. This tiny plastic debris is abundant in aquatic systems and poses a great threat to aquatic biota. To date, toxicological assessment of MPs is predominantly dependent on metazoan animals, although their applications are sometimes limited due to the high cost, narrow ecological niche, or ethical considerations. In this regard, unicellular eukaryotes (i.e., protozoa) that are ubiquitously present in nature represent a promising alternative for evaluating the toxicity of MPs. In this study, we selected Paramecium bursaria (P. bursaria) as a representative of protozoa and further investigated behavioral and molecular changes in MPs-exposed P. bursaria. Our results showed that following MPs uptake, P. bursaria exhibited various changes, including anomalies in swimming patterns, reduction in moving speed, impairment of avoidance behavior, elevation of oxidative stress, and potential disturbance of endosymbiosis. These elicited changes in P. bursaria in response to MPs exposure were pronounced and measurable. Overall, this study demonstrated that P. bursaria could serve as a promising alternative for the toxicological assessment of MPs and may be further applied to evaluate the toxicity of other environmental contaminants.

The role of microfibrillar-associated protein 2 in cancer.

Microfibrillar-associated protein 2 (MFAP2), a component of the extracellular matrix, is important in controlling growth factor signal transduction. Recent studies have shown that MFAP2, an effective prognostic molecule for various tumors, is associated with tumor occurrence and development and may be involved in remodeling the extracellular matrix and regulating proliferation, apoptosis, invasion, tumor cell metastasis, and tumor angiogenesis. However, MFAP2's specific mechanism in these tumor processes remains unclear. This article reviewed the possible mechanism of MFAP2 in tumorigenesis and progression and provided a reference for the clinical prognosis of patients with cancer and new therapeutic target discovery.

Identification of cuproptosis-related lncRNAs for prognosis and immunotherapy in glioma.

Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis-related genes have prognostic predictive value has not been clarified. In this study, uni-/multi-variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis-related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high- and low-risk groups. Either for grade 2-3 or for grade 4, glioma patients with high-risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high-risk group was functionally associated with immune responses and cancer-related pathways. The high-risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high-risk group were significantly higher than those in the low-risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T-cell co-stimulation pathways. In conclusion, we established a risk model based on cuproptosis-related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno-microenvironment status of glioma.

Microfibrillar-associated protein 2 is a prognostic marker that correlates with the immune microenvironment in glioma.

Aims: microfibrillar-associated protein 2 (MFAP2), a component of the extracellular matrix, plays key roles in regulating growth factor signal transduction and various malignant tumors. However, the clinicopathological features of microfibrillar-associated protein 2 in gliomas have not been elucidated to date. Methods: TCGA and CGGA databases were used to study the expression of microfibrillar-associated protein 2 in glioma and its relationship with clinicopathological features of patients with glioma. Western blotting was performed to detect the expression of microfibrillar-associated protein 2 protein in tissue samples from glioma patients. Gene set enrichment analysis (GSEA) was applied to detect biological processes and signal pathways related to microfibrillar-associated protein 2. Single-sample gene set enrichment analysis, TIMER 2.0, and TISIDB databases were used to evaluate the role of microfibrillar-associated protein 2 in tumor immune characteristics. The prognostic role of microfibrillar-associated protein 2 in glioma was analyzed using the Kaplan-Meier method and Cox regression. Survival data were used to establish a nomogram prediction model. Results: microfibrillar-associated protein 2 expression was significantly elevated in gliomas. receiver operating characteristic analysis revealed good discrimination of microfibrillar-associated protein 2 between glioma and normal tissues. High expression of microfibrillar-associated protein 2 was associated with malignant phenotypes, such as histological type. Based on gene set enrichment analysis, we identified pathways associated with high microfibrillar-associated protein 2 expression. High microfibrillar-associated protein 2 expression was related to the infiltration of tumor immune cells, including Th2 cells and macrophages, and correlated with key markers of T-cell exhaustion. Based on the TISIDB database, microfibrillar-associated protein 2 was observed to be associated with chemokines, chemokine receptors, and multiple immunoinhibitors in glioma. Kaplan-Meier survival analyses revealed that high microfibrillar-associated protein 2 expression predicted poor overall survival, DSS, and PFS in patients with glioma. By combining microfibrillar-associated protein 2 and other prognostic factors, a nomogram prognostic prediction model was constructed, which demonstrated an ideal prediction effect. Conclusion: microfibrillar-associated protein 2 is a potential prognostic marker that plays a key role in glioma development given its association with malignant phenotypes, cancer-related pathways and tumor immunity.

Primary Malignant Brain Tumors following Systemic Malignancies: A Population-Based Analysis.

BACKGROUND: Several reports have described glioma following different cancers. We assessed the prevalence of primary malignant brain tumors afterward systemic malignancies in patients in the USA based on Surveillance, Epidemiology, and End Results (SEER) program data. METHODS: The detailed data of patients with primary malignant brain tumors following an initial malignant tumor outside the central nervous system were extracted from SEER. Descriptive statistics were used to analyze patient demographic and clinical characteristics. We also extracted standardized incidence ratios (SIRs) stratified by age, race, sex, history of radiation or chemotherapy, histology findings, and primary cancer site. RESULTS: We identified 5,212 patients diagnosed with primary malignant brain tumors following systemic malignancies. Most patients had prostate cancer, breast cancer, and skin melanoma as the primary cancer. The median duration between the first diagnosis of cancer and that of the subsequent malignant brain tumor was 53 months. Glioblastoma was the most common subsequent malignant brain tumor type. The prognosis after subsequent malignant brain tumor diagnosis was poor. The SIRs differed most by race, cancer site, and cancer type. Patients with acute lymphocytic leukemia had the highest risk of developing primary malignant brain tumors. CONCLUSION: Our study provides a comprehensive analysis of clinical data and the SIRs of patients with primary malignant brain tumors afterward other systemic malignancies. Genetic relationships might play a key role in subsequent malignant brain tumor origin. Our data provide directions for future studies exploring the hidden associations between systemic malignancies and primary malignant brain tumors.