Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways.

BACKGROUND: In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule on tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an immune checkpoint in various malignant tumors, mediating tumor immune evasion. However, its specific molecular mechanisms, especially in glioma, remain elusive. METHODS: Lentivirus was transfected to establish cells with stable knockdown of trem2. A Transwell system was used for segregated coculture of glioma cells and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), and immunofluorescence (IF) were used to measure the expression levels of target proteins. The proliferation, invasion, and migration of cells were detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays. The cell cycle, apoptosis rate and reactive oxygen species (ROS) level of cells were assessed using flow cytometry assays. The comet assay and tube formation assay were used to detect DNA damage in glioma cells and angiogenesis activity, respectively. Gl261 cell lines and C57BL/6 mice were used to construct the glioma orthotopic transplantation tumor model. RESULTS: Trem2 was highly overexpressed in glioma TAMs. Knocking down trem2 in microglia suppressed the growth and angiogenesis activity of glioma cells in vivo and in vitro. Mechanistically, knockdown of trem2 in microglia promoted proinflammatory microglia and inhibited anti-inflammatory microglia by activating jak2/stat1 and inhibiting the NF-κB p50 signaling pathway. The proinflammatory microglia produced high concentrations of nitric oxide (NO) and high levels of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß, and caused further DNA damage and promoted the apoptosis rate of tumor cells. CONCLUSIONS: Our findings revealed that trem2 in microglia plays a significant role in the TIME of gliomas. Knockdown of trem2 in microglia might help to improve the efficiency of inhibiting glioma growth and delaying tumor progression and provide new ideas for further treatment of glioma.

Midterm Outcome of Valve Repair for Rheumatic Mitral Stenosis: 6-year Experience in a Single Mid-Volume Cardiac Center.

OBJECTIVES: Previous studies have reported satisfactory long-term results of mitral valve (MV) repair for rheumatic mitral disease. However, the effects of this procedure in isolated rheumatic mitral stenosis remain unclear. In addition, protective effects of MV repair on cardiac function have not been verified in rheumatic MV disease. This study retrospectively evaluated early mortality and mid-term results of MV repair for isolated rheumatic mitral stenosis in a mid-volume cardiac centre, and explored the effects of this procedure on cardiac function. METHODS: Between January 2015 and May 2021, 360 patients with isolated rheumatic mitral stenosis and combined (concomitant) atrial fibrillation (AF) underwent MV repair (100 patients) or MV replacement (260 patients). Perioperative characteristics were compared between the two groups and a regression analysis for early mortality and mid-term left ventricular ejection fraction was conducted. In addition, mid-term survival was compared between the two groups. RESULTS: Baseline characteristics of the two groups were balanced after matching. Compared with patients in the replacement group, patients with MV repair had a lower occurrence of postoperative hypotension and AF. There was no difference in early mortality or mid-term survival between the two groups. However, MV repair was associated with a higher mid-term left ventricular ejection fraction. During follow-up, four thromboembolic events and four haemorrhagic events occurred in the replacement group. No blood coagulation-related complications occurred in the repair group. CONCLUSION: Mitral valve repair for isolated rheumatic mitral stenosis and concomitant AF was feasible in a mid-volume cardiac centre, with satisfactory perioperative results and mid-term outcomes. Furthermore, this procedure preserved mid-term left ventricular systolic function.

Ferroptosis and Its Potential Role in Glioma: From Molecular Mechanisms to Therapeutic Opportunities.

Glioma is the most common intracranial malignant tumor, and the current main standard treatment option is a combination of tumor surgical resection, chemotherapy and radiotherapy. Due to the terribly poor five-year survival rate of patients with gliomas and the high recurrence rate of gliomas, some new and efficient therapeutic strategies are expected. Recently, ferroptosis, as a new form of cell death, has played a significant role in the treatment of gliomas. Specifically, studies have revealed key processes of ferroptosis, including iron overload in cells, occurrence of lipid peroxidation, inactivation of cysteine/glutathione antiporter system Xc- (xCT) and glutathione peroxidase 4 (GPX4). In the present review, we summarized the molecular mechanisms of ferroptosis and introduced the application and challenges of ferroptosis in the development and treatment of gliomas. Moreover, we highlighted the therapeutic opportunities of manipulating ferroptosis to improve glioma treatments, which may improve the clinical outcome.

Intracerebral hemorrhage associated with brucellosis: A case report.

Background: Intracerebral hemorrhage is a common disease, but cases of intracerebral hemorrhage with brucellosis are very rare. Here, we are presenting a case of a 60-year-old male patient diagnosed with brucellosis who has a right basal ganglia hemorrhage ruptured into bilateral lateral ventricles. Case presentation: A 60-year-old male patient with symptoms of intracerebral hemorrhage who had no common risk factors for intracerebral hemorrhage, but having been diagnosed with brucellosis 2 months earlier and telling a shepherd history for 3 years. Cranial computed tomography (CT) and cranial magnetic resonance angiography (MRA) revealed that an intracerebral hemorrhage in the right basal ganglia had broken into bilateral lateral ventricles, and a Brucella serology test was positive. The patient's condition improved significantly after receiving bilateral lateral ventricle cone drainage, hematoma cavity cone drainage and anti-brucellosis treatment. Conclusions: Herein, we discuss the possible mechanisms and clinical implications between brucellosis and intracerebral hemorrhage. This case suggests whether we can use brucellosis as a routine examination for disease diagnosis and prevention in patients with intracerebral hemorrhage from pastoral areas.

CASP4 can be a diagnostic biomarker and correlated with immune infiltrates in gliomas.

Background: Gliomas are the most common and invasive malignant tumors that originate in the central nervous system. Currently, the primary treatment modality for gliomas is maximum surgical resection, supplemented by radiotherapy and chemotherapy. However, the long-term survival rate has not signifificantly increased. Pyroptosis is a new form of programmed lytic death that has been recently discovered. Caspase 4 (CASP4) plays a key role in pyroptosis. Many studies have shown that pyroptosis is not only related to inflflammation but is also closely related to the occurrence and development of most tumors. This study aimed to prove that CASP4 has a key role in the mechanism of gliomas. Methods: We used expression data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas to explore the relationship between CASP4 expression and glioma prognosis. The differential expression of CASP4 in gliomas and normal tissues was fifirst tested, and then the connection between CASP4 and tumor prognosis was explored. The relationship between CASP4 expression and immune cell infifiltration was also investigated. Finally, the possible pathways were analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Results: CASP4 was highly expressed and associated with a signifificantly lower survival rate in patients with glioma. It could also inflfluence immune cell infifiltration by releasing cytokines. Conclusion: CASP4 can be a diagnostic biomarker and is a promising therapeutic target for gliomas.