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Background: DNA damage-induced apoptosis suppressor (DDIAS) has recently been discovered to induce cancer progression, but its functions and mechanisms in glioma have not been well studied. Methods: DDIAS expression in glioma tissues was analyzed by the Gene Expression Profiling Interactive Analysis server (GEPIA) and the Gene Expression database of Normal and Tumor tissue 2 (GENT2) databases. The role of DDIAS in glioma progression was studied by short hairpin RNA (shRNA) targeting DDIAS. The effects of DDIAS on glioma cell viability, cell proliferation, invasion, migration, and tumor sphere formation were determined by cell counting kit-8 (CCK-8), EdU, Transwell, tumor spheroid formation, extreme limiting dilution analysis assays in vitro and xenograft model construction in vivo. In addition, RNA sequencing and further functional experiments were used to analyze the DDIAS regulatory mechanism in glioma. Results: We found that DDIAS was highly expressed in glioma and that upregulated DDIAS indicated poor prognosis. Functionally, DDIAS knockdown inhibited glioma cell viability, cell proliferation, invasion and migration in vitro and tumor growth in vivo. In addition, lymphoid enhancer-binding factor 1 (LEF1) was identified as the downstream effector of DDIAS by RNA sequencing. DDIAS downregulation inhibited LEF1 mRNA and protein expression. The expression of DDIAS and LEF1 was positively correlated, and LEF1 overexpression rescued the inhibitory phenotype induced by DDIAS downregulation. We further showed that DDIAS downregulation inhibited cyclin A1, vimentin and the stemness-related factor CD133 and decreased the sphere formation capability, but these features were rescued by upregulation of LEF1. Conclusion: Taken together, these findings suggest that DDIAS promotes glioma progression and stemness by inducing LEF1 expression, proving that DDIAS may be a potential target for the treatment of glioma.
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BACKGROUND: Systemic lupus erythematosus (SLE) patients are extremely susceptible to opportunistic infections due to glucocorticoid and immunosuppressive treatments, which often occur in the respiratory system, the urinary system and the skin. However, multiple cerebral infections are rarely reported and their treatment is not standardized, especially when induced by a rare pathogen. CASE SUMMARY: A 46-year-old woman was treated with glucocorticoid and immunosuppressant for SLE involving the hematologic system and kidneys (class IV-G lupus nephritis) for more than one year. She was admitted to hospital due to headache and fever, and was diagnosed with multiple cerebral abscesses. Brain enhanced magnetic resonance imaging showed multiple nodular abnormal signals in both frontal lobes, left parietal and temporal lobes, left masseteric space (left temporalis and masseter region). The initial surgical plan was only to remove the large abscesses in the left parietal lobe and right frontal lobe. After surgery, based on the drug susceptibility test results (a rare pathogen Nocardia asteroides was found) and taking into consideration the patient's renal dysfunction, a multi-antibiotic regimen was selected for the treatment. The immunosuppressant mycophenolate mofetil was discontinued on admission and the dose of prednisone was reduced from 20 mg/d to 10 mg/d. Re-examination at 3 mo post-surgery showed that the intracranial lesions were reduced, the edema around the lesions was absorbed and dissipated, and her neurological symptoms had disappeared. The patient had no headaches or other neurological symptoms and lupus nephritis was stable during the 2-year follow-up period. CONCLUSION: In this report, we provide reasonable indications for immunosuppression, anti-infective therapy and individualized surgery for an SLE patient complicated with multiple cerebral abscesses caused by a rare pathogen, which may help improve the diagnosis and treatment of similar cases.
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Recent evidence suggests that CC chemokine ligand 20 (CCL20) is upregulated after subarachnoid hemorrhage (SAH). Here, we investigated the functions of CCL20 in SAH injury and its underlying mechanisms of action. We found that CCL20 is upregulated in an SAH mouse model and in cultured primary microglia and neurons. CCL20-neutralizing antibody alleviated SAH-induced neurological deficits, decreased brain water content and neuronal apoptosis, and repressed microglial activation. We observed increased levels of CCL20, CC chemokine receptor 6 (CCR6), interleukin 1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α), as well as of microglial activation in microglia treated with oxyhemoglobin (OxyHb). CCL20 or CCR6 knockdown reversed the effects of OxyHb on microglia. Conditioned medium from OxyHb-treated microglia induced neuronal apoptosis, while the percentage of apoptotic neurons in the conditioned medium from microglia transfected with CCL20 siRNA or CCR6 siRNA was decreased. We observed no decrease in OxyHb-induced apoptosis in CCL20-knockdown neurons. Conditioned medium from OxyHb-treated neurons led to microglial activation and induced CCR6, IL-1ß and TNF-α expression, while CCL20 knockdown in neurons or CCR6 knockdown in microglia reversed those effects. Our results thus suggest CCL20 may be targeted to elicit therapeutic benefits after SAH injury.
