More and more studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome has become the regulatory factor of inflammatory response and protective immunity, and the assembly and activation of NLRP3 inflammasomes are closely related to the anti-tumor immunity effect. Depending on the cell type and stimuli, activation of the NLRP3 inflammasome can induce immune cells to become polarized, hyperactive, or pyroptotic, releasing interleukin (IL)-1β and IL-18, which leads to cascade immune or inflammatory responses, and its role in tumor immunity has received extensive attention. Here, we review the mechanisms of the NLRP3 inflammasome enhancing CD8⁺ T cells-mediated anti-tumor immunity by inducing the pyroptosis of tumor cell, the pyroptosis or hyperactive state of dendritic cells (DCs), and the pyroptosis or polarization of the macrophages. Different anti-tumor immune roles of NLRP3 inflammasome activation in tumor cells and immune cells provide new directions for future research and may influence the development of next-generation immunotherapy.

Objective To investigate the expression of vascular endothelial growth factor (VEGF) and aquaporin 4 (AQP4) in giiomas and brain metastases, and explore the role of VEGF and AQP4 in the histopathology and formation of peritumoral edema of primary and metastatic gliomas. Methods Immunohistocbemical method was used to examine the protein expression of VEGF and AQP4 in 73 paraffin-embeded, pathologically confirmed glioma and 15 metastatic tumor specimens collected between 1999 and 2001. Eight normal brain tissue specimens were used as the control. Results VEGF protein was not detected in normal brain tissues. VEGF expression was detected in gliomas and the expression level increased obviously along with the histological grade of the tumor. Significant differences were found in VEGF expression between malignant and low-grade gliomas, between low-grade gliomas and normal brain tissues, and between intracranial metastatic tumors and normal brain tissues and low-grade gliomas (P<0.05), but not between intracranial metastatic tumors and malignant gliomas (P>0.05). AQP4 protein expression was found in all the collected samples, and its expression differed significantly between normal brain tissues and malignant gliomas or intracranial metastatic tumors, and also between low-grade gliomas and malignant gliomas or intracranial metastatic tumors (P<0.05), but not between normal brain tissues and low-grade gliomas or between intracranialmetastatic tumors and malignant gliomas (P>0.05). VEGF protein expression showed a significant positive correlation to AQP4 protein expression (r=0.516, P<0.05). Conclusion As important molecular biological factors, VEGF and AQP4 participate in the formation peritumoral brain edema of gliomas and exhibit a synergie effect in this process.

Humans ; Magnetic Resonance Imaging ; Male ; Meningeal Neoplasms ; diagnosis ; pathology ; Meningioma ; diagnosis ; pathology ; Middle Aged

Acute Disease ; Adult ; Altitude Sickness ; blood ; enzymology ; Glutathione ; blood ; Glutathione Peroxidase ; blood ; Humans ; Lipid Peroxidation ; Male ; Military Personnel ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Oxidoreductases ; metabolism ; Superoxide Dismutase ; blood

This study was purposed to investigate the effect of rapamycin on proliferation, apoptosis, cell cycle progression and the regulation of chemokine receptor CXCR4 on RPMI8226 cells. Different concentrations of rapamycin were used to treat the multiple myeloma cell line RPMI8226 for different times. The proliferation of the cells was detected by MTT assay; the apoptosis rate and cell cycle were determined by flow cytometry (FCM); apoptosis of cells was observed by inverted microscopy; the cylin D1, CXCR4 and mTOR mRNA expressions were detected by RT-PCR or FQ-PCR after treating RPMI8226 cells with different concentrations of rapamycin. The results indicated that the rapamycin could inhibit the proliferation of RPMI8226 cells and induce their apoptosis. The cell cycle was arrested at the G(0)/G(1) phase. PCR results showed the down-regulation of mTOR, cyclin D1 and mTOR mRNA expressions after treating RPMI8226 cells with different concentrations of rapamycin for 24 hours. It is concluded that the rapamycin significantly inhibits the growth of RPMI8226 cells in a dose-and time-dependent mannes and induce cell apoptosis. Cell cycle arrests at the G(0)/G(1) phase, may be due to the down-regulation of the mTOR and cyclin D1 expressions. In additions, the down-regulation of CXCR4 mRNA expression is correlated with the reduction of adhesion between myeloma cells and stromal cells.
Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Down-Regulation ; Humans ; Receptors, CXCR4 ; metabolism ; Sirolimus ; pharmacology

To explore differentially expressed genes in leukemia gene expression profile and identify main related genes in acute leukemia, gene expression profiles were analyzed in bone marrow/leucopheresis peripheral blood stem cells samples from 9 acute leukemia patients and their sibling donors with the use of oligonucleotide microarrays. 163 reported leukemia-related genes were involved in the study. The oligonucleotide primers were designed, synthesized and spotted on the chemical-material-coated-glass plates in array. The total RNAs were isolated from nine patients' bone marrow or leucopheresis peripheral blood cells and from nine their sibling donors peripheral blood stem cells treated by G-CSF, then collected by CS-3000 cell selection machine, and were reversely transcribed to cDNAs with the incorporations of fluorescent dUTP. The mixed probes were then hybridized to the oligonucleotide microarray. The results showed that in four patient/donor pairs with B-ALL, 5 up-regulated (RIZ, STK-1, T-cell leukemia/lymphoma 1A, Cbp/p300, Op18) and 1 down-regulated genes (hematopoietic proteoglycan core protein) were identified; In five patient/donor pairs with AML-M(4) and AML-M(5), 6 up-regulated (STAT5B, ligand p62 for the Lck SH2, CST3, LTC4S, myeloid leukemia factor 2 and epb72) and 1 down-regulated genes (CCR5) were identified. In conclusion, on the basis of distinguishing study of specific genetic related recipient/sibling donor pairs, screening leukemia-related genes with oligonucleotide microarrays, a set of 13 up-regulated or down-regulated genes among 163 leukemia-related genes has been identified. The result has further confirmed that above genes play critical role in the molecular mechanism of acute leukemia.
Blood Donors ; DNA-Binding Proteins ; genetics ; Gene Expression Profiling ; Glutathione Transferase ; genetics ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Microtubule Proteins ; genetics ; Milk Proteins ; genetics ; Oligonucleotide Array Sequence Analysis ; Peripheral Blood Stem Cell Transplantation ; Phosphoproteins ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; STAT5 Transcription Factor ; Siblings ; Stathmin ; Trans-Activators ; genetics

Humans ; Leukemia, Myelomonocytic, Chronic/drug therapy* ; Nitriles ; Pyrazoles/therapeutic use* ; Pyrimidines

Abstract：Objective To prepare human monoclonal antibody against spike protein（S protein）of severe acute respiratory syndrome coronavirus 2（SARS⁃CoV⁃2）by using single B cell，and determine its neutralizing activity. Methods Venous blood with high antibody level was collected from people immunized with inactivated SARS⁃CoV⁃2 vaccine（Vero cells） twice，of which peripheral blood mononuclear cells（PBMCs）were isolated by lymphocyte stratified fluid and used to isolate single B cell expressing S protein antibody by magnetic beads coupled with S1 protein. Variable region genes of IgG heavy chain and light chain were amplified by nested PCR after reverse transcription of single B cell，which were connected with CMV promoter，IgG leader sequence，IgG constant region and polyA sequence by overlapping PCR to construct antibody linear expression cassette. Linear expression cassette of the heavy chain and light chain from the same B cell was transfected to HEK293T cells to express human monoclonal antibody of SARS⁃CoV⁃2 S protein. Immunoreactivity was detected by immuno⁃ fluorescence while neutralizing activity by pseudovirus neutralization test. Results A total of 26 monoclonal antibodies against SARS⁃CoV⁃2 S protein were expressed，which showed heavy chain and light chain protein bands of IgG antibody at