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.

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

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

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.

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

To investigate the purging effect of CD3AK/iNOS on primary leukemic cells from chronic myeloid leukemia patients in vitro, amphotropic packaging cell line PA317 transfected with the whole length of iNOS gene was cultivated, amplified and screened by G418. The viral titer was determined by the NIH3T3 cells. Human peripheral blood mononuclear cells were isolated and activated by anti-CD3 monoclonal antibody in vitro. CD3AK cells were incubated with viral supernatant and selected by G418. Resistant clones were assayed for iNOS gene expression by RT-RCR. The content of nitric oxide and the activity of iNOS in the culture supernatant of CD3AK/iNOS were evaluated by the method of Griess. After BMMNC or PBMNC from CML patients were co-cultured with CD3AK/iNOS, CD3AK/Neo and CD3AK/iNOS respectively, the expression of bcr/abl fusion gene was detected by serial dilution semi-quantitative net RT-PCR assay. The results showed that anti-G418 positive packaging cell line PA317 transfected with the whole length of iNOS gene clones could stably synthesize and excrete recombinant retroviral vectors. The titer of recombinant retroviral vectors was 1.0 x 10(5) CFU/ml. After being transfected by recombinant retroviral supernatant, the iNOS cDNA was expressed in CD3AK/iNOS. The content of NO and activity of iNOS that synthesized and excreted by CD3AK/iNOS were notably increased, compared with those of CD3AK. There were statistically significant differences in NO content and iNOS activity between two groups. After BMMNC or PBMNC from CML patients were co-cultured with CD3AK/iNOS, CD3AK/Neo and CD3AK/iNOS respectively, the expression of bcr/abl fusion gene in all of them was down-regulated by serial dilution semi-quantitative RT-PCR assay. It is concluded that construction of CD3AK/iNOS can markedly increase the content of NO and the activity of iNOS, which can be more efficient in in vitro purging leukemia cells for autologous hematopoietic stem cell transplantation.
Adult ; Aged ; Animals ; CD3 Complex ; immunology ; Cell Line ; Cytotoxicity, Immunologic ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; immunology ; pathology ; Male ; Mice ; Middle Aged ; NIH 3T3 Cells ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured

OBJECTIVETo explore the relationship between genetic polymorphisms of glutathione S-transferase (GST) M1, T1 and susceptibility to mountain sickness.

METHODSForty-three soldiers with acute mountain sickness and 80 healthy soldiers matching with sex/age and training under the same condition were divided into case group and control group. A multiple polymerase chain reaction method was used to detect GSTM1 and GSTT1 genes in genomic DNA isolated from peripheral blood cells from both cases and controls.

RESULTSThe frequency of the GSTT1 positive genotype was significantly higher in cases (69.8%) than in controls (42.5%) (P = 0.004, OR = 3.12, 95% CI 1.42 approximately 6.86). The frequency of GSTM1 negative genotype was also higher in cases (72.1%) than in controls (52.5%) (P = 0.03, OR = 2.34, 95% CI 1.05 approximately 5.02). Persons with both GSTM1 and GSTT1 negative genotypes had 5-fold more risk than those with GSTT1 negative and GSTM1 positive genotypes in developing mountain sickness (OR = 5.04, 95% CI: 1.00 approximately 25.3).

CONCLUSIONGenetic polymorphisms of glutathione S-transferase M1, T1 may be the risk factors in the development of mountain sickness.

Acute Disease ; Adult ; Altitude Sickness ; genetics ; Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Risk Factors

Objective To investigate the association between serum total testosterone (TT ) levels and type 2 diabetes(T2DM )and any gender differences in elderly patients. Methods Based on the Aging Health database built from 2008 to 2012 ,935 elderly individuals over 60 years old with a mean age of 65.8 years receiving physical examinations were included.According to the 1999 WHO criteria for diabetes ,participants were assigned into four groups :a T2DM group(n＝298) ,an impaired fasting glucose(IFG)group(n＝26) ,an impaired glucose tolerance(IGT)group(n＝121) ,and a normal glucose regulation(NGR)group(n ＝ 490).We measured serum TT by ELISA and analyzed the distribution patterns in the groups.Furthermore ,we examined the gender-specific correlation of TT with T2DM and homeostasis model assessment of insulin resistance (HOMA-IR). Results The prevalence of T2DM in the participants was 31.9%(298/935).One-way ANOVA analysis showed that the TT level was higher in the NGR group than in the T2DM and IGT groups (PANOVA＝ 0.001) . Logistic regression analysis indicated a significant protective association between TT and T 2DM in the elderly.Every one unit of increase in the SD of the TT level was accompanied by a 23% reduction in the risk for T2DM (P＝ 0.001).Further gender-stratification analysis suggested that the protective role of TT against T2DM only existed in males (OR＝ 0.55 ,95% CI :0.44-0.68 ;P＜ 0.001).After adjustment for age ,blood pressure ,blood lipids ,and waist circumference ,the protective role of TT against T2DM in males still remained (OR ＝ 0.68 ,95% CI :0.53-0.86 ;P ＝ 0.002 ).Pearson correlation analysis also indicated a significant negative correlation between TT and HOMA-IR in older males(P＝0.002).As for older females ,no significant correlation of TT with T2DM and HOMA-IR was found. Conclusions The serum TT level might be an independent protective factor for T 2DM in older males ,as evidenced by its correlation with improved insulin resistance status ,which is not present in older females.

The study was aimed to investigate the possible mechanism of vitamin K(2) (VK(2)) on myelodysplastic syndrome (MDS) cell line MUTZ-1 in vitro. The flow cytometry was used to analyze apoptosis rate and the change of cell cycle. The expression of apoptosis-related genes bcl-2, survivin and bax were detected by reverse transcription-polymerase chain reaction (RT-PCR). The activity of caspase-3 was detected by chemiluminescence assay. The results indicated that the apoptosis peak on FCM and positive Annexin-V FITC on cell membrane showed that VK(2) induced apoptosis of MUTZ-1 cells in a dose-and-time-dependent manner, S and G(2) cell decrement, G(0)/G(1) cell arrest, VK(2) significantly down-regulated the expression of bcl-2 and survivin, but had no effect on the expression of bax, the activity of caspase-3 was significantly increased. It is concluded that VK(2) induces apoptosis of MUTZ-1 cells through activating caspase-3 pathways and the apoptosis-related genes bcl-2 and survivin may play important roles in the process of apoptosis induction.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Humans ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Myelodysplastic Syndromes ; drug therapy ; pathology ; Neoplasm Proteins ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Vitamin K 2 ; pharmacology ; bcl-2-Associated X Protein ; biosynthesis ; genetics