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.

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

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

OBJECTIVESTo investigate the radiological change of bilateral paravertebral muscles in degenerative lumbar scoliosis (DLS) and analyze its clinical significance.

METHODSAs a retrospective study, 66 patients with DLS and 66 patients with lumbar spinal stenosis were retrospectively enrolled from April 2004 to August 2011 as scoliosis group and lumbar spinal stenosis group, meanwhile 66 health persons with no lumbar spinal stenosis were selected as control group. No significant differences were found in the gender, age and body mass index among the three groups. The cross-sectional area (CSA) and percentage of fat infiltration area (FIA) of the bilateral paravertebral muscles at the L(1)-S(1) levels were measured using T2-weighted axial MRI and Image J software. The measured data were analyzed with a paired t-test.

RESULTSIn the DLS with bilateral symptom group, the mean percentage of FIA of the multifidus muscle on the convex side were 18% ± 4%, 21% ± 4%, 27% ± 4%, 34% ± 6%, 42% ± 10% and on the concave side were 25% ± 8%, 30% ± 7%, 35% ± 7%, 40% ± 10%, 44% ± 8% at L(1-2), L(2-3), L(3-4), L(4-5) and L(5)-S(1) levels, which showed significant differences between the convex side and the concave side (t = 7.95, 9.30, 5.35, 2.78, 2.38, P < 0.05); the mean percentage of FIA of the longissimus muscle on the convex side were 25% ± 9%, 28% ± 8% and on the concave side were 27% ± 9%, 31% ± 9% at L(3-4), L(4-5) levels, which showed significant differences between the convex side and the concave side (t = 2.52, 3.48, P < 0.05). There were no significant differences in the CSA of both muscles between the concave and convex sides (P > 0.05). In the DLS with unilateral symptom group, the mean percentage of FIA of the multifidus muscle on the convex side were 18% ± 5%, 23% ± 5%, 29% ± 5%, 34% ± 6%, 42% ± 9% and on the concave side were 23% ± 6%, 30% ± 7%, 36% ± 7%, 41% ± 10%, 45% ± 8% at L(1-2), L(2-3), L(3-4), L(4-5) and L(5)-S(1) levels, which showed significant differences between the convex side and the concave side (t = 6.67, 7.96, 6.43, 3.86, 2.15, P < 0.05). There were on significant differences in the CSA of both muscles, and in the percentage of FIA of the longissimus between the concave and convex sides (P > 0.05).

CONCLUSIONSThere exist asymmetric degeneration in paravertebral muscle in DLS, which have potential clinical importance on the evaluation of curve progression, and muscle degeneration is more often seen in the concave side. Spinal deformity and radiculopathy may contribute to the paravertebral muscle degeneration.

Aged ; Case-Control Studies ; Female ; Humans ; Lumbar Vertebrae ; diagnostic imaging ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Muscle, Skeletal ; diagnostic imaging ; pathology ; Muscular Atrophy ; pathology ; Radiography ; Retrospective Studies ; Scoliosis ; diagnostic imaging ; pathology

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

OBJECTIVETo construct a lentiviral expression vector of the PIAS-NY gene, and establish a mouse spermatocyte-derived cell line with a stable overexpression of PIAS-NY.

METHODSPIAS-NY was synthesized, amplified by PCR and cloned into the lentiviral vector expression plasmid pGC-FU. After digestion and sequencing, pGC-FU-PIAS-NY, pHelper 1.0 and pHelper 2.0 were co-transfected into 293T cells. Then the lentiviral particles were used to transfect the mouse spermatocyte-derived cells. The expression of the PIAS-NY protein was detected by Western blot.

RESULTSWe successfully constructed the lentiviral expression vector pGC-FU-PIAS-NY and established a mouse spermatocyte-derived cell line with a stable overexpression of PIAS-NY.

CONCLUSIONThe construction of the lentiviral expression vector pGC-FU-PIAS-NY and the obtainment of stably transfected mouse spermatocyte-derived cells have paved the way for further studies on the roles of the PIAS-NY gene in spermatogenesis.

Animals ; Cell Line ; Genetic Vectors ; Lentivirus ; genetics ; Male ; Mice ; Plasmids ; Protein Inhibitors of Activated STAT ; genetics ; Spermatocytes ; cytology ; Transfection

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.