[Objective] This study aimed to establish an in vitro culture model for porcine peripheral blood monocyte-derived dendritic cells (MoDCs). [Method] Fresh peripheral blood mononuclear cells (PBMCs) were separated f...[Objective] This study aimed to establish an in vitro culture model for porcine peripheral blood monocyte-derived dendritic cells (MoDCs). [Method] Fresh peripheral blood mononuclear cells (PBMCs) were separated from pig, and precursor dendritic cells were obtained by adherence method. The dendritic cells were treated by recombinant porcine granulocyte-monocyte colony stimulating factor (rpGM-CSF) and recombinant porcine interleukin-4 (rplL-4) together, and lipopolysaccharide (LPS) respectively. The cells in different time periods were collected. The morphology of the collected cells was observed by scanning electron microscopy; the expression of surface molecules and phagocytic ability to FITC-dextran were detected by flow cy- tometry; and the stimulating ability for allogeneic T cells was detected by mixed lymphocyte reaction. [Result] The DCs suffering maturation induction in vitro showed typical dendritic morphology; compared with those of DCs untreated by LPS, the cell surface expression of CDla, CD80, CD86, SLAII and CD172a of DCs treated by LPS was significantly increased, the phagocytic ability was reduced slightly, and the stimulating ability for allogeneic T cells was enhanced to some extent. [Conclusion] An in vitro culture method was successfully established for porcine MoDCs in this study, laying a foundation for further study on the role of porcine MoDCs in immunoregulation and anti-virus infection.展开更多
Objective To observe clinical therapeutic effects of warm needling and moxibustion on diabetic peripheral neuropathy (DPN) and their influence on nerve conduction velocity. Methods Fifty two cases were randomly divi...Objective To observe clinical therapeutic effects of warm needling and moxibustion on diabetic peripheral neuropathy (DPN) and their influence on nerve conduction velocity. Methods Fifty two cases were randomly divided into a treatment group (n =26) and a control group (n =26). In addition to basic treatment for lowering blood sugar in both groups, Pǐshū (BL 20), Shènshū (BL 23), Huántiào (GB 30), Zùsānlǐ (ST 36), Yánglíngquán (GB 34), Sānyīnjiāo (SP 6), Tàixī (KI 3), Qǔchí (LI 11), Wàiguān (TE 5) and Hégǔ (LI 4) were selected for warm needling and moxibustion in the treatment group. Methycobal was intramuscularly injected in the control group. Clinical symptoms and conduction velocities of the tibial nerve and common peroneal nerve were compared before and after treatment. Results Warm needling and moxibustion could alleviate such clinical symptoms as numbness of limbs, pain and hypoesthesia, and obviously improve the conduction velocities of both tibial and common peroneal nerves. Conclusion Warm needling and moxibustion exhibit good therapeutic effects on diabetic peripheral neuropathy.展开更多
AIM: To investigate the molecular mechanisms by which tea pigments exert preventive effects on liver carcinogenesis. METHODS: HepG2 cells were seeded at a density of 5×10^5/well in six-well culture dishes and i...AIM: To investigate the molecular mechanisms by which tea pigments exert preventive effects on liver carcinogenesis. METHODS: HepG2 cells were seeded at a density of 5×10^5/well in six-well culture dishes and incubated overnight. The cells then were treated with various concentrations of tea pigments over 3 d, harvested by trypsinization, and counted using a hemocytometer. Flow cytometric analysis was performed by a flow cytometer after propidium iodide labeling. Bd-2 and p21^WAF1 proteins were determined by Western blotting. In addition, DNA laddering assay was performed on treated and untreated cultured HepG2 cells. RESULTS: Tea pigments inhibited the growth of HepG2 cells in a dose-dependent manner. Flow-cytometric analysis showed that tea pigments arrested cell cycle progression at G1 phase. DNA laddering was used to investigate apoptotic cell death, and the result showed that 100 mg/L of tea pigments caused typical DNA laddering. Our study also showed that tea pigments induced upregulation of p21^WAF1 protein and downregulation of Bcl-2 protein. CONCLUSION: Tea pigments induce cell-cycle arrest and apoptosis. Tea pigments may be used as an ideal chemopreventive agent.展开更多
Objective: To investigate the effect of activation-induced cell death (AICD) on cellular immune function in the condyloma acuminatum(CA). Methods: Peripheral blood mononuclear cells (PBMC) were isolated from normal he...Objective: To investigate the effect of activation-induced cell death (AICD) on cellular immune function in the condyloma acuminatum(CA). Methods: Peripheral blood mononuclear cells (PBMC) were isolated from normal healthy individuals (control group) and patients with CA. PBMC were cultured with PHA-P for 48h in vitro. Apoptosis of the PBMC was detected by flow cytometry. Supernatant cytokines (IL-2 and IL-10) were assayed by ELISA. Results: The rate of PBMC apoptosis in both CA group and control group in fresh PBMC was very low and similar in both groups(P>0.05). The rate of PBMC apoptosis within the CA group was noticeably increased compared to that of the control (P<0.001)af-ter PBMC were cultured for 48h. The level of IL-2 was significantly lower in the CA group than in the control group (P<0.001), The level of IL-10 was significantly higher in the CA group compared to thecontrol group(P<0.001). Conclusion: Study results indicate that AICD may affect cellular mediated immune function and play an important role in the pathogenesis of CA.展开更多
In the paper, we study a super-conducting junctions device subject to an input periodic signal and a constant force. It is shown that, for this device, we can get current reversals for the current of the electron pair...In the paper, we study a super-conducting junctions device subject to an input periodic signal and a constant force. It is shown that, for this device, we can get current reversals for the current of the electron pairs versus the frequency of the periodic signal and negative conductance for the current of the electron pairs as a function of the constant force.展开更多
The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apop...The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apoptosis. In the present study, the degradation of pRB was observed in apoptotic gastric tumor cells treated with a new potent anti-tumor component, tripchlorolide (TC). The inhibition of pRB degradation by a general cysteine protease inhibitor IDAM resulted in the reduction of the apoptotic cells. Furthermore, the survival of the gastric tumor cells under the TC treatment was enhanced by an over-expression of exogenous pRB. These results suggest that the pRB degradation of the gastric tumor cells under the TC treatment involves in the apoptotic progression. In addition, the same extent of TC- induced pRB-degradation was detected in the gastric tumor cells containing a p53 dominant-negative construct, indicat- ing that this kind of pRB degradation is p53-independent.展开更多
I discuss the modification of Einstein's Theory of General Relativity based on a periodic functional approach. In this new approach, a corrected periodic gravitational coupling constant arises and plays the role of p...I discuss the modification of Einstein's Theory of General Relativity based on a periodic functional approach. In this new approach, a corrected periodic gravitational coupling constant arises and plays the role of periodic damping term acting on the theory. It is found that it is achievable to have an oscillating universe dominated by dark energy and expanding aceeleratedly in time.展开更多
DNA mismatch repair (MMR) processes the chemically induced mispairs following treatment with clinically important nucleoside analogs such as 6-thioguanine (6-TG) and 5-fluorouracil (5-FU). MMR processing of thes...DNA mismatch repair (MMR) processes the chemically induced mispairs following treatment with clinically important nucleoside analogs such as 6-thioguanine (6-TG) and 5-fluorouracil (5-FU). MMR processing of these drugs has been implicated in activation of a prolonged G2/M cell cycle arrest for repair and later induction of apoptosis and/or autophagy for irreparable DNA damage. In this study, we investigated the role of Bcl2 and adenovirus EIB Nineteen-kilodalton Interacting Protein (BNIP3) in the activation of autophagy, and the temporal relationship between a G2/M cell cycle arrest and the activation of BNIP3-mediated autophagy following MMR processing of 6-TG and 5-FU. We found that BNIP3 protein levels are upregulated in a MLHI (MMR+)-dependent manner following 6-TG and 5-FU treatment. Subsequent small-interfering RNA (siRNA)-mediated BNIP3 knockdown abrogates 6-TG- induced autophagy. We also found that p53 knockdown or inhibition of mTOR activity by rapamycin cotreatment impairs 6-TG- and 5-FU-induced upregulation of BNIP3 protein levels and autophagy. Furthermore, suppression of Checkpoint kinase 1 (Chkl) expression with a subsequent reduction in 6-TG-induced G2/M cell cycle arrest by Chkl siRNA promotes the extent of 6-TG-induced autophagy. These findings suggest that BNIP3 mediates 6-TG- and 5-FU-induced autophagy in a p53- and mTOR-dependent manner. Additionally, the duration of Chkl-activated G2/ M cell cycle arrest determines the level of autophagy following MMR processing of these nucleoside analogs.展开更多
AIM: To determine the functional significance of TC21 in esophageal squamous cell carcinoma (ESCC). METHODS: TC21 siRNA transfection was carried out using Hyperfectamine to knock down TC21, and tran- scripts were ...AIM: To determine the functional significance of TC21 in esophageal squamous cell carcinoma (ESCC). METHODS: TC21 siRNA transfection was carried out using Hyperfectamine to knock down TC21, and tran- scripts were analyzed by reverse transcription-poly- merase chain reaction and protein by Western blotting.We demonstrated the effect of TC21 downregulation of cell signaling in esophageal cancer cells by assess- ing the phosphorylation status of its downstream tar- gets, phosphoinositide 3-kinase (PI3K), phosphatase and tensin homolog (PTEN), protein kinase B (pAl〈t), nuclear factor-KB (NF-~B) and cyclinD1 using specific antibodies. Cell survival analysis after cisplatin treat- ment was carried out by cell viability assay and cell cycle analysis using flow cytometry. RESULTS: TC21 knockdown in human ESCC cell line TEl3 cells, showed only a marginal increase (14.2%) in cell death compared with control cells. The expres- sions of the signaling proteins PI3K and pAkt, transcrip- tion factor NF-KB, and cell cycle protein cyclin D1 were markedly decreased in response to TC21 downregula- tion, whereas the level of pPTEN, an antagonist of PI3K, was increased. In addition, we evaluated the potential of TC21 as a putative target for sensitizing ESCC cells to the chemotherapeutic agent cisplatin. Increased cell death (38.4%) was observed in cells treated with cis- platin after TC21 knockdown compared with cells which were treated with cisplatin alone (20% cell death). CONCLUSION: Results suggest that TC21 mediates its effects via the PI3K-Akt pathway, NF-KB and cyclin D1, and enhances chemoresistance in esophageal cancer cells.展开更多
A novel periodic mount was presented. A theoretical model was developed to describe the dynamics of wave propagation in the novel periodic mount. The model was derived using Hamilton's energy conservation principl...A novel periodic mount was presented. A theoretical model was developed to describe the dynamics of wave propagation in the novel periodic mount. The model was derived using Hamilton's energy conservation principle. The characteristics of wave propagation in unit cell were analyzed by transfer matrix formulation. Numerical examples were given to illustrate the effectiveness of the periodic mount. The experiments were carried out to identify the predications of the theoretical model. The obtained results show that the experimental results coincide with the prediction of theoretical model. No pass bands appear in the overall frequency range measured when waves propagate in the longitude direction of the periodic mount. These dramatic results demonstrate its potential as an excellent mount in attenuating and isolating vibration transmission.展开更多
Electrically conducting fabrics used as flexible sensors can be produced by vacuumed vapor deposition.The research of what impacts the wide and reliable application of the flexible sensors shows that the stability of ...Electrically conducting fabrics used as flexible sensors can be produced by vacuumed vapor deposition.The research of what impacts the wide and reliable application of the flexible sensors shows that the stability of flexible sensors is one of the critical issues.The electrical performance of weft knitted fabrics in course and wale direction does not show significant differences under different ambient conditions,which include time,temperature,and relative humidity.Tests of stimuli responding sensitivity of conductive fabrics indicate that the sensitivity keeps at a constant level and the average sensitivity is stable over 38 days.展开更多
Objective: To analyze the therapeutic effect of contralateral needling in the treatment of scapulohumeral periarthritis. Methods: A total of 68 cases of scapulohumeral periarthritis were outpatients and were randomize...Objective: To analyze the therapeutic effect of contralateral needling in the treatment of scapulohumeral periarthritis. Methods: A total of 68 cases of scapulohumeral periarthritis were outpatients and were randomized into treatment group (n=36) and control group (n=32). In treatment group, Zhiyin (BL 67), Jinmen (BL 63) and Yanglao (SI 6) on the contralateral side of the affected shoulder and local tenderpoints (Ashi-points) were punctured once every other day, with 7 days being a therapeutic course; while in control group, local Ashi-points were used for injection of Procaine and Prednisolone Acetate, once every 7 days and with 3~4 sessions being a therapeutic course. Results: Following 2 courses of treatment, of the 32 cases in control group, 8 (25.0%) were cured, 17 (53.1%) experienced improvement and 7 failed in the treatment, with a total of effective rate of 78.1%; of the 36 cases in treatment group, 18 (50.0%) were cured, 16 (44.4%) experienced improvement and 2 (5.6%) failed in the treatment, with a total effective rate of 94.4%. The therapeutic effect of contralateral needling is significantly higher than that of Ashi-point blocking method (P<0.05). Conclusion: Contralateral needling is superior to Ashi-point in the treatment of scapulohumeral periarthritis.展开更多
Objective: The aim of the study was to observe the expression of Bcl-2 and its phosphorylation in Molt-4 cells induced by tumor necrosis factor-α (TNF-α), and to investigate the possible mechanism of cell cycle s...Objective: The aim of the study was to observe the expression of Bcl-2 and its phosphorylation in Molt-4 cells induced by tumor necrosis factor-α (TNF-α), and to investigate the possible mechanism of cell cycle specificity of apoptosis. Methods: Exponentially growing Molt-4 cells were treated with TNF-α. Apoptosis was detected by DNA fragmentation assay. API method was applied to illustrate the cell cycle specificity of apoptotic cells. Cells of sub-phases were sorted by FACSvan- tage flow cytometer and then submitted to immunoblot. Results: Molt-4 cells which were treated with TNF-α went to apoptosis and showed a DNA ladder pattern. Most apoptosis happened in Gl-phase of cell cycle. Bcl-2 expression increased for the Molt-4 cells treated with TNF-α. The phosphorylation state of Bcl-2 was only presented in Gl-phase cells, in accordance with the specified time and cell cycle phase of apoptosis. Conclusion: The phosphorylation of Bcl-2 in the Molt-4 cells treated with TNF-α happened with the same cell cycle specificity as cell apoptosis. The cell cycle specificity of Bcl-2 phosphorylation was one of the mechanisms of receptor-mediated apoptosis. The cell cycle machine can trigger the apoptosis program.展开更多
OBJECTIVE To investigate the correlation of E2F-1, Rb and ER expression with peripheral papilloma (Peri-PM) and ductal carcinoma in situ of the breast (DCIS), and further explore some molecular mechanisms of the c...OBJECTIVE To investigate the correlation of E2F-1, Rb and ER expression with peripheral papilloma (Peri-PM) and ductal carcinoma in situ of the breast (DCIS), and further explore some molecular mechanisms of the canceratin of Peri-PM.METHODS Imunohistochemistry was used to examine the expression of E2F-1, Rb and ER in 60 Peri-PM, 60 Peri-PM with atypical ductal hyperplasia (Peri-PM with ADH) and 60 DCIS. Normal breast tissues were selected as a control group.RESULTS Based on immunohistochemical staining, the positive rate of E2F-1 expression in Peri-PM, Peri-PM with ADH and DCIS was 21.7%, 46.7% and 78.3% respectively. The positive rate of Rb expression was 83.3 %, 53.9% and 21.7% and the ER expression was 86.7%,61.7% and 55.0%. Significant differences were found among the 3 groups (Peri-PM, Peri-PM with ADH and DCIS) (P〈0.05). Significant differences existed between any 2 groups (P〈0.05) except for the rate of ER positive expression comparing Peri-PM with ADH verus DCIS (P〉0.05). The expression of E2F-1 was nega- tively correlated with ER and Rb, and at the same time the expression of ER was positively correlated with Rb. Following the degree of breast epithelial hyperplasia involved and its development into carcinoma, the positive rate of E2F-1 expression displayed an elevating tendency, but that of Rb and ER expression showed a tendency to decline.CONCLUSION The interaction of the 3 indexes studied may play an important role in the conversion of precancerous lesions to early in situ breast carcinoma, and the evaluation of these indexes might provide a valuable basis for screening high-risk cases of Peri-PM.展开更多
AIM: To investigate the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in human gastric cancer and it's mechanism in apoptosis and cell cycle arrest. METHODS: Expression of 15-PGDH mRNA and protein ...AIM: To investigate the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in human gastric cancer and it's mechanism in apoptosis and cell cycle arrest. METHODS: Expression of 15-PGDH mRNA and protein was examined by immunohistochemistry, immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting in tissue from human gastric cancer, gastric precancerous state (gastric polyps and atrophic gastritis), normal stomach, and gastric cancer cell lines. The relationship between gastric cancer, gastric precancerous state and 15-PGDH expression was determined. The association between expression of 15-PGDH and various clinicopathological parameters in gastric cancer was evaluated. Human gastric cancer cell line SGC-7901 was transfected with 15-PGDH expression plasmids. The effect of 15-PGDH on the cell cycle was examined by flow cytometry. The effect of 15-PGDH on apoptosis was examined by transmission electron microscopy, flow cytometry and transferasemediated nick end labeling (TUNEL) assay. Expression of cell cycle (p21, p27, p16 and p53) and apoptosis (Survivin, BCL-2, BCL-XL, BAK and BAX) genes was analyzed by RT-PCR. RESULTS: Expression of 15-PGDH mRNA and protein in human gastric cancer tissues was significantly lower than in normal gastric tissues (P < 0.01). Expression in human gastric cancer cell lines MKN-28 and MKN-45 was reduced, and absent in SGC-7901 cells (P < 0.05). Reduction of 15-PGDH expression was also found in precancerous tissues, such as gastric polyps and atrophic gastritis (P < 0.01). There was a significant difference in expression of 15-PGDH among various gastric cancer pathological types (P < 0.05), with or without distant metastasis (P < 0.05) and different TNM stage (P < 0.01). Flow cytometry demonstrated a significant increase in apoptotic cells in SGC-7901 cells transfected with pcDNA3/15-PGDH plasmid for 24 and 48 h (P < 0.01), and an increased fraction of sub-G1 phase after transfection (P < 0.05). TUNEL assay showed an increased Apoptotic Index in cells overexpressing 15-PGDH (P < 0.01). After transfection, expression of proapoptotic genes, such as BAK (P < 0.05), BAX and p53 (P < 0.01), was increased. Expression of antiapoptotic genes was decreased, such as Survivin, BCL-2 and BCL-XL (P < 0.01). Expression of cyclin-dependent kinase inhibitors p21 and p16 (P < 0.01) was significantly upregulated in cells overexpressing 15-PGDH. CONCLUSION: Reduction of 15-PGDH is associated with carcinogenesis and development of gastric carcinoma. 15-PGDH induces apoptosis and cell cycle arrest in SGC-7901 cells.展开更多
Objective: The aim of the study was to investigate the impact of 60Co y-ray on apoptosis, cell cycles and the expression of protein hypoxia-inducible factor-1α (HIF-1α) to Hep-2 cell line in the conditions of nor...Objective: The aim of the study was to investigate the impact of 60Co y-ray on apoptosis, cell cycles and the expression of protein hypoxia-inducible factor-1α (HIF-1α) to Hep-2 cell line in the conditions of normoxia and hypoxia. Methods: Hep-2 cell were divided into 2 groups: group A (normoxia) and group B (hypoxia). All of the ceils were exposed to y-ray with dosage being 0, 1, 3, 5, 10, 20, and 40 Gy. Flow cytometry was used to measure the protein level of HIF-1α and to detect apoptosis and cell cycles. The protein level of HIF-1α was also determined by immunohistochemistry and Western blotting. Results: The protein level of HIF-1α in group B was significantly higher than that in group A. In group A, low doses (1-5 Gy) of y-ray had caused G0/G1 cell cycle arrest and high doses (10-40 Gy) had caused G2/M cell cycle arrest. In group B, without exposure of y-ray (0 Gy) had caused G0/G1 cell cycle arrest, all of the different dosage of y-ray could cause G2/M cell cycle arrest. The curve of apoptosis rate in group A was a parabola, the apoptotic rate was related to the dosage of y-ray in a dosage dependent manner. The peak was at the point of 5 Gy. The apoptosis rate in group A was significantly higher than that in group B. Conclusion: Different doses of y-ray could cause different cell cycles arrest then make different impact on apoptosis to Hep-2 ceil. The lower apoptosis rate in condition of hypoxia maybe has a relationship with G2/M cell cycle arrest. Up-regulated HIF-1α protein may be one of the reasons for G2/M cell cycle arrest.展开更多
Objective To study the expression level of peptidylarginine deiminase 4(PADI4) and protein tyrosine phosphatase nonreceptor type 22(PTPN22) in the synovium of rat model of collagen-induced arthritis, and to explore th...Objective To study the expression level of peptidylarginine deiminase 4(PADI4) and protein tyrosine phosphatase nonreceptor type 22(PTPN22) in the synovium of rat model of collagen-induced arthritis, and to explore their possible therapeutic role in rheumatoid arthritis. Methods Thirty-two female Wistar rats weighing 100±20 g were randomly assigned into 3-week collagen-induced arthritis(CIA) model group(n=8), 4-week CIA model group(n=8), 6-week CIA model group(n=8), and the control group(n=8). The body weight changes of each group were recorded. The expression levels of PADI4 and PTPN22 were detected and compared by the methods of immunohistochemical staining and Western blot. Results Arthritis of rat began to form 14 days after sensitization and the joint swelling reached peak at 28 days. The weights of the rats slowly grew both in CIA model groups and the control group. Immunohistochemical staining results showed that the positive expression of PADI4 and PTPN22 was mainly located in cartilage peripheral mononuclear cells, the cytoplasm of infiltrated cells, and bone marrow cavity. There were significant differences in the optical density of PADI4 and PTPN22 among CIA model groups and the control group(PADI4, 0.2898±0.012, 0.2982±0.022, 0.2974±0.031, 0.2530±0.013 in 3-week CIA model, 4-week CIA model, 6-week CIA model and control groups; PTPN22, 0.2723±0.004, 0.2781±0.010, 0.2767±0.008, 0.2422±0.019; all P <0.05). The expression bands of PADI4 were observed in Western blot 3 weeks after initial immunization, the thickest in the 4th week, and decreased in the 6th week. The expression bands of PTPN2 were observed at all the time points, with no obvious time-dependent trend. Conclusions PADI4 and PTPN22 are obviously correlated with CIA in rat model. PADI4 is expressed at early stage of the disease, while the expression of PTPN22 sustains throughout the course.展开更多
AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly...AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly diagnosed with ECA and 26 healthy subjects were included in the current study. The frequencies of MDSCs and Th17 cells in peripheral blood were determined by flow cytometry. The mRNA expression of cytokines, arginase 1 (Arg1) and inducible NO synthase (iNOS) in peripheral blood mononuclear cells (PBMCs) and plasma Arg1 were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: There was an increased prevalence of MDSCs in the peripheral blood from ECA patients (15.21% ± 2.25%) when compared with healthy control (HC) (1.10% ± 0.12%, P < 0.0001). The plasma levels of Arg1 in ECA patients were significantly higher than those in HC (28.28 ± 4.10 ng/mL vs 9.57 ± 1.51 ng/ mL, P=0.0003). iNOS mRNA levels in the peripheral blood of ECA patients also showed a threefold increase compared with HC (P=0.0162). The frequencies of Th17 cells (CD4 + IL-17A + ) were significantly elevated in ECA patients versus HC (3.50% ± 0.33% vs 1.82% ± 0.19%, P=0.0001). Increased mRNA expression of IL-17 and ROR-γt was also observed in ECA patients compared with HC (P=0.0041 and P=0.0004, respectively), while the mRNA expression of IL-6 and tumor necrosis factor-α (TNF-α) showed significant decreases (P=0.0049 and P < 0.0001, respectively). No obvious correlations were found between the frequencies of MDSCs and Th17 cells in the peripheral blood from ECA patients(r=-0.1725, P=0.3534). Arg1 mRNA levels were positively correlated with levels of IL-6 (r=0.6404, P=0.0031) and TNF-α (r=0.7646, P=0.0001). Similarly, iNOS mRNA levels were also positively correlated with levels of IL-6 (r=0.6782, P=0.0007) and TNF-α (r=0.7633, P < 0.0001). CONCLUSION: This study reveals the relationship between circulating MDSCs and Th17 cells, which may lead to new immunotherapy approaches for ECA based on the associated metabolites and cytokines.展开更多
Objective To determine the in vitro expression of interleukin-12 (IL-12) and its effect on signal transducers and activators of transcription (STAT) signaling molecules in peripheral blood mononuclear cells (PBMCs) in...Objective To determine the in vitro expression of interleukin-12 (IL-12) and its effect on signal transducers and activators of transcription (STAT) signaling molecules in peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE).Methods Peripheral blood mononuclear cells in 39 patients with definite systemic lupus erythematosus and 11 healthy volunteers were collected. Expression of IL-12 P40mRNA in PBMCs was determined with reverse transcription-polymerase chain reaction (RT-PCR). Quantity of IL-12 protein supernatant was measured by enzyme-linked immunosorbent assay (ELISA). The levels of phosphorylated STAT3 and STAT4 signaling molecules in PBMCs were detected by immunoblot. Results Levels of IL-12 protein and mRNA expression in patients with active or inactive SLE were significantly higher than those in controls. Phytohemagglutinin (PHA) may promote the expression of IL-12. IL-12 alone induced the phosphorylation of STAT3 and STAT4 in PBMCs from patients with SLE, especially in active SLE. However it had no obvious effect on normal PBMCs. Phosphorylated STAT3 and STAT4 might be observed in normal PBMCs treated with IL-12 plus PHA.Conclusion IL-12 is produced aberrantly in patients with SLE. IL-12 might exert its biological role in SLE via the aberrantly phosphorylated STAT3 and STAT4 signaling molecules.展开更多
基金Supported by Fundamental and Advanced Research Projects of Henan Province(152300410076,2015-2017)Key Science and Technology Program of Henan Province(152102110048,2015-2017)~~
文摘[Objective] This study aimed to establish an in vitro culture model for porcine peripheral blood monocyte-derived dendritic cells (MoDCs). [Method] Fresh peripheral blood mononuclear cells (PBMCs) were separated from pig, and precursor dendritic cells were obtained by adherence method. The dendritic cells were treated by recombinant porcine granulocyte-monocyte colony stimulating factor (rpGM-CSF) and recombinant porcine interleukin-4 (rplL-4) together, and lipopolysaccharide (LPS) respectively. The cells in different time periods were collected. The morphology of the collected cells was observed by scanning electron microscopy; the expression of surface molecules and phagocytic ability to FITC-dextran were detected by flow cy- tometry; and the stimulating ability for allogeneic T cells was detected by mixed lymphocyte reaction. [Result] The DCs suffering maturation induction in vitro showed typical dendritic morphology; compared with those of DCs untreated by LPS, the cell surface expression of CDla, CD80, CD86, SLAII and CD172a of DCs treated by LPS was significantly increased, the phagocytic ability was reduced slightly, and the stimulating ability for allogeneic T cells was enhanced to some extent. [Conclusion] An in vitro culture method was successfully established for porcine MoDCs in this study, laying a foundation for further study on the role of porcine MoDCs in immunoregulation and anti-virus infection.
文摘Objective To observe clinical therapeutic effects of warm needling and moxibustion on diabetic peripheral neuropathy (DPN) and their influence on nerve conduction velocity. Methods Fifty two cases were randomly divided into a treatment group (n =26) and a control group (n =26). In addition to basic treatment for lowering blood sugar in both groups, Pǐshū (BL 20), Shènshū (BL 23), Huántiào (GB 30), Zùsānlǐ (ST 36), Yánglíngquán (GB 34), Sānyīnjiāo (SP 6), Tàixī (KI 3), Qǔchí (LI 11), Wàiguān (TE 5) and Hégǔ (LI 4) were selected for warm needling and moxibustion in the treatment group. Methycobal was intramuscularly injected in the control group. Clinical symptoms and conduction velocities of the tibial nerve and common peroneal nerve were compared before and after treatment. Results Warm needling and moxibustion could alleviate such clinical symptoms as numbness of limbs, pain and hypoesthesia, and obviously improve the conduction velocities of both tibial and common peroneal nerves. Conclusion Warm needling and moxibustion exhibit good therapeutic effects on diabetic peripheral neuropathy.
基金Supported by the National Natural Science Foundation of China, No. 39970639
文摘AIM: To investigate the molecular mechanisms by which tea pigments exert preventive effects on liver carcinogenesis. METHODS: HepG2 cells were seeded at a density of 5×10^5/well in six-well culture dishes and incubated overnight. The cells then were treated with various concentrations of tea pigments over 3 d, harvested by trypsinization, and counted using a hemocytometer. Flow cytometric analysis was performed by a flow cytometer after propidium iodide labeling. Bd-2 and p21^WAF1 proteins were determined by Western blotting. In addition, DNA laddering assay was performed on treated and untreated cultured HepG2 cells. RESULTS: Tea pigments inhibited the growth of HepG2 cells in a dose-dependent manner. Flow-cytometric analysis showed that tea pigments arrested cell cycle progression at G1 phase. DNA laddering was used to investigate apoptotic cell death, and the result showed that 100 mg/L of tea pigments caused typical DNA laddering. Our study also showed that tea pigments induced upregulation of p21^WAF1 protein and downregulation of Bcl-2 protein. CONCLUSION: Tea pigments induce cell-cycle arrest and apoptosis. Tea pigments may be used as an ideal chemopreventive agent.
文摘Objective: To investigate the effect of activation-induced cell death (AICD) on cellular immune function in the condyloma acuminatum(CA). Methods: Peripheral blood mononuclear cells (PBMC) were isolated from normal healthy individuals (control group) and patients with CA. PBMC were cultured with PHA-P for 48h in vitro. Apoptosis of the PBMC was detected by flow cytometry. Supernatant cytokines (IL-2 and IL-10) were assayed by ELISA. Results: The rate of PBMC apoptosis in both CA group and control group in fresh PBMC was very low and similar in both groups(P>0.05). The rate of PBMC apoptosis within the CA group was noticeably increased compared to that of the control (P<0.001)af-ter PBMC were cultured for 48h. The level of IL-2 was significantly lower in the CA group than in the control group (P<0.001), The level of IL-10 was significantly higher in the CA group compared to thecontrol group(P<0.001). Conclusion: Study results indicate that AICD may affect cellular mediated immune function and play an important role in the pathogenesis of CA.
基金supported by National Natural Science Foundation of ChinaK.C.Wong Magna Fund in Ningbo University of Chinathe Natural Science Foundation of Ningbo in China
文摘In the paper, we study a super-conducting junctions device subject to an input periodic signal and a constant force. It is shown that, for this device, we can get current reversals for the current of the electron pairs versus the frequency of the periodic signal and negative conductance for the current of the electron pairs as a function of the constant force.
基金This work was supported by a grant of Na-tional Natural Science Foundation#30230110a grant of Science and Technology Commission of Shanghai Mu-nicipality#O4DZ14901+1 种基金a grant of Chinese Academy of Sciences#KSCX2-SW-203a grant of the Shanghai-Hong Kong-Anson Research Foundation for CAS and CUHK(Chinese University of Hong K ong)in Molecular Biosciences(SHARF)to Jia Rui WU.
文摘The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apoptosis. In the present study, the degradation of pRB was observed in apoptotic gastric tumor cells treated with a new potent anti-tumor component, tripchlorolide (TC). The inhibition of pRB degradation by a general cysteine protease inhibitor IDAM resulted in the reduction of the apoptotic cells. Furthermore, the survival of the gastric tumor cells under the TC treatment was enhanced by an over-expression of exogenous pRB. These results suggest that the pRB degradation of the gastric tumor cells under the TC treatment involves in the apoptotic progression. In addition, the same extent of TC- induced pRB-degradation was detected in the gastric tumor cells containing a p53 dominant-negative construct, indicat- ing that this kind of pRB degradation is p53-independent.
文摘I discuss the modification of Einstein's Theory of General Relativity based on a periodic functional approach. In this new approach, a corrected periodic gravitational coupling constant arises and plays the role of periodic damping term acting on the theory. It is found that it is achievable to have an oscillating universe dominated by dark energy and expanding aceeleratedly in time.
文摘DNA mismatch repair (MMR) processes the chemically induced mispairs following treatment with clinically important nucleoside analogs such as 6-thioguanine (6-TG) and 5-fluorouracil (5-FU). MMR processing of these drugs has been implicated in activation of a prolonged G2/M cell cycle arrest for repair and later induction of apoptosis and/or autophagy for irreparable DNA damage. In this study, we investigated the role of Bcl2 and adenovirus EIB Nineteen-kilodalton Interacting Protein (BNIP3) in the activation of autophagy, and the temporal relationship between a G2/M cell cycle arrest and the activation of BNIP3-mediated autophagy following MMR processing of 6-TG and 5-FU. We found that BNIP3 protein levels are upregulated in a MLHI (MMR+)-dependent manner following 6-TG and 5-FU treatment. Subsequent small-interfering RNA (siRNA)-mediated BNIP3 knockdown abrogates 6-TG- induced autophagy. We also found that p53 knockdown or inhibition of mTOR activity by rapamycin cotreatment impairs 6-TG- and 5-FU-induced upregulation of BNIP3 protein levels and autophagy. Furthermore, suppression of Checkpoint kinase 1 (Chkl) expression with a subsequent reduction in 6-TG-induced G2/M cell cycle arrest by Chkl siRNA promotes the extent of 6-TG-induced autophagy. These findings suggest that BNIP3 mediates 6-TG- and 5-FU-induced autophagy in a p53- and mTOR-dependent manner. Additionally, the duration of Chkl-activated G2/ M cell cycle arrest determines the level of autophagy following MMR processing of these nucleoside analogs.
基金Supported by Department of Science and Technology,Government of India
文摘AIM: To determine the functional significance of TC21 in esophageal squamous cell carcinoma (ESCC). METHODS: TC21 siRNA transfection was carried out using Hyperfectamine to knock down TC21, and tran- scripts were analyzed by reverse transcription-poly- merase chain reaction and protein by Western blotting.We demonstrated the effect of TC21 downregulation of cell signaling in esophageal cancer cells by assess- ing the phosphorylation status of its downstream tar- gets, phosphoinositide 3-kinase (PI3K), phosphatase and tensin homolog (PTEN), protein kinase B (pAl〈t), nuclear factor-KB (NF-~B) and cyclinD1 using specific antibodies. Cell survival analysis after cisplatin treat- ment was carried out by cell viability assay and cell cycle analysis using flow cytometry. RESULTS: TC21 knockdown in human ESCC cell line TEl3 cells, showed only a marginal increase (14.2%) in cell death compared with control cells. The expres- sions of the signaling proteins PI3K and pAkt, transcrip- tion factor NF-KB, and cell cycle protein cyclin D1 were markedly decreased in response to TC21 downregula- tion, whereas the level of pPTEN, an antagonist of PI3K, was increased. In addition, we evaluated the potential of TC21 as a putative target for sensitizing ESCC cells to the chemotherapeutic agent cisplatin. Increased cell death (38.4%) was observed in cells treated with cis- platin after TC21 knockdown compared with cells which were treated with cisplatin alone (20% cell death). CONCLUSION: Results suggest that TC21 mediates its effects via the PI3K-Akt pathway, NF-KB and cyclin D1, and enhances chemoresistance in esophageal cancer cells.
基金Project(50775225) supported by the National Natural Science Foundation of China
文摘A novel periodic mount was presented. A theoretical model was developed to describe the dynamics of wave propagation in the novel periodic mount. The model was derived using Hamilton's energy conservation principle. The characteristics of wave propagation in unit cell were analyzed by transfer matrix formulation. Numerical examples were given to illustrate the effectiveness of the periodic mount. The experiments were carried out to identify the predications of the theoretical model. The obtained results show that the experimental results coincide with the prediction of theoretical model. No pass bands appear in the overall frequency range measured when waves propagate in the longitude direction of the periodic mount. These dramatic results demonstrate its potential as an excellent mount in attenuating and isolating vibration transmission.
文摘Electrically conducting fabrics used as flexible sensors can be produced by vacuumed vapor deposition.The research of what impacts the wide and reliable application of the flexible sensors shows that the stability of flexible sensors is one of the critical issues.The electrical performance of weft knitted fabrics in course and wale direction does not show significant differences under different ambient conditions,which include time,temperature,and relative humidity.Tests of stimuli responding sensitivity of conductive fabrics indicate that the sensitivity keeps at a constant level and the average sensitivity is stable over 38 days.
文摘Objective: To analyze the therapeutic effect of contralateral needling in the treatment of scapulohumeral periarthritis. Methods: A total of 68 cases of scapulohumeral periarthritis were outpatients and were randomized into treatment group (n=36) and control group (n=32). In treatment group, Zhiyin (BL 67), Jinmen (BL 63) and Yanglao (SI 6) on the contralateral side of the affected shoulder and local tenderpoints (Ashi-points) were punctured once every other day, with 7 days being a therapeutic course; while in control group, local Ashi-points were used for injection of Procaine and Prednisolone Acetate, once every 7 days and with 3~4 sessions being a therapeutic course. Results: Following 2 courses of treatment, of the 32 cases in control group, 8 (25.0%) were cured, 17 (53.1%) experienced improvement and 7 failed in the treatment, with a total of effective rate of 78.1%; of the 36 cases in treatment group, 18 (50.0%) were cured, 16 (44.4%) experienced improvement and 2 (5.6%) failed in the treatment, with a total effective rate of 94.4%. The therapeutic effect of contralateral needling is significantly higher than that of Ashi-point blocking method (P<0.05). Conclusion: Contralateral needling is superior to Ashi-point in the treatment of scapulohumeral periarthritis.
基金Supported by grants from the Clinical Key Subject Foundation of Health Ministry of China (No.20012537)National Science and Technology Department "973" Tumor Project (No.2004CB518705)
文摘Objective: The aim of the study was to observe the expression of Bcl-2 and its phosphorylation in Molt-4 cells induced by tumor necrosis factor-α (TNF-α), and to investigate the possible mechanism of cell cycle specificity of apoptosis. Methods: Exponentially growing Molt-4 cells were treated with TNF-α. Apoptosis was detected by DNA fragmentation assay. API method was applied to illustrate the cell cycle specificity of apoptotic cells. Cells of sub-phases were sorted by FACSvan- tage flow cytometer and then submitted to immunoblot. Results: Molt-4 cells which were treated with TNF-α went to apoptosis and showed a DNA ladder pattern. Most apoptosis happened in Gl-phase of cell cycle. Bcl-2 expression increased for the Molt-4 cells treated with TNF-α. The phosphorylation state of Bcl-2 was only presented in Gl-phase cells, in accordance with the specified time and cell cycle phase of apoptosis. Conclusion: The phosphorylation of Bcl-2 in the Molt-4 cells treated with TNF-α happened with the same cell cycle specificity as cell apoptosis. The cell cycle specificity of Bcl-2 phosphorylation was one of the mechanisms of receptor-mediated apoptosis. The cell cycle machine can trigger the apoptosis program.
基金the Research Program of Tianjin City Government in China (No.993607811)
文摘OBJECTIVE To investigate the correlation of E2F-1, Rb and ER expression with peripheral papilloma (Peri-PM) and ductal carcinoma in situ of the breast (DCIS), and further explore some molecular mechanisms of the canceratin of Peri-PM.METHODS Imunohistochemistry was used to examine the expression of E2F-1, Rb and ER in 60 Peri-PM, 60 Peri-PM with atypical ductal hyperplasia (Peri-PM with ADH) and 60 DCIS. Normal breast tissues were selected as a control group.RESULTS Based on immunohistochemical staining, the positive rate of E2F-1 expression in Peri-PM, Peri-PM with ADH and DCIS was 21.7%, 46.7% and 78.3% respectively. The positive rate of Rb expression was 83.3 %, 53.9% and 21.7% and the ER expression was 86.7%,61.7% and 55.0%. Significant differences were found among the 3 groups (Peri-PM, Peri-PM with ADH and DCIS) (P〈0.05). Significant differences existed between any 2 groups (P〈0.05) except for the rate of ER positive expression comparing Peri-PM with ADH verus DCIS (P〉0.05). The expression of E2F-1 was nega- tively correlated with ER and Rb, and at the same time the expression of ER was positively correlated with Rb. Following the degree of breast epithelial hyperplasia involved and its development into carcinoma, the positive rate of E2F-1 expression displayed an elevating tendency, but that of Rb and ER expression showed a tendency to decline.CONCLUSION The interaction of the 3 indexes studied may play an important role in the conversion of precancerous lesions to early in situ breast carcinoma, and the evaluation of these indexes might provide a valuable basis for screening high-risk cases of Peri-PM.
基金Supported by Shanghai Science and Technology Commission Fundation, No. 06BZ066
文摘AIM: To investigate the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in human gastric cancer and it's mechanism in apoptosis and cell cycle arrest. METHODS: Expression of 15-PGDH mRNA and protein was examined by immunohistochemistry, immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting in tissue from human gastric cancer, gastric precancerous state (gastric polyps and atrophic gastritis), normal stomach, and gastric cancer cell lines. The relationship between gastric cancer, gastric precancerous state and 15-PGDH expression was determined. The association between expression of 15-PGDH and various clinicopathological parameters in gastric cancer was evaluated. Human gastric cancer cell line SGC-7901 was transfected with 15-PGDH expression plasmids. The effect of 15-PGDH on the cell cycle was examined by flow cytometry. The effect of 15-PGDH on apoptosis was examined by transmission electron microscopy, flow cytometry and transferasemediated nick end labeling (TUNEL) assay. Expression of cell cycle (p21, p27, p16 and p53) and apoptosis (Survivin, BCL-2, BCL-XL, BAK and BAX) genes was analyzed by RT-PCR. RESULTS: Expression of 15-PGDH mRNA and protein in human gastric cancer tissues was significantly lower than in normal gastric tissues (P < 0.01). Expression in human gastric cancer cell lines MKN-28 and MKN-45 was reduced, and absent in SGC-7901 cells (P < 0.05). Reduction of 15-PGDH expression was also found in precancerous tissues, such as gastric polyps and atrophic gastritis (P < 0.01). There was a significant difference in expression of 15-PGDH among various gastric cancer pathological types (P < 0.05), with or without distant metastasis (P < 0.05) and different TNM stage (P < 0.01). Flow cytometry demonstrated a significant increase in apoptotic cells in SGC-7901 cells transfected with pcDNA3/15-PGDH plasmid for 24 and 48 h (P < 0.01), and an increased fraction of sub-G1 phase after transfection (P < 0.05). TUNEL assay showed an increased Apoptotic Index in cells overexpressing 15-PGDH (P < 0.01). After transfection, expression of proapoptotic genes, such as BAK (P < 0.05), BAX and p53 (P < 0.01), was increased. Expression of antiapoptotic genes was decreased, such as Survivin, BCL-2 and BCL-XL (P < 0.01). Expression of cyclin-dependent kinase inhibitors p21 and p16 (P < 0.01) was significantly upregulated in cells overexpressing 15-PGDH. CONCLUSION: Reduction of 15-PGDH is associated with carcinogenesis and development of gastric carcinoma. 15-PGDH induces apoptosis and cell cycle arrest in SGC-7901 cells.
文摘Objective: The aim of the study was to investigate the impact of 60Co y-ray on apoptosis, cell cycles and the expression of protein hypoxia-inducible factor-1α (HIF-1α) to Hep-2 cell line in the conditions of normoxia and hypoxia. Methods: Hep-2 cell were divided into 2 groups: group A (normoxia) and group B (hypoxia). All of the ceils were exposed to y-ray with dosage being 0, 1, 3, 5, 10, 20, and 40 Gy. Flow cytometry was used to measure the protein level of HIF-1α and to detect apoptosis and cell cycles. The protein level of HIF-1α was also determined by immunohistochemistry and Western blotting. Results: The protein level of HIF-1α in group B was significantly higher than that in group A. In group A, low doses (1-5 Gy) of y-ray had caused G0/G1 cell cycle arrest and high doses (10-40 Gy) had caused G2/M cell cycle arrest. In group B, without exposure of y-ray (0 Gy) had caused G0/G1 cell cycle arrest, all of the different dosage of y-ray could cause G2/M cell cycle arrest. The curve of apoptosis rate in group A was a parabola, the apoptotic rate was related to the dosage of y-ray in a dosage dependent manner. The peak was at the point of 5 Gy. The apoptosis rate in group A was significantly higher than that in group B. Conclusion: Different doses of y-ray could cause different cell cycles arrest then make different impact on apoptosis to Hep-2 ceil. The lower apoptosis rate in condition of hypoxia maybe has a relationship with G2/M cell cycle arrest. Up-regulated HIF-1α protein may be one of the reasons for G2/M cell cycle arrest.
基金Supported by the National Natural Science Foundation of China(81072450)
文摘Objective To study the expression level of peptidylarginine deiminase 4(PADI4) and protein tyrosine phosphatase nonreceptor type 22(PTPN22) in the synovium of rat model of collagen-induced arthritis, and to explore their possible therapeutic role in rheumatoid arthritis. Methods Thirty-two female Wistar rats weighing 100±20 g were randomly assigned into 3-week collagen-induced arthritis(CIA) model group(n=8), 4-week CIA model group(n=8), 6-week CIA model group(n=8), and the control group(n=8). The body weight changes of each group were recorded. The expression levels of PADI4 and PTPN22 were detected and compared by the methods of immunohistochemical staining and Western blot. Results Arthritis of rat began to form 14 days after sensitization and the joint swelling reached peak at 28 days. The weights of the rats slowly grew both in CIA model groups and the control group. Immunohistochemical staining results showed that the positive expression of PADI4 and PTPN22 was mainly located in cartilage peripheral mononuclear cells, the cytoplasm of infiltrated cells, and bone marrow cavity. There were significant differences in the optical density of PADI4 and PTPN22 among CIA model groups and the control group(PADI4, 0.2898±0.012, 0.2982±0.022, 0.2974±0.031, 0.2530±0.013 in 3-week CIA model, 4-week CIA model, 6-week CIA model and control groups; PTPN22, 0.2723±0.004, 0.2781±0.010, 0.2767±0.008, 0.2422±0.019; all P <0.05). The expression bands of PADI4 were observed in Western blot 3 weeks after initial immunization, the thickest in the 4th week, and decreased in the 6th week. The expression bands of PTPN2 were observed at all the time points, with no obvious time-dependent trend. Conclusions PADI4 and PTPN22 are obviously correlated with CIA in rat model. PADI4 is expressed at early stage of the disease, while the expression of PTPN22 sustains throughout the course.
基金Supported by Grants from the Natural Science Foundation of China, No. 30872335, 81172871The Natural Science Foundation of Jiangsu Province, No. BK2009208the Jiangsu Government Scholarship for Overseas Studies
文摘AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly diagnosed with ECA and 26 healthy subjects were included in the current study. The frequencies of MDSCs and Th17 cells in peripheral blood were determined by flow cytometry. The mRNA expression of cytokines, arginase 1 (Arg1) and inducible NO synthase (iNOS) in peripheral blood mononuclear cells (PBMCs) and plasma Arg1 were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: There was an increased prevalence of MDSCs in the peripheral blood from ECA patients (15.21% ± 2.25%) when compared with healthy control (HC) (1.10% ± 0.12%, P < 0.0001). The plasma levels of Arg1 in ECA patients were significantly higher than those in HC (28.28 ± 4.10 ng/mL vs 9.57 ± 1.51 ng/ mL, P=0.0003). iNOS mRNA levels in the peripheral blood of ECA patients also showed a threefold increase compared with HC (P=0.0162). The frequencies of Th17 cells (CD4 + IL-17A + ) were significantly elevated in ECA patients versus HC (3.50% ± 0.33% vs 1.82% ± 0.19%, P=0.0001). Increased mRNA expression of IL-17 and ROR-γt was also observed in ECA patients compared with HC (P=0.0041 and P=0.0004, respectively), while the mRNA expression of IL-6 and tumor necrosis factor-α (TNF-α) showed significant decreases (P=0.0049 and P < 0.0001, respectively). No obvious correlations were found between the frequencies of MDSCs and Th17 cells in the peripheral blood from ECA patients(r=-0.1725, P=0.3534). Arg1 mRNA levels were positively correlated with levels of IL-6 (r=0.6404, P=0.0031) and TNF-α (r=0.7646, P=0.0001). Similarly, iNOS mRNA levels were also positively correlated with levels of IL-6 (r=0.6782, P=0.0007) and TNF-α (r=0.7633, P < 0.0001). CONCLUSION: This study reveals the relationship between circulating MDSCs and Th17 cells, which may lead to new immunotherapy approaches for ECA based on the associated metabolites and cytokines.
文摘Objective To determine the in vitro expression of interleukin-12 (IL-12) and its effect on signal transducers and activators of transcription (STAT) signaling molecules in peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE).Methods Peripheral blood mononuclear cells in 39 patients with definite systemic lupus erythematosus and 11 healthy volunteers were collected. Expression of IL-12 P40mRNA in PBMCs was determined with reverse transcription-polymerase chain reaction (RT-PCR). Quantity of IL-12 protein supernatant was measured by enzyme-linked immunosorbent assay (ELISA). The levels of phosphorylated STAT3 and STAT4 signaling molecules in PBMCs were detected by immunoblot. Results Levels of IL-12 protein and mRNA expression in patients with active or inactive SLE were significantly higher than those in controls. Phytohemagglutinin (PHA) may promote the expression of IL-12. IL-12 alone induced the phosphorylation of STAT3 and STAT4 in PBMCs from patients with SLE, especially in active SLE. However it had no obvious effect on normal PBMCs. Phosphorylated STAT3 and STAT4 might be observed in normal PBMCs treated with IL-12 plus PHA.Conclusion IL-12 is produced aberrantly in patients with SLE. IL-12 might exert its biological role in SLE via the aberrantly phosphorylated STAT3 and STAT4 signaling molecules.