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Background Aluminum activates signal transducer and activator of transcription 3 (STAT3), causing microglial nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) inflammasome activation and inflammatory responses and producing neurotoxicity. Objective To explore the role of STAT3 regulated NLRP3 inflammasomes in the inflammatory response of mouse microglia cell line (BV2) cells induced by maltol aluminum [Al(mal)3]. Methods BV2 cells were assigned to five groups: one control group, three Al(mal)3 exposure groups (low, medium, and high doses at 40, 80, and 160 μmol·L−1 Al(mal)3 respectively), and one C188-9 (STAT3 antagonist) intervention group [10 μmol·L−1 C188-9 +160 μmol·L−1 Al(mal)3]. Cell viability was detected by CCK8. The expression of M1/M2 type markers, i.e. CD68/CD206, STAT3, p-STAT3, NLRP3, cleaved-casepase-1, and apoptosis-associated speck-like protein (ASC) in BV2 cells were detected by Western blotting, and proinflammatory cytokines interleukin (IL)-1β and IL-18, and anti-inflammatory cytokine IL-10 were determined by ELISA. Results The results of cell viability assay showed that cell viability gradually decreased with the increase of Al(mal)3 dose. Compared with the control group, the cell viability of the Al(mal)3 high-dose group was decreased by 18% (P<0.05); compared with the Al(mal)3 high-dose group, the cell viability of the C188-9 intervention group was significantly elevated by 14% (P<0.05). Compared with the control group, the expression levels of CD68 in the Al(mal)3 low-, medium-, and high-dose groups were elevated by 19%, 20%, and 21%, respectively (P<0.05); the expression level of CD206 in the Al(mal)3 high-dose group was decreased by 25% (P<0.05). Compared with the Al(mal)3 high-dose group, the expression level of CD68 in the C188-9 intervention group was reduced by 9% (P<0.05), whereas the expression level of CD206 was elevated by 22% (P<0.05). Compared with the control group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the Al(mal)3 high-dose group increased by 129% and 127%, respectively (P<0.05). Compared with the Al(mal)3 high-dose group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the C188-9 intervention group were decreased by 55% and 54%, respectively (P>0.05). Compared with the control group, the expression level of NLRP3 protein increased by 75% in the Al(mal)3 high-dose group (P<0.05), the expression levels of cleaved-casepase-1 protein increased by 28% and 35% in the Al(mal)3 medium- and high-dose groups (P<0.05), and the expression levels of ASC increased by 22%, 25%, and 53% in the Al(mal)3 low-, medium- and high-dose groups (P<0.05), respectively. Compared with the Al(mal)3 high-dose group, the expression levels of NLRP3, cleaved-casepase-1, and ASC proteins in the C188-9 intervention group decreased by 30%, 19%, and 32%, respectively (P<0.05). Compared with the control group, the levels of IL-1β in the Al(mal)3 medium- and high-dose groups increased by 18% and 21%, respectively (P<0.05), and the level of IL-18 in the Al(mal)3 high-dose group increased by 10% (P<0.05). Compared with the Al(mal)3 high-dose group, the IL-18 levels were reduced by 23% in the C188-9 intervention group (P<0.05). The content of anti-inflammatory factor IL-10 did not differ significantly between groups (P>0.05). Conclusion Aluminum can induce inflammatory responses in BV2 microglia and is predominantly pro-inflammatory, and the mechanism may involve STAT3 regulation of NLRP3 inflammasome secretion of inflammatory factors.
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OBJECTIVE To study the correlation between color and inner quality during the processing of Prunus mume carbon， and provide reference for the determination of processing end point of P. mume carbon. METHODS The chromaticity value of P. mume carbon powder was measured by colorimeter， and the inner quality of P. mume carbon was measured by selecting the contents of water， water-soluble extract， citric acid and tannin. The dynamic change trend of the chromaticity value， water， water- soluble extract， the contents of citric acid and tannin in P. mume carbon under different processing time was analyzed. The correlation between color and the above indexe contents was analyzed， and the regression equation of inner quality-chromaticity value was established. Combined with principal component analysis （PCA）， hierarchical cluster analysis （CA） and partial least squares discriminant analysis （PLS-DA）， the difference of P. mume carbon at different processing times was analyzed to determine the processing end point. RESULTS With the extension of processing time， the sample color gradually deepened； the chromaticity values L* and E* of the samples increased at first and then decreased， the chromaticity values a* and b* decreased， and finally all tended to be stable. The content of water-soluble extract， citric acid and tannin in the sample increased at first and then decreased， the water content of the sample decreased with time and finally stabilized. Correlation analysis showed that water， water-soluble extract， citric acid and tannin were positively correlated with L*， a*， b* and E*（P＜0.001）. PCA and HCA showed that P. mume carbon under different processing time could be clustered into two categories： the processed samples of 0-30 min and those of 40-60 min. PLS-DA showed that water and water-soluble extract were important quality indexes and b* was an important chrominance index in the processing of P. mume carbon. The chromaticity value of the samples processed for 50 min and 60 min were not significantly different. The contents of water， water- soluble extract， citric acid and tannin in the samples processed for 60 min were less than those processed for 50 min. CONCLUSIONS There is a certain correlation between the color and the inner quality of P. mume carbon. The processing time of P. mume carbon should be 40-50 min.
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Objective:To investigate the efficacy of tripterygium glycoside tablets combined with irbesartan for chronic nephritis and its effect on 24-hour urine protein and inflammatory factor levels.Methods:Ninety patients with chronic nephritis who received treatment at The Second People's Hospital of Liaocheng from April 2018 to January 2020 were included in this study. They were randomly divided into an observation group and a control group, with 45 patients in each group. The control group was treated with irbesartan. The observation group was treated with tripterygium glycoside tablets combined with irbesartan. All patients were treated for 3 successive months. Clinical efficacy and adverse reactions were compared between the two groups. Changes in 24-hour urine protein level, symptom score, and inflammatory factor levels after treatment relative to those before treatment were compared between the two groups.Results:Response rate in the observation group was significantly higher than that in the control group [95.6% (43/45) vs. 80.0% (36/45), χ2 = 5.07, P = 0.024). Before treatment, there were no significant differences in 24-hour urine protein level, symptom score, and inflammatory factor level between the two groups (all P > 0.05). After treatment, the 24-hour urine protein level in the observation group was significantly lower than that in the control group [(1.42±0.01) g/24 hours vs. (1.95 ± 0.05) g/24 hours, t = 69.72, P = 0.012). The symptom score in the observation group was significantly lower than that in the control group [(0.78 ± 0.01) points vs. (1.33 ± 0.12) points, t = 30.64, P = 0.001]. Serum levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α in the observation group were significantly lower than those in the control group ( t = 15.70, P = 0.006; t = 96.55, P = 0.003; t = 43.41, P = 0.002). There was no significant difference in the incidence of adverse reactions between the two groups ( P = 0.694). Conclusion:Tripterygium glycoside tablets combined with irbesartan is highly effective on chronic nephritis. The combined therapy can remarkably decrease 24-hour urine protein levels, reduce symptom scores, and decrease inflammatory factor levels.
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Objective:To investigate the effect of hemodiafiltration combined with Jinshuibao tablet on serum inflammatory factors and oxidative stress indices in patients with diabetic nephropathy. Methods:A total of 86 patients with diabetic nephropathy who received treatment in The Second People's Hospital of Liaocheng from April 2019 to April 2020 were included in this study. They were randomly assigned to receive either hemodiafiltration (control group, n = 42) or hemodiafiltration combined with Jinshuibao tablet (observation group, n = 44). Microinflammatory state, oxidative stress index level, renal function and nutritional status were compared between the two groups. Results:Before treatment, serum interleukin-6, high-sensitivity C-reactive protein and tumor necrosis factor-α levels in the control group were (30.13 ± 3.25) ng/L, (9.43 ± 2.57) mg/L, (46.69 ± 3.54) ng/L respectively, and they were (30.16 ± 3.34) ng/L, (9.48 ± 2.65) mg/L, (46.73 ± 3.38) ng/L respectively in the observation group. There were no significant differences in these indices between the two groups (all P > 0.05). After treatment, serum interleukin-6, high-sensitivity C-reactive protein and tumor necrosis factor-α levels in the control group were (16.69 ± 2.73) ng/L, (8.12 ± 2.21) mg/L, (35.63 ± 2.75) ng/L, respectively, and they were (12.34 ± 2.52) ng/L, (6.47 ± 1.53) mg/L, (26.65 ± 2.13) ng/L, respectively in the observation group. After treatment, serum interleukin-6, high-sensitivity C-reactive protein and tumor necrosis factor-α levels in both groups were significantly lower than those before treatment (control group: t = 20.52, 2.50, 15.99; observation group: t = 27.60, 6.16, 32.57, all P < 0.05). After treatment, serum interleukin-6, high-sensitivity C-reactive protein and tumor necrosis factor-α levels were significantly lower than those in the control group ( t = 7.68, 4.04, 16.97, all P < 0.05). Before treatment, serum levels of malondialdehyde, superoxide dismutase, and glutathione peroxidase in the control group were (5.63 ± 1.36) nmol/L, (63.38 ± 7.56) mU/L, and (195.96 ± 26.36) IU/L, respectively, while those in the observation group were (5.68 ± 1.25) nmol/L, (63.25 ± 7.38) mU/L, and (195.83 ± 26.27) IU/L, respectively. There were no significant differences in these indices between the two groups (all P > 0.05). After treatment, serum levels of malondialdehyde, superoxide dismutase, and glutathione peroxidase in the control group were (4.83 ± 1.13) nmol/L, (83.46 ± 5.75) mU/L and (236.69 ± 18.75) IU/L respectively, while those in the observation group were (4.24 ± 0.86) nmol/L, (88.75 ± 5.47) mU/L and (258.76 ± 15.47) IU/L, respectively. After treatment, serum levels of malondialdehyde, superoxide dismutase, and glutathione peroxidase in each group were superior to those before treatment (control group: t = 2.93, 13.70, 8.16, P = 0.002, < 0.001, < 0.001; observation group: t = 6.15, 17.99, 13.37, all P < 0.001). After treatment, serum levels of malondialdehyde, superoxide dismutase, and glutathione peroxidase in the observation group were superior to those in the control group ( t = 2.73, 4.37, 5.96, P = 0.004, < 0.001, < 0.001). After treatment, blood urea nitrogen, serum creatinine and 24-hour urine protein in the observation group were significantly lower than those in the control group ( t = 7.85, 8.71, 2.06, P < 0.001, < 0.001, 0.021), and creatinine clearance rate in the observation group was significantly higher than that in the control group ( t = 3.01, P = 0.002). Total protein, prealbumin and albumin levels in the observation group were significantly higher than those in the control group ( t = 9.47, 12.13, 6.18, all P < 0.001). Conclusion:Hemodiafiltration combined with Jinshuibao tablet for the treatment of diabetic nephropathy has a positive effect on microinflammatory state and oxidative stress index level and improves patient's renal function and nutritional status.
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BACKGROUND:MicroRNA plays an important role in the process of growth and aging of living body. To know the role of let-7d in inducing bone marrow mesenchymal stem celldifferentiation into neurons can promote the stem celltransplantation. OBJECTIVE:To investigate the role of let-7d in inducing bone marrow mesenchymal stem celldifferentiation into neurons. METHODS:(1) The lentiviral vector of let-7d was constructed and transfected into rat bone marrow mesenchymal stem cells. The cells were divided into non-transfected group, negative control group (transfected with FU-RNAi-NC-LV), transfected enhancement group (transfected with let-7d-LV), transfected inhibition group ( transfected with let-7d-inhibition-LV). (2) Rat bone marrow mesenchymal stem cells were treated with fasudil as an inducer for triggering the cells to differentiate into neurons. The expression of neuron-specific markers, neuron-specific enolase and microtubule-associated protein 2, were measured by immunocytochemical method. The mRNA expression of microtubule-associated protein 2 was detected by RT-PCR. The viability of bone marrow mesenchymal stem cells was determined by MTT method. RESULTS AND CONCLUSION:Under inverted fluorescence microscope, the cells were successful y transfected with let-7d. Fasudil induced bone marrow mesenchymal stem cells to differentiate into neurons. The transfection efficiency and expression levels of neuron-specific enolase and microtubule-associated protein 2 in transfected enhancement group were higher than those in the negative control group (P<0.05);while in the inhibition group, they were lower than those in the negative control group (P<0.05). These findings indicate that let-7d can promote the differentiation of bone marrow mesenchymal stem cells into neurons induced by fasudil, and by control ing the expression of let-7d we can influence the differentiation efficiency from bone marrow mesenchymal stem cells to neurons.
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Objective To explore the relationship between plasma interleukin-11(sIL-11) level and platelet count post-chemotherapy with hematological malignancy patients and analyse a sIL-11 level which may maintain a safe platelet count so as to guide the treatment. Methods Blood samples were collected from the patients with hematological malignancy at certain time point of pre-and post-chemotherapy, and serum level of sIL-11 and platelet count were determined separately. Different statistical methods were applied to test the relationship between sIL-11 level and platelet changes. Results 99 cases finished this study. The findings are: the sIL-11 level went up and reached the peak on day 6 post-chemotherapy, while the platelet count kept dropping to the lowest on day 10, the sIL-11 peak occurred before the lowest platelet count, patients with faster sIL-11 increase may maintain a comparatively higher plateled count. 99 eases were grouped according to the lowest platelet count and compared: the group with higher platelet count tend to have higher peak sIL-11, more cases with higher peak sIL-11, with faster daily average sIL-11 increase, the lowest platelet count occurred later. Logistic regression analysis showed the factors contributed to lower platelet includes slower daily average sIL-11 increase and sIL-11 level less than 2000 pg/ml on Day4 post-chemotherapy. Conclusion There were correlation between the serum sIL-11 level and platelet counts, the platelet count change may be predicted by determining the plasma sIL-11 level post-chemotherapy. Patients with sIL-11 level less than 2000 pg/ml on Day4 post-chemotherapy may be endangered with severe thrombocytopenia, rhIL-11 or platelet transfusion treatment should be considered.