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Objective:To compare the expression difference of Toll like receptor (TLR) and inflammatory factors between pancreatic cancer and normal pancreatic epithelial cells, and explore the correlation between TLR and inflammatory microenvironment.Methods:Normal pancreatic duct epithelium cells (HPNE) and pancreatic cancer cells (Panc-1 and Mia-PACA-2) were cultured and proteins were obtained. The expression of TLR family protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and myeloid differentiation factor 88 (MyD88) were examined by western blot in HPNE, Panc-1 and Mia-PACA-2. The correlations between TLR and inflammation cytokines of pancreatic cancer were analyzed by Pearson correlation analysis.Results:Compared with HPNE, the TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 were highly expressed in Panc-1 and Mia-PACA-2 (all P<0.05). Compared with Panc-1, the expression of TLR2 and TLR4 in Mia-PACA-2 were increased obviously, while the TLR9 expression was mildly decreased (all P<0.05). The expression of IL-6 in HPNE was found less than that in Panc-1 (0.52±0.03 vs. 0.76±0.04) and Mia-PACA-2 (0.52±0.03 vs. 1.12±0.09) with statistical differences ( P<0.05). Similarly, the expression of TNF-α was found significantly less than that of Panc-1 cells (0.63±0.04 vs. 0.87±0.06) and Mia-PACA-2 cells (0.63±0.04 vs. 0.95±0.10) with statistical differences (all P<0.05). The expression of IL-6 was found positively correlated with expressions of TLR2 ( r=0.964), TLR4 ( r=0.968), TLR7 ( r=0.844), TLR8 ( r=0.668) (all P<0.05), and the expression of TNF-α was found positively correlated with expressions of TLR2 ( r=0.805), TLR4 ( r=0.893), TLR7 ( r=0.847), TLR8 ( r=0.780) (all P<0.05). In contrast with HPNE, the expression of MyD88 was found highly expressed in Panc-1 (0.91±0.10 vs. 0.33±0.03) and Mia-PACA-2 (1.14±0.10 vs. 0.33±0.03) (all P<0.001). Compared with Panc-1, the expression of MyD88 in Mia-PACA-2 was obviously increased (1.14±0.10 vs. 0.91±0.10) with statistical difference ( P=0.048). Conclusion:The TLR family may play a critical role in development of pancreatic cancer by regulating the immune microenvironment, and its mechanism may be through upregulating MyD88 which functions as key signal transduction.
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Experimental autoimmune prostatitis (EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus (PVN). However, the mechanism has not yet been elucidated. Herein, we screened out the target prostate-derived inflammation cytokines (PDICs) by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid (CSF) between EAP rats and their controls. After identifying the target PDIC, qualified males in initial copulatory behavior testing (CBT) were subjected to implanting tubes onto bilateral PVN. Next, they were randomly divided into four subgroups (EAP-1, EAP-2, Control-1, and Control-2). After 1-week recovery, EAP-1 rats were microinjected with the target PDIC inhibitor, Control-1 rats were microinjected with the target PDIC, while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF (aCSF). Results showed that only interleukin-1β(IL-1β) had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls (P < 0.001) and significantly higher protein concentrations in both the serum (P = 0.001) and CSF (P < 0.001) of the EAP groups compared to the Control groups. Therefore, IL-1β was identified as the target PDIC which crosses the blood-brain barrier, thereby influencing the central nervous system. Moreover, the EAP-1 subgroup displayed a gradually prolonged ejaculation latency (EL) in the last three CBTs (all P < 0.01) and a significantly lower expression of NMDA NR1 subunit in the PVN (P = 0.043) compared to the respective control groups after a 10-day central administration of IL-1β inhibitors. However, the Control-1 subgroup showed a gradually shortened EL (P < 0.01) and a significantly higher NR1 expression (P = 0.004) after homochronous IL-1β administration. Therefore, we identified IL-1β as the primary PDIC which shortens EL in EAP rats. However, further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1β upregulates NMDA expression.
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Animals , Male , Rats , Cytokines/metabolism , Disease Models, Animal , Ejaculation/physiology , Interleukin-1beta/metabolism , N-Methylaspartate/metabolism , Prostate/metabolism , Prostatitis/metabolism , Receptors, N-Methyl-D-Aspartate/metabolismABSTRACT
@#Keratoconus(KC)is a progressive corneal thinning disease which can cause the conical appearance, scar growth and vision loss <i>via</i> corneal ectasia. Various factors were demonstrated to be related to its etiology, including the genetic factors and the environmental factors(<i>i.e.</i> the friction of eyelids and eyeball, the friction of contact lens and eyeball and the UV irradiation). In addition to the genetic and environmental factors, the inflammation cytokines has been reported as another key factor to the pathogenesis of keratoconus, thus received more attention recently. This paper then reviews the recent advances on the effect of inflammation cytokines on pathogenesis of keratoconus. The motivation of this work is to provide important guidance and thoughts for the treatment of keratoconus.
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Objective To investigate the protective mechanism of dexmedetomidine ( Dex) hydrochloride to lung ischemia/reperfusion injury ( LIRI) in mice. Methods The wild type ( WT) and Toll-like receptor 4 knockout ( TLR4-/-) C57BL/6 Balb/c female mouse randomly divided into four groups: sham group ( S group) , pulmona-ry ischemia/reperfusion group ( I/R group) , normal saline group ( NS group) and Dex group ( D group) . In S group, the chest was opened only, but in I/R group, NS group and D group, model of lung ischemia/reperfusion injury in mice was made by clamping left pulmonary hilum for 30 min, and then reperfusion for 3 h. The lung tis-sue was observed by HE staining. RT-qPCR detected the expression of TLR4 mRNA, and ELISA measured the TNF-α, IL-6 and IL-1 levels, including WT and TLR4-/-. Western blot measured the expression of NLRP3 in lung tissue in both WT and TLR4-/-. Results Dex significantly decreased the pathological damage of LIRI, re-duced the expression of levels of TLR4 mRNA and the production of inflammatory cytokines ( P＜0.01) , and also suppress production and activation of NLRP3 ( P＜0.01) in lung ischemia/reperfusion tissue in WT mice. But no cytokines was found to be inhibited in TLR4-/- mice. Conclusions Dex may decrease the release of a variety of pro-inflammatory factors and inhibit production and activation of NLRP3 inflammasome by TLR4, thereby protect lung against LIRI.
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Objective: To observe the effects of panaxtriol saponin (PTS) on CK-MB, cTnI, IL-6, TNF-α, and ultrastructure against myocardial ischemia-reperfusion injury (MIRI) in rats. Methods: Wistar rats were randomly divided into six groups: Sham, MIRI model, positive control, and 22.5, 45, and 90 mg/kg PTS groups. Animal MIRI model was made by ligating the left anterior descending coronary artery. Drug was given for seven consecutive days before the operation by ip injection. Rats were sacrificed after 30 min ischemia and 24 h reperfusion. CK-MB, cTnI, IL-6, and TNF-α in serum were measured and the changes of myocardial ultrastructure were observed. Real time PCR was used to evaluate change of NRF2 and HO-1 mRNA level in myocardial tissue. Results: Compared with model, PTS 45 and 90 mg/kg reduced the CK-MB, cTnI, IL-6, and TNF-α in serum and improve the myocardium ultrastructure. Nrf2 and HO-1 mRNA levels in PTS treatment group were higher than those in MIRI model group. Conclusion: PTS plays a crucial role in cardioprotection against the ischemia and reperfusion injury in rats. The protective mechanism suggests that PTS could stimulate NRF2/HO-1 expression in myocardial tissue and then inhibit myocardial inflammation.
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Objective To investigate the effects of preemptive analgesia with nalbuphine on inflammatory factors in elderly patients undergoing thoracotomy. Methods Eighty elderly patients with ASA I or Ⅱ undergoing thoracotomy were randomly allocated into control group (group C:n=40) and Nalbuphine group (group N:n=40). Each patient received 20 mg of Nalbuphine intravenously before induction of anesthesia in group N and same volume of normal saline in group C. Plasma levels of IL-10, TNF-α and IL-6 were measured at different time points. The VAS was recorded and the MAP, HR, SpO2 and PaCO2 were monitored. Results Compared with group C, the levels of TNF-α and IL-6 were lower, while IL-10 was higher at T2, T3, T4 in group N(P < 0.05). The VAS, MAP, HR and PaCO2 in group N were lower than those in group C at T2, T3 and T4 (P < 0.05). Conclusion Preemptive analgesia with Nalbuphine can improve the efficacy of postoperative analgesia and effectively reduce inflammatory reaction in the old patients undergoing thoracotomy.
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Objective To investigate the influence of preemptive analgesia with Hydr- omorphone Hy-drochloride on postoperative cognitive function and inflammation cytokines in the elderly patients. Methods Ninety ASA I orⅡ elder patients were randomly divided in control group (C)and Hydromorphone Hydrochloride group(H) with 45 cases each. Hydromorphone Hydrochloride 2 mg was injected iv before induction of anesthesia in group H. Observed plasma concentrations of the CRP、 TNF-α and IL-6 at different time. Cognitive function was assessed by minimental state examination. Results Plasma the CRP、 TNF-a and IL-6 concentrations were lower and MMSE scales were higher in group H than in group C. Conclusion Preemptive analgesia with Hy-dromorphone Hydrochloride 2 mg can reduce the incidence of postoperative cognitive dysfunction in the elderly patients.
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Objective To investigate the expression of pro-inflammatory cytokines in lumbar dorsal root ganglions (DRG) of rats model of high-dose fentanyl induced hyperalgesia. Methods 64 male SD rats were divided into 2 groups (n = 32), fentanyl group and normal saline (NS) group. The rats were injected with fentanyl (60 μg/kg) or NS 4 times in total subcutaneously with a 15-minute interval. Mechanical and thermal nociception were measured via the tail pressure test (tail flick thresholds, TFT) and paw withdrawal test (paw withdrawal latency, PWL) at 1 day before, at 1, 2, 3 and 4 hour and on 1 ~ 7 day after administration. 4 rats were sacrificed and the lumbar DRG were harvested to analyze the expression of PGE2 , IL-1β, IL-6 and TNF-αvia ELISA. Results There were no significant changes of TFT, PWL and the expression of pro-inflammatory cytokines in DRG compared to baseline of rats in NS group. The value of TFT , PWL in fentanyl group were above the baseline at the 1 ~ 4 hour and below the baseline at 1~3 day after fentanyl injections. PGE2 , IL-1β, TNF-α and IL-6 increased on 1,3,5,7 day after fentanyl injections significantly. Conclusions High-dose fentanyl induced significant hyperalgesia and up-regulation of pro-inflammatory cytokines in DRG. The expression pro-inflammatory cytokines peaked later and were more protracted than the change of behavior test and show no direct relationship between the two.
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Objective To investigate the changes of leukocyte derived cytokines,IL 1?,IL 6,IL 8,and TNF ?,in platelets concentrates (PCs) during storage,and to study the effect of leukodepletion on cytokine concentration in PCs and the incidence rate of febrile non hemolytic transfusion reaction (FNHTR).Methods 8 bags of apheresed PCs from 8 voluntary donors were each divided into two identical portions (A and B).Group A underwent leukocyte filtration,while group B did not.Then both groups were stored at 22℃ for 5 days.The levels of cytokines (pg/ml),white blood cell (WBC) count and platelet count in both groups were tested on the day 0,3 and 5 during storage.In clinic,240 patients were randomly divided into two groups with 120 in each group to receive non filtered or filtered PCs (1 bag/patient).The incidence of FNHTR was investigated.Paired t test and ? 2 test were used in data analysis. Results There was a significant positive correlation between the content of WBC in PCs and the level of cytokines.On the 5th day of storage,residual WBC in leukoreduced PCs were less than 1?10 6/PC,the levels of cytokines remained the same as those on 0;however,WBC in non filtered PCs was (351?81)?10 6/PC,and the levels of IL 1??IL 6?IL 8 and TNF ? were 105.0pg/ml,269.0pg/ml,1840pg/ml and 42.0pg/ml respectively and increased 18 ( P