To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore t...To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group （LC）, high- cholesterol group （HC）, high-cholesterol＋ simvastatin group （HC＋S） and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shift as- say （EMSA）, immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kB-DNA binding activity, MCP-1 protein expression, intirna thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC＋S groups were significantly lower than those in the HC group （P〈0.05）. There was no significant difference in the serum lipids between the LC and HC＋S groups （P〉0.05）, but the NF-kB-DNA binding activity, the expression of MCP-1 protein and the intirna thickness and plaque area of aorta in the HC＋S group were significantly decreased as compared to the LC group （P〈0. 05）. This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kB-DNA binding activity and by reducing the expression of MCP-1 protein.展开更多
BACKGROUND： Ventilator induced lung injury （VILI） is a serious complication in the treatment of mechanical ventilating patients, and it is also the main cause that results in exacerbation or death of patients. In t...BACKGROUND： Ventilator induced lung injury （VILI） is a serious complication in the treatment of mechanical ventilating patients, and it is also the main cause that results in exacerbation or death of patients. In this study, we produced VILI models by using glucocorticoid in rats with high tidal volume mechanical ventilation, and observed the content of macrophage inflammatory protein-1α （MIP-1α） in plasma and bronchoalveolar lavage fluid （BALF） and the expression of MIP-1α mRNA and nuclear factor-kappa B （NF-кB） p65 mRNA in the lung so as to explore the role of glucocorticoid in mechanical ventilation.METHODS： Thirty-two healthy Wistar rats were randomly divided into a control group, a ventilator induced lung injury （VILI） group, a dexamethasone （DEX） group and a budesonide （BUD） group. The content of MIP-1a in plasma and BALF was measured with ELISA and the level of MIP-1α mRNA and NF-кBp65 mRNA expressing in the lung of rats were detected by RT-PCR. The data were expressed as mean±SD and were compared between the groups.RESULTS： The content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-кBp65 mRNA in the lung in the DEX and BUD groups were signifi cantly lower than those in the VILI group （P〈0.001）. Although the content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-кBp65 mRNA in the lung in the BUD group were higher than those in the DEX group, there were no signifi cant differences between them （P〉0.05）.CONCLUSIONS： Glucocorticoid could down-regulate the expression of MIP-1α by inhibiting the activity of NF-кB in the lung and may exert preventive and therapeutic effects on VILI to some extent. The effect of local use of glucocorticoid against VILI is similar to that of systemic use, but there is lesser adverse reaction.展开更多
Objective: To investigate the effect of recombinant human osteoprotegerin combined with tinidazole on mice with periodontitis and the effect on serum RANKL and MCP-1 levels. Methods: 80 SPF-cleaned mice were randomly ...Objective: To investigate the effect of recombinant human osteoprotegerin combined with tinidazole on mice with periodontitis and the effect on serum RANKL and MCP-1 levels. Methods: 80 SPF-cleaned mice were randomly divided into 4 groups, 20 each, model group, tinidazole group and recombinant human osteoprotegerin group were modeled by Kimura et al., and tinidazole group received tinidazole. After intragastric administration, the recombinant human osteoprotegerin group was injected with recombinant human osteoprotegerin in the periodontal pocket according to the tinidazole group. The periodontal changes of the four groups of mice were observed and recorded, and the gingival rating was performed. Epithelial tissue morphology was observed by hematoxylin-eosin (HE) staining. Serum levels of IL-4, IL-6, RANKL and MCP-1 were measured by enzyme-linked immunosorbent assay. Results:After the intervention, the model group developed severe inflammatory reactions, including redness, hemorrhage, and deep periodontal pockets. The teeth were significantly loosened. The mice in the tinidazole group and the recombinant human osteoprotegerin group recovered substantially, and the gingival rating of the recombinant human osteoprotegerin group was better than that. The tinidazole group and the model group (P<0.05). The results of HE staining showed that the model group had edema, vasodilation and a large amount of inflammatory infiltration. The epithelial structure of the mice in the tinidazole group and the recombinant human osteoprotegerin group was intact and arranged closely and orderly. After intervention, the IL-4 in the tinidazole group and the recombinant human osteoprotegerin group was significantly higher than the model group and IL-6 was significantly lower than the model group (P<0.05), and the recombinant human osteoprotegerin group IL-4 was significantly higher after the intervention. IL-6 was significantly lower in the tinidazole group than in the tinidazole group (P<0.05). After the intervention, the tinidazole group and the recombinant human osteoprotegerin group were significantly reduced, and the recombinant human osteoprotegerin group RAKNL and MCP-1 were significantly lower than the model group (P>0.05). Conclusion: Recombinant human osteoprotegerin combined with tinidazole has a better therapeutic effect on gums and teeth in mice with periodontitis, and can lower the levels of RAKNL and MCP-1 in serum, inhibit bone resorption and protect teeth.展开更多
Three-dimensional quantitative structure-activity relationship （3D-QSAR） and docking studies of a series of novel dioxopyrrolinyl-amino-pyrimidine derivatives, which are potential dual inhibitors mediating a transcr...Three-dimensional quantitative structure-activity relationship （3D-QSAR） and docking studies of a series of novel dioxopyrrolinyl-amino-pyrimidine derivatives, which are potential dual inhibitors mediating a transcriptional activation towards protein-1 （AP-1） and nuclear factor kappa B （NF-κB）, have been carried out. The QS, AR models established by comparative molecular field analysis （CoMFA） and comparative molecular similarity index analysis （CoMSIA） show a good predictive ability with cross-validated coefficients q2 of 0.644 and 0.636, respectively. The docking result shows that there are quite lower average values of the flexible and rigid energy scores on the selected binding sites, meanwhile, it further shows that the binding sites just fall on the joint regions between AP-1 （and NF-κB） and DNA. The reason that these analogues have inhibition function towards AP-I and NF-κB is that their existence on these joint regions can effectively prevent free AP-I and NF-κB from binding to DNA. These results can offer a valuable theoretical reference to the pharmaceutical molecular design as well as the action mechanism analysis.展开更多
In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive...In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.展开更多
BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes(PNS).4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis(PLE)have not been reported.CAS...BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes(PNS).4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis(PLE)have not been reported.CASE SUMMARY PNS are distant effects of cancer on the nervous system,rather than syndromes in which cancer directly invades and metastasizes to the nerves and/or muscle tissues.If the limbic lobe system of the brain is involved,this will result in PLE.The detection of patients with PNS is challenging since tumors that cause paraneoplastic neurologic disorders are often asymptomatic,obscure,and thus easily misdiagnosed or missed.Currently,single-or double-antibody-positive paraneoplastic marginal encephalitis has been reported.However,no cases of three or more-antibody-positive cases have been reported.Here,we report a case of PLE that is anti-collapsing response-mediator protein-5,anti-neuronal nuclear antibody-type 1,anti-aminobutyric acid B receptor,and anti-glutamate deglutase positive,and address relevant literature to improve our understanding of the disease.CONCLUSION This article reports on the management of a case of PLE with four positive antibodies,a review of the literature,in order to raise awareness among clinicians.展开更多
Cholestatic liver disease causes significant morbidity and mortality in children.The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequ...Cholestatic liver disease causes significant morbidity and mortality in children.The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequate interventional therapy.There is no single gold standard test that accurately reflects the presence of liver disease,or that can be used to monitor fibrosis progression,particularly in conditions such as cystic fibrosis.This has lead to controversy over how suspected liver disease in children is detected and diagnosed.This review discusses the challenges in using commonly available methods to diagnose hepatic fibrosis and monitor disease progression in children with cholestatic liver disease.In addition,the review examines the mechanisms hypothesised to be involved in the development of hepatic fibrogenesis in paediatric cholestatic liver injury which may ultimately aid in identifying new modalities to assist in both disease detection and therapeutic intervention.展开更多
Summary： The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-α, NF-κB, resulting in a disruption of gut barrier. The gastrointestinal tight junction （T J） is highly ...Summary： The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-α, NF-κB, resulting in a disruption of gut barrier. The gastrointestinal tight junction （T J） is highly regulated by membrane-associated proteins including zonula occludens protein-1 （ZO-1） and oc- cludin, which can be modulated by inflammatory cytokines. As splenectomy has been shown to reduce secretion of cytokines, we hypothesized that （1） severe scald injury up-regulates TNF-α and NF-κB, meanwhile down-regulates expression of ZO-1 and occludin, leading to the increased intestinal perme- ability, and （2） splenectomy can prevent the burn-induced decrease in ZO-1 and occludin expression, resulting in improved intestinal barrier. Wistar rats undergoing a 30% total body surface area （TBSA） thermal trauma were randomized to receive an accessorial splenectomy meanwhile or not. Intestinal in- jury was assessed by histological morphological analysis, and serum endotoxin levels, TNF-α, NF-κB, ZO-1 and occludin levels were detected by Western blotting in the terminal ileum mucosal tissue. 30% TBSA bum caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the av- erage intestinal villus height and mucosal thickness were decreased significantly. Burn injury could also markedly decrease the levels of ZO-1 and occludin in terminal ileum mucosal tissue （all P〈0.01）. Sple- nectomy at 7th day after burn significantly reversed the bum-induced breakdown of ZO-1 and occludin （all P〈0.01）. The results of this study suggest that severe thermal injury damages the intestinal mucosal barrier. Splenectomy may provide a therapeutic benefit in restoring bum-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.展开更多
Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity,which is closely associated with inflammation.Benzydamine(BA)has been used as a cytokine-suppressive or non-steroidal...Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity,which is closely associated with inflammation.Benzydamine(BA)has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of proinflammatory cytokines or prostaglandins.However,its role in osteoclast differentiation and function remains unknown.Here,we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism.BA inhibited osteoclast differentiation and strongly suppressed interleukin-1β(IL-1β)production.BA inhibited osteoclast formation and bone resorption when added to bone marrowderived macrophages and differentiated osteoclasts,and the inhibitory effect was reversed by IL-1βtreatment.The reporter assay and the inhibitor study of IL-1βtranscription suggested that BA inhibited nuclear factor-κB and activator protein-1 by regulating IκB kinase,extracellular signal regulated kinase and P38,resulting in the down-regulation of IL-1βexpression.BA also promoted osteoblast differentiation.Furthermore,BA protected lipopolysaccharide-and ovariectomy-induced bone loss in mice,suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis.展开更多
Background The renoprotective mechanisms of adenosine monophosphate （AMP）-activated protein kinase （AMPK） agonist-metformin have not been stated clearly.We hypothesized that metformin may ameliorate inflammation v...Background The renoprotective mechanisms of adenosine monophosphate （AMP）-activated protein kinase （AMPK） agonist-metformin have not been stated clearly.We hypothesized that metformin may ameliorate inflammation via AMPK interaction with critical inflammatory cytokines The aim of this study was to observe the effects of metformin on expression of nuclear factor-κB （NF-κB）,monocyte chemoattractant protein-1 （MCP-1）,intercellular adhesion molecule-1 （ICAM-1） and transforming growth factor-beta 1 （TGF-β1） induced by high glucose （HG） in cultured rat glomerular mesangial cells （MCs）.Methods MCs were cultured in the medium with normal concentration glucose （group NG,5.6 mmol/L）,high concentration glucose （group HG,25 mmol/L） and different concentrations of metformin （group M1,M2,M3）.After 48-hour exposure,the supernatants and MCs were collected.The expression of NF-κB,MCP-1,ICAM-1,and TGF-β1 mRNA was analyzed by real time polymerase chain reaction.Westem blotting was used to detect the expression of AMPK,phospho-Thr-172 AMPK （p-AMPK）,NF-κB p65,MCP-1,ICAM-1,and TGF-β1 protein.Results After stimulated by HG,the expression of NF-κB,MCP-1,ICAM-1,TGF-β1 mRNA and protein of MCs in group HG increased significantly compared with group NG （P ＜0.05）.Both genes and protein expression of NF-κB,MCP-1,ICAM-1,TGF-β1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner （P ＜0.05）.The expression of p-AMPK increased with the rising of metformin concentration,presenting the opposite trend,while the level of total-AMPK protein was unchanged with exposure to HG or metformin.Conlusion Metformin can suppress the expression of NF-κB,MCP-1,ICAM-1 and TGF-β1 of glomerular MCs induced by high glucose via AMPK activation,which may partlv contribute to its reno-protection.展开更多
Connexin 43 （Cx43） is the major structural protein of gap junctions in the ventricular myocardium and a major determinant of myocardial electrical properties. Cx43 expression is decreased in the wild type mice after...Connexin 43 （Cx43） is the major structural protein of gap junctions in the ventricular myocardium and a major determinant of myocardial electrical properties. Cx43 expression is decreased in the wild type mice after myocardial infarction and this effect is attenuated in MMP-7-/- mice. Matrix metalloproteinase expression is regulated at the transcription level by the modulation of the activation of transcription factors such as activator protein （AP）-I and nuclear factor kappa-light-chain enhancer of activated B cells （NF-KB）. Methods Rat myocardial cells （H9c2） were cultured and maintained at 37 ~C and 5% CO2. H9c2 cells in 6-well plates were treated with lipopolysaccharides （LPS）, NF-kB inhibitor （JSH 23, 30 μ, Santa Cruz） ＋ LPS and c-Jun N-terminal kinase （JNK） inhibitor （SP600125, 10μM, Sigma） ＋ LPS for 6, 12 and 24 h. Apoptosis rate of cells was determined by flow cytometry. Cx43 expression was assessed by Western blotting. Results LPS induced a time-dependent apoptosis in all cell line. We have found that the treatment with LPS induced increase of apoptosis in H9c2 cells at 6 h, 12 h and 24 h, but the effect was decreased by the addition of JSH-23 and SP600125 to LPS respectively （P 〈 0.05） . LPS resulted in decreased expression of Cx43 expression at 6 h, 12 h and 24 h. However, JSH-23 and SP600125 attenuated the loss of Cx43 respectively （P 〈 0.05）. Conclusion Transcription factors NF-kB and JNK/AP-1 signaling pathway participates in the regulation of LPS-induced Cx43 expression in the H9c2 cells, and maybe play an important role in regulation of Cx43 expression.展开更多
Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cut...Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor(GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB(NF-κB), p38 mitogen-activated protein kinase(P38 MAPK) and activator protein-1(AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1β. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.展开更多
Objective： To study the mechanism of Huogu I Formula （活骨I方） in treating osteonecrosis of femoral head. Methods： Forty-eight healthy female Leghorn chickens were randomly divided into control group, model group ...Objective： To study the mechanism of Huogu I Formula （活骨I方） in treating osteonecrosis of femoral head. Methods： Forty-eight healthy female Leghorn chickens were randomly divided into control group, model group and Huogu I group, and each group consisted of 16 chickens. At the meantime of model establishment, chickens of the Huogu I group were administrated with decoction, while the model and control group with distilled water by gavage. At the 8th and 16th week after medication, blood samples were obtained for blood lipid detection while both sides of femoral head were harvested for the rest of examinations. Specifically, expressions of bone morphogenetic protein-2 （BMP2）, transforming growth factor beta1 （TGFβ1）, Smad4 and Smad7 were evaluated by immunohistochemistry, while expression of osteoprotegerin/receptor activator of nuclear factor kappaB ligand （OPG/RANKL） mRNA was detected by in situ hybridization. Results： Compared with the control group, serum levels of total cholesterol （TG）, triglyceride （TG） and low-density lipoprotein cholesterol （LDL-C） in the model group rose significantly. Positive cell counting of BMP2, TGF 131, Smad4 and OPG in femoral head of the model group dropped prominently. Positive cell counting of Smad7 and RANKL increased dramatically. In contrast with the model group, levels of TC, TG and LDL-C in Huogu I group reduced significantly. Positive cell counting of BMP2, TGFβ1, Smad4 and OPG in femoral head of the Huogu I group increased prominently. Indices of Smad7 and RANKL both decreased significantly. Especially at the 8th week, these variations were more significant. Conclusion： Huogu I Formula is effective in promoting repair of necrotic femoral head by regulating the expressions of BMP2, TGFβ1, Smads and OPG/RANKL of osteoclast in femoral head.展开更多
基金This project was supported by a grant from the NationalNatural Sciences Foundation of China (No .30470713)
文摘To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group （LC）, high- cholesterol group （HC）, high-cholesterol＋ simvastatin group （HC＋S） and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shift as- say （EMSA）, immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kB-DNA binding activity, MCP-1 protein expression, intirna thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC＋S groups were significantly lower than those in the HC group （P〈0.05）. There was no significant difference in the serum lipids between the LC and HC＋S groups （P〉0.05）, but the NF-kB-DNA binding activity, the expression of MCP-1 protein and the intirna thickness and plaque area of aorta in the HC＋S group were significantly decreased as compared to the LC group （P〈0. 05）. This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kB-DNA binding activity and by reducing the expression of MCP-1 protein.
文摘BACKGROUND： Ventilator induced lung injury （VILI） is a serious complication in the treatment of mechanical ventilating patients, and it is also the main cause that results in exacerbation or death of patients. In this study, we produced VILI models by using glucocorticoid in rats with high tidal volume mechanical ventilation, and observed the content of macrophage inflammatory protein-1α （MIP-1α） in plasma and bronchoalveolar lavage fluid （BALF） and the expression of MIP-1α mRNA and nuclear factor-kappa B （NF-кB） p65 mRNA in the lung so as to explore the role of glucocorticoid in mechanical ventilation.METHODS： Thirty-two healthy Wistar rats were randomly divided into a control group, a ventilator induced lung injury （VILI） group, a dexamethasone （DEX） group and a budesonide （BUD） group. The content of MIP-1a in plasma and BALF was measured with ELISA and the level of MIP-1α mRNA and NF-кBp65 mRNA expressing in the lung of rats were detected by RT-PCR. The data were expressed as mean±SD and were compared between the groups.RESULTS： The content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-кBp65 mRNA in the lung in the DEX and BUD groups were signifi cantly lower than those in the VILI group （P〈0.001）. Although the content of MIP-1α in plasma and BALF and the level of MIP-1α mRNA and NF-кBp65 mRNA in the lung in the BUD group were higher than those in the DEX group, there were no signifi cant differences between them （P〉0.05）.CONCLUSIONS： Glucocorticoid could down-regulate the expression of MIP-1α by inhibiting the activity of NF-кB in the lung and may exert preventive and therapeutic effects on VILI to some extent. The effect of local use of glucocorticoid against VILI is similar to that of systemic use, but there is lesser adverse reaction.
文摘Objective: To investigate the effect of recombinant human osteoprotegerin combined with tinidazole on mice with periodontitis and the effect on serum RANKL and MCP-1 levels. Methods: 80 SPF-cleaned mice were randomly divided into 4 groups, 20 each, model group, tinidazole group and recombinant human osteoprotegerin group were modeled by Kimura et al., and tinidazole group received tinidazole. After intragastric administration, the recombinant human osteoprotegerin group was injected with recombinant human osteoprotegerin in the periodontal pocket according to the tinidazole group. The periodontal changes of the four groups of mice were observed and recorded, and the gingival rating was performed. Epithelial tissue morphology was observed by hematoxylin-eosin (HE) staining. Serum levels of IL-4, IL-6, RANKL and MCP-1 were measured by enzyme-linked immunosorbent assay. Results:After the intervention, the model group developed severe inflammatory reactions, including redness, hemorrhage, and deep periodontal pockets. The teeth were significantly loosened. The mice in the tinidazole group and the recombinant human osteoprotegerin group recovered substantially, and the gingival rating of the recombinant human osteoprotegerin group was better than that. The tinidazole group and the model group (P<0.05). The results of HE staining showed that the model group had edema, vasodilation and a large amount of inflammatory infiltration. The epithelial structure of the mice in the tinidazole group and the recombinant human osteoprotegerin group was intact and arranged closely and orderly. After intervention, the IL-4 in the tinidazole group and the recombinant human osteoprotegerin group was significantly higher than the model group and IL-6 was significantly lower than the model group (P<0.05), and the recombinant human osteoprotegerin group IL-4 was significantly higher after the intervention. IL-6 was significantly lower in the tinidazole group than in the tinidazole group (P<0.05). After the intervention, the tinidazole group and the recombinant human osteoprotegerin group were significantly reduced, and the recombinant human osteoprotegerin group RAKNL and MCP-1 were significantly lower than the model group (P>0.05). Conclusion: Recombinant human osteoprotegerin combined with tinidazole has a better therapeutic effect on gums and teeth in mice with periodontitis, and can lower the levels of RAKNL and MCP-1 in serum, inhibit bone resorption and protect teeth.
基金Acknowledgments： The authors are pleased to thank the financial supports of the National Natural Science Foundation of China （Nos.： 20673148 and 90608012）. We heartily thank the Molecular Discovery Ltd. for giving us the Dock 6.0 program as a freewarc. The authors are also pleased to thank the College of Life Sciences, Sun Yat-Sen University for the Sybyl 6.9 computation environment support.
文摘Three-dimensional quantitative structure-activity relationship （3D-QSAR） and docking studies of a series of novel dioxopyrrolinyl-amino-pyrimidine derivatives, which are potential dual inhibitors mediating a transcriptional activation towards protein-1 （AP-1） and nuclear factor kappa B （NF-κB）, have been carried out. The QS, AR models established by comparative molecular field analysis （CoMFA） and comparative molecular similarity index analysis （CoMSIA） show a good predictive ability with cross-validated coefficients q2 of 0.644 and 0.636, respectively. The docking result shows that there are quite lower average values of the flexible and rigid energy scores on the selected binding sites, meanwhile, it further shows that the binding sites just fall on the joint regions between AP-1 （and NF-κB） and DNA. The reason that these analogues have inhibition function towards AP-I and NF-κB is that their existence on these joint regions can effectively prevent free AP-I and NF-κB from binding to DNA. These results can offer a valuable theoretical reference to the pharmaceutical molecular design as well as the action mechanism analysis.
文摘In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.
文摘BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes(PNS).4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis(PLE)have not been reported.CASE SUMMARY PNS are distant effects of cancer on the nervous system,rather than syndromes in which cancer directly invades and metastasizes to the nerves and/or muscle tissues.If the limbic lobe system of the brain is involved,this will result in PLE.The detection of patients with PNS is challenging since tumors that cause paraneoplastic neurologic disorders are often asymptomatic,obscure,and thus easily misdiagnosed or missed.Currently,single-or double-antibody-positive paraneoplastic marginal encephalitis has been reported.However,no cases of three or more-antibody-positive cases have been reported.Here,we report a case of PLE that is anti-collapsing response-mediator protein-5,anti-neuronal nuclear antibody-type 1,anti-aminobutyric acid B receptor,and anti-glutamate deglutase positive,and address relevant literature to improve our understanding of the disease.CONCLUSION This article reports on the management of a case of PLE with four positive antibodies,a review of the literature,in order to raise awareness among clinicians.
基金Supported by a Project Grant from the National Health and Medical Research Council of Australia(NHMRC#496602 to GAR and PJL)Dr.Tamara Pereira is Supported by the Phillip Bushell Foundation Post-Doctoral Research Fellowship from the Gastroenterological Society of AustraliaAssociate Professor Grant A Ramm is Supported by a NHMRC Senior Research Fellowship(NHMRC#552409)
文摘Cholestatic liver disease causes significant morbidity and mortality in children.The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequate interventional therapy.There is no single gold standard test that accurately reflects the presence of liver disease,or that can be used to monitor fibrosis progression,particularly in conditions such as cystic fibrosis.This has lead to controversy over how suspected liver disease in children is detected and diagnosed.This review discusses the challenges in using commonly available methods to diagnose hepatic fibrosis and monitor disease progression in children with cholestatic liver disease.In addition,the review examines the mechanisms hypothesised to be involved in the development of hepatic fibrogenesis in paediatric cholestatic liver injury which may ultimately aid in identifying new modalities to assist in both disease detection and therapeutic intervention.
基金supported by the Natural Science Foundation of Hubei Province(No.2010CDBO7804)
文摘Summary： The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-α, NF-κB, resulting in a disruption of gut barrier. The gastrointestinal tight junction （T J） is highly regulated by membrane-associated proteins including zonula occludens protein-1 （ZO-1） and oc- cludin, which can be modulated by inflammatory cytokines. As splenectomy has been shown to reduce secretion of cytokines, we hypothesized that （1） severe scald injury up-regulates TNF-α and NF-κB, meanwhile down-regulates expression of ZO-1 and occludin, leading to the increased intestinal perme- ability, and （2） splenectomy can prevent the burn-induced decrease in ZO-1 and occludin expression, resulting in improved intestinal barrier. Wistar rats undergoing a 30% total body surface area （TBSA） thermal trauma were randomized to receive an accessorial splenectomy meanwhile or not. Intestinal in- jury was assessed by histological morphological analysis, and serum endotoxin levels, TNF-α, NF-κB, ZO-1 and occludin levels were detected by Western blotting in the terminal ileum mucosal tissue. 30% TBSA bum caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the av- erage intestinal villus height and mucosal thickness were decreased significantly. Burn injury could also markedly decrease the levels of ZO-1 and occludin in terminal ileum mucosal tissue （all P〈0.01）. Sple- nectomy at 7th day after burn significantly reversed the bum-induced breakdown of ZO-1 and occludin （all P〈0.01）. The results of this study suggest that severe thermal injury damages the intestinal mucosal barrier. Splenectomy may provide a therapeutic benefit in restoring bum-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.
基金supported by the National Research Foundation(NRF)(Grant Nos.2017R1A2B2012435,2019R1C1C1011198 and 2019R1A5A6099645,Korea)funded by the Korean Ministry of Science,ICT and future Planning(MSIP).
文摘Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity,which is closely associated with inflammation.Benzydamine(BA)has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of proinflammatory cytokines or prostaglandins.However,its role in osteoclast differentiation and function remains unknown.Here,we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism.BA inhibited osteoclast differentiation and strongly suppressed interleukin-1β(IL-1β)production.BA inhibited osteoclast formation and bone resorption when added to bone marrowderived macrophages and differentiated osteoclasts,and the inhibitory effect was reversed by IL-1βtreatment.The reporter assay and the inhibitor study of IL-1βtranscription suggested that BA inhibited nuclear factor-κB and activator protein-1 by regulating IκB kinase,extracellular signal regulated kinase and P38,resulting in the down-regulation of IL-1βexpression.BA also promoted osteoblast differentiation.Furthermore,BA protected lipopolysaccharide-and ovariectomy-induced bone loss in mice,suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis.
基金This work was supported by grants from the Natural Science Foundation （No. 11040606M 159） and Natural Science Research Project （No. K J2011A157） of Anhui Province, China.
文摘Background The renoprotective mechanisms of adenosine monophosphate （AMP）-activated protein kinase （AMPK） agonist-metformin have not been stated clearly.We hypothesized that metformin may ameliorate inflammation via AMPK interaction with critical inflammatory cytokines The aim of this study was to observe the effects of metformin on expression of nuclear factor-κB （NF-κB）,monocyte chemoattractant protein-1 （MCP-1）,intercellular adhesion molecule-1 （ICAM-1） and transforming growth factor-beta 1 （TGF-β1） induced by high glucose （HG） in cultured rat glomerular mesangial cells （MCs）.Methods MCs were cultured in the medium with normal concentration glucose （group NG,5.6 mmol/L）,high concentration glucose （group HG,25 mmol/L） and different concentrations of metformin （group M1,M2,M3）.After 48-hour exposure,the supernatants and MCs were collected.The expression of NF-κB,MCP-1,ICAM-1,and TGF-β1 mRNA was analyzed by real time polymerase chain reaction.Westem blotting was used to detect the expression of AMPK,phospho-Thr-172 AMPK （p-AMPK）,NF-κB p65,MCP-1,ICAM-1,and TGF-β1 protein.Results After stimulated by HG,the expression of NF-κB,MCP-1,ICAM-1,TGF-β1 mRNA and protein of MCs in group HG increased significantly compared with group NG （P ＜0.05）.Both genes and protein expression of NF-κB,MCP-1,ICAM-1,TGF-β1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner （P ＜0.05）.The expression of p-AMPK increased with the rising of metformin concentration,presenting the opposite trend,while the level of total-AMPK protein was unchanged with exposure to HG or metformin.Conlusion Metformin can suppress the expression of NF-κB,MCP-1,ICAM-1 and TGF-β1 of glomerular MCs induced by high glucose via AMPK activation,which may partlv contribute to its reno-protection.
基金supported by the National Nature Science Foundation of China (81160152)
文摘Connexin 43 （Cx43） is the major structural protein of gap junctions in the ventricular myocardium and a major determinant of myocardial electrical properties. Cx43 expression is decreased in the wild type mice after myocardial infarction and this effect is attenuated in MMP-7-/- mice. Matrix metalloproteinase expression is regulated at the transcription level by the modulation of the activation of transcription factors such as activator protein （AP）-I and nuclear factor kappa-light-chain enhancer of activated B cells （NF-KB）. Methods Rat myocardial cells （H9c2） were cultured and maintained at 37 ~C and 5% CO2. H9c2 cells in 6-well plates were treated with lipopolysaccharides （LPS）, NF-kB inhibitor （JSH 23, 30 μ, Santa Cruz） ＋ LPS and c-Jun N-terminal kinase （JNK） inhibitor （SP600125, 10μM, Sigma） ＋ LPS for 6, 12 and 24 h. Apoptosis rate of cells was determined by flow cytometry. Cx43 expression was assessed by Western blotting. Results LPS induced a time-dependent apoptosis in all cell line. We have found that the treatment with LPS induced increase of apoptosis in H9c2 cells at 6 h, 12 h and 24 h, but the effect was decreased by the addition of JSH-23 and SP600125 to LPS respectively （P 〈 0.05） . LPS resulted in decreased expression of Cx43 expression at 6 h, 12 h and 24 h. However, JSH-23 and SP600125 attenuated the loss of Cx43 respectively （P 〈 0.05）. Conclusion Transcription factors NF-kB and JNK/AP-1 signaling pathway participates in the regulation of LPS-induced Cx43 expression in the H9c2 cells, and maybe play an important role in regulation of Cx43 expression.
基金supported by the National Natural Science Foundation of China(No.81602108)
文摘Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor(GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB(NF-κB), p38 mitogen-activated protein kinase(P38 MAPK) and activator protein-1(AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1β. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.
基金Supported by the National Natural Foundation of China(No. 81173417 and 30472131)
文摘Objective： To study the mechanism of Huogu I Formula （活骨I方） in treating osteonecrosis of femoral head. Methods： Forty-eight healthy female Leghorn chickens were randomly divided into control group, model group and Huogu I group, and each group consisted of 16 chickens. At the meantime of model establishment, chickens of the Huogu I group were administrated with decoction, while the model and control group with distilled water by gavage. At the 8th and 16th week after medication, blood samples were obtained for blood lipid detection while both sides of femoral head were harvested for the rest of examinations. Specifically, expressions of bone morphogenetic protein-2 （BMP2）, transforming growth factor beta1 （TGFβ1）, Smad4 and Smad7 were evaluated by immunohistochemistry, while expression of osteoprotegerin/receptor activator of nuclear factor kappaB ligand （OPG/RANKL） mRNA was detected by in situ hybridization. Results： Compared with the control group, serum levels of total cholesterol （TG）, triglyceride （TG） and low-density lipoprotein cholesterol （LDL-C） in the model group rose significantly. Positive cell counting of BMP2, TGF 131, Smad4 and OPG in femoral head of the model group dropped prominently. Positive cell counting of Smad7 and RANKL increased dramatically. In contrast with the model group, levels of TC, TG and LDL-C in Huogu I group reduced significantly. Positive cell counting of BMP2, TGFβ1, Smad4 and OPG in femoral head of the Huogu I group increased prominently. Indices of Smad7 and RANKL both decreased significantly. Especially at the 8th week, these variations were more significant. Conclusion： Huogu I Formula is effective in promoting repair of necrotic femoral head by regulating the expressions of BMP2, TGFβ1, Smads and OPG/RANKL of osteoclast in femoral head.
