BACKGROUND: Urinary trypsin inhibitor (UTI) inhibits the inflammatory response and protects against ischemia-reperfusion (I/R) injury. The inflammatory response is mediated by nuclear factor-kappa B (NF-kappa B) and i...BACKGROUND: Urinary trypsin inhibitor (UTI) inhibits the inflammatory response and protects against ischemia-reperfusion (I/R) injury. The inflammatory response is mediated by nuclear factor-kappa B (NF-kappa B) and its related target genes and products such as vascular endothelial cell adhesion molecule and CXC chemokines. We aimed to assess the roles of those mediators in a UTI-treated mouse model of hepatic I/R injury. METHODS: Treatment group 1 (UTI given 5 minutes prior to liver ischemia), treatment group 2 (UTI given 5 minutes after the anhepatic phase) and a control group were investigated. Blood and liver samples were obtained and compared at 1, 3, 6 and 24 hours after reperfusion. RESULTS: Attenuation of pathological hepatocellular damage was greater in the treatment groups than in the control group (P < 0.05). Compared with the control group, the UTI treatment groups showed significantly lower serum alanine aminotransferase and aspartate aminotransferase levels, decreased myeloperoxidase activity, and reduced NF-kappa B activation. Also downregulated was the expression of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2 at the mRNA level. P-selectin protein and intercellular adhesion molecule-1 protein expression were also downregulated. In addition, the treatment group I showed a better protective effect against I/R injury than the treatment group 2. CONCLUSIONS: UTI reduces NF-kappa B activation and downregulates the expression of its related mediators, followed by the inhibition of neutrophil aggregation and infiltration in hepatic I/R injury. The protective role of UTI is more effective in prevention than in treatment.展开更多
AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were inject...AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin-6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κB (NF-κB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05). CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-κB activation, which could become a remedial target for liver fibrosis.展开更多
目的研究在呼吸机所致肺损伤(VILI)的炎症反应中加用呼气末正压(PEEP)对核因子-κB(NF-κB)的活性变化的影响。方法健康成年新西兰白兔30只随机分为3组:PEEP组(致伤通气+3 cm H2O PEEP)、ZEEP组(致伤通气+0 cm H2O PEEP组)和对照组(始...目的研究在呼吸机所致肺损伤(VILI)的炎症反应中加用呼气末正压(PEEP)对核因子-κB(NF-κB)的活性变化的影响。方法健康成年新西兰白兔30只随机分为3组:PEEP组(致伤通气+3 cm H2O PEEP)、ZEEP组(致伤通气+0 cm H2O PEEP组)和对照组(始终以正常条件通气)。机械通气开始后4 h处死动物。采用Western-blot法检测家兔肺组织NF-κB及核因子抑制蛋白(IκB-α)的含量。结果家兔在致伤通气4 h后,肺组织NF-κB表达显著增加,而在致伤通气的同时加用PEEP,肺组织NF-κB表达明显减少。结论在机械通气过程中加用PEEP可通过减少NF-κB的表达保护肺组织减轻损伤。展开更多
目的:探讨围产期缺血缺氧对新生大鼠肺超微结构和肿瘤坏死因子α(TNFα-)及核因子κB抑制蛋白(κI-Bα)表达的影响。方法:结扎孕鼠一侧子宫角血管(另一侧宫内胎鼠作为对照),建立围产期缺血缺氧动物模型。电镜下观察肺组织超微结构变化...目的:探讨围产期缺血缺氧对新生大鼠肺超微结构和肿瘤坏死因子α(TNFα-)及核因子κB抑制蛋白(κI-Bα)表达的影响。方法:结扎孕鼠一侧子宫角血管(另一侧宫内胎鼠作为对照),建立围产期缺血缺氧动物模型。电镜下观察肺组织超微结构变化并分别采用ELISA、RT-PCR和W estern b lot杂交法观察不同程度缺血缺氧新生大鼠肺组织TNFα-蛋白和mRNA及I-κBα表达的变化。结果:宫内急性缺血缺氧20 m in时,新生大鼠Ⅱ型肺泡上皮细胞和毛细血管内皮细胞受损;肺组织TNFα-蛋白和mRNA表达明显增强(P均<0.01),κI-Bα表达明显减弱(P<0.05),并随缺血缺氧时间延长病变加重。结论:围产期急性缺血缺氧致新生大鼠肺损伤,Iκ-Bα和TNFα-的异常表达可能是肺损伤的重要原因。展开更多
· AIM: To investigate the effect of emodin on pseudomonas aeruginosa lipopolysaccharides(LPS)-induced corneal inflammation in rats.· METHODS: Corneal infection was induced by pseudomonas aeruginosa LPS in Wi...· AIM: To investigate the effect of emodin on pseudomonas aeruginosa lipopolysaccharides(LPS)-induced corneal inflammation in rats.· METHODS: Corneal infection was induced by pseudomonas aeruginosa LPS in Wistar rats. The inflammation induced by LPS were examined by slit lamp microscope and cytological checkup of aqueous humor.Corneal tissue structure was observed by hematoxylin and eosin(HE) staining. The activation of nuclear factor kappa B(NF-κB) was determined by Western blot.Messenger ribonucleic acid(m RNA) of tumor necrosis factor-α(TNF-α) and intercellular adhesion molecule-1(ICAM-1) in LPS-challenged rat corneas were measured with reverse transcription-polymerase chain reaction(RT-PCR).· RESULTS: Typical manifestations of acute corneal inflammation were observed in LPS-induce rat model,and the corneal inflammatory response and structure were improved in rats pretreated with emodin. Treatment with emodin could improve corneal structure, reduce corneal injure by reducing corneal inflammatory response. Emodin could inhibit the decreasing lever of inhibitor of kappa B alpha(IкBα) express, and the m RNA expression of TNF-α and ICAM-1 in corneal tissues was also inhibited by emodin. The differences were statistically significant between groups treated with emodin and those without treatment(P 【0.01).·CONCLUSION: Emodin could ameliorate LPS-induced corneal inflammation, which might via inhibiting the activation of NF-κB.展开更多
Cancer metabolism and epigenetic alteration are two critical mechanisms for tumorigenesis and cancer progres?sion; however, the dynamic interplay between them remains poorly understood. As reported in the article enti...Cancer metabolism and epigenetic alteration are two critical mechanisms for tumorigenesis and cancer progres?sion; however, the dynamic interplay between them remains poorly understood. As reported in the article entitled "Chromatin remodeling factor LSH drives cancer progression by suppressing the activity of fumarate hydratase," which was recently published in Cancer Research, our group examined the physiological role of lymphocyte?specific heli?case(LSH) in nasopharyngeal carcinoma(NPC) by focusing on cancer progression and the tricarboxylic acid cycle. We found that LSH was overexpressed in NPC, and its expression associated with Epstein?Barr virus infection. We also found that LSH directly suppressed fumarate hydratase(FH), a key component of the tricarboxylic acid cycle, in combination with euchromatic histone?lysine N?methyltransferase 2(EHMT2), also known as G9 a. Depletion of FH promoted epithelial?mesenchymal transition(EMT). Moreover, LSH controlled expression of tricarboxylic acid cycle intermediates that promote cancer progression, including EMT, through activation by inhibitor of nuclear factor kappa?B kinase alpha(IKKα), a chromatin modifier and transcriptional activator. Our study showed that LSH plays a critical role in cancer progression, which has important implications for the development of novel strategies to treat NPC.展开更多
文摘BACKGROUND: Urinary trypsin inhibitor (UTI) inhibits the inflammatory response and protects against ischemia-reperfusion (I/R) injury. The inflammatory response is mediated by nuclear factor-kappa B (NF-kappa B) and its related target genes and products such as vascular endothelial cell adhesion molecule and CXC chemokines. We aimed to assess the roles of those mediators in a UTI-treated mouse model of hepatic I/R injury. METHODS: Treatment group 1 (UTI given 5 minutes prior to liver ischemia), treatment group 2 (UTI given 5 minutes after the anhepatic phase) and a control group were investigated. Blood and liver samples were obtained and compared at 1, 3, 6 and 24 hours after reperfusion. RESULTS: Attenuation of pathological hepatocellular damage was greater in the treatment groups than in the control group (P < 0.05). Compared with the control group, the UTI treatment groups showed significantly lower serum alanine aminotransferase and aspartate aminotransferase levels, decreased myeloperoxidase activity, and reduced NF-kappa B activation. Also downregulated was the expression of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2 at the mRNA level. P-selectin protein and intercellular adhesion molecule-1 protein expression were also downregulated. In addition, the treatment group I showed a better protective effect against I/R injury than the treatment group 2. CONCLUSIONS: UTI reduces NF-kappa B activation and downregulates the expression of its related mediators, followed by the inhibition of neutrophil aggregation and infiltration in hepatic I/R injury. The protective role of UTI is more effective in prevention than in treatment.
基金Supported by Shanghai Municipal Health Bureau Youth Grant, No. 2008Y032
文摘AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin-6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κB (NF-κB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05). CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-κB activation, which could become a remedial target for liver fibrosis.
文摘目的研究在呼吸机所致肺损伤(VILI)的炎症反应中加用呼气末正压(PEEP)对核因子-κB(NF-κB)的活性变化的影响。方法健康成年新西兰白兔30只随机分为3组:PEEP组(致伤通气+3 cm H2O PEEP)、ZEEP组(致伤通气+0 cm H2O PEEP组)和对照组(始终以正常条件通气)。机械通气开始后4 h处死动物。采用Western-blot法检测家兔肺组织NF-κB及核因子抑制蛋白(IκB-α)的含量。结果家兔在致伤通气4 h后,肺组织NF-κB表达显著增加,而在致伤通气的同时加用PEEP,肺组织NF-κB表达明显减少。结论在机械通气过程中加用PEEP可通过减少NF-κB的表达保护肺组织减轻损伤。
文摘目的:探讨围产期缺血缺氧对新生大鼠肺超微结构和肿瘤坏死因子α(TNFα-)及核因子κB抑制蛋白(κI-Bα)表达的影响。方法:结扎孕鼠一侧子宫角血管(另一侧宫内胎鼠作为对照),建立围产期缺血缺氧动物模型。电镜下观察肺组织超微结构变化并分别采用ELISA、RT-PCR和W estern b lot杂交法观察不同程度缺血缺氧新生大鼠肺组织TNFα-蛋白和mRNA及I-κBα表达的变化。结果:宫内急性缺血缺氧20 m in时,新生大鼠Ⅱ型肺泡上皮细胞和毛细血管内皮细胞受损;肺组织TNFα-蛋白和mRNA表达明显增强(P均<0.01),κI-Bα表达明显减弱(P<0.05),并随缺血缺氧时间延长病变加重。结论:围产期急性缺血缺氧致新生大鼠肺损伤,Iκ-Bα和TNFα-的异常表达可能是肺损伤的重要原因。
基金Supported by Science and Technology Development Plan of Shandong Province,China(No.2014GSF118006)
文摘· AIM: To investigate the effect of emodin on pseudomonas aeruginosa lipopolysaccharides(LPS)-induced corneal inflammation in rats.· METHODS: Corneal infection was induced by pseudomonas aeruginosa LPS in Wistar rats. The inflammation induced by LPS were examined by slit lamp microscope and cytological checkup of aqueous humor.Corneal tissue structure was observed by hematoxylin and eosin(HE) staining. The activation of nuclear factor kappa B(NF-κB) was determined by Western blot.Messenger ribonucleic acid(m RNA) of tumor necrosis factor-α(TNF-α) and intercellular adhesion molecule-1(ICAM-1) in LPS-challenged rat corneas were measured with reverse transcription-polymerase chain reaction(RT-PCR).· RESULTS: Typical manifestations of acute corneal inflammation were observed in LPS-induce rat model,and the corneal inflammatory response and structure were improved in rats pretreated with emodin. Treatment with emodin could improve corneal structure, reduce corneal injure by reducing corneal inflammatory response. Emodin could inhibit the decreasing lever of inhibitor of kappa B alpha(IкBα) express, and the m RNA expression of TNF-α and ICAM-1 in corneal tissues was also inhibited by emodin. The differences were statistically significant between groups treated with emodin and those without treatment(P 【0.01).·CONCLUSION: Emodin could ameliorate LPS-induced corneal inflammation, which might via inhibiting the activation of NF-κB.
基金supported by grants from the National Basic Research Program of China[2015CB553903(YGT)]the National Natural Science Foundation of China[81171881 and 81372427(YGT)and 81271763(SL)]the Hunan Natural Science Foundation of China[12JJ1013(YGT)]
文摘Cancer metabolism and epigenetic alteration are two critical mechanisms for tumorigenesis and cancer progres?sion; however, the dynamic interplay between them remains poorly understood. As reported in the article entitled "Chromatin remodeling factor LSH drives cancer progression by suppressing the activity of fumarate hydratase," which was recently published in Cancer Research, our group examined the physiological role of lymphocyte?specific heli?case(LSH) in nasopharyngeal carcinoma(NPC) by focusing on cancer progression and the tricarboxylic acid cycle. We found that LSH was overexpressed in NPC, and its expression associated with Epstein?Barr virus infection. We also found that LSH directly suppressed fumarate hydratase(FH), a key component of the tricarboxylic acid cycle, in combination with euchromatic histone?lysine N?methyltransferase 2(EHMT2), also known as G9 a. Depletion of FH promoted epithelial?mesenchymal transition(EMT). Moreover, LSH controlled expression of tricarboxylic acid cycle intermediates that promote cancer progression, including EMT, through activation by inhibitor of nuclear factor kappa?B kinase alpha(IKKα), a chromatin modifier and transcriptional activator. Our study showed that LSH plays a critical role in cancer progression, which has important implications for the development of novel strategies to treat NPC.
