BACKGROUND Ulcer colitis(UC)is a chronic,nonspecific,and noninfectious inflammatory bowel disease.Recently,Toll-like receptors(TLRs)have been found to be closely associated with clinical inflammatory diseases.Achievin...BACKGROUND Ulcer colitis(UC)is a chronic,nonspecific,and noninfectious inflammatory bowel disease.Recently,Toll-like receptors(TLRs)have been found to be closely associated with clinical inflammatory diseases.Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging.Moreover,no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC.AIM To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC.METHODS This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021.The patients with UC were divided into two groups(control and experimental).The peripheral blood of the experimental and control groups were collected under aseptic conditions.The expression of TLR4 protein,NF-κB,IL-6,and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug.Linear co rrelation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17,and P<0.05 was considered statistically significant.RESULTS There were no significant differences in the patient characteristics between the control and experimental groups.The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group(P<0.05).The levels of IL-6 and IL-17 in the experimental group were significantly lower than those in the control group(P<0.05).The TLR4 protein expression in the experimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17(r=0.823,P<0.05).CONCLUSION Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates the inflammatory response of UC through the TLR4/NF-κB signaling pathway.展开更多
BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy optio...BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.展开更多
BACKGROUND Insomnia is a disease where individuals cannot maintain a steady and stable sleep state or fail to fall asleep.Western medicine mainly uses sedatives and hypnotic drugs to treat insomnia,and long-term use i...BACKGROUND Insomnia is a disease where individuals cannot maintain a steady and stable sleep state or fail to fall asleep.Western medicine mainly uses sedatives and hypnotic drugs to treat insomnia,and long-term use is prone to drug resistance and other adverse reactions.Acupuncture has a good curative effect and unique advantages in the treatment of insomnia.AIM To explore the molecular mechanism of acupuncture at Back-Shu point for the treatment of insomnia.METHODS We first prepared a rat model of insomnia,and then carried out acupuncture for 7 consecutive days.After treatment,the sleep time and general behavior of the rats were determined.The Morris water maze test was used to assess the learning ability and spatial memory ability of the rats.The expression levels of inflammatory cytokines in serum and the hippocampus were detected by ELISA.qRTPCR was used to detect the mRNA expression changes in the ERK/NF-κB signaling pathway.Western blot and immunohistochemistry were carried out to evaluate the protein expression levels of RAF-1,MEK-2,ERK1/2 and NF-κB.RESULTS Acupuncture can prolong sleep duration,and improve mental state,activity,diet volume,learning ability and spatial memory.In addition,acupuncture increased the release of 1L-1β,1L-6 and TNF-αin serum and the hippocampus and inhibited the mRNA and protein expression of the ERK/NF-κB signaling pathway.CONCLUSION These findings suggest that acupuncture at Back-Shu point can inhibit the ERK/NF-κB signaling pathway and treat insomnia by increasing the release of inflammatory cytokines in the hippocampus.展开更多
Nucleotide oligomerization domain 2(NOD2) is a major cytoplasmic sensor for pathogens and is critical for the clearance of cytosolic bacteria in mammals.However, studies regarding NOD2, especially the initiated signal...Nucleotide oligomerization domain 2(NOD2) is a major cytoplasmic sensor for pathogens and is critical for the clearance of cytosolic bacteria in mammals.However, studies regarding NOD2, especially the initiated signaling pathways, are scarce in teleost species. In this study, we identified a NOD2 molecule(PaNOD2) from ayu(Plecoglossus altivelis).Bioinformatics analysis showed the structure of NOD2 to be highly conserved during vertebrate evolution. Dual-luciferase reporter assays examined the activation of NF-κB signaling and Western blotting analysis detected the phosphorylation of three MAP kinases(p-38, Erk1/2, and JNK1/2).Functional study revealed that, like its mammalian counterparts, PaNOD2 was the receptor of the bacterial cell wall component muramyl dipeptide(MDP), and the leucine-rich repeat motif was responsible for the recognition and binding of Pa NOD2 with the ligand. Overexpression of PaNOD2 activated the NF-κB signaling pathway, leading to the upregulation of inflammatory cytokines, including TNF-α and IL-1β in HEK293 T cells and ayu head kidney-derived monocytes/macrophages(MO/MΦ).Particularly, we found that PaNOD2 activated the MAPK signaling pathways, as indicated by the increased phosphorylation of p-38, Erk1/2, and JNK1/2, which have not been characterized in any teleost species previously. Our findings proved that the NOD2 molecule and initiated pathways are conserved between mammals and ayu. Therefore, ayu could be used as an animal model to investigate NOD2-based diseases and therapeutic applications.展开更多
AIM To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide(LPS)-induced liver injury in vivo and in vitro.METHODS Male β-arrestin 2^(+/+) and β-arrestin 2^(-/-)C57 BL/6 J mice were used ...AIM To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide(LPS)-induced liver injury in vivo and in vitro.METHODS Male β-arrestin 2^(+/+) and β-arrestin 2^(-/-)C57 BL/6 J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines. Cultured cell extracts were collected to analyze the production of pro-inflammatory cytokines and expression of key molecules involved in the TLR4/NF-κB signaling pathway.RESULTS Compared with wild-type mice, the β-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of proinflammatory cytokines, including interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and IL-10. Compared with the control group, pro-inflammatory cytokines(including IL-1β, IL-6, TNF-α, and IL-10) produced by RAW264.7 cells in the β-arrestin 2 si RNA group were significantly increased at 6 h after treatment with LPS. Further, key molecules involved in the TLR4/NF-κB signaling pathway, including phosphoIκBα and phosho-p65, were upregulated.CONCLUSION β-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB signaling pathwaymediated inflammation.展开更多
Phycocyanin (PC), a natural algal protein, is reported for having anti-oxidant and antiinfl ammatory properties. We investigated its ability to attenuate lung infl ammation in mice subjected to X-ray radiation. Male C...Phycocyanin (PC), a natural algal protein, is reported for having anti-oxidant and antiinfl ammatory properties. We investigated its ability to attenuate lung infl ammation in mice subjected to X-ray radiation. Male C57BL/6 mice were assigned to the control, total body irradiation, PC pretreatment, and PC treatment groups. Mice in the PC pretreatment group were gavaged with 200 mg/kg PC for 7 consecutive days before irradiation, and those in the PC treatment group were gavaged with 200 mg/kg PC for 7 consecutive days after irradiation. Lungs were collected on Day 7 after irradiation exposure. Hematoxylin and eosin staining of mouse lung sections showed considerable infl ammation damage 7 days after irradiation compared with the control lung but a reduction in pathological injury in the PC treatment group. Pretreatment or treatment with PC signifi cantly decreased levels of interleukin-6 and tumor necrosis factor-α in the lung, and also increased the relative mRNA expression of superoxide dismutase and glutathione. In vivo, PC signifi cantly reduced the expression of Toll-like receptor TLR2, myeloid diff erentiation primary response Myd88, and nuclear factor NF-κB, at both the transcriptional and translation level. Taken together, these data indicated that PC attenuated lung infl ammatory damage induced by radiation by blocking the TLR2- MyD88-NF-κB signaling pathway. Therefore, PC could be a protective agent against radiation-induced infl ammatory damage in normal tissues.展开更多
Two immunomodulatory polysaccharides(Vp2a-Ⅱ and Vp3) were isolated and identified from Apocynum venetum L. flowers, and their innate immune-stimulating functions and working mechanisms were evaluated in RAW264.7 cell...Two immunomodulatory polysaccharides(Vp2a-Ⅱ and Vp3) were isolated and identified from Apocynum venetum L. flowers, and their innate immune-stimulating functions and working mechanisms were evaluated in RAW264.7 cells. Both the level of released nitric oxide(NO) and expression of inducible nitric oxide synthase(iNOS) m RNA were significantly enhanced in the RAW264.7 macrophages cells treated by Vp2a-Ⅱ and Vp3. Vp2a-Ⅱ(100–800 μg/m L) and Vp3(400 μg/mL) could significantly increase the phagocytic activity of RAW264.7 cells and the secretion and m RNA expression of TNF-α and IL-6 in a concentrationdependent manner through affecting mitogen-activated protein kinase(MAPK) activity and nuclear factor κB(NF-κB) nuclear translocation. Vp2a-Ⅱ might activate the MAPK signaling pathways and induce the nuclear translocation of NF-κB p65, whilst Vp3 likely activated the NF-κB and MAPK signaling pathways without influencing the p38 MAPK route.展开更多
[Objectives]This study aimed to explore the protective effect of Oxalis coriniculata L.on rats with acute liver injury induced by carbon tetrachloride(CCl4)and related mechanism by regulating oxidative stress and the ...[Objectives]This study aimed to explore the protective effect of Oxalis coriniculata L.on rats with acute liver injury induced by carbon tetrachloride(CCl4)and related mechanism by regulating oxidative stress and the TLR-2 TLR-2/NF-κB signaling pathway.[Methods]A total of 48 female rats were randomly and evenly divided into normal group,model group,silymarin group(0.12 g/kg),and high(16 g/kg),middle(8 g/kg)and low-dose(4 g/kg)O.coriniculata L.groups.The rats in the groups were intragastrically administered with 5 mL/kg of corresponding drugs(equal-volume distilled water for normal group and control group),respectively.The administration was conducted twice a day,for 10 consecutive days.After 2 h of the last administration,the rats in all the groups except the normal group were intraperitoneally injected with 12%carbon tetrachloride(CCl4)olive oil solution(5 mL/kg),respectively to establish liver injury rat models.After 16 h,the eyeball blood of the rats was collected,and their liver tissues were collected for preparation of HE sections.The biochemical indicators detected included aspartate aminotransferase(AST),alanine aminotransferase(ALT),total superoxide dismutase(T-SOD)and glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)content in the serum.The contents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in the serum were detected by ELISA.The expression of Toll-like receptor-2(TLR-2)and nuclear factor-κB(NF-κB)in liver tissue was detected using Western blotting.The pathological changes of liver were observed under light microscope.[Results]Compared with the normal group,the ALT,AST activity and MDA,IL-1β,IL-6,TNF-αlevels in rat serum significantly increased(P<0.01),the GSH-Px,T-SOD activity in rat serum significantly decreased(P<0.01),and the expression of TLR-2 and NF-κB in liver tissue was up-regulated(P<0.01)in the model group.Compared with the model group,the ALT,AST activity and MDA,IL-1β,IL-6 and TNF-αlevels in rat serum reduced(P<0.05,P<0.01),the GSH-Px and T-SOD activity in rat serum increased(P<0.05,P<0.01),and the expression of TLR-2 and NF-κB in liver tissue was down-regulated(P<0.05,P<0.01)in the O.coriniculata L.administration groups.Pathological sections show that O.coriniculata L.had an improving effect on rats with acute liver injury induced by CCl4.[Conclusions]O.coriniculata L.has a good protective effect on rats with acute liver injury induced by CCl4.Its mechanism may be related to inhibition of oxidative stress,inhibition of inflammatory response and regulation of the TLR-2/NF-κB signaling pathway.展开更多
基金reviewed and approved by the Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Anhui Hospital Institutional Review Board(2022AH-022).
文摘BACKGROUND Ulcer colitis(UC)is a chronic,nonspecific,and noninfectious inflammatory bowel disease.Recently,Toll-like receptors(TLRs)have been found to be closely associated with clinical inflammatory diseases.Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging.Moreover,no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC.AIM To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC.METHODS This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021.The patients with UC were divided into two groups(control and experimental).The peripheral blood of the experimental and control groups were collected under aseptic conditions.The expression of TLR4 protein,NF-κB,IL-6,and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug.Linear co rrelation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17,and P<0.05 was considered statistically significant.RESULTS There were no significant differences in the patient characteristics between the control and experimental groups.The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group(P<0.05).The levels of IL-6 and IL-17 in the experimental group were significantly lower than those in the control group(P<0.05).The TLR4 protein expression in the experimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17(r=0.823,P<0.05).CONCLUSION Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates the inflammatory response of UC through the TLR4/NF-κB signaling pathway.
基金the National Key Research and Development Program of China,No.2017YFC0908104National Science and Technology Projects,No.2017ZX10203201,No.2017ZX10201201,and No.2017ZX10202202.
文摘BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.
文摘BACKGROUND Insomnia is a disease where individuals cannot maintain a steady and stable sleep state or fail to fall asleep.Western medicine mainly uses sedatives and hypnotic drugs to treat insomnia,and long-term use is prone to drug resistance and other adverse reactions.Acupuncture has a good curative effect and unique advantages in the treatment of insomnia.AIM To explore the molecular mechanism of acupuncture at Back-Shu point for the treatment of insomnia.METHODS We first prepared a rat model of insomnia,and then carried out acupuncture for 7 consecutive days.After treatment,the sleep time and general behavior of the rats were determined.The Morris water maze test was used to assess the learning ability and spatial memory ability of the rats.The expression levels of inflammatory cytokines in serum and the hippocampus were detected by ELISA.qRTPCR was used to detect the mRNA expression changes in the ERK/NF-κB signaling pathway.Western blot and immunohistochemistry were carried out to evaluate the protein expression levels of RAF-1,MEK-2,ERK1/2 and NF-κB.RESULTS Acupuncture can prolong sleep duration,and improve mental state,activity,diet volume,learning ability and spatial memory.In addition,acupuncture increased the release of 1L-1β,1L-6 and TNF-αin serum and the hippocampus and inhibited the mRNA and protein expression of the ERK/NF-κB signaling pathway.CONCLUSION These findings suggest that acupuncture at Back-Shu point can inhibit the ERK/NF-κB signaling pathway and treat insomnia by increasing the release of inflammatory cytokines in the hippocampus.
基金supported by the National Natural Science Foundation of China(31772876,31702374)Natural Science Foundation of Zhejiang Province(LZ18C190001,LQ17C190001)+1 种基金Zhejiang Xinmiao Talents Program(2017R405023)K.C.Wong Magna Fund in Ningbo University
文摘Nucleotide oligomerization domain 2(NOD2) is a major cytoplasmic sensor for pathogens and is critical for the clearance of cytosolic bacteria in mammals.However, studies regarding NOD2, especially the initiated signaling pathways, are scarce in teleost species. In this study, we identified a NOD2 molecule(PaNOD2) from ayu(Plecoglossus altivelis).Bioinformatics analysis showed the structure of NOD2 to be highly conserved during vertebrate evolution. Dual-luciferase reporter assays examined the activation of NF-κB signaling and Western blotting analysis detected the phosphorylation of three MAP kinases(p-38, Erk1/2, and JNK1/2).Functional study revealed that, like its mammalian counterparts, PaNOD2 was the receptor of the bacterial cell wall component muramyl dipeptide(MDP), and the leucine-rich repeat motif was responsible for the recognition and binding of Pa NOD2 with the ligand. Overexpression of PaNOD2 activated the NF-κB signaling pathway, leading to the upregulation of inflammatory cytokines, including TNF-α and IL-1β in HEK293 T cells and ayu head kidney-derived monocytes/macrophages(MO/MΦ).Particularly, we found that PaNOD2 activated the MAPK signaling pathways, as indicated by the increased phosphorylation of p-38, Erk1/2, and JNK1/2, which have not been characterized in any teleost species previously. Our findings proved that the NOD2 molecule and initiated pathways are conserved between mammals and ayu. Therefore, ayu could be used as an animal model to investigate NOD2-based diseases and therapeutic applications.
基金Supported by the National Natural Science Foundation of China,No.81470848the Breeding Foundation for Young Pioneers’Research of Sun Yat-sen University,No.14ykpy27
文摘AIM To study the role and the possible mechanism of β-arrestin 2 in lipopolysaccharide(LPS)-induced liver injury in vivo and in vitro.METHODS Male β-arrestin 2^(+/+) and β-arrestin 2^(-/-)C57 BL/6 J mice were used for in vivo experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro experiments. The animal model was established via intraperitoneal injection of LPS or physiological sodium chloride solution. Blood samples and liver tissues were collected to analyze liver injury and levels of pro-inflammatory cytokines. Cultured cell extracts were collected to analyze the production of pro-inflammatory cytokines and expression of key molecules involved in the TLR4/NF-κB signaling pathway.RESULTS Compared with wild-type mice, the β-arrestin 2 knockout mice displayed more severe LPS-induced liver injury and significantly higher levels of proinflammatory cytokines, including interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and IL-10. Compared with the control group, pro-inflammatory cytokines(including IL-1β, IL-6, TNF-α, and IL-10) produced by RAW264.7 cells in the β-arrestin 2 si RNA group were significantly increased at 6 h after treatment with LPS. Further, key molecules involved in the TLR4/NF-κB signaling pathway, including phosphoIκBα and phosho-p65, were upregulated.CONCLUSION β-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB signaling pathwaymediated inflammation.
基金Supported by the National Key Research and Development Program of China(No.2018YFD0901102)
文摘Phycocyanin (PC), a natural algal protein, is reported for having anti-oxidant and antiinfl ammatory properties. We investigated its ability to attenuate lung infl ammation in mice subjected to X-ray radiation. Male C57BL/6 mice were assigned to the control, total body irradiation, PC pretreatment, and PC treatment groups. Mice in the PC pretreatment group were gavaged with 200 mg/kg PC for 7 consecutive days before irradiation, and those in the PC treatment group were gavaged with 200 mg/kg PC for 7 consecutive days after irradiation. Lungs were collected on Day 7 after irradiation exposure. Hematoxylin and eosin staining of mouse lung sections showed considerable infl ammation damage 7 days after irradiation compared with the control lung but a reduction in pathological injury in the PC treatment group. Pretreatment or treatment with PC signifi cantly decreased levels of interleukin-6 and tumor necrosis factor-α in the lung, and also increased the relative mRNA expression of superoxide dismutase and glutathione. In vivo, PC signifi cantly reduced the expression of Toll-like receptor TLR2, myeloid diff erentiation primary response Myd88, and nuclear factor NF-κB, at both the transcriptional and translation level. Taken together, these data indicated that PC attenuated lung infl ammatory damage induced by radiation by blocking the TLR2- MyD88-NF-κB signaling pathway. Therefore, PC could be a protective agent against radiation-induced infl ammatory damage in normal tissues.
基金supported by Research on Precision Nutrition and Health Food,Department of Science and Technology of Henan Province(CXJD2021006)。
文摘Two immunomodulatory polysaccharides(Vp2a-Ⅱ and Vp3) were isolated and identified from Apocynum venetum L. flowers, and their innate immune-stimulating functions and working mechanisms were evaluated in RAW264.7 cells. Both the level of released nitric oxide(NO) and expression of inducible nitric oxide synthase(iNOS) m RNA were significantly enhanced in the RAW264.7 macrophages cells treated by Vp2a-Ⅱ and Vp3. Vp2a-Ⅱ(100–800 μg/m L) and Vp3(400 μg/mL) could significantly increase the phagocytic activity of RAW264.7 cells and the secretion and m RNA expression of TNF-α and IL-6 in a concentrationdependent manner through affecting mitogen-activated protein kinase(MAPK) activity and nuclear factor κB(NF-κB) nuclear translocation. Vp2a-Ⅱ might activate the MAPK signaling pathways and induce the nuclear translocation of NF-κB p65, whilst Vp3 likely activated the NF-κB and MAPK signaling pathways without influencing the p38 MAPK route.
基金Supported by Bagui Scholar Program of Guangxi(Gui Cai Jiao Han[2017]No.143).
文摘[Objectives]This study aimed to explore the protective effect of Oxalis coriniculata L.on rats with acute liver injury induced by carbon tetrachloride(CCl4)and related mechanism by regulating oxidative stress and the TLR-2 TLR-2/NF-κB signaling pathway.[Methods]A total of 48 female rats were randomly and evenly divided into normal group,model group,silymarin group(0.12 g/kg),and high(16 g/kg),middle(8 g/kg)and low-dose(4 g/kg)O.coriniculata L.groups.The rats in the groups were intragastrically administered with 5 mL/kg of corresponding drugs(equal-volume distilled water for normal group and control group),respectively.The administration was conducted twice a day,for 10 consecutive days.After 2 h of the last administration,the rats in all the groups except the normal group were intraperitoneally injected with 12%carbon tetrachloride(CCl4)olive oil solution(5 mL/kg),respectively to establish liver injury rat models.After 16 h,the eyeball blood of the rats was collected,and their liver tissues were collected for preparation of HE sections.The biochemical indicators detected included aspartate aminotransferase(AST),alanine aminotransferase(ALT),total superoxide dismutase(T-SOD)and glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)content in the serum.The contents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in the serum were detected by ELISA.The expression of Toll-like receptor-2(TLR-2)and nuclear factor-κB(NF-κB)in liver tissue was detected using Western blotting.The pathological changes of liver were observed under light microscope.[Results]Compared with the normal group,the ALT,AST activity and MDA,IL-1β,IL-6,TNF-αlevels in rat serum significantly increased(P<0.01),the GSH-Px,T-SOD activity in rat serum significantly decreased(P<0.01),and the expression of TLR-2 and NF-κB in liver tissue was up-regulated(P<0.01)in the model group.Compared with the model group,the ALT,AST activity and MDA,IL-1β,IL-6 and TNF-αlevels in rat serum reduced(P<0.05,P<0.01),the GSH-Px and T-SOD activity in rat serum increased(P<0.05,P<0.01),and the expression of TLR-2 and NF-κB in liver tissue was down-regulated(P<0.05,P<0.01)in the O.coriniculata L.administration groups.Pathological sections show that O.coriniculata L.had an improving effect on rats with acute liver injury induced by CCl4.[Conclusions]O.coriniculata L.has a good protective effect on rats with acute liver injury induced by CCl4.Its mechanism may be related to inhibition of oxidative stress,inhibition of inflammatory response and regulation of the TLR-2/NF-κB signaling pathway.