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
Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investig...Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.展开更多
OBJECTIVE Neuroinflammation plays a critical role in neurodegenerative disorders,although the inflammation may not the initiating factor.Parkinson disease(PD)is characterized pathologically by the accumulation of alph...OBJECTIVE Neuroinflammation plays a critical role in neurodegenerative disorders,although the inflammation may not the initiating factor.Parkinson disease(PD)is characterized pathologically by the accumulation of alpha synuclein(α-syn)and the loss of the dopamine(DA)neurons in the substantia nigra(SN),which has been reported to be induced by the stereotaxic injection of lipopolysaccharide(LPS)to the SN region in rodents.This study is to investigate the therapeutic benefit of the inhibition of miR-873 in PD.METHODS Rats received the right-unilaterally injection with concentrated LV-sponge or LV-EGFP 3 d before LPS treatment,7 or 14 d after LPS treatment.The animals were tested for rotational behavior with the dopaminergic agonist apomorphine dissolved in sterile saline at 21 d after LPS injection.The regulation of miR-873 on the genes related with cholesterol transport and inflammation was assayed in SH-SY5Y cells and U251 cells.RESULTS TLR4-My D88 signaling pathway was involved the regulation of miR-873 by LPS.The luciferase assay showed that HMGCR,ABCA1 and A20 were down-stream genes of miR-873.The transfection of miR-873 decreased the cholesterol levels in cell membrane,but increased in lysosome in SH-SY5Y cells.Compared with the control SH-SY5Y cells,cholesterol levels were higher in lysosome withα-synuclein overexpression or LPS treatment.The transfection of miR-873 increased theα-syn levels in lysosome in cel s withα-synuclein overexpression.The loss of dopaminergic neuorns induced by LPS was significantly respectively decreased by 22.8%,35.6%and 57% after the inhibition of miR-873 at 3 d before LPS treatment,7 or14 d after LPS treatment.Compared with LPS-treated group,the number of the rotation of rats was decreased by 60.4%,33.5%and 13.2%after the inhibition of miR-873 at 3 d before LPS treatment,7or 14 d after LPS treatment.The inhibition of miR-873 significantly decreased accumulation ofα-syn.The m RNA levels of HMGCR,ABCA1 and A20 in SN were decreased by LPS treatment,which was attenuated by the injection of LV-sponge.CONCLUSION The selective regulation of miR-873 can protect the dopaminergic neurons from the LPS-induced damage.The inhibition of miR-873 can attenuate the relocation of cholesterol in lysosome and the accumulation ofα-syn in neurons induced by LPS via the regulation of HMGCR,ABCA1 and A20.展开更多
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 fund from the National Natural Science Foundation of China (32172322)Shandong Provincial Natural Science Foundation (ZR2023QC291)Shandong Traditional Chinese Medicine Technology Project (Q-2023130)。
文摘Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.
基金supported by National Natural Science Foundation of China(1673503)
文摘OBJECTIVE Neuroinflammation plays a critical role in neurodegenerative disorders,although the inflammation may not the initiating factor.Parkinson disease(PD)is characterized pathologically by the accumulation of alpha synuclein(α-syn)and the loss of the dopamine(DA)neurons in the substantia nigra(SN),which has been reported to be induced by the stereotaxic injection of lipopolysaccharide(LPS)to the SN region in rodents.This study is to investigate the therapeutic benefit of the inhibition of miR-873 in PD.METHODS Rats received the right-unilaterally injection with concentrated LV-sponge or LV-EGFP 3 d before LPS treatment,7 or 14 d after LPS treatment.The animals were tested for rotational behavior with the dopaminergic agonist apomorphine dissolved in sterile saline at 21 d after LPS injection.The regulation of miR-873 on the genes related with cholesterol transport and inflammation was assayed in SH-SY5Y cells and U251 cells.RESULTS TLR4-My D88 signaling pathway was involved the regulation of miR-873 by LPS.The luciferase assay showed that HMGCR,ABCA1 and A20 were down-stream genes of miR-873.The transfection of miR-873 decreased the cholesterol levels in cell membrane,but increased in lysosome in SH-SY5Y cells.Compared with the control SH-SY5Y cells,cholesterol levels were higher in lysosome withα-synuclein overexpression or LPS treatment.The transfection of miR-873 increased theα-syn levels in lysosome in cel s withα-synuclein overexpression.The loss of dopaminergic neuorns induced by LPS was significantly respectively decreased by 22.8%,35.6%and 57% after the inhibition of miR-873 at 3 d before LPS treatment,7 or14 d after LPS treatment.Compared with LPS-treated group,the number of the rotation of rats was decreased by 60.4%,33.5%and 13.2%after the inhibition of miR-873 at 3 d before LPS treatment,7or 14 d after LPS treatment.The inhibition of miR-873 significantly decreased accumulation ofα-syn.The m RNA levels of HMGCR,ABCA1 and A20 in SN were decreased by LPS treatment,which was attenuated by the injection of LV-sponge.CONCLUSION The selective regulation of miR-873 can protect the dopaminergic neurons from the LPS-induced damage.The inhibition of miR-873 can attenuate the relocation of cholesterol in lysosome and the accumulation ofα-syn in neurons induced by LPS via the regulation of HMGCR,ABCA1 and A20.
