Background Vitamin A(VA)and its metabolite,retinoic acid(RA),are of great interest for their wide range of physiological functions.However,the regulatory contribution of VA to mitochondrial and muscle fiber compositio...Background Vitamin A(VA)and its metabolite,retinoic acid(RA),are of great interest for their wide range of physiological functions.However,the regulatory contribution of VA to mitochondrial and muscle fiber composition in sheep has not been reported.Method Lambs were injected with 0(control)or 7,500 IU VA palmitate into the biceps femoris muscle on d 2 after birth.At the age of 3 and 32 weeks,longissimus dorsi(LD)muscle samples were obtained to explore the effect of VA on myofiber type composition.In vitro,we investigated the effects of RA on myofiber type composition and intrinsic mechanisms.Results The proportion of type I myofiber was greatly increased in VA-treated sheep in LD muscle at harvest.VA greatly promoted mitochondrial biogenesis and function in LD muscle of sheep.Further exploration revealed that VA elevated PGC-1αmRNA and protein contents,and enhanced the level of p38 MAPK phosphorylation in LD muscle of sheep.In addition,the number of type I myofibers with RA treatment was significantly increased,and type IIx myofibers was significantly decreased in primary myoblasts.Consistent with in vivo experiment,RA significantly improved mitochondrial biogenesis and function in primary myoblasts of sheep.We then used si-PGC-1αto inhibit PGC-1αexpression and found that si-PGC-1αsignificantly abrogated RA-induced the formation of type I myofibers,mitochondrial biogenesis,MitoTracker staining intensity,UQCRC1 and ATP5A1 expression,SDH activity,and enhanced the level of type IIx muscle fibers.These data suggested that RA improved mitochondrial biogenesis and function by promoting PGC-1αexpression,and increased type I myofibers.In order to prove that the effect of RA on the level of PGC-1αis caused by p38 MAPK signaling,we inhibited the p38 MAPK signaling using a p38 MAPK inhibitor,which significantly reduced RA-induced PGC-1αand MyHC I levels.Conclusion VA promoted PGC-1αexpression through the p38 MAPK signaling pathway,improved mitochondrial biogenesis,and altered the composition of muscle fiber type.展开更多
AIM To investigate the effects of active vitamin D3 on autophagy and interleukin(IL)-1β expression in Salmonella-infected intestinal epithelial cells(IECs).METHODS Caco-2 cells, NOD2 siR NA-, Atg16L1 siR NA- or vitam...AIM To investigate the effects of active vitamin D3 on autophagy and interleukin(IL)-1β expression in Salmonella-infected intestinal epithelial cells(IECs).METHODS Caco-2 cells, NOD2 siR NA-, Atg16L1 siR NA- or vitamin D receptor(VDR) siR NA-transfected Caco-2 cells were pretreated with 1,25-dihydroxyvitamin D3(1,25D3), and then infected by wild-type S. typhimurium strain SL1344. The conversion of LC3-I to LC3-II was detected by Western blot analysis and LC3+ autophagosome was analyzed by immunofluorescence. Caco-2 cells or VDR si RNA-transfected cells were pretreated with 1,25D3, and then infected by SL1344. Membrane protein and total RNA were analyzed by Western blot and RT-PCR for VDR and Atg16L1 protein and m RNA expression, respectively. Atg16L1 si RNA-transfected Caco-2 cells were pretreated by 1,25D3 and then infected with SL1344. Total RNA was analyzed by RT-PCR for IL-1β mR NA expression.RESULTS The active form of vitamin D, 1,25D3, showed enhanced VDR-mediated Atg16L1 mR NA expression, membranous Atg16L1 protein expression leading to autophagic LC3 II proteins expression and LC3 punctae in Salmonella-infected Caco-2 cells which was counteracted by Atg16L1 and VDR si RNA, but Atg16L1 mediated suppression of IL-1β expression. Thus, active vitamin D may enhance autophagy but suppress inflammatory IL-1β expression in Salmonella-infected IECs.CONCLUSION Active vitamin D might enhance autophagic clearance of Salmonella infection, while modulation of inflammatory responses prevents the host from detrimental effects of overwhelming inflammation.展开更多
AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus ...AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype number IV-infected patients and 25 age- and gender-matched healthy subjects. Venous blood samples were obtained. Samples were allowed to clot and sera were separated by centrifugation and stored at -20?°C. A 25 hydroxy vitamin D assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was carried out using a commercial kit purchased from Incstar Corporation. IL-17 and -23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV genotype IV-infected subjects were included in the study. The mean ± SD were determined, a t-test for comparison of means of different parameters was used. Correlation analysis was done using Pearson’s correlation. Differences among different groups were determined using the Kruskal-Wallis test. RESULTS: The mean vitamin D level in HCV patients (group?I) was 15 ± 5.2 ng/mL while in control (group II) was 39.7 ± 10.8. For active vitamin D in group?I?as 16.6 ± 4.8 ng/mL while in group II was 41.9 ± 7.9. IL-23 was 154 ± 97.8 in group?I?and 6.7 ± 2.17 in group II. IL-17 was 70.7 ± 72.5 in cases and 1.2 ± 0.4 in control. MCP-1 was 1582 ± 794.4 in group?I?and 216.1 ± 5.38 in group II. Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control group. Vitamin D insufficiency existed in 28% of HCV-infected patients and 12% of the control group. One hundred percent of the cirrhotic patients and 40% of non cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1 were markedly increased in HCV-infected patients in comparison to controls.A significant negative correlation between vitamin D and IL-17 and -23 and MCP-1 was detected. HCV-infected males and females showed no differences with respect to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P = 0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1. We classified the patients according to sonar findings into four groups. Group?Ia with bright hepatomegaly and included 14 patients. Group?Ib with perihepatic fibrosis and included 11 patients. Group?Ic with liver cirrhosis and included 11 patients. Group?Id with hepatocellular carcinoma (HCC) and included 14 patients. Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and -23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001). CONCLUSION: Whether the deficiency of vitamin D is related to HCV-induced chronic liver disease or predisposing factor for higher viral load is a matter of debate.展开更多
Background: This study aims to determine the differences of angiogenic markers sFlt-1 (soluble FMS-like tyrosine kinase-1), Placental Growth Factor (PlGF) and antioxidant (vitamin E) levels in pre-eclampsia compared w...Background: This study aims to determine the differences of angiogenic markers sFlt-1 (soluble FMS-like tyrosine kinase-1), Placental Growth Factor (PlGF) and antioxidant (vitamin E) levels in pre-eclampsia compared with normotensive pregnancies. Methods: In a cross-sectional study performed on 40 normotensive pregnancies and 40 pre-eclampsia women, serum levels of sFlt-1, PlGF and vitamin E were measured with ELISA methods. Statistical analysis used Mann Whitney. Results: The serum levels from the group of normotensive pregnancy and pre-eclampsia women consecutively are as follows: sFlt-1 2251.32 ± 416.17 pg/mL and 2950.78 ± 221.34 pg/mL, having a very significant difference (p = 0.00);PlGF 391.67 ± 293.92 pg/mL and 150.15 ± 105.34 pg/mL, having a very significant difference;vitamin E 8537.21 ± 6299.74 unit and 700.61 ± 233.70 unit, having a very significant difference. Conclusion: There is a very significant difference between an-giogenic markers and antioxidant levels in pre-eclampsia and normotensive pregnancies.展开更多
Given that vascular calcification is inversely correlated with the clinical intake of menaquinone, a rat model of warfarin-induced calcification may be useful for testing menaquinone and vitamin K-1 potential effects ...Given that vascular calcification is inversely correlated with the clinical intake of menaquinone, a rat model of warfarin-induced calcification may be useful for testing menaquinone and vitamin K-1 potential effects on vascular function. The aim of the present study was to investigate effects of vitamin K-1 and menaquinone-7 treatments on blood pressure and vascular function in warfarin-induced vascular calcification model during five-week intervention in normotensive Wistar-Kyoto rats. Blood pressure was measured weekly, and at the end of the intervention in vitro vascular reactivity measurements were done. Alizarin Red S and von Kossa stainings were used to record possible calcification of aortic sections. Routine clinical chemistry was done from serum and urine samples. Vascular calcification was seen only in a few warfarin-treated animals in histological staining. Warfarin-treatment did not change significantly blood pressure of the rats. Warfarin-treatment increased slightly the endothelium-dependent relaxation of aorta after the L-type calcium channels were blocked. Also the vascular relaxation improved after NOS inhibition in the aorta of the healthy controls and menaquinone-7 treated animals, indicating that the relaxation in those groups was not totally dependent on NO. Clinical chemistry from serum showed some differences in urea, creatinine as well as lipid and glucose metabolism between the healthy controls and warfarin-treated rats.展开更多
基金funded by the National Natural Science Foundation of China(31972559)the Distinguished and Excellent Young Scholar Cultivation Project of Shanxi Agricultural University(2022JQPYGC01).
文摘Background Vitamin A(VA)and its metabolite,retinoic acid(RA),are of great interest for their wide range of physiological functions.However,the regulatory contribution of VA to mitochondrial and muscle fiber composition in sheep has not been reported.Method Lambs were injected with 0(control)or 7,500 IU VA palmitate into the biceps femoris muscle on d 2 after birth.At the age of 3 and 32 weeks,longissimus dorsi(LD)muscle samples were obtained to explore the effect of VA on myofiber type composition.In vitro,we investigated the effects of RA on myofiber type composition and intrinsic mechanisms.Results The proportion of type I myofiber was greatly increased in VA-treated sheep in LD muscle at harvest.VA greatly promoted mitochondrial biogenesis and function in LD muscle of sheep.Further exploration revealed that VA elevated PGC-1αmRNA and protein contents,and enhanced the level of p38 MAPK phosphorylation in LD muscle of sheep.In addition,the number of type I myofibers with RA treatment was significantly increased,and type IIx myofibers was significantly decreased in primary myoblasts.Consistent with in vivo experiment,RA significantly improved mitochondrial biogenesis and function in primary myoblasts of sheep.We then used si-PGC-1αto inhibit PGC-1αexpression and found that si-PGC-1αsignificantly abrogated RA-induced the formation of type I myofibers,mitochondrial biogenesis,MitoTracker staining intensity,UQCRC1 and ATP5A1 expression,SDH activity,and enhanced the level of type IIx muscle fibers.These data suggested that RA improved mitochondrial biogenesis and function by promoting PGC-1αexpression,and increased type I myofibers.In order to prove that the effect of RA on the level of PGC-1αis caused by p38 MAPK signaling,we inhibited the p38 MAPK signaling using a p38 MAPK inhibitor,which significantly reduced RA-induced PGC-1αand MyHC I levels.Conclusion VA promoted PGC-1αexpression through the p38 MAPK signaling pathway,improved mitochondrial biogenesis,and altered the composition of muscle fiber type.
基金Supported by the Ministry of Science and Technology[MOST 103-2314-B-182-032(in part)]the Chang Gung Memorial Hospital,No.CMRPG8B1431,No.CMRPG8B1481 and No.CMRPG880443the Stem Cell Research Core Laboratory (grant CLRPG8B0052) for technical support
文摘AIM To investigate the effects of active vitamin D3 on autophagy and interleukin(IL)-1β expression in Salmonella-infected intestinal epithelial cells(IECs).METHODS Caco-2 cells, NOD2 siR NA-, Atg16L1 siR NA- or vitamin D receptor(VDR) siR NA-transfected Caco-2 cells were pretreated with 1,25-dihydroxyvitamin D3(1,25D3), and then infected by wild-type S. typhimurium strain SL1344. The conversion of LC3-I to LC3-II was detected by Western blot analysis and LC3+ autophagosome was analyzed by immunofluorescence. Caco-2 cells or VDR si RNA-transfected cells were pretreated with 1,25D3, and then infected by SL1344. Membrane protein and total RNA were analyzed by Western blot and RT-PCR for VDR and Atg16L1 protein and m RNA expression, respectively. Atg16L1 si RNA-transfected Caco-2 cells were pretreated by 1,25D3 and then infected with SL1344. Total RNA was analyzed by RT-PCR for IL-1β mR NA expression.RESULTS The active form of vitamin D, 1,25D3, showed enhanced VDR-mediated Atg16L1 mR NA expression, membranous Atg16L1 protein expression leading to autophagic LC3 II proteins expression and LC3 punctae in Salmonella-infected Caco-2 cells which was counteracted by Atg16L1 and VDR si RNA, but Atg16L1 mediated suppression of IL-1β expression. Thus, active vitamin D may enhance autophagy but suppress inflammatory IL-1β expression in Salmonella-infected IECs.CONCLUSION Active vitamin D might enhance autophagic clearance of Salmonella infection, while modulation of inflammatory responses prevents the host from detrimental effects of overwhelming inflammation.
文摘AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype number IV-infected patients and 25 age- and gender-matched healthy subjects. Venous blood samples were obtained. Samples were allowed to clot and sera were separated by centrifugation and stored at -20?°C. A 25 hydroxy vitamin D assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was carried out using a commercial kit purchased from Incstar Corporation. IL-17 and -23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV genotype IV-infected subjects were included in the study. The mean ± SD were determined, a t-test for comparison of means of different parameters was used. Correlation analysis was done using Pearson’s correlation. Differences among different groups were determined using the Kruskal-Wallis test. RESULTS: The mean vitamin D level in HCV patients (group?I) was 15 ± 5.2 ng/mL while in control (group II) was 39.7 ± 10.8. For active vitamin D in group?I?as 16.6 ± 4.8 ng/mL while in group II was 41.9 ± 7.9. IL-23 was 154 ± 97.8 in group?I?and 6.7 ± 2.17 in group II. IL-17 was 70.7 ± 72.5 in cases and 1.2 ± 0.4 in control. MCP-1 was 1582 ± 794.4 in group?I?and 216.1 ± 5.38 in group II. Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control group. Vitamin D insufficiency existed in 28% of HCV-infected patients and 12% of the control group. One hundred percent of the cirrhotic patients and 40% of non cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1 were markedly increased in HCV-infected patients in comparison to controls.A significant negative correlation between vitamin D and IL-17 and -23 and MCP-1 was detected. HCV-infected males and females showed no differences with respect to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P = 0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1. We classified the patients according to sonar findings into four groups. Group?Ia with bright hepatomegaly and included 14 patients. Group?Ib with perihepatic fibrosis and included 11 patients. Group?Ic with liver cirrhosis and included 11 patients. Group?Id with hepatocellular carcinoma (HCC) and included 14 patients. Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and -23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001). CONCLUSION: Whether the deficiency of vitamin D is related to HCV-induced chronic liver disease or predisposing factor for higher viral load is a matter of debate.
文摘Background: This study aims to determine the differences of angiogenic markers sFlt-1 (soluble FMS-like tyrosine kinase-1), Placental Growth Factor (PlGF) and antioxidant (vitamin E) levels in pre-eclampsia compared with normotensive pregnancies. Methods: In a cross-sectional study performed on 40 normotensive pregnancies and 40 pre-eclampsia women, serum levels of sFlt-1, PlGF and vitamin E were measured with ELISA methods. Statistical analysis used Mann Whitney. Results: The serum levels from the group of normotensive pregnancy and pre-eclampsia women consecutively are as follows: sFlt-1 2251.32 ± 416.17 pg/mL and 2950.78 ± 221.34 pg/mL, having a very significant difference (p = 0.00);PlGF 391.67 ± 293.92 pg/mL and 150.15 ± 105.34 pg/mL, having a very significant difference;vitamin E 8537.21 ± 6299.74 unit and 700.61 ± 233.70 unit, having a very significant difference. Conclusion: There is a very significant difference between an-giogenic markers and antioxidant levels in pre-eclampsia and normotensive pregnancies.
基金DuPont Nutrition Health, Finska Läkaresalskapet Finnish Clinical Chemistry Foundation
文摘Given that vascular calcification is inversely correlated with the clinical intake of menaquinone, a rat model of warfarin-induced calcification may be useful for testing menaquinone and vitamin K-1 potential effects on vascular function. The aim of the present study was to investigate effects of vitamin K-1 and menaquinone-7 treatments on blood pressure and vascular function in warfarin-induced vascular calcification model during five-week intervention in normotensive Wistar-Kyoto rats. Blood pressure was measured weekly, and at the end of the intervention in vitro vascular reactivity measurements were done. Alizarin Red S and von Kossa stainings were used to record possible calcification of aortic sections. Routine clinical chemistry was done from serum and urine samples. Vascular calcification was seen only in a few warfarin-treated animals in histological staining. Warfarin-treatment did not change significantly blood pressure of the rats. Warfarin-treatment increased slightly the endothelium-dependent relaxation of aorta after the L-type calcium channels were blocked. Also the vascular relaxation improved after NOS inhibition in the aorta of the healthy controls and menaquinone-7 treated animals, indicating that the relaxation in those groups was not totally dependent on NO. Clinical chemistry from serum showed some differences in urea, creatinine as well as lipid and glucose metabolism between the healthy controls and warfarin-treated rats.
