The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differen...The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro. Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo. Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence. Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro. Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain, namely the substantia nigra, compact part, dorsal tier, substantia nigra and reticular part, but was not detected in the forebrain comprising the caudate putamen and striatum. Unusual results were obtained in retrosplenial locations of adult rat brain. We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses. We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8, a secretory factor. Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells. In contrast, addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons. Our study may help delineate the important roles of fibroblast growth factor-8 in brain activities and neural stem/progenitor cell differentiation.展开更多
β-Amyloid(1-42)(Aβ_(42))can induce excessive activation of microglia,resulting in exacerbated neuroinflammation and neuronal damage.Milk fat globule-epidermal growth factor-8(MFG-E8)is known to regulate Aβ_(42)-ind...β-Amyloid(1-42)(Aβ_(42))can induce excessive activation of microglia,resulting in exacerbated neuroinflammation and neuronal damage.Milk fat globule-epidermal growth factor-8(MFG-E8)is known to regulate Aβ_(42)-induced neurotoxicity and inflammatory responses via multiple signaling pathways.However,insufficient secretion of endogenous MFG-E8 may lead to autoimmunity in the central nervous system and the accumulation of apoptotic cells.In this study,we systematically investigated the inhibitory effects and potential mechanisms of exogenously administered milk-derived MFG-E8(M-MFG-E8)on Aβ_(42)-induced inflammation in BV-2 microglia using various techniques,including cell morphology analysis,immunofluorescence staining,ELISA,q RT-PCR,and Western blot assays.The results demonstrated that Aβ_(42)significantly increased the expression levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in BV-2 microglia,whereas treatment with M-MFG-E8 effectively reversed these inflammatory responses.Furthermore,Aβ_(42)stimulation increased the secretion of pro-inflammatory cytokines(TNF-α,IL-1β)and the expression of the M1 marker cluster of differentiation 86(CD86),while suppressing the anti-inflammatory factors(arginase-1(Arg-1),interleukin-10(IL-10))and the M2 marker cluster of differentiation 206(CD206)in microglia.In contrast,M-MFG-E8 treatment promoted the polarization of microglia from the M1 to the M2 phenotype.Notably,M-MFG-E8 also inhibited the Aβ_(42)-induced upregulation of CD68,whereas M-MFG-E8 alone did not elicit this effect.Finally,our findings suggest that exogenous M-MFG-E8 may exert anti-inflammatory actions through the modulation of the NF-κB and PI3K/Akt pathways,providing new insights into neuronal cell repair and the development of functional foods.展开更多
目的分析不同胰岛素联合二甲双胍对妊娠期糖尿病血清血管内皮生长因子(VEGF)、脂联素(ADP)、血管生成素样蛋白8(ANGPTL8)表达水平的影响。方法将青岛大学附属青岛市海慈医院(青岛市中医医院)2020年5月至2023年5月门诊接收的122例妊娠期...目的分析不同胰岛素联合二甲双胍对妊娠期糖尿病血清血管内皮生长因子(VEGF)、脂联素(ADP)、血管生成素样蛋白8(ANGPTL8)表达水平的影响。方法将青岛大学附属青岛市海慈医院(青岛市中医医院)2020年5月至2023年5月门诊接收的122例妊娠期糖尿病孕妇依据随机数表法分为两组。试验组61例予以门冬胰岛素皮下注射联合二甲双胍治疗,对照组61例予以地特胰岛素皮下注射联合二甲双胍治疗。比较两组治疗前后的血清VEGF、ADP、ANGPTL8表达水平、炎症因子水平及血糖水平,随访了解两组的妊娠结局。结果治疗后,试验组的血清ADP水平较对照组升高,VEGF、ANGPTL8水平较对照组降低(P<0.05);治疗后,试验组的C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平均低于对照组(P<0.05);治疗后与对照组相比,试验组的空腹血糖(FPG)、餐后1 h血糖(1 h PPG)、餐后2 h血糖(2 h PPG)均明显改善(P<0.05);相比于对照组,试验组的不良妊娠结局明显降低(P<0.05)。结论胰岛素联合二甲双胍治疗妊娠期糖尿病均具有显著的效果,但相比于地特胰岛素,门冬胰岛素皮下注射联合二甲双胍对患者血清VEGF、ADP、ANGPTL8水平及炎症因子水平的改善效果更显著,对血糖的控制效果更佳,妊娠结局更好。展开更多
BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammat...BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammatory cyto- kines. The high level of inflammatory cytokines might ad- ditionally influence pulmonary cappillary fluid filtration. The objectives of this study were to measure the concentra- tions of tumor necrotic factor-alpha (TNF-α), interleukin- 6 (IL-6) and interleukin-8 (IL-8) during OLT and to in- vestigate the relationship between these cytokines and post- operative pulmonary complications. METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consis- ting of 8 patients with postoperative pulmonary complica- tions , and group B consisting of 14 patients without post- operative pulmonary complications. Enzyme-linked im- munoassay (ELISA) was used to determine serum TNF-α, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0 ), clamping and cross-clamping of the in- ferior cava and portal vein (T1, T2 ), 90 minutes and 3 hours after reperfusion (T3 , T4 ) and 24 hours after opera- tion (T5). RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B ( P <0. 05 ). The concentrations of TNF-α, IL-6 and IL-8 in the two groups increased rapidly at T2 , peaked at T3 , decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-α, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4(P<0.05). CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-α, IL-6 and IL-8 increased may be related to pulmonary injury after he- patic ischemic reperfusion.展开更多
Background: Tuberculosis (TB) is one of the world’s deadliest infectious diseases. Tumor necrosis factor-Alpha (TNF-α) and Interleukin 8 (IL-8) are involved in the pathogenesis of pulmonary TB (PTB). However, the co...Background: Tuberculosis (TB) is one of the world’s deadliest infectious diseases. Tumor necrosis factor-Alpha (TNF-α) and Interleukin 8 (IL-8) are involved in the pathogenesis of pulmonary TB (PTB). However, the contribution of polymorphisms of these cytokines to PTB susceptibility needed more investigation across geographic regions and ethnic groups. Purpose: The aim of this study was to investigate the association of the TNF-α-308 G/A and IL-8-251T/A polymorphisms with PTB risk in the Congolese population. Methods: This case-control study included 150 PTB patients and 160 control subjects. Blood samples were collected from all participants and were used for the TNF-α-308 G/A and IL-8-251T/A genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Odds ratios (OR) were calculated to estimate the potential polymorphism associations. A P level of Results: A significant difference was found between PTB patients and controls regarding the TNF-α-308AA genotype (P = 0.035) distribution. Moreover, this genotype was associated with risk to TB (OR = 7.19, 95% CI = 0.85 - 60.65, P = 0.035). The A allele was significantly more frequent in PTB patients than in controls, and was associated with risk to PTB (OR = 1.68, 95% CI = 1.05 - 2.68, P = 0.014). Regarding the IL-8-251T/A gene, TA and AA genotypes were significantly more frequent in PTB patients compared to controls, and were associated with increased risk to PTB (OR = 2.64, 95% CI = 0.97 - 7.18, P = 0.031 and OR = 3.0, 95% CI = 1.13 - 7.98, P = 0.014, respectively). However, the IL-8-251 A allele was not associated to PTB susceptibility (OR = 0.27, 95% CI = 0.15 - 0.44). Conclusion: TNF-α-308G/A and IL-8-251T/A polymorphisms may be associated to PTB susceptibility in the Congolese population, and the AA genotype of both cytokines could be a risk factor.展开更多
基金supported by the National Natural Science Foundation of China,No.81070614the Key Project of the Natural Science Foundation of Hubei Province of China,No. 2008CDA044the Natural Science Foundation of Hubei University of Medicine,No.2011QDZR-2
文摘The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro. Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo. Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence. Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro. Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain, namely the substantia nigra, compact part, dorsal tier, substantia nigra and reticular part, but was not detected in the forebrain comprising the caudate putamen and striatum. Unusual results were obtained in retrosplenial locations of adult rat brain. We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses. We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8, a secretory factor. Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells. In contrast, addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons. Our study may help delineate the important roles of fibroblast growth factor-8 in brain activities and neural stem/progenitor cell differentiation.
基金the financial support received from the Science and Technology Planning Project of Sichuan Province(Jiebangguashuai Project)(2023YFN0101)。
文摘β-Amyloid(1-42)(Aβ_(42))can induce excessive activation of microglia,resulting in exacerbated neuroinflammation and neuronal damage.Milk fat globule-epidermal growth factor-8(MFG-E8)is known to regulate Aβ_(42)-induced neurotoxicity and inflammatory responses via multiple signaling pathways.However,insufficient secretion of endogenous MFG-E8 may lead to autoimmunity in the central nervous system and the accumulation of apoptotic cells.In this study,we systematically investigated the inhibitory effects and potential mechanisms of exogenously administered milk-derived MFG-E8(M-MFG-E8)on Aβ_(42)-induced inflammation in BV-2 microglia using various techniques,including cell morphology analysis,immunofluorescence staining,ELISA,q RT-PCR,and Western blot assays.The results demonstrated that Aβ_(42)significantly increased the expression levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in BV-2 microglia,whereas treatment with M-MFG-E8 effectively reversed these inflammatory responses.Furthermore,Aβ_(42)stimulation increased the secretion of pro-inflammatory cytokines(TNF-α,IL-1β)and the expression of the M1 marker cluster of differentiation 86(CD86),while suppressing the anti-inflammatory factors(arginase-1(Arg-1),interleukin-10(IL-10))and the M2 marker cluster of differentiation 206(CD206)in microglia.In contrast,M-MFG-E8 treatment promoted the polarization of microglia from the M1 to the M2 phenotype.Notably,M-MFG-E8 also inhibited the Aβ_(42)-induced upregulation of CD68,whereas M-MFG-E8 alone did not elicit this effect.Finally,our findings suggest that exogenous M-MFG-E8 may exert anti-inflammatory actions through the modulation of the NF-κB and PI3K/Akt pathways,providing new insights into neuronal cell repair and the development of functional foods.
文摘目的分析不同胰岛素联合二甲双胍对妊娠期糖尿病血清血管内皮生长因子(VEGF)、脂联素(ADP)、血管生成素样蛋白8(ANGPTL8)表达水平的影响。方法将青岛大学附属青岛市海慈医院(青岛市中医医院)2020年5月至2023年5月门诊接收的122例妊娠期糖尿病孕妇依据随机数表法分为两组。试验组61例予以门冬胰岛素皮下注射联合二甲双胍治疗,对照组61例予以地特胰岛素皮下注射联合二甲双胍治疗。比较两组治疗前后的血清VEGF、ADP、ANGPTL8表达水平、炎症因子水平及血糖水平,随访了解两组的妊娠结局。结果治疗后,试验组的血清ADP水平较对照组升高,VEGF、ANGPTL8水平较对照组降低(P<0.05);治疗后,试验组的C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平均低于对照组(P<0.05);治疗后与对照组相比,试验组的空腹血糖(FPG)、餐后1 h血糖(1 h PPG)、餐后2 h血糖(2 h PPG)均明显改善(P<0.05);相比于对照组,试验组的不良妊娠结局明显降低(P<0.05)。结论胰岛素联合二甲双胍治疗妊娠期糖尿病均具有显著的效果,但相比于地特胰岛素,门冬胰岛素皮下注射联合二甲双胍对患者血清VEGF、ADP、ANGPTL8水平及炎症因子水平的改善效果更显著,对血糖的控制效果更佳,妊娠结局更好。
文摘BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammatory cyto- kines. The high level of inflammatory cytokines might ad- ditionally influence pulmonary cappillary fluid filtration. The objectives of this study were to measure the concentra- tions of tumor necrotic factor-alpha (TNF-α), interleukin- 6 (IL-6) and interleukin-8 (IL-8) during OLT and to in- vestigate the relationship between these cytokines and post- operative pulmonary complications. METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consis- ting of 8 patients with postoperative pulmonary complica- tions , and group B consisting of 14 patients without post- operative pulmonary complications. Enzyme-linked im- munoassay (ELISA) was used to determine serum TNF-α, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0 ), clamping and cross-clamping of the in- ferior cava and portal vein (T1, T2 ), 90 minutes and 3 hours after reperfusion (T3 , T4 ) and 24 hours after opera- tion (T5). RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B ( P <0. 05 ). The concentrations of TNF-α, IL-6 and IL-8 in the two groups increased rapidly at T2 , peaked at T3 , decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-α, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4(P<0.05). CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-α, IL-6 and IL-8 increased may be related to pulmonary injury after he- patic ischemic reperfusion.
文摘Background: Tuberculosis (TB) is one of the world’s deadliest infectious diseases. Tumor necrosis factor-Alpha (TNF-α) and Interleukin 8 (IL-8) are involved in the pathogenesis of pulmonary TB (PTB). However, the contribution of polymorphisms of these cytokines to PTB susceptibility needed more investigation across geographic regions and ethnic groups. Purpose: The aim of this study was to investigate the association of the TNF-α-308 G/A and IL-8-251T/A polymorphisms with PTB risk in the Congolese population. Methods: This case-control study included 150 PTB patients and 160 control subjects. Blood samples were collected from all participants and were used for the TNF-α-308 G/A and IL-8-251T/A genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Odds ratios (OR) were calculated to estimate the potential polymorphism associations. A P level of Results: A significant difference was found between PTB patients and controls regarding the TNF-α-308AA genotype (P = 0.035) distribution. Moreover, this genotype was associated with risk to TB (OR = 7.19, 95% CI = 0.85 - 60.65, P = 0.035). The A allele was significantly more frequent in PTB patients than in controls, and was associated with risk to PTB (OR = 1.68, 95% CI = 1.05 - 2.68, P = 0.014). Regarding the IL-8-251T/A gene, TA and AA genotypes were significantly more frequent in PTB patients compared to controls, and were associated with increased risk to PTB (OR = 2.64, 95% CI = 0.97 - 7.18, P = 0.031 and OR = 3.0, 95% CI = 1.13 - 7.98, P = 0.014, respectively). However, the IL-8-251 A allele was not associated to PTB susceptibility (OR = 0.27, 95% CI = 0.15 - 0.44). Conclusion: TNF-α-308G/A and IL-8-251T/A polymorphisms may be associated to PTB susceptibility in the Congolese population, and the AA genotype of both cytokines could be a risk factor.
