Vegetative growth of young apple trees trained in vertical axis were studied with ' Red Fuji', 'Jonagold', 'Orin' and ' Starkrimson' on M7, MM106, M26 interstocks in northern China. Abo...Vegetative growth of young apple trees trained in vertical axis were studied with ' Red Fuji', 'Jonagold', 'Orin' and ' Starkrimson' on M7, MM106, M26 interstocks in northern China. About 30 branches sprouted from the central leader of the trees during the 4 years after planting for ' Red Fuji' and 'Jonagold', and 26.7 and 20 branches respectively for 'Orin' and 'Starkrimson'. Moreover the 2-year-old section of the central leader had the strongest capacity to sprout new branches (and sometimes the 1-year-old section too), and sprouted more new shoots than the other section. The total new shoots including spurs on the 4-year-old trees reached 631 per tree for 'Jonagold', about 480 for 'Red Fuji' and 'Orin', and 312 for 'Starkrimson'. Percentage of spurs was about 61% for 'Red Fuji', 73% for 'Jonagold' and 'Orin', and 81% for 'Starkrimson'. Growth vigor of the central leader and limbs of the young apple trees could quickly decline: the growth of the central leader decreased markedly in the fourth year after planting, and branches from the central leader grew vigorously only in the current growth season or in the first two years after branching.展开更多
Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus m...Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.展开更多
The effects of stocking density on the growth and metabolism of Amur sturgeon were assessed. Amur sturgeon were grown for 70 days at three dif ferent stocking densities(low stocking density, LSD: 5.5 kg/m^3; medium st...The effects of stocking density on the growth and metabolism of Amur sturgeon were assessed. Amur sturgeon were grown for 70 days at three dif ferent stocking densities(low stocking density, LSD: 5.5 kg/m^3; medium stocking density, MSD: 8.0 kg/m^3; and high stocking density, HSD: 11.0 kg/m^3), and the biometric index, muscle composition, and serum biochemical parameters were evaluated. In addition, pituitary, liver, and muscle samples were collected for gene cloning and expression analyses. After 70 days of growth, the fish maintained at HSD had significantly lower fi nal body weight and specifi c growth rate, and a higher feed conversion ratio than those of the fish in the MSD and LSD groups. The HSD group had the lowest lipid and protein concentrations in serum and muscle. The serum cortisol concentration increased significantly in the HSD group, indicating that the stress-response system was activated in these fish. There was no change in the concentration of serum insulin-like growth factor 2(IGF-2), while the concentrations of serum growth hormone(GH) and insulin-like growth factor 1(IGF-1) decreased in the HSD group. The full-length cDNAs of G H and IGF-2 genes(995-bp and 1 207-bp long, respectively), were cloned and analyzed. In the HSD group, the expressions of GH in the pituitary and growth hormone receptor( GHR) and IGF-1 in the liver were down-regulated at the end of the 70-day experiment. In the HSD group, the transcript level of IGF-2 significantly decreased in the liver, but did not change in muscle. Overall, our results indicated that a HSD negatively af fects the growth performance and leads to changes in lipid and protein metabolism in Amur sturgeon. The down-regulated expression of genes related to the GH/IGF axis may be responsible for the poor growth performance of Amur sturgeon under crowding stress.展开更多
There is considerable concern that isoflavones,such as genistein in fish feed composed of soybean protein,affects somatic growth in fish.Our previous works demonstrated that 30 and 300 μg/g dietary genistein had no s...There is considerable concern that isoflavones,such as genistein in fish feed composed of soybean protein,affects somatic growth in fish.Our previous works demonstrated that 30 and 300 μg/g dietary genistein had no significant effect on growth performance in Nile tilapia(Oreochromis niloticus),but the higher level of genistein(3 000 μg/g) significantly depressed growth.This study was conducted to further examine the effects of dietary genistein on the endocrine disruption on growth hormone/insulin-like growth factor-I(GH/IGF-I) axis in Nile tilapia(O.niloticus).Juvenile fish were fed by hand twice daily to satiation with one of four isonitrogenous and isoenergetic diets,each containing either 0,30,300 or3 000 μg/g genistein.Following an 8-week feeding period,plasma GH and IGF-I levels were investigated by radioimmunoassay and gene expression levels of gh,ghrelin,gnrhs,ghr,npy,npyrs,pacap,ghrs,igf-I,igf-Ir,and igfbp3 were examined by real-time PCR.The results show that no significant change in plasma GH and IGF-I levels in fish fed with diets containing 30 μg/gand 300 μg/g genistein.mRNA expression of genes along the GH/IGF-I axis remained unaffected,except for igf-Ir,which was stimulated by the 300 μg/g genistein diet.While in fish fed the 3 000 μg/g genistein diet,the plasma GH and IGF-I levels decreased,and mRNA expression of gh,ghr2,npyr1,igf-I,and igf-Ir were also significantly depressed.In contrast,npy and igfbp3 mRNA expression were enhanced.This study provides convincing evidence for growth impediment by genistein by disturbing the GH/IGF-I axis in Nile tilapia O.niloticus.展开更多
In this article,an article published in the World Journal of Gastrointestinal Oncology,which focuses on whether the expression of programmed death-ligand 1(PD-L1)affects the effectiveness of chemotherapy regimens,incl...In this article,an article published in the World Journal of Gastrointestinal Oncology,which focuses on whether the expression of programmed death-ligand 1(PD-L1)affects the effectiveness of chemotherapy regimens,including bevacizumab,in treating patients with colorectal cancer(CRC).Through neutralization of vascular endothelial growth factor(VEGF),bevacizumab inhibits tumor angiogenesis,impairing neovascularization and thereby depriving the tumor of essential nutrients and oxygen.Conversely,PD-L1 binding to VEGF receptor 2 promotes angiogenesis,supporting tumor vasculature.The interplay between these pathways complicates the assessment of bevacizumab’s efficacy in cancer therapy,notably in CRC,where VEGF and PD-L1 significantly affect treatment response.This review examines metastatic CRC treatment strategies,focusing on bevacizumab’s mechanism of action and the role of PD-L1 in this therapeutic context.展开更多
Objective:Preeclampsia(PE)is a common complication during pregnancy.miR-100a is expressed in the placenta and regulates the survival and development of placental cells.Insulin growth factor-2(IGF-2)may serve as its do...Objective:Preeclampsia(PE)is a common complication during pregnancy.miR-100a is expressed in the placenta and regulates the survival and development of placental cells.Insulin growth factor-2(IGF-2)may serve as its downstream target.This study investigated the protective mechanisms of ginsenoside Rg3 against PE in rat model.Materials and Methods:LPS-induced rat PE models were suitable for intravenous administration of the highly expressed miR-100a ginsenoside Rg3 lentiviral vector.Human trophoblasts were cultured in vitro for JEG-3,and PE cell models were constructed.In vivo effects on tumor growth and apoptosis were observed.Ginsenoside Rg3 was treated with different concentrations of shRNA,miR-100a analogs,inhibitors,or IGF-2.Autophagy and the expression of autophagy-related proteins were examined.Trophoblast activity and migration were determined using Cell Counting Kit-8 and Transwell assays.Both drugs strongly inhibited trophoblasts under normal conditions with some synergy between them.Double-luciferase return assay confirmed the binding affinity of miR-100a for IGF-2.Results:In response to Rg3,autophagy and the expression of autophagy-related proteins LC3-I/II,Beclin1,and SQSTM1 were reduced in PE rat placental trophoblasts.Rg3 inhibited autophagy in JEG-3 cells and promoted JEG-3 survival and migration in a concentration-dependent manner.miR-100a upregulated PE expression.These results suggested that autophagy was a vital signaling system.Rg3 intervention inhibited miR-100a expression and miR-100a downregulated IGF-2 expression in placental tissues and promoted autophagy,thereby inhibiting JEG-3cell survival and migration.In rats,Rg3 inhibited PE development by regulating the activity of the miR-100a-IGF-2 signaling axis.Conclusion:Ginsenoside Rg3 positively regulates the miR-100a-IGF-2 axis and protects PE rats by inhibiting trophoblastic autophagy and promoting trophoblastic cell survival and migration.展开更多
BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few repor...BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.AIM To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week.Masson and Sirius red staining were used to examine changes in fiber levels.Inflammatory factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 treatment.RESULTS CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased significantly.Interestingly,C23 inhibited this process.On the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen I.In terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic injury.Although preclinical research has made breakthroughs,their suitability as clinical treatments is still unknown.The activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in the hepatocyte space and subse-quently forming liver fibrosis[1].Although therapeutic strategies have improved due to past few efforts there is no ideal treatment for hepatic fibrosis[2].Extracellular cold inducible RNA binding protein(CIRP)has been shown to play a role in various acute and chronic inflammatory diseases by promoting tissue inflammation and apoptosis and inducing fibrosis through its receptor Toll-like receptor 4(TLR4)[3].C23 is a recognized competitive inhibitor of CIRP that can competitively bind to CIRP receptors and reduce tissue damage in inflammatory diseases[4].C23 has been shown to significantly reduce serum tumor necrosis factor-alpha(TNF-α),IL(interleukin)-6 and IL-1βlevels.In addition,it can reduce tissue TLR4,TNF-α,IL-6 and IL-1βlevels and inhibit the colocalization of CIRP and TLR4,which plays a significant role in systemic inflammation[5].Re-search has shown that CIRP induces the inflammatory phenotype of lung fibroblasts in a TLR4-dependent manner[6].On the other hand,CIRP is associated with markers of fibrosis andα-SMA is significantly positively correlated with CIRP.Cirp-/-mice exhibit attenuated expression ofα-SMA and collagen(COL1A1 and COL3A1),decreased hydroxyproline content,decreased histological fibrosis scores,and improved pulmonary hypertension[7].C23 inhibited the release of TNF-α,the degradation of IκB and the nuclear translocation of NF-κB in CIRP-stimulated macrophages in a dose-dependent manner and C23 treatment significantly increased the serum levels of lactic dehydrogenase,alanine ami-notransferase,IL-6,TNF-αand IL-1βin septic CLP mice[8].Based on previous research we hypothesized that C23 might alleviate liver fibrosis by inhibiting acute and chronic inflammation.As a selective hepatotoxic chemical carbon tetrachloride(CCl4).can induce inflammation and activate HSCs,promoting liver fibrosis.This study reveals the role and mechanism of C23 in CCl4-induced liver fibrosis in mice.at room temperature for 30 minutes.The gray value of each group was calculated after chemiluminescence.展开更多
目的评估GH/IGF-1轴与幼龄脑瘫儿童粗大运动功能与认知发育的关系。方法纳入2012年1月至2014年12月新桥医院儿科住院的1-4岁脑瘫儿童71例作为脑瘫组,按体格发育落后与否划分为脑瘫伴发育迟滞组（cerebral palsy with retardation,CP-R...目的评估GH/IGF-1轴与幼龄脑瘫儿童粗大运动功能与认知发育的关系。方法纳入2012年1月至2014年12月新桥医院儿科住院的1-4岁脑瘫儿童71例作为脑瘫组,按体格发育落后与否划分为脑瘫伴发育迟滞组（cerebral palsy with retardation,CP-R）50例及脑瘫发育正常组（cerebral palsy with normal growth,CP-N）21例;按粗大运动功能分类系统（gross motor function classification system,GMFCS）划分为Ⅰ-Ⅱ级组20例（CP-GMFCSⅠ-Ⅱ）,Ⅲ-Ⅴ级组51例（CP-GMFCSⅢ-Ⅴ）;按Bayley评分划分智力发育指数（mental development index,MDI）≥70组15例（CP-MDI≥70）,MDI〈70组56例（CP-MDI〈70）。健康对照组为同期体检的健康儿童15例。观察上述儿童的血浆GH基础值及激发值、胰岛素样生长因子-1（insulin-like growth factorⅠ,IGF-1）、类胰岛素生长因子结合蛋白3（insulin-like growth factor-binding protein 3,IGFBP-3）水平作对照研究。结果 1CP-R组较CP-N组GH峰值显著降低,上述2组均较健康对照组GH峰值和IGF-1值显著降低（P〈0.05）。2CP-GMFCSⅠ-Ⅱ组和CP-GMFCSⅢ-Ⅴ组较健康对照组GH峰值和IGF-1值显著降低,CP-GMFCSⅢ-Ⅴ组较CPGMFCSⅠ-Ⅱ组GH峰值和IGF-1值显著降低（P〈0.05）。3CP-MDI〈70组和CP-MDI≥70组较健康对照组GH峰值显著降低（P〈0.05）;CP-MDI〈70组较CP-MDI≥70组和健康对照组IGF-1值显著降低（P〈0.05）。结论脑瘫伴体格发育迟缓、重度粗大运动功能障碍及明显MDI指数落后的儿童存在GH/IGF-1轴受损,提示GH、IGF-1低下可能是脑瘫儿童运动伴认知水平低下的原因之一。展开更多
文摘Vegetative growth of young apple trees trained in vertical axis were studied with ' Red Fuji', 'Jonagold', 'Orin' and ' Starkrimson' on M7, MM106, M26 interstocks in northern China. About 30 branches sprouted from the central leader of the trees during the 4 years after planting for ' Red Fuji' and 'Jonagold', and 26.7 and 20 branches respectively for 'Orin' and 'Starkrimson'. Moreover the 2-year-old section of the central leader had the strongest capacity to sprout new branches (and sometimes the 1-year-old section too), and sprouted more new shoots than the other section. The total new shoots including spurs on the 4-year-old trees reached 631 per tree for 'Jonagold', about 480 for 'Red Fuji' and 'Orin', and 312 for 'Starkrimson'. Percentage of spurs was about 61% for 'Red Fuji', 73% for 'Jonagold' and 'Orin', and 81% for 'Starkrimson'. Growth vigor of the central leader and limbs of the young apple trees could quickly decline: the growth of the central leader decreased markedly in the fourth year after planting, and branches from the central leader grew vigorously only in the current growth season or in the first two years after branching.
基金sponsored by the Natural Science Foundation of Hebei Province,H2012406018,H2013406096a grant from Hebei Province Department of Education,No.2006301
文摘Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.
基金Supported by the National Special Research Fund for Non-Profit Sector(Agriculture)(No.201003055)
文摘The effects of stocking density on the growth and metabolism of Amur sturgeon were assessed. Amur sturgeon were grown for 70 days at three dif ferent stocking densities(low stocking density, LSD: 5.5 kg/m^3; medium stocking density, MSD: 8.0 kg/m^3; and high stocking density, HSD: 11.0 kg/m^3), and the biometric index, muscle composition, and serum biochemical parameters were evaluated. In addition, pituitary, liver, and muscle samples were collected for gene cloning and expression analyses. After 70 days of growth, the fish maintained at HSD had significantly lower fi nal body weight and specifi c growth rate, and a higher feed conversion ratio than those of the fish in the MSD and LSD groups. The HSD group had the lowest lipid and protein concentrations in serum and muscle. The serum cortisol concentration increased significantly in the HSD group, indicating that the stress-response system was activated in these fish. There was no change in the concentration of serum insulin-like growth factor 2(IGF-2), while the concentrations of serum growth hormone(GH) and insulin-like growth factor 1(IGF-1) decreased in the HSD group. The full-length cDNAs of G H and IGF-2 genes(995-bp and 1 207-bp long, respectively), were cloned and analyzed. In the HSD group, the expressions of GH in the pituitary and growth hormone receptor( GHR) and IGF-1 in the liver were down-regulated at the end of the 70-day experiment. In the HSD group, the transcript level of IGF-2 significantly decreased in the liver, but did not change in muscle. Overall, our results indicated that a HSD negatively af fects the growth performance and leads to changes in lipid and protein metabolism in Amur sturgeon. The down-regulated expression of genes related to the GH/IGF axis may be responsible for the poor growth performance of Amur sturgeon under crowding stress.
基金Supported by the National Natural Science Foundation of China(No.31170322)
文摘There is considerable concern that isoflavones,such as genistein in fish feed composed of soybean protein,affects somatic growth in fish.Our previous works demonstrated that 30 and 300 μg/g dietary genistein had no significant effect on growth performance in Nile tilapia(Oreochromis niloticus),but the higher level of genistein(3 000 μg/g) significantly depressed growth.This study was conducted to further examine the effects of dietary genistein on the endocrine disruption on growth hormone/insulin-like growth factor-I(GH/IGF-I) axis in Nile tilapia(O.niloticus).Juvenile fish were fed by hand twice daily to satiation with one of four isonitrogenous and isoenergetic diets,each containing either 0,30,300 or3 000 μg/g genistein.Following an 8-week feeding period,plasma GH and IGF-I levels were investigated by radioimmunoassay and gene expression levels of gh,ghrelin,gnrhs,ghr,npy,npyrs,pacap,ghrs,igf-I,igf-Ir,and igfbp3 were examined by real-time PCR.The results show that no significant change in plasma GH and IGF-I levels in fish fed with diets containing 30 μg/gand 300 μg/g genistein.mRNA expression of genes along the GH/IGF-I axis remained unaffected,except for igf-Ir,which was stimulated by the 300 μg/g genistein diet.While in fish fed the 3 000 μg/g genistein diet,the plasma GH and IGF-I levels decreased,and mRNA expression of gh,ghr2,npyr1,igf-I,and igf-Ir were also significantly depressed.In contrast,npy and igfbp3 mRNA expression were enhanced.This study provides convincing evidence for growth impediment by genistein by disturbing the GH/IGF-I axis in Nile tilapia O.niloticus.
基金The Natural Science Foundation of Zhejiang Province,No.LQ23H050005The Scientific Research Project of Zhejiang Provincial Education Department,No.Y202250731 and No.Y202353130+1 种基金China Students’Innovation and Entrepreneurship Training Program,No.202310338044China Postdoctoral Science Foundation,No.2022M721720.
文摘In this article,an article published in the World Journal of Gastrointestinal Oncology,which focuses on whether the expression of programmed death-ligand 1(PD-L1)affects the effectiveness of chemotherapy regimens,including bevacizumab,in treating patients with colorectal cancer(CRC).Through neutralization of vascular endothelial growth factor(VEGF),bevacizumab inhibits tumor angiogenesis,impairing neovascularization and thereby depriving the tumor of essential nutrients and oxygen.Conversely,PD-L1 binding to VEGF receptor 2 promotes angiogenesis,supporting tumor vasculature.The interplay between these pathways complicates the assessment of bevacizumab’s efficacy in cancer therapy,notably in CRC,where VEGF and PD-L1 significantly affect treatment response.This review examines metastatic CRC treatment strategies,focusing on bevacizumab’s mechanism of action and the role of PD-L1 in this therapeutic context.
文摘Objective:Preeclampsia(PE)is a common complication during pregnancy.miR-100a is expressed in the placenta and regulates the survival and development of placental cells.Insulin growth factor-2(IGF-2)may serve as its downstream target.This study investigated the protective mechanisms of ginsenoside Rg3 against PE in rat model.Materials and Methods:LPS-induced rat PE models were suitable for intravenous administration of the highly expressed miR-100a ginsenoside Rg3 lentiviral vector.Human trophoblasts were cultured in vitro for JEG-3,and PE cell models were constructed.In vivo effects on tumor growth and apoptosis were observed.Ginsenoside Rg3 was treated with different concentrations of shRNA,miR-100a analogs,inhibitors,or IGF-2.Autophagy and the expression of autophagy-related proteins were examined.Trophoblast activity and migration were determined using Cell Counting Kit-8 and Transwell assays.Both drugs strongly inhibited trophoblasts under normal conditions with some synergy between them.Double-luciferase return assay confirmed the binding affinity of miR-100a for IGF-2.Results:In response to Rg3,autophagy and the expression of autophagy-related proteins LC3-I/II,Beclin1,and SQSTM1 were reduced in PE rat placental trophoblasts.Rg3 inhibited autophagy in JEG-3 cells and promoted JEG-3 survival and migration in a concentration-dependent manner.miR-100a upregulated PE expression.These results suggested that autophagy was a vital signaling system.Rg3 intervention inhibited miR-100a expression and miR-100a downregulated IGF-2 expression in placental tissues and promoted autophagy,thereby inhibiting JEG-3cell survival and migration.In rats,Rg3 inhibited PE development by regulating the activity of the miR-100a-IGF-2 signaling axis.Conclusion:Ginsenoside Rg3 positively regulates the miR-100a-IGF-2 axis and protects PE rats by inhibiting trophoblastic autophagy and promoting trophoblastic cell survival and migration.
基金Supported by The Panzhihua Science and Technology Planning Project of China,No.2023ZD-S-57.
文摘BACKGROUND C23,an oligo-peptide derived from cold-inducible RNA-binding protein(CIRP),has been reported to inhibit tissue inflammation,apoptosis and fibrosis by binding to the CIRP receptor;however,there are few reports on its role in liver fibrosis and the underlying mechanism is unknown.AIM To explore whether C23 plays a significant role in carbon tetrachloride(CCl4)-induced liver fibrosis.METHODS CCl4 was injected for 6 weeks to induce liver fibrosis and C23 was used beginning in the second week.Masson and Sirius red staining were used to examine changes in fiber levels.Inflammatory factors in the liver were detected and changes inα-smooth muscle actin(α-SMA)and collagen I expression were detected via immu-nohistochemical staining to evaluate the activation of hematopoietic stellate cells(HSCs).Western blotting was used to detect the activation status of the trans-forming growth factor-beta(TGF-β)/Smad3 axis after C23 treatment.RESULTS CCl4 successfully induced liver fibrosis in mice,while tumor necrosis factor-alpha(TNF-α),IL(interleukin)-1β,and IL-6 levels increased significantly and the IL-10 level decreased significantly.Interestingly,C23 inhibited this process.On the other hand,C23 significantly inhibited the activation of HSCs induced by CCl4,which inhibited the expression ofα-SMA and the synthesis of collagen I.In terms of mechanism,C23 can block Smad3 phosphorylation significantly and inhibits INTRODUCTION At present there is no specific and effective drug for treating liver fibrosis caused by acute or chronic injury.Although preclinical research has made breakthroughs,their suitability as clinical treatments is still unknown.The activation of hepatic stellate cells(HSCs)caused by chronic inflammation is a key process in the development of liver fibrosis and activated HSCs expressα-smooth muscle actin(α-SMA)and transdifferentiate into myofibroblasts with proliferation,migration and secretion abilities,synthesizing the extracellular matrix to deposit in the hepatocyte space and subse-quently forming liver fibrosis[1].Although therapeutic strategies have improved due to past few efforts there is no ideal treatment for hepatic fibrosis[2].Extracellular cold inducible RNA binding protein(CIRP)has been shown to play a role in various acute and chronic inflammatory diseases by promoting tissue inflammation and apoptosis and inducing fibrosis through its receptor Toll-like receptor 4(TLR4)[3].C23 is a recognized competitive inhibitor of CIRP that can competitively bind to CIRP receptors and reduce tissue damage in inflammatory diseases[4].C23 has been shown to significantly reduce serum tumor necrosis factor-alpha(TNF-α),IL(interleukin)-6 and IL-1βlevels.In addition,it can reduce tissue TLR4,TNF-α,IL-6 and IL-1βlevels and inhibit the colocalization of CIRP and TLR4,which plays a significant role in systemic inflammation[5].Re-search has shown that CIRP induces the inflammatory phenotype of lung fibroblasts in a TLR4-dependent manner[6].On the other hand,CIRP is associated with markers of fibrosis andα-SMA is significantly positively correlated with CIRP.Cirp-/-mice exhibit attenuated expression ofα-SMA and collagen(COL1A1 and COL3A1),decreased hydroxyproline content,decreased histological fibrosis scores,and improved pulmonary hypertension[7].C23 inhibited the release of TNF-α,the degradation of IκB and the nuclear translocation of NF-κB in CIRP-stimulated macrophages in a dose-dependent manner and C23 treatment significantly increased the serum levels of lactic dehydrogenase,alanine ami-notransferase,IL-6,TNF-αand IL-1βin septic CLP mice[8].Based on previous research we hypothesized that C23 might alleviate liver fibrosis by inhibiting acute and chronic inflammation.As a selective hepatotoxic chemical carbon tetrachloride(CCl4).can induce inflammation and activate HSCs,promoting liver fibrosis.This study reveals the role and mechanism of C23 in CCl4-induced liver fibrosis in mice.at room temperature for 30 minutes.The gray value of each group was calculated after chemiluminescence.
文摘目的评估GH/IGF-1轴与幼龄脑瘫儿童粗大运动功能与认知发育的关系。方法纳入2012年1月至2014年12月新桥医院儿科住院的1-4岁脑瘫儿童71例作为脑瘫组,按体格发育落后与否划分为脑瘫伴发育迟滞组（cerebral palsy with retardation,CP-R）50例及脑瘫发育正常组（cerebral palsy with normal growth,CP-N）21例;按粗大运动功能分类系统（gross motor function classification system,GMFCS）划分为Ⅰ-Ⅱ级组20例（CP-GMFCSⅠ-Ⅱ）,Ⅲ-Ⅴ级组51例（CP-GMFCSⅢ-Ⅴ）;按Bayley评分划分智力发育指数（mental development index,MDI）≥70组15例（CP-MDI≥70）,MDI〈70组56例（CP-MDI〈70）。健康对照组为同期体检的健康儿童15例。观察上述儿童的血浆GH基础值及激发值、胰岛素样生长因子-1（insulin-like growth factorⅠ,IGF-1）、类胰岛素生长因子结合蛋白3（insulin-like growth factor-binding protein 3,IGFBP-3）水平作对照研究。结果 1CP-R组较CP-N组GH峰值显著降低,上述2组均较健康对照组GH峰值和IGF-1值显著降低（P〈0.05）。2CP-GMFCSⅠ-Ⅱ组和CP-GMFCSⅢ-Ⅴ组较健康对照组GH峰值和IGF-1值显著降低,CP-GMFCSⅢ-Ⅴ组较CPGMFCSⅠ-Ⅱ组GH峰值和IGF-1值显著降低（P〈0.05）。3CP-MDI〈70组和CP-MDI≥70组较健康对照组GH峰值显著降低（P〈0.05）;CP-MDI〈70组较CP-MDI≥70组和健康对照组IGF-1值显著降低（P〈0.05）。结论脑瘫伴体格发育迟缓、重度粗大运动功能障碍及明显MDI指数落后的儿童存在GH/IGF-1轴受损,提示GH、IGF-1低下可能是脑瘫儿童运动伴认知水平低下的原因之一。
