[Objective] The study aimed at cloning and analyzing the insulin-like growth factor-1 （IGF-1） gene from liver of Hubei white swine. [Method] The total RNA was extracted by using Trizol from the liver of Hubei white ...[Objective] The study aimed at cloning and analyzing the insulin-like growth factor-1 （IGF-1） gene from liver of Hubei white swine. [Method] The total RNA was extracted by using Trizol from the liver of Hubei white swine and used as template to amplify IGF-1 gene cDNA by RT-PCR. The cDNA product was cloned into pCRII vector, screened with blue-white colonies, digested with double enzymes and sequenced. [Result] The sequencing result indicated that the IGF-1 gene consisted of 607 nucleotides, containing 5＇-untranslated region at nucleotides 1-145, a complete ORF at nucleotides 146-538 encoding 130 amino acids, and 3＇-untranslated region at nucleotides 539-607. It shared 100% homology with the porcine IGF-1 gene reported by Muller et al. [Conclusion] The successful cloning and sequencing of the Hubei white swine IGF-1 gene confirmed that IGF-I gene was highly conserved, which provided technical basis for the use of transgenic technology for breeding of Hubei white swine.展开更多
Objective. To explore the role of insulin-like growth factor 1 (IGF-1)gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.Methods. Diabetes was induced in Sprague Dawley rats by allox...Objective. To explore the role of insulin-like growth factor 1 (IGF-1)gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.Methods. Diabetes was induced in Sprague Dawley rats by alloxan. The parameters were measured as follows: IGF-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent assay (ELISA); electrophysiological parameters of nerves by evoked electromyogram; morphometric evaluation of sciatic nerves under light microscope and transmission electron microscope.Results. During early diabetic stage, IGF-1 mRNA [(0.430±0.031)vs. (0.370±0.016), P ＜0.01,(0.430 ± 0.031 ) vs. (0.280 ± 0.010) , P ＜0.001, respectively], IGF - 1 peptide contents [ (38.44 ± 3.60)ng/mgvs. (30.06±2.41) ng/mg, P ＜0.01, (38.44±3.6) ng/mgvs. (3.71 +2.70) ng/mg, P ＜0.001,respectively] in sciatic nerve tissue reduced in diabetic rats with hyperglycemia and varied with severity of diabetic state when compared with non-diabetic control rats, and further gradually down-regulated in the diabetic rats with duration of diabetes [IGF-1 mRNA (0. 320 ± 0. 021) ～ (0. 230 + 0. 060); IGF-1 peptide (28.80 ± 3.30) ～(19. 51 + 1.80)ng/mg]. Furthermore, they correlated with nerve functional (sensory nerve conduction velocity:r = 0. 741, P ＜0. 001; amplitude ofevokedpotential: r = 0. 716, P ＜0. 001, respectively)andstructuralabnormality (axonal areas r = 0. 81, P ＜ 0. 001 ) of sciatic nerve. No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.Conclusion. IGF-1 gene expression in tissues was down-regulated from early diabetic stage, and varied with the severity and duration of diabetic state. The decrement in IGF-1 level might contribute to the initiation and development of diabetic neuropathy via autocrine or paracrine pathway.展开更多
Objective To investigate the effects of combination adenovirusmediated HSVtk/GCV system and antisense IGF1 gene therapy for rat glioma and analyze the mechanism.Methods Using the recombinant adenovirus vector,GCV kill...Objective To investigate the effects of combination adenovirusmediated HSVtk/GCV system and antisense IGF1 gene therapy for rat glioma and analyze the mechanism.Methods Using the recombinant adenovirus vector,GCV killing effeciency after combined gene transfer of HSVtk and antisense IGF1 was observed in vitro.Rat glioma was treated with HSVtk/GCV and antisense IGF1 and the survival rate of rats was observed.Results C6 cells transfected with tk and antisense IGF1 gene were more sensitive to GCV than that transfected with tk gene alone.The survival of the combination gene therapy group was prolonged significantly and large amounts of CD+ 4,CD+ 8 lymphocytes were detected in the tumor tissues.Conclusion Antisense IGF1 gene may enhance the tumorkilling effects of HSVtk/GCV.展开更多
类胰岛素生长因子1 (IGF-1)是一种单链多肽,通过自分泌和旁分泌的方式调节骨代谢,促进骨形成。大量研究已经证实,IGF-1与骨密度呈显著正相关,对骨代谢的调节起着至关重要的作用。本文将结合近年来的研究进展,围绕概述IGF-1与骨质疏松(OP...类胰岛素生长因子1 (IGF-1)是一种单链多肽,通过自分泌和旁分泌的方式调节骨代谢,促进骨形成。大量研究已经证实,IGF-1与骨密度呈显著正相关,对骨代谢的调节起着至关重要的作用。本文将结合近年来的研究进展,围绕概述IGF-1与骨质疏松(OP)的相关性、IGF-1影响骨密度的机制等方面对IGF-1与OP的相关性研究进展作一综述。Insulin-like growth factor 1 (IGF-1) is a single chain polypeptide that regulates bone metabolism and promotes bone formation through autocrine and paracrine pathways. A large number of studies have confirmed that IGF-1 is significantly positively correlated with bone mineral density and plays a crucial role in the regulation of bone metabolism. In this paper, based on the recent research progress, the correlation between IGF-1 and osteoporosis (OP) and the mechanism of IGF-1 affecting bone mineral density will be reviewed.展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old femal...BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old female suffered from recurrent fever,visible ulcerations of the entire skin,and severe malnutrition.Genetic testing revealed a frameshift mu-tation in the coding region 4047 of the 35th intron region of COL7A1,and she was diagnosed as malnutrition-type epidermolysis bullosa.Drug therapy(immu-noglobulin,fresh frozen plasma),topical therapy(silver ion dressing),fever redu-ction,cough relief,and promotion of gastrointestinal peristalsis are mainly used for respiratory and gastrointestinal complications.The patient’s condition impro-ved after treatment.CONCLUSION Dystrophic epidermolysis bullosa caused by a new framework shift mutation in COL7A1 should be taken seriously.展开更多
目的探讨Ⅰ型神经纤维瘤病(NF1)基因变异合并细胞周期蛋白依赖性激酶13(CDK13)基因变异患儿的临床特征和遗传学特点。方法收集1例NF1合并CDK13相关疾病患儿的临床资料,对患儿及其父母进行全外显子组测序,采用Sanger测序验证可疑变异,并...目的探讨Ⅰ型神经纤维瘤病(NF1)基因变异合并细胞周期蛋白依赖性激酶13(CDK13)基因变异患儿的临床特征和遗传学特点。方法收集1例NF1合并CDK13相关疾病患儿的临床资料,对患儿及其父母进行全外显子组测序,采用Sanger测序验证可疑变异,并进行家系分析。以“CDK13基因和NF1基因”或“CDK13 gene and NF1 gene”为检索词分别检索中国知网、万方数据知识服务平台和PubMed数据库建库至2024年2月的相关文献,总结同患NF1和CDK13相关疾病患者的临床表型和遗传学特征。结果患儿,男,13岁,主要临床表现为皮肤牛奶咖啡斑,矮小身材,特殊面容(上眼睑外斜、宽眼距、内眦赘皮、鼻梁宽),智力障碍。患儿存在NF1基因杂合变异c.3610C>G(p.Arg1204Gly)和CDK13基因移码突变c.484dupG(p.Ala162Glyfs*108)(杂合)。Sanger测序验证结果显示,患儿母亲携带NF1基因杂合变异,未携带CDK13基因移码突变;父亲均未携带。未检索到关于同患NF1和CDK13相关疾病的患者的文献。共检索到CDK13相关疾病文献11篇,文献复习结果显示,97例患者主要临床表现为智力障碍或发育迟缓、特殊面容、先天性心脏缺陷,致病变异以错义突变为主。结论NF1基因变异可导致NF1。当发现有特殊面容的NF1患儿出现无法解释的现有表型或症状时,应注意2种遗传病同时存在的可能性。展开更多
基金Supported by Projects for Transgenic Research (2008ZX08006-002,2008ZX08006-003,2008ZX08010-003,2008ZX08011-004)Hubei Key Laboratory Project (2011ZD127)~~
文摘[Objective] The study aimed at cloning and analyzing the insulin-like growth factor-1 （IGF-1） gene from liver of Hubei white swine. [Method] The total RNA was extracted by using Trizol from the liver of Hubei white swine and used as template to amplify IGF-1 gene cDNA by RT-PCR. The cDNA product was cloned into pCRII vector, screened with blue-white colonies, digested with double enzymes and sequenced. [Result] The sequencing result indicated that the IGF-1 gene consisted of 607 nucleotides, containing 5＇-untranslated region at nucleotides 1-145, a complete ORF at nucleotides 146-538 encoding 130 amino acids, and 3＇-untranslated region at nucleotides 539-607. It shared 100% homology with the porcine IGF-1 gene reported by Muller et al. [Conclusion] The successful cloning and sequencing of the Hubei white swine IGF-1 gene confirmed that IGF-I gene was highly conserved, which provided technical basis for the use of transgenic technology for breeding of Hubei white swine.
基金This work was supported by the National Natural Sciences Foun-dation of China.This work was originally published in Chinese Journal of Internal Medicine (2001 40(2): 93-7)in Chinese.
文摘Objective. To explore the role of insulin-like growth factor 1 (IGF-1)gene expression abnormality in neurotrophic causes of diabetic peripheral neurophathy.Methods. Diabetes was induced in Sprague Dawley rats by alloxan. The parameters were measured as follows: IGF-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR); IGF-1 peptide by enzyme-linked immunosorbent assay (ELISA); electrophysiological parameters of nerves by evoked electromyogram; morphometric evaluation of sciatic nerves under light microscope and transmission electron microscope.Results. During early diabetic stage, IGF-1 mRNA [(0.430±0.031)vs. (0.370±0.016), P ＜0.01,(0.430 ± 0.031 ) vs. (0.280 ± 0.010) , P ＜0.001, respectively], IGF - 1 peptide contents [ (38.44 ± 3.60)ng/mgvs. (30.06±2.41) ng/mg, P ＜0.01, (38.44±3.6) ng/mgvs. (3.71 +2.70) ng/mg, P ＜0.001,respectively] in sciatic nerve tissue reduced in diabetic rats with hyperglycemia and varied with severity of diabetic state when compared with non-diabetic control rats, and further gradually down-regulated in the diabetic rats with duration of diabetes [IGF-1 mRNA (0. 320 ± 0. 021) ～ (0. 230 + 0. 060); IGF-1 peptide (28.80 ± 3.30) ～(19. 51 + 1.80)ng/mg]. Furthermore, they correlated with nerve functional (sensory nerve conduction velocity:r = 0. 741, P ＜0. 001; amplitude ofevokedpotential: r = 0. 716, P ＜0. 001, respectively)andstructuralabnormality (axonal areas r = 0. 81, P ＜ 0. 001 ) of sciatic nerve. No difference was found in the above parameters between diabetic rats with euglycemia and non-diabetic control group.Conclusion. IGF-1 gene expression in tissues was down-regulated from early diabetic stage, and varied with the severity and duration of diabetic state. The decrement in IGF-1 level might contribute to the initiation and development of diabetic neuropathy via autocrine or paracrine pathway.
文摘Objective To investigate the effects of combination adenovirusmediated HSVtk/GCV system and antisense IGF1 gene therapy for rat glioma and analyze the mechanism.Methods Using the recombinant adenovirus vector,GCV killing effeciency after combined gene transfer of HSVtk and antisense IGF1 was observed in vitro.Rat glioma was treated with HSVtk/GCV and antisense IGF1 and the survival rate of rats was observed.Results C6 cells transfected with tk and antisense IGF1 gene were more sensitive to GCV than that transfected with tk gene alone.The survival of the combination gene therapy group was prolonged significantly and large amounts of CD+ 4,CD+ 8 lymphocytes were detected in the tumor tissues.Conclusion Antisense IGF1 gene may enhance the tumorkilling effects of HSVtk/GCV.
文摘类胰岛素生长因子1 (IGF-1)是一种单链多肽,通过自分泌和旁分泌的方式调节骨代谢,促进骨形成。大量研究已经证实,IGF-1与骨密度呈显著正相关,对骨代谢的调节起着至关重要的作用。本文将结合近年来的研究进展,围绕概述IGF-1与骨质疏松(OP)的相关性、IGF-1影响骨密度的机制等方面对IGF-1与OP的相关性研究进展作一综述。Insulin-like growth factor 1 (IGF-1) is a single chain polypeptide that regulates bone metabolism and promotes bone formation through autocrine and paracrine pathways. A large number of studies have confirmed that IGF-1 is significantly positively correlated with bone mineral density and plays a crucial role in the regulation of bone metabolism. In this paper, based on the recent research progress, the correlation between IGF-1 and osteoporosis (OP) and the mechanism of IGF-1 affecting bone mineral density will be reviewed.
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
文摘BACKGROUND Dystrophic epidermolysis bullosa is characterized by fragile ulcerations of the skin caused by mutations in specific genes.However,genetic typing of this con-dition is rare.CASE SUMMARY An 11-year-old female suffered from recurrent fever,visible ulcerations of the entire skin,and severe malnutrition.Genetic testing revealed a frameshift mu-tation in the coding region 4047 of the 35th intron region of COL7A1,and she was diagnosed as malnutrition-type epidermolysis bullosa.Drug therapy(immu-noglobulin,fresh frozen plasma),topical therapy(silver ion dressing),fever redu-ction,cough relief,and promotion of gastrointestinal peristalsis are mainly used for respiratory and gastrointestinal complications.The patient’s condition impro-ved after treatment.CONCLUSION Dystrophic epidermolysis bullosa caused by a new framework shift mutation in COL7A1 should be taken seriously.
文摘目的探讨Ⅰ型神经纤维瘤病(NF1)基因变异合并细胞周期蛋白依赖性激酶13(CDK13)基因变异患儿的临床特征和遗传学特点。方法收集1例NF1合并CDK13相关疾病患儿的临床资料,对患儿及其父母进行全外显子组测序,采用Sanger测序验证可疑变异,并进行家系分析。以“CDK13基因和NF1基因”或“CDK13 gene and NF1 gene”为检索词分别检索中国知网、万方数据知识服务平台和PubMed数据库建库至2024年2月的相关文献,总结同患NF1和CDK13相关疾病患者的临床表型和遗传学特征。结果患儿,男,13岁,主要临床表现为皮肤牛奶咖啡斑,矮小身材,特殊面容(上眼睑外斜、宽眼距、内眦赘皮、鼻梁宽),智力障碍。患儿存在NF1基因杂合变异c.3610C>G(p.Arg1204Gly)和CDK13基因移码突变c.484dupG(p.Ala162Glyfs*108)(杂合)。Sanger测序验证结果显示,患儿母亲携带NF1基因杂合变异,未携带CDK13基因移码突变;父亲均未携带。未检索到关于同患NF1和CDK13相关疾病的患者的文献。共检索到CDK13相关疾病文献11篇,文献复习结果显示,97例患者主要临床表现为智力障碍或发育迟缓、特殊面容、先天性心脏缺陷,致病变异以错义突变为主。结论NF1基因变异可导致NF1。当发现有特殊面容的NF1患儿出现无法解释的现有表型或症状时,应注意2种遗传病同时存在的可能性。
