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
Objective: This research was to study the correlation between the rs1800469, rs1800470, rs2241712, rs224171 and rs4803455 of TGFβ1 gene and asthma in Baise, Guangxi children. This research also studied the relationsh...Objective: This research was to study the correlation between the rs1800469, rs1800470, rs2241712, rs224171 and rs4803455 of TGFβ1 gene and asthma in Baise, Guangxi children. This research also studied the relationship between serum concentration of TGFβ1 and childhood asthma. Method: From June 2022 to December 2023, 121 children had physical examination in affiliated Hospital of Youjiang Medical University for Nationalities were selected as control group and 118 children suffered from asthma in affiliated Hospital of Youjiang Medical University for Nationalities during the same period were selected as asthma group. Result: There was no correlation between rs1800469, rs1800470, rs2241712, rs2241715, rs4803455 and asthma in Baise, Guangxi children. Linkage disequilibrium analysis showed that there were strong linkage disequilibrium among rs1800469, rs1800470, rs2241712, rs2241715 and rs4803455. Their haplotypes had no significant correlation with childhood asthma. The serum concentration of TGFβ1 in asthma group was lower than that in control group (p β1 had no significant relationship with the genotypes of rs1800469, rs1800470, rs2241712, rs2241715 and rs4803455.展开更多
The expression of TGFβ 1 protein in normal esophageal mucosa (EM), esophageal epithelia dysplasia (EED) and squamous cell carcinoma of esophagus (SCCE) were examined immunohistochemically. In order to discover how ...The expression of TGFβ 1 protein in normal esophageal mucosa (EM), esophageal epithelia dysplasia (EED) and squamous cell carcinoma of esophagus (SCCE) were examined immunohistochemically. In order to discover how TGFβ 1 would express in EM, EED and SCCE, wether the rate of TGFβ 1 positive expression might show any correlation with established histologic grade and the presence of lymph node metastasis in SCCE. The results indicate that there isn't expression in normal cells of EM; The rates of TGFβ 1 positive expression are 62 8% in cells of EED and 77 1% in cells of SCCE, which has statisticaly significant difference compared with EM group. The positive rate of TGFβ 1 increases successively in the order to EM→well EED→moderately EED→poorly EED→SCCE. It suggests that early examination of expression of TGFβ 1 could help predict the occurrence of esophageal cancer. We can't find any correlation between the positive rate of TGFβ 1 and established histological grade as well as the presence of lymph node metastasis in SCCE.展开更多
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Objective: This research was to study the correlation between the rs1800469, rs1800470, rs2241712, rs224171 and rs4803455 of TGFβ1 gene and asthma in Baise, Guangxi children. This research also studied the relationship between serum concentration of TGFβ1 and childhood asthma. Method: From June 2022 to December 2023, 121 children had physical examination in affiliated Hospital of Youjiang Medical University for Nationalities were selected as control group and 118 children suffered from asthma in affiliated Hospital of Youjiang Medical University for Nationalities during the same period were selected as asthma group. Result: There was no correlation between rs1800469, rs1800470, rs2241712, rs2241715, rs4803455 and asthma in Baise, Guangxi children. Linkage disequilibrium analysis showed that there were strong linkage disequilibrium among rs1800469, rs1800470, rs2241712, rs2241715 and rs4803455. Their haplotypes had no significant correlation with childhood asthma. The serum concentration of TGFβ1 in asthma group was lower than that in control group (p β1 had no significant relationship with the genotypes of rs1800469, rs1800470, rs2241712, rs2241715 and rs4803455.
文摘The expression of TGFβ 1 protein in normal esophageal mucosa (EM), esophageal epithelia dysplasia (EED) and squamous cell carcinoma of esophagus (SCCE) were examined immunohistochemically. In order to discover how TGFβ 1 would express in EM, EED and SCCE, wether the rate of TGFβ 1 positive expression might show any correlation with established histologic grade and the presence of lymph node metastasis in SCCE. The results indicate that there isn't expression in normal cells of EM; The rates of TGFβ 1 positive expression are 62 8% in cells of EED and 77 1% in cells of SCCE, which has statisticaly significant difference compared with EM group. The positive rate of TGFβ 1 increases successively in the order to EM→well EED→moderately EED→poorly EED→SCCE. It suggests that early examination of expression of TGFβ 1 could help predict the occurrence of esophageal cancer. We can't find any correlation between the positive rate of TGFβ 1 and established histological grade as well as the presence of lymph node metastasis in SCCE.
