Pelvic organ prolapse （POP） is a disabling disorder in women characterized by a loss of pelvic floor support, leading to the herniation of the uterus into or through the vagina. POP is a complex problem that likely ...Pelvic organ prolapse （POP） is a disabling disorder in women characterized by a loss of pelvic floor support, leading to the herniation of the uterus into or through the vagina. POP is a complex problem that likely involves multiple mechanisms with limited therapies available, and is associated with defects in connective tissue including elastic fibers. This study was designed to investigate the expression of fibulin-5 and lysyl oxidase-like 1 （LOXL1） in the cardinal ligament in samples taken from the POP group compared to the non-POP group. Specimens were obtained during abdominal hysterectomy from the cardinal ligament of 53 women with POP and 25 age- and par- ity- matched women with non-POP among post-menopausal women with benign gynecologic pathology. Protein expression was evaluated using the immunohistochemical staining method. For statistical analyses, chi-square test and Spearman＇s correlation were used with the statistical package SPSS13.0 system. Our results showed that both fibulin-5 and LOXL1 expressions were decreased in the cardinal ligament in the POP group compared to the non- POP group （P 〈 0.05）. The expression of fibulin-5 and LOXL1 were correlated closely with the stage of POP, ac- companied by stress urinary incontinence and frequency of vaginal delivery （P 〈 0.05）, but had no relationship with post-menopausal state （P 〉 0.05）. The expression of fibulin-5 was positively associated with LOXL1 in POP （P 〈 0.05）. We conclude that changes in fibulin-5 and LOXL1 expression may play a role in the development of POP.展开更多
Dear Editor： I would like to congratulate Zhou et al.[1] on their study of the correlation between expression of lysyl oxidase-like 1 （LOX-1） and fibulin-5 （F5） in the car- dinal ligament tissue and pelvic organ ...Dear Editor： I would like to congratulate Zhou et al.[1] on their study of the correlation between expression of lysyl oxidase-like 1 （LOX-1） and fibulin-5 （F5） in the car- dinal ligament tissue and pelvic organ prolapse （POP）. In their elegant work, they evaluated the levels of LOX-1 and F5 in connective tissue of the cardinal ligament in order to demonstrate signs of elastinopa- thy in women with POP. They stress the concept that several environmental risk factors could cause qualitative and quantitative changes in the connective tissue promoting POP. The above authors conclude that the specific mechanism of LOXL1 and F5 involved in the development of POP is unclear.展开更多
AIM:To study the associations between lysyl oxidaselike 1(LOXL1)polymorphisms and primary open angle glaucoma(POAG)remain inconsistent.In this study,we have performed a meta-analysis to investigate the association of ...AIM:To study the associations between lysyl oxidaselike 1(LOXL1)polymorphisms and primary open angle glaucoma(POAG)remain inconsistent.In this study,we have performed a meta-analysis to investigate the association of LOXL1 polymorphisms with POAG risk.METHODS:Published literature from PubMed and other databases were retrieved.All studies evaluating the association between LOXL1 polymorphisms(rs2165241,rs1048661,rs3825942)and POAG risk were included.Pooled odds ratio(OR)and 95%confidence interval(CI)were calculated using random-or fixed-effects model.RESULTS:Twelve studies were identified as eligible articles,with thirteen(2098 cases and 16 473 controls),thirteen(1795 cases and 2916 controls)and sixteen population cohorts(2456 cases and 2846 controls)for the association of rs2165241,rs1048661 and rs3825942with POAG risk respectively.Overall analyses showed noassociation between each LOXL1 polymorphism and POAG risk,and the negative associations were remained when the subjects were stratified as Caucasian and Asian.The heterozygote of rs2165241 was associated with reduced POAG risk in hospital-based populations(TC vs CC:OR,0.79,95%CI:0.63-0.99),and rs1048661was associated with increased POAG risk in hospitalbased populations in a dominant model(TT vs CC+CT:OR,1.23,95%CI:1.01-1.50);however,these associations were not found in population-based subjects.CONCLUSION:This meta-analysis suggests that LOXL1 polymorphisms are not associated with POAG risk.Given the limited sample size,the associations of LOXL1 polymorphisms with POAG risk in hospital-based populations await further investigation.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been established.In this study,we investigated whether Neural Wiskott-Aldrich syndr...Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been established.In this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of PDAC.We found that N-WASP is markedly expressed in clinical patients with PDAC.Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile studies.Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and EMT.We also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were modulated.Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis.These findings may aid in the development of therapeutic strategies against pancreatic cancer.展开更多
In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive...In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.展开更多
盆底器官脱垂(pelvic organ prolapse,POP)是以盆底支持组织薄弱为特性的一类功能障碍性疾病,其发生是一个复杂的过程。盆底组织内弹性纤维结构或功能异常可直接导致POP的发生。类赖氨酰氧化酶-1(lysyl oxidase-like protein-1,LOXL-1)...盆底器官脱垂(pelvic organ prolapse,POP)是以盆底支持组织薄弱为特性的一类功能障碍性疾病,其发生是一个复杂的过程。盆底组织内弹性纤维结构或功能异常可直接导致POP的发生。类赖氨酰氧化酶-1(lysyl oxidase-like protein-1,LOXL-1)是弹性蛋白保持正常结构功能的关键酶。LOXL-1缺失或功能障碍,将导致弹性纤维功能紊乱,从而引起POP。本研究就LOXL-1在POP发生机制中的作用进行综述。展开更多
AIM:To investigate the preventive effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on bile duct ligation (BDL)induced liver fibrosis in rats. METHODS:Liver fibrosis in rats was induced by BDL and AcSDKP was in...AIM:To investigate the preventive effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on bile duct ligation (BDL)induced liver fibrosis in rats. METHODS:Liver fibrosis in rats was induced by BDL and AcSDKP was infused subcutaneously for 2 wkvia a osmotic minipump (Alzet 2ML4) immediately after BDL operation. After scarifying, serum and liver specimens were collected. Hematoxylin and eosin staining, Sirius red staining, enzyme linked immunosorbent assay, Western blot or real-time polymerase chain reaction were used to determinate liver functions, histological alterations, collagen deposition, mRNA expression of markers for fibroblasts, transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7). RESULTS:When compared to model rats, chronic exogenous AcSDKP infusion suppressed profibrogenicTGF-β1 signaling, α-smooth muscle actin positivity (α-SMA), fibroblast specific protein-1 (FSP-1) staining and collagen gene expression. Col Ⅰ, Col Ⅲ, matrix metalloproteinase-2, tissue inhibitors of metallopro-teinase-1 and tissue inhibitors of metalloproteinase-2 mRNA expressions were all significantly downregulated by AcSDKP infusion (2.02 ± 1.10vs 14.16 ± 6.50, 2.02 ± 0.45vs 10.00 ± 3.35, 2.91 ± 0.30vs 7.83 ± 1.10, 4.64 ± 1.25 vs 18.52 ± 7.61, 0.46 ± 0.16 vs 0.34 ± 0.12, respectively, P < 0.05). Chronic exogenous AcSDKP infusion attenuated BDL-induced liver injury, inflammation and fibrosis. BDL caused a remarkable increase in alanine transaminase, aspartate transaminase, total bilirubin, and prothrombin time, all of which were reduced by AcSDKP infusion. Mast cells, collagen accumulation, α-SMA, TGF-β1, FSP-1 and BMP-7 increased. The histological appearance of liver specimens was also improved. CONCLUSION:Infusion of exogenous AcSDKP attenu-ated BDL-induced fibrosis in the rat liver. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.展开更多
AIM: To investigate the association of lysyl oxidaselike 1(LOXL1) single nucleotide polymorphisms(SNPs)with exfoliation syndrome(XFS)/exfoliation glaucoma(XFG).METHODS: Published manuscripts from Pub Med and EMBASE we...AIM: To investigate the association of lysyl oxidaselike 1(LOXL1) single nucleotide polymorphisms(SNPs)with exfoliation syndrome(XFS)/exfoliation glaucoma(XFG).METHODS: Published manuscripts from Pub Med and EMBASE were identified until May 2014. Summary odds ratios(ORs) and 95% confidence intervals(CIs) for LOXL1(rs1048661, rs2165241 and rs3825942) polymorphisms and the risk of XFS/XFG were estimated using random-or fixed- effect model.· RESULTS: The three LOXL1 polymorphisms(rs1048661, rs3825942, and rs2165241) were associated with an increased risk for XFS/XFG among Caucasians,with OR 2.19(1.96-2.45), 8.8(6.05-12.79) and 3.41(3.11-3.73), respectively. On the contrast, the rs1048661 and rs2165241, but not rs3825942 polymorphism, have a potential protective effect on XFS/XFG in Asians, with OR0.06(0.02-0.18), 0.15(0.09-0.25), respectively.CONCLUSION: There is strong evidence that LOXL1 polymorphisms are associated with XFS/XFG risk. The strength of risk might be ethnicity-dependent.展开更多
文摘Pelvic organ prolapse （POP） is a disabling disorder in women characterized by a loss of pelvic floor support, leading to the herniation of the uterus into or through the vagina. POP is a complex problem that likely involves multiple mechanisms with limited therapies available, and is associated with defects in connective tissue including elastic fibers. This study was designed to investigate the expression of fibulin-5 and lysyl oxidase-like 1 （LOXL1） in the cardinal ligament in samples taken from the POP group compared to the non-POP group. Specimens were obtained during abdominal hysterectomy from the cardinal ligament of 53 women with POP and 25 age- and par- ity- matched women with non-POP among post-menopausal women with benign gynecologic pathology. Protein expression was evaluated using the immunohistochemical staining method. For statistical analyses, chi-square test and Spearman＇s correlation were used with the statistical package SPSS13.0 system. Our results showed that both fibulin-5 and LOXL1 expressions were decreased in the cardinal ligament in the POP group compared to the non- POP group （P 〈 0.05）. The expression of fibulin-5 and LOXL1 were correlated closely with the stage of POP, ac- companied by stress urinary incontinence and frequency of vaginal delivery （P 〈 0.05）, but had no relationship with post-menopausal state （P 〉 0.05）. The expression of fibulin-5 was positively associated with LOXL1 in POP （P 〈 0.05）. We conclude that changes in fibulin-5 and LOXL1 expression may play a role in the development of POP.
文摘Dear Editor： I would like to congratulate Zhou et al.[1] on their study of the correlation between expression of lysyl oxidase-like 1 （LOX-1） and fibulin-5 （F5） in the car- dinal ligament tissue and pelvic organ prolapse （POP）. In their elegant work, they evaluated the levels of LOX-1 and F5 in connective tissue of the cardinal ligament in order to demonstrate signs of elastinopa- thy in women with POP. They stress the concept that several environmental risk factors could cause qualitative and quantitative changes in the connective tissue promoting POP. The above authors conclude that the specific mechanism of LOXL1 and F5 involved in the development of POP is unclear.
基金Supported by the Zhejiang Provincial Educational Bureau Foundation,China(Y201223905)
文摘AIM:To study the associations between lysyl oxidaselike 1(LOXL1)polymorphisms and primary open angle glaucoma(POAG)remain inconsistent.In this study,we have performed a meta-analysis to investigate the association of LOXL1 polymorphisms with POAG risk.METHODS:Published literature from PubMed and other databases were retrieved.All studies evaluating the association between LOXL1 polymorphisms(rs2165241,rs1048661,rs3825942)and POAG risk were included.Pooled odds ratio(OR)and 95%confidence interval(CI)were calculated using random-or fixed-effects model.RESULTS:Twelve studies were identified as eligible articles,with thirteen(2098 cases and 16 473 controls),thirteen(1795 cases and 2916 controls)and sixteen population cohorts(2456 cases and 2846 controls)for the association of rs2165241,rs1048661 and rs3825942with POAG risk respectively.Overall analyses showed noassociation between each LOXL1 polymorphism and POAG risk,and the negative associations were remained when the subjects were stratified as Caucasian and Asian.The heterozygote of rs2165241 was associated with reduced POAG risk in hospital-based populations(TC vs CC:OR,0.79,95%CI:0.63-0.99),and rs1048661was associated with increased POAG risk in hospitalbased populations in a dominant model(TT vs CC+CT:OR,1.23,95%CI:1.01-1.50);however,these associations were not found in population-based subjects.CONCLUSION:This meta-analysis suggests that LOXL1 polymorphisms are not associated with POAG risk.Given the limited sample size,the associations of LOXL1 polymorphisms with POAG risk in hospital-based populations await further investigation.
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean Government,Ministry of Science and ICT(MSIT)(2016R1C1B102207,2022R1A2C1004141 and 2022R1A2C-1091712)the National R&D Program for Cancer Control through the National Cancer Center(NCC)funded by the Ministry of Health&Welfare,Republic of Korea(HA22C0053000022).
文摘Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been established.In this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of PDAC.We found that N-WASP is markedly expressed in clinical patients with PDAC.Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile studies.Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and EMT.We also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were modulated.Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis.These findings may aid in the development of therapeutic strategies against pancreatic cancer.
文摘In the present study, we developed silicosis of rat model by bronchial perfusion SiO2 dust, and intervenes with AcSDKP, immunohisto chemistry was used to detect NF-κb and MCP-1 expression in lung tissue, and positive cells were counted. We found that compared with silicotic model group, the positive cells of NF-κb and MCP-1 were decreased significantly in anti-fibrosis treatment of AcSDKP group. The findings suggest that AcSDKP could inhibit the expression of NF-κb and MCP-1 in lung tissue of silicosos, this may be related to AcSDKP inhibit of macrophage infiltration in lung tissue and reduced the degree of dust alveolitis.
文摘盆底器官脱垂(pelvic organ prolapse,POP)是以盆底支持组织薄弱为特性的一类功能障碍性疾病,其发生是一个复杂的过程。盆底组织内弹性纤维结构或功能异常可直接导致POP的发生。类赖氨酰氧化酶-1(lysyl oxidase-like protein-1,LOXL-1)是弹性蛋白保持正常结构功能的关键酶。LOXL-1缺失或功能障碍,将导致弹性纤维功能紊乱,从而引起POP。本研究就LOXL-1在POP发生机制中的作用进行综述。
基金Supported by Grants from National Natural Science Foundation of China, No. 30971263 and No. 81170410 (to Chen YW)Shanghai Pujiang Program, No. 10PJ1407600 (to Chen YW)
文摘AIM:To investigate the preventive effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on bile duct ligation (BDL)induced liver fibrosis in rats. METHODS:Liver fibrosis in rats was induced by BDL and AcSDKP was infused subcutaneously for 2 wkvia a osmotic minipump (Alzet 2ML4) immediately after BDL operation. After scarifying, serum and liver specimens were collected. Hematoxylin and eosin staining, Sirius red staining, enzyme linked immunosorbent assay, Western blot or real-time polymerase chain reaction were used to determinate liver functions, histological alterations, collagen deposition, mRNA expression of markers for fibroblasts, transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7). RESULTS:When compared to model rats, chronic exogenous AcSDKP infusion suppressed profibrogenicTGF-β1 signaling, α-smooth muscle actin positivity (α-SMA), fibroblast specific protein-1 (FSP-1) staining and collagen gene expression. Col Ⅰ, Col Ⅲ, matrix metalloproteinase-2, tissue inhibitors of metallopro-teinase-1 and tissue inhibitors of metalloproteinase-2 mRNA expressions were all significantly downregulated by AcSDKP infusion (2.02 ± 1.10vs 14.16 ± 6.50, 2.02 ± 0.45vs 10.00 ± 3.35, 2.91 ± 0.30vs 7.83 ± 1.10, 4.64 ± 1.25 vs 18.52 ± 7.61, 0.46 ± 0.16 vs 0.34 ± 0.12, respectively, P < 0.05). Chronic exogenous AcSDKP infusion attenuated BDL-induced liver injury, inflammation and fibrosis. BDL caused a remarkable increase in alanine transaminase, aspartate transaminase, total bilirubin, and prothrombin time, all of which were reduced by AcSDKP infusion. Mast cells, collagen accumulation, α-SMA, TGF-β1, FSP-1 and BMP-7 increased. The histological appearance of liver specimens was also improved. CONCLUSION:Infusion of exogenous AcSDKP attenu-ated BDL-induced fibrosis in the rat liver. Preservation of AcSDKP may be a useful therapeutic approach in the management of liver fibrosis.
基金Supported by Natural Science Foundation of Guangdong Province(No.S2013010016037)the National Science and Tecnology Plan Project of China(973 program,No.2011CB707501)
文摘AIM: To investigate the association of lysyl oxidaselike 1(LOXL1) single nucleotide polymorphisms(SNPs)with exfoliation syndrome(XFS)/exfoliation glaucoma(XFG).METHODS: Published manuscripts from Pub Med and EMBASE were identified until May 2014. Summary odds ratios(ORs) and 95% confidence intervals(CIs) for LOXL1(rs1048661, rs2165241 and rs3825942) polymorphisms and the risk of XFS/XFG were estimated using random-or fixed- effect model.· RESULTS: The three LOXL1 polymorphisms(rs1048661, rs3825942, and rs2165241) were associated with an increased risk for XFS/XFG among Caucasians,with OR 2.19(1.96-2.45), 8.8(6.05-12.79) and 3.41(3.11-3.73), respectively. On the contrast, the rs1048661 and rs2165241, but not rs3825942 polymorphism, have a potential protective effect on XFS/XFG in Asians, with OR0.06(0.02-0.18), 0.15(0.09-0.25), respectively.CONCLUSION: There is strong evidence that LOXL1 polymorphisms are associated with XFS/XFG risk. The strength of risk might be ethnicity-dependent.
