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
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
Long-term excessive intake of nitrite(NO_(2)^(-))poses a great threat to human health,needing a simple and fast method to detect NO_(2)-in food.Herein,via a simple and feasible strategy,Mn/Yb/Er triple-doped CeO_(2) n...Long-term excessive intake of nitrite(NO_(2)^(-))poses a great threat to human health,needing a simple and fast method to detect NO_(2)-in food.Herein,via a simple and feasible strategy,Mn/Yb/Er triple-doped CeO_(2) nanozyme(Mn/Yb/Er/CeO_(2))was synthesized for highly sensitive ratiometric detection of nitrite.By doping Mn,Yb,Er into CeO_(2) lattice structure,Mn/Yb/Er/CeO_(2) nanozyme showed enhanced oxidase-like activity,obtaining a higher density of oxygen vacancy and a higher ratio of Ce^(3+)to Ce~(4+)than that of CeO_(2).The 3,3,5,5-tetramethylbenzidine(TMB)can be effectively oxidized by Mn/Yb/Er/CeO_(2) to produce the oxidized TMB(ox TMB),showing a significant absorption signal at 652 nm.Additionally,nitrite can react with ox TMB to produce yellow diazotized ox TMB,which is accompanied by an elevated absorption signal at 445 nm and a decreased absorption signal at 652 nm.Thus,based on the oxidase-mimetic activity of Mn/Yb/Er/CeO_(2) and the diazotization reaction between NO_(2)^(-)and ox TMB,a ratiometric colorimetric assay was established for NO_(2)^(-)detection in food.Furthermore,by integrating Mn/Yb/Er/CeO_(2) with a smartphone,a colorimetric smartphone-sensing platform was successfully fabricated for visualization and quantitative detection of NO_(2)^(-).Notably,this two-detection mode showed excellent sensitivity,selectivity,reliability and practicability in monitoring the NO_(2)^(-)in real samples,impling its great potential for food safety.展开更多
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 the National Natural Science Foundation of China(Nos.22004111 and 21974125)the Tackle Key Problems in Science and Technology Project of Henan Province,China(No.222102310386)+3 种基金China Postdoctoral Science Foundation(No.2020M682327)Henan Postdoctoral Foundation(No.202002009)Program for Innovative Research Team(in Science and Technology)in University of Henan Province(No.22TRTSTHN002)Excellent Youth Foundation of Henan Scientific Committee(No.232300421021)。
文摘Long-term excessive intake of nitrite(NO_(2)^(-))poses a great threat to human health,needing a simple and fast method to detect NO_(2)-in food.Herein,via a simple and feasible strategy,Mn/Yb/Er triple-doped CeO_(2) nanozyme(Mn/Yb/Er/CeO_(2))was synthesized for highly sensitive ratiometric detection of nitrite.By doping Mn,Yb,Er into CeO_(2) lattice structure,Mn/Yb/Er/CeO_(2) nanozyme showed enhanced oxidase-like activity,obtaining a higher density of oxygen vacancy and a higher ratio of Ce^(3+)to Ce~(4+)than that of CeO_(2).The 3,3,5,5-tetramethylbenzidine(TMB)can be effectively oxidized by Mn/Yb/Er/CeO_(2) to produce the oxidized TMB(ox TMB),showing a significant absorption signal at 652 nm.Additionally,nitrite can react with ox TMB to produce yellow diazotized ox TMB,which is accompanied by an elevated absorption signal at 445 nm and a decreased absorption signal at 652 nm.Thus,based on the oxidase-mimetic activity of Mn/Yb/Er/CeO_(2) and the diazotization reaction between NO_(2)^(-)and ox TMB,a ratiometric colorimetric assay was established for NO_(2)^(-)detection in food.Furthermore,by integrating Mn/Yb/Er/CeO_(2) with a smartphone,a colorimetric smartphone-sensing platform was successfully fabricated for visualization and quantitative detection of NO_(2)^(-).Notably,this two-detection mode showed excellent sensitivity,selectivity,reliability and practicability in monitoring the NO_(2)^(-)in real samples,impling its great potential for food safety.
