In this editorial,we highlight the study by Xiao et al.Despite progress in the management of diabetic foot ulcers(DFUs),impaired wound healing remains a significant clinical challenge.Recent studies have highlighted t...In this editorial,we highlight the study by Xiao et al.Despite progress in the management of diabetic foot ulcers(DFUs),impaired wound healing remains a significant clinical challenge.Recent studies have highlighted the critical role of epigenetic modifications in diabetic wound healing,with particular emphasis on DNA and RNA methylation pathways.This editorial discusses the findings of Xiao et al,who identified the Wilms tumor 1-associated protein(WTAP)-DNA methyltransferase 1(DNMT1)axis as a pivotal regulator of endothelial dys-function in DFUs.WTAP,a regulatory subunit of N6-methyladenosine(m6A)methyltransferase,is upregulated under high-glucose conditions and drives the excessive expression of DNMT1 via m6A modification.This contributes to im-paired angiogenesis,reduced cell viability,and delayed wound closure.WTAP knockdown restored endothelial function and significantly improved wound healing in a diabetic mouse model.Furthermore,DNMT1 overexpression ab-rogated the benefits of WTAP suppression,confirming its downstream effector role.Thus,targeting the WTAP-DNMT1 axis provides a new avenue for DFU management.Moreover,epigenetic interventions that modulate both the m6A and RNA methylation pathways could restore endothelial function and enhance tissue repair in patients with diabetes.展开更多
BACKGROUND Diabetic wound injury is a significant and common complication in individuals with diabetes.N6-methyladenosine(m6A)-related epigenetic regulation is widely involved in the pathogenesis of diabetes complicat...BACKGROUND Diabetic wound injury is a significant and common complication in individuals with diabetes.N6-methyladenosine(m6A)-related epigenetic regulation is widely involved in the pathogenesis of diabetes complications.However,the function of m6A methyltransferase Wilms tumor 1-associated protein(WTAP)in diabetic wound healing remains elusive.AIM To investigate the potential epigenetic regulatory mechanism of WTAP during diabetic wound healing.METHODS Human umbilical vein endothelial cells(HUVECs)were induced with high glucose(HG)to establish in vitro cell model.Male BALB/c mice were intraperitoneally injected with streptozotocin to mimic diabetes,and full-thickness excision was made to mimic diabetic wound healing.HG-induced HUVECs and mouse models were treated with WTAP siRNAs and DNA methyltransferase 1(DNMT1)overexpression vectors.Cell viability and migration ability were detected by cell counting kit-8 and Transwell assays.In vitro angiogenesis was measured using a tube formation experiment.The images of wounds were captured,and re-epithelialization and collagen deposition of skin tissues were analyzed using hematoxylin and eosin staining and Masson’s trichrome staining.RESULTS The expression of several m6A methyltransferases,including METTL3,METTL14,METTL16,KIAA1429,WTAP,and RBM15,were measured.WTAP exhibited the most significant elevation in HG-induced HUVECs compared with the normal control.WTAP depletion notably restored cell viability and enhanced tube formation ability and migration of HUVECs suppressed by HG.The unclosed wound area of mice was smaller in WTAP knockdowntreated mice than in control mice at nine days post-wounding,along with enhanced re-epithelialization rate and collagen deposition.The m6A levels on DNMT1 mRNA in HUVECs were repressed by WTAP knockdown in HUVECs.The mRNA levels and expression of DNMT1 were inhibited by WTAP depletion in HUVECs.Overexpression of DNMT1 in HUVECs notably reversed the effects of WTAP depletion on HG-induced HUVECs.CONCLUSION WTAP expression is elevated in HG-induced HUVECs and epigenetically regulates the m6A modification of DNMT1 to impair diabetic wound healing.展开更多
BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated w...BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated with a poor prognosis in patients with WT.AIM To further elucidate this relationship,we conducted a meta-analysis.METHODS This meta-analysis was registered in INPLASY(INPLASY2023100060).We systematically searched databases including Embase,PubMed,Web of Science,Cochrane,and Google Scholar up to May 31,2020,for randomized trials reporting any intrapartum fetal surveillance approach.The meta-analysis was performed within a frequentist framework,and the quality and network inconsistency of trials were assessed.Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT.RESULTS Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT(I^(2)=25%,P<0.001).As expected,16q LOH can serve as an effective predictor of eventfree survival in patients with WT(risk ratio=1.95,95%CI:1.52–2.49,P<0.001).CONCLUSION In pediatric patients with WT,there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis.Clinical detection of 16q chromosome LOH warrants increased attention to the patient’s prognosis.展开更多
The relationship between genetic alterations at chromosomal band 11p13 and the WAGR(Wilms'tumor,aniridia,genitourinary anomalies,and mental retardation)syndrome is not clearly understood.To aid our understanding o...The relationship between genetic alterations at chromosomal band 11p13 and the WAGR(Wilms'tumor,aniridia,genitourinary anomalies,and mental retardation)syndrome is not clearly understood.To aid our understanding of this relationship,we have constructed a physical map of this region of the genome using pulsed field gel electrophoresis.Fifteen newly identified 11p13-specific probes and four previously reported probes were used to subdivide 11p13 into five intervals defined by overlapping constitutional deletions from several WAGR patients.This new repertoire of DNA probes was used to construct a physical map of this region using the infrequently cutting restriction enzymes MIuI and NotI.This map spans approximately 13 Mb and encompasses deletion and translocation breakpoints associated with genitourinary abnormalities,aniridia,and Wilms'tumor.The map also makes it possible to localize the genes for Wilms'tumor(WT)and aniridia(AN2)to a small number of specific NotI restriction fragments.展开更多
基金Supported by the Kuwait Foundation for the Advancement of Sciences and Dasman Diabetes Institute,No.RACB-2021-007.
文摘In this editorial,we highlight the study by Xiao et al.Despite progress in the management of diabetic foot ulcers(DFUs),impaired wound healing remains a significant clinical challenge.Recent studies have highlighted the critical role of epigenetic modifications in diabetic wound healing,with particular emphasis on DNA and RNA methylation pathways.This editorial discusses the findings of Xiao et al,who identified the Wilms tumor 1-associated protein(WTAP)-DNA methyltransferase 1(DNMT1)axis as a pivotal regulator of endothelial dys-function in DFUs.WTAP,a regulatory subunit of N6-methyladenosine(m6A)methyltransferase,is upregulated under high-glucose conditions and drives the excessive expression of DNMT1 via m6A modification.This contributes to im-paired angiogenesis,reduced cell viability,and delayed wound closure.WTAP knockdown restored endothelial function and significantly improved wound healing in a diabetic mouse model.Furthermore,DNMT1 overexpression ab-rogated the benefits of WTAP suppression,confirming its downstream effector role.Thus,targeting the WTAP-DNMT1 axis provides a new avenue for DFU management.Moreover,epigenetic interventions that modulate both the m6A and RNA methylation pathways could restore endothelial function and enhance tissue repair in patients with diabetes.
文摘BACKGROUND Diabetic wound injury is a significant and common complication in individuals with diabetes.N6-methyladenosine(m6A)-related epigenetic regulation is widely involved in the pathogenesis of diabetes complications.However,the function of m6A methyltransferase Wilms tumor 1-associated protein(WTAP)in diabetic wound healing remains elusive.AIM To investigate the potential epigenetic regulatory mechanism of WTAP during diabetic wound healing.METHODS Human umbilical vein endothelial cells(HUVECs)were induced with high glucose(HG)to establish in vitro cell model.Male BALB/c mice were intraperitoneally injected with streptozotocin to mimic diabetes,and full-thickness excision was made to mimic diabetic wound healing.HG-induced HUVECs and mouse models were treated with WTAP siRNAs and DNA methyltransferase 1(DNMT1)overexpression vectors.Cell viability and migration ability were detected by cell counting kit-8 and Transwell assays.In vitro angiogenesis was measured using a tube formation experiment.The images of wounds were captured,and re-epithelialization and collagen deposition of skin tissues were analyzed using hematoxylin and eosin staining and Masson’s trichrome staining.RESULTS The expression of several m6A methyltransferases,including METTL3,METTL14,METTL16,KIAA1429,WTAP,and RBM15,were measured.WTAP exhibited the most significant elevation in HG-induced HUVECs compared with the normal control.WTAP depletion notably restored cell viability and enhanced tube formation ability and migration of HUVECs suppressed by HG.The unclosed wound area of mice was smaller in WTAP knockdowntreated mice than in control mice at nine days post-wounding,along with enhanced re-epithelialization rate and collagen deposition.The m6A levels on DNMT1 mRNA in HUVECs were repressed by WTAP knockdown in HUVECs.The mRNA levels and expression of DNMT1 were inhibited by WTAP depletion in HUVECs.Overexpression of DNMT1 in HUVECs notably reversed the effects of WTAP depletion on HG-induced HUVECs.CONCLUSION WTAP expression is elevated in HG-induced HUVECs and epigenetically regulates the m6A modification of DNMT1 to impair diabetic wound healing.
基金Supported by Yunnan Provincial Department of Science and Technology Provincial Basic Research Program(Kunming Medical Joint Special Project,No.2019FE001(-276)Kunming Health Science and Technology Talents Training Project and"Ten Hundred Thousands"Project Training Plan,No.2020-SW(Backup)-121.
文摘BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated with a poor prognosis in patients with WT.AIM To further elucidate this relationship,we conducted a meta-analysis.METHODS This meta-analysis was registered in INPLASY(INPLASY2023100060).We systematically searched databases including Embase,PubMed,Web of Science,Cochrane,and Google Scholar up to May 31,2020,for randomized trials reporting any intrapartum fetal surveillance approach.The meta-analysis was performed within a frequentist framework,and the quality and network inconsistency of trials were assessed.Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT.RESULTS Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT(I^(2)=25%,P<0.001).As expected,16q LOH can serve as an effective predictor of eventfree survival in patients with WT(risk ratio=1.95,95%CI:1.52–2.49,P<0.001).CONCLUSION In pediatric patients with WT,there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis.Clinical detection of 16q chromosome LOH warrants increased attention to the patient’s prognosis.
文摘The relationship between genetic alterations at chromosomal band 11p13 and the WAGR(Wilms'tumor,aniridia,genitourinary anomalies,and mental retardation)syndrome is not clearly understood.To aid our understanding of this relationship,we have constructed a physical map of this region of the genome using pulsed field gel electrophoresis.Fifteen newly identified 11p13-specific probes and four previously reported probes were used to subdivide 11p13 into five intervals defined by overlapping constitutional deletions from several WAGR patients.This new repertoire of DNA probes was used to construct a physical map of this region using the infrequently cutting restriction enzymes MIuI and NotI.This map spans approximately 13 Mb and encompasses deletion and translocation breakpoints associated with genitourinary abnormalities,aniridia,and Wilms'tumor.The map also makes it possible to localize the genes for Wilms'tumor(WT)and aniridia(AN2)to a small number of specific NotI restriction fragments.
