Congratulations to the publisher,members of the editorial board of the journal,all the authors and readers for launching the World Journal of Medical Genetics(WJMG)as a new member of the World series journal family!Fo...Congratulations to the publisher,members of the editorial board of the journal,all the authors and readers for launching the World Journal of Medical Genetics(WJMG)as a new member of the World series journal family!Following the completion of the Human Genome Project,medical genetic research has seen spectacular progress over the last decade.The number of genes that have been linked to Mendelian human traits has grown exponentially and currently this process is peaking with the access to robust genome-wide sequencing power.The genomics revolution is also seen for elucidation of rare and common DNA variants that increase risk for common disorders.Given this fast progress,there is an increasing need for making the results of genetics and genomics studies rapidly and freely available to the larger community.Thus,the decision for inaugurating this new journal is a timely one.The WJMG is a peer-reviewed,open-access periodical centered in all aspects of medical genetics research,with multidisciplinary coverage:from human phenotype to genetic and genomic mutations and variations to the study of pathological mechanisms.If you want to share new results of your research with a link to medical genetics with your peers,you will find the WJMG a good media to publish your papers!展开更多
This short report describes a model for international collaboration on perinatal health that is innovative,highly-productive and challenging. The model,funded by the U.S. March of Dimes Foundation and entitled the &...This short report describes a model for international collaboration on perinatal health that is innovative,highly-productive and challenging. The model,funded by the U.S. March of Dimes Foundation and entitled the 'March of Dimes Global Network for Maternal and Infant Health(GNMIH)' ,allows developing country experts to more easily share their knowledge,experience,skills and materials in ways that can improve women's,maternal,newborn and child health in lower-income countries. This report begins with a brief description of the March of Dimes and its Global Programs which oversees the GNMIH. It then discusses the structure of the GNMIH,with an emphasis on the benefits and challenges of working within the network,and concludes with a brief description of the acti-vities of network members.展开更多
Protein degradation is important for the dynamic regulation of protein levels in cells.Proteins are recognized by ubiquitin ligases,which tag the target proteins with ubiquitin,which will lead to degradation of the ta...Protein degradation is important for the dynamic regulation of protein levels in cells.Proteins are recognized by ubiquitin ligases,which tag the target proteins with ubiquitin,which will lead to degradation of the tagged proteins via the proteasome.This system has been engineered to be used for novel paths of drug development like the pro-teolysis-targeting chimeras(PROTACs),1 which aim for the degradation of selected targets,and deubiquitinase-tar-geting chimeras(DUBACs),2 which aim for targeted stabilization.The PROTACs and DUBACs,mostly being large molecular chimeras,may limit their further development as drug molecules.Molecular glues,which are small che-mical molecules that can stabilize protein interactions,have also been proposed to be used for targeted protein de-gradation.3 The potential use of molecular glue for targeted protein stabilization has not yet been explored.展开更多
Acute lung injury(ALI)has been a kind of acute and severe disease that is mainly charac-terized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species(ROS)in the lu...Acute lung injury(ALI)has been a kind of acute and severe disease that is mainly charac-terized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species(ROS)in the lung tissue.Given the critical role of ROS in ALI,a Fe_(3)O_(4) loaded bovine serum albumin(BSA)nanocluster(BF)was developed to act as a nanomedicine for the treatment of ALI.Combining with NIR irradiation,it exhibited excellent ROS scavenging capacity.Significantly,it also dis-played the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides(LPS)induced macrophages(RAW264.7),and Sprague Dawley rats via lowering intracellular ROS levels,reducing inflammatory factors expression levels,inducing macrophage M2 polarization,inhibiting NF-κB signaling pathway,increasing CD4^(+)/CD8^(+)T cell ratios,as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis,reduce systemic inflammation,activate immunoregu-lation,and accelerate lung tissue repair,finally achieving the synergistic enhancement of ALI immuno-therapy.It finally provides an effective therapeutic strategy of BF+NIR for the management of inflammation related diseases.展开更多
Nonfibrillar amyloid-βoligomers(AβOs)are a major component of drusen,the sub-retinal pigmented epithelium(RPE)extracellular deposits characteristic of age-related macular degeneration(AMD),a common cause of global b...Nonfibrillar amyloid-βoligomers(AβOs)are a major component of drusen,the sub-retinal pigmented epithelium(RPE)extracellular deposits characteristic of age-related macular degeneration(AMD),a common cause of global blindness.We report that AβOs induce RPE degeneration,a clinical hallmark of geographic atrophy(GA),a vision-threatening late stage of AMD that is currently untreatable.We demonstrate that AβOs induce activation of the NLRP3 inflammasome in the mouse RPE in vivo and that RPE expression of the purinergic ATP receptor P2RX7,an upstream mediator of NLRP3 inflammasome activation,is required for AβO-induced RPE degeneration.Two classes of small molecule inflammasome inhibitors—nucleoside reverse transcriptase inhibitors(NRTIs)and their antiretrovirally inert modified analog Kamuvudines—both inhibit AβOs-induced RPE degeneration.These findings crystallize the importance of P2RX7 and NLRP3 in a disease-relevant model of AMD and identify inflammasome inhibitors as potential treatments for GA.展开更多
The hormone-secreting endocrine cells(α,β,δ,ε and PP cells)form pancreatic islets,which are strongly involved in regulation of metabolism.Deficiency of insulin-producingβcells is the major cause of type 1 diabete...The hormone-secreting endocrine cells(α,β,δ,ε and PP cells)form pancreatic islets,which are strongly involved in regulation of metabolism.Deficiency of insulin-producingβcells is the major cause of type 1 diabetes.Recent progress in cell reprogramming demonstrates the feasibility of generating functionalβcells to treat type 1 diabetes[1].However,a non-invasive in vivo approach forβcell reprogramming is still lacking.Recently,two reports in展开更多
文摘Congratulations to the publisher,members of the editorial board of the journal,all the authors and readers for launching the World Journal of Medical Genetics(WJMG)as a new member of the World series journal family!Following the completion of the Human Genome Project,medical genetic research has seen spectacular progress over the last decade.The number of genes that have been linked to Mendelian human traits has grown exponentially and currently this process is peaking with the access to robust genome-wide sequencing power.The genomics revolution is also seen for elucidation of rare and common DNA variants that increase risk for common disorders.Given this fast progress,there is an increasing need for making the results of genetics and genomics studies rapidly and freely available to the larger community.Thus,the decision for inaugurating this new journal is a timely one.The WJMG is a peer-reviewed,open-access periodical centered in all aspects of medical genetics research,with multidisciplinary coverage:from human phenotype to genetic and genomic mutations and variations to the study of pathological mechanisms.If you want to share new results of your research with a link to medical genetics with your peers,you will find the WJMG a good media to publish your papers!
文摘This short report describes a model for international collaboration on perinatal health that is innovative,highly-productive and challenging. The model,funded by the U.S. March of Dimes Foundation and entitled the 'March of Dimes Global Network for Maternal and Infant Health(GNMIH)' ,allows developing country experts to more easily share their knowledge,experience,skills and materials in ways that can improve women's,maternal,newborn and child health in lower-income countries. This report begins with a brief description of the March of Dimes and its Global Programs which oversees the GNMIH. It then discusses the structure of the GNMIH,with an emphasis on the benefits and challenges of working within the network,and concludes with a brief description of the acti-vities of network members.
文摘Protein degradation is important for the dynamic regulation of protein levels in cells.Proteins are recognized by ubiquitin ligases,which tag the target proteins with ubiquitin,which will lead to degradation of the tagged proteins via the proteasome.This system has been engineered to be used for novel paths of drug development like the pro-teolysis-targeting chimeras(PROTACs),1 which aim for the degradation of selected targets,and deubiquitinase-tar-geting chimeras(DUBACs),2 which aim for targeted stabilization.The PROTACs and DUBACs,mostly being large molecular chimeras,may limit their further development as drug molecules.Molecular glues,which are small che-mical molecules that can stabilize protein interactions,have also been proposed to be used for targeted protein de-gradation.3 The potential use of molecular glue for targeted protein stabilization has not yet been explored.
基金supported by the Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation(Nos.2024GXNSFAA010089 and 2025GXNSFBA069275,China)the National Natural Science Foundation of China(No.82160902,China)+2 种基金the China Post-doctoral Science Foundation(No.2024MD753921,China)the Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening,Education Department of Guangxi Zhuang Autono-mous Region(GXYWSX202404,China)the First-class Disci-pline Innovation-driven Talent Program of Guangxi Medical University,and the Major Talent Project of Guangxi Autonomous Region.
文摘Acute lung injury(ALI)has been a kind of acute and severe disease that is mainly charac-terized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species(ROS)in the lung tissue.Given the critical role of ROS in ALI,a Fe_(3)O_(4) loaded bovine serum albumin(BSA)nanocluster(BF)was developed to act as a nanomedicine for the treatment of ALI.Combining with NIR irradiation,it exhibited excellent ROS scavenging capacity.Significantly,it also dis-played the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides(LPS)induced macrophages(RAW264.7),and Sprague Dawley rats via lowering intracellular ROS levels,reducing inflammatory factors expression levels,inducing macrophage M2 polarization,inhibiting NF-κB signaling pathway,increasing CD4^(+)/CD8^(+)T cell ratios,as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis,reduce systemic inflammation,activate immunoregu-lation,and accelerate lung tissue repair,finally achieving the synergistic enhancement of ALI immuno-therapy.It finally provides an effective therapeutic strategy of BF+NIR for the management of inflammation related diseases.
基金J.A.has received support from NIH grants(R01EY028027,R01EY29799,R01EY031039)DuPont Guerry,III,Professorship,a gift from Mr.and Mrs.Eli W.Tullis,and the University of Virginia Strategic Investment Fund+1 种基金B.D.G.has received support from NIH grants(R01EY028027 and R01EY031039)BrightFocus Foundation,and the Owens Family Foundation.
文摘Nonfibrillar amyloid-βoligomers(AβOs)are a major component of drusen,the sub-retinal pigmented epithelium(RPE)extracellular deposits characteristic of age-related macular degeneration(AMD),a common cause of global blindness.We report that AβOs induce RPE degeneration,a clinical hallmark of geographic atrophy(GA),a vision-threatening late stage of AMD that is currently untreatable.We demonstrate that AβOs induce activation of the NLRP3 inflammasome in the mouse RPE in vivo and that RPE expression of the purinergic ATP receptor P2RX7,an upstream mediator of NLRP3 inflammasome activation,is required for AβO-induced RPE degeneration.Two classes of small molecule inflammasome inhibitors—nucleoside reverse transcriptase inhibitors(NRTIs)and their antiretrovirally inert modified analog Kamuvudines—both inhibit AβOs-induced RPE degeneration.These findings crystallize the importance of P2RX7 and NLRP3 in a disease-relevant model of AMD and identify inflammasome inhibitors as potential treatments for GA.
文摘The hormone-secreting endocrine cells(α,β,δ,ε and PP cells)form pancreatic islets,which are strongly involved in regulation of metabolism.Deficiency of insulin-producingβcells is the major cause of type 1 diabetes.Recent progress in cell reprogramming demonstrates the feasibility of generating functionalβcells to treat type 1 diabetes[1].However,a non-invasive in vivo approach forβcell reprogramming is still lacking.Recently,two reports in
