Hypertrophic scar and keloid are a major medical problem,which may lead to disfigurement,growth restriction,and permanent loss of function,causing severe physical,psychological,and economic burdens.1 When skin injury ...Hypertrophic scar and keloid are a major medical problem,which may lead to disfigurement,growth restriction,and permanent loss of function,causing severe physical,psychological,and economic burdens.1 When skin injury occurs,the wound heals through a dynamic series of physiological events,including blood clotting,granulation tissue formation,re-epithelialization,and extracellular matrix remodeling.2 However,the newly formed extracellular matrix in a scar may never achieve the flexibility or strength of the original tissue.展开更多
Skin serves as the first-order protective barrier against the environment and any significant disruptions in skin integrity must be promptly restored.Despite significant advances in therapeutic strategies,effective ma...Skin serves as the first-order protective barrier against the environment and any significant disruptions in skin integrity must be promptly restored.Despite significant advances in therapeutic strategies,effective management of large chronic skin wounds remains a clinical challenge.Dermal fibroblasts are the primary cell type responsible for remodeling the extracellular matrix(ECM)in wound healing.Here,we investigated whether ECM derived from exogenous fibroblasts,in combination with keratinocytes,promoted scarless cutaneous wound healing.To overcome the limited lifespan of primary dermal fibroblasts,we established reversibly immortalized mouse dermal fibroblasts(imDFs),which were non-tumorigenic,expressed dermal fibroblast markers,and were responsive to TGF-β1 stimulation.The decellularized ECM prepared from both imDFs and primary dermal fi-broblasts shared similar expression profiles of extracellular matrix proteins and promoted the proliferation of keratinocyte(iKera)cells.The imDFs-derived ECM solicited no local immune response.While the ECM and to a lesser extent imDFs enhanced skin wound healing with excessive fibrosis,a combination of imDFs-derived ECM and iKera cells effectively promoted the re-epithelization and scarless healing of full-thickness skin wounds.These findings strongly suggest that dermal fibroblast-derived ECM,not fibroblasts themselves,may synergize with keratinocytes in regulating scarless healing and re-epithelialization of skin wounds.Given its low immu-nogenic nature,imDFs-derived ECM should be a valuable resource of skin-specific biomaterial for wound healing and skin tissue engineering.展开更多
Summary What is known about this topic?H10 avian influenza viruses circulate in wild birds and can reassort with other subtypes.H10N8 and H10N3 have previously caused sporadic human infections in China.What is added b...Summary What is known about this topic?H10 avian influenza viruses circulate in wild birds and can reassort with other subtypes.H10N8 and H10N3 have previously caused sporadic human infections in China.What is added by this report?This report documents the first human case of coinfection with avian-origin H10N5 and seasonal H3N2 influenza viruses.Epidemiological investigations identified H10N5 in environmental samples linked to the patient,but no transmission to close contacts occurred.What are the implications for public health practice?Enhanced surveillance of avian influenza in live poultry markets and poultry populations is crucial for thoroughly characterizing the epidemiology,transmission,and pathogenesis of H10N5 viruses.Strengthening assessments of outbreak control measures is essential to guide effective management.展开更多
Recombinant adenovirus(rAdV)is a commonly used vector system for gene transfer.Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive,possibly attributable to rAdv inf...Recombinant adenovirus(rAdV)is a commonly used vector system for gene transfer.Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive,possibly attributable to rAdv infection-associated oxidative stress and reactive oxygen species(ROS)production.Here,we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells,and expedites adenovirus production.By stably overexpressing GAPDH in HEK293(293G)and 293pTP(293GP)cells,respectively,we demonstrated that rAdV-induced RoS production and cell apoptosis were significantly suppressed in 293G and 293GP cells.Transfection of 293G cells with adenoviral plasmid pAd-G2Luc yielded much higher titers of Ad-G2Luc at day 7 than that in HEK293 cells.Similarly,Ad-G2Luc was amplified more efficiently in 293G than in HEK293 cells.We further showed that transfection of 293GP cells with pAd-G2Luc produced much higher titers of Ad-G2Luc at day 5 than that of 293pTP cells.293GP cells amplified the Ad-G2Luc much more efficiently than 293pTP cells,indicating that exogenous GAPDH can further augment pTP-enhanced adenovirus production.These results demonstrate that exogenous GAPDH can effectively suppress adenovirus-induced ROS and thus accelerate adenovirus production.Therefore,the engineered 293GP cells represent a superfast rAdV production system for adenovirus-based gene transfer and gene therapy.展开更多
基金supported in part by research grants from the Natural Science Foundation of China(No.82102696 to J.F.)the Chongqing Natural Science Foundation of China(No.2024NSCQ-MSX0073 to J.F.)+1 种基金the US National Institutes of Health(No.CA226303 to T.C.H.DE030480 to R.R.R.).
文摘Hypertrophic scar and keloid are a major medical problem,which may lead to disfigurement,growth restriction,and permanent loss of function,causing severe physical,psychological,and economic burdens.1 When skin injury occurs,the wound heals through a dynamic series of physiological events,including blood clotting,granulation tissue formation,re-epithelialization,and extracellular matrix remodeling.2 However,the newly formed extracellular matrix in a scar may never achieve the flexibility or strength of the original tissue.
基金supported in part by research grants from the Natural Science Foundation of China(82102696,JF)Chongqing Nat-ural Science Foundation(2024NSCQ-MSX0073,JF)+3 种基金the National Institutes of Health(CA226303 to TCH,and DE030480 to RRR)supported in part by The University of Chicago Comprehensive Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund.
文摘Skin serves as the first-order protective barrier against the environment and any significant disruptions in skin integrity must be promptly restored.Despite significant advances in therapeutic strategies,effective management of large chronic skin wounds remains a clinical challenge.Dermal fibroblasts are the primary cell type responsible for remodeling the extracellular matrix(ECM)in wound healing.Here,we investigated whether ECM derived from exogenous fibroblasts,in combination with keratinocytes,promoted scarless cutaneous wound healing.To overcome the limited lifespan of primary dermal fibroblasts,we established reversibly immortalized mouse dermal fibroblasts(imDFs),which were non-tumorigenic,expressed dermal fibroblast markers,and were responsive to TGF-β1 stimulation.The decellularized ECM prepared from both imDFs and primary dermal fi-broblasts shared similar expression profiles of extracellular matrix proteins and promoted the proliferation of keratinocyte(iKera)cells.The imDFs-derived ECM solicited no local immune response.While the ECM and to a lesser extent imDFs enhanced skin wound healing with excessive fibrosis,a combination of imDFs-derived ECM and iKera cells effectively promoted the re-epithelization and scarless healing of full-thickness skin wounds.These findings strongly suggest that dermal fibroblast-derived ECM,not fibroblasts themselves,may synergize with keratinocytes in regulating scarless healing and re-epithelialization of skin wounds.Given its low immu-nogenic nature,imDFs-derived ECM should be a valuable resource of skin-specific biomaterial for wound healing and skin tissue engineering.
基金Supported by the National Disease Control and Prevention Administration Public Health Talent Training Program(202303)the National Key Research and Development Project(2022YFE0110100)+1 种基金the Opening foundation of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,Zhejiang University School of Medicine(SKLID2021KF04)the Scientific Research Projects of Health Commission of Anhui Province in 2021(AHWJ2021a030).
文摘Summary What is known about this topic?H10 avian influenza viruses circulate in wild birds and can reassort with other subtypes.H10N8 and H10N3 have previously caused sporadic human infections in China.What is added by this report?This report documents the first human case of coinfection with avian-origin H10N5 and seasonal H3N2 influenza viruses.Epidemiological investigations identified H10N5 in environmental samples linked to the patient,but no transmission to close contacts occurred.What are the implications for public health practice?Enhanced surveillance of avian influenza in live poultry markets and poultry populations is crucial for thoroughly characterizing the epidemiology,transmission,and pathogenesis of H10N5 viruses.Strengthening assessments of outbreak control measures is essential to guide effective management.
基金supported in part by research grants from the Natural Science Foundation of China (No.82000744 to ZT,and 82102696 to J.F.)the Chongqing Bayu Young Scholar Award (China) (to J.F.)+5 种基金the 2019 Funding for Postdoctoral Research (Chongqing Human Resources and Social Security Bureau of China) (No.298 to J.F.)the National Institutes of Health (No.CA226303 to T.C.H.,DE030480 to R.R.R.)supported by the Medical Scientist Training Program of the National Institutes of Health (USA) (No.T32 GM007281)supported in part by The University of Chicago Cancer Center Support Grant (No.P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through grant number 2UL1TR002389-06 that funds the Institute for Translational Medicine (ITM)supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund.
文摘Recombinant adenovirus(rAdV)is a commonly used vector system for gene transfer.Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive,possibly attributable to rAdv infection-associated oxidative stress and reactive oxygen species(ROS)production.Here,we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells,and expedites adenovirus production.By stably overexpressing GAPDH in HEK293(293G)and 293pTP(293GP)cells,respectively,we demonstrated that rAdV-induced RoS production and cell apoptosis were significantly suppressed in 293G and 293GP cells.Transfection of 293G cells with adenoviral plasmid pAd-G2Luc yielded much higher titers of Ad-G2Luc at day 7 than that in HEK293 cells.Similarly,Ad-G2Luc was amplified more efficiently in 293G than in HEK293 cells.We further showed that transfection of 293GP cells with pAd-G2Luc produced much higher titers of Ad-G2Luc at day 5 than that of 293pTP cells.293GP cells amplified the Ad-G2Luc much more efficiently than 293pTP cells,indicating that exogenous GAPDH can further augment pTP-enhanced adenovirus production.These results demonstrate that exogenous GAPDH can effectively suppress adenovirus-induced ROS and thus accelerate adenovirus production.Therefore,the engineered 293GP cells represent a superfast rAdV production system for adenovirus-based gene transfer and gene therapy.
