The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on elimin...The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking(Göritz et al.,2011)or inhibiting(Dias et al.,2018)the generation of scar-forming stromal cells,as well as inducing their migratory defect(Hellal et al.,2011;Ruschel et al.,2015).展开更多
Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protei...Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protein 4(HE4),a key diagnostic biomarker for ovarian cancer,is involved in fibrotic processes in several non-malignant diseases.Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis,this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC.Methods:A total of 126 patients with gynecological conditions were included and divided into normal,benign,and EOC groups.Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features.We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers(α-smooth muscle actin(α-SMA)and fibroblast activation protein(FAP))in tumor tissues from 22 HGSOC patients.In vitro,primary fibroblasts were treated with recombinant HE4(rHE4)or conditioned media from HE4-knockdown ovarian cancer cells to assess fibroblasts activation and matrix contractility(Collagen gel contraction assays).In vivo,a subcutaneous xenograft model using HE4-knockdown cells was established to evaluate the effects of HE4 suppression on tumor growth and extensive extracellular matrix(ECM)remodeling.Results:Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups,showing positive correlation with serum HE4 levels.High-stiffness HGSOC tumors exhibited upregulated expression of HE4,α-SMA,FAP,and collagen I.rHE4 stimulated fibroblast activation and enhanced matrix contractility,whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects.In vivo,HE4-silenced xenografts displayed restricted tumor growth accompanied by reduced stromal expression ofα-SMA,FAP,and collagen I.Conclusion:Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.展开更多
Blister wounds are featured with over-generated wound exudate and extensive skin peeling,call for breathable temporary skin with effective exudate management,and function as an extracellular matrix to accelerate regen...Blister wounds are featured with over-generated wound exudate and extensive skin peeling,call for breathable temporary skin with effective exudate management,and function as an extracellular matrix to accelerate regeneration of wound skin.Traditional extracellular matrix(ECM)mimicked nanofibrous 3D scaffold and corresponding hydrogel composites suffer from poor mechanical strength,and the wound exudate management behavior is seldom studied.Herein,we proposed the strategy to enhance the mechanical properties of a 3D nanofiber scaffold via constructing a long nanofiber(NF)and sodium alginate(SA)aerogel interpenetrated architecture(NF/SA).The as-prepared scaffold was then evaluated as temporary skin for a full-thickness defect wound.After absorption of blister fluid,the aerogel transferred into a hydrogel and imparted a wet wound care environment with a water-vapor transmission rate of(6001.90±522.04)g/(m^(2)·24 h),and Young s modulus of(2.97±0.38)MPa.The exudate was continuously refreshed by a directed and dynamic pump,followed by volatilization driven by Brownian motion.Meanwhile,the NF/SA scaffold exhibited decent compatibility with blister fluid.The basic fibroblast growth factor(bFGF)-loaded NF/SA improved the wound healing rate by 36.46%on Day 3 and 15.34%on Day 7 in the full-thickness defect wound model.展开更多
文摘The fibrotic scar due to excessive deposition of extracellular matrix(ECM)after spinal cord injury(SCI)remains one of formidable challenges to axonal regeneration.Previous therapeutic strategies mainly focus on eliminating fibrotic scars by blocking(Göritz et al.,2011)or inhibiting(Dias et al.,2018)the generation of scar-forming stromal cells,as well as inducing their migratory defect(Hellal et al.,2011;Ruschel et al.,2015).
文摘Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protein 4(HE4),a key diagnostic biomarker for ovarian cancer,is involved in fibrotic processes in several non-malignant diseases.Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis,this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC.Methods:A total of 126 patients with gynecological conditions were included and divided into normal,benign,and EOC groups.Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features.We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers(α-smooth muscle actin(α-SMA)and fibroblast activation protein(FAP))in tumor tissues from 22 HGSOC patients.In vitro,primary fibroblasts were treated with recombinant HE4(rHE4)or conditioned media from HE4-knockdown ovarian cancer cells to assess fibroblasts activation and matrix contractility(Collagen gel contraction assays).In vivo,a subcutaneous xenograft model using HE4-knockdown cells was established to evaluate the effects of HE4 suppression on tumor growth and extensive extracellular matrix(ECM)remodeling.Results:Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups,showing positive correlation with serum HE4 levels.High-stiffness HGSOC tumors exhibited upregulated expression of HE4,α-SMA,FAP,and collagen I.rHE4 stimulated fibroblast activation and enhanced matrix contractility,whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects.In vivo,HE4-silenced xenografts displayed restricted tumor growth accompanied by reduced stromal expression ofα-SMA,FAP,and collagen I.Conclusion:Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.
基金Natural Science Foundation of Shanghai(General Program,22ZR1409500)China Postdoctoral Science Foundation(23M742317,GZB240446)+3 种基金Shanghai Science and Technology Innovation Action Plan(22S31905500)Medical Engineering Fund of Fudan University(yg2021-032)Fundamental Research Project of CNTAC(J202104)Program of Introducing Talents of Discipline to Universities(BP0719035)。
文摘Blister wounds are featured with over-generated wound exudate and extensive skin peeling,call for breathable temporary skin with effective exudate management,and function as an extracellular matrix to accelerate regeneration of wound skin.Traditional extracellular matrix(ECM)mimicked nanofibrous 3D scaffold and corresponding hydrogel composites suffer from poor mechanical strength,and the wound exudate management behavior is seldom studied.Herein,we proposed the strategy to enhance the mechanical properties of a 3D nanofiber scaffold via constructing a long nanofiber(NF)and sodium alginate(SA)aerogel interpenetrated architecture(NF/SA).The as-prepared scaffold was then evaluated as temporary skin for a full-thickness defect wound.After absorption of blister fluid,the aerogel transferred into a hydrogel and imparted a wet wound care environment with a water-vapor transmission rate of(6001.90±522.04)g/(m^(2)·24 h),and Young s modulus of(2.97±0.38)MPa.The exudate was continuously refreshed by a directed and dynamic pump,followed by volatilization driven by Brownian motion.Meanwhile,the NF/SA scaffold exhibited decent compatibility with blister fluid.The basic fibroblast growth factor(bFGF)-loaded NF/SA improved the wound healing rate by 36.46%on Day 3 and 15.34%on Day 7 in the full-thickness defect wound model.
