·AIM: To investigate whether decellularization using different techniques can reduce immunogenicity of the cornea, and to explore the decellularized cornea as a scaffold for cultured corneal endothelial cells(CEC...·AIM: To investigate whether decellularization using different techniques can reduce immunogenicity of the cornea, and to explore the decellularized cornea as a scaffold for cultured corneal endothelial cells(CECs).Transplantation of decellularized porcine corneas increases graft transparency and survival for longer periods compared with fresh grafts.·METHODS: Six-month-old wild-type pig corneas were cut into 100-200 μm thickness, and then decellularized by three different methods: 1) 0.1% sodium dodecyl sulfate(SDS); 2) hypoxic nitrogen(N2); and 3) hypertonic NaCl. Thickness and transparency were assessed visually. Fresh and decellularized corneas were stained with hematoxylin/eosin(H&E), and for the presence of galactose-α1,3-galactose(Gal) and N-glycolylneuraminic acid(NeuGc, a nonGal antigen). Also, a human IgM/IgG binding assay was performed. Cultured porcine CECs were seeded on the surface of the decellularized cornea and examined after H&E staining.· RESULTS: All three methods of decellularization reduced the number of keratocytes in the stromal tissue by 】80% while the collagen structure remained preserved. No remaining nuclei stained positive for Gal or NeuGc, and expression of these oligosaccharides on collagen was also greatly decreased compared to expression on fresh corneas. Human IgM/IgG binding to decellularized corneal tissue was considerably reduced compared to fresh corneal tissue. The cultured CECs formed a confluent monolayer on the surface of decellularized tissue.· CONCLUSION: Though incomplete, the significant reduction in the cellular component of the decellularized cornea should be associated with a significantly reduced in vivo immune response compared to fresh corneas.展开更多
The ketogenic diet(KD)has attracted attention in recent years for its potential anticancer effects.KD is a dietary structure of high fat,moderate protein,and extremely low carbohydrate content.Originally introduced as...The ketogenic diet(KD)has attracted attention in recent years for its potential anticancer effects.KD is a dietary structure of high fat,moderate protein,and extremely low carbohydrate content.Originally introduced as a treatment for epilepsy,KD has been widely applied in weight loss programs and the management of metabolic diseases.Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells,thereby inhibiting tumor angiogenesis,reducing oxidative stress in normal cells,and affecting cancer cell signaling and other processes.Moreover,KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota,enhance the efficacy of standard cancer treatments,and mitigate the complications of chemotherapy.However,controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer.Therefore,this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.展开更多
Flaviviruses are zoonotic pathogens transmitted by infected mosquitoes and ticks,posing a persistent threat to global health.These infections lead to a diverse spectrum of diseases,broadly classified into two phenotyp...Flaviviruses are zoonotic pathogens transmitted by infected mosquitoes and ticks,posing a persistent threat to global health.These infections lead to a diverse spectrum of diseases,broadly classified into two phenotypes:systemic hemorrhagic conditions,such as dengue and yellow fever,and neurological complications,exemplified by West Nile virus(WNV)and Zika virus(ZIKV)infections.The interactions between flaviviruses and human host cells are pivotal to the viral lifecycle and the activation of host immunity.Investigating the molecular mechanisms of flavivirus-host interactions is essential for understanding viral pathogenesis,managing epidemics,optimizing therapeutic strategies,and enhancing public health security.Flaviviruses utilize various strategies to evade the host immune system,and understanding these mechanisms is critical for the development of antiviral therapeutics.This study employs bibliometric methods,leveraging CiteSpace and vOSviewer software,to analyze literature on flavivirus-host interactions and the associated immune responses.By examining developmental trends and pivotal research areas,this analysis provides insights and guidance for future studies in this field.展开更多
Over the past decade,research has increasingly identified unique dysregulations in lipid metabolism within the tumor microenvironment(TME).Lipids,diverse biomolecules,not only constitute biological membranes but also ...Over the past decade,research has increasingly identified unique dysregulations in lipid metabolism within the tumor microenvironment(TME).Lipids,diverse biomolecules,not only constitute biological membranes but also function as signaling molecules and energy sources.Enhanced synthesis or uptake of lipids in the TME significantly promotes tumorigenesis and proliferation.Moreover,lipids secreted into the TME influence tumor-resident immune cells(TRICs),thereby aiding tumor survival against chemotherapy and immunotherapy.This review aims to highlight recent advancements in under-standing lipid metabolism in both tumor cells and TRICs,with a particular emphasis on exogenous lipid uptake and endogenous lipid de novo synthesis.Targeting lipid metabolism for intervention in anticancer therapies offers a promising therapeutic avenue for cancer treatment.Nano-drug delivery systems(NDDSs)have emerged as a means to maximize anti-tumor effects by rewiring tumor metabolism.This review provides a comprehensive overview of recent literature on the development of NDDSs targeting tumor lipid metabolism,particularly in the context of tumor immunotherapy.It covers four key aspects:reprogramming lipid uptake,reprogramming lipolysis,reshaping fatty acid oxidation(FAO),and reshuf-fing lipid composition on the cell membrane.The review concludes with a discussion of future prospects and challenges in this burgeoning field of research.展开更多
基金Supported in part by NIH Grants#1RO3A 1096296-01 (HH), #IU19A1090959-01 (DKCC), #U01A 1066331 (DKCC), and #5P01 HL107152-02 (DKCC)Ocular Tissue Engineering and Regenerative Ophthalmology (OTERO) Postdoctoral Fellowship (WL)Sponsored Research Agreements Between the University of Pittsburgh and Revivicor, Blacksburg, VA
文摘·AIM: To investigate whether decellularization using different techniques can reduce immunogenicity of the cornea, and to explore the decellularized cornea as a scaffold for cultured corneal endothelial cells(CECs).Transplantation of decellularized porcine corneas increases graft transparency and survival for longer periods compared with fresh grafts.·METHODS: Six-month-old wild-type pig corneas were cut into 100-200 μm thickness, and then decellularized by three different methods: 1) 0.1% sodium dodecyl sulfate(SDS); 2) hypoxic nitrogen(N2); and 3) hypertonic NaCl. Thickness and transparency were assessed visually. Fresh and decellularized corneas were stained with hematoxylin/eosin(H&E), and for the presence of galactose-α1,3-galactose(Gal) and N-glycolylneuraminic acid(NeuGc, a nonGal antigen). Also, a human IgM/IgG binding assay was performed. Cultured porcine CECs were seeded on the surface of the decellularized cornea and examined after H&E staining.· RESULTS: All three methods of decellularization reduced the number of keratocytes in the stromal tissue by 】80% while the collagen structure remained preserved. No remaining nuclei stained positive for Gal or NeuGc, and expression of these oligosaccharides on collagen was also greatly decreased compared to expression on fresh corneas. Human IgM/IgG binding to decellularized corneal tissue was considerably reduced compared to fresh corneal tissue. The cultured CECs formed a confluent monolayer on the surface of decellularized tissue.· CONCLUSION: Though incomplete, the significant reduction in the cellular component of the decellularized cornea should be associated with a significantly reduced in vivo immune response compared to fresh corneas.
基金supported by a special program from the National Key Research and Development Program of China(2021YFA1101000,2022YFA1105200)the National Natural Science Fundation of China(92169122,82473119,32125016,T2321005,U20A201376,U20A20393,31925013)+3 种基金Excellent Youth Fund of Jiangsu Province(BK2024014)Suzhou Innovation and Entrepreneurship Leading Talent Program(ZXL2022442,ZXL2022505)Suzhou Medical College Basic Frontier Innovation Cross Project(YXY2302017,YXY2303027)the Priority Acadamic Program Development of Jiangsu Higher Education Institutions。
文摘The ketogenic diet(KD)has attracted attention in recent years for its potential anticancer effects.KD is a dietary structure of high fat,moderate protein,and extremely low carbohydrate content.Originally introduced as a treatment for epilepsy,KD has been widely applied in weight loss programs and the management of metabolic diseases.Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells,thereby inhibiting tumor angiogenesis,reducing oxidative stress in normal cells,and affecting cancer cell signaling and other processes.Moreover,KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota,enhance the efficacy of standard cancer treatments,and mitigate the complications of chemotherapy.However,controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer.Therefore,this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.
基金supported by the National Key Research and Development Plan of China(2021YFC2300200)the National Natural Science Foundation of China(32122008).
文摘Flaviviruses are zoonotic pathogens transmitted by infected mosquitoes and ticks,posing a persistent threat to global health.These infections lead to a diverse spectrum of diseases,broadly classified into two phenotypes:systemic hemorrhagic conditions,such as dengue and yellow fever,and neurological complications,exemplified by West Nile virus(WNV)and Zika virus(ZIKV)infections.The interactions between flaviviruses and human host cells are pivotal to the viral lifecycle and the activation of host immunity.Investigating the molecular mechanisms of flavivirus-host interactions is essential for understanding viral pathogenesis,managing epidemics,optimizing therapeutic strategies,and enhancing public health security.Flaviviruses utilize various strategies to evade the host immune system,and understanding these mechanisms is critical for the development of antiviral therapeutics.This study employs bibliometric methods,leveraging CiteSpace and vOSviewer software,to analyze literature on flavivirus-host interactions and the associated immune responses.By examining developmental trends and pivotal research areas,this analysis provides insights and guidance for future studies in this field.
基金National Natural Science Foundation of China(82174095,China)Natural Science Foundation of Zhejiang Province(LZ22H290001,China)Zhejiang Province Traditional Chinese Medicine Science and Technology Project(2023ZL362,China).
文摘Over the past decade,research has increasingly identified unique dysregulations in lipid metabolism within the tumor microenvironment(TME).Lipids,diverse biomolecules,not only constitute biological membranes but also function as signaling molecules and energy sources.Enhanced synthesis or uptake of lipids in the TME significantly promotes tumorigenesis and proliferation.Moreover,lipids secreted into the TME influence tumor-resident immune cells(TRICs),thereby aiding tumor survival against chemotherapy and immunotherapy.This review aims to highlight recent advancements in under-standing lipid metabolism in both tumor cells and TRICs,with a particular emphasis on exogenous lipid uptake and endogenous lipid de novo synthesis.Targeting lipid metabolism for intervention in anticancer therapies offers a promising therapeutic avenue for cancer treatment.Nano-drug delivery systems(NDDSs)have emerged as a means to maximize anti-tumor effects by rewiring tumor metabolism.This review provides a comprehensive overview of recent literature on the development of NDDSs targeting tumor lipid metabolism,particularly in the context of tumor immunotherapy.It covers four key aspects:reprogramming lipid uptake,reprogramming lipolysis,reshaping fatty acid oxidation(FAO),and reshuf-fing lipid composition on the cell membrane.The review concludes with a discussion of future prospects and challenges in this burgeoning field of research.
