BACKGROUND Burn wound management is challenging,and while mesenchymal stem cellderived exosomes show therapeutic potential,optimal delivery methods are unclear.AIM To study chitosan(CS)-αβ-glycerophosphate(CS-αβ-G...BACKGROUND Burn wound management is challenging,and while mesenchymal stem cellderived exosomes show therapeutic potential,optimal delivery methods are unclear.AIM To study chitosan(CS)-αβ-glycerophosphate(CS-αβ-GP)hydrogel crosslinked with adipose-derived stem cell exosomes(ASC-Exos)for healing deep burn injuries.METHODS Rats with deep burn injuries were divided into the CS+ASCs-Exos group,the ASCs-Exos group,the CS group,and the control group.The healing rates on days 4,7,and 14 after treatment were analyzed using ImageJ software.On day 14,the tissues were stained with hematoxylin and eosin staining,Masson’s trichrome staining,and immunohistochemical analysis to evaluate tumor necrosis factorα,interleukin-6(IL-6),IL-1α,IL-10,transforming growth factorβ,and epidermal growth factor.The mRNA levels of IL-1α,CD86,C-C motif chemokine ligand 22,and CD163 were evaluated through quantitative polymerase chain reaction.RESULTS The CS+ASC-Exos group exhibited enhanced healing,reduced lymphocyte infiltration,blood vessels,and muscle fiber distribution.Increased IL-10,transforming growth factorβ,and epidermal growth factor and decreased tumor necrosis factorα,IL-1α,and IL-6 expression were observed.Quantitative polymerase chain reaction revealed reduced IL-1αand CD86 and increased C-C motif chemokine ligand 22 and CD163 expression.Protein analysis showed downregulation of phosphorylated inhibitor of kappa Balpha and P65 in the nuclear factorκB(NF-κB)pathway.ASC-Exos crosslinked with CS-αβ-GP hydrogel demonstrates superior effects in anti-inflammation,wound healing promotion,and promotion of M1 macrophage transformation to M2 macrophage by blocking the NF-κB pathway compared to ASC-Exos alone.CONCLUSION Our research demonstrates that the ASC-Exos cross-linked CS-αβ-GP hydrogel represents an advanced therapeutic approach for treating deep burn wounds.It has anti-inflammatory effects,promotes wound healing,and facilitates the transition of M1 macrophages to M2 macrophages by blocking the NF-κB pathway.展开更多
Objective:Hepatocyte nuclear factor 4α(HNF4 A)has been demonstrated to be an oncogene in gastric cancer(GC).However,the roles of different HNF4 A isoforms derived from the 2 different promoters(P1 and P2)and the unde...Objective:Hepatocyte nuclear factor 4α(HNF4 A)has been demonstrated to be an oncogene in gastric cancer(GC).However,the roles of different HNF4 A isoforms derived from the 2 different promoters(P1 and P2)and the underlying mechanisms remain obscure.Methods:The expression and prognostic values of P1-and P2-HNF4 A were evaluated in The Cancer Genome Atlas(TCGA)databases and GC tissues.Then,functional assays of P1-and P2-HNF4 A were conducted both in vivo and in vitro.High-throughput RNA-seq was employed to profile downstream pathways in P1-and P2-HNF4 A-overexpressing GC cells.The expression and gene regulation network of the candidate target genes identified by RNA-seq were characterized based on data mining and functional assays.Results:HNF4 A amplification was a key characteristic of GC in TCGA databases,especially for the intestinal type and early stage.Moreover,P1-HNF4 A expression was significantly higher in tumor tissues than in adjacent non-tumor tissues(P<0.05),but no significant differences were found in P2-HNF4 A expression(P>0.05).High P1-HNF4 A expression indicated poor prognoses in GC patients(P<0.01).Furthermore,P1-HNF4 A overexpression significantly promoted SGC7901 and BGC823 cell proliferation,invasion and migration in vitro(P<0.01).Murine xenograft experiments showed that P1-HNF4 A overexpression promoted tumor growth(P<0.05).Mechanistically,RNA-seq showed that the cytokine-cytokine receptor interactions pathway was mostly enriched in P1-HNF4 A-overexpressing GC cells.Finally,chemokine(C-C motif)ligand 15 was identified as a direct target of P1-HNF4 A in GC tissues.Conclusions:P1-HNF4 A was the main oncogene during GC progression.The cytokine-cytokine receptor interaction pathway played a pivotal role and may be a promising therapeutic target.展开更多
基金the Incubation Program of the General Hospital of the Western Theater Command,No.2021-XZYG-C29 and No.2021-XZYG-B32.
文摘BACKGROUND Burn wound management is challenging,and while mesenchymal stem cellderived exosomes show therapeutic potential,optimal delivery methods are unclear.AIM To study chitosan(CS)-αβ-glycerophosphate(CS-αβ-GP)hydrogel crosslinked with adipose-derived stem cell exosomes(ASC-Exos)for healing deep burn injuries.METHODS Rats with deep burn injuries were divided into the CS+ASCs-Exos group,the ASCs-Exos group,the CS group,and the control group.The healing rates on days 4,7,and 14 after treatment were analyzed using ImageJ software.On day 14,the tissues were stained with hematoxylin and eosin staining,Masson’s trichrome staining,and immunohistochemical analysis to evaluate tumor necrosis factorα,interleukin-6(IL-6),IL-1α,IL-10,transforming growth factorβ,and epidermal growth factor.The mRNA levels of IL-1α,CD86,C-C motif chemokine ligand 22,and CD163 were evaluated through quantitative polymerase chain reaction.RESULTS The CS+ASC-Exos group exhibited enhanced healing,reduced lymphocyte infiltration,blood vessels,and muscle fiber distribution.Increased IL-10,transforming growth factorβ,and epidermal growth factor and decreased tumor necrosis factorα,IL-1α,and IL-6 expression were observed.Quantitative polymerase chain reaction revealed reduced IL-1αand CD86 and increased C-C motif chemokine ligand 22 and CD163 expression.Protein analysis showed downregulation of phosphorylated inhibitor of kappa Balpha and P65 in the nuclear factorκB(NF-κB)pathway.ASC-Exos crosslinked with CS-αβ-GP hydrogel demonstrates superior effects in anti-inflammation,wound healing promotion,and promotion of M1 macrophage transformation to M2 macrophage by blocking the NF-κB pathway compared to ASC-Exos alone.CONCLUSION Our research demonstrates that the ASC-Exos cross-linked CS-αβ-GP hydrogel represents an advanced therapeutic approach for treating deep burn wounds.It has anti-inflammatory effects,promotes wound healing,and facilitates the transition of M1 macrophages to M2 macrophages by blocking the NF-κB pathway.
基金supported by the National Natural Science Foundation of China(Grant No.81873554)Shaanxi Foundation for Innovation Team of Science and Technology(Grant No.2018TD-003)。
文摘Objective:Hepatocyte nuclear factor 4α(HNF4 A)has been demonstrated to be an oncogene in gastric cancer(GC).However,the roles of different HNF4 A isoforms derived from the 2 different promoters(P1 and P2)and the underlying mechanisms remain obscure.Methods:The expression and prognostic values of P1-and P2-HNF4 A were evaluated in The Cancer Genome Atlas(TCGA)databases and GC tissues.Then,functional assays of P1-and P2-HNF4 A were conducted both in vivo and in vitro.High-throughput RNA-seq was employed to profile downstream pathways in P1-and P2-HNF4 A-overexpressing GC cells.The expression and gene regulation network of the candidate target genes identified by RNA-seq were characterized based on data mining and functional assays.Results:HNF4 A amplification was a key characteristic of GC in TCGA databases,especially for the intestinal type and early stage.Moreover,P1-HNF4 A expression was significantly higher in tumor tissues than in adjacent non-tumor tissues(P<0.05),but no significant differences were found in P2-HNF4 A expression(P>0.05).High P1-HNF4 A expression indicated poor prognoses in GC patients(P<0.01).Furthermore,P1-HNF4 A overexpression significantly promoted SGC7901 and BGC823 cell proliferation,invasion and migration in vitro(P<0.01).Murine xenograft experiments showed that P1-HNF4 A overexpression promoted tumor growth(P<0.05).Mechanistically,RNA-seq showed that the cytokine-cytokine receptor interactions pathway was mostly enriched in P1-HNF4 A-overexpressing GC cells.Finally,chemokine(C-C motif)ligand 15 was identified as a direct target of P1-HNF4 A in GC tissues.Conclusions:P1-HNF4 A was the main oncogene during GC progression.The cytokine-cytokine receptor interaction pathway played a pivotal role and may be a promising therapeutic target.
