Resorption and loss of alveolar bone leads to oral dysfunction and loss of natural or implant teeth. Biomimetic delivery of growth factors based on stem cell recruitment and osteogenic differentiation, as the key step...Resorption and loss of alveolar bone leads to oral dysfunction and loss of natural or implant teeth. Biomimetic delivery of growth factors based on stem cell recruitment and osteogenic differentiation, as the key steps in natural alveolar bone regenerative process, has been an area of intense research in recent years. A mesoporous self-healing hydrogel(DFH) with basic fibroblast growth factor(bFGF) entrapment and transforming growth factor β3(TGFβ3)-loaded chitosan microspheres(CMs) was developed. The formulation was optimized by multiple tests of self-healing, in-bottle inversion, SEM, rheological, swelling rate and in vitro degradation. In vitro tubule formation assays, cell migration assays, and osteogenic differentiation assays confirmed the ability of DFH to promote blood vessels, recruit stem cells, and promote osteogenic differentiation. The optimum DFH formula is 0.05 ml 4ArmPEG-DF(20%) added to 1 ml CsGlu(2%) containing bFGF(80 ng) and TGFβ3-microspheres(5 mg). The results of in vitro release studied by Elisa kit, indicated an 95% release of b FGF in7 d and long-term sustained release of TGFβ3. For alveolar defects rat models, the expression levels of CD29 and CD45, the bone volume fraction, trabecular number, and trabecular thickness of new bone monitored by Micro-CT in DFH treatment groups were significantly higher than others(*P < 0.05, vs Model). HE and Masson staining show the same results.In conclusion, DFH is a design of bionic alveolar remodelling microenvironment, that is in early time microvessels formed by b FGF provide nutritious to recruited endogenous stem cells, then TGFβ3 slowly released speed up the process of new bones formation to common facilitate rat alveolar defect repair. The DFH with higher regenerative efficiency dovetails nicely with great demand due to the requirement of complicated biological processes.展开更多
The accumulation of advanced glycation end products(AGEs)plays a crucial role in chronic inflammation and delayed wound healing in individuals with diabetes.In this context,fibronectin has been identified as a crucial...The accumulation of advanced glycation end products(AGEs)plays a crucial role in chronic inflammation and delayed wound healing in individuals with diabetes.In this context,fibronectin has been identified as a crucial protein that promotes the differentiation of human periodontal ligament stem cells(hPDLSCs)into myofibroblasts,which play a vital role in the repair of diabetic skin ulcers.This process is intimately associated with the integrinβ1 receptor and the NF-κB signaling pathway,both crucial for cellular responses to fibronectin.To validate our hypothesis,we expressed rhFN1024,a recombinant protein containing the integrinβ1 affinity-binding domain from human fibronectin segments 12–14.This protein was used to formulate a hydrogel for hPDLSCs.rhFN1024's binding affinity to integrinβ1 was confirmed by molecular docking and the cellular thermal shift assay(CETSA).We developed sh-ITGB1-hPDLSCs with stable ITGB1 knockdown using shRNA-ITGB1 and compared their proliferation,migration and adhesion to wildtype hPDLSCs.Morphological changes were observed via SEM,andα-SMA expression levels were measured in AGEs-damaged hPDLSCs.We created full-thickness wound models in diabetic mice to assess pharmacodynamics.The study showed that rhFN1024 stimulated hPDLSCs differentiation into myofibroblasts by boosting ITGB1 expression.rhFN1024 also reduced AGEs'negative effects on hPDLSCs,as seen through SEM analysis andα-SMA levels.In full-thickness wound models,hPDLSCs and rhFN1024 accelerated re-epithelialization and collagen synthesis.rhFN1024 is proposed to interact with the ITGB1 receptor on hPDLSCs,activating the NF-κB pathway to neutralize AGEs-induced pro-inflammatory cytokines.This study suggests rhFN1024 as a potential biomedical material for tissue repair.展开更多
This study explored the developmental changes in small intestinal barrier function and the potential regulatory roles of intestinal microbiota and metabolites in different breeds of piglets during suckling and weaning...This study explored the developmental changes in small intestinal barrier function and the potential regulatory roles of intestinal microbiota and metabolites in different breeds of piglets during suckling and weaning periods.Taoyuan black(TB),Xiangcun black(XB),and Duroc(DR)piglets(10 litters per breed;half male and half female)were selected for sampling to evaluate the intestinal barrier-related indexes and intestinal microbiota and metabolites at 1,10,21(weaned),and 24(3 d after weaning)d old.The results showed that weaning led to severe shedding of small intestinal microvilli and sparse microvilli arrangement.D-lactate level in the ileum of TB and XB piglets during suckling and weaning periods was lower(P<0.01)than that of DR piglets,as well as the ileal diamine oxidase level at 1 d old.The expression level of mucin 1 was higher(P<0.05)in the ileum of TB and XB piglets than that of DR piglets,and it was the highest in the ileum of TB piglets at 21 d old.The expression levels of mucin 2 and mucin 13 were higher(P<0.10)in TB and XB piglets than those of DR piglets at 21 d old,whereas mucin2 and mucin 13 in the ileum of TB and XB piglets were higher(P<0.05)than those of DR piglets at 24 d old.TB and XB piglets had a lower relative abundance of Escherichia_Shigella at 21 and 24 d old,but they had higher Streptococcus at 1 and 24 d old than DR piglets(P<0.01).Differential metabolites between the three breeds of piglets were mainly related to oxidative phosphorylation,steroid biosynthesis,and bile acid synthesis.Collectively,these findings suggest that different pig breeds present differences in the development of the small intestinal barrier function.Compared with DR piglets,TB and XB piglets had higher intestinal permeability during the suckling period and a stronger intestinal mechanical barrier after weaning.Moreover,intestinal microbiota and metabolites are the key factors for developing small intestinal barrier functions in different breeds of piglets.展开更多
基金supported by grants from the Guangzhou Science and Technology Program Key Project(Grant No.201803010044)Guangdong Province College Characteristic Innovation Project(2019KTSCX011)+2 种基金Guangdong Province Natural Sciences Fund Project(2021A1515012480)the Key Areas Research and Development Program of Guangzhou(202103030003)Guangdong Province Special Fund Projects(Yueziranzihe,2021,No.50).
文摘Resorption and loss of alveolar bone leads to oral dysfunction and loss of natural or implant teeth. Biomimetic delivery of growth factors based on stem cell recruitment and osteogenic differentiation, as the key steps in natural alveolar bone regenerative process, has been an area of intense research in recent years. A mesoporous self-healing hydrogel(DFH) with basic fibroblast growth factor(bFGF) entrapment and transforming growth factor β3(TGFβ3)-loaded chitosan microspheres(CMs) was developed. The formulation was optimized by multiple tests of self-healing, in-bottle inversion, SEM, rheological, swelling rate and in vitro degradation. In vitro tubule formation assays, cell migration assays, and osteogenic differentiation assays confirmed the ability of DFH to promote blood vessels, recruit stem cells, and promote osteogenic differentiation. The optimum DFH formula is 0.05 ml 4ArmPEG-DF(20%) added to 1 ml CsGlu(2%) containing bFGF(80 ng) and TGFβ3-microspheres(5 mg). The results of in vitro release studied by Elisa kit, indicated an 95% release of b FGF in7 d and long-term sustained release of TGFβ3. For alveolar defects rat models, the expression levels of CD29 and CD45, the bone volume fraction, trabecular number, and trabecular thickness of new bone monitored by Micro-CT in DFH treatment groups were significantly higher than others(*P < 0.05, vs Model). HE and Masson staining show the same results.In conclusion, DFH is a design of bionic alveolar remodelling microenvironment, that is in early time microvessels formed by b FGF provide nutritious to recruited endogenous stem cells, then TGFβ3 slowly released speed up the process of new bones formation to common facilitate rat alveolar defect repair. The DFH with higher regenerative efficiency dovetails nicely with great demand due to the requirement of complicated biological processes.
基金funded by the National Key Research and Development Program of China(2022YFC2403102)Kea-Area Research and Development Program of Guangdong Province,China(2022B1111080007)Guangzhou Research and Development Plan in Key Fields,China(202103030003).
文摘The accumulation of advanced glycation end products(AGEs)plays a crucial role in chronic inflammation and delayed wound healing in individuals with diabetes.In this context,fibronectin has been identified as a crucial protein that promotes the differentiation of human periodontal ligament stem cells(hPDLSCs)into myofibroblasts,which play a vital role in the repair of diabetic skin ulcers.This process is intimately associated with the integrinβ1 receptor and the NF-κB signaling pathway,both crucial for cellular responses to fibronectin.To validate our hypothesis,we expressed rhFN1024,a recombinant protein containing the integrinβ1 affinity-binding domain from human fibronectin segments 12–14.This protein was used to formulate a hydrogel for hPDLSCs.rhFN1024's binding affinity to integrinβ1 was confirmed by molecular docking and the cellular thermal shift assay(CETSA).We developed sh-ITGB1-hPDLSCs with stable ITGB1 knockdown using shRNA-ITGB1 and compared their proliferation,migration and adhesion to wildtype hPDLSCs.Morphological changes were observed via SEM,andα-SMA expression levels were measured in AGEs-damaged hPDLSCs.We created full-thickness wound models in diabetic mice to assess pharmacodynamics.The study showed that rhFN1024 stimulated hPDLSCs differentiation into myofibroblasts by boosting ITGB1 expression.rhFN1024 also reduced AGEs'negative effects on hPDLSCs,as seen through SEM analysis andα-SMA levels.In full-thickness wound models,hPDLSCs and rhFN1024 accelerated re-epithelialization and collagen synthesis.rhFN1024 is proposed to interact with the ITGB1 receptor on hPDLSCs,activating the NF-κB pathway to neutralize AGEs-induced pro-inflammatory cytokines.This study suggests rhFN1024 as a potential biomedical material for tissue repair.
基金supported by the Key Project of Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(U20A2056)Youth Foundation of Guangxi Natural Science Foundation(2021JJB130431)+1 种基金Open Foundation of the Key Laboratory of Agro-Ecological Processes in Subtropical Region of Chinese Academy of Sciences(ISA2022105)Special Funds for Construction of Innovative Provinces in Hunan Province(2019RS3022)
文摘This study explored the developmental changes in small intestinal barrier function and the potential regulatory roles of intestinal microbiota and metabolites in different breeds of piglets during suckling and weaning periods.Taoyuan black(TB),Xiangcun black(XB),and Duroc(DR)piglets(10 litters per breed;half male and half female)were selected for sampling to evaluate the intestinal barrier-related indexes and intestinal microbiota and metabolites at 1,10,21(weaned),and 24(3 d after weaning)d old.The results showed that weaning led to severe shedding of small intestinal microvilli and sparse microvilli arrangement.D-lactate level in the ileum of TB and XB piglets during suckling and weaning periods was lower(P<0.01)than that of DR piglets,as well as the ileal diamine oxidase level at 1 d old.The expression level of mucin 1 was higher(P<0.05)in the ileum of TB and XB piglets than that of DR piglets,and it was the highest in the ileum of TB piglets at 21 d old.The expression levels of mucin 2 and mucin 13 were higher(P<0.10)in TB and XB piglets than those of DR piglets at 21 d old,whereas mucin2 and mucin 13 in the ileum of TB and XB piglets were higher(P<0.05)than those of DR piglets at 24 d old.TB and XB piglets had a lower relative abundance of Escherichia_Shigella at 21 and 24 d old,but they had higher Streptococcus at 1 and 24 d old than DR piglets(P<0.01).Differential metabolites between the three breeds of piglets were mainly related to oxidative phosphorylation,steroid biosynthesis,and bile acid synthesis.Collectively,these findings suggest that different pig breeds present differences in the development of the small intestinal barrier function.Compared with DR piglets,TB and XB piglets had higher intestinal permeability during the suckling period and a stronger intestinal mechanical barrier after weaning.Moreover,intestinal microbiota and metabolites are the key factors for developing small intestinal barrier functions in different breeds of piglets.
