Objective:Investigate the effects of Hexokinase-3 on the proliferation,cell cycle,migration and immunologic invasion of RKO and HCT116.Methods:The expression levels of HK3 in tumor and normal colon samples were analyz...Objective:Investigate the effects of Hexokinase-3 on the proliferation,cell cycle,migration and immunologic invasion of RKO and HCT116.Methods:The expression levels of HK3 in tumor and normal colon samples were analyzed by bioinformatics.RKO and HCT116 were transfected with the control group(si-NC)and interference group HK3(si-HK3#1,si-HK3#2).CCK-8,Flow cytometry,wound healing and Transwell were used to examine the effects of interference with HK3 on the proliferation,cell cycle and migration of RKO and HCT116 cells.The expression levels of vimentin and E-cadherin,which are related to epithelial-mesenchymal transition(EMT),were detected by Western blot.Results:HK3 is associated with infiltration of multiple immune cells and co-expression with multiple immune checkpoints in colorectal cancer.Compared with the Control group(si-NC),the protein expression level of HK3 in interference group(si-HK3#1,si-HK3#2)was significantly decreased(P<0.05);the proliferation and migration of RKO and HCT116 cells were significantly inhibited(P<0.05);the cell cycle of RKO and HCT116 cells was arrested in S phase(P<0.05)and the expression of E-cadherin protein was increased,but the expression of vimentin protein was inhibited(P<0.05).Conclusion:HK3 affects the level of immunologic invasion of colon cancer.Interference with HK3 inhibits the proliferation,cell cycle and migration of colon cancer cells by inhibiting EMT behavior.展开更多
Asthma is characterized by reversible airflow obstruction, bronchial hyper-reactivity, and chronic airway remodeling (Al-Muhsen et al., 2011). Pulmonary macrophages have been implicated in asthmatic inflammation (Lee ...Asthma is characterized by reversible airflow obstruction, bronchial hyper-reactivity, and chronic airway remodeling (Al-Muhsen et al., 2011). Pulmonary macrophages have been implicated in asthmatic inflammation (Lee et al., 2015;Qian et al., 2015). The p38 mitogen-activated protein kinase (MAPK) plays an essential role in inflammation, but its role in asthma has not been determined (Kim et al., 2008). Here, our data show that macrophage-specific p38α MAPK-deficient mice displayed attenuated asthmatic inflammation in response to three allergens (dust mite, ragweed, and Aspergillus;DRA). Furthermore, we found that the protective effect was strongly associated with a reduction in the alternatively activated macrophage (AAM) polarization in vivo and in vitro. Taken together, our data indicate that p38α MAPK in macrophages contributes to AAM polarization and could be a therapeutic target for asthma.展开更多
Critical-sized bone defects caused by traumatic fractures,tumour resection and congenital malformation are unlikely to heal spontaneously.Bone tissue engineering is a promising strategy aimed at developing in vitro re...Critical-sized bone defects caused by traumatic fractures,tumour resection and congenital malformation are unlikely to heal spontaneously.Bone tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone grafts.In this study,we developed an innovative bone engineering scaffold based on gelatin methacrylate(GelMA)hydrogel,obtained via a two-step procedure:first,solid lipid nanoparticles(SLNs)were loaded with resveratrol(Res),a drug that can promote osteogenic differentiation and bone formation;these particles were then encapsulated at different concentrations(0.01%,0.02%,0.04%and 0.08%)in GelMA to obtain the final Res-SLNs/GelMA scaffolds.The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and bone regeneration in rat cranial defects were evaluated using various characterization assays.Our in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs,with the ideally slow and steady release of Res;the optimal scaffold was 0.02 Res-SLNs/GelMA.Therefore,the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility,osteoconduction and osteoinduction,thereby showing potential for application in bone tissue engineering.展开更多
基金Natural Science Foundation of Anhui Province(No.2108085MH291)512 Talents Training Program of Bengbu Medical College(No.by51201107)Postgraduate Research Innovation Program of Bengbu Medical College(No.Byycx21084)。
文摘Objective:Investigate the effects of Hexokinase-3 on the proliferation,cell cycle,migration and immunologic invasion of RKO and HCT116.Methods:The expression levels of HK3 in tumor and normal colon samples were analyzed by bioinformatics.RKO and HCT116 were transfected with the control group(si-NC)and interference group HK3(si-HK3#1,si-HK3#2).CCK-8,Flow cytometry,wound healing and Transwell were used to examine the effects of interference with HK3 on the proliferation,cell cycle and migration of RKO and HCT116 cells.The expression levels of vimentin and E-cadherin,which are related to epithelial-mesenchymal transition(EMT),were detected by Western blot.Results:HK3 is associated with infiltration of multiple immune cells and co-expression with multiple immune checkpoints in colorectal cancer.Compared with the Control group(si-NC),the protein expression level of HK3 in interference group(si-HK3#1,si-HK3#2)was significantly decreased(P<0.05);the proliferation and migration of RKO and HCT116 cells were significantly inhibited(P<0.05);the cell cycle of RKO and HCT116 cells was arrested in S phase(P<0.05)and the expression of E-cadherin protein was increased,but the expression of vimentin protein was inhibited(P<0.05).Conclusion:HK3 affects the level of immunologic invasion of colon cancer.Interference with HK3 inhibits the proliferation,cell cycle and migration of colon cancer cells by inhibiting EMT behavior.
基金The University Synergy Innovation Program of Anhui Province(GXXT-2022-064)the Natural Science Foundation of Anhui Province(2108085MH294)+3 种基金Climbing Program in General Project of Bengbu Medical College(2020bypd005)the Key Program of Anhui Educational Committee(KJ2021A0713)National Nature Science Foundation of Anhui(2108085MH286)the Program for Graduates Research of Bengbu Medical College(Byycx21002)。
文摘Asthma is characterized by reversible airflow obstruction, bronchial hyper-reactivity, and chronic airway remodeling (Al-Muhsen et al., 2011). Pulmonary macrophages have been implicated in asthmatic inflammation (Lee et al., 2015;Qian et al., 2015). The p38 mitogen-activated protein kinase (MAPK) plays an essential role in inflammation, but its role in asthma has not been determined (Kim et al., 2008). Here, our data show that macrophage-specific p38α MAPK-deficient mice displayed attenuated asthmatic inflammation in response to three allergens (dust mite, ragweed, and Aspergillus;DRA). Furthermore, we found that the protective effect was strongly associated with a reduction in the alternatively activated macrophage (AAM) polarization in vivo and in vitro. Taken together, our data indicate that p38α MAPK in macrophages contributes to AAM polarization and could be a therapeutic target for asthma.
基金supported by the Natural Science Foundation of Anhui Province(Grant No.2008085QH362)Key Program of Anhui Educational Committee(Grant No.KJ2020ZD51)+2 种基金Translational Medicine Key Projects of Bengbu Medical College(Grant Nos.BYTM2019006 and BYTM 2019012)Scientific Research Innovation Team of Bengbu Medical College(Grant No.BYKC201910)512 Talents Development Project of Bengbu Medical College(Grant Nos.by51202302 and by51202309).
文摘Critical-sized bone defects caused by traumatic fractures,tumour resection and congenital malformation are unlikely to heal spontaneously.Bone tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone grafts.In this study,we developed an innovative bone engineering scaffold based on gelatin methacrylate(GelMA)hydrogel,obtained via a two-step procedure:first,solid lipid nanoparticles(SLNs)were loaded with resveratrol(Res),a drug that can promote osteogenic differentiation and bone formation;these particles were then encapsulated at different concentrations(0.01%,0.02%,0.04%and 0.08%)in GelMA to obtain the final Res-SLNs/GelMA scaffolds.The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and bone regeneration in rat cranial defects were evaluated using various characterization assays.Our in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs,with the ideally slow and steady release of Res;the optimal scaffold was 0.02 Res-SLNs/GelMA.Therefore,the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility,osteoconduction and osteoinduction,thereby showing potential for application in bone tissue engineering.