Objective To explore the role and potential mechanisms of plasma-activated solution(PAS)in alleviating dextran sulfate sodium salt(DSS)-induced ulcerative colitis.Methods We constructed a DSS-induced ulcerative colitis mouse model and evaluated the effect of PAS in vivo by observing mouse weight,calculating disease activity indexes,detecting inflammatory factors and oxidative stress indicators through ELISA.We also evaluated the effect of PAS on colon cell proliferation and migration ability through clone formation experiments,scratch experiments,and used Western blotting to determine the expression levels of proliferation-related proteins.Results PAS significantly reversed DSS-induced weight loss and increased disease activity indexes in mice(P＜0.05).The serum inflammatory cytokine levels(TNF-α,IL-6 and IL-1β)in PAS group were significantly reduced compared to those in DSS group(P＜0.05).PAS treatment could improve the imbalance of colonic redox homeostasis including changes of malondialdehyde,catalase and superoxide dismutase caused by DSS(P＜0.05).After the use of endothelial nitric oxide synthase inhibitors,changes in various indicators caused by in vivo PAS disappeared(P＜0.001).The clone formation ability of colon cells was stronger in the group treated with PAS,and the expression of proliferation-related proteins increased.Cell scratch experiments suggested that intervention with PAS could reverse the decrease in cell migration ability caused by lipopolysaccharide(P＜0.001).After the application of endothelial nitric oxide synthase inhibitors,the pro-proliferative and migratory effects of PAS disappeared(P＜0.05).Conclusion PAS alleviate DSS-induced colitis in mice and promote colonic epithelial cell repair through the eNOS pathway.

Objective To explore the application of plasma-activated solution(PAS)in the treatment of peritoneal metastasis in mice.Methods A mice model of peritoneal tumor transplantation was established,and PAS was prepared for intervention in the mice.The growth of the peritoneally transplanted tumor was assessed using in vivo imaging technology,while the apoptosis level was evaluated through flow cytometry,immunofluorescence,and Western blotting.Results At the in vitro level,there was no significant impact on tumor cell apoptosis level under adherent conditions observed when utilizing PAS(P＞0.05).Under non-adherent condition,PAS significantly augmented tumor cell apoptosis level(P＜0.05),substantially increased the proportion of deceased cells(P＜0.05),and markedly elevated intracellular total and mitochondrial reactive oxygen species levels(P＜0.05).In vivo level,using PAS following peritoneal transplanted tumor formation exhibited no noteworthy influence on peritoneal transplanted tumor growth(P＞0.05),while immediate utilization of PAS during model conducting effectively reduced abdominal tumor spread(P＜0.05).Conclusion PAS inhibits tumor peritoneal dissemination in mice by promoting tumor cell anoikis.

Objective:To analyze the changes of serum metabolites in patients with acute pancreatitis (AP) by non-targeted metabolomics method.Methods:Serum samples and clinical data of 15 AP patients hospitalized in the Affiliated Hospital of Jiangnan University from August to September 2024 were collected and included in the AP group, including 9 males and 6 females, aged (55.4±15.3) years. The serum and clinical data of 25 patients with colon polyps in the same hospital during the same period of time were collected, including 15 males and 10 females, aged (61.2±11.5) years, and were included in the control group. Serum metabolomic detection was performed using the ultra-high performance liquid chromatography tandem Fourier transform mass spectrometer. The modeling method was orthogonal partial least square discriminant analysis, and principal component analysis was performed on the data matrix to screen the differential metabolites in serum of AP patients. The Kyoto Encyclopedia database of Genes and Genomes was used to annotate differential metabolites, and the pathway of differential metabolite enrichment was analyzed by software.Results:The principal component analysis showed that the contribution ratio of the first principal component was 15.1%, the proportion of the second principal component was 10.8%, and the total proportion of the two was 25.9%. In principal component analysis, two groups of samples can be clearly distinguished and show obvious clustering characteristics. According to the analysis of OPLS-DA model, there were significant differences in serum metabolic profiles between AP group and control group. There were 683 differentially expressed metabolites between the two groups, with 367 differentially expressed metabolites up-regulated compared with the control group and 316 differentially expressed metabolites down-regulated compared with the control group. It is mainly Phosphatidic Acid (Lte4/8: 0) (+ 218%), Omeprazole Sulphone (-38%), and 2-(Propylthio) Nicotinic Acid (2-propyl thionicotinic acid) (-58%), Gein (salicyricetin) (-47%) and so on. Pathway enrichment analysis showed that the differential metabolites in AP patients were mainly concentrated in citric acid cycle, arginine biosynthesis and glycerophospholipid metabolism pathways.Conclusion:Serum metabolites in AP patients change significantly, including citric acid cycle, arginine biosynthesis, glycerophospholipid metabolism.

Objective To explore the role and potential mechanisms of plasma-activated solution(PAS)in alleviating dextran sulfate sodium salt(DSS)-induced ulcerative colitis.Methods We constructed a DSS-induced ulcerative colitis mouse model and evaluated the effect of PAS in vivo by observing mouse weight,calculating disease activity indexes,detecting inflammatory factors and oxidative stress indicators through ELISA.We also evaluated the effect of PAS on colon cell proliferation and migration ability through clone formation experiments,scratch experiments,and used Western blotting to determine the expression levels of proliferation-related proteins.Results PAS significantly reversed DSS-induced weight loss and increased disease activity indexes in mice(P＜0.05).The serum inflammatory cytokine levels(TNF-α,IL-6 and IL-1β)in PAS group were significantly reduced compared to those in DSS group(P＜0.05).PAS treatment could improve the imbalance of colonic redox homeostasis including changes of malondialdehyde,catalase and superoxide dismutase caused by DSS(P＜0.05).After the use of endothelial nitric oxide synthase inhibitors,changes in various indicators caused by in vivo PAS disappeared(P＜0.001).The clone formation ability of colon cells was stronger in the group treated with PAS,and the expression of proliferation-related proteins increased.Cell scratch experiments suggested that intervention with PAS could reverse the decrease in cell migration ability caused by lipopolysaccharide(P＜0.001).After the application of endothelial nitric oxide synthase inhibitors,the pro-proliferative and migratory effects of PAS disappeared(P＜0.05).Conclusion PAS alleviate DSS-induced colitis in mice and promote colonic epithelial cell repair through the eNOS pathway.

Objective To explore the application of plasma-activated solution(PAS)in the treatment of peritoneal metastasis in mice.Methods A mice model of peritoneal tumor transplantation was established,and PAS was prepared for intervention in the mice.The growth of the peritoneally transplanted tumor was assessed using in vivo imaging technology,while the apoptosis level was evaluated through flow cytometry,immunofluorescence,and Western blotting.Results At the in vitro level,there was no significant impact on tumor cell apoptosis level under adherent conditions observed when utilizing PAS(P＞0.05).Under non-adherent condition,PAS significantly augmented tumor cell apoptosis level(P＜0.05),substantially increased the proportion of deceased cells(P＜0.05),and markedly elevated intracellular total and mitochondrial reactive oxygen species levels(P＜0.05).In vivo level,using PAS following peritoneal transplanted tumor formation exhibited no noteworthy influence on peritoneal transplanted tumor growth(P＞0.05),while immediate utilization of PAS during model conducting effectively reduced abdominal tumor spread(P＜0.05).Conclusion PAS inhibits tumor peritoneal dissemination in mice by promoting tumor cell anoikis.

Objective:To analyze the changes of serum metabolites in patients with acute pancreatitis (AP) by non-targeted metabolomics method.Methods:Serum samples and clinical data of 15 AP patients hospitalized in the Affiliated Hospital of Jiangnan University from August to September 2024 were collected and included in the AP group, including 9 males and 6 females, aged (55.4±15.3) years. The serum and clinical data of 25 patients with colon polyps in the same hospital during the same period of time were collected, including 15 males and 10 females, aged (61.2±11.5) years, and were included in the control group. Serum metabolomic detection was performed using the ultra-high performance liquid chromatography tandem Fourier transform mass spectrometer. The modeling method was orthogonal partial least square discriminant analysis, and principal component analysis was performed on the data matrix to screen the differential metabolites in serum of AP patients. The Kyoto Encyclopedia database of Genes and Genomes was used to annotate differential metabolites, and the pathway of differential metabolite enrichment was analyzed by software.Results:The principal component analysis showed that the contribution ratio of the first principal component was 15.1%, the proportion of the second principal component was 10.8%, and the total proportion of the two was 25.9%. In principal component analysis, two groups of samples can be clearly distinguished and show obvious clustering characteristics. According to the analysis of OPLS-DA model, there were significant differences in serum metabolic profiles between AP group and control group. There were 683 differentially expressed metabolites between the two groups, with 367 differentially expressed metabolites up-regulated compared with the control group and 316 differentially expressed metabolites down-regulated compared with the control group. It is mainly Phosphatidic Acid (Lte4/8: 0) (+ 218%), Omeprazole Sulphone (-38%), and 2-(Propylthio) Nicotinic Acid (2-propyl thionicotinic acid) (-58%), Gein (salicyricetin) (-47%) and so on. Pathway enrichment analysis showed that the differential metabolites in AP patients were mainly concentrated in citric acid cycle, arginine biosynthesis and glycerophospholipid metabolism pathways.Conclusion:Serum metabolites in AP patients change significantly, including citric acid cycle, arginine biosynthesis, glycerophospholipid metabolism.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.