Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in rece...Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis.In this study,we used a murine model of lipopolysaccharide(LPS)-induced endotoxemia to assess the therapeutic potential of 6H2,a monoclonal antibody that targets A-FABP.In comparison to untreated septic mice,6H2 treatment significantly increased survival rates,decreased histopathological damage in the liver,lungs,kidneys,and heart,and reduced systemic inflammation.According to biochemical analyses,6H2 treatment decreased circulating levels of A-FABP,and this was associated with a reduction in inflammatory markers.These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis,with 6H2 demonstrating strong therapeutic efficacy.展开更多
This study investigates the role of Interleukin 17(IL-17)in exacerbating periapical lesions caused by Porphyromonas gingivalis(Pg)lipopolysaccharides(LPS)in the context of metabolic disease and its potential impact on...This study investigates the role of Interleukin 17(IL-17)in exacerbating periapical lesions caused by Porphyromonas gingivalis(Pg)lipopolysaccharides(LPS)in the context of metabolic disease and its potential impact on glucose tolerance.Researchers developed a unique mouse model where mice were monocolonized with Pg to induce periapical lesions.After 1 month,they were fed a highfat diet(HFD)for 2 months to simulate metabolic disease and oral microbiota dysbiosis.To explore the role of LPS from Pg,wildtype(WT)mice were challenged with purified LPS from Porphyromonas gingivalis,as well as with LPS-depleted and non-depleted Pg bacteria;IL-17 knockout(KO)mice were also included to assess the role of IL-17 signaling.The impact on bone lysis,periapical injury,glucose intolerance,and immune response was assessed.Results showed that in WT mice,the presence of LPS significantly worsened bone lysis,Th17 cell recruitment,and periapical injury.IL-17 KO mice exhibited reduced bone loss,glucose intolerance,and immune cell infiltration.Additionally,inflammatory markers in adipose tissue were lower in IL-17 KO mice,despite increased dysbiosis.The findings suggest that IL-17 plays a critical role in amplifying Pg-induced periapical lesions and systemic metabolic disturbances.Targeting IL-17 recruitment could offer a novel approach to improving glycemic control and reducing type 2 diabetes(T2D)risk in individuals with periapical disease.展开更多
目的:由连梅汤(LMD)对脂多糖(LPS)诱导的脓毒症小鼠回肠屏障及肝肺损伤的保护作用的研究。方法:采用随机方式,将C57/6J雄性小鼠分为对照组(CON组)、LPS模型组(LPS组)和连梅汤治疗组(LMD组),每组各6只。适应性喂养7天后,分别经口给予生...目的:由连梅汤(LMD)对脂多糖(LPS)诱导的脓毒症小鼠回肠屏障及肝肺损伤的保护作用的研究。方法:采用随机方式,将C57/6J雄性小鼠分为对照组(CON组)、LPS模型组(LPS组)和连梅汤治疗组(LMD组),每组各6只。适应性喂养7天后,分别经口给予生理盐水与治疗剂量的连梅汤(LMD) 21天。第22天,PBS注入对照组腹腔,另两组LPS注入5 mg/kg腹腔,建立脓毒症模型小鼠。腹腔注射24小时后进行回肠和肝、肺组织的收集。用HE染色组织病理鉴定;通过RT-qPCR检测回肠屏障因子水平(ZO-1, Occludin)和肝肺组织炎性因子(IL-1α, IL-8, TNF-α)。结果LPS组与CON相比,体重下降明显(n = 6;P β、IL-8、TNF-α)水平(n = 6;P Objective: The protective effect of Lianmei Decoction on the intestine was studied to the intestinal barrier, liver, and lung damage caused by lipopolysaccharide (LPS) in septic mice. Methods: C57/6J male mice were randomly assigned to the control group (CON group), LPS model group (LPS group), and Lianmei Decoction treatment group (LMD group), with 6 mice in each group. After 7 days of adaptive feeding, normal saline and a therapeutic dose of LMD were given orally for 21 days. In the 22 days of the study, PBS was injected intraperitoneally into the CON group, and 5 mg/kg LPS was administered intraperitoneally to the remaining two groups to create a sepsis mouse model. Ileum, liver, and lung tissues were gathered 24 hours after intraperitoneal injection. Histopathological examination was done using HE staining;the amounts of ileal barrier factors (ZO-1, Occludin) and inflammatory factors (IL-1β, IL-8, TNF-α) in liver and lung tissues were detected by RT-qPCR. Results: Compared with the CON group, the body weight of the LPS group decreased dramatically (n = 6;P β, IL-8, TNF-a) in liver and lung tissues (n = 6;P < 0.05), reduce the pathological damage of liver and pulmonary tissue. Conclusion: Lianmei Decoction can effectively improve ileal barrier damage, liver and lung injury, and inflammatory imbalance in LPS-induced sepsis mice.展开更多
文摘Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis.In this study,we used a murine model of lipopolysaccharide(LPS)-induced endotoxemia to assess the therapeutic potential of 6H2,a monoclonal antibody that targets A-FABP.In comparison to untreated septic mice,6H2 treatment significantly increased survival rates,decreased histopathological damage in the liver,lungs,kidneys,and heart,and reduced systemic inflammation.According to biochemical analyses,6H2 treatment decreased circulating levels of A-FABP,and this was associated with a reduction in inflammatory markers.These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis,with 6H2 demonstrating strong therapeutic efficacy.
基金supported by the Paul Calas Award from the French Society of Endodontics(SFE)。
文摘This study investigates the role of Interleukin 17(IL-17)in exacerbating periapical lesions caused by Porphyromonas gingivalis(Pg)lipopolysaccharides(LPS)in the context of metabolic disease and its potential impact on glucose tolerance.Researchers developed a unique mouse model where mice were monocolonized with Pg to induce periapical lesions.After 1 month,they were fed a highfat diet(HFD)for 2 months to simulate metabolic disease and oral microbiota dysbiosis.To explore the role of LPS from Pg,wildtype(WT)mice were challenged with purified LPS from Porphyromonas gingivalis,as well as with LPS-depleted and non-depleted Pg bacteria;IL-17 knockout(KO)mice were also included to assess the role of IL-17 signaling.The impact on bone lysis,periapical injury,glucose intolerance,and immune response was assessed.Results showed that in WT mice,the presence of LPS significantly worsened bone lysis,Th17 cell recruitment,and periapical injury.IL-17 KO mice exhibited reduced bone loss,glucose intolerance,and immune cell infiltration.Additionally,inflammatory markers in adipose tissue were lower in IL-17 KO mice,despite increased dysbiosis.The findings suggest that IL-17 plays a critical role in amplifying Pg-induced periapical lesions and systemic metabolic disturbances.Targeting IL-17 recruitment could offer a novel approach to improving glycemic control and reducing type 2 diabetes(T2D)risk in individuals with periapical disease.
文摘目的:由连梅汤(LMD)对脂多糖(LPS)诱导的脓毒症小鼠回肠屏障及肝肺损伤的保护作用的研究。方法:采用随机方式,将C57/6J雄性小鼠分为对照组(CON组)、LPS模型组(LPS组)和连梅汤治疗组(LMD组),每组各6只。适应性喂养7天后,分别经口给予生理盐水与治疗剂量的连梅汤(LMD) 21天。第22天,PBS注入对照组腹腔,另两组LPS注入5 mg/kg腹腔,建立脓毒症模型小鼠。腹腔注射24小时后进行回肠和肝、肺组织的收集。用HE染色组织病理鉴定;通过RT-qPCR检测回肠屏障因子水平(ZO-1, Occludin)和肝肺组织炎性因子(IL-1α, IL-8, TNF-α)。结果LPS组与CON相比,体重下降明显(n = 6;P β、IL-8、TNF-α)水平(n = 6;P Objective: The protective effect of Lianmei Decoction on the intestine was studied to the intestinal barrier, liver, and lung damage caused by lipopolysaccharide (LPS) in septic mice. Methods: C57/6J male mice were randomly assigned to the control group (CON group), LPS model group (LPS group), and Lianmei Decoction treatment group (LMD group), with 6 mice in each group. After 7 days of adaptive feeding, normal saline and a therapeutic dose of LMD were given orally for 21 days. In the 22 days of the study, PBS was injected intraperitoneally into the CON group, and 5 mg/kg LPS was administered intraperitoneally to the remaining two groups to create a sepsis mouse model. Ileum, liver, and lung tissues were gathered 24 hours after intraperitoneal injection. Histopathological examination was done using HE staining;the amounts of ileal barrier factors (ZO-1, Occludin) and inflammatory factors (IL-1β, IL-8, TNF-α) in liver and lung tissues were detected by RT-qPCR. Results: Compared with the CON group, the body weight of the LPS group decreased dramatically (n = 6;P β, IL-8, TNF-a) in liver and lung tissues (n = 6;P < 0.05), reduce the pathological damage of liver and pulmonary tissue. Conclusion: Lianmei Decoction can effectively improve ileal barrier damage, liver and lung injury, and inflammatory imbalance in LPS-induced sepsis mice.
