目的:观察蒲公英多糖(dandelion polysaccharide,DP)对大鼠多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)肺、小肠组织炎症反应及S100钙结合蛋白A8/A9(S100 calcium-binding protein A8/A9,S100A8/A9)表达的影响。方...目的:观察蒲公英多糖(dandelion polysaccharide,DP)对大鼠多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)肺、小肠组织炎症反应及S100钙结合蛋白A8/A9(S100 calcium-binding protein A8/A9,S100A8/A9)表达的影响。方法:应用失血性休克及腹腔注射脂多糖“二次打击”的方法,构建大鼠MODS模型,分为假手术组、模型组、DP低剂量组、DP高剂量组。观察各组大鼠肺和小肠脏器系数及湿/干重比值;苏木精-伊红(hematoxylin-eosinstaining,HE)染色观察肺和小肠组织病理形态学改变;免疫组织化学染色观察肺和小肠组织白细胞介素(interleukin,IL)1β、IL-6、IL-10的表达;蛋白质免疫印迹法(Western blot)检测肺和小肠组织S100A8/A9蛋白表达变化。结果:与假手术组相比,模型组大鼠肺脏系数(5.849±0.824)、湿/干重比值(6.556±0.631)和小肠湿/干重比值(6.356±0.535)、湿重/长度比值(73.950±5.569)均上升。HE染色显示肺泡腔及肺间质可见大量炎细胞浸润,肺泡壁增厚;小肠绒毛崩解碎裂,可见炎细胞浸润及节段性集合淋巴滤泡增生。S100A8/A9主要表达于中性粒细胞和巨噬细胞,大鼠肺和小肠组织S100A8/A9、IL-1β、IL-6表达上调,IL-10表达下调。给予高剂量DP治疗后,大鼠肺脏系数(4.297±0.462)、湿/干重比值(5.313±0.495)和小肠湿/干重比值(5.398±0.388)、湿重/长度比值(59.417±2.891)均下降。肺和小肠组织病理损伤减轻,肺和小肠组织S100A8/A9、IL-1β、IL-6表达下调,IL-10表达上调。结论:DP可能通过抑制S100A8/A9的表达,减轻大鼠MODS肺和小肠组织损伤的炎症反应。展开更多
BACKGROUND SLC16A8,a lactate efflux transporter,is upregulated in various cancers,but its effects on tumor microenvironments remain understudied.This research explores its role in colorectal cancer(CRC)and the impact ...BACKGROUND SLC16A8,a lactate efflux transporter,is upregulated in various cancers,but its effects on tumor microenvironments remain understudied.This research explores its role in colorectal cancer(CRC)and the impact on the associated microenvir-onment consisting of vascular endothelial cells.AIM To explore the role in CRC and the impact on the associated microenvironment consisting of vascular endothelial cells.METHODS Hypoxic conditions prompted examination of SLC16A8 expression,glycolysis,lactate efflux,and Warburg effect correlations in CRC cell lines.Co-culture with HUVEC allowed for endothelial-mesenchymal transition(EndMT)character-ization,revealing lactate efflux's influence.Knockdown of SLC16A8 in CRC cells enabled relevant phenotype tests and tumorigenesis experiments,investigating tumor growth,blood vessel distribution,and signaling pathway alterations.RESULTS SLC16A8 expression was significantly upregulated in CRC tissues compared to adjacent normal tissues and correlated with disease progression(P<0.05).Under hypoxic conditions,HIF-1αinduced SLC16A8 expression,leading to enhanced metabolic reprogramming and increased lactate production.siRNA-mediated SLC16A8 knockdown effectively reversed hypoxia-induced changes,including reduced glucose consumption and lactate production.Co-culture experiments revealed that SLC16A8 knockdown significantly inhibited hypoxia-induced EndMT in HUVEC cells.In vivo studies demonstrated that SLC16A8 knockdown suppressed tumor growth,reduced Ki67 expression,and decreased HIF-1αlevels.Furthermore,SLC16A8 silencing led to decreased ex-pression of key metabolic enzymes PKM2 and LDHA,indicating its role in glycolytic regulation.CONCLUSION Our findings reveal that SLC16A8 functions as a critical mediator of hypoxia-induced metabolic reprogramming in CRC progression.展开更多
文摘目的:观察蒲公英多糖(dandelion polysaccharide,DP)对大鼠多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)肺、小肠组织炎症反应及S100钙结合蛋白A8/A9(S100 calcium-binding protein A8/A9,S100A8/A9)表达的影响。方法:应用失血性休克及腹腔注射脂多糖“二次打击”的方法,构建大鼠MODS模型,分为假手术组、模型组、DP低剂量组、DP高剂量组。观察各组大鼠肺和小肠脏器系数及湿/干重比值;苏木精-伊红(hematoxylin-eosinstaining,HE)染色观察肺和小肠组织病理形态学改变;免疫组织化学染色观察肺和小肠组织白细胞介素(interleukin,IL)1β、IL-6、IL-10的表达;蛋白质免疫印迹法(Western blot)检测肺和小肠组织S100A8/A9蛋白表达变化。结果:与假手术组相比,模型组大鼠肺脏系数(5.849±0.824)、湿/干重比值(6.556±0.631)和小肠湿/干重比值(6.356±0.535)、湿重/长度比值(73.950±5.569)均上升。HE染色显示肺泡腔及肺间质可见大量炎细胞浸润,肺泡壁增厚;小肠绒毛崩解碎裂,可见炎细胞浸润及节段性集合淋巴滤泡增生。S100A8/A9主要表达于中性粒细胞和巨噬细胞,大鼠肺和小肠组织S100A8/A9、IL-1β、IL-6表达上调,IL-10表达下调。给予高剂量DP治疗后,大鼠肺脏系数(4.297±0.462)、湿/干重比值(5.313±0.495)和小肠湿/干重比值(5.398±0.388)、湿重/长度比值(59.417±2.891)均下降。肺和小肠组织病理损伤减轻,肺和小肠组织S100A8/A9、IL-1β、IL-6表达下调,IL-10表达上调。结论:DP可能通过抑制S100A8/A9的表达,减轻大鼠MODS肺和小肠组织损伤的炎症反应。
基金Supported by Nanchong Science and Technology Plan Project,No.23JCYJPT0064Project of Sichuan Provincial Administration of Traditional Chinese Medicine,No.2024MS590。
文摘BACKGROUND SLC16A8,a lactate efflux transporter,is upregulated in various cancers,but its effects on tumor microenvironments remain understudied.This research explores its role in colorectal cancer(CRC)and the impact on the associated microenvir-onment consisting of vascular endothelial cells.AIM To explore the role in CRC and the impact on the associated microenvironment consisting of vascular endothelial cells.METHODS Hypoxic conditions prompted examination of SLC16A8 expression,glycolysis,lactate efflux,and Warburg effect correlations in CRC cell lines.Co-culture with HUVEC allowed for endothelial-mesenchymal transition(EndMT)character-ization,revealing lactate efflux's influence.Knockdown of SLC16A8 in CRC cells enabled relevant phenotype tests and tumorigenesis experiments,investigating tumor growth,blood vessel distribution,and signaling pathway alterations.RESULTS SLC16A8 expression was significantly upregulated in CRC tissues compared to adjacent normal tissues and correlated with disease progression(P<0.05).Under hypoxic conditions,HIF-1αinduced SLC16A8 expression,leading to enhanced metabolic reprogramming and increased lactate production.siRNA-mediated SLC16A8 knockdown effectively reversed hypoxia-induced changes,including reduced glucose consumption and lactate production.Co-culture experiments revealed that SLC16A8 knockdown significantly inhibited hypoxia-induced EndMT in HUVEC cells.In vivo studies demonstrated that SLC16A8 knockdown suppressed tumor growth,reduced Ki67 expression,and decreased HIF-1αlevels.Furthermore,SLC16A8 silencing led to decreased ex-pression of key metabolic enzymes PKM2 and LDHA,indicating its role in glycolytic regulation.CONCLUSION Our findings reveal that SLC16A8 functions as a critical mediator of hypoxia-induced metabolic reprogramming in CRC progression.
