Nootka rose (</span><i><span style="font-family:Verdana;">Rosa nutkana </span></i><span style="font-family:Verdana;">C. Presl) and stinging nettle (</span>...Nootka rose (</span><i><span style="font-family:Verdana;">Rosa nutkana </span></i><span style="font-family:Verdana;">C. Presl) and stinging nettle (</span></span><i><span style="font-family:Verdana;">Urtica dioica </span></i><span style="font-family:Verdana;">L.</span><span style="font-family:""><span style="font-family:Verdana;">) have been traditionally used in the treatment of skin infection by Indigenous peoples of Vancouver Island, British Columbia, Canada. The main objective of this study was to examine the antibacterial efficacy of extracts of Nootka </span><span style="font-family:Verdana;">rose and stinging nettle against the common pathogenic skin bacteria</span> </span><i><span style="font-family:Verdana;">Staphylococcus aureus</span></i><span style="font-family:""><span style="font-family:Verdana;">,</span><i><span style="font-family:Verdana;"> Micrococcus luteus</span></i><span style="font-family:Verdana;">, and </span><i><span style="font-family:Verdana;">Pseudomonas aeruginosa</span></i> </span><span style="font-family:Verdana;">using </span><span style="font-family:Verdana;">Indigenous science and standard methods of analysis. The Indigenous science method of plant extraction by steeping as advised by the Traditional Knowledge keeper</span><span style="font-family:Verdana;"> was performed to examine minimum inhibitory concentration </span><span style="font-family:Verdana;">(MIC) </span><span style="font-family:Verdana;">values and minimum bactericidal concentrations </span><span style="font-family:Verdana;">(MBC) by serial dilution and bacterial population counts. </span><span style="font-family:Verdana;">Soxhlet extractions and Kirby Bauer disc sensitivity testing showed that Nootka rose </span><span style="font-family:Verdana;">extracts possessed antibacterial effectiveness against all three bacterial species while stinging nettle extracts were effective against </span><i><span style="font-family:Verdana;">M. luteus</span></i><span style="font-family:""><span style="font-family:Verdana;">. Results for MIC and MBC indicated antibacterial activity against </span><i><span style="font-family:Verdana;">M. luteus</span></i><span style="font-family:Verdana;"> and </span><i><span style="font-family:Verdana;">S. aureus</span></i><span style="font-family:Verdana;"> for the </span></span><span style="font-family:Verdana;">Nootka rose when using </span><span style="font-family:""><span style="font-family:Verdana;">full-strength solutions;all three bacterial species exhibited growth when undiluted stinging nettle treatments were used. When considering bacterial population counts for</span><b> </b><i><span style="font-family:Verdana;">S. aureus,</span></i><span style="font-family:Verdana;"> results indicated</span><b> </b><span style="font-family:Verdana;">that only the Nootka rose treatment offered effective inhibition. Chemical analysis showed that alkaloid percentage was greater in the stinging nettle (0.17%) than </span></span><span style="font-family:Verdana;">Nootka rose </span><span style="font-family:Verdana;">(0.07%), while saponin percentage was greater in the </span><span style="font-family:Verdana;">Nootka rose </span><span style="font-family:Verdana;">(0.87%) than stinging nettle (0.17%). Overall, </span><span style="font-family:""><span style="font-family:Verdana;">Nootka rose showed a greater level of</span><b> </b><span style="font-family:Verdana;">antibacterial effectiveness than </span></span><span style="font-family:Verdana;">stinging nettle by Indigenous and Western scientific methods of plant extract preparation.展开更多
目的探讨益气活血化浊解毒方调控KAT3B/STING轴介导的小胶质细胞极化对缺血性脑卒中大鼠神经功能的影响。方法复制缺血性脑卒中大鼠模型。将复制成功的60只大鼠分为缺血性脑卒中组、益气活血化浊解毒方低剂量组(低剂量组)、益气活血化...目的探讨益气活血化浊解毒方调控KAT3B/STING轴介导的小胶质细胞极化对缺血性脑卒中大鼠神经功能的影响。方法复制缺血性脑卒中大鼠模型。将复制成功的60只大鼠分为缺血性脑卒中组、益气活血化浊解毒方低剂量组(低剂量组)、益气活血化浊解毒方高剂量组(高剂量组)、益气活血化浊解毒方高剂量+2,5-己酮可可碱(DMXAA)组(高剂量+DMXAA组),每组15只。另取15只正常大鼠为Sham组。低剂量组大鼠灌胃0.2 mL 27.5 g/mL的益气活血化浊解毒方药液,高剂量组大鼠灌胃0.2 mL 55.0 g/mL的益气活血化浊解毒方药液,高剂量+DMXAA组大鼠灌胃0.2 mL 55.0 g/mL的益气活血化浊解毒方药液和25 mg/kg的DMXAA,Sham组和缺血性脑卒中组给予等体积生理盐水代替药物;除高剂量+DMXAA组外,其余组大鼠再给予等体积二甲基亚砜溶液灌胃,1 d/次,连续4周。Zea-Longa评分和网屏试验评分评估大鼠神经功能和神经行为学;检测大鼠脑组织含水量;TTC染色法检测大鼠脑梗死面积;酶联免疫吸附试验检测大鼠血清LDH和NGF水平和缺血侧皮层组织TNF-α、IL-6、IL-10水平;HE染色观察大鼠缺血侧皮层组织病理变化;Western blotting检测大鼠缺血侧皮层组织iNOS、Iba1、CD68、CD40、CD206、Arg-1、Cleaved caspase-3、KAT3B、STING蛋白表达。结果缺血性脑卒中组大鼠Zea-Longa评分和网屏试验评分、脑组织含水量、脑梗死面积百分比均高于Sham组(P<0.05),低剂量组和高剂量组大鼠Zea-Longa评分和网屏试验评分、脑组织含水量、脑梗死面积百分比均低于缺血性脑卒中组(P<0.05),高剂量+DMXAA组大鼠Zea-Longa评分和网屏试验评分、脑组织含水量、脑梗死面积百分比均高于高剂量组(P<0.05)。缺血性脑卒中组大鼠NGF和IL-10水平低于Sham组,LDH、TNF-α和IL-6水平高于Sham组(P<0.05);低剂量组和高剂量组大鼠NGF和IL-10水平高于缺血性脑卒中组,LDH、TNF-α和IL-6水平低于缺血性脑卒中组(P<0.05);高剂量+DMXAA组大鼠NGF和IL-10水平低于高剂量组,LDH、TNF-α和IL-6高于高剂量组(P<0.05)。与缺血性脑卒中组比较,低剂量组和高剂量组缺血侧皮层神经元形态有明显改善。缺血性脑卒中组大鼠缺血侧皮层组织中iNOS、Iba1、CD68和CD40蛋白相对表达量比Sham组高,CD206和Arg-1蛋白相对表达量比Sham组低(P<0.05);低剂量组和高剂量组大鼠缺血侧皮层组织中iNOS、Iba1、CD68和CD40蛋白相对表达量比缺血性脑卒中组低,CD206和Arg-1蛋白相对表达量比缺血性脑卒中组高(P<0.05);高剂量+DMXAA组大鼠缺血侧皮层组织中iNOS、Iba1、CD68和CD40蛋白相对表达量比高剂量组高,CD206和Arg-1蛋白相对表达量比高剂量组低(P<0.05)。结论益气活血化浊解毒方可调节缺血性脑卒中大鼠小胶质细胞极化,减轻神经炎症和神经损伤,改善神经功能,可能与抑制KAT3B/STING轴有关。展开更多
The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically revie...The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.展开更多
The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia ...The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.展开更多
文摘Nootka rose (</span><i><span style="font-family:Verdana;">Rosa nutkana </span></i><span style="font-family:Verdana;">C. Presl) and stinging nettle (</span></span><i><span style="font-family:Verdana;">Urtica dioica </span></i><span style="font-family:Verdana;">L.</span><span style="font-family:""><span style="font-family:Verdana;">) have been traditionally used in the treatment of skin infection by Indigenous peoples of Vancouver Island, British Columbia, Canada. The main objective of this study was to examine the antibacterial efficacy of extracts of Nootka </span><span style="font-family:Verdana;">rose and stinging nettle against the common pathogenic skin bacteria</span> </span><i><span style="font-family:Verdana;">Staphylococcus aureus</span></i><span style="font-family:""><span style="font-family:Verdana;">,</span><i><span style="font-family:Verdana;"> Micrococcus luteus</span></i><span style="font-family:Verdana;">, and </span><i><span style="font-family:Verdana;">Pseudomonas aeruginosa</span></i> </span><span style="font-family:Verdana;">using </span><span style="font-family:Verdana;">Indigenous science and standard methods of analysis. The Indigenous science method of plant extraction by steeping as advised by the Traditional Knowledge keeper</span><span style="font-family:Verdana;"> was performed to examine minimum inhibitory concentration </span><span style="font-family:Verdana;">(MIC) </span><span style="font-family:Verdana;">values and minimum bactericidal concentrations </span><span style="font-family:Verdana;">(MBC) by serial dilution and bacterial population counts. </span><span style="font-family:Verdana;">Soxhlet extractions and Kirby Bauer disc sensitivity testing showed that Nootka rose </span><span style="font-family:Verdana;">extracts possessed antibacterial effectiveness against all three bacterial species while stinging nettle extracts were effective against </span><i><span style="font-family:Verdana;">M. luteus</span></i><span style="font-family:""><span style="font-family:Verdana;">. Results for MIC and MBC indicated antibacterial activity against </span><i><span style="font-family:Verdana;">M. luteus</span></i><span style="font-family:Verdana;"> and </span><i><span style="font-family:Verdana;">S. aureus</span></i><span style="font-family:Verdana;"> for the </span></span><span style="font-family:Verdana;">Nootka rose when using </span><span style="font-family:""><span style="font-family:Verdana;">full-strength solutions;all three bacterial species exhibited growth when undiluted stinging nettle treatments were used. When considering bacterial population counts for</span><b> </b><i><span style="font-family:Verdana;">S. aureus,</span></i><span style="font-family:Verdana;"> results indicated</span><b> </b><span style="font-family:Verdana;">that only the Nootka rose treatment offered effective inhibition. Chemical analysis showed that alkaloid percentage was greater in the stinging nettle (0.17%) than </span></span><span style="font-family:Verdana;">Nootka rose </span><span style="font-family:Verdana;">(0.07%), while saponin percentage was greater in the </span><span style="font-family:Verdana;">Nootka rose </span><span style="font-family:Verdana;">(0.87%) than stinging nettle (0.17%). Overall, </span><span style="font-family:""><span style="font-family:Verdana;">Nootka rose showed a greater level of</span><b> </b><span style="font-family:Verdana;">antibacterial effectiveness than </span></span><span style="font-family:Verdana;">stinging nettle by Indigenous and Western scientific methods of plant extract preparation.
文摘目的探讨益气活血化浊解毒方调控KAT3B/STING轴介导的小胶质细胞极化对缺血性脑卒中大鼠神经功能的影响。方法复制缺血性脑卒中大鼠模型。将复制成功的60只大鼠分为缺血性脑卒中组、益气活血化浊解毒方低剂量组(低剂量组)、益气活血化浊解毒方高剂量组(高剂量组)、益气活血化浊解毒方高剂量+2,5-己酮可可碱(DMXAA)组(高剂量+DMXAA组),每组15只。另取15只正常大鼠为Sham组。低剂量组大鼠灌胃0.2 mL 27.5 g/mL的益气活血化浊解毒方药液,高剂量组大鼠灌胃0.2 mL 55.0 g/mL的益气活血化浊解毒方药液,高剂量+DMXAA组大鼠灌胃0.2 mL 55.0 g/mL的益气活血化浊解毒方药液和25 mg/kg的DMXAA,Sham组和缺血性脑卒中组给予等体积生理盐水代替药物;除高剂量+DMXAA组外,其余组大鼠再给予等体积二甲基亚砜溶液灌胃,1 d/次,连续4周。Zea-Longa评分和网屏试验评分评估大鼠神经功能和神经行为学;检测大鼠脑组织含水量;TTC染色法检测大鼠脑梗死面积;酶联免疫吸附试验检测大鼠血清LDH和NGF水平和缺血侧皮层组织TNF-α、IL-6、IL-10水平;HE染色观察大鼠缺血侧皮层组织病理变化;Western blotting检测大鼠缺血侧皮层组织iNOS、Iba1、CD68、CD40、CD206、Arg-1、Cleaved caspase-3、KAT3B、STING蛋白表达。结果缺血性脑卒中组大鼠Zea-Longa评分和网屏试验评分、脑组织含水量、脑梗死面积百分比均高于Sham组(P<0.05),低剂量组和高剂量组大鼠Zea-Longa评分和网屏试验评分、脑组织含水量、脑梗死面积百分比均低于缺血性脑卒中组(P<0.05),高剂量+DMXAA组大鼠Zea-Longa评分和网屏试验评分、脑组织含水量、脑梗死面积百分比均高于高剂量组(P<0.05)。缺血性脑卒中组大鼠NGF和IL-10水平低于Sham组,LDH、TNF-α和IL-6水平高于Sham组(P<0.05);低剂量组和高剂量组大鼠NGF和IL-10水平高于缺血性脑卒中组,LDH、TNF-α和IL-6水平低于缺血性脑卒中组(P<0.05);高剂量+DMXAA组大鼠NGF和IL-10水平低于高剂量组,LDH、TNF-α和IL-6高于高剂量组(P<0.05)。与缺血性脑卒中组比较,低剂量组和高剂量组缺血侧皮层神经元形态有明显改善。缺血性脑卒中组大鼠缺血侧皮层组织中iNOS、Iba1、CD68和CD40蛋白相对表达量比Sham组高,CD206和Arg-1蛋白相对表达量比Sham组低(P<0.05);低剂量组和高剂量组大鼠缺血侧皮层组织中iNOS、Iba1、CD68和CD40蛋白相对表达量比缺血性脑卒中组低,CD206和Arg-1蛋白相对表达量比缺血性脑卒中组高(P<0.05);高剂量+DMXAA组大鼠缺血侧皮层组织中iNOS、Iba1、CD68和CD40蛋白相对表达量比高剂量组高,CD206和Arg-1蛋白相对表达量比高剂量组低(P<0.05)。结论益气活血化浊解毒方可调节缺血性脑卒中大鼠小胶质细胞极化,减轻神经炎症和神经损伤,改善神经功能,可能与抑制KAT3B/STING轴有关。
基金supported by Yuan Du Scholars,Clinical Research Center of Affiliated Hospital of Shandong Second Medical University,No.2022WYFYLCYJ02Weifang Key Laboratory,Weifang Science and Technology Development Plan Project Medical Category,No.2022YX093.
文摘The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.
基金supported by the National Natural Science Foundation of China,Nos.82071387(to HT),81971172(to YW)the Natural Science Foundation of Zhejiang Province,China,No.LY22H090012(to HT)the Basic Research Project of Wenzhou City,China,No.Y20220923(to MZ)。
文摘The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.
