The aim of the present article is twofold:firstly,to prove that the expression animal+young du_(3)(-a),which is basically documented in texts from the 3rd millennium BC,refers to a dam that has just given birth,and se...The aim of the present article is twofold:firstly,to prove that the expression animal+young du_(3)(-a),which is basically documented in texts from the 3rd millennium BC,refers to a dam that has just given birth,and secondly,to show the information concerning female animals and their newborns available in the texts.展开更多
Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various disea...Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.展开更多
Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we re...Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.展开更多
目的研究肝细胞肝癌(HCC)中长链非编码RNA(LncRNA)氧化应激反应丝氨酸丰富1反义RNA1(OSER1-AS1)靶向调控微小RNA(miR)-433-3p的作用及生物学意义。方法选择唐山市第九医院手术切除的HCC组织和癌旁组织,培养HCC细胞株SMMC-7721、HepG2、M...目的研究肝细胞肝癌(HCC)中长链非编码RNA(LncRNA)氧化应激反应丝氨酸丰富1反义RNA1(OSER1-AS1)靶向调控微小RNA(miR)-433-3p的作用及生物学意义。方法选择唐山市第九医院手术切除的HCC组织和癌旁组织,培养HCC细胞株SMMC-7721、HepG2、MHCC97H及正常肝细胞株HL-7702。检测LncRNA OSER1-AS1、miR-433-3p的表达水平,比较HCC组织与癌旁组织、HCC细胞株与正常肝细胞株中LncRNA OSER1-AS1、miR-433-3p表达水平的差异。对转染MHCC97H细胞进行分组,转染阴性对照(NC)-siRNA为si-NC组,转染LncRNA OSER1-AS1-siRNA为si-OSER1-AS1组,转染LncRNA OSER1-AS1-siRNA及NC miR为si-OSER1-AS1+miR-NC组,转染LncRNA OSER1-AS1-siRNA及miR-433-3p抑制物为si-OSER1-AS1+miR-433-3p抑制物组。检测细胞增殖活力、凋亡率、增殖细胞核抗原(PCNA)及裂解型caspase-3(cleaved caspase-3)的表达水平,采用双荧光素酶报告基因实验验证LncRNA OSER1-AS1靶向miR-433-3p。结果HCC组织中LncRNA OSER1-AS1的表达水平高于癌旁组织(1.77±0.34 vs1.00±0.21)、miR-433-3p的表达水平低于癌旁组织(0.65±0.09 vs 1.00±0.28)(P<0.05)且LncRNA OSER1-AS1与miR-433-3p呈负相关(r=-0.351,P<0.05);HCC细胞株中LncRNA OSER1-AS1的表达水平高于HL-7702细胞、miR-433-3p的表达水平低于HL-7702细胞(P<0.05)且MHCC97H细胞中上述变化最显著。si-OSER1-AS1组MHCC97H细胞中LncRNA OSER1-AS1、PCNA的表达水平及增殖活力低于si-NC组(0.37±0.05 vs 1.00±0.11,0.33±0.05 vs 0.92±0.12,0.51±0.09 vs 1.03±0.12),miR-433-3p、cleaved caspase-3的表达水平及凋亡率高于si-NC组(1.88±0.25 vs 1.00±0.09,0.96±0.11 vs 0.44±0.06,9.39%±1.15%vs 3.82%±0.55%)(P<0.05);si-OSER1-AS1+miR-433-3p抑制物组MHCC97H细胞中cleaved caspase-3表达水平及凋亡率低于si-OSER1-AS1+miR-NC组(0.27±0.05 vs 0.91±0.10,6.04%±0.77%vs 11.32%±1.32%),PCNA的表达水平及增殖活力高于si-OSER1-AS1+miR-NC组(0.94±0.12 vs 0.48±0.06,0.95±0.11 vs 0.34±0.05)(P<0.05)。结论LncRNA OSER1-AS1靶向miR-433-3p调控HCC细胞的增殖和凋亡。展开更多
文摘The aim of the present article is twofold:firstly,to prove that the expression animal+young du_(3)(-a),which is basically documented in texts from the 3rd millennium BC,refers to a dam that has just given birth,and secondly,to show the information concerning female animals and their newborns available in the texts.
基金supported by National Natural Science Foundation of China,No.32102745(to XL).
文摘Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.
基金supported by research funds from Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd(Grant Nos.:437b8f31,d6092dae,YHT-19064 to Chundong Yu)the National Natural Science Foundation of China(Grant Nos.:81970485,82173086 to Chundong Yu)the Natural Science Foundation of Fujian Province(Grant No.:2023J01249 to Shicong Wang).
文摘Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.
文摘目的研究肝细胞肝癌(HCC)中长链非编码RNA(LncRNA)氧化应激反应丝氨酸丰富1反义RNA1(OSER1-AS1)靶向调控微小RNA(miR)-433-3p的作用及生物学意义。方法选择唐山市第九医院手术切除的HCC组织和癌旁组织,培养HCC细胞株SMMC-7721、HepG2、MHCC97H及正常肝细胞株HL-7702。检测LncRNA OSER1-AS1、miR-433-3p的表达水平,比较HCC组织与癌旁组织、HCC细胞株与正常肝细胞株中LncRNA OSER1-AS1、miR-433-3p表达水平的差异。对转染MHCC97H细胞进行分组,转染阴性对照(NC)-siRNA为si-NC组,转染LncRNA OSER1-AS1-siRNA为si-OSER1-AS1组,转染LncRNA OSER1-AS1-siRNA及NC miR为si-OSER1-AS1+miR-NC组,转染LncRNA OSER1-AS1-siRNA及miR-433-3p抑制物为si-OSER1-AS1+miR-433-3p抑制物组。检测细胞增殖活力、凋亡率、增殖细胞核抗原(PCNA)及裂解型caspase-3(cleaved caspase-3)的表达水平,采用双荧光素酶报告基因实验验证LncRNA OSER1-AS1靶向miR-433-3p。结果HCC组织中LncRNA OSER1-AS1的表达水平高于癌旁组织(1.77±0.34 vs1.00±0.21)、miR-433-3p的表达水平低于癌旁组织(0.65±0.09 vs 1.00±0.28)(P<0.05)且LncRNA OSER1-AS1与miR-433-3p呈负相关(r=-0.351,P<0.05);HCC细胞株中LncRNA OSER1-AS1的表达水平高于HL-7702细胞、miR-433-3p的表达水平低于HL-7702细胞(P<0.05)且MHCC97H细胞中上述变化最显著。si-OSER1-AS1组MHCC97H细胞中LncRNA OSER1-AS1、PCNA的表达水平及增殖活力低于si-NC组(0.37±0.05 vs 1.00±0.11,0.33±0.05 vs 0.92±0.12,0.51±0.09 vs 1.03±0.12),miR-433-3p、cleaved caspase-3的表达水平及凋亡率高于si-NC组(1.88±0.25 vs 1.00±0.09,0.96±0.11 vs 0.44±0.06,9.39%±1.15%vs 3.82%±0.55%)(P<0.05);si-OSER1-AS1+miR-433-3p抑制物组MHCC97H细胞中cleaved caspase-3表达水平及凋亡率低于si-OSER1-AS1+miR-NC组(0.27±0.05 vs 0.91±0.10,6.04%±0.77%vs 11.32%±1.32%),PCNA的表达水平及增殖活力高于si-OSER1-AS1+miR-NC组(0.94±0.12 vs 0.48±0.06,0.95±0.11 vs 0.34±0.05)(P<0.05)。结论LncRNA OSER1-AS1靶向miR-433-3p调控HCC细胞的增殖和凋亡。
