[目的]探讨核转录因子(NF-kappa B p65)和血管内皮生成因子(VEGF)在晚期原发性肝癌(HCC)组织和正常肝脏组织中的表达及其意义。[方法]采用免疫组织化学染色SP法检测65例晚期HCC组织切片(其中36例直径≥5cm,16例5cm>直径>2cm,13例...[目的]探讨核转录因子(NF-kappa B p65)和血管内皮生成因子(VEGF)在晚期原发性肝癌(HCC)组织和正常肝脏组织中的表达及其意义。[方法]采用免疫组织化学染色SP法检测65例晚期HCC组织切片(其中36例直径≥5cm,16例5cm>直径>2cm,13例直径≤2cm;28例肝内病灶数目大于1个,37例肝内病灶数目为1个)和30例正常肝脏组织(对照组)中NF-kappa B p65和VEGF抗体的表达水平,采用秩和检验方法分析其差异性,并再以直线相关方法分析NF-kappa B p65和VEGF在HCC中表达的相关性。[结果]各肿瘤组随肿瘤直径的增大,NF-kappa B p65和VEGF表达水平均出现递增的趋势。肝内(肿瘤数目>1个)NF-kappa B p65和VEGF表达水平强于肝内无转移组(P<0.05)。NF-kappa B p65和VEGF在HCC中表达呈正相关。[结论]VEGF有促进肝癌生长和侵袭转移作用,而NF-kappaBp65在HCC生长中有促进VEGF表达上调的作用。展开更多
BACKGROUND: Toll-like receptors (TLRs) are a family of type 1 transmembrane receptors, which can recognize different pathogen-associated molecular patterns. Among them, TLR-4 is specific to lipopolysaccharide. It tran...BACKGROUND: Toll-like receptors (TLRs) are a family of type 1 transmembrane receptors, which can recognize different pathogen-associated molecular patterns. Among them, TLR-4 is specific to lipopolysaccharide. It transfers the infection signal into the cell and promotes the translocation of nuclear factor kappa B (NF-kappa B) to the nucleus and the subsequent transcriptional activation of genes encoding pro- and anti-inflammatory cytokines and chemokines. Acute cholangitis (AC) is a common biliary tract infection in oriental countries, and often leads to liver injury. The activation of TLR-4 and its significance in liver injury in rats with AC remain unclear. METHODS: Rat models of AC (biliary tract obstruction+E. coli injection, n=36) and control models (biliary tract obstruction+saline, n=18) were made. Liver tissue injury was investigated by pathological examination. The levels of serum TNF-alpha and IL-10 were measured by enzyme-linked immunosorbent assay, and the expressions of TLR-4, NF-kappa B mRNAs and proteins in the liver were detected by RT-PCR, immunohistochemical staining and Western blotting, respectively. RESULTS: Severe liver tissue injury in rats with AC was evident as shown by pathological examination. TLR-4 and NF-kappa B were strongly expressed in the cytoplasm of hepatocytes in the AC group. They were negative or slightly positive in the control group. TLR-4 mRNA and protein in the liver of rats with AC increased 1 hour after biliary tract ligation and E. coli injection, and peaked at 6 hours after surgery. Twenty-four hours later, they began to decrease. The expression of TLR-4 was paralleled by that of NF-kappa B in the liver and TNF-alpha in serum. CONCLUSION: The higher expression of TLR-4 in the liver of rats with AC may be involved in liver injury through the activation of NF-kappa B and release of cytokines such as TNF-alpha.展开更多
BACKGROUND: Biliary atresia, the etiology of which still remains unclear, occurs exclusively in newborns and most are infected with rotavirus. In this study, we aimed to investigate the histopathological patterns of d...BACKGROUND: Biliary atresia, the etiology of which still remains unclear, occurs exclusively in newborns and most are infected with rotavirus. In this study, we aimed to investigate the histopathological patterns of different kinds of rotavirus in the liver and biliary tract of neonatal mice and the expression of NF-kappa B in the liver and biliary tract of infected mice. METHODS: Twenty-three adult mice (8 were male and 15 female) were divided into 8 breeding pairs, and each pair (I male and 2 females) was housed in a cage in a laminar flow hood. Newborn mice, 24-48 hours old were randomly divided into A, B and C groups. The A and B groups were respectively inoculated with MMU18006 and SA11 rotavirus through the intraperitoneal route, while group C as blank control was only inoculated with culture medium. The liver was dissected after 5, 10, 15, 21 and 28 days; the weight of each mouse and the histopathological patterns in the liver were recorded. The expression of NF-kappa B in the liver and intrahepatic bile ducts was detected by immunohistochemical staining and the expression intensity was analyzed with a GT-2 imaging instrument. RESULTS: The average increase in weight of infected mice was significantly slower than that of the normal control, while the growth rate of group A (injected with MMU18006 rotavirus) was slower than that of group B (SA11 rotavirus). In infected mice, the acute and chronic inflammation of liver and intra- and extra-hepatic bile ducts was more significant in group A. Stenosis was found in most intrahepatic bile ducts, and sporadically in extrahepatic bile ducts. The expression of NF-kappa B in infected mice was dramatically higher than that of the normal control, while the expression in group A was higher than in group B. CONCLUSIONS: Significant damage to the liver and biliary tract of neonatal mice can be induced by inoculating MMU18006 rotavirus through the intraperitoneal route, which is very similar to the pathology of biliary atresia in the newborn human. Similar inoculation with SA11 rotavirus can only result in moderate impairment that disappears quickly. The difference of pathogenicity between the two rotaviruses may depend on their differing capacities to increase the expression of NF-kappa B in the liver and biliary tract.展开更多
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and nuclear factor kappa B (NF-kappa B) play important roles in liver fibrosis. This study aimed to investigate the effects of Dan-shao-hua-xia...BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and nuclear factor kappa B (NF-kappa B) play important roles in liver fibrosis. This study aimed to investigate the effects of Dan-shao-hua-xian, a preparation of traditional Chinese medicine, on the expression of PPAR-gamma and NF-kappa B in the fibrotic livers of rats. METHODS: Seventy Wistar rats were randomly divided into 4 groups: treatment (model, 8 weeks+treatment, 8 weeks; group A), natural recovery (model, 8 weeks+ saline, 8 weeks; group B), model (model only, 8 weeks; group Q, and control (normal, untreated, 16 weeks; group D). Each group consisted of 20 rats (except for group D, which had 10). Fibrotic liver models were induced in rats by subcutaneous injection of CCI4, oral administration of alcohol and a high-lipid/low-protein diet for 8 weeks. After the models were established, the rats in group A were orally given Dan-shao-hua-xian capsules daily for another 8 weeks. Then, the liver indices serum hyaluronic acid (HA), tumor necrosis factor-alpha (TNF-alpha) and alanine aminotransferase (ALT) were measured. The degree of hepatic fibrosis was evaluated by optical microscopy. Hydroxyproline (Hyp) in the liver tissue was determined. The expression of PPAR-gamma was detected by immunohistochemical techniques. The protein levels of PPAR-gamma and NF-kappa B were determined by Western blotting. RESULTS: The concentrations of serum HA, TNF-alpha and Hyp in group C increased compared with group D (P<0.05), and they decreased in group A compared with group C (P<0.05). The expression of PPAR-gamma in group C decreased compared with group D (P<0.05), and it increased in group A compared with groups B and C (P<0.05). Similarly, Western blotting showed that the expression of PPAR-gamma in group C decreased compared with group D, and it increased in group A compared with group C. The expression of NF-kappa B increased in group C compared with group D (P<0.05), and it decreased in group A compared with group C (P<0.05). CONCLUSION: Dan-shao-hua-xian capsules enhance the expression of PPAR-gamma but decrease that of TNF-alpha and NF-kappa B in the liver tissues of CCI4-induced hepatic fibrotic rats. These effects may play a role in its activity in treating hepatic fibrosis.展开更多
OBJECTIVE To study the expression of the nuclear factor kappa B (NF-kappa B) in non-small cell lung cancer (NSCLC),to explore the apoptotic ratio in NSCLC related to different NF-kappa Bs,and to understand the clinica...OBJECTIVE To study the expression of the nuclear factor kappa B (NF-kappa B) in non-small cell lung cancer (NSCLC),to explore the apoptotic ratio in NSCLC related to different NF-kappa Bs,and to understand the clinical significance of NF-kappa B in NSCLC apoptosis. METHODS NF-kappa B expression in 45 new samples of NSCLC,collected during a period from October to December,2005,was assayed using Western blots,and the apoptotic ratio of NSCLC was determined by the Tunel method. RESULTS Of the 45 patients,the average relative expression of NF-kappa B was 0.6047±0.3572.The expression of NF-kappa B was higher in the poorly differentiated lung cancer cells than in the well-differentiated tumors(P<0.05).The apoptotic ratio was 56.4% in the lung cancer cells with higher NF-kappa B expression,and was 76.7% in those with lower NF-kappa B expression(P<0.05). CONCLUSION The expression of NF-kappa B is correlated with the differentiation of NSCLC.NF-kappa B inhibits apoptosis in NSCLC.As a transcription factor,NF-kappa B plays a very important role both in formation and in development of NSCLC. NF-kappa B might serve as a target for NSCLC gene therapy.展开更多
Objective:To investigate the effects of ivabradine on Notch and NF-kappa B signaling pathway in myocardial cells of rats with myocardial infarction.Methods: The model of myocardial infarction was established by ligati...Objective:To investigate the effects of ivabradine on Notch and NF-kappa B signaling pathway in myocardial cells of rats with myocardial infarction.Methods: The model of myocardial infarction was established by ligating the left anterior descending coronary artery. The surviving rats were randomly divided into model group (MI group,n=8) and treatment group (IVA group,n=8). Rats with the same location but without ligation of the left anterior descending coronary artery were used as control group (CON group,n = 8). IVA was administered for 28 d. Hemodynamic and cardiac function indexes of all rats were measured: heart rate (HR), systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximum rate of increase and decrease of left ventricular internal pressure (+dp/dt);left ventricular mass index, left ventricular cross-sectional diameter and infarct area;The expression of Notch signaling pathway components mRNA (Notch-1, Dll-4, Hes-1) in rat cardiomyocytes was detected by PT-PCR, and the expression of DICD-1 and P65 protein was detected by western-blot. One-way ANOVA was used for comparison between groups, and SNK was used for comparison between groups.Results: SBP, DBP, MAP, LASP, LVEDP and (+dp/dt) in MI group were lower than those in control group (P<0.05), while IVA was higher than those in MI group (P<0.05). Left ventricular mass index and left ventricular sectional diameter in MI group were significantly higher than those in control group (P<0.05), but lower than those in IVA group (P<0.05). The expression of Notch-1 in MI group was significantly higher than that in control group (P<0.05), but lower than that in IVA group (P<0.05). There was no significant difference in the expression of Dll-4 and Hes-1 mRNA between the three groups (P>0.05). The expression levels of NICD-1 and P 65 in MI group were significantly higher than those in CON group (P<0.05), but lower than those in IVA group (P<0.05). Conclusion: IVA may improve cardiac function and inhibit ventricular remodeling in rats with myocardial infarction through Notch and NF-kappa B signaling pathways.展开更多
OBJECTIVE:To investigate the therapeutic effect of Weimishu prescription(胃糜舒方,WMSP)on chronic gastritis with liver-stomach disharmony(CG-LSD)and elucidate its molecular mechanisms involved in regulating the nuclea...OBJECTIVE:To investigate the therapeutic effect of Weimishu prescription(胃糜舒方,WMSP)on chronic gastritis with liver-stomach disharmony(CG-LSD)and elucidate its molecular mechanisms involved in regulating the nuclear factor kappa-B(NF-κB)inflammatory response and gastric stem cell(GSC)differentiation.METHODS:A CG-LSD rat model was established through a combined protocol involving 56%ethanol and tail-clip stimulation.Rats were administered with low-,medium-,or high-dose WMSP,the positive control drug omeprazole,or high-dose WMSP with the NF-κB agonist phorbol 12-myristate 13-acetate(PMA).Histopathological changes were assessed via hematoxylin and eosin and Td T-mediated d UTP nick end labeling staining.Flow cytometry,immunofluorescence,real-time quantitative polymerase chain reaction,Western blotting,and enzyme-linked immunosorbent assay were performed to evaluate the underlying mechanisms.RESULTS:WMSP significantly increased rat locomotor activity,improved Traditional Chinese Medicine syndrome scores,and ameliorated pathological damage to the gastric mucosa while reducing gastric mucosal epithelial cells apoptosis.WMSP also increased the proportion of Lgr5+Ki67+cells;upregulated muscle,intestine,and stomach specific transcript 1,sex determining region Y-box 2,sex determining region Y-box 9,and homing cell adhesion molecule;and enhanced the levels of pepsinogen C,somatostatin,mucin-6,H+-K+ATPase,and E-cadherin proteins,thereby promoting gastric stem cell survival and differentiation.Furthermore,WMSP alleviated systemic and gastric mucosal inflammation in CG-LSD rats.Mechanistically,WMSP suppressed NF-κB expression,thereby reducing Smadspecific E3 ubiquitin ligase 2 levels,which enhancedβ-catenin and subsequently increased myelocytomatosis oncogene,and axis inhibition protein 2 expression.PMA administration reversed the protective effect of WMSP on CG-LSD rats.CONCLUSIONS:WMSP ameliorated gastric mucosal injury in CG-LSD rats by regulating the NF-κB/β-catenin signaling pathway,thereby suppressing inflammation and promoting gastric stem cell differentiation.These findings highlight the therapeutic potential of WMSP,providing the foundation for further clinical evaluations of WMSP in CGLSD treatment.展开更多
OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with e...OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with experimental validation,focusing on the modulation of inflammatory signaling.METHODS:A chronic UC model was induced in C57BL/6 mice by cyclical administration of DSS.Mice were treated with either a low(15 m L/kg)or high(30 m L/kg)dose of PD.Disease severity was assessed clinically and via histopathology.Serum levels of inflammatory cytokines were quantified.A network pharmacology approach was employed to predict the core targets and pathways of PD against UC.Key predictions concerning the toll-like receptor 4/nuclear factor-kappa B(TLR4/NF-κB)pathway were subsequently verified in colonic tissue using quantitative polymerase chain reaction and Western blotting.RESULTS:PD treatment significantly ameliorated DSSinduced UC symptoms,including reducing disease activity,preventing colon shortening,and improving histological architecture.PD effectively rebalanced the systemic inflammatory milieu by decreasing proinflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)and elevating anti-inflammatory cytokines interleukin-10(IL-10).Network pharmacology analysis identified the TLR4/NF-κB signaling pathway as a central target.Experimental validation confirmed that PD markedly suppressed the upregulation of both TLR4 and NF-κB at the transcriptional and protein levels in the inflamed colon.CONCLUSION:PD demonstrates protective effects against experimental UC.Its mechanism is associated with the inhibition of the TLR4/NF-κB signaling pathway and the subsequent attenuation of inflammatory responses.This study provides a modern pharmacological basis for the classical application of PD in treating heat-toxin related intestinal disorders,bridging traditional use and mechanistic understanding.展开更多
OBJECTIVE:To elucidate the anti-inflammatory mechanisms of modified Shoutai pills(改良寿胎丸,MSTP)in miscarriages,we performed transcriptome sequencing on the decidua and placental tissues of pregnancy mice.METHODS:Th...OBJECTIVE:To elucidate the anti-inflammatory mechanisms of modified Shoutai pills(改良寿胎丸,MSTP)in miscarriages,we performed transcriptome sequencing on the decidua and placental tissues of pregnancy mice.METHODS:The therapeutic effects and antiinflammatory mechanisms of MSTP were studied in mice with lipopolysaccharide(LPS)-induced miscarriage.First,the effects of MSTP on pregnancy outcomes and the maternal-fetal interface,in LPS-induced miscarriage mice were examined.RNA sequencing was used to further investigate gene expression changes in LPS-induced miscarriage mice and to assess the effects of MSTP intervention.Finally,the expression levels of inflammation-related genes in the decidua and placental tissues were determined using quantitative real-time polymerase chain reaction(q RT-PCR).RESULTS:A high dose of MSTP significantly decreased the resorption rate(P<0.05)and reduced apoptosis of the decidua and placental tissues in mice.Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that inflammatory and immune-related signals were enriched.q RT-PCR results confirmed that in decidual and placental tissues,MSTP reduced the gene expression levels of toll-like receptor 4(TLR4),nuclear factor kappa-B(NF-κB),c-Jun N-terminal kinase 1,p38,and tumor necrosis factor-α.CONCLUSIONS:In this study,we demonstrated that MSTP effectively prevented embryo loss with an antiinflammatory mechanism through downregulation of the TLR4-NF-κB/MAPK signaling pathway,in LPS-induced miscarriage mice model.To our knowledge,this is the first study to reveal the therapeutic mechanism of MSTP in LPS-induced miscarriage in mice.展开更多
文摘[目的]探讨核转录因子(NF-kappa B p65)和血管内皮生成因子(VEGF)在晚期原发性肝癌(HCC)组织和正常肝脏组织中的表达及其意义。[方法]采用免疫组织化学染色SP法检测65例晚期HCC组织切片(其中36例直径≥5cm,16例5cm>直径>2cm,13例直径≤2cm;28例肝内病灶数目大于1个,37例肝内病灶数目为1个)和30例正常肝脏组织(对照组)中NF-kappa B p65和VEGF抗体的表达水平,采用秩和检验方法分析其差异性,并再以直线相关方法分析NF-kappa B p65和VEGF在HCC中表达的相关性。[结果]各肿瘤组随肿瘤直径的增大,NF-kappa B p65和VEGF表达水平均出现递增的趋势。肝内(肿瘤数目>1个)NF-kappa B p65和VEGF表达水平强于肝内无转移组(P<0.05)。NF-kappa B p65和VEGF在HCC中表达呈正相关。[结论]VEGF有促进肝癌生长和侵袭转移作用,而NF-kappaBp65在HCC生长中有促进VEGF表达上调的作用。
文摘BACKGROUND: Toll-like receptors (TLRs) are a family of type 1 transmembrane receptors, which can recognize different pathogen-associated molecular patterns. Among them, TLR-4 is specific to lipopolysaccharide. It transfers the infection signal into the cell and promotes the translocation of nuclear factor kappa B (NF-kappa B) to the nucleus and the subsequent transcriptional activation of genes encoding pro- and anti-inflammatory cytokines and chemokines. Acute cholangitis (AC) is a common biliary tract infection in oriental countries, and often leads to liver injury. The activation of TLR-4 and its significance in liver injury in rats with AC remain unclear. METHODS: Rat models of AC (biliary tract obstruction+E. coli injection, n=36) and control models (biliary tract obstruction+saline, n=18) were made. Liver tissue injury was investigated by pathological examination. The levels of serum TNF-alpha and IL-10 were measured by enzyme-linked immunosorbent assay, and the expressions of TLR-4, NF-kappa B mRNAs and proteins in the liver were detected by RT-PCR, immunohistochemical staining and Western blotting, respectively. RESULTS: Severe liver tissue injury in rats with AC was evident as shown by pathological examination. TLR-4 and NF-kappa B were strongly expressed in the cytoplasm of hepatocytes in the AC group. They were negative or slightly positive in the control group. TLR-4 mRNA and protein in the liver of rats with AC increased 1 hour after biliary tract ligation and E. coli injection, and peaked at 6 hours after surgery. Twenty-four hours later, they began to decrease. The expression of TLR-4 was paralleled by that of NF-kappa B in the liver and TNF-alpha in serum. CONCLUSION: The higher expression of TLR-4 in the liver of rats with AC may be involved in liver injury through the activation of NF-kappa B and release of cytokines such as TNF-alpha.
文摘BACKGROUND: Biliary atresia, the etiology of which still remains unclear, occurs exclusively in newborns and most are infected with rotavirus. In this study, we aimed to investigate the histopathological patterns of different kinds of rotavirus in the liver and biliary tract of neonatal mice and the expression of NF-kappa B in the liver and biliary tract of infected mice. METHODS: Twenty-three adult mice (8 were male and 15 female) were divided into 8 breeding pairs, and each pair (I male and 2 females) was housed in a cage in a laminar flow hood. Newborn mice, 24-48 hours old were randomly divided into A, B and C groups. The A and B groups were respectively inoculated with MMU18006 and SA11 rotavirus through the intraperitoneal route, while group C as blank control was only inoculated with culture medium. The liver was dissected after 5, 10, 15, 21 and 28 days; the weight of each mouse and the histopathological patterns in the liver were recorded. The expression of NF-kappa B in the liver and intrahepatic bile ducts was detected by immunohistochemical staining and the expression intensity was analyzed with a GT-2 imaging instrument. RESULTS: The average increase in weight of infected mice was significantly slower than that of the normal control, while the growth rate of group A (injected with MMU18006 rotavirus) was slower than that of group B (SA11 rotavirus). In infected mice, the acute and chronic inflammation of liver and intra- and extra-hepatic bile ducts was more significant in group A. Stenosis was found in most intrahepatic bile ducts, and sporadically in extrahepatic bile ducts. The expression of NF-kappa B in infected mice was dramatically higher than that of the normal control, while the expression in group A was higher than in group B. CONCLUSIONS: Significant damage to the liver and biliary tract of neonatal mice can be induced by inoculating MMU18006 rotavirus through the intraperitoneal route, which is very similar to the pathology of biliary atresia in the newborn human. Similar inoculation with SA11 rotavirus can only result in moderate impairment that disappears quickly. The difference of pathogenicity between the two rotaviruses may depend on their differing capacities to increase the expression of NF-kappa B in the liver and biliary tract.
文摘BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) and nuclear factor kappa B (NF-kappa B) play important roles in liver fibrosis. This study aimed to investigate the effects of Dan-shao-hua-xian, a preparation of traditional Chinese medicine, on the expression of PPAR-gamma and NF-kappa B in the fibrotic livers of rats. METHODS: Seventy Wistar rats were randomly divided into 4 groups: treatment (model, 8 weeks+treatment, 8 weeks; group A), natural recovery (model, 8 weeks+ saline, 8 weeks; group B), model (model only, 8 weeks; group Q, and control (normal, untreated, 16 weeks; group D). Each group consisted of 20 rats (except for group D, which had 10). Fibrotic liver models were induced in rats by subcutaneous injection of CCI4, oral administration of alcohol and a high-lipid/low-protein diet for 8 weeks. After the models were established, the rats in group A were orally given Dan-shao-hua-xian capsules daily for another 8 weeks. Then, the liver indices serum hyaluronic acid (HA), tumor necrosis factor-alpha (TNF-alpha) and alanine aminotransferase (ALT) were measured. The degree of hepatic fibrosis was evaluated by optical microscopy. Hydroxyproline (Hyp) in the liver tissue was determined. The expression of PPAR-gamma was detected by immunohistochemical techniques. The protein levels of PPAR-gamma and NF-kappa B were determined by Western blotting. RESULTS: The concentrations of serum HA, TNF-alpha and Hyp in group C increased compared with group D (P<0.05), and they decreased in group A compared with group C (P<0.05). The expression of PPAR-gamma in group C decreased compared with group D (P<0.05), and it increased in group A compared with groups B and C (P<0.05). Similarly, Western blotting showed that the expression of PPAR-gamma in group C decreased compared with group D, and it increased in group A compared with group C. The expression of NF-kappa B increased in group C compared with group D (P<0.05), and it decreased in group A compared with group C (P<0.05). CONCLUSION: Dan-shao-hua-xian capsules enhance the expression of PPAR-gamma but decrease that of TNF-alpha and NF-kappa B in the liver tissues of CCI4-induced hepatic fibrotic rats. These effects may play a role in its activity in treating hepatic fibrosis.
基金a grant from Educational Commission of Heilongjiang Province,China (No.115113049)
文摘OBJECTIVE To study the expression of the nuclear factor kappa B (NF-kappa B) in non-small cell lung cancer (NSCLC),to explore the apoptotic ratio in NSCLC related to different NF-kappa Bs,and to understand the clinical significance of NF-kappa B in NSCLC apoptosis. METHODS NF-kappa B expression in 45 new samples of NSCLC,collected during a period from October to December,2005,was assayed using Western blots,and the apoptotic ratio of NSCLC was determined by the Tunel method. RESULTS Of the 45 patients,the average relative expression of NF-kappa B was 0.6047±0.3572.The expression of NF-kappa B was higher in the poorly differentiated lung cancer cells than in the well-differentiated tumors(P<0.05).The apoptotic ratio was 56.4% in the lung cancer cells with higher NF-kappa B expression,and was 76.7% in those with lower NF-kappa B expression(P<0.05). CONCLUSION The expression of NF-kappa B is correlated with the differentiation of NSCLC.NF-kappa B inhibits apoptosis in NSCLC.As a transcription factor,NF-kappa B plays a very important role both in formation and in development of NSCLC. NF-kappa B might serve as a target for NSCLC gene therapy.
文摘Objective:To investigate the effects of ivabradine on Notch and NF-kappa B signaling pathway in myocardial cells of rats with myocardial infarction.Methods: The model of myocardial infarction was established by ligating the left anterior descending coronary artery. The surviving rats were randomly divided into model group (MI group,n=8) and treatment group (IVA group,n=8). Rats with the same location but without ligation of the left anterior descending coronary artery were used as control group (CON group,n = 8). IVA was administered for 28 d. Hemodynamic and cardiac function indexes of all rats were measured: heart rate (HR), systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximum rate of increase and decrease of left ventricular internal pressure (+dp/dt);left ventricular mass index, left ventricular cross-sectional diameter and infarct area;The expression of Notch signaling pathway components mRNA (Notch-1, Dll-4, Hes-1) in rat cardiomyocytes was detected by PT-PCR, and the expression of DICD-1 and P65 protein was detected by western-blot. One-way ANOVA was used for comparison between groups, and SNK was used for comparison between groups.Results: SBP, DBP, MAP, LASP, LVEDP and (+dp/dt) in MI group were lower than those in control group (P<0.05), while IVA was higher than those in MI group (P<0.05). Left ventricular mass index and left ventricular sectional diameter in MI group were significantly higher than those in control group (P<0.05), but lower than those in IVA group (P<0.05). The expression of Notch-1 in MI group was significantly higher than that in control group (P<0.05), but lower than that in IVA group (P<0.05). There was no significant difference in the expression of Dll-4 and Hes-1 mRNA between the three groups (P>0.05). The expression levels of NICD-1 and P 65 in MI group were significantly higher than those in CON group (P<0.05), but lower than those in IVA group (P<0.05). Conclusion: IVA may improve cardiac function and inhibit ventricular remodeling in rats with myocardial infarction through Notch and NF-kappa B signaling pathways.
文摘目的:研究中草药岩黄连总碱(YHL-TA)和脱氢阿卟卡维丁(YHL-2)对人舌鳞癌细胞Tca8113细胞中NF-kappaB表达活性的影响,并进一步探讨其抗癌机制。方法:采用PCR法和Western-blotting法检测经YHL-TA和YHL-2作用后的Tca8113细胞中NF-kappa B核酸水平以及蛋白水平的表达活性变化。结果:YHL-TA和YHL-2均能抑制Tca8113细胞增殖,并在核酸水平和蛋白水平抑制NF-kappa B P50、P65亚基的表达活性。其中YHL-2抑制作用最强;并且随作用时间延长和药物浓度的增高,抑制作用增强。结论:YHL-TA和YHL-2可以明显抑制Tca8113细胞的增殖,并显著降低其NF-kappa B的表达,其中YHL-2作用最明显。这可能是岩黄连抗癌作用机制之一。
基金Supported by the 2023 Traditional Chinese Medicine Innovation Capability Enhancement Project from the National Administration of Traditional Chinese Medicine(no number)2024 Qinghai Province“Kunlun Talents·High-End Innovative and Entrepreneurial Talents”Top Notch Talent Project(No.QHKLYC-GDCXCY-2024-152)both for Study the Mechanism of Weimishu Prescription in the Treatment of Chronic Gastritis with Liver-Stomach Disharmony。
文摘OBJECTIVE:To investigate the therapeutic effect of Weimishu prescription(胃糜舒方,WMSP)on chronic gastritis with liver-stomach disharmony(CG-LSD)and elucidate its molecular mechanisms involved in regulating the nuclear factor kappa-B(NF-κB)inflammatory response and gastric stem cell(GSC)differentiation.METHODS:A CG-LSD rat model was established through a combined protocol involving 56%ethanol and tail-clip stimulation.Rats were administered with low-,medium-,or high-dose WMSP,the positive control drug omeprazole,or high-dose WMSP with the NF-κB agonist phorbol 12-myristate 13-acetate(PMA).Histopathological changes were assessed via hematoxylin and eosin and Td T-mediated d UTP nick end labeling staining.Flow cytometry,immunofluorescence,real-time quantitative polymerase chain reaction,Western blotting,and enzyme-linked immunosorbent assay were performed to evaluate the underlying mechanisms.RESULTS:WMSP significantly increased rat locomotor activity,improved Traditional Chinese Medicine syndrome scores,and ameliorated pathological damage to the gastric mucosa while reducing gastric mucosal epithelial cells apoptosis.WMSP also increased the proportion of Lgr5+Ki67+cells;upregulated muscle,intestine,and stomach specific transcript 1,sex determining region Y-box 2,sex determining region Y-box 9,and homing cell adhesion molecule;and enhanced the levels of pepsinogen C,somatostatin,mucin-6,H+-K+ATPase,and E-cadherin proteins,thereby promoting gastric stem cell survival and differentiation.Furthermore,WMSP alleviated systemic and gastric mucosal inflammation in CG-LSD rats.Mechanistically,WMSP suppressed NF-κB expression,thereby reducing Smadspecific E3 ubiquitin ligase 2 levels,which enhancedβ-catenin and subsequently increased myelocytomatosis oncogene,and axis inhibition protein 2 expression.PMA administration reversed the protective effect of WMSP on CG-LSD rats.CONCLUSIONS:WMSP ameliorated gastric mucosal injury in CG-LSD rats by regulating the NF-κB/β-catenin signaling pathway,thereby suppressing inflammation and promoting gastric stem cell differentiation.These findings highlight the therapeutic potential of WMSP,providing the foundation for further clinical evaluations of WMSP in CGLSD treatment.
基金Supported by Shandong Provincial Natural Science,Study on the Structure-Activity Relationship and Mechanism of Licorice Chalcone Components in Synergizing with Immune Checkpoint Inhibitors for Anticancer Therapy(No.ZR2020MH380)Mechanisms of the Novel Flavone C-Glycoside 6'-ORhamnosyllutonarin from Dianthus superbus Improves Non-alcoholic Fatty Liver Disease via Modulating the Juxtaposed with Another Zinc Finger gene 1/Adenosine Monophosphate-activated Protein Kinase/Sterol Regulatory Element-Binding Protein Pathway(No.ZR2024MC209)。
文摘OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with experimental validation,focusing on the modulation of inflammatory signaling.METHODS:A chronic UC model was induced in C57BL/6 mice by cyclical administration of DSS.Mice were treated with either a low(15 m L/kg)or high(30 m L/kg)dose of PD.Disease severity was assessed clinically and via histopathology.Serum levels of inflammatory cytokines were quantified.A network pharmacology approach was employed to predict the core targets and pathways of PD against UC.Key predictions concerning the toll-like receptor 4/nuclear factor-kappa B(TLR4/NF-κB)pathway were subsequently verified in colonic tissue using quantitative polymerase chain reaction and Western blotting.RESULTS:PD treatment significantly ameliorated DSSinduced UC symptoms,including reducing disease activity,preventing colon shortening,and improving histological architecture.PD effectively rebalanced the systemic inflammatory milieu by decreasing proinflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)and elevating anti-inflammatory cytokines interleukin-10(IL-10).Network pharmacology analysis identified the TLR4/NF-κB signaling pathway as a central target.Experimental validation confirmed that PD markedly suppressed the upregulation of both TLR4 and NF-κB at the transcriptional and protein levels in the inflamed colon.CONCLUSION:PD demonstrates protective effects against experimental UC.Its mechanism is associated with the inhibition of the TLR4/NF-κB signaling pathway and the subsequent attenuation of inflammatory responses.This study provides a modern pharmacological basis for the classical application of PD in treating heat-toxin related intestinal disorders,bridging traditional use and mechanistic understanding.
基金Supported by the‘Pioneer’R&D Program of Zhejiang:Research on Key Technologies for the Development of Traditional Chinese Medicine New Drugs(No.2023C03004)National Key Research and Development Program of China:Mechanism Study and Clinical Exploration of Electroacupuncture Promoting Immune Normalization+4 种基金Supporting the Body and Inhibiting Cancer,Synergistic Programmed Death Receptor 1/Programmed Cell Death Ligand 1 Monoclonal Antibody therapy for Intestinal and Biliary Tumors(No.2023YFC3504600)Zhejiang Province Traditional Chinese Medicine Science and Technology Project:Clinical Metabolomics Based Discovery of Effective Markers for Nourishing Yin of Radix Ophiopogonis in the Treatment of Gestational Diabetes(No.GZY-ZJKJ-24076)the‘Pioneer’R&D Program of Zhejiang:Analysis of the Complex System of Traditional Chinese Medicine and Development of New Chinese Medicine Drugs-Analysis of the Complex Cross Organ Action Mode of Traditional Chinese Medicine for Anti-Coronary Heart Disease and Blood Stasis Syndrome and Development of New Drugs(No.2024C03106)Health and Medicinal Research Fund from Health Burden,Hong Kong Special Administrative Region of the People's Republic of China:Chinese Versus Western Medicine for Threatened Miscarriage:Abridged Secondary Publication(No.15160971)Transverse Research Project of Zhejiang University:Development of Traditional Chinese Medicine Big Health Formula for Reproductive Health(No.2023-KYY-A070350007)。
文摘OBJECTIVE:To elucidate the anti-inflammatory mechanisms of modified Shoutai pills(改良寿胎丸,MSTP)in miscarriages,we performed transcriptome sequencing on the decidua and placental tissues of pregnancy mice.METHODS:The therapeutic effects and antiinflammatory mechanisms of MSTP were studied in mice with lipopolysaccharide(LPS)-induced miscarriage.First,the effects of MSTP on pregnancy outcomes and the maternal-fetal interface,in LPS-induced miscarriage mice were examined.RNA sequencing was used to further investigate gene expression changes in LPS-induced miscarriage mice and to assess the effects of MSTP intervention.Finally,the expression levels of inflammation-related genes in the decidua and placental tissues were determined using quantitative real-time polymerase chain reaction(q RT-PCR).RESULTS:A high dose of MSTP significantly decreased the resorption rate(P<0.05)and reduced apoptosis of the decidua and placental tissues in mice.Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that inflammatory and immune-related signals were enriched.q RT-PCR results confirmed that in decidual and placental tissues,MSTP reduced the gene expression levels of toll-like receptor 4(TLR4),nuclear factor kappa-B(NF-κB),c-Jun N-terminal kinase 1,p38,and tumor necrosis factor-α.CONCLUSIONS:In this study,we demonstrated that MSTP effectively prevented embryo loss with an antiinflammatory mechanism through downregulation of the TLR4-NF-κB/MAPK signaling pathway,in LPS-induced miscarriage mice model.To our knowledge,this is the first study to reveal the therapeutic mechanism of MSTP in LPS-induced miscarriage in mice.
