Colorectal cancer(CRC)is the third most common malignancy.However,the efficacy of current treatment strategies remains limited.In recent years,monomeric compounds from traditional Chinese medicine have received extens...Colorectal cancer(CRC)is the third most common malignancy.However,the efficacy of current treatment strategies remains limited.In recent years,monomeric compounds from traditional Chinese medicine have received extensive attention in cancer therapy.Rosmarinic acid(RA),a natural phenolic acid,has multiple biological activities and exhibits anti-oncogenic effects in several cancers.Liu et al previously uncovered that RA could serve as a dual-action therapeutic agent in CRC.By suppressing nuclear factor-kappa B signaling via direct inhibition of inhibitory kappa B kinase beta,RA not only impedes tumor progression but also synergizes with first-line chemotherapeutics(5-fluorouracil/oxaliplatin)to reverse drug resistance.The authors demonstrate RA’s capacity to downregulate nuclear factor-kappa B-driven oncogenes and enhance chemotherapeutic cytotoxicity in vitro through integrative approaches,including molecular docking,luciferase assays,and functional validation.While these findings position RA as a cost-effective adjuvant in precision oncology,critical clinical translational gaps remain,including optimizing RA’s in vivo bioavailability,validating systemic safety in combinatorial regimens,and elucidating its immunomodulatory effects within the tumor microenvironment.This underscores the urgency of bridging phytochemistry and clinical oncology,advocating for biomarker-driven animal studies and phase I trials to translate RA’s potential into actionable CRC therapies.By addressing these hurdles,RA could emerge as a paradigm-shifting agent,harmonizing natural product efficacy with modern therapeutic precision.展开更多
BACKGROUND Rosmarinic acid(RA)is a natural polyphenol carboxylic acid known for its role in chemoprevention.Given its widespread use as a food additive,we are interested in whether RA affects the development of colore...BACKGROUND Rosmarinic acid(RA)is a natural polyphenol carboxylic acid known for its role in chemoprevention.Given its widespread use as a food additive,we are interested in whether RA affects the development of colorectal cancer(CRC).AIM To examine the anti-tumor effects of RA on various CRC cell lines,and to further investigate the possible mechanisms.METHODS Cell Counting Kit-8 assay and optical microscopy imaging were used to evaluate the viability of CRC cell lines.Western blot,quantitative real-time polymerase chain reaction,and flow cytometry analyses were performed to assess cell viability and activation of nuclear factor-kappa B(NF-κB)signaling.Molecular modeling was used to assess the interaction between RA and inhibitory kappa B kinase beta.Luciferase assay was used to examine the activity of NF-κB-driven transcription.The combinations of RA with 5-fluorouracil or oxaliplatin were utilized to evaluate the potential synergistic action of RA with the chemotherapeutics.RESULTS RA exerted potent cytotoxic actions on all six CRC cell lines examined.RA was docked nicely into the binding pocket of inhibitory kappa B kinase beta by molecular modeling.The activity of NF-κB-driven luciferase and the phosphorylation of NF-κB p65 were decreased after exposure to the compound.Lipopolysaccharide-induced NF-κB activation was effectively inhibited by RA,too.Further,RA downregulated the expression of cell proliferationrelated cyclin D1 and MYC,which are target genes of NF-κB.Of note,the cytotoxic actions of 5-fluorouracil and oxaliplatin were markedly enhanced by RA in those CRC cells.CONCLUSION Our results indicate that RA inhibits NF-κB signaling and induces apoptosis in CRC cells.It enhances the cytotoxic actions of chemotherapeutics and might help to improve the chemotherapy of CRC.展开更多
Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as a prominent and pervasive global health challenge.Bicuculline(BIC),which is a key active component of the anti-MASLD prescriptio...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as a prominent and pervasive global health challenge.Bicuculline(BIC),which is a key active component of the anti-MASLD prescription"Eight Zhes Decoction",has been preliminarily shown by our research team to have significant potential in treating MASLD.AIM To determine BIC's efficacy in treating MASLD by regulating lipid metabolism and suppressing hepatic inflammation via nuclear factor-kappa B(NF-κB)pathway,identifying it as a therapeutic candidate.METHODS This study explored the potential of BIC in preventing and treating MASLD using zebrafish,cellular(HepG2 and AML12),and mouse models.RESULTS Our results indicate that BIC significantly reduces lipid accumulation and inflammation both in vivo and in vitro.Transcriptomic analysis suggested that the anti-MASLD effects of BIC are linked to the inhibition of the NF-κB pathway,which plays a critical role in mitigating inflammation and lipid deposition.CONCLUSION This study is the first to demonstrate that BIC specifically alleviates lipid accumulation and hepatic steatosis in MASLD models via the NF-κB signaling pathway.Overall,BIC has emerged as a promising candidate for treating MASLD.展开更多
BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteo...BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteoprotegerin(OPG).The ratio of RANKL/OPG is a crucial determinant of OC-mediated bone resorption,which plays an integral role in bone remodeling and scaffold degradation.Elevated levels of RANKL relative to OPG enhance osteoclastogenesis,thereby accelerating the degradation process essential for integrating bone scaffolds into the host tissue.AIM To elucidate the effects of OPG gene silencing on osteoclastogenesis within rat bone marrow-derived mesenchymal stem cells(BMSCs).By investigating these effects,the study aimed to provide deeper insights into the regulatory mechanisms that influence bone scaffold degradation,potentially leading to improved bone repair and regeneration strategies.METHODS We employed recombinant lentiviral plasmids to silence the OPG gene in rat BMSCs to achieve the aims.The efficacy of gene silencing was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis to measure the expression levels of OPG and RANKL.Tartrate-resistant acid phosphatase staining was utilized to evaluate the formation of OCs.Additionally,co-immunoprecipitation assays were conducted to explore the interactions between RANKL and OPG proteins,further assessing the biochemical pathways involved in osteoclastogenesis.RESULTS The silencing of the OPG gene in BMSCs resulted in a significant increase in the RANKL/OPG ratio,evidenced by decreased expression levels of OPG and increased levels of RANKL.Enhanced osteoclastogenesis was observed through tartrate-resistant acid phosphatase staining,which indicated a substantial rise in OC formation in response to the altered RANKL/OPG balance.The co-immunoprecipitation assays provided concrete evidence of the direct interaction between RANKL and OPG proteins,substantiating their pivotal roles in regulating OC activity.CONCLUSION The findings from this study underscore the critical role of the RANKL/OPG axis in osteoclastogenesis.Silencing of the OPG gene in BMSCs effectively increases the RANKL/OPG ratio,promoting OC activity and potentially enhancing bone scaffold degradation.This regulatory mechanism offers a promising avenue for modulating bone remodeling processes,which is essential for effective bone repair and the successful integration of bone scaffolds into damaged sites.Future research might focus on optimizing the control of this axis to better facilitate bone tissue engineering and regenerative therapies.展开更多
●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were tre...●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0,125,250,or 500 ng/mL for 24,48,or 72h in vitro.Transepithelial electrical resistance(TEER)as well as Dextran-fluorescein isothiocyanate(FITC)permeability assays were conducted to assess barrier function.To quantify tight junctions(TJs)such as occludin and zonula occludens-1(ZO-1)at the mRNA level,reverse transcriptionpolymerase chain reaction(RT-PCR)analysis was performed.Immunoblotting was used to examine the activity of the nuclear factor-kappa B(NF-κB)signaling pathway and the production of TJs proteins.Immunofluorescence analyses were employed to localize the TJs.Enzyme-linked immunosorbent assay(ELISA)and RT-PCR were utilized to observe changes in interleukin(IL)-1βlevels.To investigate the role of NF-κB signaling activation and IL^(-1)βin Sema7A’s anti-barrier mechanism,we employed 0.1μmol/L IκB kinase 2(IKK2)inhibitor IV or 500 ng/mL IL^(-1)receptor(IL-1R)antagonist.●RESULTS:Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time-and dose-dependent manner,as well as altering the localization of TJs.Furthermore,Sema7A stimulated the activation of inhibitor of kappa B alpha(IκBα)and expression of IL-1β.The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists.●CONCLUSION:Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins,as well as the expression of IL-1β.These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.展开更多
BACKGROUND: The active form of nuclear factor-kappa B (NF-kappa B) is involved in the initiation, generation, and development of hepatocellular carcinoma (HCC), and is up-regulated in inflammation-associated malignanc...BACKGROUND: The active form of nuclear factor-kappa B (NF-kappa B) is involved in the initiation, generation, and development of hepatocellular carcinoma (HCC), and is up-regulated in inflammation-associated malignancies. We investigated the dynamic expression of NF-kappa B and its influences on the occurrence of HCC through antiangiogenic (thalidomide) intervention in NF-kappa B activation. METHODS : Hepatoma models were induced with 2-fluorenylacetamide (2-FAA, 0.05%) in male Sprague-Dawley rats, and thalidomide (100 mg/kg body weight) was administered intragastrically to intervene in NF-kappa B activation. The pathological changes in the liver of sacrificed rats were assessed after hematoxylin and eosin staining. NF-kappa B mRNA was amplified by RT-nested PCR. The alterations of NF-kappa B and vascular endothelial growth factor (VEGF) expression were analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blotting. RESULTS: Rat hepatocytes showed denatured, precancerous, and cancerous stages in hepatocarcinogenesis, with an increasing tendency of hepatic NF-kappa B, NF-kappa B mRNA, and VEGF expression, and their values in the HCC group were higher than those in controls (P<0.001). In the thalidomide-treated group, the morphologic changes generated only punctiform denaturation and necrosis at the early or middle stages, and nodular hyperplasia or a little atypical hyperplasia at the final stages, with the expression of NF-kappa B (chi(2)=9.93, P<0.001) and VEGF (chi(2)=8.024, P<0.001) lower than that in the 2-FAA group. CONCLUSION: NF-kappa B is overexpressed in hepatocarcinogenesis and antiangiogenic treatment down-regulates the expression of NF-kappa B and VEGF, and delays the occurrence of HCC. (Hepatobiliary Pancreat Dis Int 2010; 9: 169-174)展开更多
BACKGROUND: Urinary trypsin inhibitor (UTI) inhibits the inflammatory response and protects against ischemia-reperfusion (I/R) injury. The inflammatory response is mediated by nuclear factor-kappa B (NF-kappa B) and i...BACKGROUND: Urinary trypsin inhibitor (UTI) inhibits the inflammatory response and protects against ischemia-reperfusion (I/R) injury. The inflammatory response is mediated by nuclear factor-kappa B (NF-kappa B) and its related target genes and products such as vascular endothelial cell adhesion molecule and CXC chemokines. We aimed to assess the roles of those mediators in a UTI-treated mouse model of hepatic I/R injury. METHODS: Treatment group 1 (UTI given 5 minutes prior to liver ischemia), treatment group 2 (UTI given 5 minutes after the anhepatic phase) and a control group were investigated. Blood and liver samples were obtained and compared at 1, 3, 6 and 24 hours after reperfusion. RESULTS: Attenuation of pathological hepatocellular damage was greater in the treatment groups than in the control group (P < 0.05). Compared with the control group, the UTI treatment groups showed significantly lower serum alanine aminotransferase and aspartate aminotransferase levels, decreased myeloperoxidase activity, and reduced NF-kappa B activation. Also downregulated was the expression of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2 at the mRNA level. P-selectin protein and intercellular adhesion molecule-1 protein expression were also downregulated. In addition, the treatment group I showed a better protective effect against I/R injury than the treatment group 2. CONCLUSIONS: UTI reduces NF-kappa B activation and downregulates the expression of its related mediators, followed by the inhibition of neutrophil aggregation and infiltration in hepatic I/R injury. The protective role of UTI is more effective in prevention than in treatment.展开更多
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. We analyzed the expression of miclear-transcription factor-kappa B (NF-kappa B) during hepatocarcinogenesis in order to evaluate i...BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. We analyzed the expression of miclear-transcription factor-kappa B (NF-kappa B) during hepatocarcinogenesis in order to evaluate its dynamic expression and its clinical value in the development and diagnosis of HCC. METHODS: Hepatoma models were induced by oral administration of 2-acetamidoflurene (2-FAA) to male Sprague-Dawley rats. Morphological changes were observed after hematoxylin and eosin staining. The cellular distribution of NF-kappa B expression during different stages of cancer development was investigated by immunohistochemistry, and the level of NF-kappa B expression in liver tissues was quantitatively analyzed by ELISA. The gene fragments of hepatic NF-kappa B were amplified by nested-polymerase chain reaction assay. RESULTS: Hepatocytes showed vacuole-like degeneration during the early stages, then had a hyperplastic nodal appearance during the middle stages, and finally progressed to tubercles of cancerous nests with high differentiation. The NF-kappa B-positive material was buff-colored, fine particles localized in the nucleus, and the incidence of NF-kappa B-positive cells was 81.8% in degeneration, 83.3% in precancerous lesions, and 100% in cancerous tissues. All of these values were higher than those in controls (P<0.01). Hepatic NF-kappa B expression and hepatic NF-kappa B-mRNA were also higher during the course of HCC development (P<0.01). CONCLUSION: The NF-kappa B signal transduction pathway is activated during the early stages of HCC development, and its abnormal expression may be associated with the occurrence of HCC.展开更多
AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation.METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid (PUFA)-enriched diet. Pr...AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation.METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid (PUFA)-enriched diet. Primary hepatocytes were treated with either saturated fatty acids (SFAs) or PUFAs as well as combined with lipopolysaccharide (LPS). The expression of NOD-like receptor protein 3 (NLRP3) inflammasome, peroxisome proliferator-activated receptor-γ and nuclear factor-kappa B (NF-κB) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1β production were measured.RESULTS: High-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NLRP3 inflammasome. SFA palmitic acid (PA) directly activated NLRP3 inflammasome and increased sensitization to LPS-induced inflammasome activation in hepatocytes. In contrast, PUFA docosahexaenoic acid (DHA) had the potential to inhibit NLRP3 inflammasome expression in hepatocytes and partly abolished LPS-induced NLRP3 inflammasome activation. Furthermore, a high-fat diet increased but PUFA-enriched diet decreased sensitization to LPS-induced hepatic NLRP3 inflammasome activation in vivo. Moreover, PA increased but DHA decreased phosphorylated NF-κB p65 protein expression in hepatocytes.CONCLUSION: Hepatic NLRP3 inflammasome activation played an important role in the development of non-alcoholic fatty liver disease. Dietary SFAs and PUFAs oppositely regulated the activity of NLRP3 inflammasome through direct activation or inhibition of NF-κB.展开更多
We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor(TFPI)gene expression through the androgen receptor in endothelial cells.This study further inves...We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor(TFPI)gene expression through the androgen receptor in endothelial cells.This study further investigated the impact of testosterone on TFPI levels in response to inflammatory cytokine tumor necrosis factor-alpha(TNF-α).Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-α.TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction.To study the cellular mechanism of testosterone’s action,nuclear factor-kappa B(NF-κB)translocation was confirmed by electrophoretic mobility shift assays.We found that after NF-κB was activated by TNF-α,TFPI protein levels declined significantly by 37.3%compared with controls(P<0.001),and the mRNA levels of TFPI also decreased greatly(P<0.001).A concentration of 30 nmol L-1 testosterone increased the secretion of TFPI compared with the TNF-α-treated group.NF-κB DNA-binding activity was significantly suppressed by testosterone(P<0.05).This suggests that physiological testosterone concentrations may exert their antithrombotic effects on TFPI expression during inflammation by downregulating NF-κB activity.展开更多
Previous studies have confirmed that the anti-virus effects of Shuanghuanglian injection may be associated with nuclear factor-kappa B activity. This study observed nuclear factor-kappa B expression in mice with viral...Previous studies have confirmed that the anti-virus effects of Shuanghuanglian injection may be associated with nuclear factor-kappa B activity. This study observed nuclear factor-kappa B expression in mice with viral encephalitis, and showed significant decreases in nuclear factor-kappa B protein and mRNA levels following Shuanghuanglian injection. The inhibitory effect was more significant with prolonged intervention duration and increased treatment dose. These findings verify that Shuanghuanglian injection plays a therapeutic role in viral encephalitis by reducing expression of nuclear factor-kappa B in a time- and dose-dependent manner.展开更多
A mouse model of viral encephalitis was induced by intracranial injection of a Coxsackie virus B3 suspension. Quantitative real-time reverse transcription-PCR and western blot assay were applied to detect mRNA and pro...A mouse model of viral encephalitis was induced by intracranial injection of a Coxsackie virus B3 suspension. Quantitative real-time reverse transcription-PCR and western blot assay were applied to detect mRNA and protein expression of intelectin-2 and nuclear factor-kappa B in the viral encephalitis and control groups. Nuclear factor-kappa B and intelectin-2 mRNA and protein expression were significantly increased in mice with viral encephalitis. After intraperitoneal injection of Shuanghuanglian at a dose of 1.5 mg/kg for 5 successive days, intelectin-2 and nuclear factor-kappa B protein and mRNA expression were significantly decreased. To elucidate the relationship between intelectin-2 and nuclear factor-kappa B, mice with viral encephalitis were administered an intracerebral injection of 107 pfu recombinant lentivirus expressing intelectin shRNA. Both protein and mRNA levels of intelectin and nuclear factor-kappa B in brain tissue of mice were significantly decreased. Experimental findings suggest that Shuanghuanglian injection may downregulate nuclear factor-kappa B production via suppression of intelectin production, thus inhibiting inflammation associated with viral encephalitis.展开更多
The effects of five chito-oligomers, from dimer to hexamer （chitobiose, chitotriose, chitotetraose, chitopentaose, chitohexaose） separated from chitosan oligosaccharides, on nuclear factor -kappaB （NF-rd3） signali...The effects of five chito-oligomers, from dimer to hexamer （chitobiose, chitotriose, chitotetraose, chitopentaose, chitohexaose） separated from chitosan oligosaccharides, on nuclear factor -kappaB （NF-rd3） signaling pathway were investigated by using luciferase assay and laser scanning microscopy. The expression of NF-rd3 downstream genes （cyclin DI, TNFa and IL-6） were tested by real time PCR. We found that all five chitosan oligosaccharides increased NF-KB-dependent luciferase gene expression and NF-KB downstream genes transcription, and the most significant were chitotetraose and chitohexaose. In addition, laser scanning microscopy experiments showed that chitotetraose and chitohexaose also activated the p65 subunite of NF-kB translocating from cytoplasm to nucleus, which suggested that they were the most potent activators of NF-kB signaling pathway.展开更多
BACKGROUND： It has been reported that nuclear factor-kappa B （NF- κB）, activated after spinal cord injury in rats, plays a key role in inflammatory responses in the central nervous system. OBJECTIVE： To investiga...BACKGROUND： It has been reported that nuclear factor-kappa B （NF- κB）, activated after spinal cord injury in rats, plays a key role in inflammatory responses in the central nervous system. OBJECTIVE： To investigate the effects of transplantation of microencapsulated rabbit sciatic nerve on NF- κB expression and motor function after spinal cord injury in rats, and to compare the results with the transplantation of rabbit sciatic nerve alone. DESIGN, TIME AND SETTING： This completely randomized, controlled study was performed at the Department of Neurobiology, Medical College of Nanchang University between December 2007 and July 2008. MATERIALS： A rabbit anti-NF- κB P65 monoclonal antibody was made by the Santa Cruz Company, USA and a streptavidin peroxidase immunohistochemical kit was provided by the Sequoia Company, China. METHODS： Eight rabbits were used to prepare a sciatic nerve cell suspension that was divided into two parts： one stored for transplantation, and the other mixed with a 1.5% sodium alginate solution. One hundred and twenty adult Sprague Dawley rats weighing 220-250 g were randomly divided into four groups： the microencapsulated cell group （n = 36）, the non-encapsulated cell group （n = 36）, the saline group （n = 36） and the sham operation group （n = 12）. The first three groups underwent a right hemisection injury of the spinal cord at the T10 level, into which was transplanted a gelatin sponge soaked with 10 μL of a microencapsulated nerve tissue/cell suspension （microencapsulated cell group）, a tissue/cell suspension （non-encapsulated cell group） or physiological saline （saline group）. In the sham operation group the vertebrae were exposed, but the spinal cord was not injured, and no implantation was given. MAIN OUTCOME MEASURES： Pathological changes were detected using hematoxylin-eosin staining; NF- κB expression was quantified using immunohistochemical staining; motor function was assessed using the Basso, Beattie and Bresnahan （BBB） scale. RESULTS： Spinal cord injuries, such as neuronal death and inflammatory cell infiltration, were found in the microencapsulated cell group, the non-encapsulated cell group and the saline group. However, the damage in the microencapsulated cell group was milder than in the non-encapsulated cell or saline groups. NF- κB expression in the microencapsulated cell group, the non-encapsulated cell group and the saline group was increased after spinal cord injury; it reached a peak after 24 hours, gradually decreased after 3 days, and was close to normal levels after 7 days. NF- κB expression in the microencapsulated cell group was significantly lower than in the saline group and the non-encapsulated cell group （P 〈 0.05）. With time, the motor function of the animals in each group improved to a certain extent, but did not reach normal levels. There were no significant differences in BBB scores between the different groups on post-operative day 3; however, the BBB scores for the microencapsulated cell group and the non-encapsulated cell group were significantly higher than the saline group on post-operative day 7 （P 〈 0.05）. In addition, the motor function recovered better in the microencapsulated cell group than in the non-encapsulated cell group （P 〈 0.05）. CONCLUSION： The transplantation of microencapsulated rabbit sciatic nerve can inhibit NF- κB expression and inflammatory reactions and promote recovery of motor function after spinal cord injury in rats. The effects of microencapsulated cell transplantation are superior to those of transplantation of cells alone.展开更多
OBJECTIVE:To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-alpha (TNF-cα) and nuclear factor-kappa B (NF-KB) levels in patients who have chronic heart failure with syndromes of def...OBJECTIVE:To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-alpha (TNF-cα) and nuclear factor-kappa B (NF-KB) levels in patients who have chronic heart failure with syndromes of deficiency of heart Yang.METHODS:A total of 63 patients with syndromes of deficiency of heart Yang (chronic heart failure)were enrolled.Patients were randomly divided into the control group and Jiawei Shenfu group.All patients received standard medications for treatment of chronic heart failure.Patients in the Jiawei Shenfu group were additionally provided Jiawei Shenfu decoction one dose daily.Treatments continued for 4 consecutive weeks.The primary endpoint was the change in plasma B-type natriuretic peptide (BNP),NF-KB,and TNF-cα levels during 4 weeks of treatment.RESULTS:At the 4-week follow-up,a significant reduction in BNP levels compared with baseline was observed in both groups,but the Jiawei Shenfu decoction group showed a significantly greater reduction than did the control group.The Jiawei Shenfu group also showed superior performance regarding the Minnesota Living with Heart Failure Questionnaire score,the Chinese medicine syndrome score,heart rate,left ventricular ejection fraction,and 6-min walking distance compared with the control group.The degree of changes in NF-KB and TNF-α levels in the Jiawei Shenfu group was more significant than that in the control group.CONCLUSION:Routine medicine combined with Jiawei Shenfu decoction for patients with heart Yang deficiency syndrome in chronic heart failure can improve the left ventricular ejection fraction and cardiac function,and reduce BNP levels.The mechanism may be related to inhibition of pro-inflammatory cytokines and the NF-KB-induced kinase pathway,leading to amelioration of the inflammatory response.展开更多
In order to investigate the effect of nuclear factor kappa B (NF κB) on vascular endothelial growth factor (VEGF) mRNA expression of human pulmonary artery smooth muscle cells (HPASMCs) in hypoxia, the cultured HPA...In order to investigate the effect of nuclear factor kappa B (NF κB) on vascular endothelial growth factor (VEGF) mRNA expression of human pulmonary artery smooth muscle cells (HPASMCs) in hypoxia, the cultured HPASMCs in vitro were stimulated with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF κB. The NF κB p65 nuclei positive expression was detected by immunocytochemical technique. The IκBα protein expression was measured by Western blot. RT PCR was used to detect the VEGF mRNA expression of HPASMCs. The results showed that no significant change was observed in the NF κB p65 nuclei positive expression of cultured HPASMCs during 6 h-24 h in normoxia, but the levels of NF κB p65 nuclei positive expression of cultured HPASMCs were significantly increased in hypoxia groups as compared with those in all normoxia groups ( P <0.05). The IκBα protein expression of cultured HPASMCs showed no significant change during 6 h-24 h in normoxia, but significantly decreased in hypoxia as comapred with that in normoxia groups ( P <0.05). PDTC (1 to 100 μmol/L) could inhibit the VEGF mRNA expression of HPASMCs in a concentration dependent manner in hypoxia. In conclusion, NF κB can be partly translocation activated from cytoplasm into nuclei in the cultured HPASMCs under hypoxia. The inhibition of NF κB activation can decrease the VEGF mRNA expression. It is suggested that the activation of NF κB is involved in the VEGF mRNA expression of HPASMCs under hypoxia.展开更多
Heavy infection of the virus leads to overproduction of cytokines. The overproduction of cytokine (cytokines storms) is responsible for the critical cases and deaths of COVID-19. The nuclear factor kappa-B stimulates ...Heavy infection of the virus leads to overproduction of cytokines. The overproduction of cytokine (cytokines storms) is responsible for the critical cases and deaths of COVID-19. The nuclear factor kappa-B stimulates the expression of the genes, which is responsible for cytokines storm and RNA transcription. The COVID-19 virus can be controlled by inhibition of nuclear factor kappa-B. Nuclear factor kappa-B is controlled by inhibition of hydrogen peroxide and inhibitor kappa-B kinase enzyme.展开更多
文摘Colorectal cancer(CRC)is the third most common malignancy.However,the efficacy of current treatment strategies remains limited.In recent years,monomeric compounds from traditional Chinese medicine have received extensive attention in cancer therapy.Rosmarinic acid(RA),a natural phenolic acid,has multiple biological activities and exhibits anti-oncogenic effects in several cancers.Liu et al previously uncovered that RA could serve as a dual-action therapeutic agent in CRC.By suppressing nuclear factor-kappa B signaling via direct inhibition of inhibitory kappa B kinase beta,RA not only impedes tumor progression but also synergizes with first-line chemotherapeutics(5-fluorouracil/oxaliplatin)to reverse drug resistance.The authors demonstrate RA’s capacity to downregulate nuclear factor-kappa B-driven oncogenes and enhance chemotherapeutic cytotoxicity in vitro through integrative approaches,including molecular docking,luciferase assays,and functional validation.While these findings position RA as a cost-effective adjuvant in precision oncology,critical clinical translational gaps remain,including optimizing RA’s in vivo bioavailability,validating systemic safety in combinatorial regimens,and elucidating its immunomodulatory effects within the tumor microenvironment.This underscores the urgency of bridging phytochemistry and clinical oncology,advocating for biomarker-driven animal studies and phase I trials to translate RA’s potential into actionable CRC therapies.By addressing these hurdles,RA could emerge as a paradigm-shifting agent,harmonizing natural product efficacy with modern therapeutic precision.
基金Supported by Natural Science Foundation of Heilongjiang Province of China Under Grant,No.PL2024H020High-Quality Innovation Platform of Science and Education Innovation Zone in Suzhou Industrial Park-Key Platform Project,No.YZCXPT2023104.
文摘BACKGROUND Rosmarinic acid(RA)is a natural polyphenol carboxylic acid known for its role in chemoprevention.Given its widespread use as a food additive,we are interested in whether RA affects the development of colorectal cancer(CRC).AIM To examine the anti-tumor effects of RA on various CRC cell lines,and to further investigate the possible mechanisms.METHODS Cell Counting Kit-8 assay and optical microscopy imaging were used to evaluate the viability of CRC cell lines.Western blot,quantitative real-time polymerase chain reaction,and flow cytometry analyses were performed to assess cell viability and activation of nuclear factor-kappa B(NF-κB)signaling.Molecular modeling was used to assess the interaction between RA and inhibitory kappa B kinase beta.Luciferase assay was used to examine the activity of NF-κB-driven transcription.The combinations of RA with 5-fluorouracil or oxaliplatin were utilized to evaluate the potential synergistic action of RA with the chemotherapeutics.RESULTS RA exerted potent cytotoxic actions on all six CRC cell lines examined.RA was docked nicely into the binding pocket of inhibitory kappa B kinase beta by molecular modeling.The activity of NF-κB-driven luciferase and the phosphorylation of NF-κB p65 were decreased after exposure to the compound.Lipopolysaccharide-induced NF-κB activation was effectively inhibited by RA,too.Further,RA downregulated the expression of cell proliferationrelated cyclin D1 and MYC,which are target genes of NF-κB.Of note,the cytotoxic actions of 5-fluorouracil and oxaliplatin were markedly enhanced by RA in those CRC cells.CONCLUSION Our results indicate that RA inhibits NF-κB signaling and induces apoptosis in CRC cells.It enhances the cytotoxic actions of chemotherapeutics and might help to improve the chemotherapy of CRC.
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
基金Supported by Joint TCM Science&Technology Projects of National Demonstration Zones for Comprehensive TCM Reform,No.GZYKJS-ZJ-2025-044Ningbo Top Medical and Health Research Program,No.2023020612.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as a prominent and pervasive global health challenge.Bicuculline(BIC),which is a key active component of the anti-MASLD prescription"Eight Zhes Decoction",has been preliminarily shown by our research team to have significant potential in treating MASLD.AIM To determine BIC's efficacy in treating MASLD by regulating lipid metabolism and suppressing hepatic inflammation via nuclear factor-kappa B(NF-κB)pathway,identifying it as a therapeutic candidate.METHODS This study explored the potential of BIC in preventing and treating MASLD using zebrafish,cellular(HepG2 and AML12),and mouse models.RESULTS Our results indicate that BIC significantly reduces lipid accumulation and inflammation both in vivo and in vitro.Transcriptomic analysis suggested that the anti-MASLD effects of BIC are linked to the inhibition of the NF-κB pathway,which plays a critical role in mitigating inflammation and lipid deposition.CONCLUSION This study is the first to demonstrate that BIC specifically alleviates lipid accumulation and hepatic steatosis in MASLD models via the NF-κB signaling pathway.Overall,BIC has emerged as a promising candidate for treating MASLD.
基金Supported by the National Natural Science Foundation of China,No.82160192and Guangxi Science and Technology Program,No.2023AB23037.
文摘BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteoprotegerin(OPG).The ratio of RANKL/OPG is a crucial determinant of OC-mediated bone resorption,which plays an integral role in bone remodeling and scaffold degradation.Elevated levels of RANKL relative to OPG enhance osteoclastogenesis,thereby accelerating the degradation process essential for integrating bone scaffolds into the host tissue.AIM To elucidate the effects of OPG gene silencing on osteoclastogenesis within rat bone marrow-derived mesenchymal stem cells(BMSCs).By investigating these effects,the study aimed to provide deeper insights into the regulatory mechanisms that influence bone scaffold degradation,potentially leading to improved bone repair and regeneration strategies.METHODS We employed recombinant lentiviral plasmids to silence the OPG gene in rat BMSCs to achieve the aims.The efficacy of gene silencing was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis to measure the expression levels of OPG and RANKL.Tartrate-resistant acid phosphatase staining was utilized to evaluate the formation of OCs.Additionally,co-immunoprecipitation assays were conducted to explore the interactions between RANKL and OPG proteins,further assessing the biochemical pathways involved in osteoclastogenesis.RESULTS The silencing of the OPG gene in BMSCs resulted in a significant increase in the RANKL/OPG ratio,evidenced by decreased expression levels of OPG and increased levels of RANKL.Enhanced osteoclastogenesis was observed through tartrate-resistant acid phosphatase staining,which indicated a substantial rise in OC formation in response to the altered RANKL/OPG balance.The co-immunoprecipitation assays provided concrete evidence of the direct interaction between RANKL and OPG proteins,substantiating their pivotal roles in regulating OC activity.CONCLUSION The findings from this study underscore the critical role of the RANKL/OPG axis in osteoclastogenesis.Silencing of the OPG gene in BMSCs effectively increases the RANKL/OPG ratio,promoting OC activity and potentially enhancing bone scaffold degradation.This regulatory mechanism offers a promising avenue for modulating bone remodeling processes,which is essential for effective bone repair and the successful integration of bone scaffolds into damaged sites.Future research might focus on optimizing the control of this axis to better facilitate bone tissue engineering and regenerative therapies.
基金Supported by the National Natural Science Foundation of China(No.81770889)Zhuhai Science and Technology Program(No.ZH22036201210134PWC).
文摘●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0,125,250,or 500 ng/mL for 24,48,or 72h in vitro.Transepithelial electrical resistance(TEER)as well as Dextran-fluorescein isothiocyanate(FITC)permeability assays were conducted to assess barrier function.To quantify tight junctions(TJs)such as occludin and zonula occludens-1(ZO-1)at the mRNA level,reverse transcriptionpolymerase chain reaction(RT-PCR)analysis was performed.Immunoblotting was used to examine the activity of the nuclear factor-kappa B(NF-κB)signaling pathway and the production of TJs proteins.Immunofluorescence analyses were employed to localize the TJs.Enzyme-linked immunosorbent assay(ELISA)and RT-PCR were utilized to observe changes in interleukin(IL)-1βlevels.To investigate the role of NF-κB signaling activation and IL^(-1)βin Sema7A’s anti-barrier mechanism,we employed 0.1μmol/L IκB kinase 2(IKK2)inhibitor IV or 500 ng/mL IL^(-1)receptor(IL-1R)antagonist.●RESULTS:Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time-and dose-dependent manner,as well as altering the localization of TJs.Furthermore,Sema7A stimulated the activation of inhibitor of kappa B alpha(IκBα)and expression of IL-1β.The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists.●CONCLUSION:Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins,as well as the expression of IL-1β.These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.
基金supported by grants from the Project of Elitist Peak in Six Fields(No.2006-B-063)the Project of Medical Sciences(H200727),the Bureau of Health,Jiangsu Province,China
文摘BACKGROUND: The active form of nuclear factor-kappa B (NF-kappa B) is involved in the initiation, generation, and development of hepatocellular carcinoma (HCC), and is up-regulated in inflammation-associated malignancies. We investigated the dynamic expression of NF-kappa B and its influences on the occurrence of HCC through antiangiogenic (thalidomide) intervention in NF-kappa B activation. METHODS : Hepatoma models were induced with 2-fluorenylacetamide (2-FAA, 0.05%) in male Sprague-Dawley rats, and thalidomide (100 mg/kg body weight) was administered intragastrically to intervene in NF-kappa B activation. The pathological changes in the liver of sacrificed rats were assessed after hematoxylin and eosin staining. NF-kappa B mRNA was amplified by RT-nested PCR. The alterations of NF-kappa B and vascular endothelial growth factor (VEGF) expression were analyzed by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blotting. RESULTS: Rat hepatocytes showed denatured, precancerous, and cancerous stages in hepatocarcinogenesis, with an increasing tendency of hepatic NF-kappa B, NF-kappa B mRNA, and VEGF expression, and their values in the HCC group were higher than those in controls (P<0.001). In the thalidomide-treated group, the morphologic changes generated only punctiform denaturation and necrosis at the early or middle stages, and nodular hyperplasia or a little atypical hyperplasia at the final stages, with the expression of NF-kappa B (chi(2)=9.93, P<0.001) and VEGF (chi(2)=8.024, P<0.001) lower than that in the 2-FAA group. CONCLUSION: NF-kappa B is overexpressed in hepatocarcinogenesis and antiangiogenic treatment down-regulates the expression of NF-kappa B and VEGF, and delays the occurrence of HCC. (Hepatobiliary Pancreat Dis Int 2010; 9: 169-174)
文摘BACKGROUND: Urinary trypsin inhibitor (UTI) inhibits the inflammatory response and protects against ischemia-reperfusion (I/R) injury. The inflammatory response is mediated by nuclear factor-kappa B (NF-kappa B) and its related target genes and products such as vascular endothelial cell adhesion molecule and CXC chemokines. We aimed to assess the roles of those mediators in a UTI-treated mouse model of hepatic I/R injury. METHODS: Treatment group 1 (UTI given 5 minutes prior to liver ischemia), treatment group 2 (UTI given 5 minutes after the anhepatic phase) and a control group were investigated. Blood and liver samples were obtained and compared at 1, 3, 6 and 24 hours after reperfusion. RESULTS: Attenuation of pathological hepatocellular damage was greater in the treatment groups than in the control group (P < 0.05). Compared with the control group, the UTI treatment groups showed significantly lower serum alanine aminotransferase and aspartate aminotransferase levels, decreased myeloperoxidase activity, and reduced NF-kappa B activation. Also downregulated was the expression of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2 at the mRNA level. P-selectin protein and intercellular adhesion molecule-1 protein expression were also downregulated. In addition, the treatment group I showed a better protective effect against I/R injury than the treatment group 2. CONCLUSIONS: UTI reduces NF-kappa B activation and downregulates the expression of its related mediators, followed by the inhibition of neutrophil aggregation and infiltration in hepatic I/R injury. The protective role of UTI is more effective in prevention than in treatment.
基金supported by grants from the Project of Elitist Peak in Six Fields(No.2006-B-063)the Projectof Medical Sciences(H200727),the Bureau of Health,Jiangsu Province,China
文摘BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. We analyzed the expression of miclear-transcription factor-kappa B (NF-kappa B) during hepatocarcinogenesis in order to evaluate its dynamic expression and its clinical value in the development and diagnosis of HCC. METHODS: Hepatoma models were induced by oral administration of 2-acetamidoflurene (2-FAA) to male Sprague-Dawley rats. Morphological changes were observed after hematoxylin and eosin staining. The cellular distribution of NF-kappa B expression during different stages of cancer development was investigated by immunohistochemistry, and the level of NF-kappa B expression in liver tissues was quantitatively analyzed by ELISA. The gene fragments of hepatic NF-kappa B were amplified by nested-polymerase chain reaction assay. RESULTS: Hepatocytes showed vacuole-like degeneration during the early stages, then had a hyperplastic nodal appearance during the middle stages, and finally progressed to tubercles of cancerous nests with high differentiation. The NF-kappa B-positive material was buff-colored, fine particles localized in the nucleus, and the incidence of NF-kappa B-positive cells was 81.8% in degeneration, 83.3% in precancerous lesions, and 100% in cancerous tissues. All of these values were higher than those in controls (P<0.01). Hepatic NF-kappa B expression and hepatic NF-kappa B-mRNA were also higher during the course of HCC development (P<0.01). CONCLUSION: The NF-kappa B signal transduction pathway is activated during the early stages of HCC development, and its abnormal expression may be associated with the occurrence of HCC.
基金Supported by The National Natural Science Foundation of ChinaNO.81170374 and NO.81470842 to Hua J
文摘AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation.METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid (PUFA)-enriched diet. Primary hepatocytes were treated with either saturated fatty acids (SFAs) or PUFAs as well as combined with lipopolysaccharide (LPS). The expression of NOD-like receptor protein 3 (NLRP3) inflammasome, peroxisome proliferator-activated receptor-γ and nuclear factor-kappa B (NF-κB) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1β production were measured.RESULTS: High-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NLRP3 inflammasome. SFA palmitic acid (PA) directly activated NLRP3 inflammasome and increased sensitization to LPS-induced inflammasome activation in hepatocytes. In contrast, PUFA docosahexaenoic acid (DHA) had the potential to inhibit NLRP3 inflammasome expression in hepatocytes and partly abolished LPS-induced NLRP3 inflammasome activation. Furthermore, a high-fat diet increased but PUFA-enriched diet decreased sensitization to LPS-induced hepatic NLRP3 inflammasome activation in vivo. Moreover, PA increased but DHA decreased phosphorylated NF-κB p65 protein expression in hepatocytes.CONCLUSION: Hepatic NLRP3 inflammasome activation played an important role in the development of non-alcoholic fatty liver disease. Dietary SFAs and PUFAs oppositely regulated the activity of NLRP3 inflammasome through direct activation or inhibition of NF-κB.
基金the National Natural Science Foundation of China(No.30670842)the Natural Science Foundation of Guangdong Province,China(No.5300582).
文摘We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor(TFPI)gene expression through the androgen receptor in endothelial cells.This study further investigated the impact of testosterone on TFPI levels in response to inflammatory cytokine tumor necrosis factor-alpha(TNF-α).Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-α.TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction.To study the cellular mechanism of testosterone’s action,nuclear factor-kappa B(NF-κB)translocation was confirmed by electrophoretic mobility shift assays.We found that after NF-κB was activated by TNF-α,TFPI protein levels declined significantly by 37.3%compared with controls(P<0.001),and the mRNA levels of TFPI also decreased greatly(P<0.001).A concentration of 30 nmol L-1 testosterone increased the secretion of TFPI compared with the TNF-α-treated group.NF-κB DNA-binding activity was significantly suppressed by testosterone(P<0.05).This suggests that physiological testosterone concentrations may exert their antithrombotic effects on TFPI expression during inflammation by downregulating NF-κB activity.
基金the Health Research Fund from Health Department of Shaanxi Province,China,No. 04015
文摘Previous studies have confirmed that the anti-virus effects of Shuanghuanglian injection may be associated with nuclear factor-kappa B activity. This study observed nuclear factor-kappa B expression in mice with viral encephalitis, and showed significant decreases in nuclear factor-kappa B protein and mRNA levels following Shuanghuanglian injection. The inhibitory effect was more significant with prolonged intervention duration and increased treatment dose. These findings verify that Shuanghuanglian injection plays a therapeutic role in viral encephalitis by reducing expression of nuclear factor-kappa B in a time- and dose-dependent manner.
基金funded by the Health Research Fund from the Health Department of Shanxi Province, China, No.04015
文摘A mouse model of viral encephalitis was induced by intracranial injection of a Coxsackie virus B3 suspension. Quantitative real-time reverse transcription-PCR and western blot assay were applied to detect mRNA and protein expression of intelectin-2 and nuclear factor-kappa B in the viral encephalitis and control groups. Nuclear factor-kappa B and intelectin-2 mRNA and protein expression were significantly increased in mice with viral encephalitis. After intraperitoneal injection of Shuanghuanglian at a dose of 1.5 mg/kg for 5 successive days, intelectin-2 and nuclear factor-kappa B protein and mRNA expression were significantly decreased. To elucidate the relationship between intelectin-2 and nuclear factor-kappa B, mice with viral encephalitis were administered an intracerebral injection of 107 pfu recombinant lentivirus expressing intelectin shRNA. Both protein and mRNA levels of intelectin and nuclear factor-kappa B in brain tissue of mice were significantly decreased. Experimental findings suggest that Shuanghuanglian injection may downregulate nuclear factor-kappa B production via suppression of intelectin production, thus inhibiting inflammation associated with viral encephalitis.
基金Funded by the State High-Technology R&D Project of China (863 Program) ( 2007AA091603)
文摘The effects of five chito-oligomers, from dimer to hexamer （chitobiose, chitotriose, chitotetraose, chitopentaose, chitohexaose） separated from chitosan oligosaccharides, on nuclear factor -kappaB （NF-rd3） signaling pathway were investigated by using luciferase assay and laser scanning microscopy. The expression of NF-rd3 downstream genes （cyclin DI, TNFa and IL-6） were tested by real time PCR. We found that all five chitosan oligosaccharides increased NF-KB-dependent luciferase gene expression and NF-KB downstream genes transcription, and the most significant were chitotetraose and chitohexaose. In addition, laser scanning microscopy experiments showed that chitotetraose and chitohexaose also activated the p65 subunite of NF-kB translocating from cytoplasm to nucleus, which suggested that they were the most potent activators of NF-kB signaling pathway.
基金Supported by:the National Natural Science Foundation of China,No.30060034
文摘BACKGROUND： It has been reported that nuclear factor-kappa B （NF- κB）, activated after spinal cord injury in rats, plays a key role in inflammatory responses in the central nervous system. OBJECTIVE： To investigate the effects of transplantation of microencapsulated rabbit sciatic nerve on NF- κB expression and motor function after spinal cord injury in rats, and to compare the results with the transplantation of rabbit sciatic nerve alone. DESIGN, TIME AND SETTING： This completely randomized, controlled study was performed at the Department of Neurobiology, Medical College of Nanchang University between December 2007 and July 2008. MATERIALS： A rabbit anti-NF- κB P65 monoclonal antibody was made by the Santa Cruz Company, USA and a streptavidin peroxidase immunohistochemical kit was provided by the Sequoia Company, China. METHODS： Eight rabbits were used to prepare a sciatic nerve cell suspension that was divided into two parts： one stored for transplantation, and the other mixed with a 1.5% sodium alginate solution. One hundred and twenty adult Sprague Dawley rats weighing 220-250 g were randomly divided into four groups： the microencapsulated cell group （n = 36）, the non-encapsulated cell group （n = 36）, the saline group （n = 36） and the sham operation group （n = 12）. The first three groups underwent a right hemisection injury of the spinal cord at the T10 level, into which was transplanted a gelatin sponge soaked with 10 μL of a microencapsulated nerve tissue/cell suspension （microencapsulated cell group）, a tissue/cell suspension （non-encapsulated cell group） or physiological saline （saline group）. In the sham operation group the vertebrae were exposed, but the spinal cord was not injured, and no implantation was given. MAIN OUTCOME MEASURES： Pathological changes were detected using hematoxylin-eosin staining; NF- κB expression was quantified using immunohistochemical staining; motor function was assessed using the Basso, Beattie and Bresnahan （BBB） scale. RESULTS： Spinal cord injuries, such as neuronal death and inflammatory cell infiltration, were found in the microencapsulated cell group, the non-encapsulated cell group and the saline group. However, the damage in the microencapsulated cell group was milder than in the non-encapsulated cell or saline groups. NF- κB expression in the microencapsulated cell group, the non-encapsulated cell group and the saline group was increased after spinal cord injury; it reached a peak after 24 hours, gradually decreased after 3 days, and was close to normal levels after 7 days. NF- κB expression in the microencapsulated cell group was significantly lower than in the saline group and the non-encapsulated cell group （P 〈 0.05）. With time, the motor function of the animals in each group improved to a certain extent, but did not reach normal levels. There were no significant differences in BBB scores between the different groups on post-operative day 3; however, the BBB scores for the microencapsulated cell group and the non-encapsulated cell group were significantly higher than the saline group on post-operative day 7 （P 〈 0.05）. In addition, the motor function recovered better in the microencapsulated cell group than in the non-encapsulated cell group （P 〈 0.05）. CONCLUSION： The transplantation of microencapsulated rabbit sciatic nerve can inhibit NF- κB expression and inflammatory reactions and promote recovery of motor function after spinal cord injury in rats. The effects of microencapsulated cell transplantation are superior to those of transplantation of cells alone.
基金Supported by the Traditional Chinese Medicine Research Program of Zhejiang Province(No.2014ZB124)Scientific Research Projects of Shaoxing Science and Technology Bureau(No.2018C30128)
文摘OBJECTIVE:To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-alpha (TNF-cα) and nuclear factor-kappa B (NF-KB) levels in patients who have chronic heart failure with syndromes of deficiency of heart Yang.METHODS:A total of 63 patients with syndromes of deficiency of heart Yang (chronic heart failure)were enrolled.Patients were randomly divided into the control group and Jiawei Shenfu group.All patients received standard medications for treatment of chronic heart failure.Patients in the Jiawei Shenfu group were additionally provided Jiawei Shenfu decoction one dose daily.Treatments continued for 4 consecutive weeks.The primary endpoint was the change in plasma B-type natriuretic peptide (BNP),NF-KB,and TNF-cα levels during 4 weeks of treatment.RESULTS:At the 4-week follow-up,a significant reduction in BNP levels compared with baseline was observed in both groups,but the Jiawei Shenfu decoction group showed a significantly greater reduction than did the control group.The Jiawei Shenfu group also showed superior performance regarding the Minnesota Living with Heart Failure Questionnaire score,the Chinese medicine syndrome score,heart rate,left ventricular ejection fraction,and 6-min walking distance compared with the control group.The degree of changes in NF-KB and TNF-α levels in the Jiawei Shenfu group was more significant than that in the control group.CONCLUSION:Routine medicine combined with Jiawei Shenfu decoction for patients with heart Yang deficiency syndrome in chronic heart failure can improve the left ventricular ejection fraction and cardiac function,and reduce BNP levels.The mechanism may be related to inhibition of pro-inflammatory cytokines and the NF-KB-induced kinase pathway,leading to amelioration of the inflammatory response.
文摘In order to investigate the effect of nuclear factor kappa B (NF κB) on vascular endothelial growth factor (VEGF) mRNA expression of human pulmonary artery smooth muscle cells (HPASMCs) in hypoxia, the cultured HPASMCs in vitro were stimulated with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF κB. The NF κB p65 nuclei positive expression was detected by immunocytochemical technique. The IκBα protein expression was measured by Western blot. RT PCR was used to detect the VEGF mRNA expression of HPASMCs. The results showed that no significant change was observed in the NF κB p65 nuclei positive expression of cultured HPASMCs during 6 h-24 h in normoxia, but the levels of NF κB p65 nuclei positive expression of cultured HPASMCs were significantly increased in hypoxia groups as compared with those in all normoxia groups ( P <0.05). The IκBα protein expression of cultured HPASMCs showed no significant change during 6 h-24 h in normoxia, but significantly decreased in hypoxia as comapred with that in normoxia groups ( P <0.05). PDTC (1 to 100 μmol/L) could inhibit the VEGF mRNA expression of HPASMCs in a concentration dependent manner in hypoxia. In conclusion, NF κB can be partly translocation activated from cytoplasm into nuclei in the cultured HPASMCs under hypoxia. The inhibition of NF κB activation can decrease the VEGF mRNA expression. It is suggested that the activation of NF κB is involved in the VEGF mRNA expression of HPASMCs under hypoxia.
文摘Heavy infection of the virus leads to overproduction of cytokines. The overproduction of cytokine (cytokines storms) is responsible for the critical cases and deaths of COVID-19. The nuclear factor kappa-B stimulates the expression of the genes, which is responsible for cytokines storm and RNA transcription. The COVID-19 virus can be controlled by inhibition of nuclear factor kappa-B. Nuclear factor kappa-B is controlled by inhibition of hydrogen peroxide and inhibitor kappa-B kinase enzyme.
