INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 a...INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .展开更多
To solve the problem of immune incompatibility, nuclear transplantation has been envisaged as a means to produce cells or tissues for human autologous transplantation. Here we have derived embryonic stem cells by the ...To solve the problem of immune incompatibility, nuclear transplantation has been envisaged as a means to produce cells or tissues for human autologous transplantation. Here we have derived embryonic stem cells by the transfer of human somatic nuclei into rabbit oocytes. The number of blastocysts that developed from the fused nuclear transfer was comparable among nuclear donors at ages of 5, 42, 52 and 60 years, and nuclear transfer (NT) embryonic stem cells (ntES cells) were subsequently derived from each of the four age groups. These results suggest that human somatic nuclei can form ntES cells independent of the age of the donor. The derived ntES cells are human based on karyotype, isogenicity, in situ hybridization, PCR and immunocytochemistry with probes that distinguish between the various species. The ntES cells maintain the capability of sustained growth in an undifferentiated state, and form embryoid bodies, which, on further induction, give rise to cell types such as neuron and muscle, as well as mixed cell populations that express markers representative of all three germ layers. Thus, ntES cells derived from human somatic cells by NT to rabbit eggs retain phenotypes similar to those of conventional human ES cells, including the ability to undergo multilineage cellular differentiation.展开更多
This paper demonstrates capabilities of low-field nuclear magnetic resonance (NMR) and microfocus X-ray computed tomography (μCT) in advanced, nondestructive, and quantitative characterization of pore types, producib...This paper demonstrates capabilities of low-field nuclear magnetic resonance (NMR) and microfocus X-ray computed tomography (μCT) in advanced, nondestructive, and quantitative characterization of pore types, producible porosity, pore structure, and spatial disposition of pore-fractures in coals. Results show that the NMR transverse relaxation time (T2) at 0.5–2.5, 20–50, and 】100 ms correspond to pores of 【0.1 μm, 】0.1 μm, and fractures, respectively. A much higher T2 spectrum peak reflects a much better development of pores (or fractures) corresponding to the T2, and vice versa. Three basic components in coals, i.e., the pores (or fractures), coal matrix, and minerals have their distinctive range of CT numbers. Among these, the CT number of pores is commonly less than 600 HU. The producible porosity, which is a determination of permeability, can be calculated by T2 cutoff value (T2C) of coal NMR. The coal pore structure can be efficiently estimated by the newly proposed "T2C based model". Finally, μCT scan was proven capable of modeling and spatial visualization of pores and fractures.展开更多
In many organisms, the difference in codon usage patterns among genes reflects variation in local base compositional biases and the intensity of natural selection. In this study, a comparative analysis was performed t...In many organisms, the difference in codon usage patterns among genes reflects variation in local base compositional biases and the intensity of natural selection. In this study, a comparative analysis was performed to investigate the characteristics of codon bias and factors in shaping the codon usage patterns among mitochondrion, chloroplast and nuclear genes in common wheat （Triticum aestivum L.）. GC contents in nuclear genes were higher than that in mitochondrion and chloroplast genes. The neutrality and correspondence analyses indicated that the codon usage in nuclear genes would be a result of relative strong mutational bias, while the codon usage patterns of mitochondrion and chloroplast genes were more conserved in GC content and influenced by translation level. The Parity Rule 2 （PR2） plot analysis showed that pyrimidines were used more frequently than purines at the third codon position in the three genomes. In addition, using a new alterative strategy, 11, 12, and 24 triplets were defined as preferred codons in the mitochondrion, chloroplast and nuclear genes, respectively. These findings suggested that the mitochondrion, chloroplast and nuclear genes shared particularly different features of codon usage and evolutionary constraints.展开更多
Environmental characteristics and phytoplankton community structure were investigated in two aquaculture areas in Dapeng Cove of Daya Bay, South China Sea, between April 2005 and June 2006. Phytoplankton abundance ran...Environmental characteristics and phytoplankton community structure were investigated in two aquaculture areas in Dapeng Cove of Daya Bay, South China Sea, between April 2005 and June 2006. Phytoplankton abundance ranged between 5.0 and 8877.5 cells/mL, with an average of 751.8 cells/mL. The seasonal cycle of phytoplankton were demonstrated by frequent oscillations, with recurrent high abundances from late spring to autumn and a peak stage in late winter. Diatoms were the predominant phytoplankton group, accounting for 93.21% of the total abundance. The next most abundant group was the dinoflagellates, which made up only 1.24% of total abundance. High concentrations of Alexandrium tamarense （Lebour） Balech with a maximum of 603.0 cells/mL were firstly recorded in this area known for high rates of paralytic shellfish poisoning （PSP） contamination. Temperatures and salinities were within the suitable values for the growth of phytoplankton, and were important in phytoplankton seasonal fluctuations. The operation of the Daya Bay Nuclear Power Station （DNPS） exerts influences on the phytoplankton community and resulted in the high abundances of toxic dinoflagellate species during the winter months. Dissolved inorganic nitrogen （DIN） and dissolved silicate （DSi） were sufficient, and rarely limited for the growth of phytoplankton. Dissolved inorganic phosphorus （DIP） was the most necessary element for phytoplankton growth. The enriched environments accelerated the growth of small diatoms, and made for the shift in predominant species from large diatom Rhizosolenia spp. to chain-forming diatoms such as Skeletonema costatum, Pseudo-nitzschia spp. and Thalassiosira subtilis.展开更多
AIM:To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis(UC),and their effect on inflammatory mediators and nuclear factor(NF)κB activation in these patients.METHODS:Thirty patients...AIM:To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis(UC),and their effect on inflammatory mediators and nuclear factor(NF)κB activation in these patients.METHODS:Thirty patients with mild to moderate UC were randomly classified into two groups:sulfasalazine group,who received sulfasalazine 2400 mg/d;and probiotic group,who received sulfasalazine 2400 mg/d with probiotic.The patients were investigated before and after 8 wk of treatment with probiotic(Lactobacillus delbruekii and Lactobacillus fermentum).Colonic activity of myeloperoxidase(MPO)was assayed with UV spectrophotometry,the colonic content of interleukin(IL)-6 was determined by enzyme-linked immunosorbent assay(ELISA),fecal calprotectin was determined by ELISA,and expression of NF-κB p65 and tumor necrosis factor (TNF)-αproteins in colonic tissue was identified by immunohistochemistry and reverse transcription polymerase chain reaction,respectively.RESULTS:At the start of the study,colonic mucosal injury and inflammation were demonstrated in UC patients by hematoxylin and eosin staining,and an increase in colonic MPO activity,fecal calprotectin,and expression of colonic TNF-αand NF-κB p65 proteins.The use of probiotic for 8 wk significantly ameliorated the inflammation by decreasing the colonic concentration of IL-6,expression of TNF-αand NF-κB p65,leukocyte recruitment,as demonstrated by a decrease in colonic MPO activity,and the level of fecal calprotectin compared to sulfasalazine group and the control group(P<0.05).CONCLUSION:Oral supplementation with probiotics could be helpful in maintaining remission and preventing relapse of UC.展开更多
Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health p...Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.展开更多
AIM To find out the difference of humanprimary liver carcinogenesis between Han andminority ethnic patients in Xinjiang.METHODS Expression of p53,c-erbB-2,H-rasp21 protein and proliferating cell nuclearantigen(PCNA)in...AIM To find out the difference of humanprimary liver carcinogenesis between Han andminority ethnic patients in Xinjiang.METHODS Expression of p53,c-erbB-2,H-rasp21 protein and proliferating cell nuclearantigen(PCNA)in tumor tissues of 50 patients(Han 38,minority 12)with primary hepaticcarcinoma was detected byimmunohistochemistry(LSAB).RESULTS The positive frequency of p53,c-erbB-2,H-rasp21 and PCNA expression was46.0%(23/50),70.0%(35/50),68.0%(34/50)and 82.0%(41/50)in tumor tissues;4.0%(2/50),22.0%(11/50),64.0%(32/50)and 52.0%(26/ 50)in peritumors respectively and asignificant difference,except for H-rasp21,ofoncogene alteration was found(P【0.05)between tumor and non-tumorous tissues.Combined the three oncogenes alteration,26%(13/50)tumor tissues had positiveimmunoreactivity,but in peritumor and normallivers it was negative.The positive rate of p53,c-erbB-2 and H-rasp21 protein expression was39.5%(15/38),60.5%(23/38)and 39.5%(15/38)in tumors of Han patients;66.7%(8/12),100%(12/12)and 75.0%(9/12)in minoritiesrespectively,with statistical difference (P【0.05).CONCLUSION Overexpression of p53,c-erbB-2and H-rasp21 in human primary liver carcinoma isan important biomarker of genetic alteration.The different frequency of these oncogeneticchanges may reflect some environmental or/andethnic hereditary factors affecting the livercarcinogenesis.The special life style of Han,Uygur,Kazak and Mongolia nationalities inXinjiang may also be related to theetiopathogenesis of this disease.展开更多
AIM： To investigate the suppressive effect of saikosaponin-d （SSd） on hepatic fibrosis in rats induced by CCh injections in combination with alcohol and high fat, low protein feeding and its relationship with the e...AIM： To investigate the suppressive effect of saikosaponin-d （SSd） on hepatic fibrosis in rats induced by CCh injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-κB （NF-κB）, tumor necrosis factor-alpha （TNF-α） and interleukins-6 （IL-6）. METHODS： Hepatic fibrosis models were induced by subcutaneous injection of CCh at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses （1.0, 1.5 and 2.0 mg/kg） once daily for 6 wk in combination with CCh, while the control group received olive oil instead of CCh. At the end of the experiment, rats were anesthetized and killed （except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in lowdose group）. Hernatoxylin and eosin （HE） staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase （ALT）, triglyeride （TG）, albumin （ALB）, globulin （GLB）, hyaluronic acid （HA） and larninin （LN） in serum and the content of hydroxyproline （HYP） in liver were measured by biochemical examinations and radioimmuneoassay, respectively. In addition, the expression of TNF-α and IL-6 in liver homogenate was evaluated by enzymelinked immunosorbent assay （ELISA） and the levels of NF-κBp65 and I-κBa in liver tissue were analyzed by Western blotting. RESULTS： Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-α and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas, the treatment with SScl markedly reduced all the above parameters compared with the model group, especially in the medium gr展开更多
Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats....Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment （intravenous injection） re- duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-a in brain tissue. Pretreatment with puerarin （intravenous injection） attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 （JAK2） and signal transducers and activators of transcription 3 （STAT3） activation and nuclear factor kappa B （NF-KB） inhibition. These observa- tions were inhibited by the alpha7 nicotinic acetylcholine receptor （a7nAchR） antagonist a-bungarotoxin （a-BGT）. In addition, puerarin pretreatment increased the expression of a7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re- sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi- ated through the activation of the cholinergic anti-inflammatory pathway.展开更多
Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage （SAH）. Nuclear factor-kappa B （NF-κB） regulates many genes essential for inflammation...Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage （SAH）. Nuclear factor-kappa B （NF-κB） regulates many genes essential for inflammation and immunity and is activated by toll-like receptor （TLR）. This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B （TLR4/NF-κB） signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-κB activity and concentrations of tumor necrosis factor-alpha （TNF-α）, interleukin-lbeta （IL-1β） and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay （ELISA）. Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein： an initial peak （2-6 hours） and a sustained elevation （12-48 hours）. Immunohistochemical staining showed the inducible expression of TLR4-like immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-κB subunit p65 as well as the production of NF-κB-regulated proinflammatory cytokines （TNF-α, IL-1β and IL-6） were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-κB signaling in early brain injury. Activation of the TLR4/NF-κB signaling may regulate the inflammatory responses after SAH.展开更多
To investigate the therapeutic effect of Jianpi Qingchang decoction (JPQCD) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice.METHODSC57BL/c mice were injected intragastrically with 5% DSS instea...To investigate the therapeutic effect of Jianpi Qingchang decoction (JPQCD) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice.METHODSC57BL/c mice were injected intragastrically with 5% DSS instead of drinking water for 7 d, and their body weight, diarrhea severity and fecal bleeding were monitored, while the mice in the control group were treated with standard drinking water, without DSS. After 7 d, the DSS drinking water was changed to normal water and the DSS group continued with DSS water. The control and DSS groups were given normal saline by intragastric injection. The 5-aminosalicylic acid (5-ASA) group was treated orally with 5-ASA at a dose of 100 mg/kg daily. The JPQCD group was treated orally with JPQCD at a dose of 17.1 g/kg daily. On day 14, the colon length was measured, the colorectal histopathological damage score was assessed, and protein levels of interleukin (IL)-1β, IL-8 and tumor necrosis factor-alpha (TNF-α) in colon supernatants were measured by enzyme-linked immunosorbent assay. mRNA expression of IL-1β, IL-8, TNF-α and nuclear factor-kappa B (NF-κB) was detected by real-time quantitative polymerase chain reaction. Western blotting was used to detect the protein expression of NF-κB and inhibitor of kappa B.RESULTSAcute inflammation occurred in the mice administered DSS, including the symptoms of losing body weight, loose feces/watery diarrhea and presence of fecal blood; all these symptoms worsened at 7 d. The colons of mice treated with DSS were assessed by histological examination, and the results confirmed that acute inflammation had occurred, as evidenced by loss of colonic mucosa and chronic inflammatory cell infiltration, and these features extended into the deeper layer of the colon walls. The expression levels of IL-1β, IL-8 and TNF-α in the DSS group were higher than those in the control group (P < 0.05), and the expression levels of IL-1β, IL-8 and TNF-α in the JPQCD and 5-ASA groups were lower than those in the DSS group after treating with JPQCD a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
AIM： To determine the effect of ellagic acid on apoptosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid.METHODS： The effect of ellagic acid o...AIM： To determine the effect of ellagic acid on apoptosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid.METHODS： The effect of ellagic acid on apoptosis was assessed by measuring Phosphatidylserine externalization, caspase activity, mitochondrial membrane potential and DNA fragmentation; and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells, and in isolated mitochondria. Nuclear factor κB （NF-κB） activity was measured by electromobility shift assay （EMSA）. RESULTS： We show that ellagic acid, a polyphenolic compound in fruits and berries, at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further, ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. Ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization, cytochrome C release, and the downstream caspase activation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-κB binding activity. Furthermore, inhibition of NF-κB activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis. CONCLUSION： Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosurvival transcription factor NF-κB.展开更多
AIM:To investigate whether curcumin could attenuate nuclear factor(NF)-κB p65 expression and macromolecular leakage in the gastric mucosa of Helicobacter pylori(H.pylori)-infected rats.METHODS:Twenty-five male Spragu...AIM:To investigate whether curcumin could attenuate nuclear factor(NF)-κB p65 expression and macromolecular leakage in the gastric mucosa of Helicobacter pylori(H.pylori)-infected rats.METHODS:Twenty-five male Sprague-Dawley rats were equally divided into five groups:control rats(Control),control rats supplemented with 600 mg/kg curcumin,H.pylori-infected rats(Hp),H.pylori-infected rats supplemented with 200 mg/kg curcumin(Hp + curIn H.pylori-infected groups,rats were inoculated with H.pylori suspension twice a day at an interval of 4 h for 3 d.Two weeks later,200 or 600 mg/kg curcumin was given once daily to curcuminsupplemented groups for 7 d.On the day of the experiment,macromolecular leakage in gastric mucosa was examined by intravital fluorescence microscopy.The stomach tissue was removed to examine NF-κB p65 expression in gastric epithelial cells by immunohistochemistry.RESULTS:The expression of NF-κB p65 in gastric epithelial cells and the macromolecular leakage from gastric mucosal microcirculation significantly increased in the Hp group compared with the Control group.The percentages of NF-κB p65 immunoreactive cells in Control and Hp groups were 10.72% ± 2.10% vs 16.02% ± 2.98%,P = 0.004,respectively.The percentages of macromolecular leakage in Control and Hp groups were 10.69% ± 1.43% vs 15.41% ± 2.83%,P = 0.001,respectively.Curcumin supplementation in Hp + cur-CONCLUSION:H.pylori-induced gastric inflammation in rats is associated with increased NF-κB activation and macromolecular leakage which can be reduced by curcumin supplementation.展开更多
Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral ischemia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ische...Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral ischemia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin （100 mg/kg） was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin significantly improved neurological deficit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-α in the ischemic region. These data indicate that puerarin exerts an anti-inflammatory protective effect on brain tissue with ischemia/reperfusion damage by downregulating the expression of multiple inflammatory factors.展开更多
The tissue destruction characteristic of syphilis infection may be caused by inflammation due to Treponema pallidum and the ensuing immune responses to the pathogen.T.pallidum membrane proteins are thought to be poten...The tissue destruction characteristic of syphilis infection may be caused by inflammation due to Treponema pallidum and the ensuing immune responses to the pathogen.T.pallidum membrane proteins are thought to be potent inducers of inflammation during the early stages of infection.However,the actual membrane proteins that induce inflammatory cytokine production are not known,nor are the molecular mechanisms responsible for triggering and sustaining the inflammatory cascades.In the present study,Tp0751 recombinant protein from T.pallidum was found to induce the production of proinflammatory cytokines,including TNF-α,IL-1βand IL-6,in a THP-1 human monocyte cell line.The signal transduction pathways involved in the production of these cytokines were then further investigated.No inhibition of TNF-a,IL-1β,or IL-6 production was observed following treatment with the SAPK/JNK specific inhibitor SP600125 or with an ERK inhibitor PD98059.By contrast,anti-TLR2 mAb,anti-CD14 mAb,and the p38 inhibitor SB203580 significantly inhibited the production of all three cytokines.In addition,pyrrolidine dithiocarbamate (PDTC),a specific inhibitor of NF-κB,profoundly inhibited the production of these cytokines.Tp0751 treatment strongly activated NF-κB,as revealed by Western blotting.However,NF-κB translocation was significantly inhibited by treatment with PDTC.These results indicated that TLR2,CD14,MAPKs/p38,and NF-κB might be implicated in the inflammatory reaction caused by T.pallidum infection.展开更多
African swine fever(ASF)is an infectious transboundary disease of domestic pigs and wild boar and spreading throughout Eurasia.There is no vaccine and treatment available.Complex immune escape strategies of African sw...African swine fever(ASF)is an infectious transboundary disease of domestic pigs and wild boar and spreading throughout Eurasia.There is no vaccine and treatment available.Complex immune escape strategies of African swine fever virus(ASFV)are crucial factors affecting immune prevention and vaccine development.MGF360 genes have been implicated in the modulation of the IFN-Ⅰresponse.The molecular mechanisms contributing to innate immunity are poorly understood.In this study,we demonstrated that ASFV MGF360-12 L(MGF360 families 12 L protein)significantly inhibited the mRNA transcription and promoter activity of IFN-βand NF-κB,accompanied by decreases of IRF3,STING,TBK1,ISG54,ISG56 and AP-1 m RNA transcription.Also,MGF360-12 L might suppress the nuclear localization of p50 and p65 mediated by classical nuclear localization signal(NLS).Additionally,MGF360-12 L could interact with KPNA2,KPNA3,and KPNA4,which interrupted the interaction between p65 and KPNA2,KPNA3,KPNA4.We further found that MGF360-12 L could interfere with the NF-κB nuclear translocation by competitively inhibiting the interaction between NF-κB and nuclear transport proteins.These findings suggested that MGF360-12 L could inhibit the IFN-Ⅰproduction by blocking the interaction of importinαand NF-κB signaling pathway,which might reveal a novel strategy for ASFV to escape the host innate immune response.展开更多
Bone metastasis is the leading cause of death in prostate cancer patients,for which there is currently no effective treatment.Since the bone microenvironment plays an important role in this process,attentions have bee...Bone metastasis is the leading cause of death in prostate cancer patients,for which there is currently no effective treatment.Since the bone microenvironment plays an important role in this process,attentions have been directed to the interactions between cancer cells and the bone microenvironment,including osteoclasts,osteoblasts,and bone stromal cells.Here,we explained the mechanism of interactions between prostate cancer cells and metastasis-associated cells within the bone microenvironment and further discussed the recent advances in targeted therapy of prostate cancer bone metastasis.This review also summarized the effects of bone microenvironment on prostate cancer metastasis and the related mechanisms,and provides insights for future prostate cancer metastasis studies.展开更多
基金Supported by the Medical Research Foundation of Guangdong Province,No.1997423
文摘INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .
基金supported by grants from the Major State Basic Research Development Program of China(No.001CB5099)the National High Technology Research and Development Program of China(No.2001AA216121)+3 种基金National Natural Science Foundation of China(No.30040003)Projects of Shanghai Science&Technology Development Foundation(No.99DJ14002,00DJ14033,01DJ14003)the Chinese Academy of Sciences(No.KSCX-2-3-08)Shanghai Municipal Education Commission and by Shanghai Second Medical University
文摘To solve the problem of immune incompatibility, nuclear transplantation has been envisaged as a means to produce cells or tissues for human autologous transplantation. Here we have derived embryonic stem cells by the transfer of human somatic nuclei into rabbit oocytes. The number of blastocysts that developed from the fused nuclear transfer was comparable among nuclear donors at ages of 5, 42, 52 and 60 years, and nuclear transfer (NT) embryonic stem cells (ntES cells) were subsequently derived from each of the four age groups. These results suggest that human somatic nuclei can form ntES cells independent of the age of the donor. The derived ntES cells are human based on karyotype, isogenicity, in situ hybridization, PCR and immunocytochemistry with probes that distinguish between the various species. The ntES cells maintain the capability of sustained growth in an undifferentiated state, and form embryoid bodies, which, on further induction, give rise to cell types such as neuron and muscle, as well as mixed cell populations that express markers representative of all three germ layers. Thus, ntES cells derived from human somatic cells by NT to rabbit eggs retain phenotypes similar to those of conventional human ES cells, including the ability to undergo multilineage cellular differentiation.
基金supported by National Major Research Program for Science and Technology of China (Grant Nos. 2008ZX05034-01 and 2008ZX05062-001)National Basic Research Program of China (Grant No. 2009CB219604)+2 种基金National Natural Science Foundation of China (Grant No. 40972107)Petro China Innovation Foundation (Grant No. 2008D-5006-01-04)Program for Changjiang Scholars and Innovative Research Team in University (Grant No. IRT0864)
文摘This paper demonstrates capabilities of low-field nuclear magnetic resonance (NMR) and microfocus X-ray computed tomography (μCT) in advanced, nondestructive, and quantitative characterization of pore types, producible porosity, pore structure, and spatial disposition of pore-fractures in coals. Results show that the NMR transverse relaxation time (T2) at 0.5–2.5, 20–50, and 】100 ms correspond to pores of 【0.1 μm, 】0.1 μm, and fractures, respectively. A much higher T2 spectrum peak reflects a much better development of pores (or fractures) corresponding to the T2, and vice versa. Three basic components in coals, i.e., the pores (or fractures), coal matrix, and minerals have their distinctive range of CT numbers. Among these, the CT number of pores is commonly less than 600 HU. The producible porosity, which is a determination of permeability, can be calculated by T2 cutoff value (T2C) of coal NMR. The coal pore structure can be efficiently estimated by the newly proposed "T2C based model". Finally, μCT scan was proven capable of modeling and spatial visualization of pores and fractures.
基金Supported by the Sate Key Basic Research and Development Plan of China （2003CB715904） and the National Science Foundation for 0verseas Distinguished Young Scholar （30428003）
文摘In many organisms, the difference in codon usage patterns among genes reflects variation in local base compositional biases and the intensity of natural selection. In this study, a comparative analysis was performed to investigate the characteristics of codon bias and factors in shaping the codon usage patterns among mitochondrion, chloroplast and nuclear genes in common wheat （Triticum aestivum L.）. GC contents in nuclear genes were higher than that in mitochondrion and chloroplast genes. The neutrality and correspondence analyses indicated that the codon usage in nuclear genes would be a result of relative strong mutational bias, while the codon usage patterns of mitochondrion and chloroplast genes were more conserved in GC content and influenced by translation level. The Parity Rule 2 （PR2） plot analysis showed that pyrimidines were used more frequently than purines at the third codon position in the three genomes. In addition, using a new alterative strategy, 11, 12, and 24 triplets were defined as preferred codons in the mitochondrion, chloroplast and nuclear genes, respectively. These findings suggested that the mitochondrion, chloroplast and nuclear genes shared particularly different features of codon usage and evolutionary constraints.
基金supported by the National Natural Science Foundation of China(No.40673062,40773063, U0633006)
文摘Environmental characteristics and phytoplankton community structure were investigated in two aquaculture areas in Dapeng Cove of Daya Bay, South China Sea, between April 2005 and June 2006. Phytoplankton abundance ranged between 5.0 and 8877.5 cells/mL, with an average of 751.8 cells/mL. The seasonal cycle of phytoplankton were demonstrated by frequent oscillations, with recurrent high abundances from late spring to autumn and a peak stage in late winter. Diatoms were the predominant phytoplankton group, accounting for 93.21% of the total abundance. The next most abundant group was the dinoflagellates, which made up only 1.24% of total abundance. High concentrations of Alexandrium tamarense （Lebour） Balech with a maximum of 603.0 cells/mL were firstly recorded in this area known for high rates of paralytic shellfish poisoning （PSP） contamination. Temperatures and salinities were within the suitable values for the growth of phytoplankton, and were important in phytoplankton seasonal fluctuations. The operation of the Daya Bay Nuclear Power Station （DNPS） exerts influences on the phytoplankton community and resulted in the high abundances of toxic dinoflagellate species during the winter months. Dissolved inorganic nitrogen （DIN） and dissolved silicate （DSi） were sufficient, and rarely limited for the growth of phytoplankton. Dissolved inorganic phosphorus （DIP） was the most necessary element for phytoplankton growth. The enriched environments accelerated the growth of small diatoms, and made for the shift in predominant species from large diatom Rhizosolenia spp. to chain-forming diatoms such as Skeletonema costatum, Pseudo-nitzschia spp. and Thalassiosira subtilis.
文摘AIM:To demonstrate the therapeutic effect of probiotics in patients with ulcerative colitis(UC),and their effect on inflammatory mediators and nuclear factor(NF)κB activation in these patients.METHODS:Thirty patients with mild to moderate UC were randomly classified into two groups:sulfasalazine group,who received sulfasalazine 2400 mg/d;and probiotic group,who received sulfasalazine 2400 mg/d with probiotic.The patients were investigated before and after 8 wk of treatment with probiotic(Lactobacillus delbruekii and Lactobacillus fermentum).Colonic activity of myeloperoxidase(MPO)was assayed with UV spectrophotometry,the colonic content of interleukin(IL)-6 was determined by enzyme-linked immunosorbent assay(ELISA),fecal calprotectin was determined by ELISA,and expression of NF-κB p65 and tumor necrosis factor (TNF)-αproteins in colonic tissue was identified by immunohistochemistry and reverse transcription polymerase chain reaction,respectively.RESULTS:At the start of the study,colonic mucosal injury and inflammation were demonstrated in UC patients by hematoxylin and eosin staining,and an increase in colonic MPO activity,fecal calprotectin,and expression of colonic TNF-αand NF-κB p65 proteins.The use of probiotic for 8 wk significantly ameliorated the inflammation by decreasing the colonic concentration of IL-6,expression of TNF-αand NF-κB p65,leukocyte recruitment,as demonstrated by a decrease in colonic MPO activity,and the level of fecal calprotectin compared to sulfasalazine group and the control group(P<0.05).CONCLUSION:Oral supplementation with probiotics could be helpful in maintaining remission and preventing relapse of UC.
文摘Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.
文摘AIM To find out the difference of humanprimary liver carcinogenesis between Han andminority ethnic patients in Xinjiang.METHODS Expression of p53,c-erbB-2,H-rasp21 protein and proliferating cell nuclearantigen(PCNA)in tumor tissues of 50 patients(Han 38,minority 12)with primary hepaticcarcinoma was detected byimmunohistochemistry(LSAB).RESULTS The positive frequency of p53,c-erbB-2,H-rasp21 and PCNA expression was46.0%(23/50),70.0%(35/50),68.0%(34/50)and 82.0%(41/50)in tumor tissues;4.0%(2/50),22.0%(11/50),64.0%(32/50)and 52.0%(26/ 50)in peritumors respectively and asignificant difference,except for H-rasp21,ofoncogene alteration was found(P【0.05)between tumor and non-tumorous tissues.Combined the three oncogenes alteration,26%(13/50)tumor tissues had positiveimmunoreactivity,but in peritumor and normallivers it was negative.The positive rate of p53,c-erbB-2 and H-rasp21 protein expression was39.5%(15/38),60.5%(23/38)and 39.5%(15/38)in tumors of Han patients;66.7%(8/12),100%(12/12)and 75.0%(9/12)in minoritiesrespectively,with statistical difference (P【0.05).CONCLUSION Overexpression of p53,c-erbB-2and H-rasp21 in human primary liver carcinoma isan important biomarker of genetic alteration.The different frequency of these oncogeneticchanges may reflect some environmental or/andethnic hereditary factors affecting the livercarcinogenesis.The special life style of Han,Uygur,Kazak and Mongolia nationalities inXinjiang may also be related to theetiopathogenesis of this disease.
基金the National Natural Science Foundation of China, No. 30471982
文摘AIM： To investigate the suppressive effect of saikosaponin-d （SSd） on hepatic fibrosis in rats induced by CCh injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-κB （NF-κB）, tumor necrosis factor-alpha （TNF-α） and interleukins-6 （IL-6）. METHODS： Hepatic fibrosis models were induced by subcutaneous injection of CCh at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses （1.0, 1.5 and 2.0 mg/kg） once daily for 6 wk in combination with CCh, while the control group received olive oil instead of CCh. At the end of the experiment, rats were anesthetized and killed （except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in lowdose group）. Hernatoxylin and eosin （HE） staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase （ALT）, triglyeride （TG）, albumin （ALB）, globulin （GLB）, hyaluronic acid （HA） and larninin （LN） in serum and the content of hydroxyproline （HYP） in liver were measured by biochemical examinations and radioimmuneoassay, respectively. In addition, the expression of TNF-α and IL-6 in liver homogenate was evaluated by enzymelinked immunosorbent assay （ELISA） and the levels of NF-κBp65 and I-κBa in liver tissue were analyzed by Western blotting. RESULTS： Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-α and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas, the treatment with SScl markedly reduced all the above parameters compared with the model group, especially in the medium gr
基金supported by the Young Scientists Foundation of Hubei Provincial Health Department,No.QJX2012-16
文摘Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment （intravenous injection） re- duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-a in brain tissue. Pretreatment with puerarin （intravenous injection） attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 （JAK2） and signal transducers and activators of transcription 3 （STAT3） activation and nuclear factor kappa B （NF-KB） inhibition. These observa- tions were inhibited by the alpha7 nicotinic acetylcholine receptor （a7nAchR） antagonist a-bungarotoxin （a-BGT）. In addition, puerarin pretreatment increased the expression of a7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re- sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi- ated through the activation of the cholinergic anti-inflammatory pathway.
文摘Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage （SAH）. Nuclear factor-kappa B （NF-κB） regulates many genes essential for inflammation and immunity and is activated by toll-like receptor （TLR）. This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B （TLR4/NF-κB） signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-κB activity and concentrations of tumor necrosis factor-alpha （TNF-α）, interleukin-lbeta （IL-1β） and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay （ELISA）. Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein： an initial peak （2-6 hours） and a sustained elevation （12-48 hours）. Immunohistochemical staining showed the inducible expression of TLR4-like immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-κB subunit p65 as well as the production of NF-κB-regulated proinflammatory cytokines （TNF-α, IL-1β and IL-6） were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-κB signaling in early brain injury. Activation of the TLR4/NF-κB signaling may regulate the inflammatory responses after SAH.
基金Supported by the National Natural Science Foundation of China,No.81403355 and No.81573892the Project of 3-Year Action Plan for Shanghai Municipal Chinese Medicine Development,No.ZY3-RCPY-2-2001
文摘To investigate the therapeutic effect of Jianpi Qingchang decoction (JPQCD) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice.METHODSC57BL/c mice were injected intragastrically with 5% DSS instead of drinking water for 7 d, and their body weight, diarrhea severity and fecal bleeding were monitored, while the mice in the control group were treated with standard drinking water, without DSS. After 7 d, the DSS drinking water was changed to normal water and the DSS group continued with DSS water. The control and DSS groups were given normal saline by intragastric injection. The 5-aminosalicylic acid (5-ASA) group was treated orally with 5-ASA at a dose of 100 mg/kg daily. The JPQCD group was treated orally with JPQCD at a dose of 17.1 g/kg daily. On day 14, the colon length was measured, the colorectal histopathological damage score was assessed, and protein levels of interleukin (IL)-1β, IL-8 and tumor necrosis factor-alpha (TNF-α) in colon supernatants were measured by enzyme-linked immunosorbent assay. mRNA expression of IL-1β, IL-8, TNF-α and nuclear factor-kappa B (NF-κB) was detected by real-time quantitative polymerase chain reaction. Western blotting was used to detect the protein expression of NF-κB and inhibitor of kappa B.RESULTSAcute inflammation occurred in the mice administered DSS, including the symptoms of losing body weight, loose feces/watery diarrhea and presence of fecal blood; all these symptoms worsened at 7 d. The colons of mice treated with DSS were assessed by histological examination, and the results confirmed that acute inflammation had occurred, as evidenced by loss of colonic mucosa and chronic inflammatory cell infiltration, and these features extended into the deeper layer of the colon walls. The expression levels of IL-1β, IL-8 and TNF-α in the DSS group were higher than those in the control group (P < 0.05), and the expression levels of IL-1β, IL-8 and TNF-α in the JPQCD and 5-ASA groups were lower than those in the DSS group after treating with JPQCD a
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the Department of Veterans Affairs Merit Review (to A.S.G), the Hirshberg foundation and the NIH/NCCAM (1P01AT003960-01)
文摘AIM： To determine the effect of ellagic acid on apoptosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid.METHODS： The effect of ellagic acid on apoptosis was assessed by measuring Phosphatidylserine externalization, caspase activity, mitochondrial membrane potential and DNA fragmentation; and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells, and in isolated mitochondria. Nuclear factor κB （NF-κB） activity was measured by electromobility shift assay （EMSA）. RESULTS： We show that ellagic acid, a polyphenolic compound in fruits and berries, at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further, ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. Ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization, cytochrome C release, and the downstream caspase activation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-κB binding activity. Furthermore, inhibition of NF-κB activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis. CONCLUSION： Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosurvival transcription factor NF-κB.
基金Supported by Thailand Research fund (code RMU 4980032)Graduate Thesis Grant,Graduate School,Chulalongkorn University,Thailand
文摘AIM:To investigate whether curcumin could attenuate nuclear factor(NF)-κB p65 expression and macromolecular leakage in the gastric mucosa of Helicobacter pylori(H.pylori)-infected rats.METHODS:Twenty-five male Sprague-Dawley rats were equally divided into five groups:control rats(Control),control rats supplemented with 600 mg/kg curcumin,H.pylori-infected rats(Hp),H.pylori-infected rats supplemented with 200 mg/kg curcumin(Hp + curIn H.pylori-infected groups,rats were inoculated with H.pylori suspension twice a day at an interval of 4 h for 3 d.Two weeks later,200 or 600 mg/kg curcumin was given once daily to curcuminsupplemented groups for 7 d.On the day of the experiment,macromolecular leakage in gastric mucosa was examined by intravital fluorescence microscopy.The stomach tissue was removed to examine NF-κB p65 expression in gastric epithelial cells by immunohistochemistry.RESULTS:The expression of NF-κB p65 in gastric epithelial cells and the macromolecular leakage from gastric mucosal microcirculation significantly increased in the Hp group compared with the Control group.The percentages of NF-κB p65 immunoreactive cells in Control and Hp groups were 10.72% ± 2.10% vs 16.02% ± 2.98%,P = 0.004,respectively.The percentages of macromolecular leakage in Control and Hp groups were 10.69% ± 1.43% vs 15.41% ± 2.83%,P = 0.001,respectively.Curcumin supplementation in Hp + cur-CONCLUSION:H.pylori-induced gastric inflammation in rats is associated with increased NF-κB activation and macromolecular leakage which can be reduced by curcumin supplementation.
基金supported by the Chinese Traditional Medical Science Foundation of Zhejiang Province in China,No.2010ZA072the Health Bureau Foundation of Zhejiang Province in China,No.2012ZDA023the Qianjiang Project of Zhejiang Science and Technology Bureau in China,No.2010 R10073
文摘Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral ischemia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin （100 mg/kg） was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin significantly improved neurological deficit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-α in the ischemic region. These data indicate that puerarin exerts an anti-inflammatory protective effect on brain tissue with ischemia/reperfusion damage by downregulating the expression of multiple inflammatory factors.
基金supported by the National Natural Science Foundation of China (Grant No. 30800996)the National Natural Science Foundation of Hunan Province (Grant No. 07ii3028)
文摘The tissue destruction characteristic of syphilis infection may be caused by inflammation due to Treponema pallidum and the ensuing immune responses to the pathogen.T.pallidum membrane proteins are thought to be potent inducers of inflammation during the early stages of infection.However,the actual membrane proteins that induce inflammatory cytokine production are not known,nor are the molecular mechanisms responsible for triggering and sustaining the inflammatory cascades.In the present study,Tp0751 recombinant protein from T.pallidum was found to induce the production of proinflammatory cytokines,including TNF-α,IL-1βand IL-6,in a THP-1 human monocyte cell line.The signal transduction pathways involved in the production of these cytokines were then further investigated.No inhibition of TNF-a,IL-1β,or IL-6 production was observed following treatment with the SAPK/JNK specific inhibitor SP600125 or with an ERK inhibitor PD98059.By contrast,anti-TLR2 mAb,anti-CD14 mAb,and the p38 inhibitor SB203580 significantly inhibited the production of all three cytokines.In addition,pyrrolidine dithiocarbamate (PDTC),a specific inhibitor of NF-κB,profoundly inhibited the production of these cytokines.Tp0751 treatment strongly activated NF-κB,as revealed by Western blotting.However,NF-κB translocation was significantly inhibited by treatment with PDTC.These results indicated that TLR2,CD14,MAPKs/p38,and NF-κB might be implicated in the inflammatory reaction caused by T.pallidum infection.
基金sponsored by National key Research and Development Program(Grant No.2017YFD0502301)National College Students’innovation and entrepreneurship training program(201910504017)。
文摘African swine fever(ASF)is an infectious transboundary disease of domestic pigs and wild boar and spreading throughout Eurasia.There is no vaccine and treatment available.Complex immune escape strategies of African swine fever virus(ASFV)are crucial factors affecting immune prevention and vaccine development.MGF360 genes have been implicated in the modulation of the IFN-Ⅰresponse.The molecular mechanisms contributing to innate immunity are poorly understood.In this study,we demonstrated that ASFV MGF360-12 L(MGF360 families 12 L protein)significantly inhibited the mRNA transcription and promoter activity of IFN-βand NF-κB,accompanied by decreases of IRF3,STING,TBK1,ISG54,ISG56 and AP-1 m RNA transcription.Also,MGF360-12 L might suppress the nuclear localization of p50 and p65 mediated by classical nuclear localization signal(NLS).Additionally,MGF360-12 L could interact with KPNA2,KPNA3,and KPNA4,which interrupted the interaction between p65 and KPNA2,KPNA3,KPNA4.We further found that MGF360-12 L could interfere with the NF-κB nuclear translocation by competitively inhibiting the interaction between NF-κB and nuclear transport proteins.These findings suggested that MGF360-12 L could inhibit the IFN-Ⅰproduction by blocking the interaction of importinαand NF-κB signaling pathway,which might reveal a novel strategy for ASFV to escape the host innate immune response.
基金This work was supported the National Natural Science Foundation of China(Nos.81803097 and 81602727)the Natural Science Foundation of Shandong Province(No.ZR2017QH005).
文摘Bone metastasis is the leading cause of death in prostate cancer patients,for which there is currently no effective treatment.Since the bone microenvironment plays an important role in this process,attentions have been directed to the interactions between cancer cells and the bone microenvironment,including osteoclasts,osteoblasts,and bone stromal cells.Here,we explained the mechanism of interactions between prostate cancer cells and metastasis-associated cells within the bone microenvironment and further discussed the recent advances in targeted therapy of prostate cancer bone metastasis.This review also summarized the effects of bone microenvironment on prostate cancer metastasis and the related mechanisms,and provides insights for future prostate cancer metastasis studies.
