Expression vector p301-bG1 contains a Sw gene and a bialaphos resistance gene both driven by glyceraldehydes-3-phosphate dehydrogenase (GPD) gene promoter isolated from Lentinus edodes ( Berk.) Sing. Using p301-bG1, P...Expression vector p301-bG1 contains a Sw gene and a bialaphos resistance gene both driven by glyceraldehydes-3-phosphate dehydrogenase (GPD) gene promoter isolated from Lentinus edodes ( Berk.) Sing. Using p301-bG1, PEG-mediated transformation of protoplast of L. edodes was studied. Mixed with PEG-purified plasmid DNA, the protoplasts of L. edodes were treated with PEG solution and cultured on CYM regeneration plate containing 40 mug/mL bialaphos. Bialaphos-resistant and GUS-positive transformants were obtained using this transformation system. Although the transformation efficiency was relatively low, the protocols release large expenses on expensive instrument and restriction enzymes, providing a simple and economical method for mushroom breeding at the molecular level.展开更多
[Objective]The research aimed to construct deficient strain generated by Selenomonas ruminantium mutant with the acetic acid and analyze its fermentation characteristics.[Method]Based on the transposon tagging method,...[Objective]The research aimed to construct deficient strain generated by Selenomonas ruminantium mutant with the acetic acid and analyze its fermentation characteristics.[Method]Based on the transposon tagging method,Selenomonas ruminantium(recipient strain)was carried out the transposon mutagenesis via the transposon donor strain E.coli S17-1/pZJ25∷Tn5.The zygote was screened by using the selective medium which included kanamycin and sodium fluoroacetate.[Result]Seven transposon engineered strains which had the stable resistance to kanamycin and fluoroethanoic acid were screened.Selenomonas ruminantium mutant was carried out 16S rRNA and Tn5 PCR identification.Moreover,the specific activities of AK and PTA were analyzed.The mutant belonged to fluoroethanoic acid resistance strain with pta gene deficiency.[Conclusion]The research laid the foundation for further studying the cellular metabolic network and regulation of acetic acid in rumen microorganism of ruminant animal.展开更多
Activities of selected soil enzymes (invertase, acid phosphatase, proteinase,catalase, peroxidase and polyphenoloxi-dase) were determined under different spruce forests withrestoration histories of 5, 13, 18, 23, 27 y...Activities of selected soil enzymes (invertase, acid phosphatase, proteinase,catalase, peroxidase and polyphenoloxi-dase) were determined under different spruce forests withrestoration histories of 5, 13, 18, 23, 27 years and an old growth forest over 400 years old in theeastern Qinghai-Tibetan Plateau, China, and their possible use as indicators of ecosystems healthwere analyzed. Plots 10 X 10 m with 4 replications were established to investigate three hypotheses:soil enzyme activities a) would increase with the restoration process; b) would be greater insurface soils than at lower depths; and c) would be correlated to selected physicochemicalproperties. Results showed that as the forests developed after restoration, invertase and peroxidaseactivities usually increased up to the 23 year point. Also soil enzyme activities were associatedwith surface soils and decreased with depths, suggesting that in earlier restoration stages surfaceaddition of organic fertilizer to soils might be more effective than additions at depth. In the 0-20cm soil, there were significant correlations (P < 0.01 or < 0.05) between some soil enzymeactivities and some selected chemical properties. Therefore, temporal changes in enzyme activitiesshould be included as an indicator when evaluating sustainable forest management practices.展开更多
AIM: To test the hypothesis that the variant UDP- glucuronosyltransferase 1A1 (UGT1A1) gene, glucose-6- phosphate dehydrogenase (G6PD) deficiency, and thalassemia influence bilirubin metabolism and play a role in...AIM: To test the hypothesis that the variant UDP- glucuronosyltransferase 1A1 (UGT1A1) gene, glucose-6- phosphate dehydrogenase (G6PD) deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis. METHODS: A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups, respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1 091, and 1 456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency. RESULTS: Variation frequencies for the cholelithiasis patients were 16.1%, 25.8%, 5.4%, and 4.3% for A(TA)6 TAA/A(TA)TTAA (6/7), heterozygosity within the coding region, compound heterozygosity, and homozygosity of the UGT1A1 gene, respectively. Comparing the case and control groups, a statistically significant difference in frequency was demonstrated for the homozygous variation of the UGT1A1 gene (P = 0.012, Z2 test), but not for the other variations. Further, no difference was demonstrated in a between-group comparison of the incidence of G6PD deficiency and thalassemia (2.7% vs 2.4% and 5.1% vs 5.1%, respectively). The bilirubin levels for the cholelithiasis patients with the homozygous variant-UGT1A1 gene were significantly different from the control analog (18.0±6.5 and 12.7±2.9 μmol/L, respectively; P〈0.001, Student's ttest).CONCLUSION: Our results show that the homozygous variation in the UGT1A1 gene is a risk factor for the development of cholelithiasis in Taiwan Chinese. 2005 The WJG Press and Elsevier Inc. All rights reserved展开更多
1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is an important enzyme involved in the 2-C-methyi-D- erythritol-4-phosphate (MEP) pathway which provides the basic five-carbon units for isoprenoid biosynthesi...1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is an important enzyme involved in the 2-C-methyi-D- erythritol-4-phosphate (MEP) pathway which provides the basic five-carbon units for isoprenoid biosynthesis. To investigate the role of the MEP pathway in plant development and metabolism, we carried out detailed analyses on a dxr mutant (GK_215C01) and two DXR transgenic co-suppression fines, OX-DXR-L2 and OX-DXR-L7. We found that the dxr mutant was albino and dwarf. It never bolted, had significantly reduced number of trichomes and most of the stomata could not close normally in the leaves. The two co-suppression lines produced more yellow inflorescences and albino sepals with no trichomes. The transcription levels of genes involved in tricbome initiation were found to be strongly affected, including GLABRA1, TRANSPARENT TESTA GLABROUS 1, TRIPTYCHON and SPINDLY, expression of which is regulated by gibberellic acids (GAs). Exogenous application of GA3 could partially rescue the dwarf phenotype and the trichome initiation of dxr, whereas exogenous application of abscisic acid (ABA) could rescue the stomata closure defect, suggesting that lower levels of both GA and ABA contribute to the phenotype in the dxr mutants. We further found that genes involved in the biosynthetic pathways of GA and ABA were coordinately regulated. These results indicate that disruption of the plastidial MEP pathway leads to biosynthetic deficiency of photosynthetic pigments, GAs and ABA, and thus the developmental abnormalities, and that the flux from the cytoplasmic mevalonate pathway is not sufficient to rescue the deficiency caused by the blockage of the plastidial MEP pathway. These results reveal a critical role for the MEP biosynthetic pathway in controlling the biosynthesis of isoprenoids.展开更多
AIM: Single nucleotide polymorphisms (SNPs) of uridinediphosphoglucuro -nosyltransferase 1A7 (UGT1A7) gene are associated with the development of orolaryngeal cancer, hepatocellular carcinoma, and colorectal cancer. W...AIM: Single nucleotide polymorphisms (SNPs) of uridinediphosphoglucuro -nosyltransferase 1A7 (UGT1A7) gene are associated with the development of orolaryngeal cancer, hepatocellular carcinoma, and colorectal cancer. We performed this research to establish the techniques for determining UGT1A7 gene and basic data of this gene for Taiwan Chinese. METHODS: We collected blood samples from 112 healthy adults and 505 subjects carrying different genotypes of UGT1A1, and determined the promoter area and the entire sequence of UGT1A7 exon 1 by polymerase chain reaction. We designed appropriate primers and restriction enzymes to detect variant UGT1A7 genotypes found in the study subjects. RESULTS: Six SNPs at nucleotides 33, 387, 391, 392, 622, and 756 within the coding region of UGT1A7 exon 1 were found. The incidence of UGT1A7*l/*2 (N129R131W208/ K129K131W208) was predominant (35.7%) while that of UGT1A7 *3/*3 (K129K131R208/K129K131R208) was the least (2.7%). The allele frequency of UGT1A7*3, which exists in a considerable proportion of Caucasians (0.361) and Japanese (0.255), was identified only to be 0.152 in our study subjects. A novel variation at nucleotide -57 in the upstream was found, which was associated with SNPs at nucleotides 33, 387, 391, 392, and 622 in one of the variant haplotypes. The nucleotide changes at positions 387, 391, 392 and 756 were in linkage in another variant haplotype. The allele frequency of UGT1A7*3 was 0.018, 0.158, 0.242, 0.433, and 0.920 in subjects carrying wild, A(TA)6TAA/A(TA)7TAA, A(TA)7TAA/A(TA)7TAA, 211G/211A, and 211A/211A variants of UGT1A1 gene, respectively. By using natural or mutagenesis primers, we successfully detected the variations at nucleotides -57, 33, 387, and 622 with the restriction enzymes HpyCH4 Ⅳ, TaqⅠ, AflⅡ, and Rsa Ⅰ, respectively. CONCLUSION: The results indicate that the allele frequencies of UGT1A7 gene in Taiwan Chinese are different from those in Caucasians and Japanese. Carriage of the nucleotide 211- variant UGT1A gene is highly associated with UGT1A7*3. The restriction-enzymedigestion method for the determination of nucleotides-57 (or 33, or 622) and 387 can rapidly identify genotypes of UGT1A7 in an individual.展开更多
AIM: To obtain the active human recombinant uridine diphosphate glucuronosyltransferase 1A3 (UGT1A3) enzyme from Chinese hamster lung (CHL) cells.METHODS: The full-length UGT1A3 gene was amplified by reverse transcrip...AIM: To obtain the active human recombinant uridine diphosphate glucuronosyltransferase 1A3 (UGT1A3) enzyme from Chinese hamster lung (CHL) cells.METHODS: The full-length UGT1A3 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR)using total RNA from human liver as template. The correct fragment confirmed by sequencing was subcloned into the mammalian expression vector pcDNA3.1 (+), and the recombinant vector was transfected into CHL cells using a calcium phosphate method. Expressed UGT1A3 protein was prepared from CHL cells resistant to neomycin (G418). Then the protein was added into a reaction mixture for glucuronidation of quercetin. The glucuronidation activity of UGT1A3 was determined by reverse phase-high performance liquid chromatography (RP-HPLC) coupled with a diode array detector (DAD). The quercetin glucuronide was confirmed by hydrolysis with β-glucuronidase. Control experiments were performed in parallel. The transcriptions of recombinants were also determined by RT-PCR.RESULTS: The gene was confirmed to be an allele (UGT1A3-3) of UGT1A3 by DNA sequencing. The fragment was introduced into pcDNA3.1 (+) successfully. Several colonies were obtained under the selection pressure of G418.The result of RT-PCR showed transcription of recombinants in mRNA level. Glucuronidation assay and HPLC analysis indicated UGT1A3 expressed heterologously in CHL cells was in an active form, and one of the gulcuronides corresponding to quercetin was also detected.CONCLUSION: Correct sequence of UGT1A3 gene can be obtained, and active UGT1A3 enzyme is expressed heterologously in CHL cells.展开更多
The present study aims to clarify the protective effect of supplementation with some antioxidants,such as idebenone(200 mg/kg,ip),melatonin(10 mg/kg,ip) and arginine(200 mg/kg,ip) and their combination,on liver functi...The present study aims to clarify the protective effect of supplementation with some antioxidants,such as idebenone(200 mg/kg,ip),melatonin(10 mg/kg,ip) and arginine(200 mg/kg,ip) and their combination,on liver function(T.protein,albumin,alanine aminotransferase,aspartate aminotransferase and alkaline phosphatase),energetic parameters(adenosine triphosphate,adenosine diphosphate,adenosine monophosphate,inorganic phosphate,total adenylate,adenylate energy charge and potential phosphate).The effect on glycolytic and glycogenolytic enzymes(glucose,glycogen,glycogen phosphorylase,pyruvate kinase and phosphofructokinase against hypoxia) was also studied.The drugs were administered 24 and 1 h prior sodium nitrite intoxication.All biochemical parameters were estimated 1 h after sodium nitrite injection.Injection of sodium nitrite(75 mg/kg,sc) produced a significant disturbance in all biochemical parameters of liver function,energetic parameters and glycolytic and glycogenolytic enzymes.Hepatic damage was confirmed by histopathological examination of the liver as compared to controls.The marked changes in hepatic cells induced by sodium nitrite were completely abolished by pretreatment with the drug combination,suggesting potential protection against sodium nitrite-induced hypoxia.It could be concluded that a combination of both idebenone and melatonin or idebenone and arginine provides potential protection against sodium nitrite-induced hypoxia by improving biochemical parameters and preserving liver histology.展开更多
One mutant line eto with salt tolerance was screened from a T-DNA insertion mutant collection of Arabidopsis thaliana. In addition to a reduced rate of seed germination, NaCl and ABA also inhibited the growth and the ...One mutant line eto with salt tolerance was screened from a T-DNA insertion mutant collection of Arabidopsis thaliana. In addition to a reduced rate of seed germination, NaCl and ABA also inhibited the growth and the greening of cotyledons of wild-type seedlings, but not the eto mutant. TAIL-PCR analysis showed that T-DNA tag insertion in the eto was located at nucleotide 27,502 in BAC F3M18, upstream (at position -487 relative to the translation initiation codon) of gene At lg77740 (encoding a putative phosphatidylinositol-4-phosphate 5-kinase, AtPIP5K2). This inserted mutation cosegregated closely with the eto phenotype, Another analysis not only indicated that AtPIP5K2 transcript is expressed predominantly in roots and rosette leaves, but also showed the T-DNA insertion resulted higher accumulation of the AtPIP5K2 in eto mutant plants and did not influenced the expression of the upstream At lg77730 gene. This change may play an essential role in the tolerance of eto mutant plant to the osmotic stress.展开更多
Sweet potato [Ipomoea batatas (L.) Lam.] is an important food crop in the world as well as in Vietnam. It is well known as a recalcitrant crop for gene transformation and tissue culture because of its genotype depen...Sweet potato [Ipomoea batatas (L.) Lam.] is an important food crop in the world as well as in Vietnam. It is well known as a recalcitrant crop for gene transformation and tissue culture because of its genotype dependent in vitro responses. In present study, Agrobacterium-mediated transformation of cry8Db from Bacillus thuringiensis into KB 1 sweet potato variety has been studied. The C58cv strain carrying a pBl 121 backbone which contained cry8Db delta-endotoxin gene regulated under 35 S CaMV prom oter, and the selection marker gene, neomycin phosphotransferase (npt11) gene, was subjected for plant transformation. Callus induced from shoot tips and leaf explants were inoculated and cocultured with A. tumefaciens. The selection occurred during callus producing and plant regenerating steps. A total of 201 transgenic putative plant lines were produced, and 21 transgenic lines were positively confirmed by PCR and finalized by Southern blot. Four putative transgenic lines confirming a single copy of the crySEIb gene were transferred into soil pots in greenhouse. Biological activity evaluation for the insecticidal capacity of these transgenic lines under controlled conditions showed that the level of infestation by sweet potato weevils (Cylasformicarius) in untransformed plants was higher than that of transgenic lines.展开更多
AIM: To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS: Rat fibroblastic-like liver derived cells (...AIM: To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS: Rat fibroblastic-like liver derived cells (rFLDC) were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry, immunocyto- chemistry, reverse transcription polymerase chain reac- tion and functional assays. RESULTS: rFLDC exhibit fibroblastoid morphology, ex- press mesenchymal (CD73, CD90, vimentin, m-smooth muscle actin), hepatocyte (UGTIA1, CK8) and biliary (CK19) markers. Moreover, these cells are able to store glycogen, and have glucose 6 phosphatase activity, but not UGTIA1 activity. Under the hepatogenic differentia- tion protocol, rFLDC display an up-regulation of hepatocyte markers expression (albumin, tryptophan 2,3-di- oxygenase, G6Pase) correlated to a down-regulation of the expression of the biliary marker CK19. CONCLUSION: Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC. However, we demonstrated the presence of an original rodent hepato-biliary cell type.展开更多
AIM:To investigate the association of variations in the cyclooxygenase-2 (COX2) and uridine diphosphate glucuronosyltransferase 1A6 (UGTIA6) genes and non-steroidal anti-inflammatory drugs (NSAIDs) use with ris...AIM:To investigate the association of variations in the cyclooxygenase-2 (COX2) and uridine diphosphate glucuronosyltransferase 1A6 (UGTIA6) genes and non-steroidal anti-inflammatory drugs (NSAIDs) use with risk of colon cancer.METHODS: NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms (SNPs) in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS: No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk (P 〉 0.05),and we did not observe that these variants modify the protective effect of NSAIDs (P 〉 0.05). We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION: Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.展开更多
AIM:To determine whether expression of certain enzymes related to 5-fluorouracil(5-FU)metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma(CCA).METHODS:The histoculture drug response assay(HDRA)was performe...AIM:To determine whether expression of certain enzymes related to 5-fluorouracil(5-FU)metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma(CCA).METHODS:The histoculture drug response assay(HDRA)was performed using surgically resected CCA tissues.Tumor cell viability was determined morphologically with hematoxylin and eosin-and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained tissues.The mRNA expression of thymidine phosphorylase(TP),orotate phosphoribosyl transferase(OPRT),thymidylate synthase(TS),and dihydropyrimidine dehydrogenase(DPD)was determined with realtime reverse transcriptase-polymerase chain reaction.The levels of gene expression and the sensitivity to 5-FU were evaluated.RESULTS:Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital,Khon Kaen University from 2007 to 2009.HDRA was used to determine the response of these CCA tissues to 5-FU.Based on the dose-response curve,200μg/mL 5-FU was selected as the test concentration.The percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to 5-FU.When the relationship between TP,OPRT,TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined,only OPRT mRNA expression was significantly correlated with the response to 5-FU.The mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group(0.41±0.25 vs 0.22±0.12,P<0.05).CONCLUSION:OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of CCA.Whether OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients.展开更多
AIM: To evaluate the hepatoprotective activity of a hydroalcoholic extract of the bark of Anogeissus latifolia; in vitro in primary rat hepatocyte monolayer culture and in vivo in the liver of Wistar rats intoxicated...AIM: To evaluate the hepatoprotective activity of a hydroalcoholic extract of the bark of Anogeissus latifolia; in vitro in primary rat hepatocyte monolayer culture and in vivo in the liver of Wistar rats intoxicated by carbon tetrachloride (CCl4). METHODS: In the in vitro study, a primary hepatocyte monolayer culture was treated with CCh and extract of Anogeissus latifolia. Hepatoprotective activity was demonstrated in the CCh damaged primary monolayer culture. In the in vivo study, the hepatoprotective activity of a hydroalcoholic extract ofAnogeissus latifolia was analyzed in liver injured CCh-treated rats. Biochemical parameters including serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and alkaline phosphatase (ALP) in serum wereanalyzed. The biochemical findings were supplemented with histopathological examination of rat liver sections. RESULTS: In vitro: primary hepatocyte monolayer cultures were treated with CCh and extract of Anogeissus latifolia. A protective activity could be demonstrated in the CCh damaged primary monolayer cultUre. In vivo: Hydroalcoholic extract of Anogeissus latifolia (300 mg/kg) was found to have protective activity in rats with CCh-induced liver damage as judged from serum marker enzyme activity. CONCLUSION: The above findings lead to the conclusion that the hydroalcoholic extract of Anogeissus latifol/a is hepatoprotective. Hence, we suggest that the inclusion of this plant in the management of liver disorders is justified.展开更多
F_1-ATPase, a part of ATP synthase, can synthesize and hydrolyze ATP moleculars in which the centralγ-subunit rotates inside the α_3β_3 cylinder.A stochastic four-state mechanochemical coupling model of F_1-ATPase ...F_1-ATPase, a part of ATP synthase, can synthesize and hydrolyze ATP moleculars in which the centralγ-subunit rotates inside the α_3β_3 cylinder.A stochastic four-state mechanochemical coupling model of F_1-ATPase isstudied with the aid of the master equation.In this model, the ATP hydrolysis and synthesis are dependent on ATP,ADP, and Pi concentrations.The effects of ATP concentration, ADP concentration, and the external torque on theoccupation probability of binding-state, the rotation rate and the diffusion coefficient of F_1-ATPase are investigated.Moreover, the results from this model are compared with experiments.The mechanochemical mechanism F_1-ATPase isqualitatively explained by the model.展开更多
Calcineurin dephosphorylates multiple serine residues near the N terminus of NFAT proteins enabling them to translocate from cytoplasm to nucleus, where they activate a subset of hypertrophic response genes. Transgeni...Calcineurin dephosphorylates multiple serine residues near the N terminus of NFAT proteins enabling them to translocate from cytoplasm to nucleus, where they activate a subset of hypertrophic response genes. Transgenic mice over-expressing a constitu- tively active form of calcineurin or NFAT3, developed obviously hypertrophy and heart failure or sudden death proving its pathogenic role. Here we used literatures on MEDLINE (2000-2011), systematically reviewed the new development of calcineurin signaling pathway in myocardial hypertrophy展开更多
Transketolase (TK), a thiamine diphosphate (ThDP)-dependent enzyme, catalyzes several key reactions of nonoxidative branch of pentose phosphate pathway. TK is a homodimer with two active sites that locate at the i...Transketolase (TK), a thiamine diphosphate (ThDP)-dependent enzyme, catalyzes several key reactions of nonoxidative branch of pentose phosphate pathway. TK is a homodimer with two active sites that locate at the interface between the contacting monomers. Both ThDP and bivalent cations are strictly needed for TK activation, just like that for all ThDPdependent enzymes. TK exists in all organisms that have been investigated. Up to now, one TK gene (TKT) and two transketolase-like genes (TKTL1 and TKTL2) have been identified in human genome. TKTL1 is reported to play a pivotal role in carcinogenesis and may have important implications in the nutrition and future treatment of patients with cancer. Research- ers have found TK variants and reduced activities of TK enzyme in patients with neurodegenerative diseases, diabetes, and cancer. Recent studies indicated TK as a novel role in the prevention and therapy of these diseases.展开更多
We studied the responses of the activities of adenosine-triphosphate (ATP) sulfurylase (ATPS) and serine acetyltransferase (SAT) to cadmium (Cd) levels and treatment time in hyperaccumulating ecotype (HE) Sedum alfred...We studied the responses of the activities of adenosine-triphosphate (ATP) sulfurylase (ATPS) and serine acetyltransferase (SAT) to cadmium (Cd) levels and treatment time in hyperaccumulating ecotype (HE) Sedum alfredii Hance, as compared with its non-hyperaccumulating ecotype (NHE). The results show that plant growth was inhibited in NHE but promoted in HE when exposed to high Cd level. Cd concentrations in leaves and shoots rapidly increased in HE rather than in NHE, and they became much higher in HE than in NHE along with increasing treatment time and Cd supply levels. ATPS activity was higher in HE than in NHE in all Cd treatments, and increased with increasing Cd supply levels in both HE and NHE when exposed to Cd treatment within 8 h. However, a marked difference of ATPS activity between HE and NHE was found with Cd treatment for 168 h, where ATPS activity increased in HE but decreased in NHE. Similarly, SAT activity was higher in HE than in NHE at all Cd treatments, but was more sensitive in NHE than in HE. Both ATPS and SAT activities in NHE leaves tended to decrease with increasing treatment time after 8 h at all Cd levels. The results reveal the different responses in sulfur assimilation enzymes and Cd accumulation between HE and NHE. With increasing Cd stress, the activities of sulfur assimilation enzymes (ATPS and SAT) were induced in HE, which may contribute to Cd accumulation in the hyperaccumulator Sedum alfredii Hance.展开更多
Inhibitory leukocyte immunoglobulin-like receptors(LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs(ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, ...Inhibitory leukocyte immunoglobulin-like receptors(LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs(ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, non-receptor type 6(PTPN6, SHP-1), protein tyrosine phosphatase, non-receptor type 6(PTPN6, SHP-2), or Src homology 2 domain containing inositol phosphatase(SHIP) to negatively regulate immune cell activation. These receptors are known to play important regulatory roles in immune and neuronal functions. Recent studies demonstrated that several of these receptors are expressed by cancer cells. Importantly, they may directly regulate development, drug resistance, and relapse of cancer, and the activity of cancer stem cells. Although counterintuitive, these findings are consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. This review focuses on the ligands, expression pattern, signaling, and function of LILRB family in the context of cancer development. Because inhibition of the signaling of certain LILRBs directly blocks cancer growth and stimulates immunity that may suppress tumorigenesis, but does not disturb normal development, LILRB signaling pathways may represent ideal targets for treating hematological malignancies and perhaps other tumors.展开更多
文摘Expression vector p301-bG1 contains a Sw gene and a bialaphos resistance gene both driven by glyceraldehydes-3-phosphate dehydrogenase (GPD) gene promoter isolated from Lentinus edodes ( Berk.) Sing. Using p301-bG1, PEG-mediated transformation of protoplast of L. edodes was studied. Mixed with PEG-purified plasmid DNA, the protoplasts of L. edodes were treated with PEG solution and cultured on CYM regeneration plate containing 40 mug/mL bialaphos. Bialaphos-resistant and GUS-positive transformants were obtained using this transformation system. Although the transformation efficiency was relatively low, the protocols release large expenses on expensive instrument and restriction enzymes, providing a simple and economical method for mushroom breeding at the molecular level.
基金Supported by National Natural Science Fund Item(30230260,30600441)~~
文摘[Objective]The research aimed to construct deficient strain generated by Selenomonas ruminantium mutant with the acetic acid and analyze its fermentation characteristics.[Method]Based on the transposon tagging method,Selenomonas ruminantium(recipient strain)was carried out the transposon mutagenesis via the transposon donor strain E.coli S17-1/pZJ25∷Tn5.The zygote was screened by using the selective medium which included kanamycin and sodium fluoroacetate.[Result]Seven transposon engineered strains which had the stable resistance to kanamycin and fluoroethanoic acid were screened.Selenomonas ruminantium mutant was carried out 16S rRNA and Tn5 PCR identification.Moreover,the specific activities of AK and PTA were analyzed.The mutant belonged to fluoroethanoic acid resistance strain with pta gene deficiency.[Conclusion]The research laid the foundation for further studying the cellular metabolic network and regulation of acetic acid in rumen microorganism of ruminant animal.
基金Project supported by the Knowledge Innovation Project of the Chinese Academy of Sciences (Nos. KZCX3-SW-339 and KSCX1-07) the Ministry of Science and Technology of China (No. 2001CCB00600).
文摘Activities of selected soil enzymes (invertase, acid phosphatase, proteinase,catalase, peroxidase and polyphenoloxi-dase) were determined under different spruce forests withrestoration histories of 5, 13, 18, 23, 27 years and an old growth forest over 400 years old in theeastern Qinghai-Tibetan Plateau, China, and their possible use as indicators of ecosystems healthwere analyzed. Plots 10 X 10 m with 4 replications were established to investigate three hypotheses:soil enzyme activities a) would increase with the restoration process; b) would be greater insurface soils than at lower depths; and c) would be correlated to selected physicochemicalproperties. Results showed that as the forests developed after restoration, invertase and peroxidaseactivities usually increased up to the 23 year point. Also soil enzyme activities were associatedwith surface soils and decreased with depths, suggesting that in earlier restoration stages surfaceaddition of organic fertilizer to soils might be more effective than additions at depth. In the 0-20cm soil, there were significant correlations (P < 0.01 or < 0.05) between some soil enzymeactivities and some selected chemical properties. Therefore, temporal changes in enzyme activitiesshould be included as an indicator when evaluating sustainable forest management practices.
基金Supported by a grant from the Cathay Medical Research Center, Taipei, Taiwan, China
文摘AIM: To test the hypothesis that the variant UDP- glucuronosyltransferase 1A1 (UGT1A1) gene, glucose-6- phosphate dehydrogenase (G6PD) deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis. METHODS: A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups, respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1 091, and 1 456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency. RESULTS: Variation frequencies for the cholelithiasis patients were 16.1%, 25.8%, 5.4%, and 4.3% for A(TA)6 TAA/A(TA)TTAA (6/7), heterozygosity within the coding region, compound heterozygosity, and homozygosity of the UGT1A1 gene, respectively. Comparing the case and control groups, a statistically significant difference in frequency was demonstrated for the homozygous variation of the UGT1A1 gene (P = 0.012, Z2 test), but not for the other variations. Further, no difference was demonstrated in a between-group comparison of the incidence of G6PD deficiency and thalassemia (2.7% vs 2.4% and 5.1% vs 5.1%, respectively). The bilirubin levels for the cholelithiasis patients with the homozygous variant-UGT1A1 gene were significantly different from the control analog (18.0±6.5 and 12.7±2.9 μmol/L, respectively; P〈0.001, Student's ttest).CONCLUSION: Our results show that the homozygous variation in the UGT1A1 gene is a risk factor for the development of cholelithiasis in Taiwan Chinese. 2005 The WJG Press and Elsevier Inc. All rights reserved
基金Acknowledgments This work was supported by the National Natural Science Foundation of China (NSFC Grant 90717003 to L-J Qu).
文摘1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is an important enzyme involved in the 2-C-methyi-D- erythritol-4-phosphate (MEP) pathway which provides the basic five-carbon units for isoprenoid biosynthesis. To investigate the role of the MEP pathway in plant development and metabolism, we carried out detailed analyses on a dxr mutant (GK_215C01) and two DXR transgenic co-suppression fines, OX-DXR-L2 and OX-DXR-L7. We found that the dxr mutant was albino and dwarf. It never bolted, had significantly reduced number of trichomes and most of the stomata could not close normally in the leaves. The two co-suppression lines produced more yellow inflorescences and albino sepals with no trichomes. The transcription levels of genes involved in tricbome initiation were found to be strongly affected, including GLABRA1, TRANSPARENT TESTA GLABROUS 1, TRIPTYCHON and SPINDLY, expression of which is regulated by gibberellic acids (GAs). Exogenous application of GA3 could partially rescue the dwarf phenotype and the trichome initiation of dxr, whereas exogenous application of abscisic acid (ABA) could rescue the stomata closure defect, suggesting that lower levels of both GA and ABA contribute to the phenotype in the dxr mutants. We further found that genes involved in the biosynthetic pathways of GA and ABA were coordinately regulated. These results indicate that disruption of the plastidial MEP pathway leads to biosynthetic deficiency of photosynthetic pigments, GAs and ABA, and thus the developmental abnormalities, and that the flux from the cytoplasmic mevalonate pathway is not sufficient to rescue the deficiency caused by the blockage of the plastidial MEP pathway. These results reveal a critical role for the MEP biosynthetic pathway in controlling the biosynthesis of isoprenoids.
基金Supported by a grant from the National Science Council, Taipei,Taiwan, China. No. NSC 92-2314-B-242-010
文摘AIM: Single nucleotide polymorphisms (SNPs) of uridinediphosphoglucuro -nosyltransferase 1A7 (UGT1A7) gene are associated with the development of orolaryngeal cancer, hepatocellular carcinoma, and colorectal cancer. We performed this research to establish the techniques for determining UGT1A7 gene and basic data of this gene for Taiwan Chinese. METHODS: We collected blood samples from 112 healthy adults and 505 subjects carrying different genotypes of UGT1A1, and determined the promoter area and the entire sequence of UGT1A7 exon 1 by polymerase chain reaction. We designed appropriate primers and restriction enzymes to detect variant UGT1A7 genotypes found in the study subjects. RESULTS: Six SNPs at nucleotides 33, 387, 391, 392, 622, and 756 within the coding region of UGT1A7 exon 1 were found. The incidence of UGT1A7*l/*2 (N129R131W208/ K129K131W208) was predominant (35.7%) while that of UGT1A7 *3/*3 (K129K131R208/K129K131R208) was the least (2.7%). The allele frequency of UGT1A7*3, which exists in a considerable proportion of Caucasians (0.361) and Japanese (0.255), was identified only to be 0.152 in our study subjects. A novel variation at nucleotide -57 in the upstream was found, which was associated with SNPs at nucleotides 33, 387, 391, 392, and 622 in one of the variant haplotypes. The nucleotide changes at positions 387, 391, 392 and 756 were in linkage in another variant haplotype. The allele frequency of UGT1A7*3 was 0.018, 0.158, 0.242, 0.433, and 0.920 in subjects carrying wild, A(TA)6TAA/A(TA)7TAA, A(TA)7TAA/A(TA)7TAA, 211G/211A, and 211A/211A variants of UGT1A1 gene, respectively. By using natural or mutagenesis primers, we successfully detected the variations at nucleotides -57, 33, 387, and 622 with the restriction enzymes HpyCH4 Ⅳ, TaqⅠ, AflⅡ, and Rsa Ⅰ, respectively. CONCLUSION: The results indicate that the allele frequencies of UGT1A7 gene in Taiwan Chinese are different from those in Caucasians and Japanese. Carriage of the nucleotide 211- variant UGT1A gene is highly associated with UGT1A7*3. The restriction-enzymedigestion method for the determination of nucleotides-57 (or 33, or 622) and 387 can rapidly identify genotypes of UGT1A7 in an individual.
基金Supported by the National Natural Science Foundation of China,No. C30100232to Xin Li,No.C30225047to Su Zeng,and the Zhejiang Provincial Natural Science Foundation,No.C300487to Xin Li
文摘AIM: To obtain the active human recombinant uridine diphosphate glucuronosyltransferase 1A3 (UGT1A3) enzyme from Chinese hamster lung (CHL) cells.METHODS: The full-length UGT1A3 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR)using total RNA from human liver as template. The correct fragment confirmed by sequencing was subcloned into the mammalian expression vector pcDNA3.1 (+), and the recombinant vector was transfected into CHL cells using a calcium phosphate method. Expressed UGT1A3 protein was prepared from CHL cells resistant to neomycin (G418). Then the protein was added into a reaction mixture for glucuronidation of quercetin. The glucuronidation activity of UGT1A3 was determined by reverse phase-high performance liquid chromatography (RP-HPLC) coupled with a diode array detector (DAD). The quercetin glucuronide was confirmed by hydrolysis with β-glucuronidase. Control experiments were performed in parallel. The transcriptions of recombinants were also determined by RT-PCR.RESULTS: The gene was confirmed to be an allele (UGT1A3-3) of UGT1A3 by DNA sequencing. The fragment was introduced into pcDNA3.1 (+) successfully. Several colonies were obtained under the selection pressure of G418.The result of RT-PCR showed transcription of recombinants in mRNA level. Glucuronidation assay and HPLC analysis indicated UGT1A3 expressed heterologously in CHL cells was in an active form, and one of the gulcuronides corresponding to quercetin was also detected.CONCLUSION: Correct sequence of UGT1A3 gene can be obtained, and active UGT1A3 enzyme is expressed heterologously in CHL cells.
文摘The present study aims to clarify the protective effect of supplementation with some antioxidants,such as idebenone(200 mg/kg,ip),melatonin(10 mg/kg,ip) and arginine(200 mg/kg,ip) and their combination,on liver function(T.protein,albumin,alanine aminotransferase,aspartate aminotransferase and alkaline phosphatase),energetic parameters(adenosine triphosphate,adenosine diphosphate,adenosine monophosphate,inorganic phosphate,total adenylate,adenylate energy charge and potential phosphate).The effect on glycolytic and glycogenolytic enzymes(glucose,glycogen,glycogen phosphorylase,pyruvate kinase and phosphofructokinase against hypoxia) was also studied.The drugs were administered 24 and 1 h prior sodium nitrite intoxication.All biochemical parameters were estimated 1 h after sodium nitrite injection.Injection of sodium nitrite(75 mg/kg,sc) produced a significant disturbance in all biochemical parameters of liver function,energetic parameters and glycolytic and glycogenolytic enzymes.Hepatic damage was confirmed by histopathological examination of the liver as compared to controls.The marked changes in hepatic cells induced by sodium nitrite were completely abolished by pretreatment with the drug combination,suggesting potential protection against sodium nitrite-induced hypoxia.It could be concluded that a combination of both idebenone and melatonin or idebenone and arginine provides potential protection against sodium nitrite-induced hypoxia by improving biochemical parameters and preserving liver histology.
基金Supported by the National Program for Transgenic Plants from China ( GN. J99-A-001 ) and National Natural Science Foundation of China ( GN. 30221120261 ).
文摘One mutant line eto with salt tolerance was screened from a T-DNA insertion mutant collection of Arabidopsis thaliana. In addition to a reduced rate of seed germination, NaCl and ABA also inhibited the growth and the greening of cotyledons of wild-type seedlings, but not the eto mutant. TAIL-PCR analysis showed that T-DNA tag insertion in the eto was located at nucleotide 27,502 in BAC F3M18, upstream (at position -487 relative to the translation initiation codon) of gene At lg77740 (encoding a putative phosphatidylinositol-4-phosphate 5-kinase, AtPIP5K2). This inserted mutation cosegregated closely with the eto phenotype, Another analysis not only indicated that AtPIP5K2 transcript is expressed predominantly in roots and rosette leaves, but also showed the T-DNA insertion resulted higher accumulation of the AtPIP5K2 in eto mutant plants and did not influenced the expression of the upstream At lg77730 gene. This change may play an essential role in the tolerance of eto mutant plant to the osmotic stress.
文摘Sweet potato [Ipomoea batatas (L.) Lam.] is an important food crop in the world as well as in Vietnam. It is well known as a recalcitrant crop for gene transformation and tissue culture because of its genotype dependent in vitro responses. In present study, Agrobacterium-mediated transformation of cry8Db from Bacillus thuringiensis into KB 1 sweet potato variety has been studied. The C58cv strain carrying a pBl 121 backbone which contained cry8Db delta-endotoxin gene regulated under 35 S CaMV prom oter, and the selection marker gene, neomycin phosphotransferase (npt11) gene, was subjected for plant transformation. Callus induced from shoot tips and leaf explants were inoculated and cocultured with A. tumefaciens. The selection occurred during callus producing and plant regenerating steps. A total of 201 transgenic putative plant lines were produced, and 21 transgenic lines were positively confirmed by PCR and finalized by Southern blot. Four putative transgenic lines confirming a single copy of the crySEIb gene were transferred into soil pots in greenhouse. Biological activity evaluation for the insecticidal capacity of these transgenic lines under controlled conditions showed that the level of infestation by sweet potato weevils (Cylasformicarius) in untransformed plants was higher than that of transgenic lines.
基金Supported by Fonds pour la formation à la recherche dans l’industrie et dans l’agriculture (FRIA)
文摘AIM: To evaluate the presence of progenitor cells in healthy adult rat liver displaying the equivalent ad- vanced hepatogenic profile as that obtained in humans. METHODS: Rat fibroblastic-like liver derived cells (rFLDC) were obtained from collagenase-isolated liver cell suspensions and characterized and their phenotype profile determined using flow cytometry, immunocyto- chemistry, reverse transcription polymerase chain reac- tion and functional assays. RESULTS: rFLDC exhibit fibroblastoid morphology, ex- press mesenchymal (CD73, CD90, vimentin, m-smooth muscle actin), hepatocyte (UGTIA1, CK8) and biliary (CK19) markers. Moreover, these cells are able to store glycogen, and have glucose 6 phosphatase activity, but not UGTIA1 activity. Under the hepatogenic differentia- tion protocol, rFLDC display an up-regulation of hepatocyte markers expression (albumin, tryptophan 2,3-di- oxygenase, G6Pase) correlated to a down-regulation of the expression of the biliary marker CK19. CONCLUSION: Advanced hepatic features observed in human liver progenitor cells could not be demonstrated in rFLDC. However, we demonstrated the presence of an original rodent hepato-biliary cell type.
基金Supported by A Damon Runyon Cancer Research Foundation Clinical Investigator Award,CI-8An R25 training grant from the National Cancer Institute,R25T CA094186+1 种基金The Case Center for Transdisciplinary Research on Energetics and Cancer,1U54 CA-116867-01A National Cancer Institute K22 Award,1K22 CA120545-01
文摘AIM:To investigate the association of variations in the cyclooxygenase-2 (COX2) and uridine diphosphate glucuronosyltransferase 1A6 (UGTIA6) genes and non-steroidal anti-inflammatory drugs (NSAIDs) use with risk of colon cancer.METHODS: NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms (SNPs) in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS: No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk (P 〉 0.05),and we did not observe that these variants modify the protective effect of NSAIDs (P 〉 0.05). We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION: Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.
基金Supported by The Research Team Strengthening Grant,National Genetic Engineering and Biotechnology Center,National Science and Technology Development Agency,ThailandThe Liver Fluke and Cholangiocarcinoma Research Center,Faculty of Medicine,Khon Kaen University,Thailand(to Chaiyagool J)
文摘AIM:To determine whether expression of certain enzymes related to 5-fluorouracil(5-FU)metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma(CCA).METHODS:The histoculture drug response assay(HDRA)was performed using surgically resected CCA tissues.Tumor cell viability was determined morphologically with hematoxylin and eosin-and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained tissues.The mRNA expression of thymidine phosphorylase(TP),orotate phosphoribosyl transferase(OPRT),thymidylate synthase(TS),and dihydropyrimidine dehydrogenase(DPD)was determined with realtime reverse transcriptase-polymerase chain reaction.The levels of gene expression and the sensitivity to 5-FU were evaluated.RESULTS:Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital,Khon Kaen University from 2007 to 2009.HDRA was used to determine the response of these CCA tissues to 5-FU.Based on the dose-response curve,200μg/mL 5-FU was selected as the test concentration.The percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to 5-FU.When the relationship between TP,OPRT,TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined,only OPRT mRNA expression was significantly correlated with the response to 5-FU.The mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group(0.41±0.25 vs 0.22±0.12,P<0.05).CONCLUSION:OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of CCA.Whether OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients.
文摘AIM: To evaluate the hepatoprotective activity of a hydroalcoholic extract of the bark of Anogeissus latifolia; in vitro in primary rat hepatocyte monolayer culture and in vivo in the liver of Wistar rats intoxicated by carbon tetrachloride (CCl4). METHODS: In the in vitro study, a primary hepatocyte monolayer culture was treated with CCh and extract of Anogeissus latifolia. Hepatoprotective activity was demonstrated in the CCh damaged primary monolayer culture. In the in vivo study, the hepatoprotective activity of a hydroalcoholic extract ofAnogeissus latifolia was analyzed in liver injured CCh-treated rats. Biochemical parameters including serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and alkaline phosphatase (ALP) in serum wereanalyzed. The biochemical findings were supplemented with histopathological examination of rat liver sections. RESULTS: In vitro: primary hepatocyte monolayer cultures were treated with CCh and extract of Anogeissus latifolia. A protective activity could be demonstrated in the CCh damaged primary monolayer cultUre. In vivo: Hydroalcoholic extract of Anogeissus latifolia (300 mg/kg) was found to have protective activity in rats with CCh-induced liver damage as judged from serum marker enzyme activity. CONCLUSION: The above findings lead to the conclusion that the hydroalcoholic extract of Anogeissus latifol/a is hepatoprotective. Hence, we suggest that the inclusion of this plant in the management of liver disorders is justified.
基金Supported by the National Natural Science Foundation of China under Grant No.10847118the National Natural Science Foundation of the City of Tianjin under Grant No.08JCYBJC00900 the Science Research Program of Education office of Hebei Province under Grant No.2008427
文摘F_1-ATPase, a part of ATP synthase, can synthesize and hydrolyze ATP moleculars in which the centralγ-subunit rotates inside the α_3β_3 cylinder.A stochastic four-state mechanochemical coupling model of F_1-ATPase isstudied with the aid of the master equation.In this model, the ATP hydrolysis and synthesis are dependent on ATP,ADP, and Pi concentrations.The effects of ATP concentration, ADP concentration, and the external torque on theoccupation probability of binding-state, the rotation rate and the diffusion coefficient of F_1-ATPase are investigated.Moreover, the results from this model are compared with experiments.The mechanochemical mechanism F_1-ATPase isqualitatively explained by the model.
文摘Calcineurin dephosphorylates multiple serine residues near the N terminus of NFAT proteins enabling them to translocate from cytoplasm to nucleus, where they activate a subset of hypertrophic response genes. Transgenic mice over-expressing a constitu- tively active form of calcineurin or NFAT3, developed obviously hypertrophy and heart failure or sudden death proving its pathogenic role. Here we used literatures on MEDLINE (2000-2011), systematically reviewed the new development of calcineurin signaling pathway in myocardial hypertrophy
基金the National Natural Science Foundation of China (No. 30870871).
文摘Transketolase (TK), a thiamine diphosphate (ThDP)-dependent enzyme, catalyzes several key reactions of nonoxidative branch of pentose phosphate pathway. TK is a homodimer with two active sites that locate at the interface between the contacting monomers. Both ThDP and bivalent cations are strictly needed for TK activation, just like that for all ThDPdependent enzymes. TK exists in all organisms that have been investigated. Up to now, one TK gene (TKT) and two transketolase-like genes (TKTL1 and TKTL2) have been identified in human genome. TKTL1 is reported to play a pivotal role in carcinogenesis and may have important implications in the nutrition and future treatment of patients with cancer. Research- ers have found TK variants and reduced activities of TK enzyme in patients with neurodegenerative diseases, diabetes, and cancer. Recent studies indicated TK as a novel role in the prevention and therapy of these diseases.
基金supported by the National Natural Science Foundation of China (No. 30630046)the Hi-Tech Research and Development Program (863) of China (No. 2006AA06Z386)the Program for Changjiang Scholars and Innovative Research Team in University, China (No. IRT0536)
文摘We studied the responses of the activities of adenosine-triphosphate (ATP) sulfurylase (ATPS) and serine acetyltransferase (SAT) to cadmium (Cd) levels and treatment time in hyperaccumulating ecotype (HE) Sedum alfredii Hance, as compared with its non-hyperaccumulating ecotype (NHE). The results show that plant growth was inhibited in NHE but promoted in HE when exposed to high Cd level. Cd concentrations in leaves and shoots rapidly increased in HE rather than in NHE, and they became much higher in HE than in NHE along with increasing treatment time and Cd supply levels. ATPS activity was higher in HE than in NHE in all Cd treatments, and increased with increasing Cd supply levels in both HE and NHE when exposed to Cd treatment within 8 h. However, a marked difference of ATPS activity between HE and NHE was found with Cd treatment for 168 h, where ATPS activity increased in HE but decreased in NHE. Similarly, SAT activity was higher in HE than in NHE at all Cd treatments, but was more sensitive in NHE than in HE. Both ATPS and SAT activities in NHE leaves tended to decrease with increasing treatment time after 8 h at all Cd levels. The results reveal the different responses in sulfur assimilation enzymes and Cd accumulation between HE and NHE. With increasing Cd stress, the activities of sulfur assimilation enzymes (ATPS and SAT) were induced in HE, which may contribute to Cd accumulation in the hyperaccumulator Sedum alfredii Hance.
基金supported b y the Na tional In stitu te o f Health(1R01CA172268)the Leukemia&Lymphoma Society(1024-14+7 种基金TRP-6024-14)the Robert A.Welch Foundation(I-1834)the Cancer Prevention and Research Institute of Texas(RP140402 and DP150056)the Innovation Program of Shanghai Municipal Education Commission(13G20)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learningthe National Natural Science Foundation of China(813706548142200181471524)
文摘Inhibitory leukocyte immunoglobulin-like receptors(LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs(ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, non-receptor type 6(PTPN6, SHP-1), protein tyrosine phosphatase, non-receptor type 6(PTPN6, SHP-2), or Src homology 2 domain containing inositol phosphatase(SHIP) to negatively regulate immune cell activation. These receptors are known to play important regulatory roles in immune and neuronal functions. Recent studies demonstrated that several of these receptors are expressed by cancer cells. Importantly, they may directly regulate development, drug resistance, and relapse of cancer, and the activity of cancer stem cells. Although counterintuitive, these findings are consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. This review focuses on the ligands, expression pattern, signaling, and function of LILRB family in the context of cancer development. Because inhibition of the signaling of certain LILRBs directly blocks cancer growth and stimulates immunity that may suppress tumorigenesis, but does not disturb normal development, LILRB signaling pathways may represent ideal targets for treating hematological malignancies and perhaps other tumors.