Water scarcity and pollution pose a threat to the sustainable development of cities and society.Therefore,it is crucial to analyze the hydrochemical characteristics and carbon dynamics of waterdeficient areas.Taking t...Water scarcity and pollution pose a threat to the sustainable development of cities and society.Therefore,it is crucial to analyze the hydrochemical characteristics and carbon dynamics of waterdeficient areas.Taking the Taiyuan section of Fenhe River as the research object,we systematically explored the hydrochemical characteristics of surface water and its evolutionary processes,as well as the ecological effect of algal carbonic anhydrase in carbon cycle using the hydrochemical evolution method and correlation analysis.The ternary diagram demonstrates that the main water chemical type in Fenhe River was SO^(2-)_(4)·Cl^(-)-Na^(+).The Gibbs and end-member diagrams of each ion display that the chemical composition of surface water was mainly controlled by silicate decomposition.The chemical ions originated mainly from dissolution of some minerals,such as plagioclase,halite,dolomite,calcite,and gypsum.The diatoms had a lower CO_(2)requirement because they exhibited a higher abundance at a lower partial pressure of CO_(2)(p CO_(2)).However,high CO_(2)concentration had a positive effect on cyanobacteria,which reduced the active transport of HCO_(3)^(-),saved the energy needed for this part of active transport,and indirectly improved the overall photosynthetic efficiency of algae.Carbonic anhydrase(CA)activity was significantly negatively correlated with p CO_(2)and positively correlated with HCO_(3)^(-)concentration,indicating that CA in water promoted the conversion of CO_(2)to HCO_(3)^(-).The HCO_(3)^(-)generated from this process continued to participate in the erosion of silicate rocks,sequestering CO_(2)in the form of Ca CO_(3),which has a non-negligible impact on the carbon sink in the Fenhe River.These consequences may have important implications for the biogeochemical cycling occurring in urban water.展开更多
Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitate...Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitates identification and characterisation of novel drug targets and their potential inhibitors.We identified the carbonic anhydrase(CA) genes in P.falciparum.The pfGA gene encodes an α-carbonic anhydrase,a Zn^(2+)-metalloenzme,possessing catalytic properties distinct from that of the human host CA enzyme.The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes.A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions.The structure of the groups substituting the aromatic-ureido-or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides.One derivative,that is,4-(3,4-dichlorophenylureido)thioureidobcnzcnesulfonamide(compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor,and was also the most effective antimalarial compound on the in vitro P.falciparum growth inhibition.The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei,an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria.展开更多
The conversion of CO2 into H+ and is a relatively slow reaction. Hence, its kinetics may be rate determining in carbonate rock dissolution. Carbonic anhydrase (CA), which is widespread in nature, was used to catalyze ...The conversion of CO2 into H+ and is a relatively slow reaction. Hence, its kinetics may be rate determining in carbonate rock dissolution. Carbonic anhydrase (CA), which is widespread in nature, was used to catalyze the CO2 conversion process in dissolution experiments of limestone and dolomite. It was found that the rate of dissolution increases by a factor of about 10 after the addition of CA at a high CO2 partial pressure (Pco2) for limestone and about 3 at low Pco2 for dolomite. This shows that reappraisal is necessary for the importance of chemical weathering (including carbonate rock dissolution and silicate weathering) in the atmospheric CO2 sink and the mysterious missing sink in carbon cycling. It is doubtless that previous studies of weathering underestimated weathering rates due to the ignorance of CA as an activator in weathering, thus the contribution of weathering to the atmospheric CO2 sink is also underestimated. This finding also shows the need to examine the situ distribution and activity of CA in different waters and to investigate the role of CA in weathering.展开更多
AIM:To analyze possible relationships between CA IX/ CA XII and pVHL expression in normal and neoplastic colorectal mucosa. METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients...AIM:To analyze possible relationships between CA IX/ CA XII and pVHL expression in normal and neoplastic colorectal mucosa. METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA IX, CA XII and pVHL. VHL mRNAs from 14 fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and G412mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGFas an indicator of hypoxia that uncouples the pVHL control. RESULTS: Tumor tissues were associated with a borderline increase of CA IX staining signal and slight but significant decrease of CA XII immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/ mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL and CA IX/CA XII proteins as well as between MEGFand CA9 mRNAs, but the tumor-associated changes in mRNA levels of VEGFand CA12 showed a significant inverse relationship. CONCLUSION: Our results indicate that CA9and CA12 are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA IX/CA XII and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA IX/CA XII in colorectal tumors seems rather complex and is not evident merely at the expression levels.展开更多
Works on exploring an environmentally clean method for producing an Mg,Al-hydrotalcite(Mg6Al2(OH) 16CO3·4H2O) layer and/or calcium carbonate(CaCO3) layer on Mg alloy in a carbonic acid solution system(aqueous HCO...Works on exploring an environmentally clean method for producing an Mg,Al-hydrotalcite(Mg6Al2(OH) 16CO3·4H2O) layer and/or calcium carbonate(CaCO3) layer on Mg alloy in a carbonic acid solution system(aqueous HCO3-/CO3 2-or Ca 2+ /HCO3-) at 50℃ were reviewed.Conversion treatment for the Mg,Al-hydrotalcite conversion coating was as follows.Mg alloy was treated first in acidic HCO3-/CO3 2-aqueous for precursor layer formation on Mg alloy surface and then in alkaline HCO3-/CO3 2-aqueous to form a crystallized Mg,Al-hydrotalcite coating.Duration of an Mg,Al-hydrotalcite coating on Mg alloy surface was reduced from 12 h to 4 h by the conversion treatment.On the other hand,for reducing the formation time of CaCO3 coating on Mg alloy,the aqueous Ca 2+ /HCO3-with a saturated Ca 2+ content was employed for developing a CaCO3 coating on Mg alloy.A dense CaCO3 coating could yield on Mg alloy surface in 2 h.Corrosion rate(corrosion current density,Jcorr) of the Mg,Al-hydrotalcite-coated sample and CaCO3-coated AZ91D sample was 7-10μA/cm 2,roughly two orders less than the Jcorr of the as-diecast sample(about 200μA/cm 2) . No corrosion spot on the Mg,Al-hydrotalcite-coated sample and CaCO3-coated sample was observed after 72 h and 192 h salt spray test,respectively.展开更多
AIM: To investigate the expression and prognostic value of carbonic anhydrase Ⅱ (CA Ⅱ) and Ki-67 in gastrointestinal stromal tumors (GISTs). METHODS: One hundred and thirteen GIST patients admitted to Chinese People...AIM: To investigate the expression and prognostic value of carbonic anhydrase Ⅱ (CA Ⅱ) and Ki-67 in gastrointestinal stromal tumors (GISTs). METHODS: One hundred and thirteen GIST patients admitted to Chinese People's Liberation Army General Hospital from January 2004 to December 2010 were retrospectively followed up, and immunohistochemistry was used to detect CA Ⅱ, Ki-67 and CD117 expression in tumor samples. The survival rates of the patients were analyzed using the Kaplan-Meier method. Log-rank test, χ 2 test and Cox proportional hazards model were used to determine the relationships between CA Ⅱ, Ki-67 and CD117 expression and prognostic value in GISTs. RESULTS: The survival rates at 1, 3 and 5 years were 90.0%, 82.0% and 72.0% in all patients. However, in patients with positive CA Ⅱ or Ki-67, the survival rates were 92.0%, 83.0% and 77.0% or 83.0%, 66.6% and 53.0%, respectively. Compared with the negative groups, the survival rates in the positive groups were significantly lower (CA Ⅱ log-rankP = 0.000; Ki-67 logrank P = 0.004). Multivariate Cox analysis revealed that CA Ⅱ, CD117 and Ki-67 were considerable immune factors in prognosis of GIST patients (CA Ⅱ P = 0.043; CD117 P = 0.042; Ki-67 P = 0.007). Besides, tumor diameter, mitotic rate, tumor site, depth of invasion, complete resection, intraoperative rupture, and adjuvant therapy were important prognosis predictive factors. Our study indicated that CA Ⅱ had strong expression in GISTs and the prognosis of GISTs with high CA Ⅱ expression was better than that of GISTs with low or no expression, suggesting that CA Ⅱ is both a diagnostic and prognostic biomarker for GIST. CONCLUSION: CA Ⅱ and Ki-67 are significant prognostic factors for GISTs. CA Ⅱ associated with neovascular endothelia could serve as a potential target for cancer therapy.展开更多
Carbonic anhydrase(CA)as a typical metalloenzyme in biological system can accelerate the hydration/dehydration of carbon dioxide(CO2,the major components of greenhouse gases),which performer with high selectivity,envi...Carbonic anhydrase(CA)as a typical metalloenzyme in biological system can accelerate the hydration/dehydration of carbon dioxide(CO2,the major components of greenhouse gases),which performer with high selectivity,environmental friendliness and superior efficiency.However,the free form of CA is quite expensive(~RMB 3000/100 mg),unstable,and non-reusable as the free form of CA is not easy for recovery from the reaction environment,which severely limits its large-scale industrial applications.The immobilization may solve these problems at the same time.In this context,many efforts have been devoted to improving the chemical and thermal stabilities of CA through immobilization strategy.Very recently,a wide range of available inorganic,organic and hybrid compounds have been explored as carrier materials for CA immobilization,which could not only improve the tolerance of CA in hazardous environments,but also improve the efficiency and recovery to reduce the cost of large-scale application of CA.Several excellent reviews about immobilization methods and application potential of CA have been published.By contrast,in our review,we stressed on the way to better retain the biocatalytic activity of immobilized CA system based on different carrier materials and to solve the problems facing in practical operations well.The concluding remarks are presented with a perspective on constructing efficient CO2 conversion systems through rational combining CA and advanced carrier materials.展开更多
AIM To investigate expression of four alpha-carbonic anhydrases(CAs) in colorectal carcinomas(CRC) and compare the results with patients' survival.METHODS Colorectal carcinoma samples from 539 CRC patients and con...AIM To investigate expression of four alpha-carbonic anhydrases(CAs) in colorectal carcinomas(CRC) and compare the results with patients' survival.METHODS Colorectal carcinoma samples from 539 CRC patients and control tissues were arranged as tissue microarrays and analyzed with antibodies against CA Ⅱ, CA Ⅶ, CA Ⅸ, and CA Ⅻ. Intensity and extent of staining were both scored from 0 to 3 in each sample. These enzyme expression levels were then correlated to patients' survival and clinicopathological parameters, which were tumor differentiation grade and stage, site of tumor, patients' age, and gender. Kaplan-Meier analysis and Cox regression hazard ratio model were used to analyze survival data. RESULTS CA Ⅱ and CA Ⅻ staining intensities correlated with patients' survival in that higher expression indicated poorer prognosis. In Cox regression analysis one unit increase in the CA Ⅱ intensity increased the hazard ratio to 1.19 fold(CI: 1.04-1.37, P = 0.009). A significant correlation was also found when comparing CA Ⅻ staining intensity with survival of CRC patients(HR = 1.18, 95%CI: 1.01-1.38, P = 0.036). The extent of CA Ⅻ immunostaining did not correlate to the patients' survival(P = 0.242, Kaplan-Meier analysis). A significant interaction between age group and extent of the CA Ⅱ staining was found. Increased extent of CA Ⅱ had a significant hazard ratio among patients 65 years and older(1.42, 95%CI: 1.16-1.73, P = 0.0006). No correlations were found between CA Ⅶ(intensity P = 0.566, extent P = 0.495, Kaplan-Meier analysis), or CA Ⅸ(intensity P = 0.879, extent P = 0.315, KaplanMeier analysis) immunostaining results and survival, or the other parameters. CONCLUSION The present findings indicate that CA Ⅱ and CA Ⅻ could be useful in predicting survival in CRC.展开更多
Carbonic anhydrases (CAs) catalyse the hydration of C02 to bicarbonate at physiological pH. This chemical interconversion is crucial since HCO3- is the substrate for several biosynthetic reactions. This review is focu...Carbonic anhydrases (CAs) catalyse the hydration of C02 to bicarbonate at physiological pH. This chemical interconversion is crucial since HCO3- is the substrate for several biosynthetic reactions. This review is focused on the distribution and role of CA isoenzymes in both normal and pathological gastrointestinal (GI) tract tissues. It has been known for many years that CAs are widely present in the GI tract and play important roles in several physiological functions such as production of saliva, gastric acid, bile, and pancreatic juice as well as in absorption of salt and water in intestine. New information suggests that these enzymes participate in several processes that were not envisioned earlier. Especially, the recent reports on plasma membrane-bound isoenzymes IX and XII have raised considerable interest since they were reported to participate in cancer invasion and spread. They are induced by tumour hypoxia and may also play a role in von Hippel-Lindau (VHL)-mediated carcinogenesis.展开更多
Carbonate decomposition of carbonic refractory gold ore and the following pressure oxidation were studied.In the carbonate decomposition procedure,the effects of liquid-to-solid ratio and reaction time on decompositio...Carbonate decomposition of carbonic refractory gold ore and the following pressure oxidation were studied.In the carbonate decomposition procedure,the effects of liquid-to-solid ratio and reaction time on decomposition ratio of carbonate were investigated.The experimental result shows that the decomposition ratio of carbonate is 98.24%under the conditions of liquid-to-solid ratio of 5:1,Fe^(3+)concentration of 20 g/L,sulfuric acid concentration of 20 g/L,reaction temperature of 80 ℃ and reaction time of 2 h.Then,the slurry obtained from carbonate decomposition was put into the titanium autoclave for pressure oxidation leaching.Effects of liquid-to-solid ratio,temperature,time and oxygen partial pressure on sulfur oxidation ratio were studied during pressure oxidation.With the prolonged time,pyrite and arsenopyrite are oxidized to ferric subsulfate,hydrated ferric sulfate and jarosite,resulting in the increasing residue ratio.The residue ratio and the sulfur content in the residue can be decreased by ferric subsulfate dissolution.The oxidation ratio of the sulfur is 99.35% under the conditions of oxidation time of 4 h,temperature of 210 ℃,oxygen partial pressure of 0.8 MPa and stirring speed of 600 r/min.展开更多
AIM: To study the expression of carbonic anhydrase(CA) 9 in human hepatocellular carcinoma(HCC) cells.METHODS: We studied CA9 protein, CA9 m RNA and hypoxia-inducible factor-1 alpha(HIF-1α) protein levels in Hep3 B c...AIM: To study the expression of carbonic anhydrase(CA) 9 in human hepatocellular carcinoma(HCC) cells.METHODS: We studied CA9 protein, CA9 m RNA and hypoxia-inducible factor-1 alpha(HIF-1α) protein levels in Hep3 B cells exposed in different parallel approaches. In one of these approaches, HCC cells were exposed to extreme in vitro hypoxia(24 h 0.1% O2) without or with interleukin(IL)-1, IL-6, tumor necrosis factoralpha(TNF-α) and transforming growth factor-beta(TGF-β) stimulation for the same hypoxic exposure time or exposed to normoxic oxygenation conditions without or with cytokine stimulation.RESULTS: The tumour cell line analysed showed a strong hypoxic CA9 m RNA expression pattern in response to prolonged severe hypoxia with cell-line specific patterns and a marked induction of CA9 protein in response to severe hypoxia. These results were paralleled by the results for HIF-1α protein under identical oxygenation conditions with a similar expression tendency to that displayed during the CA9 protein expression experimental series. Continuous stimulation with the cytokines, IL-1, IL-6, TNF-α and TGF-β, under normoxic conditions significantly increased the carbonic anhydrase 9 expression level at both the protein and m RNA level, almost doubling the CA9 m RNA and CA9 and HIF-1α protein expression levels found under hypoxia. The findings from these experiments indicated that hypoxia is a positive regulator of CA9 expression in HCC, and the four signal transduction pathways, IL-1, IL-6, TNF-α and TGF-β, positively influence CA9 expression under both normoxic and hypoxic conditions.CONCLUSION: These findings may potentially be considered in the design of anti- cancer therapeutic approaches involving hypoxia-induced or cytokine stimulatory effects on expression. In addition, they provideevidence of the stimulatory role of the examined cytokine families resulting in an increase in CA9 expression under different oxygenation conditions in human cancer, especially HCC, and on the role of the CA9 gene as a positive disease regulator in human cancer.展开更多
The reaction between carbonic acid and montmorillonite minerals was studied in order to provide a theoretical basis for analyzing changes in the physical properties of coal seams after CO_(2)injection and for optimizi...The reaction between carbonic acid and montmorillonite minerals was studied in order to provide a theoretical basis for analyzing changes in the physical properties of coal seams after CO_(2)injection and for optimizing CO_(2) pumping parameters.A single montmorillonite mineral of purity[90%was selected and subjected to reactions at 25,35,and 45℃in carbonic acid solutions of varying acidity.The Si and Al concentrations in the solutions and the structure and elemental compositions of the montmorillonite before and after the reactions were analyzed using a spectrophotometer,an X-ray diffractometer,and an energy-dispersive X-ray spectrometer;kinetic reaction models were established for the dissolution of Si and Al in carbonic acid solutions in order to estimate the apparent activation energy of Si dissolution under different acidity conditions.The results indicate that Al dissolved rapidly and soon reached solubility equilibrium.On the other hand,Si concentration in the solutions increased rapidly and then gradually declined with vibrations,with maximum values at 25,35,and 45℃,which were observed at approximately 96,72,and 48 h,respectively.In addition,Si dissolution fitted the diffusion-controlled reaction model well;as the pH value decreased,the apparent activation energy of Si dissolution decreased,and Si became easier to dissolve.Furthermore,it was concluded that as a weak acid,carbonic acid causes little damage to the mineral structure of montmorillonite.展开更多
Carbonic anhydrase VII (CA VII) is a cytosolic enzyme expressed in several organs, including the human brain, but it has not been investigated earlier in any tumors. We designed the present study to evaluate CA VII ex...Carbonic anhydrase VII (CA VII) is a cytosolic enzyme expressed in several organs, including the human brain, but it has not been investigated earlier in any tumors. We designed the present study to evaluate CA VII expression in a cohort of human diffuse astrocytomas, mixed oligoastrocytomas and oligodendrogliomas. CA VII immunostaining was correlated to clinico-pathologic findings, survival data, and expres-sion of other molecular factors, including Ki-67, p53 protein and epidermal growth factor receptor. CA VII-positive staining was observed in 94% of astrocytomas and 85% of oligodendrogliomas. In the tumor specimens, strong positive areas were often located in close proximity to necrosis. The CA VII immunoreactivity showed positive correlation with tumor malignancy grades of astrocytomas (p = 0.02, chi-square test). In all tumor categories, CA VII-positive staining was often seen in the en-dothelial cells of neovessels in addition to the tumor cells. CA VII intensity showed no significant association with p53 nor did it correlate with the amplification of epidermal growth factor receptor (analyzed only in astrocytomas) or cell proliferation. Our present results show that CA VII may act as a useful biomarker in histopathologic diagnostics of gliomas. The high expression of CA VII in the tumor cells and endothelium suggests important roles for the enzyme in tumor metabolism. The results also led us to conclude that CA VII might serve as a marker of poor prognosis in diffuse astrocytomas.展开更多
Hepatocellular carcinoma (HCC) is among most common terminal cancer types in the world. Primary etiological factors include cirrhosis, hepatitis, aflatoxin and alcohol. The current study was conducted to determine cyt...Hepatocellular carcinoma (HCC) is among most common terminal cancer types in the world. Primary etiological factors include cirrhosis, hepatitis, aflatoxin and alcohol. The current study was conducted to determine cytosolic erythrocyte carbonic anhydrase and catalase enzyme activities and levels of some trace elements. For this purpose, 40 patients with primary and metastatic hepatic cancer and 29 healthy volunteers enrolled to the study. Catalase and carbonic anhydrase enzyme activities and serum trace element levels were measured in patient and control groups. In the current study, serum copper, magnesium, manganese and zinc levels were lower in the primary and metastatic hepatic cancer group in comparison with the control group (P < 0.05). In contrast, serum iron, cobalt, cadmium and lead levels were higher in the patient relative to the control group (P < 0.05). In comparison with the control group, the catalase level was lower in primary and metastatic cancer group, while the carbonic anhydrase level was higher in the cancer group (P < 0.05). Changes in levels of trace elements and anti-oxidant enzymes may be the factors which influence the development and progression of liver cancer. The carbonic anhydrase enzyme can be a useful indicator in the diagnosis of cancer. However, this issue warrants further investigation.展开更多
Dunaliella salina, a halotolerant unicellular green alga without a rigid cell wall, can live in salinities ranging from 0.05 to 5 mol/L NaC1. These features of D. salina make it an ideal host for the production of ant...Dunaliella salina, a halotolerant unicellular green alga without a rigid cell wall, can live in salinities ranging from 0.05 to 5 mol/L NaC1. These features of D. salina make it an ideal host for the production of antibodies, oral vaccine, and commercially valuable polypeptides. To produce high level of heterologous proteins from D. salina, highly efficient promoters are required to drive expression of target genes under controlled condition. In the present study, we cloned a 5＇ franking region of 1.4 kb from the carbonic anhydrase （CAH） gene ofD. salina by genomic walking and PCR. The fragment was ligated to the pMD18-T vector and characterized. Sequence analysis indicated that this region contained conserved motifs, including a TATA- like box and CAAT-box. Tandem （GT）n repeats that had a potential role of transcriptional control, were also found in this region. The transcription start site （TSS） of the CAH gene was determined by 5＇ RACE and nested PCR method. Transformation assays showed that the 1.4 kb fragment was able to drive expression of the selectable bar （bialaphos resistance） gene when the fusion was transformed into D. salina by biolistics. Northern blotting hybridizations showed that the bar transcript was most abundant in cells grown in 2 mol/L NaCl, and less abundant in 0.5 mol/L NaCl, indicating that expression of the bar gene was induced at high salinity. These results suggest the potential use of the CAH gene promoter to induce the expression of heterologous genes in D. salina under varied salt condition.展开更多
Carbonic anhydrases(CA, EC 4.2.1.1) catalyze the interconversion bewteen carbon dioxide and bicarbonate with generation of protons. The carbonic anhydrase isozyme Ⅸ(CA Ⅸ) is highly overexpresed in hypoxic tumors and...Carbonic anhydrases(CA, EC 4.2.1.1) catalyze the interconversion bewteen carbon dioxide and bicarbonate with generation of protons. The carbonic anhydrase isozyme Ⅸ(CA Ⅸ) is highly overexpresed in hypoxic tumors and shows very restricted expression in normal tissues. CA Ⅸ is a dimeric protein possessing very high catalytic activity for the hydration of carbon dioxide to protons and bicarbonate. Its quaternary structure is unique among members of this family of enzymes, allowing for structure-based drug design campaigns of selective inhibitors. Inhibition of CA Ⅸ with sulfonamide and/or coumarin inhibitors was recently shown to lead to a potent retardation for the growth of both primary tumors and metastases. Some fluorescent sulfonamides were shown to accumulate only in hypoxic tumor cells overexpressing CA Ⅸ, and might be used as diagnostic tools for imaging of hypoxic cancers. Sulfonamide inhibitors were also more effective in inhibiting the growth of the primary tumors when associated with irrdiation. CA Ⅸ is thus both a diagnostic and therapeutic validated target for the management of hypoxic tumors normally non-responsive to classical chemio- and radiotherapy.展开更多
A carbonic anhydrase( CA) transcript was obtained from the Contig library according to the published sequencing information of the buckwheat transcripts. The full length of the CA gene was amplified by reverse transcr...A carbonic anhydrase( CA) transcript was obtained from the Contig library according to the published sequencing information of the buckwheat transcripts. The full length of the CA gene was amplified by reverse transcription PCR( RT-PCR). The bioinformatics analysis showed that the full length of Fs CA1 gene was 1233 bp and open reading frame was 978 bp,and encoding 325 amino acids. The molecular weight was 35. 11 ku and the isoelectric point was 7. 59; there were 9 α helices,6 β folds,many randon coil and extension chain,containing one signal peptide and one transmembrane region,having a 2 amino acid conserved domains with typical beta-type carbonic anhydrase. Subcellular localization showed that the protein is most likely to appear in the chloroplast. The three-dimensional structure model of Fs CA1 was built by homologous modeling method,indicating that the homo-octamer of buckwheat CA and pea CA could match well,so it can be inferred that buckwheat CA is also homo-octamer. Real-time quantitative PCR was used to detect the expression of Fs CA1 in different organs of buckwheat.The results showed that Fs CA1 had the highest expression level in leaves,then in the stems,and the lowest in roots.展开更多
Many cancer cells in solid tumors are hypoxic or pseudohypoxic and create acidic environment for malignancy progression. Under low oxygen conditions (hypoxia), hypoxia-inducible factors (HIFs) play pathological roles ...Many cancer cells in solid tumors are hypoxic or pseudohypoxic and create acidic environment for malignancy progression. Under low oxygen conditions (hypoxia), hypoxia-inducible factors (HIFs) play pathological roles in cancer cell survival and spreading. HIF regulates several genes such as genes of glucose transporters that enhance anaerobic glycolysis, angiogenesis, erythropoiesis and carbonic anhydrase IX (CA-IX). CA-IX is a cell-surface glycoprotein that catalyzes the hydration of CO2 to protons and bicarbonate ions (respiratory acidification). This process is involved in adaptation to acidosis and implicated in cancer progression. Therefore, CA-IX inhibitors (such as sulfonamide-based compounds) showed hoping results in reduction malignancy progression. The article aims to reversal the malignant hypoxic environment in solid tumors to create a condition of weakness within the cancer for further focused cisplatin potency. This article suggests the use of modified synthesized HIF as a drug delivery molecule for both carbonic anhydrase IX inhibitor and glycosylated cisplatin that damages the DNA of malignant cell. HIF molecule has high affinity to bind with CA IX-expressing malignant cells, which is followed by cell entrance via endocytosis. Once the HIF-Cisplatin-CA-inhibitor complex enters the cell, the carbonic anhydrase inhibitor will improve the cellular pH that makes the environment unsuitable for HIF 1α function and it may be ubiquitinated. So, the raise in target genes transcription will be arrested. On the other hand, once the synthetized HIF is degraded, the cisplatin molecules will be released inside the malignant cell and start to damage its DNA. This approach may be a good solution for many solid tumors.展开更多
This paper deals the randomness effect of the pressure of carbonic gas on the carbonation phenomenon of the reinforced concrete. This analysis concentrates on the evaluation of carbonation depth (Xc) and the carbonati...This paper deals the randomness effect of the pressure of carbonic gas on the carbonation phenomenon of the reinforced concrete. This analysis concentrates on the evaluation of carbonation depth (Xc) and the carbonation time (T1) which is the time necessary so that the face of carbonation arrives until the reinforcement from a probabilistic analysis. Monte Carlo simulations are realized under the assumption that the carbonic gas on the surface of the concrete is random variable with a log-normal probability distribution.展开更多
Carbonic anhydrase isozyme CA3 protects cells against oxidative stress. Ectopic expression of murine Ca3, but not Ca2, protects proto-oncogene Evi1 expressing Rat1 fibroblast cells (ca3low) against hydrogen peroxide (...Carbonic anhydrase isozyme CA3 protects cells against oxidative stress. Ectopic expression of murine Ca3, but not Ca2, protects proto-oncogene Evi1 expressing Rat1 fibroblast cells (ca3low) against hydrogen peroxide (H2O2) induced stress. Ca3 is S-glutathionylated via glutathione adducts with cysteines 181 and 186. Substitution of both Ca3 cysteines with serine fails to protect cells from oxidative stress. Insertion of cysteine at 181 and 186 in Ca2 is insufficient for conferring efficient anti-oxidant activity. This shows for the first time that S-glutathionylation of cys181 and cys186 residues is required for Ca3 anti-oxidant activity but that additional factors are also required.展开更多
基金Supported by the Fundamental Research Program of Shanxi Province(Nos.202103021223266,202203021211313,202303021211114,202303021222246)the Excellent Doctoral Research Project in Shanxi Province(No.QZX-2023005)the Shanxi Scientific and Technological Innovation Team of Halophiles Resources Utilization(No.202204051001035)。
文摘Water scarcity and pollution pose a threat to the sustainable development of cities and society.Therefore,it is crucial to analyze the hydrochemical characteristics and carbon dynamics of waterdeficient areas.Taking the Taiyuan section of Fenhe River as the research object,we systematically explored the hydrochemical characteristics of surface water and its evolutionary processes,as well as the ecological effect of algal carbonic anhydrase in carbon cycle using the hydrochemical evolution method and correlation analysis.The ternary diagram demonstrates that the main water chemical type in Fenhe River was SO^(2-)_(4)·Cl^(-)-Na^(+).The Gibbs and end-member diagrams of each ion display that the chemical composition of surface water was mainly controlled by silicate decomposition.The chemical ions originated mainly from dissolution of some minerals,such as plagioclase,halite,dolomite,calcite,and gypsum.The diatoms had a lower CO_(2)requirement because they exhibited a higher abundance at a lower partial pressure of CO_(2)(p CO_(2)).However,high CO_(2)concentration had a positive effect on cyanobacteria,which reduced the active transport of HCO_(3)^(-),saved the energy needed for this part of active transport,and indirectly improved the overall photosynthetic efficiency of algae.Carbonic anhydrase(CA)activity was significantly negatively correlated with p CO_(2)and positively correlated with HCO_(3)^(-)concentration,indicating that CA in water promoted the conversion of CO_(2)to HCO_(3)^(-).The HCO_(3)^(-)generated from this process continued to participate in the erosion of silicate rocks,sequestering CO_(2)in the form of Ca CO_(3),which has a non-negligible impact on the carbon sink in the Fenhe River.These consequences may have important implications for the biogeochemical cycling occurring in urban water.
基金Supported by a grant from UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases(No.900142,930143,960103,970074,990490)the National Science and Technology Development Agency of Thailand(Career Development Award ID no.01-38-007)the Thailand Research Fund(BasicResearch Grants ID No.BRG/13/2543.BRG4580020.BRG 4880006)
文摘Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitates identification and characterisation of novel drug targets and their potential inhibitors.We identified the carbonic anhydrase(CA) genes in P.falciparum.The pfGA gene encodes an α-carbonic anhydrase,a Zn^(2+)-metalloenzme,possessing catalytic properties distinct from that of the human host CA enzyme.The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes.A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions.The structure of the groups substituting the aromatic-ureido-or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides.One derivative,that is,4-(3,4-dichlorophenylureido)thioureidobcnzcnesulfonamide(compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor,and was also the most effective antimalarial compound on the in vitro P.falciparum growth inhibition.The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei,an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria.
基金Financial supports for this research was provided by the National Nature Science Foundation of China(Grant 40073026)Ministry of Science and Technology of China(Grant 164)+1 种基金Natural Science Foundation of Guangxi(Grant 9824021)Ministry of Land and Resources of China(Grant 9806)and Bremen University of Germany.
文摘The conversion of CO2 into H+ and is a relatively slow reaction. Hence, its kinetics may be rate determining in carbonate rock dissolution. Carbonic anhydrase (CA), which is widespread in nature, was used to catalyze the CO2 conversion process in dissolution experiments of limestone and dolomite. It was found that the rate of dissolution increases by a factor of about 10 after the addition of CA at a high CO2 partial pressure (Pco2) for limestone and about 3 at low Pco2 for dolomite. This shows that reappraisal is necessary for the importance of chemical weathering (including carbonate rock dissolution and silicate weathering) in the atmospheric CO2 sink and the mysterious missing sink in carbon cycling. It is doubtless that previous studies of weathering underestimated weathering rates due to the ignorance of CA as an activator in weathering, thus the contribution of weathering to the atmospheric CO2 sink is also underestimated. This finding also shows the need to examine the situ distribution and activity of CA in different waters and to investigate the role of CA in weathering.
基金Supported by the Grants From Sigrid Juselius Foundation, from Finnish Cultural Foundation and Finnish Dental Society from the National Institutes of Health (DK40163, GM34182, and GM53405)from Slovak Grant Agency (2/2025) from the Slovak Government (Cancer Genomics SP 51/0280800) and from Bayer Corporation
文摘AIM:To analyze possible relationships between CA IX/ CA XII and pVHL expression in normal and neoplastic colorectal mucosa. METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA IX, CA XII and pVHL. VHL mRNAs from 14 fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and G412mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGFas an indicator of hypoxia that uncouples the pVHL control. RESULTS: Tumor tissues were associated with a borderline increase of CA IX staining signal and slight but significant decrease of CA XII immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/ mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL and CA IX/CA XII proteins as well as between MEGFand CA9 mRNAs, but the tumor-associated changes in mRNA levels of VEGFand CA12 showed a significant inverse relationship. CONCLUSION: Our results indicate that CA9and CA12 are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA IX/CA XII and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA IX/CA XII in colorectal tumors seems rather complex and is not evident merely at the expression levels.
基金Project supported by the Ministry of Education Under the ATU Plan
文摘Works on exploring an environmentally clean method for producing an Mg,Al-hydrotalcite(Mg6Al2(OH) 16CO3·4H2O) layer and/or calcium carbonate(CaCO3) layer on Mg alloy in a carbonic acid solution system(aqueous HCO3-/CO3 2-or Ca 2+ /HCO3-) at 50℃ were reviewed.Conversion treatment for the Mg,Al-hydrotalcite conversion coating was as follows.Mg alloy was treated first in acidic HCO3-/CO3 2-aqueous for precursor layer formation on Mg alloy surface and then in alkaline HCO3-/CO3 2-aqueous to form a crystallized Mg,Al-hydrotalcite coating.Duration of an Mg,Al-hydrotalcite coating on Mg alloy surface was reduced from 12 h to 4 h by the conversion treatment.On the other hand,for reducing the formation time of CaCO3 coating on Mg alloy,the aqueous Ca 2+ /HCO3-with a saturated Ca 2+ content was employed for developing a CaCO3 coating on Mg alloy.A dense CaCO3 coating could yield on Mg alloy surface in 2 h.Corrosion rate(corrosion current density,Jcorr) of the Mg,Al-hydrotalcite-coated sample and CaCO3-coated AZ91D sample was 7-10μA/cm 2,roughly two orders less than the Jcorr of the as-diecast sample(about 200μA/cm 2) . No corrosion spot on the Mg,Al-hydrotalcite-coated sample and CaCO3-coated sample was observed after 72 h and 192 h salt spray test,respectively.
文摘AIM: To investigate the expression and prognostic value of carbonic anhydrase Ⅱ (CA Ⅱ) and Ki-67 in gastrointestinal stromal tumors (GISTs). METHODS: One hundred and thirteen GIST patients admitted to Chinese People's Liberation Army General Hospital from January 2004 to December 2010 were retrospectively followed up, and immunohistochemistry was used to detect CA Ⅱ, Ki-67 and CD117 expression in tumor samples. The survival rates of the patients were analyzed using the Kaplan-Meier method. Log-rank test, χ 2 test and Cox proportional hazards model were used to determine the relationships between CA Ⅱ, Ki-67 and CD117 expression and prognostic value in GISTs. RESULTS: The survival rates at 1, 3 and 5 years were 90.0%, 82.0% and 72.0% in all patients. However, in patients with positive CA Ⅱ or Ki-67, the survival rates were 92.0%, 83.0% and 77.0% or 83.0%, 66.6% and 53.0%, respectively. Compared with the negative groups, the survival rates in the positive groups were significantly lower (CA Ⅱ log-rankP = 0.000; Ki-67 logrank P = 0.004). Multivariate Cox analysis revealed that CA Ⅱ, CD117 and Ki-67 were considerable immune factors in prognosis of GIST patients (CA Ⅱ P = 0.043; CD117 P = 0.042; Ki-67 P = 0.007). Besides, tumor diameter, mitotic rate, tumor site, depth of invasion, complete resection, intraoperative rupture, and adjuvant therapy were important prognosis predictive factors. Our study indicated that CA Ⅱ had strong expression in GISTs and the prognosis of GISTs with high CA Ⅱ expression was better than that of GISTs with low or no expression, suggesting that CA Ⅱ is both a diagnostic and prognostic biomarker for GIST. CONCLUSION: CA Ⅱ and Ki-67 are significant prognostic factors for GISTs. CA Ⅱ associated with neovascular endothelia could serve as a potential target for cancer therapy.
基金the National Natural Science Fundation of China(21776213)Natural Science Fund of Tianjin(19JCYBJC19700)for financial support。
文摘Carbonic anhydrase(CA)as a typical metalloenzyme in biological system can accelerate the hydration/dehydration of carbon dioxide(CO2,the major components of greenhouse gases),which performer with high selectivity,environmental friendliness and superior efficiency.However,the free form of CA is quite expensive(~RMB 3000/100 mg),unstable,and non-reusable as the free form of CA is not easy for recovery from the reaction environment,which severely limits its large-scale industrial applications.The immobilization may solve these problems at the same time.In this context,many efforts have been devoted to improving the chemical and thermal stabilities of CA through immobilization strategy.Very recently,a wide range of available inorganic,organic and hybrid compounds have been explored as carrier materials for CA immobilization,which could not only improve the tolerance of CA in hazardous environments,but also improve the efficiency and recovery to reduce the cost of large-scale application of CA.Several excellent reviews about immobilization methods and application potential of CA have been published.By contrast,in our review,we stressed on the way to better retain the biocatalytic activity of immobilized CA system based on different carrier materials and to solve the problems facing in practical operations well.The concluding remarks are presented with a perspective on constructing efficient CO2 conversion systems through rational combining CA and advanced carrier materials.
基金Supported by the Sigrid Jusélius Foundation,the Academy of Finland,the Medical Research Funds of Tampere University Hospital and Helsinki University Hospital,and Jane and Aatos Erkko Foundation
文摘AIM To investigate expression of four alpha-carbonic anhydrases(CAs) in colorectal carcinomas(CRC) and compare the results with patients' survival.METHODS Colorectal carcinoma samples from 539 CRC patients and control tissues were arranged as tissue microarrays and analyzed with antibodies against CA Ⅱ, CA Ⅶ, CA Ⅸ, and CA Ⅻ. Intensity and extent of staining were both scored from 0 to 3 in each sample. These enzyme expression levels were then correlated to patients' survival and clinicopathological parameters, which were tumor differentiation grade and stage, site of tumor, patients' age, and gender. Kaplan-Meier analysis and Cox regression hazard ratio model were used to analyze survival data. RESULTS CA Ⅱ and CA Ⅻ staining intensities correlated with patients' survival in that higher expression indicated poorer prognosis. In Cox regression analysis one unit increase in the CA Ⅱ intensity increased the hazard ratio to 1.19 fold(CI: 1.04-1.37, P = 0.009). A significant correlation was also found when comparing CA Ⅻ staining intensity with survival of CRC patients(HR = 1.18, 95%CI: 1.01-1.38, P = 0.036). The extent of CA Ⅻ immunostaining did not correlate to the patients' survival(P = 0.242, Kaplan-Meier analysis). A significant interaction between age group and extent of the CA Ⅱ staining was found. Increased extent of CA Ⅱ had a significant hazard ratio among patients 65 years and older(1.42, 95%CI: 1.16-1.73, P = 0.0006). No correlations were found between CA Ⅶ(intensity P = 0.566, extent P = 0.495, Kaplan-Meier analysis), or CA Ⅸ(intensity P = 0.879, extent P = 0.315, KaplanMeier analysis) immunostaining results and survival, or the other parameters. CONCLUSION The present findings indicate that CA Ⅱ and CA Ⅻ could be useful in predicting survival in CRC.
基金Supported by the Grants from Sigrid Juselius Foundation, The Academy of Finland (SP), Finnish Cultural Foundation and Finnish Dental Society UK)
文摘Carbonic anhydrases (CAs) catalyse the hydration of C02 to bicarbonate at physiological pH. This chemical interconversion is crucial since HCO3- is the substrate for several biosynthetic reactions. This review is focused on the distribution and role of CA isoenzymes in both normal and pathological gastrointestinal (GI) tract tissues. It has been known for many years that CAs are widely present in the GI tract and play important roles in several physiological functions such as production of saliva, gastric acid, bile, and pancreatic juice as well as in absorption of salt and water in intestine. New information suggests that these enzymes participate in several processes that were not envisioned earlier. Especially, the recent reports on plasma membrane-bound isoenzymes IX and XII have raised considerable interest since they were reported to participate in cancer invasion and spread. They are induced by tumour hypoxia and may also play a role in von Hippel-Lindau (VHL)-mediated carcinogenesis.
基金Project(51404296)supported by the Young Scientists Fund of National Natural Science Foundation of ChinaProject(134414)supported by the Postdoctoral Funded Program of Central South University,China
文摘Carbonate decomposition of carbonic refractory gold ore and the following pressure oxidation were studied.In the carbonate decomposition procedure,the effects of liquid-to-solid ratio and reaction time on decomposition ratio of carbonate were investigated.The experimental result shows that the decomposition ratio of carbonate is 98.24%under the conditions of liquid-to-solid ratio of 5:1,Fe^(3+)concentration of 20 g/L,sulfuric acid concentration of 20 g/L,reaction temperature of 80 ℃ and reaction time of 2 h.Then,the slurry obtained from carbonate decomposition was put into the titanium autoclave for pressure oxidation leaching.Effects of liquid-to-solid ratio,temperature,time and oxygen partial pressure on sulfur oxidation ratio were studied during pressure oxidation.With the prolonged time,pyrite and arsenopyrite are oxidized to ferric subsulfate,hydrated ferric sulfate and jarosite,resulting in the increasing residue ratio.The residue ratio and the sulfur content in the residue can be decreased by ferric subsulfate dissolution.The oxidation ratio of the sulfur is 99.35% under the conditions of oxidation time of 4 h,temperature of 210 ℃,oxygen partial pressure of 0.8 MPa and stirring speed of 600 r/min.
基金Supported by Deutsche Forschungsgemeinschaft DFG,VO 871/2-3,to Vordermark Dthe IZKF Würzburg,B25,to Hagemenn C+1 种基金Turkish Research Council(TUBITAK)Project,TBAG 105T326,to Kockar F and Yildrim HBalikesir University Research Project,2008/15,to Sagkan RI
文摘AIM: To study the expression of carbonic anhydrase(CA) 9 in human hepatocellular carcinoma(HCC) cells.METHODS: We studied CA9 protein, CA9 m RNA and hypoxia-inducible factor-1 alpha(HIF-1α) protein levels in Hep3 B cells exposed in different parallel approaches. In one of these approaches, HCC cells were exposed to extreme in vitro hypoxia(24 h 0.1% O2) without or with interleukin(IL)-1, IL-6, tumor necrosis factoralpha(TNF-α) and transforming growth factor-beta(TGF-β) stimulation for the same hypoxic exposure time or exposed to normoxic oxygenation conditions without or with cytokine stimulation.RESULTS: The tumour cell line analysed showed a strong hypoxic CA9 m RNA expression pattern in response to prolonged severe hypoxia with cell-line specific patterns and a marked induction of CA9 protein in response to severe hypoxia. These results were paralleled by the results for HIF-1α protein under identical oxygenation conditions with a similar expression tendency to that displayed during the CA9 protein expression experimental series. Continuous stimulation with the cytokines, IL-1, IL-6, TNF-α and TGF-β, under normoxic conditions significantly increased the carbonic anhydrase 9 expression level at both the protein and m RNA level, almost doubling the CA9 m RNA and CA9 and HIF-1α protein expression levels found under hypoxia. The findings from these experiments indicated that hypoxia is a positive regulator of CA9 expression in HCC, and the four signal transduction pathways, IL-1, IL-6, TNF-α and TGF-β, positively influence CA9 expression under both normoxic and hypoxic conditions.CONCLUSION: These findings may potentially be considered in the design of anti- cancer therapeutic approaches involving hypoxia-induced or cytokine stimulatory effects on expression. In addition, they provideevidence of the stimulatory role of the examined cytokine families resulting in an increase in CA9 expression under different oxygenation conditions in human cancer, especially HCC, and on the role of the CA9 gene as a positive disease regulator in human cancer.
基金This research was supported by the National Science and Technology Special Foundation for Major Large Oil and Gas Fields and Coal Bed Methane Development(2011ZX05042-003)the Provincial Ministry of State Key Laboratory Breeding Base of Open Projects Henan Gas Geology and Gas Control Laboratory(WS2013B06).
文摘The reaction between carbonic acid and montmorillonite minerals was studied in order to provide a theoretical basis for analyzing changes in the physical properties of coal seams after CO_(2)injection and for optimizing CO_(2) pumping parameters.A single montmorillonite mineral of purity[90%was selected and subjected to reactions at 25,35,and 45℃in carbonic acid solutions of varying acidity.The Si and Al concentrations in the solutions and the structure and elemental compositions of the montmorillonite before and after the reactions were analyzed using a spectrophotometer,an X-ray diffractometer,and an energy-dispersive X-ray spectrometer;kinetic reaction models were established for the dissolution of Si and Al in carbonic acid solutions in order to estimate the apparent activation energy of Si dissolution under different acidity conditions.The results indicate that Al dissolved rapidly and soon reached solubility equilibrium.On the other hand,Si concentration in the solutions increased rapidly and then gradually declined with vibrations,with maximum values at 25,35,and 45℃,which were observed at approximately 96,72,and 48 h,respectively.In addition,Si dissolution fitted the diffusion-controlled reaction model well;as the pH value decreased,the apparent activation energy of Si dissolution decreased,and Si became easier to dissolve.Furthermore,it was concluded that as a weak acid,carbonic acid causes little damage to the mineral structure of montmorillonite.
文摘Carbonic anhydrase VII (CA VII) is a cytosolic enzyme expressed in several organs, including the human brain, but it has not been investigated earlier in any tumors. We designed the present study to evaluate CA VII expression in a cohort of human diffuse astrocytomas, mixed oligoastrocytomas and oligodendrogliomas. CA VII immunostaining was correlated to clinico-pathologic findings, survival data, and expres-sion of other molecular factors, including Ki-67, p53 protein and epidermal growth factor receptor. CA VII-positive staining was observed in 94% of astrocytomas and 85% of oligodendrogliomas. In the tumor specimens, strong positive areas were often located in close proximity to necrosis. The CA VII immunoreactivity showed positive correlation with tumor malignancy grades of astrocytomas (p = 0.02, chi-square test). In all tumor categories, CA VII-positive staining was often seen in the en-dothelial cells of neovessels in addition to the tumor cells. CA VII intensity showed no significant association with p53 nor did it correlate with the amplification of epidermal growth factor receptor (analyzed only in astrocytomas) or cell proliferation. Our present results show that CA VII may act as a useful biomarker in histopathologic diagnostics of gliomas. The high expression of CA VII in the tumor cells and endothelium suggests important roles for the enzyme in tumor metabolism. The results also led us to conclude that CA VII might serve as a marker of poor prognosis in diffuse astrocytomas.
文摘Hepatocellular carcinoma (HCC) is among most common terminal cancer types in the world. Primary etiological factors include cirrhosis, hepatitis, aflatoxin and alcohol. The current study was conducted to determine cytosolic erythrocyte carbonic anhydrase and catalase enzyme activities and levels of some trace elements. For this purpose, 40 patients with primary and metastatic hepatic cancer and 29 healthy volunteers enrolled to the study. Catalase and carbonic anhydrase enzyme activities and serum trace element levels were measured in patient and control groups. In the current study, serum copper, magnesium, manganese and zinc levels were lower in the primary and metastatic hepatic cancer group in comparison with the control group (P < 0.05). In contrast, serum iron, cobalt, cadmium and lead levels were higher in the patient relative to the control group (P < 0.05). In comparison with the control group, the catalase level was lower in primary and metastatic cancer group, while the carbonic anhydrase level was higher in the cancer group (P < 0.05). Changes in levels of trace elements and anti-oxidant enzymes may be the factors which influence the development and progression of liver cancer. The carbonic anhydrase enzyme can be a useful indicator in the diagnosis of cancer. However, this issue warrants further investigation.
基金Supported by National High-Tech Research and Development Pro-gram of China (863 Program, No. 2002AA628050) and National Natural Science Foundation of China (No. 30270031).
文摘Dunaliella salina, a halotolerant unicellular green alga without a rigid cell wall, can live in salinities ranging from 0.05 to 5 mol/L NaC1. These features of D. salina make it an ideal host for the production of antibodies, oral vaccine, and commercially valuable polypeptides. To produce high level of heterologous proteins from D. salina, highly efficient promoters are required to drive expression of target genes under controlled condition. In the present study, we cloned a 5＇ franking region of 1.4 kb from the carbonic anhydrase （CAH） gene ofD. salina by genomic walking and PCR. The fragment was ligated to the pMD18-T vector and characterized. Sequence analysis indicated that this region contained conserved motifs, including a TATA- like box and CAAT-box. Tandem （GT）n repeats that had a potential role of transcriptional control, were also found in this region. The transcription start site （TSS） of the CAH gene was determined by 5＇ RACE and nested PCR method. Transformation assays showed that the 1.4 kb fragment was able to drive expression of the selectable bar （bialaphos resistance） gene when the fusion was transformed into D. salina by biolistics. Northern blotting hybridizations showed that the bar transcript was most abundant in cells grown in 2 mol/L NaCl, and less abundant in 0.5 mol/L NaCl, indicating that expression of the bar gene was induced at high salinity. These results suggest the potential use of the CAH gene promoter to induce the expression of heterologous genes in D. salina under varied salt condition.
基金Supported by The 7th Framework Programme Grant of the European Union Metoxia
文摘Carbonic anhydrases(CA, EC 4.2.1.1) catalyze the interconversion bewteen carbon dioxide and bicarbonate with generation of protons. The carbonic anhydrase isozyme Ⅸ(CA Ⅸ) is highly overexpresed in hypoxic tumors and shows very restricted expression in normal tissues. CA Ⅸ is a dimeric protein possessing very high catalytic activity for the hydration of carbon dioxide to protons and bicarbonate. Its quaternary structure is unique among members of this family of enzymes, allowing for structure-based drug design campaigns of selective inhibitors. Inhibition of CA Ⅸ with sulfonamide and/or coumarin inhibitors was recently shown to lead to a potent retardation for the growth of both primary tumors and metastases. Some fluorescent sulfonamides were shown to accumulate only in hypoxic tumor cells overexpressing CA Ⅸ, and might be used as diagnostic tools for imaging of hypoxic cancers. Sulfonamide inhibitors were also more effective in inhibiting the growth of the primary tumors when associated with irrdiation. CA Ⅸ is thus both a diagnostic and therapeutic validated target for the management of hypoxic tumors normally non-responsive to classical chemio- and radiotherapy.
基金Supported by Project of National Natural Science Foundation(31360300&31560362)Key Project of the Tibet Autonomous Region(XZXTCX-2016)
文摘A carbonic anhydrase( CA) transcript was obtained from the Contig library according to the published sequencing information of the buckwheat transcripts. The full length of the CA gene was amplified by reverse transcription PCR( RT-PCR). The bioinformatics analysis showed that the full length of Fs CA1 gene was 1233 bp and open reading frame was 978 bp,and encoding 325 amino acids. The molecular weight was 35. 11 ku and the isoelectric point was 7. 59; there were 9 α helices,6 β folds,many randon coil and extension chain,containing one signal peptide and one transmembrane region,having a 2 amino acid conserved domains with typical beta-type carbonic anhydrase. Subcellular localization showed that the protein is most likely to appear in the chloroplast. The three-dimensional structure model of Fs CA1 was built by homologous modeling method,indicating that the homo-octamer of buckwheat CA and pea CA could match well,so it can be inferred that buckwheat CA is also homo-octamer. Real-time quantitative PCR was used to detect the expression of Fs CA1 in different organs of buckwheat.The results showed that Fs CA1 had the highest expression level in leaves,then in the stems,and the lowest in roots.
文摘Many cancer cells in solid tumors are hypoxic or pseudohypoxic and create acidic environment for malignancy progression. Under low oxygen conditions (hypoxia), hypoxia-inducible factors (HIFs) play pathological roles in cancer cell survival and spreading. HIF regulates several genes such as genes of glucose transporters that enhance anaerobic glycolysis, angiogenesis, erythropoiesis and carbonic anhydrase IX (CA-IX). CA-IX is a cell-surface glycoprotein that catalyzes the hydration of CO2 to protons and bicarbonate ions (respiratory acidification). This process is involved in adaptation to acidosis and implicated in cancer progression. Therefore, CA-IX inhibitors (such as sulfonamide-based compounds) showed hoping results in reduction malignancy progression. The article aims to reversal the malignant hypoxic environment in solid tumors to create a condition of weakness within the cancer for further focused cisplatin potency. This article suggests the use of modified synthesized HIF as a drug delivery molecule for both carbonic anhydrase IX inhibitor and glycosylated cisplatin that damages the DNA of malignant cell. HIF molecule has high affinity to bind with CA IX-expressing malignant cells, which is followed by cell entrance via endocytosis. Once the HIF-Cisplatin-CA-inhibitor complex enters the cell, the carbonic anhydrase inhibitor will improve the cellular pH that makes the environment unsuitable for HIF 1α function and it may be ubiquitinated. So, the raise in target genes transcription will be arrested. On the other hand, once the synthetized HIF is degraded, the cisplatin molecules will be released inside the malignant cell and start to damage its DNA. This approach may be a good solution for many solid tumors.
文摘This paper deals the randomness effect of the pressure of carbonic gas on the carbonation phenomenon of the reinforced concrete. This analysis concentrates on the evaluation of carbonation depth (Xc) and the carbonation time (T1) which is the time necessary so that the face of carbonation arrives until the reinforcement from a probabilistic analysis. Monte Carlo simulations are realized under the assumption that the carbonic gas on the surface of the concrete is random variable with a log-normal probability distribution.
文摘Carbonic anhydrase isozyme CA3 protects cells against oxidative stress. Ectopic expression of murine Ca3, but not Ca2, protects proto-oncogene Evi1 expressing Rat1 fibroblast cells (ca3low) against hydrogen peroxide (H2O2) induced stress. Ca3 is S-glutathionylated via glutathione adducts with cysteines 181 and 186. Substitution of both Ca3 cysteines with serine fails to protect cells from oxidative stress. Insertion of cysteine at 181 and 186 in Ca2 is insufficient for conferring efficient anti-oxidant activity. This shows for the first time that S-glutathionylation of cys181 and cys186 residues is required for Ca3 anti-oxidant activity but that additional factors are also required.
