Large quantities of mussel shells （66000-94000 t year^-1）, an alkaline material that can be used as a soil amendment, are generated as waste in Galicia, NW Spain. A field trial was carried out by planting different ...Large quantities of mussel shells （66000-94000 t year^-1）, an alkaline material that can be used as a soil amendment, are generated as waste in Galicia, NW Spain. A field trial was carried out by planting different pasture species in a Haplic Umbrisol using a randomized block design with four blocks and six treatments （not amended control or soil amended with lime, finely ground shell, coarsely ground shell, finely ground calcined shell or coarsely ground calcined shell） to compare the effects of lime and mussel shells additions on a soil with a low cation exchange capacity and high AI saturation. The trial was established in March 2007, and samples of plants and soil were collected when plots were harvested in summer 2008 （separating the bulk and rhizosphere soil）. The soils were analyzed for pH, total C, total N, available P, exchangeable cations, effective cation exchange capacity and available micronutrients. Dry matter yield was measured in all plots and plants were analyzed for nutrients. Application of mussel shells and the commercial lime resulted in an increase in pH and exchangeable Ca and a decrease in exchangeable Al and Al were most noticeable in the rhizosphere. The amendment of Ca in the plant. saturation. The stability of pH over time was high. These effects also had a positive effect on dry matter yield and concentration展开更多
Excessive activation of G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK) pathways has been linked to prostate cancer metastasis. Rac activation
BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1(PREX1)was reported to be overexpressed in some cancers and involved in cancer development,but its expression and significance in gast...BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1(PREX1)was reported to be overexpressed in some cancers and involved in cancer development,but its expression and significance in gastric cancer remain unclear.AIM To evaluate the expression of PREX1 in gastric cancer and its significance in the development of gastric cancer,especially to evaluate the potential mechanism of PREX1 in gastric cancer.METHODS Bioinformatic analysis was performed in order to examine the expression of PREX1 in gastric cancer.The relationship between the survival rate of gastric cancer patients and PREX1 expression was assessed by Kaplan Meier portal.The Gene Set Enrichment Analysis and the correlation between PREX1 and transforming growth factor(TGF)β1 pathway-related mediators were evaluated by cBioPortal for Cancer Genomics.Western blotting and reverse transcriptase polymerase chain reaction assay were used to test the role of TGFβ1 on the expression of PREX1.Western blotting and dual-luciferase reporter system was used to evaluate the effect of PREX1 on the activation of TGFβ1 pathway.Wound healing and Transwell assay were used to assess the effect of PREX1 on the metastasis activity of gastric cancer cells.RESULTS PREX1 was overexpressed in the gastric tumors,and the expression levels were positively associated with the development of gastric cancer.Also,the high expression of PREX1 revealed poor prognosis,especially for those advanced and specific intestinal gastric cancer patients.PREX1 was closely involved in the positive regulation of cell adhesion and positively correlated with TGFβ1-related mediators.Furthermore,TGFβ1 could induce the expression of PREX1 at both the protein and mRNA level.Also,PREX1 could activate the TGFβ1 pathway.The induced PREX1 could increase the migration and invasion activity of gastric cancer cells.CONCLUSION PREX1 is overexpressed in gastric cancer,and the high level of PREX1 predicts poor prognosis.PREX1 is closely associated with TGFβsignaling and promotes the metastasis of gastric cancer cells.展开更多
Objective： Chronic lymphocytic leukemia （CLL） and mantle cell lymphoma （MCL） cells over-express a guanine exchange factor （GEF）, Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from R...Objective： Chronic lymphocytic leukemia （CLL） and mantle cell lymphoma （MCL） cells over-express a guanine exchange factor （GEF）, Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods： N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor （BCR） and chemokine signaling pathways were compared in the Rasgrf-I over-expressing and a control transfected cell line. Results： Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions： This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells.展开更多
Objective: To explore the roles of intracellular pH value (pHi) and sodium-hydrogen exchanger isoform-1 (NHE-1) in the mechanism of multidrug resistance of leukemia cells. Methods: Multidrug resistant cell line HL-60 ...Objective: To explore the roles of intracellular pH value (pHi) and sodium-hydrogen exchanger isoform-1 (NHE-1) in the mechanism of multidrug resistance of leukemia cells. Methods: Multidrug resistant cell line HL-60 induced by doxorubicin(DOX) (called as HL-60/DOX cells) and their parent cell line HL-60 were employed as experiment group and control group. The proliferation and chemosensitivity of the cells were studied by MTT assay, and the expression of multidrug resistance protein (MRP) was detected by immol/Lunocytochemistry. Meanwhile, pHi was measured by spectrofluorometery with a fluorescence dye BCECF-AM. Based on the pHi recovery curve after intracellular acid loading, the activity of NHE-1 was analyzed. The expression of NHE-1 mRNA and MRP mRNA were determined by semi-quantitative RT-PCR. Cell apoptosis was observed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and apoptotic DNA was extracted and electrophoresed. Results: ① The IC 50 values for DOX, MTZ, VCR and homoharringtonine(HT), in HL-60/DOX cells were significantly higher than those in HL-60 cells (P<0.01). HL-60/DOX cells expressed abundant MRP, but HL-60 cells did not. ② pHi of HL-60/DOX cells were significantly higher than that of HL-60 cells(P<0.001). The expression and activity of NHE-1 in HL-60/DOX cells were significantly stronger than those of HL-60 cells. ③After administration of the specific NHE-1 inhibitor dimethyl amiloride (DMA) at a certain range of concentrations, compared with HL-60 cells, the rate of growth inhibition of HL-60/DOX cells increased significantly (P<0.05), the drug-sensitivity of HL-60/DOX cells was significantly sensitive (P<0.01), the expression of MRP and MRP mRNA decreased significantly (P<0.01), the apoptosis rate increased significantly (P<0.01). Conclusion: NHE-1 is involved in the drug-resistant mechanisms of multidrug-resistant HL-60 cells induced by DOX. The specific NHE-1 inhibitor DMA can partly reverse the multidrug resistance of HL-60 cells induced by DOX.展开更多
BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1(PRex1)was reported to be a risk factor in several cancers,including breast cancer,lung cancer,and melanoma,but its expression and rol...BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1(PRex1)was reported to be a risk factor in several cancers,including breast cancer,lung cancer,and melanoma,but its expression and role in hepatocellular carcinoma(HCC)have not yet been fully studied.AIM To explore the expression of P-Rex1 in HCC,and further evaluate its potential application in the diagnosis and prognosis of HCC,especially in hepatitis B virus(HBV)-related patients.METHODS P-Rex1 expression in HCC was evaluated by real-time-quantitative polymerase chain reaction.The expression of P-Rex1 was subjected to correlation analysis with clinical features,such as lymph node invasion,distant metastasis,HBV infection,patient’s age and gender.Receiver operating characteristic analysis was used to examine the potential role of P-Rex1 as a diagnostic biomarker in HCC.Kaplan-Meier analysis was used to determine the association between P-Rex1 expression and overall survival,progression-free survival and relapse-free survival.Bioinformatic analysis was used to validate the clinical findings.RESULTS P-Rex1 expression was significantly increased in HCC tumors than adjacent tissues.The expression of P-Rex1 was higher in HCC patients with lymph node invasion,distant metastasis,HBV infection and positive alpha-fetoprotein,respectively.The receiver operating characteristic analysis showed that P-Rex1 was a diagnostic biomarker with a higher area under the curve value,especially in patients with HBV infection.Survival analysis showed that patients with higher P-Rex1 expression had a favorable survival rate,even in early-stage patients.CONCLUSION P-Rex1 expression was highly increased in HCC,and the expression level of PRex1 was positively correlated with tumor progression.P-Rex1 has a higher efficiency in the diagnosis of HBV-related HCC,and could also be used as a favorable prognostic factor for HCC patients.展开更多
Strongly acidic cation exchange resin(1x1,H form)has been successfully used as a catalyst in synthesis of diphenyl N-benzyloxycarbonyl-1-aminobenzylphosphonate, N-benzyloxycarbonyl-1-aminobenzylphenylphosphinic acid a...Strongly acidic cation exchange resin(1x1,H form)has been successfully used as a catalyst in synthesis of diphenyl N-benzyloxycarbonyl-1-aminobenzylphosphonate, N-benzyloxycarbonyl-1-aminobenzylphenylphosphinic acid and N-p-tolylsulfonyl-1-aminobenzyl phenylphosphinic acid in high yields.展开更多
1.Introduction The rapid spread of COVID-19 is the challenge for all the countries and their economies.The sugges-t ions presented in media show that the COVID-19 pandemic will result in recession.This seems a fairly ...1.Introduction The rapid spread of COVID-19 is the challenge for all the countries and their economies.The sugges-t ions presented in media show that the COVID-19 pandemic will result in recession.This seems a fairly obvious observation resulting from the growing number of infections in most countries,closing schools and workplaces and promoting social distancing measures,as well as sharp declines on global stock exchanges.展开更多
Sodium-glucose cotransporter 2(SGLT2)inhibitors have been reapproved for heart failure(HF)therapy in patients with and without diabetes.However,the initial glucose-lowering indication of SGLT2i has impeded their uses ...Sodium-glucose cotransporter 2(SGLT2)inhibitors have been reapproved for heart failure(HF)therapy in patients with and without diabetes.However,the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice.A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect.To address this issue,we conducted structural repurposing of EMPA,a representative SGLT2 inhibitor,to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2.Compared to EMPA,the optimal derivative JX01,which was produced by methylation of C2—OH of the glucose ring,exhibited weaker SGLT2-inhibitory activity(IC_(50)>100 nmol/L),and lower glycosuria and glucose-lowering side-effect,better NHE1-inhibitory activity and cardioprotective effect in HF mice.Furthermore,JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity,and good pharmacokinetic properties in both mouse and rat species.Collectively,the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs,and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.展开更多
基金Supported by the Government of Spain(No.CTM2005-05922)
文摘Large quantities of mussel shells （66000-94000 t year^-1）, an alkaline material that can be used as a soil amendment, are generated as waste in Galicia, NW Spain. A field trial was carried out by planting different pasture species in a Haplic Umbrisol using a randomized block design with four blocks and six treatments （not amended control or soil amended with lime, finely ground shell, coarsely ground shell, finely ground calcined shell or coarsely ground calcined shell） to compare the effects of lime and mussel shells additions on a soil with a low cation exchange capacity and high AI saturation. The trial was established in March 2007, and samples of plants and soil were collected when plots were harvested in summer 2008 （separating the bulk and rhizosphere soil）. The soils were analyzed for pH, total C, total N, available P, exchangeable cations, effective cation exchange capacity and available micronutrients. Dry matter yield was measured in all plots and plants were analyzed for nutrients. Application of mussel shells and the commercial lime resulted in an increase in pH and exchangeable Ca and a decrease in exchangeable Al and Al were most noticeable in the rhizosphere. The amendment of Ca in the plant. saturation. The stability of pH over time was high. These effects also had a positive effect on dry matter yield and concentration
文摘Excessive activation of G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK) pathways has been linked to prostate cancer metastasis. Rac activation
文摘BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1(PREX1)was reported to be overexpressed in some cancers and involved in cancer development,but its expression and significance in gastric cancer remain unclear.AIM To evaluate the expression of PREX1 in gastric cancer and its significance in the development of gastric cancer,especially to evaluate the potential mechanism of PREX1 in gastric cancer.METHODS Bioinformatic analysis was performed in order to examine the expression of PREX1 in gastric cancer.The relationship between the survival rate of gastric cancer patients and PREX1 expression was assessed by Kaplan Meier portal.The Gene Set Enrichment Analysis and the correlation between PREX1 and transforming growth factor(TGF)β1 pathway-related mediators were evaluated by cBioPortal for Cancer Genomics.Western blotting and reverse transcriptase polymerase chain reaction assay were used to test the role of TGFβ1 on the expression of PREX1.Western blotting and dual-luciferase reporter system was used to evaluate the effect of PREX1 on the activation of TGFβ1 pathway.Wound healing and Transwell assay were used to assess the effect of PREX1 on the metastasis activity of gastric cancer cells.RESULTS PREX1 was overexpressed in the gastric tumors,and the expression levels were positively associated with the development of gastric cancer.Also,the high expression of PREX1 revealed poor prognosis,especially for those advanced and specific intestinal gastric cancer patients.PREX1 was closely involved in the positive regulation of cell adhesion and positively correlated with TGFβ1-related mediators.Furthermore,TGFβ1 could induce the expression of PREX1 at both the protein and mRNA level.Also,PREX1 could activate the TGFβ1 pathway.The induced PREX1 could increase the migration and invasion activity of gastric cancer cells.CONCLUSION PREX1 is overexpressed in gastric cancer,and the high level of PREX1 predicts poor prognosis.PREX1 is closely associated with TGFβsignaling and promotes the metastasis of gastric cancer cells.
文摘Objective： Chronic lymphocytic leukemia （CLL） and mantle cell lymphoma （MCL） cells over-express a guanine exchange factor （GEF）, Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods： N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor （BCR） and chemokine signaling pathways were compared in the Rasgrf-I over-expressing and a control transfected cell line. Results： Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions： This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells.
文摘Objective: To explore the roles of intracellular pH value (pHi) and sodium-hydrogen exchanger isoform-1 (NHE-1) in the mechanism of multidrug resistance of leukemia cells. Methods: Multidrug resistant cell line HL-60 induced by doxorubicin(DOX) (called as HL-60/DOX cells) and their parent cell line HL-60 were employed as experiment group and control group. The proliferation and chemosensitivity of the cells were studied by MTT assay, and the expression of multidrug resistance protein (MRP) was detected by immol/Lunocytochemistry. Meanwhile, pHi was measured by spectrofluorometery with a fluorescence dye BCECF-AM. Based on the pHi recovery curve after intracellular acid loading, the activity of NHE-1 was analyzed. The expression of NHE-1 mRNA and MRP mRNA were determined by semi-quantitative RT-PCR. Cell apoptosis was observed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and apoptotic DNA was extracted and electrophoresed. Results: ① The IC 50 values for DOX, MTZ, VCR and homoharringtonine(HT), in HL-60/DOX cells were significantly higher than those in HL-60 cells (P<0.01). HL-60/DOX cells expressed abundant MRP, but HL-60 cells did not. ② pHi of HL-60/DOX cells were significantly higher than that of HL-60 cells(P<0.001). The expression and activity of NHE-1 in HL-60/DOX cells were significantly stronger than those of HL-60 cells. ③After administration of the specific NHE-1 inhibitor dimethyl amiloride (DMA) at a certain range of concentrations, compared with HL-60 cells, the rate of growth inhibition of HL-60/DOX cells increased significantly (P<0.05), the drug-sensitivity of HL-60/DOX cells was significantly sensitive (P<0.01), the expression of MRP and MRP mRNA decreased significantly (P<0.01), the apoptosis rate increased significantly (P<0.01). Conclusion: NHE-1 is involved in the drug-resistant mechanisms of multidrug-resistant HL-60 cells induced by DOX. The specific NHE-1 inhibitor DMA can partly reverse the multidrug resistance of HL-60 cells induced by DOX.
文摘BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1(PRex1)was reported to be a risk factor in several cancers,including breast cancer,lung cancer,and melanoma,but its expression and role in hepatocellular carcinoma(HCC)have not yet been fully studied.AIM To explore the expression of P-Rex1 in HCC,and further evaluate its potential application in the diagnosis and prognosis of HCC,especially in hepatitis B virus(HBV)-related patients.METHODS P-Rex1 expression in HCC was evaluated by real-time-quantitative polymerase chain reaction.The expression of P-Rex1 was subjected to correlation analysis with clinical features,such as lymph node invasion,distant metastasis,HBV infection,patient’s age and gender.Receiver operating characteristic analysis was used to examine the potential role of P-Rex1 as a diagnostic biomarker in HCC.Kaplan-Meier analysis was used to determine the association between P-Rex1 expression and overall survival,progression-free survival and relapse-free survival.Bioinformatic analysis was used to validate the clinical findings.RESULTS P-Rex1 expression was significantly increased in HCC tumors than adjacent tissues.The expression of P-Rex1 was higher in HCC patients with lymph node invasion,distant metastasis,HBV infection and positive alpha-fetoprotein,respectively.The receiver operating characteristic analysis showed that P-Rex1 was a diagnostic biomarker with a higher area under the curve value,especially in patients with HBV infection.Survival analysis showed that patients with higher P-Rex1 expression had a favorable survival rate,even in early-stage patients.CONCLUSION P-Rex1 expression was highly increased in HCC,and the expression level of PRex1 was positively correlated with tumor progression.P-Rex1 has a higher efficiency in the diagnosis of HBV-related HCC,and could also be used as a favorable prognostic factor for HCC patients.
文摘Strongly acidic cation exchange resin(1x1,H form)has been successfully used as a catalyst in synthesis of diphenyl N-benzyloxycarbonyl-1-aminobenzylphosphonate, N-benzyloxycarbonyl-1-aminobenzylphenylphosphinic acid and N-p-tolylsulfonyl-1-aminobenzyl phenylphosphinic acid in high yields.
文摘1.Introduction The rapid spread of COVID-19 is the challenge for all the countries and their economies.The sugges-t ions presented in media show that the COVID-19 pandemic will result in recession.This seems a fairly obvious observation resulting from the growing number of infections in most countries,closing schools and workplaces and promoting social distancing measures,as well as sharp declines on global stock exchanges.
基金supported by the National key R&D Program of China(2021YFA0804904)the National Natural Science Foundation of China(22107030)+4 种基金the Chinese Postdoctoral Science Foundation(2020M681211)the Shanghai Morning Light Program(20CG36,China)the Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism(2021 Sci&Tech 03-28,China)the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZDCX20212702,China)the Chinese Special Fund for State Key Laboratory of Bioreactor Engineering(2060204)。
文摘Sodium-glucose cotransporter 2(SGLT2)inhibitors have been reapproved for heart failure(HF)therapy in patients with and without diabetes.However,the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice.A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect.To address this issue,we conducted structural repurposing of EMPA,a representative SGLT2 inhibitor,to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2.Compared to EMPA,the optimal derivative JX01,which was produced by methylation of C2—OH of the glucose ring,exhibited weaker SGLT2-inhibitory activity(IC_(50)>100 nmol/L),and lower glycosuria and glucose-lowering side-effect,better NHE1-inhibitory activity and cardioprotective effect in HF mice.Furthermore,JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity,and good pharmacokinetic properties in both mouse and rat species.Collectively,the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs,and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.
