Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], ...Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], 5-diphenyl tetraxolium bromid (MTT) assay. Apoptosis and the expression of P-glycoprotein (P-gp) were detected by flow cytometry (FCM). The intracellular ADM concentration was measured by HPLC. Results: Nef at 1, 5, 10 mol/L decreased the IC50 of ADM to MCF-7/ADM from 11.63 g/mL to 4.59, 2.44, 0.27 g/mL respectively. MCF-7/ADM could resist the apoptosis induced by ADM while Nef (1-10 mol/L) could augment ADR-mediated apoptosis. Nef (10 mol/L) increased the accumulation of ADM up to 2.88 fold in MCF-7/ADM but not in sensitive cells MCF-7/S and reduced the expression of P-gp in MCF-7/ADM cells. Conclusion: Nef can circumvent multidrug resistance (MDR) of MCF-7/ADM cells and the mechanism was associated with the increase of intracellular accumulation of ADM and the reduced expression of P-gp in MCF-7/ADM cells.展开更多
Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. For...Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.展开更多
AIM: To evaluate the efficacy of adalimumab induction therapy in patients with ulcerative colitis who previously responded to infliximab and then lost response or became intolerant. METHODS: Ten patients with ulcerati...AIM: To evaluate the efficacy of adalimumab induction therapy in patients with ulcerative colitis who previously responded to infliximab and then lost response or became intolerant. METHODS: Ten patients with ulcerative colitis were enrolled in a 4-wk open-label trial. The patients received a loading dose of 160 mg adalimumab at wk 0 followed by 80 mg at wk 2. The primary efficacy measure was clinical improvement at wk 4, as defined by a decrease in clinical activity index (CAI) of more than 4. RESULTS: Four of 10 patients (40%) benefited from subsequent adalimumab therapy; one patient achieved remission (CAI < 4) and 3 had clinical improvement at wk 4. 6 patients had no response (60%); 2 of 6 (33.3%) subsequently underwent colectomy. This was accompanied by a decrease in median CRP concentration from 16.8 mg/mL at baseline to 3.85 mg/mL at wk 4, excluding two patients who underwent colectomy after two infusions of adalimumab. Among the 6 patients with severe colitis (CAI > 12) at baseline, none achieved remission and only one patient had clinical improvement at wk 4. CONCLUSION: The small advantage of adalimumab in patients with mild to moderate ulcerative colitis and lost response or intolerance to infliximab needs to be confirmed in randomised, double-blind, placebo- controlled trials.展开更多
P-glycoprotein plays an important role in highly drug resistant cells. But its high expression cannot be acheived by chemotherapy. In order to study the effect of P-glycoprotein on clinical tumors, we established a lo...P-glycoprotein plays an important role in highly drug resistant cells. But its high expression cannot be acheived by chemotherapy. In order to study the effect of P-glycoprotein on clinical tumors, we established a low ADM resistant colon cancer cell line HR/ADM and determined the amplification and expression of mdr-1 gene. The GLC/ADM showed a resistant pattern similar to classical MDR and the transcription of mdr-1 gene determined by RT-PCR increased. The immunocytochemical analysis showed strong positive staining with monoclonal antibody. The gene amplification of mdr-1 was clearly demonstrated by southernblot. Our results suggested that moderate expression of P-glycoprotein might be enough for a high resistantpattern.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
A halotolerant, gram positive, motile and rod, was isolated from the E1 Gol6a lake of Ghardaia, Alegria and screened for its antimicrobial potential. The strain showed an inhibitory effect to gram positive and gram ne...A halotolerant, gram positive, motile and rod, was isolated from the E1 Gol6a lake of Ghardaia, Alegria and screened for its antimicrobial potential. The strain showed an inhibitory effect to gram positive and gram negative bacteria against Cladosporium spp. and a slight inhibitory effect against C. albicans using chloroform as the extraction solvent and the nutrient broth as production medium. 16S rRNA sequencing showed that the isolate named LMB3981 is a new taxon in the family of Bacillaceae （with 96% similarity）. The strain is close to Filobacillus milosensis and Bacillus haloalkaliphilum with 95% similarity. The phenotypic study showed differences between LMB3981 and two strains that are near and have confirmed the results of 16S rRNA sequencing by specific metabolic properties of the strain.展开更多
Soil, water, sediments and air are frequently contaminated with heavy metals. In Saudi Arabia, heavy metals contamination may result from petroleum and mining operations, refining ores, sludge, waste treatment, electr...Soil, water, sediments and air are frequently contaminated with heavy metals. In Saudi Arabia, heavy metals contamination may result from petroleum and mining operations, refining ores, sludge, waste treatment, electrical equipment, paints, alloys, pesticides, batteries and fuel transportation. Microbial processes lead to appreciable and even complete remediation of heavy metals contaminated environments. The chief ways, by which such remediation may be accomplished, include biosorption, bioaugmentation, bioventing, biostimulation, bioaccumulation, biosolubilization, bioreduction, bioprecipitation, mineralization and methylation. Other technologies and methods are fully developed and now are being used in practice, such as heavy metals nanotechnology bioremediation. An area of fungal biotechnology currently in vogue is the use of fungal biornass to absorb metal ions from contaminated solutions. Such biological approaches of metal ions recovery can be used to clean up polluted effluents or to recover precious metal ions from solutions. The present review provides information on fungal bioremediation of heavy metal contamination for use in future studies in Saudi Arabia as well as in the Arabian Gulf Region.展开更多
Silver nitrate could inhibit the clinical multidrug resistant isolates at high concentrations（with minimal inhibitory concentrations（MICs） from 32 μM to 64 μM）. The activities of amikacin in the presence of sub-...Silver nitrate could inhibit the clinical multidrug resistant isolates at high concentrations（with minimal inhibitory concentrations（MICs） from 32 μM to 64 μM）. The activities of amikacin in the presence of sub-lethal silver nitrate（15 μM） were tested for the combinational effects against multidrug resistant clinical isolates in vitro. Silver nitrate restored the susceptibility of drug-resistant Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus to amikacin. It lowered the MICs of amikacin from 〉128 μg/mL to（2–16） μg/mL and 32 μg/mL, respectively, and lowered the MICs of amikacin on extended spectrum β-lactamase-producing Pseudomonas aeruginosa and Escherichia coli from（16–32） μg/mL and 16 μg/mL to（〈1–4） μg/mL and 〈1 μg/mL, respectively.展开更多
文摘Objective: To study the reversal effect of neferine on adriamycin (ADM) resistant human breast cancer cell line MCF-7/ADM. Methods: The cytotoxic effect of Nef or ADM was determined by 3-[4, 5-dimethylthiazol-2.-yl], 5-diphenyl tetraxolium bromid (MTT) assay. Apoptosis and the expression of P-glycoprotein (P-gp) were detected by flow cytometry (FCM). The intracellular ADM concentration was measured by HPLC. Results: Nef at 1, 5, 10 mol/L decreased the IC50 of ADM to MCF-7/ADM from 11.63 g/mL to 4.59, 2.44, 0.27 g/mL respectively. MCF-7/ADM could resist the apoptosis induced by ADM while Nef (1-10 mol/L) could augment ADR-mediated apoptosis. Nef (10 mol/L) increased the accumulation of ADM up to 2.88 fold in MCF-7/ADM but not in sensitive cells MCF-7/S and reduced the expression of P-gp in MCF-7/ADM cells. Conclusion: Nef can circumvent multidrug resistance (MDR) of MCF-7/ADM cells and the mechanism was associated with the increase of intracellular accumulation of ADM and the reduced expression of P-gp in MCF-7/ADM cells.
文摘Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.
文摘AIM: To evaluate the efficacy of adalimumab induction therapy in patients with ulcerative colitis who previously responded to infliximab and then lost response or became intolerant. METHODS: Ten patients with ulcerative colitis were enrolled in a 4-wk open-label trial. The patients received a loading dose of 160 mg adalimumab at wk 0 followed by 80 mg at wk 2. The primary efficacy measure was clinical improvement at wk 4, as defined by a decrease in clinical activity index (CAI) of more than 4. RESULTS: Four of 10 patients (40%) benefited from subsequent adalimumab therapy; one patient achieved remission (CAI < 4) and 3 had clinical improvement at wk 4. 6 patients had no response (60%); 2 of 6 (33.3%) subsequently underwent colectomy. This was accompanied by a decrease in median CRP concentration from 16.8 mg/mL at baseline to 3.85 mg/mL at wk 4, excluding two patients who underwent colectomy after two infusions of adalimumab. Among the 6 patients with severe colitis (CAI > 12) at baseline, none achieved remission and only one patient had clinical improvement at wk 4. CONCLUSION: The small advantage of adalimumab in patients with mild to moderate ulcerative colitis and lost response or intolerance to infliximab needs to be confirmed in randomised, double-blind, placebo- controlled trials.
文摘P-glycoprotein plays an important role in highly drug resistant cells. But its high expression cannot be acheived by chemotherapy. In order to study the effect of P-glycoprotein on clinical tumors, we established a low ADM resistant colon cancer cell line HR/ADM and determined the amplification and expression of mdr-1 gene. The GLC/ADM showed a resistant pattern similar to classical MDR and the transcription of mdr-1 gene determined by RT-PCR increased. The immunocytochemical analysis showed strong positive staining with monoclonal antibody. The gene amplification of mdr-1 was clearly demonstrated by southernblot. Our results suggested that moderate expression of P-glycoprotein might be enough for a high resistantpattern.
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A halotolerant, gram positive, motile and rod, was isolated from the E1 Gol6a lake of Ghardaia, Alegria and screened for its antimicrobial potential. The strain showed an inhibitory effect to gram positive and gram negative bacteria against Cladosporium spp. and a slight inhibitory effect against C. albicans using chloroform as the extraction solvent and the nutrient broth as production medium. 16S rRNA sequencing showed that the isolate named LMB3981 is a new taxon in the family of Bacillaceae （with 96% similarity）. The strain is close to Filobacillus milosensis and Bacillus haloalkaliphilum with 95% similarity. The phenotypic study showed differences between LMB3981 and two strains that are near and have confirmed the results of 16S rRNA sequencing by specific metabolic properties of the strain.
文摘Soil, water, sediments and air are frequently contaminated with heavy metals. In Saudi Arabia, heavy metals contamination may result from petroleum and mining operations, refining ores, sludge, waste treatment, electrical equipment, paints, alloys, pesticides, batteries and fuel transportation. Microbial processes lead to appreciable and even complete remediation of heavy metals contaminated environments. The chief ways, by which such remediation may be accomplished, include biosorption, bioaugmentation, bioventing, biostimulation, bioaccumulation, biosolubilization, bioreduction, bioprecipitation, mineralization and methylation. Other technologies and methods are fully developed and now are being used in practice, such as heavy metals nanotechnology bioremediation. An area of fungal biotechnology currently in vogue is the use of fungal biornass to absorb metal ions from contaminated solutions. Such biological approaches of metal ions recovery can be used to clean up polluted effluents or to recover precious metal ions from solutions. The present review provides information on fungal bioremediation of heavy metal contamination for use in future studies in Saudi Arabia as well as in the Arabian Gulf Region.
基金Peking Union Medical College(PUMC)Youth Fund and the Fundamental Research Funds for the Central Universities,China(Grant No.333203084)
文摘Silver nitrate could inhibit the clinical multidrug resistant isolates at high concentrations（with minimal inhibitory concentrations（MICs） from 32 μM to 64 μM）. The activities of amikacin in the presence of sub-lethal silver nitrate（15 μM） were tested for the combinational effects against multidrug resistant clinical isolates in vitro. Silver nitrate restored the susceptibility of drug-resistant Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus to amikacin. It lowered the MICs of amikacin from 〉128 μg/mL to（2–16） μg/mL and 32 μg/mL, respectively, and lowered the MICs of amikacin on extended spectrum β-lactamase-producing Pseudomonas aeruginosa and Escherichia coli from（16–32） μg/mL and 16 μg/mL to（〈1–4） μg/mL and 〈1 μg/mL, respectively.
