The multidrug resistance P-glycoprotein (P-gp) expression and func-tion in hematopoietic stem/progenitor cells were studied to investigate whether the inhibition of hematopoietic cell P-gp function by multidrug resist...The multidrug resistance P-glycoprotein (P-gp) expression and func-tion in hematopoietic stem/progenitor cells were studied to investigate whether the inhibition of hematopoietic cell P-gp function by multidrug resistance reversal agent increases the cytotoxicity of chemotherapy drugs on the hematopoietic cells.The expression of P-gp on the surface of CD cells from healthy human marrow was examined by flow cytometry. The multidrug resistance reversal agent MS-209 was used to measure the effects of MS-209 on the Rhodamin-123 uptaking o fCD hematopoietic cells. By using methylcellulose semi-solid culture, normal human granulocyte-macrophage clonal formation unit (CFU-GM) was cultured. The changes in CFU-GM inhibitory rate caused by daunorubicin were determined in the presence or absence of MS-2O9. The results showed that the P-gp expression rate of bone marrow CDL cells was 13. 3 %. MS-209 obviously increased the Rhodamin-123 uptake of CD positive cells. The mean inhibitory rate of daunorubicin for CFU-GM was 29. 6 %, but it was increased to 43. 3 % in the presence of MS-209 with the difference being significant (P< 0. 05). It was concluded that hematopoietic cells expressed P-gp protein and possessed active function- MS-209could inhibit the membrane efflux pump and increase the cytotoxicity of chemotherapy drugs to the clonal growth of hematopoeitic stem cells, suggesting the side effects of these drugs on the hematopoietic system should be taken into consideration in the clinical use.展开更多
Aim: The rationale and technique underlying a novel concept of non-invasive removal of an intravasal vas deferens poly-meric contraceptive drug to reverse drag injection-induced azoospermia are explained. Thus the con...Aim: The rationale and technique underlying a novel concept of non-invasive removal of an intravasal vas deferens poly-meric contraceptive drug to reverse drag injection-induced azoospermia are explained. Thus the conventional methods ofsurgical exploration to remove vas deferens plugs and intravasal injection of solvents to flush out contraceptive drugs are tobe replaced by steps which will be readily accepted by subjects. Methods: The approach is based upon the non-invasiveapplication of specific forces to various segments of the vas deferens so that non-sclerosing and non-tissue-adherent com-pounds, in particular styrene maleic anhydride (SMA) can be expelled. Forces are generated by palpation; percuta-neous electrical stimulation; vibration application; and percussion. The forces help to propel the intravasal polymer to-wards the ejaculatory duct for expulsion during ejaculation. All aspects of the total technique are clinically acceptable,simple, atraumatic, unlikely to cause pain and discomfort even without tranquilizers, local or general anaesthetics. Theprocedure may be repeated several times in different sittings spaced apart by about one week to achieve adequate plug ex-pulsion. Results: Model experiments demonstrated the feasibility of the concept. The polymer was nonadherent andcould be moved within the vas deferens by the application of specific forces. Sufficient removal was possible to enablespermatic fluid to be transported along a region previously occupied by the polymer. A corroborating subhuman primatestudy by an independent investigator has shown that the semen profile becomes normal following the reversal. Conclu-sion: Adoption of the new technique may provide a means of non surgical restoration of normal semen profile after a pe-riod of fertility control obtained by intravasal drag injection. (Asian J Androl 1999 Sep ; 1: 131 - 134)展开更多
Neuromuscular blocking agents(NMBAs)were introduced into clinical anesthesia in the 1940s^([1]),and have enabled anesthesiologists to safely anesthetize patients with significant cardiopulmonary diseases.By employing ...Neuromuscular blocking agents(NMBAs)were introduced into clinical anesthesia in the 1940s^([1]),and have enabled anesthesiologists to safely anesthetize patients with significant cardiopulmonary diseases.By employing neuromuscular blockade patient movement could be abolished, without producing excessive cardiovascular depression.展开更多
Through embedding modified nano-silica particles on the surface of polystyrene using the method of Pickering emulsion polymerization,a kind of nano/micro oleophobic agent named OL-1 was developed.The effects of OL-1 o...Through embedding modified nano-silica particles on the surface of polystyrene using the method of Pickering emulsion polymerization,a kind of nano/micro oleophobic agent named OL-1 was developed.The effects of OL-1 on the rock surface properties and its performance in inhibiting the oil phase imbibition into the rock were explored.The performance and mechanisms of OL-1 in improving the wellbore stability of shale gas wells were evaluated and analyzed.OL-1 could absorb on the surface of the shale core to form a membrane with a micro-nano two-stage roughness,making the surface energy of the core decrease to 0.13 mN/m and the contact angle of the white oil on the core surface increase from 16.39°to 153.03°.Compared with the untreated capillary tube,when immersed into 3#white oil,the capillary tube treated by OL-1 had a reversal of capillary pressure from 273.76 Pa to-297.71 Pa,and the oil imbibition height inside the capillary tube decreased from 31 mm above the external liquid level to 33 mm below the external liquid level.The amount of oil invading into the rock core modified by OL-1 decreased by 64.29%compared with the untreated one.The shale core immersed into the oil-based drilling fluids with 1%OL-1 had a porosity reduction rate of only 4.5%.Compared with the core immersed in the drilling fluids without OL-1,the inherent force of the core treated by 1%OL-1 increased by 24.9%,demonstrating that OL-1 could effectively improve the rock mechanical stability by inhibiting oil phase imbibition.展开更多
Our recent studies demonstrated that the natural product nobiletin(NOB)served as a promising multidrug resistance(MDR)reversal agent and improved the effectiveness of cancer chemotherapy in vitro.However,low aqueous s...Our recent studies demonstrated that the natural product nobiletin(NOB)served as a promising multidrug resistance(MDR)reversal agent and improved the effectiveness of cancer chemotherapy in vitro.However,low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent.To tackle these challenges,NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy.All the compounds showed improved sensitivity to paclitaxel(PTX)in P-glycoprotein(P-gp)overexpressing MDR cancer cells.Among them,compound 29 d exhibited water solubility 280-fold higher than NOB.A drug-resistance A549/T xenograft model showed that 29 d,at a dose of 50 mg/kg co-administered with PTX(15 mg/kg),inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition.Moreover,Western blot experiments revealed that 29 d inhibited expression of NRF2,phosphorylated ERK and AKT in MDR cancer cells,thus implying 29 d of multiple mechanisms to reverse MDR in lung cancer.展开更多
文摘The multidrug resistance P-glycoprotein (P-gp) expression and func-tion in hematopoietic stem/progenitor cells were studied to investigate whether the inhibition of hematopoietic cell P-gp function by multidrug resistance reversal agent increases the cytotoxicity of chemotherapy drugs on the hematopoietic cells.The expression of P-gp on the surface of CD cells from healthy human marrow was examined by flow cytometry. The multidrug resistance reversal agent MS-209 was used to measure the effects of MS-209 on the Rhodamin-123 uptaking o fCD hematopoietic cells. By using methylcellulose semi-solid culture, normal human granulocyte-macrophage clonal formation unit (CFU-GM) was cultured. The changes in CFU-GM inhibitory rate caused by daunorubicin were determined in the presence or absence of MS-2O9. The results showed that the P-gp expression rate of bone marrow CDL cells was 13. 3 %. MS-209 obviously increased the Rhodamin-123 uptake of CD positive cells. The mean inhibitory rate of daunorubicin for CFU-GM was 29. 6 %, but it was increased to 43. 3 % in the presence of MS-209 with the difference being significant (P< 0. 05). It was concluded that hematopoietic cells expressed P-gp protein and possessed active function- MS-209could inhibit the membrane efflux pump and increase the cytotoxicity of chemotherapy drugs to the clonal growth of hematopoeitic stem cells, suggesting the side effects of these drugs on the hematopoietic system should be taken into consideration in the clinical use.
文摘Aim: The rationale and technique underlying a novel concept of non-invasive removal of an intravasal vas deferens poly-meric contraceptive drug to reverse drag injection-induced azoospermia are explained. Thus the conventional methods ofsurgical exploration to remove vas deferens plugs and intravasal injection of solvents to flush out contraceptive drugs are tobe replaced by steps which will be readily accepted by subjects. Methods: The approach is based upon the non-invasiveapplication of specific forces to various segments of the vas deferens so that non-sclerosing and non-tissue-adherent com-pounds, in particular styrene maleic anhydride (SMA) can be expelled. Forces are generated by palpation; percuta-neous electrical stimulation; vibration application; and percussion. The forces help to propel the intravasal polymer to-wards the ejaculatory duct for expulsion during ejaculation. All aspects of the total technique are clinically acceptable,simple, atraumatic, unlikely to cause pain and discomfort even without tranquilizers, local or general anaesthetics. Theprocedure may be repeated several times in different sittings spaced apart by about one week to achieve adequate plug ex-pulsion. Results: Model experiments demonstrated the feasibility of the concept. The polymer was nonadherent andcould be moved within the vas deferens by the application of specific forces. Sufficient removal was possible to enablespermatic fluid to be transported along a region previously occupied by the polymer. A corroborating subhuman primatestudy by an independent investigator has shown that the semen profile becomes normal following the reversal. Conclu-sion: Adoption of the new technique may provide a means of non surgical restoration of normal semen profile after a pe-riod of fertility control obtained by intravasal drag injection. (Asian J Androl 1999 Sep ; 1: 131 - 134)
基金supported by University of California Davis HealthNIH grant UL1 TR001860 of the University of Califomia Davis Health
文摘Neuromuscular blocking agents(NMBAs)were introduced into clinical anesthesia in the 1940s^([1]),and have enabled anesthesiologists to safely anesthetize patients with significant cardiopulmonary diseases.By employing neuromuscular blockade patient movement could be abolished, without producing excessive cardiovascular depression.
基金Supported by the CNPC Scientific Research and Technological Development Project(2021DJ3804)Scientific Research and Technological Development Project of PetroChina Company Limited(2020E-2803(JT))China CNPC Low Carbon Strategic Forward-Looking Major Science and Technology Project(2021DJ6601).
文摘Through embedding modified nano-silica particles on the surface of polystyrene using the method of Pickering emulsion polymerization,a kind of nano/micro oleophobic agent named OL-1 was developed.The effects of OL-1 on the rock surface properties and its performance in inhibiting the oil phase imbibition into the rock were explored.The performance and mechanisms of OL-1 in improving the wellbore stability of shale gas wells were evaluated and analyzed.OL-1 could absorb on the surface of the shale core to form a membrane with a micro-nano two-stage roughness,making the surface energy of the core decrease to 0.13 mN/m and the contact angle of the white oil on the core surface increase from 16.39°to 153.03°.Compared with the untreated capillary tube,when immersed into 3#white oil,the capillary tube treated by OL-1 had a reversal of capillary pressure from 273.76 Pa to-297.71 Pa,and the oil imbibition height inside the capillary tube decreased from 31 mm above the external liquid level to 33 mm below the external liquid level.The amount of oil invading into the rock core modified by OL-1 decreased by 64.29%compared with the untreated one.The shale core immersed into the oil-based drilling fluids with 1%OL-1 had a porosity reduction rate of only 4.5%.Compared with the core immersed in the drilling fluids without OL-1,the inherent force of the core treated by 1%OL-1 increased by 24.9%,demonstrating that OL-1 could effectively improve the rock mechanical stability by inhibiting oil phase imbibition.
基金supported by National Key R&D Program of China(2017YFB0202600)Macao Science and Technology Development Fund,Macao Special Administrative Region(003/2017/A1to Ying Xie,China)+1 种基金National Natural Science Foundation of China(21572279,21877134,81602955 and 81703341)Guangdong Province Higher Vocational Colleges&Schools Pearl River Scholar Funded Scheme(2016,China).
文摘Our recent studies demonstrated that the natural product nobiletin(NOB)served as a promising multidrug resistance(MDR)reversal agent and improved the effectiveness of cancer chemotherapy in vitro.However,low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent.To tackle these challenges,NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy.All the compounds showed improved sensitivity to paclitaxel(PTX)in P-glycoprotein(P-gp)overexpressing MDR cancer cells.Among them,compound 29 d exhibited water solubility 280-fold higher than NOB.A drug-resistance A549/T xenograft model showed that 29 d,at a dose of 50 mg/kg co-administered with PTX(15 mg/kg),inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition.Moreover,Western blot experiments revealed that 29 d inhibited expression of NRF2,phosphorylated ERK and AKT in MDR cancer cells,thus implying 29 d of multiple mechanisms to reverse MDR in lung cancer.
