Objective:To evaluate the antioxidant activity of aqueous extract of Atoringa oleifeta M.oleifera) young leaves by in vivo as well as in vitro assays.Methods:In vitro study included estimation of total phenolic,total ...Objective:To evaluate the antioxidant activity of aqueous extract of Atoringa oleifeta M.oleifera) young leaves by in vivo as well as in vitro assays.Methods:In vitro study included estimation of total phenolic,total ilavonol,total flavonoid and total antioxidant power(FRAP assay).Tn addition, in vivo study was done with the identified most effective dose of 200 nig/kg of its lyophilized powder on normal and diabetic rats.Its effect on different oxidative free radical scavenging enzymes,viz,superoxide dismutase(SOD),catalase(CAT),glutathione-S-transferase(GST),lipid peroxide(LPO) contents were measured.Results:Significant increase in activities of SOD.CAT, GST while,a decrease in LPO content was observed.Whereas,total phenolic,flavonoid and ilavonol contents in the extract were found to be 120 mg/g of CAK,40.5 mg/g of QEK and 12.12 mg/g of QE,respectively.On the other hand.FRAP assay results of M.oleifera leaves was(85.00±5.00)μM of Fe^+/g of extract powder.Conclusions:The significant antioxidant activities of M.oleifera leaves from both in vivo as well as in vitro studies suggests that the regular intake of its leaves through diet can protect normal as well as diabetic patients against oxidative damage.展开更多
This phase I clinical trial （NCT01935843） is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell （CART） immunotherapy tar- geting human epidermal growth factor receptor...This phase I clinical trial （NCT01935843） is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell （CART） immunotherapy tar- geting human epidermal growth factor receptor 2 （HER2） in patients with advanced biliary tract cancers （BTCs） and pancreatic cancers （PCs）. Eligible patients with HER2-positive （〉50%） BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab- paclitaxel （100-200 mg/m2） and cyclophosphamide （15-35 mglkg）. CAR transgene copy number in the peripheral blood was serially measured to monitor the expansion and persistence of CART-HER2 cells in vivo. Eleven enrolled patients received 1 to 2-cycle CART- HER2 cell infusion （median CAR＋ T cell 2.1× 10^6/kg）. The conditioning treatment resulted in mild-to-moderate fatigue, nausea/vomiting, myalgialarthralgia, and lym- phopenia. Except one grade-3 acute febrile syndrome and one abnormal elevation of transaminase （〉9 ULN）, adverse events related to the infusion of CART-HER2 cells were mild-to-moderate. Post-infusion toxicities included one case of reversible severe upper gastroin- testinal hemorrhage which occurred in a patient with gastric antrum invaded by metastasis 11 days after the CART-HER2 cell infusion, and 2 cases of grade 1-2delayed fever, accompanied by the release of C-reactive protein and interleukin-6. All patients were evaluable for assessment of clinical response, among which 1 obtained a 4.5-months partial response and 5 achieved stable disease. The median progression free survival was 4.8 months （range, 1.5-8.3 months）. Finally, data from this study demonstrated the safety and feasibility of CART-HER2 immunotherapy, and showed encourag- ing signals of clinical activity.展开更多
Lymph node (LN) targeti ng through interstitial drain age of nan oparticles (NPs) is an attractive strategy to stimulate a pote nt immune respo nse, as LNs are the primary site for lymphocyte priming by antigen presen...Lymph node (LN) targeti ng through interstitial drain age of nan oparticles (NPs) is an attractive strategy to stimulate a pote nt immune respo nse, as LNs are the primary site for lymphocyte priming by antigen presenting cells (APCs) and triggering of an adaptive immune response. NP size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable NPs are preferred as carrier for vaccine delivery. However, the selective "size gateM for effective LN-drainage, particularly the kinetics of LN trafficking, is less well defined. This is partly due to the challenge in generating size-controlled NPs from biodegradable polymers in the sub-100-nm range. Here, we report the preparation of three sets of poly(lactic-co-glycolic)-b-poly(ethylene-glycol)(PLGA-b-PEG) NPs with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanoprecipitation. Using NPs labeled with a near-infrared dye, we showed that 20-nm NPs drain rapidly across proximal and distal LNs following subcutaneous inoculation in mice and are retai ned in LNs more effectively than NPs with a nu mber average diameter of 40-nm. The drain age of 100-nm NPs was n egligible. Furthermore, the 20-nm NPs showed the highest degree of penetration around the paracortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled PLGA-b-PEG NPs at the lower threshold of about 30-nm are most effective for LN trafficking, retention, and APC uptake after s.c. administration. This report could inform the design of LN-targeted NP carrier for the delivery of therapeutic or prophylactic vaccines.展开更多
基金National Medicinal Plants Board. Govt,of India,New Delhi,India for providing financial assistance in the form of Senior Research Fellowship to cam' out the present study
文摘Objective:To evaluate the antioxidant activity of aqueous extract of Atoringa oleifeta M.oleifera) young leaves by in vivo as well as in vitro assays.Methods:In vitro study included estimation of total phenolic,total ilavonol,total flavonoid and total antioxidant power(FRAP assay).Tn addition, in vivo study was done with the identified most effective dose of 200 nig/kg of its lyophilized powder on normal and diabetic rats.Its effect on different oxidative free radical scavenging enzymes,viz,superoxide dismutase(SOD),catalase(CAT),glutathione-S-transferase(GST),lipid peroxide(LPO) contents were measured.Results:Significant increase in activities of SOD.CAT, GST while,a decrease in LPO content was observed.Whereas,total phenolic,flavonoid and ilavonol contents in the extract were found to be 120 mg/g of CAK,40.5 mg/g of QEK and 12.12 mg/g of QE,respectively.On the other hand.FRAP assay results of M.oleifera leaves was(85.00±5.00)μM of Fe^+/g of extract powder.Conclusions:The significant antioxidant activities of M.oleifera leaves from both in vivo as well as in vitro studies suggests that the regular intake of its leaves through diet can protect normal as well as diabetic patients against oxidative damage.
基金We would like to thank all patients who participated in this trial. This study was supported by the grants from the National Natural Science Foundation of China （Grant No. 81230061 to WDH）, the Science and Technology Planning Project of Beijing City （No. Z151100003915076 to WDH）, the National Key Research and Development Program of China （Nos. 2016YFC1303501 and 2016YFC1303504 to WDH）.
文摘This phase I clinical trial （NCT01935843） is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell （CART） immunotherapy tar- geting human epidermal growth factor receptor 2 （HER2） in patients with advanced biliary tract cancers （BTCs） and pancreatic cancers （PCs）. Eligible patients with HER2-positive （〉50%） BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab- paclitaxel （100-200 mg/m2） and cyclophosphamide （15-35 mglkg）. CAR transgene copy number in the peripheral blood was serially measured to monitor the expansion and persistence of CART-HER2 cells in vivo. Eleven enrolled patients received 1 to 2-cycle CART- HER2 cell infusion （median CAR＋ T cell 2.1× 10^6/kg）. The conditioning treatment resulted in mild-to-moderate fatigue, nausea/vomiting, myalgialarthralgia, and lym- phopenia. Except one grade-3 acute febrile syndrome and one abnormal elevation of transaminase （〉9 ULN）, adverse events related to the infusion of CART-HER2 cells were mild-to-moderate. Post-infusion toxicities included one case of reversible severe upper gastroin- testinal hemorrhage which occurred in a patient with gastric antrum invaded by metastasis 11 days after the CART-HER2 cell infusion, and 2 cases of grade 1-2delayed fever, accompanied by the release of C-reactive protein and interleukin-6. All patients were evaluable for assessment of clinical response, among which 1 obtained a 4.5-months partial response and 5 achieved stable disease. The median progression free survival was 4.8 months （range, 1.5-8.3 months）. Finally, data from this study demonstrated the safety and feasibility of CART-HER2 immunotherapy, and showed encourag- ing signals of clinical activity.
文摘Lymph node (LN) targeti ng through interstitial drain age of nan oparticles (NPs) is an attractive strategy to stimulate a pote nt immune respo nse, as LNs are the primary site for lymphocyte priming by antigen presenting cells (APCs) and triggering of an adaptive immune response. NP size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable NPs are preferred as carrier for vaccine delivery. However, the selective "size gateM for effective LN-drainage, particularly the kinetics of LN trafficking, is less well defined. This is partly due to the challenge in generating size-controlled NPs from biodegradable polymers in the sub-100-nm range. Here, we report the preparation of three sets of poly(lactic-co-glycolic)-b-poly(ethylene-glycol)(PLGA-b-PEG) NPs with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanoprecipitation. Using NPs labeled with a near-infrared dye, we showed that 20-nm NPs drain rapidly across proximal and distal LNs following subcutaneous inoculation in mice and are retai ned in LNs more effectively than NPs with a nu mber average diameter of 40-nm. The drain age of 100-nm NPs was n egligible. Furthermore, the 20-nm NPs showed the highest degree of penetration around the paracortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled PLGA-b-PEG NPs at the lower threshold of about 30-nm are most effective for LN trafficking, retention, and APC uptake after s.c. administration. This report could inform the design of LN-targeted NP carrier for the delivery of therapeutic or prophylactic vaccines.
