Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To ad...Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To address these challenges,IL-2-So-Lipo,a novel liposomal formulation combining IL-2 with sorafenib derivative,was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth.Sorafenib derivatives could target at melanoma-specific receptors,further enhancing liposomal specificity at the tumor site.Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies,as well as their combination.In a B16F10 melanoma model,IL-2-So-Lipo was found to significantly inhibit tumor progression(tumor volume of 108.01±62.99 mm^(3))compared to the control group(tumor volume of 1,397.13±75.55 mm^(3)),improving the therapeutic efficacy.This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes.Additionally,liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency,promoting tumor cell apoptosis and suppressing angiogenesis.Mechanistically,IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype.Furthermore,IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway,exerting a significant role in mediating tumor resistance to sorafenib.These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers.Moreover,the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy,offering a synergistic approach to improve therapeutic outcomes for solid tumors.展开更多
BACKGROUND Laparoscopic cholecystectomy is the primary method for treating cholecystitis.Traditional postoperative care has poor outcomes for patient recovery.The enhanced recovery after surgery(ERAS)model is increasi...BACKGROUND Laparoscopic cholecystectomy is the primary method for treating cholecystitis.Traditional postoperative care has poor outcomes for patient recovery.The enhanced recovery after surgery(ERAS)model is increasingly applied in clinical settings.However,the impact of this nursing model on patients undergoing laparoscopic cholecystectomy remains unclear.AIM To evaluate the effects of ERAS on postoperative gastrointestinal recovery and quality of life in patients undergoing laparoscopic cholecystectomy.METHODS This is a retrospective study design in which we collected clinical data from 120 patients who underwent laparoscopic cholecystectomy at our hospital.Patients were divided into a control group(n=60)and a study group(n=60)based on the type of nursing intervention.The control group received conventional care,while the study group received ERAS.We assessed gastrointestinal recovery,quality of life,and nursing satisfaction before and after the nursing interventions in both groups.RESULTS After nursing care,the gastrointestinal recovery times(time to bowel sounds return,time to flatus,time to first bowel movement,and time to first meal)in the study group were significantly shorter than those in the control group,with statistically significant differences between the two groups(P<0.05).Additionally,the quality of life in the study group was significantly higher than that in the control group(P<0.05).The nursing satisfaction in the study group was also significantly higher than that in the control group,with statistically significant differences between the two groups(P<0.05).CONCLUSION In summary,compared to conventional nursing,ERAS can more rapidly promote gastrointestinal recovery and improve the quality of life in patients after laparoscopic cholecystectomy.Further clinical application of this approach is warranted.展开更多
In crustaceans,20-hydroxyecdysone(20E),the primary bioactive form of ecdysteroid hormones,regulates molting and ovarian development.In vivo and in vitro approaches were used to examine the potential nongenomic mechani...In crustaceans,20-hydroxyecdysone(20E),the primary bioactive form of ecdysteroid hormones,regulates molting and ovarian development.In vivo and in vitro approaches were used to examine the potential nongenomic mechanisms through which 20E modulates ovarian maturation in Chinese mitten crabs(Eriocheir sinensis)and its effects on signaling components and associated genes within the phospholipase C(PLC)-protein kinase C(PKC)pathway.The results demonstrate that the administration of 20E considerably upregulated the hepatopancreatic mRNA expression of G proteins(Gs and Gq),calmodulin-dependent protein kinase II,and inositol 1,4,5-trisphosphate receptors.Concurrent increases in phosphatidylinositol-specific PLC activity were observed,along with elevated levels of its catalytic products(i.e.,inositol 1,4,5-trisphosphate and diacylglycerol).Moreover,20E stimulation activated the phosphorylation and enhanced the transcriptional expression of PKC.Notably,in vitro pharmacological inhibition with U73122(a PLC inhibitor)and Go6983(a PKC inhibitor)resulted in the effective suppression of 20E-induced expression of downstream target genes,including the ecdysone receptor(Ec R),retinoid X receptor(RXR),vitellogenin(Vg),and Vg receptor(VgR).These findings suggest that 20E modulates hepatopancreatic Vg synthesis in the Chinese mitten crab through PLC-PKC signaling transduction,thereby exerting indirect regulatory effects on ovarian development.展开更多
Objective:The biosynthesis of pilose antler polysaccharides(PAPS)with anti-aging activity relies on the precise regulation of key enzymes;however,the identification of these enzymes is limited by traditional low-throu...Objective:The biosynthesis of pilose antler polysaccharides(PAPS)with anti-aging activity relies on the precise regulation of key enzymes;however,the identification of these enzymes is limited by traditional low-throughput techniques.This study constructed an integrated system combining metabolic engineering and high-throughput screening of fluorescent substrates,aiming to overcome the technical bottlenecks in the identification of key enzymes for PAPS synthesis and the optimization of their catalytic efficiency.Methods:Eighteen candidate genes related to carbohydrate metabolism were screened via transcriptome sequencing of deer antler stem cells.After prokaryotic expression and preliminary screening by high-performance liquid chromatography(HPLC),a self-designed fluorescent substrate(FAM-Glc-β1-3-PNPG)combined with a 96-well plate platform was used to achieve high-throughput optimization and screening of catalytic efficiency.Enzyme function was verified through kinetic analysis and in vitro antioxidant experiments.Results:The screened high-efficiency glycosyltransferase UGT-Wnt3a showed a 2.1-fold increase in catalytic efficiency compared with the wild type,with a maximum reaction rate(Vmax)of12.3μmol·min^(-1)·mg^(-1)and a Michaelis constant(Km)of 0.87 mM.The catalytic product of UGT-Wnt3a increased the superoxide dismutase(SOD)activity by 42%(P<0.01)and decreased the malondialdehyde(MDA)content by 28%(P<0.05)in the oxidative damage system.The detection efficiency of the new platform was 9 times higher than that of HPLC,and the limit of detection was reduced by 50 times.Conclusion:The screening system established in this study provides an innovative technical solution for the directed synthesis of PAPS and the development of anti-aging components,promoting the transformation of active components in traditional Chinese medicine from natural extraction to bioengineering-based production.展开更多
基金supported by the Macao Science and Technology Development Fund (FDCT 0148/2022/A3 and 0019/2024/RIA1)the National Natural Science Foundation of China (No. 81572979)
文摘Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To address these challenges,IL-2-So-Lipo,a novel liposomal formulation combining IL-2 with sorafenib derivative,was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth.Sorafenib derivatives could target at melanoma-specific receptors,further enhancing liposomal specificity at the tumor site.Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies,as well as their combination.In a B16F10 melanoma model,IL-2-So-Lipo was found to significantly inhibit tumor progression(tumor volume of 108.01±62.99 mm^(3))compared to the control group(tumor volume of 1,397.13±75.55 mm^(3)),improving the therapeutic efficacy.This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes.Additionally,liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency,promoting tumor cell apoptosis and suppressing angiogenesis.Mechanistically,IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype.Furthermore,IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway,exerting a significant role in mediating tumor resistance to sorafenib.These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers.Moreover,the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy,offering a synergistic approach to improve therapeutic outcomes for solid tumors.
文摘BACKGROUND Laparoscopic cholecystectomy is the primary method for treating cholecystitis.Traditional postoperative care has poor outcomes for patient recovery.The enhanced recovery after surgery(ERAS)model is increasingly applied in clinical settings.However,the impact of this nursing model on patients undergoing laparoscopic cholecystectomy remains unclear.AIM To evaluate the effects of ERAS on postoperative gastrointestinal recovery and quality of life in patients undergoing laparoscopic cholecystectomy.METHODS This is a retrospective study design in which we collected clinical data from 120 patients who underwent laparoscopic cholecystectomy at our hospital.Patients were divided into a control group(n=60)and a study group(n=60)based on the type of nursing intervention.The control group received conventional care,while the study group received ERAS.We assessed gastrointestinal recovery,quality of life,and nursing satisfaction before and after the nursing interventions in both groups.RESULTS After nursing care,the gastrointestinal recovery times(time to bowel sounds return,time to flatus,time to first bowel movement,and time to first meal)in the study group were significantly shorter than those in the control group,with statistically significant differences between the two groups(P<0.05).Additionally,the quality of life in the study group was significantly higher than that in the control group(P<0.05).The nursing satisfaction in the study group was also significantly higher than that in the control group,with statistically significant differences between the two groups(P<0.05).CONCLUSION In summary,compared to conventional nursing,ERAS can more rapidly promote gastrointestinal recovery and improve the quality of life in patients after laparoscopic cholecystectomy.Further clinical application of this approach is warranted.
基金the National Natural Science Foundation of China(No.U23A20248)the K.C.Wong Magna Fund at Ningbo University。
文摘In crustaceans,20-hydroxyecdysone(20E),the primary bioactive form of ecdysteroid hormones,regulates molting and ovarian development.In vivo and in vitro approaches were used to examine the potential nongenomic mechanisms through which 20E modulates ovarian maturation in Chinese mitten crabs(Eriocheir sinensis)and its effects on signaling components and associated genes within the phospholipase C(PLC)-protein kinase C(PKC)pathway.The results demonstrate that the administration of 20E considerably upregulated the hepatopancreatic mRNA expression of G proteins(Gs and Gq),calmodulin-dependent protein kinase II,and inositol 1,4,5-trisphosphate receptors.Concurrent increases in phosphatidylinositol-specific PLC activity were observed,along with elevated levels of its catalytic products(i.e.,inositol 1,4,5-trisphosphate and diacylglycerol).Moreover,20E stimulation activated the phosphorylation and enhanced the transcriptional expression of PKC.Notably,in vitro pharmacological inhibition with U73122(a PLC inhibitor)and Go6983(a PKC inhibitor)resulted in the effective suppression of 20E-induced expression of downstream target genes,including the ecdysone receptor(Ec R),retinoid X receptor(RXR),vitellogenin(Vg),and Vg receptor(VgR).These findings suggest that 20E modulates hepatopancreatic Vg synthesis in the Chinese mitten crab through PLC-PKC signaling transduction,thereby exerting indirect regulatory effects on ovarian development.
文摘Objective:The biosynthesis of pilose antler polysaccharides(PAPS)with anti-aging activity relies on the precise regulation of key enzymes;however,the identification of these enzymes is limited by traditional low-throughput techniques.This study constructed an integrated system combining metabolic engineering and high-throughput screening of fluorescent substrates,aiming to overcome the technical bottlenecks in the identification of key enzymes for PAPS synthesis and the optimization of their catalytic efficiency.Methods:Eighteen candidate genes related to carbohydrate metabolism were screened via transcriptome sequencing of deer antler stem cells.After prokaryotic expression and preliminary screening by high-performance liquid chromatography(HPLC),a self-designed fluorescent substrate(FAM-Glc-β1-3-PNPG)combined with a 96-well plate platform was used to achieve high-throughput optimization and screening of catalytic efficiency.Enzyme function was verified through kinetic analysis and in vitro antioxidant experiments.Results:The screened high-efficiency glycosyltransferase UGT-Wnt3a showed a 2.1-fold increase in catalytic efficiency compared with the wild type,with a maximum reaction rate(Vmax)of12.3μmol·min^(-1)·mg^(-1)and a Michaelis constant(Km)of 0.87 mM.The catalytic product of UGT-Wnt3a increased the superoxide dismutase(SOD)activity by 42%(P<0.01)and decreased the malondialdehyde(MDA)content by 28%(P<0.05)in the oxidative damage system.The detection efficiency of the new platform was 9 times higher than that of HPLC,and the limit of detection was reduced by 50 times.Conclusion:The screening system established in this study provides an innovative technical solution for the directed synthesis of PAPS and the development of anti-aging components,promoting the transformation of active components in traditional Chinese medicine from natural extraction to bioengineering-based production.
