Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence...Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive investigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflammation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors'bioactivity.展开更多
In this study,three new germacranolide sesquiterpenes(1–3),together with six related known analogues(4–9)were isolated from the whole plant of Carpesium cernuum.Their structures were established by a combination of ...In this study,three new germacranolide sesquiterpenes(1–3),together with six related known analogues(4–9)were isolated from the whole plant of Carpesium cernuum.Their structures were established by a combination of extensive NMR spectroscopic analysis,HR-ESIMS data,and ECD calculations.The anti-leukemia activities of all compounds towards three cell lines(HEL,KG-1a,and K562)were evaluated in vitro.Compounds 1–3 exhibited moderate cytotoxicity with IC50 values ranging from 1.59 to 5.47μmol·L^(−1).Mechanistic studies indicated that 2 induced apoptosis by decreasing anti-apoptotic protein Bcl-2 and activating the caspase family in K562 cells.These results suggest that compound 2 is a potential anti-leukemia agent.展开更多
The secondary metabolites produced by algae(including macroalgae and microalgae)possess several human health benefits.The bioactive compounds in algae have potential to be used in the medical and pharmaceutical indust...The secondary metabolites produced by algae(including macroalgae and microalgae)possess several human health benefits.The bioactive compounds in algae have potential to be used in the medical and pharmaceutical industries for drug discovery.The rapid development of genetic tools and omics approaches has extended the understanding of algal metabolism along with enhanced productivity and improving the properties of bioactive compounds.Thus,the focus of this review is to discuss the molecular progress on algae for bioactive compound production which includes genomics,transcriptomics,proteomics,and metabolomics.The comprehensive discussion on multi-omics approaches provides the potential knowledge for future research.The structural and functional genomics,application of genetic tools,molecular mechanisms of bioactive compound synthesis,protein modification,and the omics performance of algae at various levels under abiotic stress are discussed.Gene annotation and identification of key functions are the basis of genomics which provides the comprehensive overview of genetic modification.The recent development of molecular modifications and their application in algae to produce high-yield bioactive compounds that meet human needs through the optimization of algal target strains are also emphasized.The exploration of the molecular mechanisms of bioactive compounds under abiotic stress is of great practical significance to guide the optimization of culture conditions.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82260827 and U1812403-4-4)the Guizhou Provincial Science and Technology Projects,China(Grant Nos.:[2020]1Z069,ZK[2022]380,and ZK[2023]303)+3 种基金the Cultivation Project of National Natural Science Foundation of Guizhou Medical University,China(Grant No.:20NSP050)the Guizhou Provincial Scientific and Technologic Innovation Base,China(Grant No.:[2023]003)the High-level Innovation Talents of Guizhou Province,China(Grant No.:GCC[2023]048)the Startup Fund for High-Level Talent Research at Guizhou Medical University,China(Grant No.:26242020107).
文摘Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive investigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflammation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors'bioactivity.
基金supported by the Science and Technology Department of Guizhou Province(No.QKHJC[2016]1002,81872772,81960546,and U1812403)the National Natural Science Foundation of China(Nos.81872772,81960546,and U1812403)+1 种基金the Science and Technology Department of Anshun City(No.ASKP[2019]3)the 100 Leading Talents of Guizhou Province(fund for LI Yan-Mei,Nos.P2018-KF11 and QZYY-019-022).
文摘In this study,three new germacranolide sesquiterpenes(1–3),together with six related known analogues(4–9)were isolated from the whole plant of Carpesium cernuum.Their structures were established by a combination of extensive NMR spectroscopic analysis,HR-ESIMS data,and ECD calculations.The anti-leukemia activities of all compounds towards three cell lines(HEL,KG-1a,and K562)were evaluated in vitro.Compounds 1–3 exhibited moderate cytotoxicity with IC50 values ranging from 1.59 to 5.47μmol·L^(−1).Mechanistic studies indicated that 2 induced apoptosis by decreasing anti-apoptotic protein Bcl-2 and activating the caspase family in K562 cells.These results suggest that compound 2 is a potential anti-leukemia agent.
基金supported by the startup fund for the construction of the double first-class project(No.561119201),Lanzhou University,China.
文摘The secondary metabolites produced by algae(including macroalgae and microalgae)possess several human health benefits.The bioactive compounds in algae have potential to be used in the medical and pharmaceutical industries for drug discovery.The rapid development of genetic tools and omics approaches has extended the understanding of algal metabolism along with enhanced productivity and improving the properties of bioactive compounds.Thus,the focus of this review is to discuss the molecular progress on algae for bioactive compound production which includes genomics,transcriptomics,proteomics,and metabolomics.The comprehensive discussion on multi-omics approaches provides the potential knowledge for future research.The structural and functional genomics,application of genetic tools,molecular mechanisms of bioactive compound synthesis,protein modification,and the omics performance of algae at various levels under abiotic stress are discussed.Gene annotation and identification of key functions are the basis of genomics which provides the comprehensive overview of genetic modification.The recent development of molecular modifications and their application in algae to produce high-yield bioactive compounds that meet human needs through the optimization of algal target strains are also emphasized.The exploration of the molecular mechanisms of bioactive compounds under abiotic stress is of great practical significance to guide the optimization of culture conditions.
