Plants posses a complex co-regulatory network which helps them to elicit a response under diverse adverse conditions. We used an in silico approach to identify the genes with both DRE and ABRE motifs in their promoter...Plants posses a complex co-regulatory network which helps them to elicit a response under diverse adverse conditions. We used an in silico approach to identify the genes with both DRE and ABRE motifs in their promoter regions in Arabidopsis thaliana. Our results showed that Arabidopsis contains a set of 2,052 genes with ABRE and DRE motifs in their promoter regions. Approximately 72~o or more of the total predicted 2,052 genes had a gap distance of less than 40o bp between DRE and ABRE motifs. For positional orientation of the DRE and ABRE motifs, we found that the DR form （one in direct and the other one in reverse orientation） was more prevalent than other forms. These predicted 2,o52 genes include 155 transcription factors. Using microarray data from The Arabidopsis Information Resource （TAIR） database, we present 44 transcription factors out of 155 which are upregulated by more than twofold in response to osmotic stress and ABA treatment. Fifty-one transcripts from the one predicted above were validated using semiquantitative expression analysis to support the microarray data in TAIR. Taken together, we report a set of genes containing both DRE and ABRE motifs in their promoter regions in A. thaliana, which can be useful to understand the role of ABA under osmotic stress condition.展开更多
Early pathogenesis of ischemia-reperfusion(I/R)-induced acute kidney injury(AKI)is dominated by intracellular calcium overload,which induces oxidative stress,intracellular energy metabolism disorder,inflammatory activ...Early pathogenesis of ischemia-reperfusion(I/R)-induced acute kidney injury(AKI)is dominated by intracellular calcium overload,which induces oxidative stress,intracellular energy metabolism disorder,inflammatory activation,and a series of pathologic cascaded reactions that are closely intertwined with self-amplifying and interactive feedback loops,ultimately resulting in cell damage and kidney failure.Currently,most nanomedicines originate from the perspective of antioxidant stress,which can only quench existing reactive oxide species(ROS)but cannot prevent the continuous production of ROS,resulting in insufficient efficacy.As a safe and promising drug,BAPTA-AM is hydrolyzed into BAPTA by intracellular esterase upon entering cells,which can rapidly chelate with overloaded Ca^(2+),restoring intracellular calcium homeostasis,thus inhibiting ROS regeneration at the source.Here,we designed a KTP-targeting peptide-modified yolk-shell structure of liposome–poly(ethylene glycol)methyl ether-block-poly(L-lactide-co-glycolic)(mPLGA)hybrid nanoparticles(<100 nm),with the characteristics of high encapsulation rate,high colloid stability,facile modification,and prolonged blood circulation time.Once the BA/mPLGA@Lipo-KTP was targeted to the site of kidney injury,the cholesteryl hemisuccinate(CHEMS)in the phospholipid bilayer,as an acidic cholesterol ester,was protonated in the simulated inflammatory slightly acidic environment(pH 6.5),causing the liposomes to rupture and release the BA/mPLGA nanoparticles,which were then depolymerized by intracellular esterase.The BAPTA-AM was diffused and hydrolyzed to produce BAPTA,which can rapidly cut off the malignant loop of calcium overload/ROS generation at its source,blocking the endoplasmic reticulum(ER)apoptosis pathway(ATF4–CHOP–Bax/Bcl-2,Casp-12–Casp-3)and the inflammatory pathway(TNF-α–NF-κB–IL-6 axes),thus alleviating pathological changes in kidney tissue,thereby inhibiting the expression of renal tubular marker kidney injury molecule 1(Kim-1)(reduced by 82.9%)and展开更多
Drug delivery systems(DDSs)are of paramount importance to deliver drugs at the intended targets,e.g.,tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical profiles.However,the therape...Drug delivery systems(DDSs)are of paramount importance to deliver drugs at the intended targets,e.g.,tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical profiles.However,the therapeutic efficacy of DDSs is severely impaired by insufficient or non-specific drug release.Dynamic chemical bonds having stimuli-liable prope rties are the refore introduced into DDSs for regulating the drug release kinetics.This review summarizes the recent advances of dynamic covalent chemistry in the DDSs for improving cancer therapy.The review discusses the constitutions of the major classes of dynamic covalent bonds,and the respective applications in the tumor-targe ted DDSs which are based on the different responsive mechanisms,including acid-activatable and reduction-activatable.Furthermore,the review also discusses combination strategies of dual dynamic covale nt bonds which can response to the complex tumor microenvironment much more accurately,and then summarizes and analyzes the prospects for the application of dynamic covalent chemistry in DDSs.展开更多
In this work,we propose a nanoparticle-based strategy of self-motivated supramolecular combination chemotherapy that carries drugs stably and releases them actively in the acidic tumor microenvironment to overcome the...In this work,we propose a nanoparticle-based strategy of self-motivated supramolecular combination chemotherapy that carries drugs stably and releases them actively in the acidic tumor microenvironment to overcome the drug resistance of cancer cells.This self-motivated nanoparticle consists of a cucurbit[7]uril-containing polymer(PCB)-based core.展开更多
基金the INSA young scientist projectBSC-0109 CSIR-Network project for financial support
文摘Plants posses a complex co-regulatory network which helps them to elicit a response under diverse adverse conditions. We used an in silico approach to identify the genes with both DRE and ABRE motifs in their promoter regions in Arabidopsis thaliana. Our results showed that Arabidopsis contains a set of 2,052 genes with ABRE and DRE motifs in their promoter regions. Approximately 72~o or more of the total predicted 2,052 genes had a gap distance of less than 40o bp between DRE and ABRE motifs. For positional orientation of the DRE and ABRE motifs, we found that the DR form （one in direct and the other one in reverse orientation） was more prevalent than other forms. These predicted 2,o52 genes include 155 transcription factors. Using microarray data from The Arabidopsis Information Resource （TAIR） database, we present 44 transcription factors out of 155 which are upregulated by more than twofold in response to osmotic stress and ABA treatment. Fifty-one transcripts from the one predicted above were validated using semiquantitative expression analysis to support the microarray data in TAIR. Taken together, we report a set of genes containing both DRE and ABRE motifs in their promoter regions in A. thaliana, which can be useful to understand the role of ABA under osmotic stress condition.
基金supported by the Taishan Scholar Foundation of Shandong Province(No.tsqn202211065)Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(No.2021JJLH0037)+1 种基金the Natural Science Foundation of China(No.82003673)the Fundamental Research Funds for the Central Universities(No.202113049)。
文摘Early pathogenesis of ischemia-reperfusion(I/R)-induced acute kidney injury(AKI)is dominated by intracellular calcium overload,which induces oxidative stress,intracellular energy metabolism disorder,inflammatory activation,and a series of pathologic cascaded reactions that are closely intertwined with self-amplifying and interactive feedback loops,ultimately resulting in cell damage and kidney failure.Currently,most nanomedicines originate from the perspective of antioxidant stress,which can only quench existing reactive oxide species(ROS)but cannot prevent the continuous production of ROS,resulting in insufficient efficacy.As a safe and promising drug,BAPTA-AM is hydrolyzed into BAPTA by intracellular esterase upon entering cells,which can rapidly chelate with overloaded Ca^(2+),restoring intracellular calcium homeostasis,thus inhibiting ROS regeneration at the source.Here,we designed a KTP-targeting peptide-modified yolk-shell structure of liposome–poly(ethylene glycol)methyl ether-block-poly(L-lactide-co-glycolic)(mPLGA)hybrid nanoparticles(<100 nm),with the characteristics of high encapsulation rate,high colloid stability,facile modification,and prolonged blood circulation time.Once the BA/mPLGA@Lipo-KTP was targeted to the site of kidney injury,the cholesteryl hemisuccinate(CHEMS)in the phospholipid bilayer,as an acidic cholesterol ester,was protonated in the simulated inflammatory slightly acidic environment(pH 6.5),causing the liposomes to rupture and release the BA/mPLGA nanoparticles,which were then depolymerized by intracellular esterase.The BAPTA-AM was diffused and hydrolyzed to produce BAPTA,which can rapidly cut off the malignant loop of calcium overload/ROS generation at its source,blocking the endoplasmic reticulum(ER)apoptosis pathway(ATF4–CHOP–Bax/Bcl-2,Casp-12–Casp-3)and the inflammatory pathway(TNF-α–NF-κB–IL-6 axes),thus alleviating pathological changes in kidney tissue,thereby inhibiting the expression of renal tubular marker kidney injury molecule 1(Kim-1)(reduced by 82.9%)and
基金Financial supports from the National Natural Science Foundation of China(Nos.31671024,51873228 and 31622025)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2014218)+1 种基金the Fusion Grant between Fudan University and Shanghai Institute of Materia Medica,CAS(No.FU-SIMM20182006)the Open Project Program of Key Lab of Smart Drug Delivery(Ministry of Education),Department of Pharmaceutics,School of Pharmacy,Fudan University,China。
文摘Drug delivery systems(DDSs)are of paramount importance to deliver drugs at the intended targets,e.g.,tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical profiles.However,the therapeutic efficacy of DDSs is severely impaired by insufficient or non-specific drug release.Dynamic chemical bonds having stimuli-liable prope rties are the refore introduced into DDSs for regulating the drug release kinetics.This review summarizes the recent advances of dynamic covalent chemistry in the DDSs for improving cancer therapy.The review discusses the constitutions of the major classes of dynamic covalent bonds,and the respective applications in the tumor-targe ted DDSs which are based on the different responsive mechanisms,including acid-activatable and reduction-activatable.Furthermore,the review also discusses combination strategies of dual dynamic covale nt bonds which can response to the complex tumor microenvironment much more accurately,and then summarizes and analyzes the prospects for the application of dynamic covalent chemistry in DDSs.
基金supported by the Ministry of Science and Technology of China(no.2018 YFA0208900)the National Natural Science Foundation of China(nos.21821001 and 21805058)the Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDB36000000).
文摘In this work,we propose a nanoparticle-based strategy of self-motivated supramolecular combination chemotherapy that carries drugs stably and releases them actively in the acidic tumor microenvironment to overcome the drug resistance of cancer cells.This self-motivated nanoparticle consists of a cucurbit[7]uril-containing polymer(PCB)-based core.
