A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-（4-N, N-dimethylaminophenyl）-pyr- imidine-5-carbonitrile （AHDMAPPC）, was synthesized. It was employed to investigate the binding in- teraction with ...A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-（4-N, N-dimethylaminophenyl）-pyr- imidine-5-carbonitrile （AHDMAPPC）, was synthesized. It was employed to investigate the binding in- teraction with the bovine serum albumin （BSA） in detail using different spectroscopic methods. It ex- hibited antibacterial activity against Escherichia cali and Staphylococcus aureus which are common food poisoning bacteria. The experimental results showed that the fluorescence quenching of model carrier protein BSA by AHDMAPPC was due to static quenching. The site binding constants and number of binding sites （n ≈ 1） were determined at three different temperatures based on fluorescence quenching results. The thermodynamic parameters, enthalpy change （AH）, free energy （AG） and entropy change （AS） for the reaction were calculated to be 15.15 kJ/mol, -36.11 kJ/mol and 51.26J/mol K according to van＇t Hoff equation, respectively. The results indicated that the reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in the binding between drug and BSA. The distance between donor and acceptor is 2.79 nm according to Forster＇s theory. The alterations of the BSA secondary structure in the presence of AHDMAPPC were confirmed by UV-visible, synchronous fluorescence, circular dichroism （CD） and three-dimensional fluorescence spectra. All these results in- dicated that AHDMAPPC can bind to BSA and be effectively transported and eliminated in the body. It can be a useful guideline for further drug design.展开更多
The transformation of free state organic micro-pollutants(MPs)has been widely studied;however,few studies have focused on mixed and bound states MPs,even though numerous ionizable organic MPs process a strong tendency...The transformation of free state organic micro-pollutants(MPs)has been widely studied;however,few studies have focused on mixed and bound states MPs,even though numerous ionizable organic MPs process a strong tendency to combine with dissolved organic matters in aquatic environments.This study systemically investigated the distribution and toxicity assessment of tetracycline(TET)transformation products in free,mixed and bound states during UV,UV/H2O2,UV/PS and CNTs/PS processes.A total of 33 major transformation products were identified by UPLC-Q-TOF-MSMS analysis,combining the double bond equivalence and aromaticity index calculations.The binding interaction would weaken the attack on the dimethylamino(-N(CH3)2)group and induce the direct destruction of rings A and B of TET through the analysis of 2D Kernel Density changes and density functional theory(DFT)calculations.Toxicity assessment and statistics revealed that the intermediate products with medium molecular weight(230m/z380)exhibited higher toxicity,which was closely related to the number of the rings in molecular structures(followed as 2»3>1z4).A predicted toxicity accumulation model(PTAM)was established to evaluate the overall toxicity changes during various oxidation processes.This finding provides new insight into the fate of bound MPs during various oxidation processes in the natural water matrix.展开更多
Interaction of 10-methylacridinium iodide (MAI) as fluorescence probe with nucleobases, nucleosides and nucleic acids has been studied by UV-visible absorption and fluorescence spectroscopy. It was found that fluoresc...Interaction of 10-methylacridinium iodide (MAI) as fluorescence probe with nucleobases, nucleosides and nucleic acids has been studied by UV-visible absorption and fluorescence spectroscopy. It was found that fluorescence of MAI is strongly quenched by the nucleobases, nucleosides and nucleic acids, respectively. The quenching follows the Stern-Volmer linear equation. The fluorescence quenching rate constant (k(q)) was measured to be 10(9)-10(10) (L/mol)/s within the range of diffusion-controlled rate limit, indicating that the interaction between MAI and nucleic acid and their precursors is characteristic of electron transfer mechanism. In addition, the binding interaction model of MAI to calf thymus DNA (ct-DNA) was further investigated. Apparent hypochromism in the absorption spectra of MAI was observed when MAI binds to ct-DNA. Three spectroscopic methods, which include (1) UV spectroscopy, (2) fluorescence quenching of MAI, (3) competitive dual-probe method of MAI and ethidium bromide (EB), were utilized to determine the affinity binding constants (K)of MAI and ct-DNA. The binding constants K obtained from the above methods gave consistent data in the same range (1.0-5.5) x 10(4) L/mol, which lend credibility to these measurements. The binding site number was determined to be 1.9. The influence of thermal denaturation and phosphate concentration on the binding was examined. The binding model of MAI to ct-DNA including intercalation and outside binding was investigated.展开更多
Tumor detection can be carried out via the detection of proteins,such as p53,which is known to play vital role in more than 50%of all cancers affecting humans.Early diagnosis of tumor detection can be achieved by decr...Tumor detection can be carried out via the detection of proteins,such as p53,which is known to play vital role in more than 50%of all cancers affecting humans.Early diagnosis of tumor detection can be achieved by decreasing the lower detection limit of p53 bioassays.Microwave-accelerated bioassay(MAB)technique,which is based on the use of circular bioassay platforms in combination with microwave heating,is employed for the rapid and sensitive detection of p53 protein.Direct sandwich ELISA was constructed on our circular bioassay platforms based on DNA-protein binding interactions.Colorimetric and fluorescence based detection methods were used for room temperature bioassay(control bioassay;total bioassay time is 27 hours)and bioassay using microwave heating(i.e.,the MAB technique;total bioassay time is 10 minutes).In the colorimetric based detection,a very high background signal due to the non-specific binding of proteins for the bioassay carried out at room temperature and a LLOD of 0.01 ng/mL for p53 was observed using the MAB technique.The LLOD for the fluorescence-based detection using the MAB technique was found to be 0.01 ng/mL.The use of circular bioassay platforms in the MAB technique results in microwave-induced temperature gradient,where the specific protein binding interactions are significantly accelerated;thereby reducing the background signal and the lower limit of detection of p53 protein.展开更多
BACKGROUND Colorectal cancer(CRC)causes many deaths worldwide.Synaptotagmin binding cytoplasmic RNA interacting protein(SYNCRIP)is an RNA-binding protein that plays an important role in multiple cancers by epigenetica...BACKGROUND Colorectal cancer(CRC)causes many deaths worldwide.Synaptotagmin binding cytoplasmic RNA interacting protein(SYNCRIP)is an RNA-binding protein that plays an important role in multiple cancers by epigenetically targeting some genes.Our study will examine the expression,potential effect,biological function and clinical value of SYNCRIP in CRC.AIM To examine the expression,potential effect,biological function and clinical value METHODS The expression of SYNCRIP was examined by immunohistochemistry arrays and high-throughput data.The effect of SYNCRIP gene in CRC cell growth was evaluated by CRISPR-Cas9 technology.The target genes of SYNCRIP were calculated using various algorithms,and the molecular mechanism of SYNCRIP in CRC was explored by mutation analysis and pathway analysis.The clinical value of SYNCRIP in prognosis and radiotherapy was revealed via evidence-based medicine methods.RESULTS The protein and mRNA levels of SYNCRIP were both highly expressed in CRC samples compared to nontumorous tissue based on 330 immunohistochemistry arrays and 3640 CRC samples.Cells grew more slowly in eleven CRC cell lines after knocking out the SYNCRIP gene.SYNCRIP could epigenetically target genes to promote the occurrence and development of CRC by boosting the cell cycle and affecting the tumor microenvironment.In addition,CRC patients with high SYNCRIP expression are more sensitive to radiotherapy.CONCLUSION SYNCRIP is upregulated in CRC,and highly expressed SYNCRIP can accelerate CRC cell division by exerting its epigenetic regulatory effects.In addition,SYNCRIP is expected to become a potential biomarker to predict the effect of radiotherapy.展开更多
Receptor-ligand interactions in blood flow are crucial to initiate such biological processes as inflammatory cascade,platelet thrombosis,as well as tumor metastasis.To mediate cell adhesion,the interacting receptors a...Receptor-ligand interactions in blood flow are crucial to initiate such biological processes as inflammatory cascade,platelet thrombosis,as well as tumor metastasis.To mediate cell adhesion,the interacting receptors and ligands must be anchored onto two apposing surfaces of two cells or a cell and a substratum,i.e.,two-dimensional（2D）binding,which is different from the binding of a soluble ligand in fluid phase to a receptor,i.e.,three-dimensional（3D） binding.While numerous works have been focused on3 D kinetics of receptor-ligand interactions in the immune system,2D kinetics and its regulations have been less understood,since no theoretical framework or experimental assays were established until 1993.Not only does the molecular structure dominate 2D binding kinetics,but the shear force in blood flow also regulates cell adhesion mediated by interacting receptors and ligands.Here,we provide an overview of current progress in 2D binding and regulations,mainly from our group.Relevant issues of theoretical frameworks,experimental measurements,kinetic rates and binding affinities,and force regulations are discussed.展开更多
Environmental control of the alcohol dehydrogenase(Adh)and other stress response genes in plants is in part brought about by transcriptional regulation involving the G-box cis-acting DNA element and bZIP G-box Binding...Environmental control of the alcohol dehydrogenase(Adh)and other stress response genes in plants is in part brought about by transcriptional regulation involving the G-box cis-acting DNA element and bZIP G-box Binding Factors(GBFs).The mechanisms of GBF regulation and requirements for additional factors in this control process are not well understood.In an effort to identify potential GBF binding and control partners,maize GBF1 was used as bait in a yeast two-hybrid screen of an A.thaliana cDNA library.GBF Interacting Protein 1(GIP1)arose from the screen as a 496 amino acid protein with a predicted molecular weight of 53,748 kDa that strongly interacts with GBFs.Northern analysis of A.thaliana tissue suggests a 1.8-1.9 kb GIP1 transcript,predominantly in roots.Immunolocalization studies indicate that GIP1 protein is mainly localized to the nucleus.In vitro electrophoretic mobility shift assays using an Adh G-box DNA probe and recombinant A.thaliana GBF3 or maize GBF1,showed that the presence of GIP1 resulted in a tenfold increase in GBF DNA binding activity without altering the migration,suggesting a transient association between GIP1 and GBF.Addition of GIP1 to intentionally aggregated GBF converted GBF to lower molecular weight macromolecular complexes and GIP1 also refolded denatured rhodanese in the absence of ATP.These data suggest GIP1 functions to enhance GBF DNA binding activity by acting as a potent nuclear chaperone or crowbar,and potentially regulates the multimeric state of GBFs,thereby contributing to bZIP-mediated gene regulation.展开更多
Two new complexes [Cu（dafo）2（en）]（ClO4）2·2H2O （en=NH2CH2CH2NH2） 1 and [Cu（dafo）2（dap）]（ClO4）2·2H2O [dap=NH2CH2CH（CH3）NH2] 2 （dafo=4,5-diazafluoren-9-one） have been synthesized and character...Two new complexes [Cu（dafo）2（en）]（ClO4）2·2H2O （en=NH2CH2CH2NH2） 1 and [Cu（dafo）2（dap）]（ClO4）2·2H2O [dap=NH2CH2CH（CH3）NH2] 2 （dafo=4,5-diazafluoren-9-one） have been synthesized and characterized by elemental analysis, IR and UV spectra. Meanwhile, the complex 1 has been characterized by single crystal X-ray diffraction analysis. The initial DNA binding interactions of the complexes 1 and 2 have been investigated by UV spectra, emission spectra and cyclic voltammogram. Concluding the results of three methods used to measure the interaction of complexes 1 and 2 with DNA, the action mode of the two complexes with DNA is intercalation, and character of ligands and steric effect may affect the interaction of the complexes with DNA.展开更多
AIM: To investigate the role of nuclear translocation of calcyclin binding protein, also called Siah-1 interacting protein (CacyBP/SIP), in gastric carcinogenesis.
Objective To investigate endothelial cell heterogeneity in diabetic cardiomyopathy (DCM) and identify potential therapeutic targets of dapagliflozin in cardiac vascular endothelial cells.Methods ePharmaLib reverse vir...Objective To investigate endothelial cell heterogeneity in diabetic cardiomyopathy (DCM) and identify potential therapeutic targets of dapagliflozin in cardiac vascular endothelial cells.Methods ePharmaLib reverse virtual screening was performed on 15 148 protein crystals to identify the binding interactions between humanderived proteins and dapagliflozin.展开更多
Objective Oral squamous cell carcinoma(OSCC)is an aggressive cancer with a high mortality rate.San-Zhong-Kui-Jian-Tang(SZKJT),a Chinese herbal formula,has long been used as an adjuvant therapy in cancer clinical pract...Objective Oral squamous cell carcinoma(OSCC)is an aggressive cancer with a high mortality rate.San-Zhong-Kui-Jian-Tang(SZKJT),a Chinese herbal formula,has long been used as an adjuvant therapy in cancer clinical practice.Although its therapeutic effects and molecular mechanisms in OSCC have been previously elucidated,the potential interactions and mechanisms between the active phytochemicals and their therapeutic targets are still lacking.Methods The present study employed network pharmacology and topology approaches to establish a“herbal ingredients–active phytochemicals–target interaction”network to explore the potential therapeutic targets of SZKJT-active phytochemicals in the treatment of OSCC.The role of the target proteins in oncogenesis was assessed via GO and KEGG enrichment analyses,and their interactions with the active phytochemicals of SZKJT were calculated via molecular docking and dynamic simulations.The pharmacokinetic properties and toxicity of the active phytochemicals were also predicted.Results A total of 171 active phytochemicals of SZKJT fulfilled the bioavailability and drug-likeness screening criteria,with the flavonoids quercetin,kaempferol,and naringenin having the greatest potential.The 4 crucial targets of these active phytochemicals are PTGS2,TNF,BCL2,and CASP3,which encode cyclooxygenase-2,tumor necrosis factor(TNF),BCL-2 apoptosis regulator,and caspase-3,respectively.The interactions between phytochemicals and target proteins were predicted to be thermodynamically feasible and stable via molecular docking and dynamics simulations.Finally,the results revealed that the IL-6/JAK/STAT3 pathway and TNF signaling via NF-κB are the two prominent pathways targeted by SZKJT.Conclusion In summary,this study provides computational data for in-depth exploration of the mechanism by which SZKJT activates phytochemicals to treat OSCC.展开更多
Dissolved organic matter(DOM) is a group of compounds that have complex chemical structures and multiple interactions with their surrounding materials. More than one trillion tons of DOM are stocked in the world's...Dissolved organic matter(DOM) is a group of compounds that have complex chemical structures and multiple interactions with their surrounding materials. More than one trillion tons of DOM are stocked in the world's aquatic ecosystems. DOM is a very important part of aquatic ecosystem productivity and plays a crucial role in global carbon cycling. DOM has rich environmental behaviors and effects such as influencing the bioavailability of contaminants, serving as an important inducer of reactive oxygen species(ROS), and protecting aquatic organisms from the harm of dangerous ultraviolet radiation. There have been many systematic studies on the composition, structure, and sources of DOM because such studies are much easier to conduct than studies on the environmental behaviors and effects of DOM. Due to many factors, the research systems of DOM's environmental behaviors and effects are still being developed and have become a hotspot of environmental science. This review paper focuses on some critical progress, problems, and trends of DOM's environmental behaviors and effects in aquatic ecosystems, including mutual exchange mechanisms between DOM and particulate organic matter(POM) with influencing factors, photochemical behaviors of DOM especially inducing ROS, binding interactions between DOM and anthropogenic organic contaminants(AOC), interactions between DOM and microorganisms, effects of DOM on pollutants' bioavailability, ecotoxicity, and ecological risks. Hopefully, this paper will contribute to a more systematic understanding of the DOM environmental behaviors and effects and to promoting further relevant studies.展开更多
基金receiving a fellowship from UGCNew Delhi[University Grant Commission,the XIth plan(Faculty Improvement Programme)]DST and UGC for providing funds to the department under FIST and SAP programme
文摘A biologically active antibacterial reagent, 2-amino-6-hydroxy-4-（4-N, N-dimethylaminophenyl）-pyr- imidine-5-carbonitrile （AHDMAPPC）, was synthesized. It was employed to investigate the binding in- teraction with the bovine serum albumin （BSA） in detail using different spectroscopic methods. It ex- hibited antibacterial activity against Escherichia cali and Staphylococcus aureus which are common food poisoning bacteria. The experimental results showed that the fluorescence quenching of model carrier protein BSA by AHDMAPPC was due to static quenching. The site binding constants and number of binding sites （n ≈ 1） were determined at three different temperatures based on fluorescence quenching results. The thermodynamic parameters, enthalpy change （AH）, free energy （AG） and entropy change （AS） for the reaction were calculated to be 15.15 kJ/mol, -36.11 kJ/mol and 51.26J/mol K according to van＇t Hoff equation, respectively. The results indicated that the reaction was an endothermic and spontaneous process, and hydrophobic interactions played a major role in the binding between drug and BSA. The distance between donor and acceptor is 2.79 nm according to Forster＇s theory. The alterations of the BSA secondary structure in the presence of AHDMAPPC were confirmed by UV-visible, synchronous fluorescence, circular dichroism （CD） and three-dimensional fluorescence spectra. All these results in- dicated that AHDMAPPC can bind to BSA and be effectively transported and eliminated in the body. It can be a useful guideline for further drug design.
基金The authors would like to thank the National Natural Science Foundation of China(NO.51878422)Science and Technology Projects of Sichuan Province(2018 HH0104)+1 种基金Science and Technology Bureau of Chengdu(2017-GH02-00010-342 HZ)Innovation Spark Project in Sichuan University(Grant No.2082604401254)for the financial support.
文摘The transformation of free state organic micro-pollutants(MPs)has been widely studied;however,few studies have focused on mixed and bound states MPs,even though numerous ionizable organic MPs process a strong tendency to combine with dissolved organic matters in aquatic environments.This study systemically investigated the distribution and toxicity assessment of tetracycline(TET)transformation products in free,mixed and bound states during UV,UV/H2O2,UV/PS and CNTs/PS processes.A total of 33 major transformation products were identified by UPLC-Q-TOF-MSMS analysis,combining the double bond equivalence and aromaticity index calculations.The binding interaction would weaken the attack on the dimethylamino(-N(CH3)2)group and induce the direct destruction of rings A and B of TET through the analysis of 2D Kernel Density changes and density functional theory(DFT)calculations.Toxicity assessment and statistics revealed that the intermediate products with medium molecular weight(230m/z380)exhibited higher toxicity,which was closely related to the number of the rings in molecular structures(followed as 2»3>1z4).A predicted toxicity accumulation model(PTAM)was established to evaluate the overall toxicity changes during various oxidation processes.This finding provides new insight into the fate of bound MPs during various oxidation processes in the natural water matrix.
文摘Interaction of 10-methylacridinium iodide (MAI) as fluorescence probe with nucleobases, nucleosides and nucleic acids has been studied by UV-visible absorption and fluorescence spectroscopy. It was found that fluorescence of MAI is strongly quenched by the nucleobases, nucleosides and nucleic acids, respectively. The quenching follows the Stern-Volmer linear equation. The fluorescence quenching rate constant (k(q)) was measured to be 10(9)-10(10) (L/mol)/s within the range of diffusion-controlled rate limit, indicating that the interaction between MAI and nucleic acid and their precursors is characteristic of electron transfer mechanism. In addition, the binding interaction model of MAI to calf thymus DNA (ct-DNA) was further investigated. Apparent hypochromism in the absorption spectra of MAI was observed when MAI binds to ct-DNA. Three spectroscopic methods, which include (1) UV spectroscopy, (2) fluorescence quenching of MAI, (3) competitive dual-probe method of MAI and ethidium bromide (EB), were utilized to determine the affinity binding constants (K)of MAI and ct-DNA. The binding constants K obtained from the above methods gave consistent data in the same range (1.0-5.5) x 10(4) L/mol, which lend credibility to these measurements. The binding site number was determined to be 1.9. The influence of thermal denaturation and phosphate concentration on the binding was examined. The binding model of MAI to ct-DNA including intercalation and outside binding was investigated.
基金supported by National Institute of Biomedical Imaging and Bioengineering,award number 5-K25EB007565-05。
文摘Tumor detection can be carried out via the detection of proteins,such as p53,which is known to play vital role in more than 50%of all cancers affecting humans.Early diagnosis of tumor detection can be achieved by decreasing the lower detection limit of p53 bioassays.Microwave-accelerated bioassay(MAB)technique,which is based on the use of circular bioassay platforms in combination with microwave heating,is employed for the rapid and sensitive detection of p53 protein.Direct sandwich ELISA was constructed on our circular bioassay platforms based on DNA-protein binding interactions.Colorimetric and fluorescence based detection methods were used for room temperature bioassay(control bioassay;total bioassay time is 27 hours)and bioassay using microwave heating(i.e.,the MAB technique;total bioassay time is 10 minutes).In the colorimetric based detection,a very high background signal due to the non-specific binding of proteins for the bioassay carried out at room temperature and a LLOD of 0.01 ng/mL for p53 was observed using the MAB technique.The LLOD for the fluorescence-based detection using the MAB technique was found to be 0.01 ng/mL.The use of circular bioassay platforms in the MAB technique results in microwave-induced temperature gradient,where the specific protein binding interactions are significantly accelerated;thereby reducing the background signal and the lower limit of detection of p53 protein.
基金Supported by Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220415 and No.Z20210442The First Affiliated Hospital of Guangxi Medical University Provincial and Ministerial Key Laboratory Cultivation Project:Guangxi Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer,No.21-220-18.
文摘BACKGROUND Colorectal cancer(CRC)causes many deaths worldwide.Synaptotagmin binding cytoplasmic RNA interacting protein(SYNCRIP)is an RNA-binding protein that plays an important role in multiple cancers by epigenetically targeting some genes.Our study will examine the expression,potential effect,biological function and clinical value of SYNCRIP in CRC.AIM To examine the expression,potential effect,biological function and clinical value METHODS The expression of SYNCRIP was examined by immunohistochemistry arrays and high-throughput data.The effect of SYNCRIP gene in CRC cell growth was evaluated by CRISPR-Cas9 technology.The target genes of SYNCRIP were calculated using various algorithms,and the molecular mechanism of SYNCRIP in CRC was explored by mutation analysis and pathway analysis.The clinical value of SYNCRIP in prognosis and radiotherapy was revealed via evidence-based medicine methods.RESULTS The protein and mRNA levels of SYNCRIP were both highly expressed in CRC samples compared to nontumorous tissue based on 330 immunohistochemistry arrays and 3640 CRC samples.Cells grew more slowly in eleven CRC cell lines after knocking out the SYNCRIP gene.SYNCRIP could epigenetically target genes to promote the occurrence and development of CRC by boosting the cell cycle and affecting the tumor microenvironment.In addition,CRC patients with high SYNCRIP expression are more sensitive to radiotherapy.CONCLUSION SYNCRIP is upregulated in CRC,and highly expressed SYNCRIP can accelerate CRC cell division by exerting its epigenetic regulatory effects.In addition,SYNCRIP is expected to become a potential biomarker to predict the effect of radiotherapy.
基金supported by Natural Science Foundation of China(grants 10042001,10072071,10128205,30225027, 10332060,30730032,11072251,and 31110103918)National Key Basic Research Foundation of China(grants 2006CB910303 and 2011CB710904)+2 种基金National High Technology Research and Development Program of China(grants 2007AA02Z306 and 2011AA020109)Chinese Academy of Sciences(grants KJCX2-L02,KJCX2-SW-L06, 2005-1-16,KJCX2-YW-L08,Y2010030,XDA01030102,XDA04073 801)NIH Fogarty International Research Collaboration Award TW 05774-01
文摘Receptor-ligand interactions in blood flow are crucial to initiate such biological processes as inflammatory cascade,platelet thrombosis,as well as tumor metastasis.To mediate cell adhesion,the interacting receptors and ligands must be anchored onto two apposing surfaces of two cells or a cell and a substratum,i.e.,two-dimensional（2D）binding,which is different from the binding of a soluble ligand in fluid phase to a receptor,i.e.,three-dimensional（3D） binding.While numerous works have been focused on3 D kinetics of receptor-ligand interactions in the immune system,2D kinetics and its regulations have been less understood,since no theoretical framework or experimental assays were established until 1993.Not only does the molecular structure dominate 2D binding kinetics,but the shear force in blood flow also regulates cell adhesion mediated by interacting receptors and ligands.Here,we provide an overview of current progress in 2D binding and regulations,mainly from our group.Relevant issues of theoretical frameworks,experimental measurements,kinetic rates and binding affinities,and force regulations are discussed.
基金This research was supported by the U S Department of Agriculture Grants 00-35304-96Ol and 98-35301-6083.
文摘Environmental control of the alcohol dehydrogenase(Adh)and other stress response genes in plants is in part brought about by transcriptional regulation involving the G-box cis-acting DNA element and bZIP G-box Binding Factors(GBFs).The mechanisms of GBF regulation and requirements for additional factors in this control process are not well understood.In an effort to identify potential GBF binding and control partners,maize GBF1 was used as bait in a yeast two-hybrid screen of an A.thaliana cDNA library.GBF Interacting Protein 1(GIP1)arose from the screen as a 496 amino acid protein with a predicted molecular weight of 53,748 kDa that strongly interacts with GBFs.Northern analysis of A.thaliana tissue suggests a 1.8-1.9 kb GIP1 transcript,predominantly in roots.Immunolocalization studies indicate that GIP1 protein is mainly localized to the nucleus.In vitro electrophoretic mobility shift assays using an Adh G-box DNA probe and recombinant A.thaliana GBF3 or maize GBF1,showed that the presence of GIP1 resulted in a tenfold increase in GBF DNA binding activity without altering the migration,suggesting a transient association between GIP1 and GBF.Addition of GIP1 to intentionally aggregated GBF converted GBF to lower molecular weight macromolecular complexes and GIP1 also refolded denatured rhodanese in the absence of ATP.These data suggest GIP1 functions to enhance GBF DNA binding activity by acting as a potent nuclear chaperone or crowbar,and potentially regulates the multimeric state of GBFs,thereby contributing to bZIP-mediated gene regulation.
基金Project supported by the Program for Changjiang Scholars and Innovative Research Team in University, PCSIRT （No. IRT 0559）, the National Natural Science Foundation of China （No. 20671076）, the Major State Basic Research Development Program of China （the 973 Program, No. 2003CB214606）, the Key Laboratory Research and Establishment Program of Shaanxi Education Section （No. 03JS006）, and the Special Foundation of Shaanxi Education Section （No. 04JK143）.
文摘Two new complexes [Cu（dafo）2（en）]（ClO4）2·2H2O （en=NH2CH2CH2NH2） 1 and [Cu（dafo）2（dap）]（ClO4）2·2H2O [dap=NH2CH2CH（CH3）NH2] 2 （dafo=4,5-diazafluoren-9-one） have been synthesized and characterized by elemental analysis, IR and UV spectra. Meanwhile, the complex 1 has been characterized by single crystal X-ray diffraction analysis. The initial DNA binding interactions of the complexes 1 and 2 have been investigated by UV spectra, emission spectra and cyclic voltammogram. Concluding the results of three methods used to measure the interaction of complexes 1 and 2 with DNA, the action mode of the two complexes with DNA is intercalation, and character of ligands and steric effect may affect the interaction of the complexes with DNA.
基金Supported by National Natural Science Foundation of China,No.81072040
文摘AIM: To investigate the role of nuclear translocation of calcyclin binding protein, also called Siah-1 interacting protein (CacyBP/SIP), in gastric carcinogenesis.
文摘Objective To investigate endothelial cell heterogeneity in diabetic cardiomyopathy (DCM) and identify potential therapeutic targets of dapagliflozin in cardiac vascular endothelial cells.Methods ePharmaLib reverse virtual screening was performed on 15 148 protein crystals to identify the binding interactions between humanderived proteins and dapagliflozin.
文摘Objective Oral squamous cell carcinoma(OSCC)is an aggressive cancer with a high mortality rate.San-Zhong-Kui-Jian-Tang(SZKJT),a Chinese herbal formula,has long been used as an adjuvant therapy in cancer clinical practice.Although its therapeutic effects and molecular mechanisms in OSCC have been previously elucidated,the potential interactions and mechanisms between the active phytochemicals and their therapeutic targets are still lacking.Methods The present study employed network pharmacology and topology approaches to establish a“herbal ingredients–active phytochemicals–target interaction”network to explore the potential therapeutic targets of SZKJT-active phytochemicals in the treatment of OSCC.The role of the target proteins in oncogenesis was assessed via GO and KEGG enrichment analyses,and their interactions with the active phytochemicals of SZKJT were calculated via molecular docking and dynamic simulations.The pharmacokinetic properties and toxicity of the active phytochemicals were also predicted.Results A total of 171 active phytochemicals of SZKJT fulfilled the bioavailability and drug-likeness screening criteria,with the flavonoids quercetin,kaempferol,and naringenin having the greatest potential.The 4 crucial targets of these active phytochemicals are PTGS2,TNF,BCL2,and CASP3,which encode cyclooxygenase-2,tumor necrosis factor(TNF),BCL-2 apoptosis regulator,and caspase-3,respectively.The interactions between phytochemicals and target proteins were predicted to be thermodynamically feasible and stable via molecular docking and dynamics simulations.Finally,the results revealed that the IL-6/JAK/STAT3 pathway and TNF signaling via NF-κB are the two prominent pathways targeted by SZKJT.Conclusion In summary,this study provides computational data for in-depth exploration of the mechanism by which SZKJT activates phytochemicals to treat OSCC.
基金supported by the National Project for Water Pollution Control in China(Grant No.2012ZX07103-002)the National Natural Science Foundation of China(Grant Nos.4150308341271462&41030529)
文摘Dissolved organic matter(DOM) is a group of compounds that have complex chemical structures and multiple interactions with their surrounding materials. More than one trillion tons of DOM are stocked in the world's aquatic ecosystems. DOM is a very important part of aquatic ecosystem productivity and plays a crucial role in global carbon cycling. DOM has rich environmental behaviors and effects such as influencing the bioavailability of contaminants, serving as an important inducer of reactive oxygen species(ROS), and protecting aquatic organisms from the harm of dangerous ultraviolet radiation. There have been many systematic studies on the composition, structure, and sources of DOM because such studies are much easier to conduct than studies on the environmental behaviors and effects of DOM. Due to many factors, the research systems of DOM's environmental behaviors and effects are still being developed and have become a hotspot of environmental science. This review paper focuses on some critical progress, problems, and trends of DOM's environmental behaviors and effects in aquatic ecosystems, including mutual exchange mechanisms between DOM and particulate organic matter(POM) with influencing factors, photochemical behaviors of DOM especially inducing ROS, binding interactions between DOM and anthropogenic organic contaminants(AOC), interactions between DOM and microorganisms, effects of DOM on pollutants' bioavailability, ecotoxicity, and ecological risks. Hopefully, this paper will contribute to a more systematic understanding of the DOM environmental behaviors and effects and to promoting further relevant studies.
