Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study desc...Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research.展开更多
HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity a...HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity and mortality worldwide. Currently,there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects,price and drug resistance,it is essential to discover new targets,to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.展开更多
Making use of the fact that the combination of a drug substance with DNA may inhibit the duplication, synthesis and proliferation of DNA and the consistency of the in vivo and in vitro interactions, the authors worked...Making use of the fact that the combination of a drug substance with DNA may inhibit the duplication, synthesis and proliferation of DNA and the consistency of the in vivo and in vitro interactions, the authors worked out a preliminary screening method for testing complex agents as potential antitumor drugs using ethidium bromide as a fluorescence probe. In this report, the method was applied for in vitro testing fourteen synthesized palladium(Ⅱ)/phenanthroline/amino acid/chloride complexes as potential non-platinum antitumor agents. The fluorimetric screening method was compared with methylene blue tube test and trypan blue dye exclusion assay. All three methods gave agreeable results. Among the complexes tested, [Pd(phen)(lys)]Cl, [Pd(phen)(arg)]Cl and [Pd(phen)(pro)]Cl showed antineoplastic ratios for animal tumor S-180 56%, 50% and 48%, respectively, in accordance with the order of their binding constants with DNA, 7.96×10~6, 4.52×10~6 and 1.0×10~6, respectively. The test results show that fluorimetric method is simple, cheap and rapid. suitable for preliminary screening of antitumor complexes.展开更多
Xenobiotic drugs and chemicals directly interact with DNA,proteins,or other biomolecules in cells. These direct interactions with molecular targets may trigger a series of downstream effects on metabolic-biochemical a...Xenobiotic drugs and chemicals directly interact with DNA,proteins,or other biomolecules in cells. These direct interactions with molecular targets may trigger a series of downstream effects on metabolic-biochemical and regulatory-signaling networks that can invoke cellular consequences leading to adaptive homeostatic or adverse pathological responses. Regulators for drug and chemicals safety have therefore since long required the testing of toxicity in animal models before drugs and pesticides can enter the market. The US National Research Council of the National Academy of Sciences,in its report,Toxicity Testing in the 21st Century: a Vision and a Strategy [1] ,proposed that toxicity testing should become less reliant on apical endpoints from whole animal tests and eventually rely instead on quantitative,doseresponse models based on information from in vitro assays and in vivo biomarkers,which can be used to screen large numbers of chemicals. The present paper reports about a combination of HTS in vitro assays that can be used to study the potential tumorigenic effect of xenobiotics ( drug targets,environmental chemicals) via a set of"sentinel"genes [2] that are functionally interrelated based on evidence weighted functional linkage network ( FLN ) log-likelihood scores ( Linghu et al [3] ) .展开更多
This review was based on a literature search of PubM ed and Scielo databases using the keywords "quercetin,rutin,isoquercitrin,isoquercitin(IQ),quercetin-3-glucoside,bioavailability,flavonols and favonoids,and ca...This review was based on a literature search of PubM ed and Scielo databases using the keywords "quercetin,rutin,isoquercitrin,isoquercitin(IQ),quercetin-3-glucoside,bioavailability,flavonols and favonoids,and cancer" and combinations of all the words.We collected relevant scientific publications from 1990 to 2015 about the absorption,bioavailability,chemoprevention activity,and treatment effects as well as the underlying anticancer mechanisms of isoquercitin.Flavonoids are a group of polyphenolic compounds widely distributed throughout the plant kingdom.The subclass of flavonols receives special attention owing to their health benefits.The main components of this class are quercetin,rutin,and IQ,which is a flavonoid and although mostly found as a glycoside,is an aglycone(lacks a glycoside side chain).This compound presents similar therapeutic profiles to quercetin but with superior bioavailability,resulting in increased efficacy compared to the aglycone form.IQ has therapeutic applications owing to its wide range of pharmacological effects including antioxidant,antiproliferative,anti-inflammatory,anti-hypertensive,and anti-diabetic.The protective effects of IQ in cancer may be due to actions on lipid peroxidation.In addition,the antitumor effect of IQ and its underlying mechanism are related to interactions with Wnt signaling pathway,mixed-lineage protein kinase 3,mitogen-activated protein kinase,apoptotic pathways,as well proinflammatory protein signaling.This review contributed to clarifying the mechanisms of absorption,metabolism,and actions of IQ and isoquercitrin in cancer.展开更多
基金supported by the National Natural Science Foundation of China(Nos.51975400 and 62031022)Shanxi Provincial Key Medical Scientific Research Project(Nos.2020XM06 and 2021XM12)+3 种基金Fundamental Research Program of Shanxi Province(No.202103021224081)Shanxi Provincial Basic Research Project(Nos.202103021221006 and 202103021223040)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L044)Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD026).
文摘Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research.
文摘HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent,treat and to better understand the disease,it is one of the main causes of morbidity and mortality worldwide. Currently,there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects,price and drug resistance,it is essential to discover new targets,to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.
基金Project supported by the National Education Commission Foundation and the National Natural Science Foundation of China.
文摘Making use of the fact that the combination of a drug substance with DNA may inhibit the duplication, synthesis and proliferation of DNA and the consistency of the in vivo and in vitro interactions, the authors worked out a preliminary screening method for testing complex agents as potential antitumor drugs using ethidium bromide as a fluorescence probe. In this report, the method was applied for in vitro testing fourteen synthesized palladium(Ⅱ)/phenanthroline/amino acid/chloride complexes as potential non-platinum antitumor agents. The fluorimetric screening method was compared with methylene blue tube test and trypan blue dye exclusion assay. All three methods gave agreeable results. Among the complexes tested, [Pd(phen)(lys)]Cl, [Pd(phen)(arg)]Cl and [Pd(phen)(pro)]Cl showed antineoplastic ratios for animal tumor S-180 56%, 50% and 48%, respectively, in accordance with the order of their binding constants with DNA, 7.96×10~6, 4.52×10~6 and 1.0×10~6, respectively. The test results show that fluorimetric method is simple, cheap and rapid. suitable for preliminary screening of antitumor complexes.
文摘Xenobiotic drugs and chemicals directly interact with DNA,proteins,or other biomolecules in cells. These direct interactions with molecular targets may trigger a series of downstream effects on metabolic-biochemical and regulatory-signaling networks that can invoke cellular consequences leading to adaptive homeostatic or adverse pathological responses. Regulators for drug and chemicals safety have therefore since long required the testing of toxicity in animal models before drugs and pesticides can enter the market. The US National Research Council of the National Academy of Sciences,in its report,Toxicity Testing in the 21st Century: a Vision and a Strategy [1] ,proposed that toxicity testing should become less reliant on apical endpoints from whole animal tests and eventually rely instead on quantitative,doseresponse models based on information from in vitro assays and in vivo biomarkers,which can be used to screen large numbers of chemicals. The present paper reports about a combination of HTS in vitro assays that can be used to study the potential tumorigenic effect of xenobiotics ( drug targets,environmental chemicals) via a set of"sentinel"genes [2] that are functionally interrelated based on evidence weighted functional linkage network ( FLN ) log-likelihood scores ( Linghu et al [3] ) .
基金Supported by Sao Paulo Research Foundation-FAPESP,No.2012-04634-1
文摘This review was based on a literature search of PubM ed and Scielo databases using the keywords "quercetin,rutin,isoquercitrin,isoquercitin(IQ),quercetin-3-glucoside,bioavailability,flavonols and favonoids,and cancer" and combinations of all the words.We collected relevant scientific publications from 1990 to 2015 about the absorption,bioavailability,chemoprevention activity,and treatment effects as well as the underlying anticancer mechanisms of isoquercitin.Flavonoids are a group of polyphenolic compounds widely distributed throughout the plant kingdom.The subclass of flavonols receives special attention owing to their health benefits.The main components of this class are quercetin,rutin,and IQ,which is a flavonoid and although mostly found as a glycoside,is an aglycone(lacks a glycoside side chain).This compound presents similar therapeutic profiles to quercetin but with superior bioavailability,resulting in increased efficacy compared to the aglycone form.IQ has therapeutic applications owing to its wide range of pharmacological effects including antioxidant,antiproliferative,anti-inflammatory,anti-hypertensive,and anti-diabetic.The protective effects of IQ in cancer may be due to actions on lipid peroxidation.In addition,the antitumor effect of IQ and its underlying mechanism are related to interactions with Wnt signaling pathway,mixed-lineage protein kinase 3,mitogen-activated protein kinase,apoptotic pathways,as well proinflammatory protein signaling.This review contributed to clarifying the mechanisms of absorption,metabolism,and actions of IQ and isoquercitrin in cancer.
