首页 > 最新文献

Combinatorial chemistry & high throughput screening最新文献

英文 中文
Preparation of DOX-TPP/HA-ss-OA Nanoparticles, Investigation of Drug Release Behavior In Vitro, and Evaluation of Anti-proliferative Activity In Vitro. DOX-TPP/HA-ss-OA纳米颗粒的制备、体外药物释放行为研究和体外抗增殖活性评估。
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-06 DOI: 10.2174/0113862073330016240911094247
Xuanting Fei, Qiaohong Hu

Objective: This study aimed to develop and characterize DOX-TPP/HA-ss-OA nanoparticles, utilizing the mitochondria-targeting prodrug doxorubicin-triphenylphosphine (DOXTPP) and a reduction-sensitive amphiphilic polymer, hyaluronic acid-disulfide-oleic acid (HAss- OA). The research focused on evaluating the drug release behavior of these nanoparticles under varying glutathione (GSH) concentrations and their anti-tumor activity in vitro.

Methods: DOX-TPP/HA-ss-OA nanoparticles were prepared using probe ultrasound technology. The study examined the impact of different organic solvents on drug loading capacity and encapsulation efficiency to determine the optimal conditions. A single-factor experimental design was used to optimize the formulation process. Key parameters, including particle size and zeta potential, were measured to assess nanoparticle stability and performance. The dynamic dialysis method was employed to evaluate the reduction-sensitive drug release characteristics in media with different GSH concentrations. The MTT assay was used to analyze the growth-inhibitory effects of the nanoparticles on human breast cancer cells (MCF-7) and drug-resistant cells (MCF-7/ADR).

Results: The optimized preparation process for DOX-TPP/HA-ss-OA nanoparticles included a drug dosage of 2.0 mg, an oil-to-water volume ratio of 1:5, ultrasonic power of 500 W, and ultrasonic time of 15 minutes. The nanoparticles had an average particle size of 203.72 ± 2.30 nm and a zeta potential of 25.82 ± 0.58 mV, indicating favorable stability and effective drug delivery properties. The nanoparticles exhibited a slow, sustained release of DOX-TPP in pH 7.4 phosphate buffer solution (PBS) and accelerated release in high GSH concentrations, demonstrating reduction-responsive drug release. In vitro studies showed that DOX-TPP/HA-ss-OA nanoparticles significantly inhibited the proliferation of MCF-7 and MCF-7/ADR cells in a dosedependent manner, with enhanced efficacy compared to free DOX and other formulations.

Conclusion: DOX-TPP/HA-ss-OA nanoparticles demonstrate excellent reduction sensitivity, effective tumor cell growth inhibition in vitro, and the ability to overcome drug resistance. Including particle size and zeta potential measurements supports their suitability as drug carriers, highlighting their potential for targeted cancer therapy and further development.

研究目的本研究旨在利用线粒体靶向原药多柔比星-三苯基膦(DOXTPP)和还原敏感性两性聚合物透明质酸-二硫代-油酸(HAss- OA),开发 DOX-TPP/HA-ss-OA 纳米粒子并确定其特性。研究重点是评估这些纳米颗粒在不同谷胱甘肽(GSH)浓度下的药物释放行为及其体外抗肿瘤活性:方法:采用探针超声技术制备 DOX-TPP/HA-ss-OA 纳米粒子。研究考察了不同有机溶剂对药物负载能力和封装效率的影响,以确定最佳条件。采用单因素实验设计来优化制剂过程。测量了包括粒度和 zeta 电位在内的关键参数,以评估纳米粒子的稳定性和性能。采用动态透析法评估不同 GSH 浓度介质中还原敏感药物释放特性。采用 MTT 法分析纳米颗粒对人乳腺癌细胞(MCF-7)和耐药细胞(MCF-7/ADR)的生长抑制作用:DOX-TPP/HA-ss-OA纳米颗粒的优化制备工艺包括:药物剂量为2.0毫克,油水体积比为1:5,超声功率为500瓦,超声时间为15分钟。纳米颗粒的平均粒径为 203.72 ± 2.30 nm,zeta 电位为 25.82 ± 0.58 mV,显示出良好的稳定性和有效的给药特性。纳米颗粒在 pH 值为 7.4 的磷酸盐缓冲溶液(PBS)中表现出缓慢、持续的 DOX-TPP 释放,而在高浓度 GSH 溶液中则表现出加速释放,显示出还原反应性药物释放。体外研究表明,DOX-TPP/HA-ss-OA 纳米颗粒以剂量依赖的方式显著抑制了 MCF-7 和 MCF-7/ADR 细胞的增殖,与游离 DOX 和其他制剂相比,疗效更佳:结论:DOX-TPP/HA-ss-OA 纳米颗粒具有出色的还原敏感性、体外有效抑制肿瘤细胞生长以及克服耐药性的能力。包括粒度和 zeta 电位在内的测量结果表明它们适合作为药物载体,凸显了它们在癌症靶向治疗和进一步开发方面的潜力。
{"title":"Preparation of DOX-TPP/HA-ss-OA Nanoparticles, Investigation of Drug Release Behavior In Vitro, and Evaluation of Anti-proliferative Activity In Vitro.","authors":"Xuanting Fei, Qiaohong Hu","doi":"10.2174/0113862073330016240911094247","DOIUrl":"10.2174/0113862073330016240911094247","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to develop and characterize DOX-TPP/HA-ss-OA nanoparticles, utilizing the mitochondria-targeting prodrug doxorubicin-triphenylphosphine (DOXTPP) and a reduction-sensitive amphiphilic polymer, hyaluronic acid-disulfide-oleic acid (HAss- OA). The research focused on evaluating the drug release behavior of these nanoparticles under varying glutathione (GSH) concentrations and their anti-tumor activity in vitro.</p><p><strong>Methods: </strong>DOX-TPP/HA-ss-OA nanoparticles were prepared using probe ultrasound technology. The study examined the impact of different organic solvents on drug loading capacity and encapsulation efficiency to determine the optimal conditions. A single-factor experimental design was used to optimize the formulation process. Key parameters, including particle size and zeta potential, were measured to assess nanoparticle stability and performance. The dynamic dialysis method was employed to evaluate the reduction-sensitive drug release characteristics in media with different GSH concentrations. The MTT assay was used to analyze the growth-inhibitory effects of the nanoparticles on human breast cancer cells (MCF-7) and drug-resistant cells (MCF-7/ADR).</p><p><strong>Results: </strong>The optimized preparation process for DOX-TPP/HA-ss-OA nanoparticles included a drug dosage of 2.0 mg, an oil-to-water volume ratio of 1:5, ultrasonic power of 500 W, and ultrasonic time of 15 minutes. The nanoparticles had an average particle size of 203.72 ± 2.30 nm and a zeta potential of 25.82 ± 0.58 mV, indicating favorable stability and effective drug delivery properties. The nanoparticles exhibited a slow, sustained release of DOX-TPP in pH 7.4 phosphate buffer solution (PBS) and accelerated release in high GSH concentrations, demonstrating reduction-responsive drug release. In vitro studies showed that DOX-TPP/HA-ss-OA nanoparticles significantly inhibited the proliferation of MCF-7 and MCF-7/ADR cells in a dosedependent manner, with enhanced efficacy compared to free DOX and other formulations.</p><p><strong>Conclusion: </strong>DOX-TPP/HA-ss-OA nanoparticles demonstrate excellent reduction sensitivity, effective tumor cell growth inhibition in vitro, and the ability to overcome drug resistance. Including particle size and zeta potential measurements supports their suitability as drug carriers, highlighting their potential for targeted cancer therapy and further development.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Potential Cardiovascular Disease Treatment by Natural Drugs Targeting the HIF-1α Factor and its Pathway. 以 HIF-1α 因子及其通路为靶点的天然药物治疗心血管疾病的潜力
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-05 DOI: 10.2174/0113862073331615241018081811
Weihan Gao, Danyang Wang, Yanmei Shi, Yu Sun, Jinlan Deng, Xiayinan Song, Jie Li, Min Zhang

Cardiovascular diseases (CVDs) remain a key contributor to global morbidity and mortality. Being a vital regulator of hypoxia, hypoxia-inducible factor-1α (HIF-1α) is a crucial player in CVD treatment. Recently, increasing attention has been paid to the effect of natural drugs on CVDs. According to some studies, HIF-1α is a potential target for CVD treatment in traditional Chinese medicine. In this study, we describe the mechanism underlying the regulatory role of HIF-1α in CVDs and summarize 30 natural drugs and 3 formulations for CVD treatment through HIF-1α and its signaling pathway. The study provides new ideas for CVD prevention and treatment.

心血管疾病(CVDs)仍然是导致全球发病率和死亡率的主要因素。作为缺氧的重要调节因子,缺氧诱导因子-1α(HIF-1α)是治疗心血管疾病的关键因素。最近,人们越来越关注天然药物对心血管疾病的影响。一些研究表明,HIF-1α是中药治疗心血管疾病的潜在靶点。本研究阐述了HIF-1α在心血管疾病中的调控作用机制,并总结了通过HIF-1α及其信号通路治疗心血管疾病的30种天然药物和3种配方。该研究为心血管疾病的预防和治疗提供了新思路。
{"title":"Potential Cardiovascular Disease Treatment by Natural Drugs Targeting the HIF-1α Factor and its Pathway.","authors":"Weihan Gao, Danyang Wang, Yanmei Shi, Yu Sun, Jinlan Deng, Xiayinan Song, Jie Li, Min Zhang","doi":"10.2174/0113862073331615241018081811","DOIUrl":"10.2174/0113862073331615241018081811","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) remain a key contributor to global morbidity and mortality. Being a vital regulator of hypoxia, hypoxia-inducible factor-1α (HIF-1α) is a crucial player in CVD treatment. Recently, increasing attention has been paid to the effect of natural drugs on CVDs. According to some studies, HIF-1α is a potential target for CVD treatment in traditional Chinese medicine. In this study, we describe the mechanism underlying the regulatory role of HIF-1α in CVDs and summarize 30 natural drugs and 3 formulations for CVD treatment through HIF-1α and its signaling pathway. The study provides new ideas for CVD prevention and treatment.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Research on the Therapeutic Effect of Qizhu Anti Cancer Recipe on Colorectal Cancer Based on RNA Sequencing Analysis. 基于RNA测序分析的杞菊抗癌方对结直肠癌疗效研究
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-11-04 DOI: 10.2174/0113862073322752241016110001
Pingping Zhai, Xueshen Qian, Guangyao Liu, Jingjing Wang, Lei Xie, Decai Tang

Background: Colorectal cancer is one of the common malignant tumors in clinical practice, and traditional Chinese medicine, as an important adjuvant treatment method, plays important roles in the treatment of malignant tumors.

Objective: This study aims to explore the mechanism of action of the Qizhu anti-cancer recipe on colorectal cancer through transcriptome sequencing.

Methods: The control group and Qizhu anti-cancer recipe group were established separately, and sequencing of the cells of the two groups was performed using the Illumina sequencing platform. Two sets of Differentially Expressed Genes (DEGs) were screened using the DESeq2 algorithm, and Principal Component Analysis (PCA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, Disease Ontology (DO), and Protein-Protein Interaction (PPI) were used to comprehensively analyze the molecular functions and signaling pathways enriched by DEGs.

Result: A total of 122 DEGs were identified through differential analysis, including 24 upregulated genes and 98 downregulated genes. GO analysis showed that DEGs were mainly enriched in functions such as alkaline phase activity, ion transport, cell differentiation, etc.; KEGG analysis showed that DEGs were mainly enriched in pathways such as Thiamine metabolism, apoptosis, signaling pathways regulating pluripotency of stem cells, cellular senescence and so on. Reactom analysis showed that DEGs were mainly enriched in response pathways such as EGR1,2,3 bind to the NAB2 promoter, EGR binds ARC gene, EGR-dependent NAB2 gene expression, etc.; DO analysis showed that differentially expressed genes were mainly enriched in diseases such as disease of cellular proliferation, disease of anatomical entity, organ system cancer, etc.; PPI analysis identified key differentially expressed genes, including DDIT3, CHAC1, TRIB3, and ASNS.

Conclusion: Based on transcriptome sequencing and bioinformatics analysis, it was found that the Qizhu anti-cancer recipe may involve DEGs and signaling pathways in the treatment of colorectal cancer. Our study may provide potential drug targets for developing new treatment strategies for colorectal cancer.

背景:大肠癌是临床常见的恶性肿瘤之一,中医药作为重要的辅助治疗手段,在恶性肿瘤治疗中发挥着重要作用:结直肠癌是临床上常见的恶性肿瘤之一,中医药作为一种重要的辅助治疗方法,在恶性肿瘤的治疗中发挥着重要作用:本研究旨在通过转录组测序探讨杞菊抗癌方对结直肠癌的作用机制:方法:分别设立对照组和杞菊抗癌方组,利用Illumina测序平台对两组细胞进行测序。采用DESeq2算法筛选两组差异表达基因(DEGs),并利用主成分分析(PCA)、基因本体(GO)、京都基因组百科全书(KEGG)、反应组(Reactome)、疾病本体(DO)和蛋白-蛋白相互作用(PPI)等方法全面分析DEGs富集的分子功能和信号通路:结果:通过差异分析共鉴定出122个DEGs,包括24个上调基因和98个下调基因。GO分析表明,DEGs主要富集在碱性相活动、离子转运、细胞分化等功能中;KEGG分析表明,DEGs主要富集在硫胺素代谢、细胞凋亡、调控干细胞多能性的信号通路、细胞衰老等通路中。Reactom分析表明,DEGs主要富集在EGR1,2,3结合NAB2启动子、EGR结合ARC基因、EGR依赖NAB2基因表达等反应通路中;DO分析表明,差异表达基因主要富集在细胞增殖疾病、解剖实体疾病、器官系统癌症等疾病中;PPI分析发现了DDIT3、CHAC1、TRIB3和ASNS等关键差异表达基因:结论:基于转录组测序和生物信息学分析发现,杞菊抗癌方可能涉及治疗结直肠癌的DEGs和信号通路。我们的研究可能为开发新的结直肠癌治疗策略提供潜在的药物靶点。
{"title":"Research on the Therapeutic Effect of Qizhu Anti Cancer Recipe on Colorectal Cancer Based on RNA Sequencing Analysis.","authors":"Pingping Zhai, Xueshen Qian, Guangyao Liu, Jingjing Wang, Lei Xie, Decai Tang","doi":"10.2174/0113862073322752241016110001","DOIUrl":"https://doi.org/10.2174/0113862073322752241016110001","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer is one of the common malignant tumors in clinical practice, and traditional Chinese medicine, as an important adjuvant treatment method, plays important roles in the treatment of malignant tumors.</p><p><strong>Objective: </strong>This study aims to explore the mechanism of action of the Qizhu anti-cancer recipe on colorectal cancer through transcriptome sequencing.</p><p><strong>Methods: </strong>The control group and Qizhu anti-cancer recipe group were established separately, and sequencing of the cells of the two groups was performed using the Illumina sequencing platform. Two sets of Differentially Expressed Genes (DEGs) were screened using the DESeq2 algorithm, and Principal Component Analysis (PCA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, Disease Ontology (DO), and Protein-Protein Interaction (PPI) were used to comprehensively analyze the molecular functions and signaling pathways enriched by DEGs.</p><p><strong>Result: </strong>A total of 122 DEGs were identified through differential analysis, including 24 upregulated genes and 98 downregulated genes. GO analysis showed that DEGs were mainly enriched in functions such as alkaline phase activity, ion transport, cell differentiation, etc.; KEGG analysis showed that DEGs were mainly enriched in pathways such as Thiamine metabolism, apoptosis, signaling pathways regulating pluripotency of stem cells, cellular senescence and so on. Reactom analysis showed that DEGs were mainly enriched in response pathways such as EGR1,2,3 bind to the NAB2 promoter, EGR binds ARC gene, EGR-dependent NAB2 gene expression, etc.; DO analysis showed that differentially expressed genes were mainly enriched in diseases such as disease of cellular proliferation, disease of anatomical entity, organ system cancer, etc.; PPI analysis identified key differentially expressed genes, including DDIT3, CHAC1, TRIB3, and ASNS.</p><p><strong>Conclusion: </strong>Based on transcriptome sequencing and bioinformatics analysis, it was found that the Qizhu anti-cancer recipe may involve DEGs and signaling pathways in the treatment of colorectal cancer. Our study may provide potential drug targets for developing new treatment strategies for colorectal cancer.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anchored Chitosan-Functionalized Magnetite Nanoparticles for Crystal Violet Decolorization from Aqueous Samples. 锚定壳聚糖功能化磁铁矿纳米粒子用于水样中水晶紫的脱色。
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-29 DOI: 10.2174/0113862073350298241015071020
Mahsa Bandari, Mohsen Mohammadi Galangash, Shahab Shariati, Atefeh Ghavidast

Introduction: In this research, 3-(triethoxysilyl)propyl isocyanate (TESPIC) functionalized chitosan was successfully synthesized to fabricate silica-coated magnetite nanoparticles (Fe3O4@SiO2-CS MNPs).

Method: The synthesized MNPs were characterized using XRD, FT-IR, SEM, and TEM instruments and were utilized for the decolorization of Crystal Violet cationic dye (CV). The affecting variables controlling CV removal efficiency were investigated using the Taguchi fractional factorial design method (L16 array).

Result: Under the optimized removal conditions (adsorbent amount = 0.12 g (4.8 g L-1), pH = 4, ionic strength = 0.05 mol L-1 NaCl, and 30 min stirring), 98.2% of the CV dye was eliminated. The kinetic and equilibrium adsorption isotherms were explained by the pseudo-second-order kinetic (R2 = 0.999) and Freundlich isotherm models, respectively. MATLAB's fmincon function as an efficient solution was applied in order to compare the Redlich-Peterson three-parametric isotherm model with two-parametric models. Moreover, the Fe3O4@SiO2-CS-TESPIC MNPs showed recyclability and reusability for subsequent runs.

Conclusion: The findings confirmed that these functional MNPs can be considered as proper adsorbents for the removal of CV dye from the aqueous solutions.

引言本研究成功合成了 3-(三乙氧基硅烷基)丙基异氰酸酯(TESPIC)功能化壳聚糖,用于制造硅包覆的磁铁矿纳米粒子(Fe3O4@SiO2-CS MNPs):利用 XRD、FT-IR、SEM 和 TEM 仪器对合成的 MNPs 进行了表征,并将其用于水晶紫阳离子染料(CV)的脱色。采用田口分数因子设计法(L16 阵列)研究了控制 CV 去除效率的影响变量:结果:在优化的去除条件下(吸附剂用量 = 0.12 g (4.8 g L-1),pH = 4,离子强度 = 0.05 mol L-1 NaCl,搅拌 30 分钟),98.2%的 CV 染料被去除。动力学吸附等温线和平衡吸附等温线分别由假二阶动力学模型(R2 = 0.999)和 Freundlich 等温线模型解释。为了比较 Redlich-Peterson 三参数等温线模型和二参数模型,使用了 MATLAB 的 fmincon 函数作为有效的解决方案。此外,Fe3O4@SiO2-CS-TESPIC MNPs 还具有可回收性和可重复使用性:研究结果证实,这些功能性 MNPs 可被视为从水溶液中去除 CV 染料的适当吸附剂。
{"title":"Anchored Chitosan-Functionalized Magnetite Nanoparticles for Crystal Violet Decolorization from Aqueous Samples.","authors":"Mahsa Bandari, Mohsen Mohammadi Galangash, Shahab Shariati, Atefeh Ghavidast","doi":"10.2174/0113862073350298241015071020","DOIUrl":"https://doi.org/10.2174/0113862073350298241015071020","url":null,"abstract":"<p><strong>Introduction: </strong>In this research, 3-(triethoxysilyl)propyl isocyanate (TESPIC) functionalized chitosan was successfully synthesized to fabricate silica-coated magnetite nanoparticles (Fe3O4@SiO2-CS MNPs).</p><p><strong>Method: </strong>The synthesized MNPs were characterized using XRD, FT-IR, SEM, and TEM instruments and were utilized for the decolorization of Crystal Violet cationic dye (CV). The affecting variables controlling CV removal efficiency were investigated using the Taguchi fractional factorial design method (L16 array).</p><p><strong>Result: </strong>Under the optimized removal conditions (adsorbent amount = 0.12 g (4.8 g L-1), pH = 4, ionic strength = 0.05 mol L-1 NaCl, and 30 min stirring), 98.2% of the CV dye was eliminated. The kinetic and equilibrium adsorption isotherms were explained by the pseudo-second-order kinetic (R2 = 0.999) and Freundlich isotherm models, respectively. MATLAB's fmincon function as an efficient solution was applied in order to compare the Redlich-Peterson three-parametric isotherm model with two-parametric models. Moreover, the Fe3O4@SiO2-CS-TESPIC MNPs showed recyclability and reusability for subsequent runs.</p><p><strong>Conclusion: </strong>The findings confirmed that these functional MNPs can be considered as proper adsorbents for the removal of CV dye from the aqueous solutions.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antiproliferative Activity of Cephalotaxus Esters: Overcoming Chemoresistance. 头孢羟氨酯类化合物的抗增殖活性:克服化疗抗药性。
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-23 DOI: 10.2174/0113862073322175240823104921
Vladimir Yong-Gonzalez, Constantin Radu, Paul A Calder, David Shum, David Y Gin, Mark G Frattini, Hakim Djaballah

Introduction: Omacetaxine, a semisynthetic form of Homoharringtonine (HHT), was approved for the treatment of Chronic Myeloid Leukemia (CML). Previously, we have published the synthesis of this natural alkaloid and three of its derivatives: Deoxyharringtonine (DHT), Deoxyhomoharringtonine (DHHT), and Bis(demethyl)-deoxyharringtonine (BDHT), and reported its refractory activity against the HL-60/RV+ cells over-expressing P-glycoprotein 1 (MDR1).

Methods: In this study, we have explored the extent of this resistance by first expanding the panel of established cell lines and using a panel of 21 leukemia patient-derived primary cells.

Results: Herein, we have reported consistent resistance to HTT of K562-derived cells and to mitoxantrone of MES-SA/MX2-derived cells; all of them have been found to overexpress MDR1, while we have found U87MG-ABCG2 and H69AR cells to be very sensitive to HTT. In contrast, DHT, DHHT, and BDHT seemingly overcame this resistance due to the changes made to the acyl chain of HTT, rendering the derivatives less susceptible to efflux. Surprisingly, the leukemia primary cells were very sensitive to HHT and its derivatives with low nanomolar potencies, followed by a new class of CDC7 kinase inhibitors, the anthracycline class of topoisomerase inhibitors, the DNA intercalator actinomycin-D, and the vinca alkaloid class of microtubule inhibitors. The mechanism of cell death induced by HTT and DHHT was found to be mediated via caspase 3 cleavage, leading to apoptosis.

Conclusion: Taken together, our results confirm that HHT is a substrate for MDR1. It opens the door to a new opportunity to clinically evaluate HHT and its derivatives for the treatment of AML and other cancers.

简介奥美他辛(Omacetaxine)是高金刚烷碱(HHT)的一种半合成形式,已被批准用于治疗慢性粒细胞白血病(CML)。此前,我们已发表了这种天然生物碱及其三种衍生物的合成方法:并报道了它对过度表达 P 糖蛋白 1(MDR1)的 HL-60/RV+ 细胞的难治性活性:在这项研究中,我们首先扩大了已建立的细胞系,并使用了 21 种白血病患者来源的原代细胞,从而探索了这种耐药性的程度:结果:在本研究中,我们发现 K562 衍生细胞对 HTT 和 MES-SA/MX2 衍生细胞对米托蒽醌具有一致的耐药性;所有这些细胞都过度表达 MDR1,而我们发现 U87MG-ABCG2 和 H69AR 细胞对 HTT 非常敏感。相比之下,DHT、DHHT 和 BDHT 似乎克服了这种耐药性,因为 HTT 的酰基链发生了变化,使衍生物不易外流。令人惊讶的是,白血病原代细胞对 HHT 及其低纳摩尔效力的衍生物非常敏感,其次是新型 CDC7 激酶抑制剂、蒽环类拓扑异构酶抑制剂、DNA 中间体放线菌素-D 和长春花生物碱类微管抑制剂。HTT和DHHT诱导细胞死亡的机制是通过caspase 3裂解介导细胞凋亡:综上所述,我们的研究结果证实,HHT 是 MDR1 的底物。总之,我们的研究结果证实,HHT 是 MDR1 的底物,这为临床评估 HHT 及其衍生物治疗急性髓细胞性白血病和其他癌症提供了新的契机。
{"title":"Antiproliferative Activity of Cephalotaxus Esters: Overcoming Chemoresistance.","authors":"Vladimir Yong-Gonzalez, Constantin Radu, Paul A Calder, David Shum, David Y Gin, Mark G Frattini, Hakim Djaballah","doi":"10.2174/0113862073322175240823104921","DOIUrl":"https://doi.org/10.2174/0113862073322175240823104921","url":null,"abstract":"<p><strong>Introduction: </strong>Omacetaxine, a semisynthetic form of Homoharringtonine (HHT), was approved for the treatment of Chronic Myeloid Leukemia (CML). Previously, we have published the synthesis of this natural alkaloid and three of its derivatives: Deoxyharringtonine (DHT), Deoxyhomoharringtonine (DHHT), and Bis(demethyl)-deoxyharringtonine (BDHT), and reported its refractory activity against the HL-60/RV+ cells over-expressing P-glycoprotein 1 (MDR1).</p><p><strong>Methods: </strong>In this study, we have explored the extent of this resistance by first expanding the panel of established cell lines and using a panel of 21 leukemia patient-derived primary cells.</p><p><strong>Results: </strong>Herein, we have reported consistent resistance to HTT of K562-derived cells and to mitoxantrone of MES-SA/MX2-derived cells; all of them have been found to overexpress MDR1, while we have found U87MG-ABCG2 and H69AR cells to be very sensitive to HTT. In contrast, DHT, DHHT, and BDHT seemingly overcame this resistance due to the changes made to the acyl chain of HTT, rendering the derivatives less susceptible to efflux. Surprisingly, the leukemia primary cells were very sensitive to HHT and its derivatives with low nanomolar potencies, followed by a new class of CDC7 kinase inhibitors, the anthracycline class of topoisomerase inhibitors, the DNA intercalator actinomycin-D, and the vinca alkaloid class of microtubule inhibitors. The mechanism of cell death induced by HTT and DHHT was found to be mediated via caspase 3 cleavage, leading to apoptosis.</p><p><strong>Conclusion: </strong>Taken together, our results confirm that HHT is a substrate for MDR1. It opens the door to a new opportunity to clinically evaluate HHT and its derivatives for the treatment of AML and other cancers.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring You-gui Pill for the Treatment of Diabetic Erectile Dysfunction: Data Mining Analysis, Network Pharmacology and Experiments In Vitro. 探索治疗糖尿病勃起功能障碍的 "友桂丸":数据挖掘分析、网络药理学和体外实验。
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-22 DOI: 10.2174/0113862073329189241014102457
Jiaqi Chen, Yanan Gao, Yanqiu Zhang, Yue Sun, Yue Jiang, Yong Yang, Mingxing Wang

Introduction: The You-gui pill (YGP) is a classical compound used for treating antidiabetic erectile dysfunction (DMED). However, the specific active ingredients responsible for its effects on DMED and their mechanisms remain unclear.

Methods: In this paper, we used data mining techniques to analyze high-frequency herbs and herb combinations used in Chinese medicine for the treatment of DMED based on existing literature. Using network pharmacology to study the active components and mechanism of action of YGP against DMED, molecular docking was used to analyze the interactions of the active components with major structural proteins, nonstructural proteins, and mutants. Also, the therapeutic effect of YGP on hyperglycemic modelling and its underlying mechanisms were experimentally validated in CCEC cells by analyzing the expression of its relevant target mRNAs.

Results: Network pharmacological analysis identified the three core components of YGP as quercetin, kaempferol, and β-sitosterol, and constructed a PPI network map of common targets of YGP and DMED, which included HIF-1α, ALB, Bcl-2, INS, IL-1β, IL-6, TNF-α, CASP3, and TP53. Combined with molecular docking results, these targets had a strong binding affinity between them and the active ingredient compounds, with the highest affinity for HIF-1α and TNF-α. During the in vitro cellular assay validation, the HIF-1α, ALB, Bcl-2, TNF-α, and IL-6 mRNA in CCECs cells showed positive regulation after YGP intervention.

Conclusion: The combination of "data mining - network pharmacology - molecular docking - experimental validation" provides a powerful methodological basis for the study of the main active components and mechanism of action of YGP against DMED, as well as the development and application of the drug.

简介右归丸(YGP)是一种用于治疗抗糖尿病勃起功能障碍(DMED)的经典复方制剂。然而,该药对勃起功能障碍的具体有效成分及其作用机制仍不清楚:本文在现有文献的基础上,利用数据挖掘技术分析了中医治疗 DMED 的高频中草药和中草药组合。利用网络药理学研究YGP对DMED的活性成分和作用机制,利用分子对接分析活性成分与主要结构蛋白、非结构蛋白和突变体的相互作用。此外,还通过分析 YGP 相关靶 mRNA 的表达,在 CCEC 细胞中实验验证了 YGP 对高血糖模型的治疗效果及其内在机制:网络药理学分析确定了YGP的三种核心成分为槲皮素、山奈酚和β-谷甾醇,并构建了YGP和DMED共同靶点的PPI网络图,包括HIF-1α、ALB、Bcl-2、INS、IL-1β、IL-6、TNF-α、CASP3和TP53。结合分子对接结果,这些靶点与活性成分化合物之间具有很强的结合亲和力,其中与 HIF-1α 和 TNF-α 的亲和力最高。在体外细胞检测验证中,YGP干预后,CCECs细胞中的HIF-1α、ALB、Bcl-2、TNF-α和IL-6 mRNA均呈现正向调节:结论:"数据挖掘-网络药理学-分子对接-实验验证 "相结合的方法为研究YGP抗DMED的主要活性成分和作用机制以及该药物的开发和应用提供了强有力的方法学基础。
{"title":"Exploring You-gui Pill for the Treatment of Diabetic Erectile Dysfunction: Data Mining Analysis, Network Pharmacology and Experiments In Vitro.","authors":"Jiaqi Chen, Yanan Gao, Yanqiu Zhang, Yue Sun, Yue Jiang, Yong Yang, Mingxing Wang","doi":"10.2174/0113862073329189241014102457","DOIUrl":"https://doi.org/10.2174/0113862073329189241014102457","url":null,"abstract":"<p><strong>Introduction: </strong>The You-gui pill (YGP) is a classical compound used for treating antidiabetic erectile dysfunction (DMED). However, the specific active ingredients responsible for its effects on DMED and their mechanisms remain unclear.</p><p><strong>Methods: </strong>In this paper, we used data mining techniques to analyze high-frequency herbs and herb combinations used in Chinese medicine for the treatment of DMED based on existing literature. Using network pharmacology to study the active components and mechanism of action of YGP against DMED, molecular docking was used to analyze the interactions of the active components with major structural proteins, nonstructural proteins, and mutants. Also, the therapeutic effect of YGP on hyperglycemic modelling and its underlying mechanisms were experimentally validated in CCEC cells by analyzing the expression of its relevant target mRNAs.</p><p><strong>Results: </strong>Network pharmacological analysis identified the three core components of YGP as quercetin, kaempferol, and β-sitosterol, and constructed a PPI network map of common targets of YGP and DMED, which included HIF-1α, ALB, Bcl-2, INS, IL-1β, IL-6, TNF-α, CASP3, and TP53. Combined with molecular docking results, these targets had a strong binding affinity between them and the active ingredient compounds, with the highest affinity for HIF-1α and TNF-α. During the in vitro cellular assay validation, the HIF-1α, ALB, Bcl-2, TNF-α, and IL-6 mRNA in CCECs cells showed positive regulation after YGP intervention.</p><p><strong>Conclusion: </strong>The combination of \"data mining - network pharmacology - molecular docking - experimental validation\" provides a powerful methodological basis for the study of the main active components and mechanism of action of YGP against DMED, as well as the development and application of the drug.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
To Reveal the Potential Mechanism of Quercetin against NSCLC Based on Network Pharmacology and Experimental Validation. 基于网络药理学和实验验证,揭示槲皮素抗 NSCLC 的潜在机制。
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-21 DOI: 10.2174/0113862073332751241008072644
Baibai Ye, Ping Chen, Cheng Lin, Xinyu Liu, Jia Chen, Chenning Zhang, Linfu Li

Purpose: This study aimed to initially clarify the potential mechanism of quercetin in the treatment of non-small cell lung cancer (NSCLC) based on network pharmacology, molecular docking and in vitro experiments.

Method: TCMSP, SwissTargetPrediction, TCMIP, STITCH, and ETCM databases were applied to obtain the targets of quercetin. NSCLC-related targets were retrieved from GeneCards, OMIM, PharmGKB, TTD, and NCBI databases. Their intersection targets were imported into the STRING database to construct a protein-protein interaction (PPI) network and core targets were identified through the Cytoscape 3.10.0 soft and the CytoHubba tool. Furthermore, Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersection targets. A compound-targetspathways network was subsequently constructed to screen for key targets and pathways. Molecular docking was performed with Discovery Studio software to verify the interactions between quercetin and core targets. In vitro validations were conducted employing CCK-8 assays, flow cytometry, and Western blotting (WB).

Results: 193 potential targets of quercetin for treating NSCLC were obtained. The top ten core targets identified within the PPI network included TP53, HSP90AA1, AKT1, JUN, SRC, EGFR, ACTB, TNF, MAPK1, and VEGFA. GO analysis yielded 2319 items, and KEGG analysis resulted in 211 enriched pathways. Molecular docking results demonstrated a high affinity of quercetin towards the core targets. Based on the compound-targets-pathways network and molecular docking, the PI3K/AKT/P53 pathway and its key-related proteins (PIK3R1, AKT1, and TP53) were selected for further validation. Quercetin(20 and 40 μg/mL) significantly decreased the viability of A549 NSCLC cells but not BEAS-2B normal cells via CCK-8 assays. Flow cytometry and WB analyses further corroborated that quercetin could promote apoptosis of A549 cells by downregulating and upregulating the expression of Bcl-2 and Bax (P<0.05), respectively. Notably, quercetin did not significantly alter the total protein levels of PI3K, AKT, and P53 but downregulated the phosphorylation levels of PI3K and AKT (P<0.05) and upregulated the phosphorylation level of P53 (P<0.05).

Conclusion: Quercetin exhibits therapeutic potential in NSCLC by regulating the PI3K/AKT/P53 pathway to promote cell apoptosis.

目的:本研究旨在基于网络药理学、分子对接和体外实验,初步阐明槲皮素治疗非小细胞肺癌(NSCLC)的潜在机制:方法:应用 TCMSP、SwissTargetPrediction、TCMIP、STITCH 和 ETCM 数据库获取槲皮素的靶点。从 GeneCards、OMIM、PharmGKB、TTD 和 NCBI 数据库中检索 NSCLC 相关靶标。通过Cytoscape 3.10.0软件和CytoHubba工具确定了核心靶点。此外,还对交叉靶点进行了基因本体(GO)功能分析和京都基因组百科全书(KEGG)通路富集分析。随后构建了化合物-靶点-通路网络,以筛选关键靶点和通路。利用 Discovery Studio 软件进行了分子对接,以验证槲皮素与核心靶点之间的相互作用。利用 CCK-8 检测法、流式细胞术和 Western 印迹法(WB)进行了体外验证:结果:获得了193个槲皮素治疗NSCLC的潜在靶点。在PPI网络中发现的前十大核心靶点包括TP53、HSP90AA1、AKT1、JUN、SRC、表皮生长因子受体、ACTB、TNF、MAPK1和VEGFA。GO 分析产生了 2319 个项目,KEGG 分析产生了 211 个富集通路。分子对接结果表明,槲皮素对核心靶点具有很高的亲和力。根据化合物-靶标-通路网络和分子对接,选择了 PI3K/AKT/P53 通路及其关键相关蛋白(PIK3R1、AKT1 和 TP53)进行进一步验证。通过CCK-8测定,槲皮素(20和40 μg/mL)能显著降低A549 NSCLC细胞的活力,但不能降低BEAS-2B正常细胞的活力。流式细胞术和WB分析进一步证实,槲皮素可通过下调和上调Bcl-2和Bax的表达来促进A549细胞的凋亡:槲皮素通过调节PI3K/AKT/P53通路促进细胞凋亡,对NSCLC具有治疗潜力。
{"title":"To Reveal the Potential Mechanism of Quercetin against NSCLC Based on Network Pharmacology and Experimental Validation.","authors":"Baibai Ye, Ping Chen, Cheng Lin, Xinyu Liu, Jia Chen, Chenning Zhang, Linfu Li","doi":"10.2174/0113862073332751241008072644","DOIUrl":"https://doi.org/10.2174/0113862073332751241008072644","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to initially clarify the potential mechanism of quercetin in the treatment of non-small cell lung cancer (NSCLC) based on network pharmacology, molecular docking and in vitro experiments.</p><p><strong>Method: </strong>TCMSP, SwissTargetPrediction, TCMIP, STITCH, and ETCM databases were applied to obtain the targets of quercetin. NSCLC-related targets were retrieved from GeneCards, OMIM, PharmGKB, TTD, and NCBI databases. Their intersection targets were imported into the STRING database to construct a protein-protein interaction (PPI) network and core targets were identified through the Cytoscape 3.10.0 soft and the CytoHubba tool. Furthermore, Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersection targets. A compound-targetspathways network was subsequently constructed to screen for key targets and pathways. Molecular docking was performed with Discovery Studio software to verify the interactions between quercetin and core targets. In vitro validations were conducted employing CCK-8 assays, flow cytometry, and Western blotting (WB).</p><p><strong>Results: </strong>193 potential targets of quercetin for treating NSCLC were obtained. The top ten core targets identified within the PPI network included TP53, HSP90AA1, AKT1, JUN, SRC, EGFR, ACTB, TNF, MAPK1, and VEGFA. GO analysis yielded 2319 items, and KEGG analysis resulted in 211 enriched pathways. Molecular docking results demonstrated a high affinity of quercetin towards the core targets. Based on the compound-targets-pathways network and molecular docking, the PI3K/AKT/P53 pathway and its key-related proteins (PIK3R1, AKT1, and TP53) were selected for further validation. Quercetin(20 and 40 μg/mL) significantly decreased the viability of A549 NSCLC cells but not BEAS-2B normal cells via CCK-8 assays. Flow cytometry and WB analyses further corroborated that quercetin could promote apoptosis of A549 cells by downregulating and upregulating the expression of Bcl-2 and Bax (P<0.05), respectively. Notably, quercetin did not significantly alter the total protein levels of PI3K, AKT, and P53 but downregulated the phosphorylation levels of PI3K and AKT (P<0.05) and upregulated the phosphorylation level of P53 (P<0.05).</p><p><strong>Conclusion: </strong>Quercetin exhibits therapeutic potential in NSCLC by regulating the PI3K/AKT/P53 pathway to promote cell apoptosis.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Steiner 3-Wiener Index of Zigzag Polyhex Nanotubes. 之字形聚己纳米管的 Steiner 3-Wiener 指数。
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-15 DOI: 10.2174/0113862073329237240929214731
Medha Itagi Huilgol, P HShobha HShobha, H Jayakrishna Udupa, Ismail Naci Cangul

Background: Let G be a connected graph and S be a k element subset of the vertex set V(G) of G. Steiner distance is a natural generalization of the usual graph distance. The Steiner-k distance dG(S) between the vertices of S is the minimum size among all connected subgraphs whose vertex set contains S. The generalized indices based on Steiner distances have several applications in the real world. It is a well-known fact that "Steiner Problem" is NP-complete and hence any parameter based on Steiner distance is also an NP problem.

Objective: The objective of this work is to determine the Steiner 3-Wiener index for an important chemical structure called the zigzag polyhex nanotube.

Methods: In this paper, we present an algorithm for computing the Steiner 3-Wiener index (SW3) for zigzag polyhex nanotubes. The developed algorithm addresses the complexities associated with exponential increments in the number of vertices as the nanotube's circumference or length expands. The obtained SW3 values for zigzag polyhex nanotubes can be used for Quantitative Structure-Activity Relationship (QSAR) and Quantitative Structure-Property Relationship (QSPR) analyses.

Results: We have presented an algorithm and listed the numerical values of SW3 for various parameters of circumference and length of a zigzag polyhex nanotube to facilitate their utilization in QSAR/ QSPR analyses. We have obtained the time complexity for the algorithm, which shows that the SW3 values are computationally intensive. To explain this complex nature, we have used multiple linear regression to fit log SW3 values corresponding to log p and log q, the radius and length of a nanotube.

Conclusion: The algorithm addresses the complexities associated with the exponential increase in vertices as the nanotube's circumference or length expands. Furthermore, we provide SW3 values for various parameter combinations up to circumference or length 17, and a general relation to determine the value of SW3, facilitating its utilization in real-world applications. These values serve as crucial descriptors for understanding the structural nuances of zigzag polyhex nanotubes, that find applications in material science, drug design, drug discovery, etc.

背景:设 G 是连通图,S 是 G 的顶点集 V(G) 的 k 元素子集。斯坦纳距离是通常图距离的自然概括。S 的顶点之间的 Steiner-k 距离 dG(S) 是顶点集包含 S 的所有连通子图中的最小尺寸。众所周知,"斯坦纳问题 "是一个 NP-完全问题,因此任何基于斯坦纳距离的参数也是一个 NP 问题:这项工作的目的是确定一种重要化学结构--人字形聚己纳米管--的斯坦纳 3 维纳指数:本文提出了一种计算人字形多六边形纳米管的 Steiner 3-Wiener 指数 (SW3) 的算法。所开发的算法解决了随着纳米管周长或长度的增加,顶点数量呈指数增长的复杂性问题。获得的人字形多六边形纳米管 SW3 值可用于定量结构-活性关系(QSAR)和定量结构-性能关系(QSPR)分析:我们提出了一种算法,并列出了 "人 "字形聚合纳米管周长和长度的各种参数的 SW3 数值,以方便在 QSAR/ QSPR 分析中使用。我们获得了该算法的时间复杂度,这表明 SW3 值的计算量很大。为了解释这种复杂性,我们使用了多元线性回归法来拟合与纳米管的半径和长度对数 p 和 q 相对应的 SW3 对数值:该算法解决了随着纳米管周长或长度的增加,顶点呈指数增长的复杂性问题。此外,我们还为周长或长度为 17 的各种参数组合提供了 SW3 值,并提供了确定 SW3 值的一般关系式,便于在实际应用中使用。这些值是了解人字形多六边形纳米管结构细微差别的关键描述符,可应用于材料科学、药物设计、药物发现等领域。
{"title":"Steiner 3-Wiener Index of Zigzag Polyhex Nanotubes.","authors":"Medha Itagi Huilgol, P HShobha HShobha, H Jayakrishna Udupa, Ismail Naci Cangul","doi":"10.2174/0113862073329237240929214731","DOIUrl":"https://doi.org/10.2174/0113862073329237240929214731","url":null,"abstract":"<p><strong>Background: </strong>Let G be a connected graph and S be a k element subset of the vertex set V(G) of G. Steiner distance is a natural generalization of the usual graph distance. The Steiner-k distance dG(S) between the vertices of S is the minimum size among all connected subgraphs whose vertex set contains S. The generalized indices based on Steiner distances have several applications in the real world. It is a well-known fact that \"Steiner Problem\" is NP-complete and hence any parameter based on Steiner distance is also an NP problem.</p><p><strong>Objective: </strong>The objective of this work is to determine the Steiner 3-Wiener index for an important chemical structure called the zigzag polyhex nanotube.</p><p><strong>Methods: </strong>In this paper, we present an algorithm for computing the Steiner 3-Wiener index (SW3) for zigzag polyhex nanotubes. The developed algorithm addresses the complexities associated with exponential increments in the number of vertices as the nanotube's circumference or length expands. The obtained SW3 values for zigzag polyhex nanotubes can be used for Quantitative Structure-Activity Relationship (QSAR) and Quantitative Structure-Property Relationship (QSPR) analyses.</p><p><strong>Results: </strong>We have presented an algorithm and listed the numerical values of SW3 for various parameters of circumference and length of a zigzag polyhex nanotube to facilitate their utilization in QSAR/ QSPR analyses. We have obtained the time complexity for the algorithm, which shows that the SW3 values are computationally intensive. To explain this complex nature, we have used multiple linear regression to fit log SW3 values corresponding to log p and log q, the radius and length of a nanotube.</p><p><strong>Conclusion: </strong>The algorithm addresses the complexities associated with the exponential increase in vertices as the nanotube's circumference or length expands. Furthermore, we provide SW3 values for various parameter combinations up to circumference or length 17, and a general relation to determine the value of SW3, facilitating its utilization in real-world applications. These values serve as crucial descriptors for understanding the structural nuances of zigzag polyhex nanotubes, that find applications in material science, drug design, drug discovery, etc.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Wuzi-Yanzong-Wan Prevents the Defect of Cell-Cell Junctions between Sertoli-Germ Cells by Up-Regulating the Expression of TAp73. 五子衍宗丸通过上调 TAp73 的表达防止 Sertoli-Germ 细胞间的细胞-细胞连接缺陷
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-15 DOI: 10.2174/0113862073328011241004110538
Li Li, Min Pan, Ziao Liu, Hongsu Zhao, Fengqing Xu, Xiaohui Tong, Yajuan Wang, Bin Chen, Lihua Yu, Tongsheng Wang

Background: The TAp73 gene is an anti-cancer gene that also affects the junction between Sertoli and germ cells. Inhibition of this gene causes infertility in male mice. Our previous research proved that Wuzi-Yanzong-Wan (WZYZW) can protect spermatogenesis and maturation by preventing TAp73 inhibition.

Objective: This study aimed to investigate the effect of drug-containing serum of WZYZW on the defect of cell-cell junctions in the Sertoli-germ cells co-culture system in vitro.

Methods: LC-HRMS was used to analyze the content of active ingredients in WZYZWmedicated serum. Then, primary extraction and co-culture of germ cells and Sertoli cells were carried out. Co-cultured cells were added with PFT-α to induce the TAp73 inhibition model, with WZYZW-medicated serum at 2.5%, 5%, and 10% treated in parallel. Sloughing of germ cells from Sertoli cells was calculated. Transmission electron microscopy (TEM), Immunofluorescence, qRT-PCR, and western blot methods were employed.

Results: The drug-containing serum of WZYZW contained schisandrin, hyperoside, geniposidic acid, ellagic acid, and quercetin. Using TEM assay, we observed restoration of the desmosomelike (Des), tight junctions (TJ), and basal ectoplasmic specialization (ES) structure following WZYZW treatment. WZYZW caused inhibition of peptidase and protease inhibitors (tissue inhibitor of metalloproteinase-1 (TIMP1), Serpina3n) by immunofluorescence analysis. Western blot and qRT-PCR analysis revealed that WZYZW was able to ameliorate the expressions of peptidase and protease inhibitors and cell adhesion factors, such as TAp73, TIMP1, Serpina3n, Desmocollin-3, N-cadherin, and Nectin-2.

Conclusion: WZYZW-medicated serum could prevent the defect of cell-cell junctions between Sertoli-germ cells co-culture system in vitro by up-regulating the expression of TAp73.

背景:TAp73 基因是一种抗癌基因,也会影响 Sertoli 细胞和生殖细胞之间的连接。抑制该基因会导致雄性小鼠不育。我们之前的研究证明,五子衍宗丸(WZYZW)可通过阻止 TAp73 的抑制作用来保护精子发生和成熟:本研究旨在探讨五子衍宗丸含药血清对体外Sertoli-germ细胞共培养系统中细胞-细胞连接缺陷的影响:方法:采用LC-HRMS分析WZYZW药用血清中有效成分的含量。然后,对生殖细胞和 Sertoli 细胞进行原代提取和共培养。在共培养细胞中加入 PFT-α,诱导 TAp73 抑制模型,并同时处理 2.5%、5% 和 10%的 WZYZW 给药血清。计算Sertoli细胞中生殖细胞的脱落情况。研究采用了透射电子显微镜(TEM)、免疫荧光、qRT-PCR和Western印迹等方法:结果:WZYZW的含药血清中含有五味子素、金丝桃苷、玄参苷酸、鞣花酸和槲皮素。通过TEM检测,我们观察到WZYZW处理后的脱丝体(Des)、紧密连接(TJ)和基底外质特化(ES)结构得到恢复。通过免疫荧光分析,WZYZW 可抑制肽酶和蛋白酶抑制剂(金属蛋白酶组织抑制剂-1(TIMP1)、Serpina3n)。Western印迹和qRT-PCR分析显示,WZYZW能够改善肽酶和蛋白酶抑制剂以及TAp73、TIMP1、Serpina3n、Desmocollin-3、N-cadherin和Nectin-2等细胞粘附因子的表达:结论:WZYZW药用血清可通过上调TAp73的表达,防止体外Sertol-germ细胞共培养系统细胞间连接的缺陷。
{"title":"Wuzi-Yanzong-Wan Prevents the Defect of Cell-Cell Junctions between Sertoli-Germ Cells by Up-Regulating the Expression of TAp73.","authors":"Li Li, Min Pan, Ziao Liu, Hongsu Zhao, Fengqing Xu, Xiaohui Tong, Yajuan Wang, Bin Chen, Lihua Yu, Tongsheng Wang","doi":"10.2174/0113862073328011241004110538","DOIUrl":"https://doi.org/10.2174/0113862073328011241004110538","url":null,"abstract":"<p><strong>Background: </strong>The TAp73 gene is an anti-cancer gene that also affects the junction between Sertoli and germ cells. Inhibition of this gene causes infertility in male mice. Our previous research proved that Wuzi-Yanzong-Wan (WZYZW) can protect spermatogenesis and maturation by preventing TAp73 inhibition.</p><p><strong>Objective: </strong>This study aimed to investigate the effect of drug-containing serum of WZYZW on the defect of cell-cell junctions in the Sertoli-germ cells co-culture system in vitro.</p><p><strong>Methods: </strong>LC-HRMS was used to analyze the content of active ingredients in WZYZWmedicated serum. Then, primary extraction and co-culture of germ cells and Sertoli cells were carried out. Co-cultured cells were added with PFT-α to induce the TAp73 inhibition model, with WZYZW-medicated serum at 2.5%, 5%, and 10% treated in parallel. Sloughing of germ cells from Sertoli cells was calculated. Transmission electron microscopy (TEM), Immunofluorescence, qRT-PCR, and western blot methods were employed.</p><p><strong>Results: </strong>The drug-containing serum of WZYZW contained schisandrin, hyperoside, geniposidic acid, ellagic acid, and quercetin. Using TEM assay, we observed restoration of the desmosomelike (Des), tight junctions (TJ), and basal ectoplasmic specialization (ES) structure following WZYZW treatment. WZYZW caused inhibition of peptidase and protease inhibitors (tissue inhibitor of metalloproteinase-1 (TIMP1), Serpina3n) by immunofluorescence analysis. Western blot and qRT-PCR analysis revealed that WZYZW was able to ameliorate the expressions of peptidase and protease inhibitors and cell adhesion factors, such as TAp73, TIMP1, Serpina3n, Desmocollin-3, N-cadherin, and Nectin-2.</p><p><strong>Conclusion: </strong>WZYZW-medicated serum could prevent the defect of cell-cell junctions between Sertoli-germ cells co-culture system in vitro by up-regulating the expression of TAp73.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulation of Curcumin on Follicle Initiation Rate in Diminished Ovarian Reserve. 姜黄素对卵巢储备功能减退时卵泡启动率的调节作用
IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-14 DOI: 10.2174/0113862073327087240926065629
Wanjing Li, Jinbang Xu, Jingyi Wang, Junxin Zhang, Disi Deng

Aim: To study the mechanism by which curcumin regulates ovarian primordial follicle initiation in rats with triptolide-induced diminished ovarian reserve (DOR).

Methods: An in vitro gelatin sponge culture was performed on 3-day-old rat ovaries. After the establishment of the DOR model with triptolide, curcumin was administered for 3 days. Histological analysis and follicle counts were performed using H&E staining. ELISA detection of ovarian hormones in the culture medium (E2, FSH and LH), western blotting and Q-PCR for protein and mRNA expression (LTCONS-00011173, TGF-β1, Smad1, AMH, PTEN and GDF-9).

Results: Ovarian primordial and growing follicles increased significantly after curcumin intervention (p < 0.05), FSH/LH and E2 levels were increased significantly (p < 0.05). Curcumin also significantly decreased the expression of LTCONS-00011173. Meanwhile, curcumin increased the expression of TGF-β, AMH, and GDF-9 (p < 0.05). In addition, curcumin increased Smad1 gene expression and protein phosphorylation in the ovary on the one hand (p < 0.05), but inhibited Smad1 and p-Smad1 protein expression on the other hand (p < 0.05). Moreover, curcumin decreased PTEN protein and mRNA expression (p < 0.05).

Conclusion: Curcumin activates primordial follicles in DOR model rats through TGF-β1 and downstream AMH signaling pathways and may limit follicle exhaustion through LncRNA.

目的:研究姜黄素调节三苯氧胺诱导的卵巢储备功能减退(DOR)大鼠卵巢原始卵泡启动的机制:方法:对3日龄大鼠卵巢进行体外明胶海绵培养。方法:对 3 天大的大鼠卵巢进行体外明胶海绵培养。使用 H&E 染色法进行组织学分析和卵泡计数。ELISA检测培养基中的卵巢激素(E2、FSH和LH),Western印迹和Q-PCR检测蛋白和mRNA表达(LTCONS-00011173、TGF-β1、Smad1、AMH、PTEN和GDF-9):结果:姜黄素干预后,卵巢原始卵泡和生长卵泡明显增加(P < 0.05),FSH/LH和E2水平明显增加(P < 0.05)。姜黄素还明显降低了LTCONS-00011173的表达。同时,姜黄素增加了 TGF-β、AMH 和 GDF-9 的表达(p < 0.05)。此外,姜黄素一方面增加了卵巢中Smad1基因的表达和蛋白磷酸化(p < 0.05),另一方面抑制了Smad1和p-Smad1蛋白的表达(p < 0.05)。此外,姜黄素还降低了PTEN蛋白和mRNA的表达(p < 0.05):姜黄素通过TGF-β1和下游AMH信号通路激活DOR模型大鼠的原始卵泡,并可通过LncRNA限制卵泡衰竭。
{"title":"Regulation of Curcumin on Follicle Initiation Rate in Diminished Ovarian Reserve.","authors":"Wanjing Li, Jinbang Xu, Jingyi Wang, Junxin Zhang, Disi Deng","doi":"10.2174/0113862073327087240926065629","DOIUrl":"https://doi.org/10.2174/0113862073327087240926065629","url":null,"abstract":"<p><strong>Aim: </strong>To study the mechanism by which curcumin regulates ovarian primordial follicle initiation in rats with triptolide-induced diminished ovarian reserve (DOR).</p><p><strong>Methods: </strong>An in vitro gelatin sponge culture was performed on 3-day-old rat ovaries. After the establishment of the DOR model with triptolide, curcumin was administered for 3 days. Histological analysis and follicle counts were performed using H&E staining. ELISA detection of ovarian hormones in the culture medium (E2, FSH and LH), western blotting and Q-PCR for protein and mRNA expression (LTCONS-00011173, TGF-β1, Smad1, AMH, PTEN and GDF-9).</p><p><strong>Results: </strong>Ovarian primordial and growing follicles increased significantly after curcumin intervention (p < 0.05), FSH/LH and E2 levels were increased significantly (p < 0.05). Curcumin also significantly decreased the expression of LTCONS-00011173. Meanwhile, curcumin increased the expression of TGF-β, AMH, and GDF-9 (p < 0.05). In addition, curcumin increased Smad1 gene expression and protein phosphorylation in the ovary on the one hand (p < 0.05), but inhibited Smad1 and p-Smad1 protein expression on the other hand (p < 0.05). Moreover, curcumin decreased PTEN protein and mRNA expression (p < 0.05).</p><p><strong>Conclusion: </strong>Curcumin activates primordial follicles in DOR model rats through TGF-β1 and downstream AMH signaling pathways and may limit follicle exhaustion through LncRNA.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Combinatorial chemistry & high throughput screening
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1