Background: Biejiaruangan capsule (BJRGC) is a commonly used traditional Chinese medicine preparation for treating oftreating liver fibrosis (LF), but its specific molecular mechanism is unclear. This study used mass spectrometry, network pharmacology and experimental verification to explore the mechanism of BJRGC against LF.
Methods: Ultrahigh-performance liquid chromatography-quadrupole-exactive-orbitrap-mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS) and network pharmacology were employed to identify and screen the potential components, targets, and signaling pathways of BJRGC against LF. The interaction between the active ingredients and targets was validated using molecular docking. Finally, 5-ethynyl-2'-deoxyuridine (EDU) staining, western blotting (WB), and flow cytometry (FCM) were utilized to further verify the mechanism of BJRGC against LF.
Results: A total of 9 prototype components of BJRGC were identified in serum, most derived from iridoid glycosides and triterpenes in Gardenia jasminoides Ellis and Artemisia scoparia Waldst.et Kit. Network pharmacology predicts that medicine prototype components in serum mostly influence targets such as CDK2, CDK6, and PIK3CG, with the key route being the PI3K/AKT signaling pathway. Molecular docking showed that the major components have good binding properties with key target proteins. The experimental results showed that BJRGC could inhibit the proliferation of HSCs, induce cell cycle arrest and reduce the protein expression of CDK2, CDK6 and PIK3CG.
Conclusions: BJRGC can inhibit the proliferation of HSCs by targeting the protein expression of CDK2, CDK6, and PIK3CG in the PI3K/AKT signaling pathway through its prototype components, such as hyperoside, tumulosic acid, and hederagenin, thereby alleviating LF disease.
{"title":"Effective Components and Molecular Mechanism of Biejiaruangan Capsule Against Liver Fibrosis: High-resolution Mass Spectrometry, Network Pharmacological Analysis and Experimental Verification.","authors":"Kefeng Cao, Hui Jiang, Lili Zhang, Chang Fan, Zhigang Feng, Biao Li, Laicheng Song, Qun Zhang","doi":"10.2174/0113862073338867240930031800","DOIUrl":"https://doi.org/10.2174/0113862073338867240930031800","url":null,"abstract":"<p><strong>Background: </strong>Biejiaruangan capsule (BJRGC) is a commonly used traditional Chinese medicine preparation for treating oftreating liver fibrosis (LF), but its specific molecular mechanism is unclear. This study used mass spectrometry, network pharmacology and experimental verification to explore the mechanism of BJRGC against LF.</p><p><strong>Methods: </strong>Ultrahigh-performance liquid chromatography-quadrupole-exactive-orbitrap-mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS) and network pharmacology were employed to identify and screen the potential components, targets, and signaling pathways of BJRGC against LF. The interaction between the active ingredients and targets was validated using molecular docking. Finally, 5-ethynyl-2'-deoxyuridine (EDU) staining, western blotting (WB), and flow cytometry (FCM) were utilized to further verify the mechanism of BJRGC against LF.</p><p><strong>Results: </strong>A total of 9 prototype components of BJRGC were identified in serum, most derived from iridoid glycosides and triterpenes in Gardenia jasminoides Ellis and Artemisia scoparia Waldst.et Kit. Network pharmacology predicts that medicine prototype components in serum mostly influence targets such as CDK2, CDK6, and PIK3CG, with the key route being the PI3K/AKT signaling pathway. Molecular docking showed that the major components have good binding properties with key target proteins. The experimental results showed that BJRGC could inhibit the proliferation of HSCs, induce cell cycle arrest and reduce the protein expression of CDK2, CDK6 and PIK3CG.</p><p><strong>Conclusions: </strong>BJRGC can inhibit the proliferation of HSCs by targeting the protein expression of CDK2, CDK6, and PIK3CG in the PI3K/AKT signaling pathway through its prototype components, such as hyperoside, tumulosic acid, and hederagenin, thereby alleviating LF disease.</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":"142459767","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}
Objective: In this study, we aimed to identify novel biomarkers related to Peripheral Neural Invasion (PNI) in head and neck squamous cell carcinoma (HNSCC).
Methods: The PNI-related differentially expressed mRNAs (DE-mRNAs) in HNSCC were identified to construct a PNI-related risk score model. The expression level and ROC curve for Tachykinin Precursor 1 (TAC1) were calculated. Additionally, two kinds of in vitro models of PNI were established for investigation, including the Matrigel-PNI model and the Transwell-PNI model. Furthermore, the transcription factor of the TAC1 was predicted and verified by qRTPCR.
Results: A total of 139 DE-mRNAs were identified in PNI positive and negative groups of HNSCC patients. The risk-score marker model incorporating 20 PNI-related DE-mRNAs was established. The TAC1 was identified as a potential highly expressed PNI marker, which exhibited good performance in predicting PNI events. Patients with higher TAC1 expressions demonstrated significantly shorter survival rates compared to those with lower TAC1 expressions in HNSCC. Besides, the knockdown of TAC1 significantly repressed neural invasion in HNSCC cells in vitro, according to the Matrigel-PNI model and Transwell-PNI model. Furthermore, KLF15 was predicted and verified as a transcription activator of TAC1 in HNSCC.
Conclusion: This study highlights that the activation of KLF15 transcription of TAC1 promotes PNI in HNSCC cells, which provides guidance regarding the molecular diagnosis of PNI in HNSCC cells.
{"title":"KLF15 Transcription Activated Tachykinin Precursor 1 to Induce Perineural Invasion in Head and Neck Squamous Cell Carcinoma.","authors":"Yupeng Shen, Yong Shi, Xin Liu, Ming Zhang, Liang Zhou, Chengzhi Xu","doi":"10.2174/0113862073331908241002044719","DOIUrl":"https://doi.org/10.2174/0113862073331908241002044719","url":null,"abstract":"<p><strong>Objective: </strong>In this study, we aimed to identify novel biomarkers related to Peripheral Neural Invasion (PNI) in head and neck squamous cell carcinoma (HNSCC).</p><p><strong>Methods: </strong>The PNI-related differentially expressed mRNAs (DE-mRNAs) in HNSCC were identified to construct a PNI-related risk score model. The expression level and ROC curve for Tachykinin Precursor 1 (TAC1) were calculated. Additionally, two kinds of in vitro models of PNI were established for investigation, including the Matrigel-PNI model and the Transwell-PNI model. Furthermore, the transcription factor of the TAC1 was predicted and verified by qRTPCR.</p><p><strong>Results: </strong>A total of 139 DE-mRNAs were identified in PNI positive and negative groups of HNSCC patients. The risk-score marker model incorporating 20 PNI-related DE-mRNAs was established. The TAC1 was identified as a potential highly expressed PNI marker, which exhibited good performance in predicting PNI events. Patients with higher TAC1 expressions demonstrated significantly shorter survival rates compared to those with lower TAC1 expressions in HNSCC. Besides, the knockdown of TAC1 significantly repressed neural invasion in HNSCC cells in vitro, according to the Matrigel-PNI model and Transwell-PNI model. Furthermore, KLF15 was predicted and verified as a transcription activator of TAC1 in HNSCC.</p><p><strong>Conclusion: </strong>This study highlights that the activation of KLF15 transcription of TAC1 promotes PNI in HNSCC cells, which provides guidance regarding the molecular diagnosis of PNI in HNSCC cells.</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":"142459768","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}
Actaea racemosa (AR), sometimes also known as black cohosh, is a perennial herb that grows in the Ranunculaceae family that effloresces in the middle of summer. This herb is currently present throughout south and west North America despite being endangered in the eastern section of the continent. Certain information about the photochemistry and biological potential of this herb is available. In accordance with the scant available ethno-medical reports, this herb possesses antioxidant, antidiabetic, anti-inflammatory, antiosteoporosis, and anticancer properties. As per the available literature, caffeic acid, isoferulic acid, actein, 23-epi-26 deoxycatein, cimicifugoside, and ferukinolic acid are the key components found in different parts of AR. To date, no thorough research or systematic review has been done to highlight the traditional, biological, and phytochemical benefits of this herb. Consequently, further research is needed to gain a deeper understanding of this therapeutic herb, particularly about its separation and pharmacological screening of its insulating portion for a range of biological functions. The goal of this review was to compile the most recent data on the phytochemical presence of AR. in relation to its ethnomedical applications, methods of extraction, pharmacological applications, and future potential.
Actaea racemosa(AR)有时也被称为黑升麻,是一种生长在毛茛科的多年生草本植物,在盛夏开花。这种草本植物目前遍布北美南部和西部,尽管在北美大陆东部已濒临灭绝。关于这种草本植物的光化学和生物潜力,目前已有一定的资料。根据现有的少量民族医学报告,这种草药具有抗氧化、抗糖尿病、抗炎、抗骨质疏松症和抗癌特性。根据现有文献,咖啡酸、异阿魏酸、猕猴桃苷、23-epi-26 deoxycatein、升麻苷和阿魏酸是 AR 不同部位的主要成分。迄今为止,还没有深入研究或系统综述来强调这种草药的传统、生物和植物化学功效。因此,需要进行进一步的研究,以加深对这种治疗性草药的了解,特别是对其绝缘部分的分离和药理筛选,以了解其一系列生物功能。本综述旨在汇编 AR.植物化学成分的最新数据,这些数据与 AR.的民族医药应用、提取方法、药理应用和未来潜力有关。
{"title":"Discovering the Untouched Perspective of Endangered North American Herb Actaea racemosa.","authors":"Genevive Kharumnuid, Rashmi Saxena Pal, Yogendra Pal, Motamarri Naga Lalitha Chaitanya, Preeti Srivastava","doi":"10.2174/0113862073309185240923053809","DOIUrl":"https://doi.org/10.2174/0113862073309185240923053809","url":null,"abstract":"<p><p>Actaea racemosa (AR), sometimes also known as black cohosh, is a perennial herb that grows in the Ranunculaceae family that effloresces in the middle of summer. This herb is currently present throughout south and west North America despite being endangered in the eastern section of the continent. Certain information about the photochemistry and biological potential of this herb is available. In accordance with the scant available ethno-medical reports, this herb possesses antioxidant, antidiabetic, anti-inflammatory, antiosteoporosis, and anticancer properties. As per the available literature, caffeic acid, isoferulic acid, actein, 23-epi-26 deoxycatein, cimicifugoside, and ferukinolic acid are the key components found in different parts of AR. To date, no thorough research or systematic review has been done to highlight the traditional, biological, and phytochemical benefits of this herb. Consequently, further research is needed to gain a deeper understanding of this therapeutic herb, particularly about its separation and pharmacological screening of its insulating portion for a range of biological functions. The goal of this review was to compile the most recent data on the phytochemical presence of AR. in relation to its ethnomedical applications, methods of extraction, pharmacological applications, and future potential.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459766","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}
Background: Astaxanthin (AST) has been widely recognized for its therapeutic potential in chronic inflammatory ailments. This study investigates the therapeutic efficacy and underlying mechanisms of AST in the management of chronic prostatitis (CP).
Methods: Male Sprague-Dawley (SD) rats were randomly divided into control, complete Freund's adjuvant (CFA), and CFA + AST groups. CFA was used to induce the CP model, and saline was used for the control group. Inflammation of the prostate was detected 28 days after oral administration of AST. qRT-PCR and ELISA were used to detect pro-inflammatory factors in RWPE-1 and WPMY-1 cells. Potential targets of AST for CP were explored by network pharmacology, and related proteins were detected by Western blotting.
Results: Oral administration of AST alleviated the increase in prostate stroma and reduced inflammatory cell infiltration in CP rats. The IC50 of AST-treated RWPE-1 and WPMY-1 cells for 48 h were 171 and 212.1 μM, respectively. AST pretreatment reduced IL-6 and IL-8 expression in these cells. PPI network, GO, and KEGG enrichment analyses suggested that the antiinflammatory effect of AST was associated with the ERK1/2 pathway. Western blotting showed that AST inhibited ERK1/2 phosphorylation. In addition, AST and ERK1/2 pathway inhibitors (U0126) synergistically inhibited LPS-induced inflammation in prostate cells.
Conclusion: Our study identified the potential of AST in the treatment of CP. However, subsequent randomized controlled trials are needed to validate its clinical efficacy.
{"title":"Astaxanthin Alleviates Chronic Prostatitis via the ERK1/2 Signaling Pathway: Evidence from Network Pharmacology and Experimental Validation.","authors":"Yifu Liu, Liang Huang, Zhicheng Zhang, Qiqi Zhu, Ping Xi, Ting Sun, Binbin Gong","doi":"10.2174/0113862073331381240923080152","DOIUrl":"https://doi.org/10.2174/0113862073331381240923080152","url":null,"abstract":"<p><strong>Background: </strong>Astaxanthin (AST) has been widely recognized for its therapeutic potential in chronic inflammatory ailments. This study investigates the therapeutic efficacy and underlying mechanisms of AST in the management of chronic prostatitis (CP).</p><p><strong>Methods: </strong>Male Sprague-Dawley (SD) rats were randomly divided into control, complete Freund's adjuvant (CFA), and CFA + AST groups. CFA was used to induce the CP model, and saline was used for the control group. Inflammation of the prostate was detected 28 days after oral administration of AST. qRT-PCR and ELISA were used to detect pro-inflammatory factors in RWPE-1 and WPMY-1 cells. Potential targets of AST for CP were explored by network pharmacology, and related proteins were detected by Western blotting.</p><p><strong>Results: </strong>Oral administration of AST alleviated the increase in prostate stroma and reduced inflammatory cell infiltration in CP rats. The IC50 of AST-treated RWPE-1 and WPMY-1 cells for 48 h were 171 and 212.1 μM, respectively. AST pretreatment reduced IL-6 and IL-8 expression in these cells. PPI network, GO, and KEGG enrichment analyses suggested that the antiinflammatory effect of AST was associated with the ERK1/2 pathway. Western blotting showed that AST inhibited ERK1/2 phosphorylation. In addition, AST and ERK1/2 pathway inhibitors (U0126) synergistically inhibited LPS-induced inflammation in prostate cells.</p><p><strong>Conclusion: </strong>Our study identified the potential of AST in the treatment of CP. However, subsequent randomized controlled trials are needed to validate its clinical efficacy.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459765","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}
Pub Date : 2024-10-09DOI: 10.2174/0113862073302157240920115002
Yongshuang Wang, Xiangxiang Xu, Shuhao Yang, Chao Gu, Zhentao An, Xuefei Ding, Yaozhou Tian, Chengyu Pan, Hui Li
Background: Constipation-predominant irritable bowel syndrome (IBS-C) is a chronic functional intestinal disease that can significantly reduce patients' quality of life.
Objective: This study aims to evaluate the clinical effect and mechanism of YunPi RouGan (YPRG) prescription on IBS-C patients with liver-depression and spleen-deficiency syndrome.
Methods: 42 IBS-C patients receiving treatment at Jiangsu Provincial Hospital of Integrated Traditional Chinese and Western Medicine from May 2022 to March 2023 were recruited and randomly assigned to either the treatment or control group, with 21 patients in each group. The patients received either a YPRG prescription or a linalotide capsule for 4 weeks. A series of scales were utilized to evaluate the clinical symptoms, psychological aspects, and quality of life in IBS patients. Meanwhile, fresh fecal samples were collected to analyze the changes in gut microbiota by 16SrDNA sequencing.
Results: In terms of clinical treatment, both YPRG prescription and the first-line drug linaclotide have similar effects for IBS-C. However, YPRG prescription has demonstrated significant improvements in several symptoms, such as abdominal distension and belching. Furthermore, it has been shown to upregulate the diversity of gut microbiota and induce changes in the types of dominant microbiota in IBS-C patients. At the phylum level, Firmicutes and Bacteroides increased, while Proteobacteria, actinobacteria, and desulphurobacteria decreased. At the genus level, Bacteroides, Spirillum, Clostridium praxis, Roxella, Para-salmonella, Haemophilus, koala bacillus, Micrococcus rare, Spirillum, and Streptococcus increased significantly.
Conclusion: The effect of YPRG prescription on improving the clinical symptoms of IBS-C may be attributed to its potential to regulate gut microbiota.
{"title":"Yunpi Rougan Prescription in Treating Constipation-Predominant IBS: Clinical Observation and Gut Microbiota Effects.","authors":"Yongshuang Wang, Xiangxiang Xu, Shuhao Yang, Chao Gu, Zhentao An, Xuefei Ding, Yaozhou Tian, Chengyu Pan, Hui Li","doi":"10.2174/0113862073302157240920115002","DOIUrl":"https://doi.org/10.2174/0113862073302157240920115002","url":null,"abstract":"<p><strong>Background: </strong>Constipation-predominant irritable bowel syndrome (IBS-C) is a chronic functional intestinal disease that can significantly reduce patients' quality of life.</p><p><strong>Objective: </strong>This study aims to evaluate the clinical effect and mechanism of YunPi RouGan (YPRG) prescription on IBS-C patients with liver-depression and spleen-deficiency syndrome.</p><p><strong>Methods: </strong>42 IBS-C patients receiving treatment at Jiangsu Provincial Hospital of Integrated Traditional Chinese and Western Medicine from May 2022 to March 2023 were recruited and randomly assigned to either the treatment or control group, with 21 patients in each group. The patients received either a YPRG prescription or a linalotide capsule for 4 weeks. A series of scales were utilized to evaluate the clinical symptoms, psychological aspects, and quality of life in IBS patients. Meanwhile, fresh fecal samples were collected to analyze the changes in gut microbiota by 16SrDNA sequencing.</p><p><strong>Results: </strong>In terms of clinical treatment, both YPRG prescription and the first-line drug linaclotide have similar effects for IBS-C. However, YPRG prescription has demonstrated significant improvements in several symptoms, such as abdominal distension and belching. Furthermore, it has been shown to upregulate the diversity of gut microbiota and induce changes in the types of dominant microbiota in IBS-C patients. At the phylum level, Firmicutes and Bacteroides increased, while Proteobacteria, actinobacteria, and desulphurobacteria decreased. At the genus level, Bacteroides, Spirillum, Clostridium praxis, Roxella, Para-salmonella, Haemophilus, koala bacillus, Micrococcus rare, Spirillum, and Streptococcus increased significantly.</p><p><strong>Conclusion: </strong>The effect of YPRG prescription on improving the clinical symptoms of IBS-C may be attributed to its potential to regulate gut microbiota.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459784","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}
Pub Date : 2024-10-09DOI: 10.2174/0113862073341577240925100048
Nawal S Alhaiqi, Sherine M Afifi, Jazem A Mahyoub, Rewaida A Abdel-Gaber, Denis Delic, Mohamed A Dkhil
Introduction: Helminthiasis remains a major global health concern. Exploring natural alternatives due to drug resistance and synthetic drug side effects has become increasingly urgent.
Method: This study investigates the anthelmintic potential of Carica papaya leaf extracts (CPLE) against Allolobophora caliginosa, along with elucidating the underlying structural alterations and molecular interactions. Carica papaya underwent methanolic extraction. Gas chromatography- mass spectrometry analysis revealed 11 active phytochemical compounds within CPLE. The anthelmintic activity was evaluated against A. caliginosa, with CPLE demonstrating efficacy comparable to albendazole. Light microscopy and scanning electron microscopy depicted structural modifications in worms exposed to CPLE, characterized by reduced size, uniform shrinkage, and increased cuticle thickness.
Result: Molecular docking studies with proteins Ascaris lumbricoides β-tubulin and Trichuris trichiura β-tubulin revealed potential binding interactions of CPLE compounds, notably Hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester, and Albendazole oxide. Conclusión: These findings suggest the anthelmintic efficacy of CPLE and provide insights into its mode of action at the molecular level.
{"title":"Anthelmintic Activity of Carica papaya Leaf Extracts: Insights from In Vitro and In Silico Investigations.","authors":"Nawal S Alhaiqi, Sherine M Afifi, Jazem A Mahyoub, Rewaida A Abdel-Gaber, Denis Delic, Mohamed A Dkhil","doi":"10.2174/0113862073341577240925100048","DOIUrl":"https://doi.org/10.2174/0113862073341577240925100048","url":null,"abstract":"<p><strong>Introduction: </strong>Helminthiasis remains a major global health concern. Exploring natural alternatives due to drug resistance and synthetic drug side effects has become increasingly urgent.</p><p><strong>Method: </strong>This study investigates the anthelmintic potential of Carica papaya leaf extracts (CPLE) against Allolobophora caliginosa, along with elucidating the underlying structural alterations and molecular interactions. Carica papaya underwent methanolic extraction. Gas chromatography- mass spectrometry analysis revealed 11 active phytochemical compounds within CPLE. The anthelmintic activity was evaluated against A. caliginosa, with CPLE demonstrating efficacy comparable to albendazole. Light microscopy and scanning electron microscopy depicted structural modifications in worms exposed to CPLE, characterized by reduced size, uniform shrinkage, and increased cuticle thickness.</p><p><strong>Result: </strong>Molecular docking studies with proteins Ascaris lumbricoides β-tubulin and Trichuris trichiura β-tubulin revealed potential binding interactions of CPLE compounds, notably Hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester, and Albendazole oxide. Conclusión: These findings suggest the anthelmintic efficacy of CPLE and provide insights into its mode of action at the molecular level.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459764","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}
Pub Date : 2024-10-07DOI: 10.2174/0113862073298128240918110357
Fariba Zamani-Hargalani, Faezeh Shafaei
<p><strong>Aims and objective: </strong>In this research, multicomponent reactions of cefixime, isothiocyanates, and alkyl bromides were carried out for the synthesis of new iminothiazole derivatives with high yields in water as the solvent at room temperature in the presence of catalytic amounts of Cu@KF/CP NPs as catalysts. Also, the ability of Cu@KF/Clinoptilolite nanoparticles (NPs) to adsorb and remove 4-NP and cefixime from water was investigated. The Cu@KF/Clinoptilolite nanoparticles were synthesized by employing a water extract of Petasites hybridus rhizomes.</p><p><strong>Materials and methods: </strong>For this experiment, all of the components obtained from Fluka and Merck were subjected to further purification. The antibiotic used in this investigation, cefixime, was obtained from a pharmaceutical facility situated in Sari, Mazandaran, Iran. The antibiotic factory is located in Sari City, Iran. All solutions were prepared using distilled water. The shape of Cu@KF/CP nanoparticles was analyzed using images obtained from a Holland Philips XL30 scanning electron microscope. An analysis was performed on the crystalline structure of Cu@KF/CP nanoparticles (NPs), and a room temperature X-ray diffraction (XRD) examination was carried out utilizing a Holland Philips Xpert X-ray powder diffractometer. The X-ray diffraction (XRD) examination was conducted using CuK radiation, which has a wavelength of 0.15406 nm. The analysis covered a 2ε angle range from 20 to 80°. The nanostructures that were produced were chemically analyzed using X-ray energy dispersive spectroscopy (EDS) with an S3700N equipment. The morphology and dimensions of Cu@KF/CP nanoparticles were characterized using a Philips EM208 transmission electron microscope operated at an acceleration voltage of 90 kV.</p><p><strong>Results: </strong>The primary objective of this study was to develop a sustainable approach for producing new iminothiazole derivatives 4. This was achieved using a highly efficient three-component reaction combining cefixime 1, isothiocyanates 2, and alkyl bromides 3. The reaction was carried out in water at ambient temperature, using Cu@KF/CP NPs as a highly effective catalyst, leading to excellent yields. Moreover, the study findings showed that the synthesized compounds demonstrated a significant antioxidant activity compared to conventional antioxidants. The antibacterial efficacy of the synthesized compounds was evaluated against both Gram-positive and Gram-negative bacteria. Furthermore, Cu@KF/CP nanoparticles were utilized to adsorb CFX and 4-NP from water-based solutions.</p><p><strong>Conclusion: </strong>This study showcases the effective synthesis of innovative iminothiazole derivatives through the use of multicomponent reactions, involving the combination of cefixime, isothiocyanates, and alkyl bromides. The reactions were conducted in a water-based solvent. The reactions were carried out at room temperature, utilizing Cu@KF/CP NPs as catalysts. T
{"title":"Green Synthesis of New Derivatives of Iminothiazole Using Cefixime and Removing Organic Pollutants from Aqueous Environment by Employing Cu@KF/Clinoptilolite NPs.","authors":"Fariba Zamani-Hargalani, Faezeh Shafaei","doi":"10.2174/0113862073298128240918110357","DOIUrl":"https://doi.org/10.2174/0113862073298128240918110357","url":null,"abstract":"<p><strong>Aims and objective: </strong>In this research, multicomponent reactions of cefixime, isothiocyanates, and alkyl bromides were carried out for the synthesis of new iminothiazole derivatives with high yields in water as the solvent at room temperature in the presence of catalytic amounts of Cu@KF/CP NPs as catalysts. Also, the ability of Cu@KF/Clinoptilolite nanoparticles (NPs) to adsorb and remove 4-NP and cefixime from water was investigated. The Cu@KF/Clinoptilolite nanoparticles were synthesized by employing a water extract of Petasites hybridus rhizomes.</p><p><strong>Materials and methods: </strong>For this experiment, all of the components obtained from Fluka and Merck were subjected to further purification. The antibiotic used in this investigation, cefixime, was obtained from a pharmaceutical facility situated in Sari, Mazandaran, Iran. The antibiotic factory is located in Sari City, Iran. All solutions were prepared using distilled water. The shape of Cu@KF/CP nanoparticles was analyzed using images obtained from a Holland Philips XL30 scanning electron microscope. An analysis was performed on the crystalline structure of Cu@KF/CP nanoparticles (NPs), and a room temperature X-ray diffraction (XRD) examination was carried out utilizing a Holland Philips Xpert X-ray powder diffractometer. The X-ray diffraction (XRD) examination was conducted using CuK radiation, which has a wavelength of 0.15406 nm. The analysis covered a 2ε angle range from 20 to 80°. The nanostructures that were produced were chemically analyzed using X-ray energy dispersive spectroscopy (EDS) with an S3700N equipment. The morphology and dimensions of Cu@KF/CP nanoparticles were characterized using a Philips EM208 transmission electron microscope operated at an acceleration voltage of 90 kV.</p><p><strong>Results: </strong>The primary objective of this study was to develop a sustainable approach for producing new iminothiazole derivatives 4. This was achieved using a highly efficient three-component reaction combining cefixime 1, isothiocyanates 2, and alkyl bromides 3. The reaction was carried out in water at ambient temperature, using Cu@KF/CP NPs as a highly effective catalyst, leading to excellent yields. Moreover, the study findings showed that the synthesized compounds demonstrated a significant antioxidant activity compared to conventional antioxidants. The antibacterial efficacy of the synthesized compounds was evaluated against both Gram-positive and Gram-negative bacteria. Furthermore, Cu@KF/CP nanoparticles were utilized to adsorb CFX and 4-NP from water-based solutions.</p><p><strong>Conclusion: </strong>This study showcases the effective synthesis of innovative iminothiazole derivatives through the use of multicomponent reactions, involving the combination of cefixime, isothiocyanates, and alkyl bromides. The reactions were conducted in a water-based solvent. The reactions were carried out at room temperature, utilizing Cu@KF/CP NPs as catalysts. T","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388639","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}
Background: The incidence of depression is increasing year by year, and Zhizichi Decoction(ZZCD)has shown significant efficiency in the clinical treatment of mild depression, but its mechanism of action is still unclear. In this research, network pharmacology and metagenomics combined and metabolomics were used as research methods to explain the scientific connotation of the antidepressant effect of ZZCD from the aspects of the overall effect of organisms and microbial structure and function.
Methods: The rat model of depression was established by chronic unpredictable mild stress (CUMS), and the improvement of depressive symptoms was evaluated by behavioral and histopathological methods. Network pharmacology predicted possible targets and important pathways of ZZCD. Metabolomics revealed its possible related biological pathways. Metagenomics showed the disturbance of ZZCD on intestinal microbial diversity structure and associated biological functions in depressed rats.
Results: ZZCD can improve the behavioral performance of CUMS rats, and can significantly regulate the content of 5-HT, NE and other neurotransmitters in serum and brain tissue, and improve the damaged state of neurons in the hippocampus. Network pharmacology predicts that it mainly acts on biological processes such as inflammatory response and oxidative stress response. Metabolomics found that it affected metabolic pathways such as amino acid metabolism and lipid metabolism. The results of metagenomics showed that it significantly regulated the abundance of Firmicutes and Bacteroidetes. The above results predicted that it may affect signaling pathways such as the nervous system, inflammatory diseases and cell processing.
Conclusion: ZZCD may play an antidepressant role by regulating intestinal probiotics, energy metabolism, and inflammation reduction. This provides a scientific basis for the clinical application of ZZCD in traditional Chinese medicine and also makes it an optional alternative for the treatment of depression.
{"title":"Study on the Antidepressant Effect of Zhizichi Decoction by Regulating Metabolism and Intestinal Flora.","authors":"WanRu Dong, ShuFa Hu, JiaMin Yu, Ying Liu, ShuTing Zeng, Xiaodong Duan, YongAn Deng, Yi Wang, Jian Yin, Beiyu Xing, Zunpeng Shu","doi":"10.2174/0113862073312654240918072945","DOIUrl":"https://doi.org/10.2174/0113862073312654240918072945","url":null,"abstract":"<p><strong>Background: </strong>The incidence of depression is increasing year by year, and Zhizichi Decoction(ZZCD)has shown significant efficiency in the clinical treatment of mild depression, but its mechanism of action is still unclear. In this research, network pharmacology and metagenomics combined and metabolomics were used as research methods to explain the scientific connotation of the antidepressant effect of ZZCD from the aspects of the overall effect of organisms and microbial structure and function.</p><p><strong>Methods: </strong>The rat model of depression was established by chronic unpredictable mild stress (CUMS), and the improvement of depressive symptoms was evaluated by behavioral and histopathological methods. Network pharmacology predicted possible targets and important pathways of ZZCD. Metabolomics revealed its possible related biological pathways. Metagenomics showed the disturbance of ZZCD on intestinal microbial diversity structure and associated biological functions in depressed rats.</p><p><strong>Results: </strong>ZZCD can improve the behavioral performance of CUMS rats, and can significantly regulate the content of 5-HT, NE and other neurotransmitters in serum and brain tissue, and improve the damaged state of neurons in the hippocampus. Network pharmacology predicts that it mainly acts on biological processes such as inflammatory response and oxidative stress response. Metabolomics found that it affected metabolic pathways such as amino acid metabolism and lipid metabolism. The results of metagenomics showed that it significantly regulated the abundance of Firmicutes and Bacteroidetes. The above results predicted that it may affect signaling pathways such as the nervous system, inflammatory diseases and cell processing.</p><p><strong>Conclusion: </strong>ZZCD may play an antidepressant role by regulating intestinal probiotics, energy metabolism, and inflammation reduction. This provides a scientific basis for the clinical application of ZZCD in traditional Chinese medicine and also makes it an optional alternative for the treatment of depression.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371179","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}
Pub Date : 2024-10-03DOI: 10.2174/0113862073326170240923061119
Jie Lin, Linying Liu, Xintong Cai, Anyang Li, Yixin Fu, Huaqing Huang, Yang Sun
Background: Ovarian Cancer (OC) is a lethal malignant tumor with a poor prognosis. Disulfidptosis is a newly identified form of cell death caused by disulfide stress. Targeting disulfidptosis is a new metabolic therapeutic strategy in cancer treatment. We aimed to establish a disulfidptosis- related lncRNA signature for prognosis prediction and explore its treatment values in OC patients.
Method: Data from the TCGA and GTEx databases and a disulfidptosis gene set were used to establish a disulfidptosis-related lncRNA signature for prognosis prediction in OC patients. Then, we internally and externally (PCR) validated our model. We also built a nomogram to improve our model's predictive power. Afterward, GSEA was employed to explore our model's potential functions. The ESTIMATE, CIBERSORT, TIMER, and ssGSEA were applied to estimate the immune landscape. Finally, the drug sensitivity of certain drugs for OC patients was analyzed.
Results: We built a prognosis model based on seven drlncRNAs, including AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1. Our model performed well by internal validation. PCR data also confirmed the same trend in the lncRNA levels. Furthermore, the nomogram-integrated age, grade, stage, and risk score could accurately predict the survival outcomes of OC patients. Subsequently, GSEA unveiled that our model genes enriched the Hedgehog signaling pathway, a key regulator in OC tumorigenesis. Our predictive signature was associated with immune checkpoints, such as PD-1(P < 0.01), PD-L1(P < 0.001), and CTLA4 (P < 0.01), which might help screen out OC patients who are sensitive to immunotherapy. Small molecule drugs, such as AZD-2281, GDC-0449, imatinib, and nilotinib, might benefit OC patients with different risk scores.
Conclusion: Our disulfidptosis-related lncRNA signature comprised of AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1 could serve as a prognostic biomarker and guidance to therapy response for OC patients.
{"title":"Identification of Disulfidptosis-Related LncRNA Subtypes, Establishment of a Prognostic Signature, and Characterization of Immune Infiltration in Ovarian Cancer.","authors":"Jie Lin, Linying Liu, Xintong Cai, Anyang Li, Yixin Fu, Huaqing Huang, Yang Sun","doi":"10.2174/0113862073326170240923061119","DOIUrl":"https://doi.org/10.2174/0113862073326170240923061119","url":null,"abstract":"<p><strong>Background: </strong>Ovarian Cancer (OC) is a lethal malignant tumor with a poor prognosis. Disulfidptosis is a newly identified form of cell death caused by disulfide stress. Targeting disulfidptosis is a new metabolic therapeutic strategy in cancer treatment. We aimed to establish a disulfidptosis- related lncRNA signature for prognosis prediction and explore its treatment values in OC patients.</p><p><strong>Method: </strong>Data from the TCGA and GTEx databases and a disulfidptosis gene set were used to establish a disulfidptosis-related lncRNA signature for prognosis prediction in OC patients. Then, we internally and externally (PCR) validated our model. We also built a nomogram to improve our model's predictive power. Afterward, GSEA was employed to explore our model's potential functions. The ESTIMATE, CIBERSORT, TIMER, and ssGSEA were applied to estimate the immune landscape. Finally, the drug sensitivity of certain drugs for OC patients was analyzed.</p><p><strong>Results: </strong>We built a prognosis model based on seven drlncRNAs, including AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1. Our model performed well by internal validation. PCR data also confirmed the same trend in the lncRNA levels. Furthermore, the nomogram-integrated age, grade, stage, and risk score could accurately predict the survival outcomes of OC patients. Subsequently, GSEA unveiled that our model genes enriched the Hedgehog signaling pathway, a key regulator in OC tumorigenesis. Our predictive signature was associated with immune checkpoints, such as PD-1(P < 0.01), PD-L1(P < 0.001), and CTLA4 (P < 0.01), which might help screen out OC patients who are sensitive to immunotherapy. Small molecule drugs, such as AZD-2281, GDC-0449, imatinib, and nilotinib, might benefit OC patients with different risk scores.</p><p><strong>Conclusion: </strong>Our disulfidptosis-related lncRNA signature comprised of AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1 could serve as a prognostic biomarker and guidance to therapy response for OC patients.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371178","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}
Pub Date : 2024-10-02DOI: 10.2174/0113862073328860240910103148
Masood Ur Rehman, Muhammad Salman, Javaria Iqbal
Background: The number of atoms producing a bond with an atom a in a molecular structure (graph) is regarded as the valency of a. A number of molecular structures have been topologically characterized via a large number of valency-based topological indices, which correlate certain physio-chemical properties like boiling point, stability, strain energy, and many more chemical compounds.
Objective: Our intention is to perform the topological characterization of primitive coronoid structures initially on the base of seven different valency-based topological indices. Fundamentally, our purpose is to provide the universal formula by using the topological characterization of any primitive coronoid structures with any valency-based topological index.
Method: The technique of atom-bonds partitions according to the valency of atoms besides counting principals are used to find the results.
Results: Exact values of valency-based topological index, namely the Randic index, sum connectivity index, harmonic index, atom bond connectivity index, geometric arithmetic index, forgotten index, and symmetric division index are calculated coronoid structures initially constructed with at most three benzene lyres. All these indices are valency-dependent structural invariants that have been used to elaborate several chemical properties of compounds of the structure.
Conclusion: Moreover, we provide the general formula to compute any valency-based topological index for any type of coronoid structure constructed with any number of benzene lyres.
背景:分子结构(图)中与原子 a 生成键的原子数被视为原子 a 的化合价。通过大量基于化合价的拓扑指数,对许多分子结构进行了拓扑表征,这些指数与某些物理化学性质(如沸点、稳定性、应变能以及更多化合物)相关联:我们的目的是根据七种不同的基于价的拓扑指数,对原始冠状结构进行初步的拓扑表征。从根本上说,我们的目的是利用任何原始冠状结构的拓扑特征和任何基于价的拓扑指数来提供通用公式:方法:除了计数原理之外,我们还使用了根据原子价进行原子键分区的技术来寻找结果:结果:计算了最初由最多三个苯裂片构建的冠状结构的基于价的拓扑指数的精确值,即兰迪克指数、和连接指数、谐波指数、原子键连接指数、几何算术指数、遗忘指数和对称分割指数。所有这些指数都是依赖于价的结构不变式,已被用于阐述该结构化合物的若干化学特性:此外,我们还提供了一个通用公式,用于计算由任意数量苯裂片构建的任何类型冠状结构的任何基于价的拓扑指数。
{"title":"Topological Characterization of Coronoid Structures via Valency Based Topological Indices.","authors":"Masood Ur Rehman, Muhammad Salman, Javaria Iqbal","doi":"10.2174/0113862073328860240910103148","DOIUrl":"https://doi.org/10.2174/0113862073328860240910103148","url":null,"abstract":"<p><strong>Background: </strong>The number of atoms producing a bond with an atom a in a molecular structure (graph) is regarded as the valency of a. A number of molecular structures have been topologically characterized via a large number of valency-based topological indices, which correlate certain physio-chemical properties like boiling point, stability, strain energy, and many more chemical compounds.</p><p><strong>Objective: </strong>Our intention is to perform the topological characterization of primitive coronoid structures initially on the base of seven different valency-based topological indices. Fundamentally, our purpose is to provide the universal formula by using the topological characterization of any primitive coronoid structures with any valency-based topological index.</p><p><strong>Method: </strong>The technique of atom-bonds partitions according to the valency of atoms besides counting principals are used to find the results.</p><p><strong>Results: </strong>Exact values of valency-based topological index, namely the Randic index, sum connectivity index, harmonic index, atom bond connectivity index, geometric arithmetic index, forgotten index, and symmetric division index are calculated coronoid structures initially constructed with at most three benzene lyres. All these indices are valency-dependent structural invariants that have been used to elaborate several chemical properties of compounds of the structure.</p><p><strong>Conclusion: </strong>Moreover, we provide the general formula to compute any valency-based topological index for any type of coronoid structure constructed with any number of benzene lyres.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364706","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}