Current pharmaceutical design最新文献

筛选
英文 中文
Recent Advancements in Refashioning of NSAIDs and their Derivatives as Anticancer Candidates 将非甾体抗炎药及其衍生物改造为抗癌候选药物的最新进展
IF 3.1 4区 医学
Current pharmaceutical design Pub Date : 2024-04-15 DOI: 10.2174/0113816128304230240327044201
Asmaa E. Kassab, Ehab M. Gedawy
{"title":"Recent Advancements in Refashioning of NSAIDs and their Derivatives as Anticancer Candidates","authors":"Asmaa E. Kassab, Ehab M. Gedawy","doi":"10.2174/0113816128304230240327044201","DOIUrl":"https://doi.org/10.2174/0113816128304230240327044201","url":null,"abstract":":: Inflammation is critical to the formation and development of tumors and is closely associated with cancer. Therefore, addressing inflammation and the mediators that contribute to the inflammatory process may be a useful strategy for both cancer prevention and treatment. Tumor predisposition can be attributed to inflammation. It has been demonstrated that NSAIDs can modify the tumor microenvironment by enhancing apoptosis and chemosensitivity and reducing cell migration. There has been a recent rise in interest in drug repositioning or repurposing because the development of innovative medications is expensive, timeconsuming, and presents a considerable obstacle to drug discovery. Repurposing drugs is crucial for the quicker and less expensive development of anticancer medicines, according to an increasing amount of research. This review summarizes the antiproliferative activity of derivatives of NSAIDs such as Diclofenac, Etodolac, Celecoxib, Ibuprofen, Tolmetin, and Sulindac, published between 2017 and 2023. Their mechanism of action and structural activity relationships (SARs) were also discussed to set the path for potential future repositioning of NSAIDs for clinical deployment in the treatment of cancer.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"2014 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571405","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
Protective Effects and Mechanisms of Luteolin against Acute Respiratory Distress Syndrome: Network Pharmacology and In vivo and In vitro Studies 木犀草素对急性呼吸窘迫综合征的保护作用和机制:网络药理学与体内外研究
IF 3.1 4区 医学
Current pharmaceutical design Pub Date : 2024-04-15 DOI: 10.2174/0113816128289341240327072531
Quan Li, Juan Chen, Yi Ren, Zhizhou Yang, Mengmeng Wang, Wei Zhang, Liping Cao, Haijun Sun, Shinan Nie, Zhaorui Sun
{"title":"Protective Effects and Mechanisms of Luteolin against Acute Respiratory Distress Syndrome: Network Pharmacology and In vivo and In vitro Studies","authors":"Quan Li, Juan Chen, Yi Ren, Zhizhou Yang, Mengmeng Wang, Wei Zhang, Liping Cao, Haijun Sun, Shinan Nie, Zhaorui Sun","doi":"10.2174/0113816128289341240327072531","DOIUrl":"https://doi.org/10.2174/0113816128289341240327072531","url":null,"abstract":"Background: Acute Respiratory Distress Syndrome (ARDS) is an acute life-threatening disease, and luteolin has the potential to become a therapeutic agent for ARDS. However, its mechanism of action has not yet been clarified. Objective: The present study explored the potential effects and mechanisms of luteolin in the treatment of ARDS through network pharmacology analysis and verified them through biological experiments. Methods: The potential targets of luteolin and ARDS were obtained from online databases. Functional enrichment and protein-protein interaction (PPI) analyses were performed to explore the underlying molecular mechanisms and to identify hub targets. Molecular docking was used to verify the relationship between luteolin and target proteins. Finally, the effects of luteolin on key signaling pathways and biological processes were verified by in vitro and in vivo experiments. Results: A total of 146 luteolin- and 496 ARDS-related targets were extracted from public databases. The network pharmacological analysis suggested that luteolin could inhibit ARDS through the following potential therapeutic targets: AKT1, RELA, and NFKBIA. Inflammatory and oxidative stress responses were the main biological processes involved, with the AKT/NF-κB signaling pathway being the key signaling pathway targeted by luteolin for the treatment of ARDS. Molecular docking analysis indicated that luteolin had a good binding affinity to AKT1, RELA, and NFKBIA. The in vitro and in vivo experiments revealed that luteolin could regulate the inflammatory response and oxidative stress in the treatment of ARDS by inhibiting the AKT/NF- κB signaling pathway. Conclusion: Luteolin could reduce the production of reactive oxygen species and inflammatory factors by inhibiting the AKT/NF-κB signaling pathway, thus reducing apoptosis and attenuating ARDS.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"50 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571670","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
In vitro Modified Release Studies on Melatoninergic Fluorinated Phenylalkylamides: Circumventing their Lipophilicity for Oral Administration 褪黑素能氟化苯烷基酰胺的体外修正释放研究:规避其口服亲脂性
IF 3.1 4区 医学
Current pharmaceutical design Pub Date : 2024-04-15 DOI: 10.2174/0113816128304967240328065809
Marilena Vlachou, Angeliki Siamidi, Chrystalla Protopapa, Michalis Vlachos, Sofia Kloutsou, Chrysoula-Christina Dreliozi, Ioannis P. Papanastasiou
{"title":"In vitro Modified Release Studies on Melatoninergic Fluorinated Phenylalkylamides: Circumventing their Lipophilicity for Oral Administration","authors":"Marilena Vlachou, Angeliki Siamidi, Chrystalla Protopapa, Michalis Vlachos, Sofia Kloutsou, Chrysoula-Christina Dreliozi, Ioannis P. Papanastasiou","doi":"10.2174/0113816128304967240328065809","DOIUrl":"https://doi.org/10.2174/0113816128304967240328065809","url":null,"abstract":"Introduction: In an attempt to circumvent the lipophilicity burden for the oral administration of new potent synthetic melatoninergic fluorine-substituted methoxyphenylalkyl amides, we conducted in vitro modified release studies using carefully selected matrix tablets’ biopolymeric materials in different ratios. Method: In particular, we sought to attain release profiles of these analogues similar to that of the parent compound, the chronobiotic hormone Melatonin (MLT), and also of the commercially available drug, Circadin®. Result: It was found that some of these systems, albeit being more lipophilic than MLT, mimic the in vitro release patterns of melatonin and Circadin®. Conclusion: Moreover, a number of these derivatives were proven suitable for dealing with sleep onset problems, whilst others for dealing with combined sleep onset/sleep maintenance dysfunctions.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"35 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571404","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
Revolutionizing Neurological Disorder Treatment: Integrating Innovations in Pharmaceutical Interventions and Advanced Therapeutic Technologies 革新神经系统疾病治疗:整合创新药物干预和先进治疗技术
IF 3.1 4区 医学
Current pharmaceutical design Pub Date : 2024-04-15 DOI: 10.2174/0113816128284824240328071911
Rimpi Arora, Ashish Baldi
{"title":"Revolutionizing Neurological Disorder Treatment: Integrating Innovations in Pharmaceutical Interventions and Advanced Therapeutic Technologies","authors":"Rimpi Arora, Ashish Baldi","doi":"10.2174/0113816128284824240328071911","DOIUrl":"https://doi.org/10.2174/0113816128284824240328071911","url":null,"abstract":":: Neurological disorders impose a significant burden on individuals, leading to disabilities and a reduced quality of life. However, recent years have witnessed remarkable advancements in pharmaceutical interventions aimed at treating these disorders. This review article aims to provide an overview of the latest innovations and breakthroughs in neurological disorder treatment, with a specific focus on key therapeutic areas such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and stroke. This review explores emerging trends in drug development, including the identification of novel therapeutic targets, the development of innovative drug delivery systems, and the application of personalized medicine approaches. Furthermore, it highlights the integration of advanced therapeutic technologies such as gene therapy, optogenetics, and neurostimulation techniques. These technologies hold promise for precise modulation of neural circuits, restoration of neuronal function, and even disease modification. While these advancements offer hopeful prospects for more effective and tailored treatments, challenges such as the need for improved diagnostic tools, identification of new targets for intervention, and optimization of drug delivery methods remain. By addressing these challenges and continuing to invest in research and collaboration, we can revolutionize the treatment of neurological disorders and significantly enhance the lives of those affected by these conditions.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571403","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
Network Pharmacology, Molecular Docking Analysis and Molecular Dynamics Simulation of Scutellaria baicalensis in the Treatment of Liver Fibrosis 黄芩治疗肝纤维化的网络药理学、分子对接分析和分子动力学模拟
IF 3.1 4区 医学
Current pharmaceutical design Pub Date : 2024-04-15 DOI: 10.2174/0113816128297074240327090020
Junrui Wang, Zhuoqing Wu, Xiaolei Chen, Ying Sun, Shuyao Ma, Jingdan Weng, Yuxin Zhang, Keke Dong, Jiangjuan Shao, Shizhong Zheng
{"title":"Network Pharmacology, Molecular Docking Analysis and Molecular Dynamics Simulation of Scutellaria baicalensis in the Treatment of Liver Fibrosis","authors":"Junrui Wang, Zhuoqing Wu, Xiaolei Chen, Ying Sun, Shuyao Ma, Jingdan Weng, Yuxin Zhang, Keke Dong, Jiangjuan Shao, Shizhong Zheng","doi":"10.2174/0113816128297074240327090020","DOIUrl":"https://doi.org/10.2174/0113816128297074240327090020","url":null,"abstract":"Background: Traditional Chinese medicine Scutellaria Baicalensis (SB), one of the clinical firstline heat-clearing drugs, has obvious symptomatic advantages for hepatic fibrosis with dampness-heat stasis as its syndrome. We aim to predict and validate the potential mechanism of Scutellaria baicalensis active ingredients against liver fibrosis more scientifically and effectively. Methods: The underlying mechanism of Scutellaria baicalensis in inhibiting hepatic fibrosis was studied by applying network pharmacology, molecular docking and molecular dynamics simulation. Expression levels of markers in activated Hepatic Stellate Cells (HSC) after administration of three Scutellaria baicalensis extracts were determined by Western blot and Real-time PCR, respectively, in order to verify the anti-fibrosis effect of the active ingredients objective: We aim to predict and validate the potential mechanism of SB active ingredients against liver fibrosis in a more scientific and effective way. Results: There are 164 common targets of drugs and diseases screened and 115 signaling pathways obtained, which were mainly associated with protein phosphorylation, senescence and negative regulation of the apoptotic process. Western blot and Real-time PCR showed that Scutellaria baicalensis extracts could reduce the expression of HSC activation markers, and Oroxylin A had the strongest inhibitory effect on it. Molecular docking results showed that Oroxylin A had high binding activity to target proteins. Molecular dynamics simulation demonstrates promising stability of the Oroxylin A-AKT1 complex over the simulated MD time of 200 ns. Conclusion: Scutellaria baicalensis active ingredients may inhibit HSC proliferation, reduce the generation of pro-inflammatory factors and block the anti-inflammatory effect of inflammatory signal transduction by inducing HSC apoptosis and senescence, thus achieving the effect of anti-fibrosis.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"1 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571275","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
Elucidation of the Molecular Mechanism of Compound Danshen Dripping Pills Against Angina Pectoris based on Network Pharmacology and Molecular Docking 基于网络药理学和分子对接的复方丹参滴丸治疗心绞痛的分子机理阐明
IF 3.1 4区 医学
Current pharmaceutical design Pub Date : 2024-04-05 DOI: 10.2174/0113816128287109240321074628
Xiaocui Tian, Shiqi Yin, Zhiguang Liu, Jinglin Cao, Xinyu Liu, Qi Qiu
{"title":"Elucidation of the Molecular Mechanism of Compound Danshen Dripping Pills Against Angina Pectoris based on Network Pharmacology and Molecular Docking","authors":"Xiaocui Tian, Shiqi Yin, Zhiguang Liu, Jinglin Cao, Xinyu Liu, Qi Qiu","doi":"10.2174/0113816128287109240321074628","DOIUrl":"https://doi.org/10.2174/0113816128287109240321074628","url":null,"abstract":"Background: Compound Danshen dripping pills (CDDP), a traditional Chinese medicine, has had an extensive application in the treatment of angina pectoris (AP) in China. However, research on the bioactive ingredients and underlying mechanisms of CDDP in AP remains unclear. background: CDDP, a traditional Chinese medicine, has had an extensive application in the treatment of AP in China. However, research on the bioactive ingredients and underlying mechanisms of CDDP in AP remains unclear. Objective: In the present study, we explored the major chemical components and potential molecular mechanisms linked to the anti-angina effects of CDDP through the application of network pharmacology and molecular docking. objective: In the present study, we explored the major chemical components and potential molecular mechanisms linked to the anti-angina effects of CDDP through the application of network pharmacology and molecular docking. Methods: The potential targets of active ingredients in CDDP were sourced from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and the Swiss Target Prediction Database (STPD). Additionally, targets related to angina pectoris (AP) were retrieved from various databases, including Gene Cards, DisGeNET, Dis Genet, the Drug Bank database (DBD), and the Therapeutic Target Database (TDD). Protein- protein interaction [1] networks were also established, and core targets were identified based on their topological significance. GO enrichment analysis and KEGG pathway analysis were conducted using the R software. Interactions between active ingredients and potential targets selected through the above process were investigated through molecular docking. method: The potential targets of active ingredients in CDDP were sourced from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and the Swiss Target Prediction Database (STPD). Additionally, targets related to AP were retrieved from various databases, including Gene Cards, DisGeNET, Dis Genet, the Drug Bank database (DBD), and the Therapeutic Target Database (TDD). Protein-protein interaction (PPI) networks were also established, and core targets were identified based on their topological significance. GO enrichment analysis and KEGG pathway analysis were conducted using the R software. Interactions between active ingredients and potential targets selected through above processwere investigated through molecular docking. Results: Seventy-six active ingredients were selected with the following criteria: OB ≥ 30%, DL ≥ 0.18. 383 targets of CDDP and 1488 targets on AP were gathered, respectively. Afterwards, 194 common targets of CDDP and anti-AP targets were defined, of which 12 were core targets. GO enrichment analysis indicated that CDDP acted on AP by response to lipopolysaccharide, regulating the reactive oxygen species and metal ion metabolism, and epithelial cell proliferation. In addition, KEGG enrichment analysis indicated that the signalin","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"50 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571411","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
CRISPR and Gene Editing: A Game-Changer in Drug Development CRISPR 和基因编辑:改变药物开发的游戏规则
IF 3.1 4区 医学
Current pharmaceutical design Pub Date : 2024-04-05 DOI: 10.2174/0113816128298080240328053845
Abhishek Verma, Tarun Sharma, Ankit Awasthi
{"title":"CRISPR and Gene Editing: A Game-Changer in Drug Development","authors":"Abhishek Verma, Tarun Sharma, Ankit Awasthi","doi":"10.2174/0113816128298080240328053845","DOIUrl":"https://doi.org/10.2174/0113816128298080240328053845","url":null,"abstract":": CRISPR and gene editing technologies have emerged as transformative tools in medicine, offering unprecedented precision in targeting genetic disorders and revolutionizing drug development. This review explores the multifaceted impact of CRISPR across various medical domains, from hereditary diseases to infectious diseases and cancer. The potential of CRISPR in personalized medicine, therapeutic innovation, and pandemic prevention is highlighted, along with its role in reshaping traditional drug development processes. However, alongside its promise, ethical considerations loom large, particularly regarding germline editing and equitable access to treatments. The commercialization of CRISPR poses further challenges, raising questions about affordability and healthcare equity. Collaboration among scientists, policymakers, and the public is emphasized to navigate the ethical and societal implications of CRISPR responsibly. As the field advances, it is essential to ensure that the benefits of CRISPR are realized while addressing potential risks and maintaining a commitment to the well-being of future generations.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"2014 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571270","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
Neuropilin-1 Binding Peptide as Fusion to Diphtheria Toxin Induces Apoptosis in Non-small Cell Lung Cancer Cell Line 与白喉毒素融合的神经肽-1 结合肽诱导非小细胞肺癌细胞株凋亡
IF 3.1 4区 医学
Current pharmaceutical design Pub Date : 2024-04-05 DOI: 10.2174/0113816128292382240325074032
Sara Eghtedari, Mahdi Behdani, Fatemeh Kazemi-Lomedasht
{"title":"Neuropilin-1 Binding Peptide as Fusion to Diphtheria Toxin Induces Apoptosis in Non-small Cell Lung Cancer Cell Line","authors":"Sara Eghtedari, Mahdi Behdani, Fatemeh Kazemi-Lomedasht","doi":"10.2174/0113816128292382240325074032","DOIUrl":"https://doi.org/10.2174/0113816128292382240325074032","url":null,"abstract":"Background:: Targeted cancer therapy can be considered as a new strategy to overcome the side effects of current cancer treatments. Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that is expressed in endothelial cells and tumor vessels to stimulate angiogenesis progression. Targeted diphtheria toxin (DT)- based therapeutics are promising tools for cancer treatment. This study aimed to construct a novel NRP-1 binding peptide (as three repeats) (CRGDK) as a fusion to truncated DT (DTA) (DTA-triCRGDK) for targeted delivery of DT into NRP-1 expressing cells. Methods:: The concept of DTA-triCRGDK was designed, synthesized and cloned into the bacterial host. Expression of DTA-triCRGDK was induced by Isopropyl ß-D-1-thiogalactopyranoside (IPTG) and purification was performed using Ni-NTA chromatography. Biological activity of DTA-triCRGDK was evaluated using MTT, apoptosis, and wound healing assays. In addition, expression levels of apoptotic Bax, Bcl2, and Casp3 genes were determined by Real-time PCR Results:: Cytotoxicity analysis showed the IC50 values of DTA-triCRGDK for A549 and MRC5 were 0.43 nM and 4.12 nM after 24h, respectively. Bcl2 expression levels decreased 0.4 and 0.72 fold in A549 and MRC5, respectively. However, Bax and Casp3 expression level increased by 6.75 and 8.19 in A549 and 2.51 and 3.6 in MRC5 cells. Conclusion:: Taken together, DTA-triCRGDK is a promising tool for targeted therapy of NRP-1 overexpressing cancer cells.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"107 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571407","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
Association of Parity with the Risks of Gestational Diabetes and Macrosomia: A Retrospective Cohort Study in Nanjing, China 妊娠期糖尿病和巨大儿风险与胎次的关系:中国南京的一项回顾性队列研究
IF 3.1 4区 医学
Current pharmaceutical design Pub Date : 2024-04-05 DOI: 10.2174/0113816128294311240322041144
Shijie Geng, Junya Wang, Zhi Geng, Juan Wen
{"title":"Association of Parity with the Risks of Gestational Diabetes and Macrosomia: A Retrospective Cohort Study in Nanjing, China","authors":"Shijie Geng, Junya Wang, Zhi Geng, Juan Wen","doi":"10.2174/0113816128294311240322041144","DOIUrl":"https://doi.org/10.2174/0113816128294311240322041144","url":null,"abstract":"Background: After implementing the two-child policy, more Chinese women who had a previous delivery had their second child. Nevertheless, the impacts of parity on Gestational Diabetes (GDM) and macrosomia have not been fully confirmed. Therefore, we aimed to analyse the characteristics of pregnancy by parity and evaluate the association of parity with risks of GDM/macrosomia in a Chinese population Methods: A total of 193,410 pregnant women (including 148,293 primiparae and 45,117 multiparae) with complete information were included. Univariate and multivariate logistic regression analyses were used to examine the association between parity and risks of GDM/macrosomia. Results: With the gradual implementation of the two-child policy, the proportion of multiparae increased rapidly and then decreased slightly. Multiparae were more likely to be older and have higher intrapartum BMI, as compared to primiparae (P < 0.001). Univariate regression analyses suggested that parity could increase the risks of GDM and macrosomia; while after adjustment, the association between parity and GDM risk disappeared, and the effects of parity on macrosomia risk and birth weight of babies were also weakened. Further, stratified analysis showed that parity only increased the risk of GDM in women over 30 years, and the effects of parity on macrosomia risk and birth weight were more pronounced among women over 30 years compared to women under 30 years. Conclusion: Parity was not associated with GDM risk, but mildly associated with macrosomia risk. Particular attention should be paid to multiparae with advanced age to reduce the risks of GDM and macrosomia","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"6 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571329","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
Celastrol Elicits Antitumor Effects through Inducing Immunogenic Cell Death and Downregulating PD-L1 in ccRCC Celastrol 通过诱导免疫原性细胞死亡和下调 PD-L1 在 ccRCC 中发挥抗肿瘤作用
IF 3.1 4区 医学
Current pharmaceutical design Pub Date : 2024-04-05 DOI: 10.2174/0113816128288970240321073436
Hong-Fang Li, Neng Zhu, Jia-Jun Wu, Ya-Ning Shi, Jia Gu, Li Qin
{"title":"Celastrol Elicits Antitumor Effects through Inducing Immunogenic Cell Death and Downregulating PD-L1 in ccRCC","authors":"Hong-Fang Li, Neng Zhu, Jia-Jun Wu, Ya-Ning Shi, Jia Gu, Li Qin","doi":"10.2174/0113816128288970240321073436","DOIUrl":"https://doi.org/10.2174/0113816128288970240321073436","url":null,"abstract":"Background:: Targeting immunogenic cell death (ICD) is considered a promising therapeutic strategy for cancer. However, the commonly identified ICD inducers promote the expression of programmed cell death ligand 1 (PD-L1) in tumor cells, thus aiding them to evade the recognition and killing by the immune system. Therefore, the finding of novel ICD inducers to avoid enhanced PD-L1 expression is of vital significance for cancer therapy. Celastrol (CeT), a triterpene isolated from Tripterygium wilfordii Hook. F induces various forms of cell death to exert anti-cancer effects, which may make celastrol an attractive candidate as an inducer of ICD. Methods:: In the present study, bioinformatics analysis was combined with experimental validation to explore the underlying mechanism by which CeT induces ICD and regulates PD-L1 expression in clear cell renal cell carcinoma (ccRCC). Results:: The results showed that EGFR, IKBKB, PRKCQ and MAPK1 were the crucial targets for CeT-induced ICD, and only MAPK1 was an independent prognostic factor for the overall survival (OS) of ccRCC patients. In addition, CeT triggered autophagy and up-regulated the expressions of HMGB1 and CRT to induce ICD in 786-O cells in vitro. Importantly, CeT can down-regulate PD-L1 expression through activating autophagy. At the molecular level, CeT suppressed PD-L1 via the inhibition of MAPK1 expression. Immunologically, the core target of celastrol, MAPK1, was tightly correlated with CD8+ T cells and CD4+ T cells in ccRCC. Conclusion:: These findings indicate that CeT not only induces ICD but also suppresses PD-L1 by down-regulating MAPK1 expression, which will provide an attractive strategy for ccRCC immunotherapy.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140571409","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
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
确定
请完成安全验证×
相关产品
×
本文献相关产品
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信