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Exercise therapy: Anti-tumor and improving chemotherapy efficacy 运动疗法:抗肿瘤和提高化疗疗效
Pub Date : 2024-09-01 DOI: 10.1016/j.jhip.2024.09.001
Zhongyu Wang , Zongming Wang , Huitong Chen , Siyuan Li , Junhua Yang , Yuxin Ma , Chang Zhou , Xiaobao Jin , Jing Liu , Xin Wang

The extant research evidence indicates that sensible exercise has a beneficial impact on the prevention and treatment of cancer. This paper presents a comprehensive literature review of the field of sports oncology. Its objective is to synthesize and analyze the impact of exercise training on cancer, as well as to elucidate the mechanisms through which exercise affects cancer progression. Additionally, it offers valuable insights for advancing fundamental and clinical research in sports oncology. Firstly, this paper provides a summary of the relationship between exercise and various aspects of tumor progression, including tumor size, weight, metastasis, tumor vascularity, myokine production, immune response, and the efficacy of cancer chemotherapy. Secondly, due to the diversity of tumor properties, we also explore the fact that the specificity of exercise prescription should be tailored to the different tumor types and patient profiles. Furthermore, we discuss the importance of considering individual differences when determining the type of exercise, intensity, intervention, and duration of exercise. Finally, this paper emphasizes the necessity of evaluating the interaction between exercise and conventional or novel immunotherapies and pharmacodynamics in future preclinical studies.

现有研究证据表明,合理的运动对预防和治疗癌症有益。本文对运动肿瘤学领域进行了全面的文献综述。其目的是综合分析运动训练对癌症的影响,并阐明运动影响癌症进展的机制。此外,本文还为推进运动肿瘤学的基础和临床研究提供了有价值的见解。首先,本文总结了运动与肿瘤进展各方面的关系,包括肿瘤大小、重量、转移、肿瘤血管、肌肽分泌、免疫反应和肿瘤化疗的疗效。其次,由于肿瘤特性的多样性,我们还探讨了运动处方的特异性应针对不同的肿瘤类型和患者情况。此外,我们还讨论了在确定运动类型、强度、干预措施和运动持续时间时考虑个体差异的重要性。最后,本文强调了在未来临床前研究中评估运动与传统或新型免疫疗法和药效学之间相互作用的必要性。
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引用次数: 0
The research advance on the theory of Chinese medicine-exterior-interior correlation between the Lung and Large Intestine in the treatment of chronic cough 肺与大肠相表里的中医理论在慢性咳嗽治疗中的研究进展
Pub Date : 2024-09-01 DOI: 10.1016/j.jhip.2024.09.004
Meng Yuan , Hongyuan Chen , Wen Rui

Coughing as the main symptom of a chronic cough is a persistent respiratory disease that poses a substantial challenge to Western medicine and traditional Chinese medicine (TCM). The Large Intestine and Lung are intimately related, impacting each other's pathology and physiology, according to TCM theory. This complex interaction emphasizes how crucial it is to treat both organs at the same time while treating cough to support gut health. This viewpoint is further supported by current research, which demonstrates the connections between the Large Intestine and the Lung through a variety of pathways, including neurological pathways, mucosal immune system modulation, gas exchange dynamics, and microbiota composition. To clarify the mechanisms and practical applications of treating chronic cough by concurrently targeting the Lung and Intestine in TCM, this paper merges ideas from TCM theory and empirical research in Western medicine. This provides insightful information for efficiently managing chronic cough.

以咳嗽为主要症状的慢性咳嗽是一种顽固性呼吸道疾病,对西医和中医都是一个巨大的挑战。中医理论认为,大肠与肺关系密切,在病理和生理上相互影响。这种复杂的相互作用强调了在治疗咳嗽的同时治疗这两个器官以支持肠道健康的重要性。目前的研究进一步支持了这一观点,研究表明大肠与肺之间通过神经通路、粘膜免疫系统调节、气体交换动力学和微生物群组成等多种途径存在联系。为了阐明中医 "肺肠同治 "治疗慢性咳嗽的机制和实际应用,本文融合了中医理论和西医实证研究的观点。这为有效治疗慢性咳嗽提供了具有洞察力的信息。
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引用次数: 0
Safety and risk control study of antibody preparation based on CiteSpace 基于 CiteSpace 的抗体制备的安全性和风险控制研究
Pub Date : 2024-09-01 DOI: 10.1016/j.jhip.2024.08.002
Chanyuan Chen , Rong Wang , Yuanxuan Cai , Yuhang Zhao , Zherui Chen , Ke Li , Li Zhao , Rui Huang , Nooruldeen Riyadh Ibrahim , Xiaofang Shangguan

Objective

To analyze the hotspots, patterns, and distribution of research on the safety and risk of antibody preparations in the past 20 years. It also seeks to summarize the current status and trends of research on the safety and risk control of antibody preparations.

Methods

Taking “antibody preparation”, “safety” and “risk” as keywords, relevant articles were searched in the databases Web of Science. CiteSpace was utilized to analyze the annual number of publications, countries, authors, institutions, highly cited literature and keywords of the screened literature, and the relevant maps were drawn and the results were analyzed.

Results

A total of 1693 articles were included. The annual number of publications in the field of antibody preparation safety has shown stable growth followed by a rapid increase between 2002 and 2022. Among the countries, the United States accounted for 36.7% of the total publications, ranking first in the world. Large foreign pharmaceutical companies, research institutions, comprehensive university and their affiliated hospitals were the most high-yield institutions. Current hot topics in the field of antibody preparation safety research include “ADC”, “monoclonal antibody”, “anti-tumor activity”, “immunotherapy”, etc.

Conclusion

Over the past 20 years, research on antibody formulations has garnered increasing attention both domestically and internationally, with a focus mainly on efficacy and safety. There has been relatively little research on risk control. In the future, more in-depth research is needed on the mechanisms of adverse reactions in antibody formulations to provide more effective strategies for risk control.
目的分析近 20 年来抗体制剂安全性和风险研究的热点、模式和分布情况,总结抗体制剂安全性和风险控制研究的现状和趋势。方法以 "抗体制剂"、"安全性 "和 "风险 "为关键词,在 Web of Science 数据库中检索相关文章。结果共收录 1693 篇文章。2002-2022年间,抗体制备安全性领域的年发文量呈现出先稳定增长后快速增长的态势。其中,美国的论文数量占论文总数的 36.7%,居世界首位。国外大型制药公司、研究机构、综合性大学及其附属医院是高产机构。目前抗体制剂安全性研究领域的热点话题包括 "ADC"、"单克隆抗体"、"抗肿瘤活性"、"免疫治疗 "等。对风险控制的研究相对较少。未来,需要对抗体制剂的不良反应机制进行更深入的研究,以提供更有效的风险控制策略。
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引用次数: 0
Potential anti-colon cancer agents: Molecular modelling, docking, pharmacokinetics studies and molecular dynamic simulations 潜在的抗结肠癌药物:分子建模、对接、药代动力学研究和分子动力学模拟
Pub Date : 2024-09-01 DOI: 10.1016/j.jhip.2024.09.003
Auwal Salisu Isa , Adamu Uzairu , Umar Mele Umar , Muhammad Tukur Ibrahim , Abdullahi Bello Umar , Iqrar Ahmad

Objective

The objective of this investigation is to create a trustworthy Quantitative Structure-Activity Relationship (QSAR) model that generates little to no side effects and is low-cost for treating colon cancer using experimental data obtained from the literature.

Methods

ChemDraw software was used for creating molecular structures, which were then optimized using Spartan 14 software to generate quantum chemical descriptors. Data pre-treatment and data division were performed using specific software packages. Additionally, analysis and validation tasks were carried out using software tools such as Discovery Studio Visualizer, PyRx for docking, SwissADME for pharmacokinetics studies, and Desmond for molecular dynamic (MD) simulation.

Results

The developed QSAR model demonstrates good predictive quality with a Mean Absolute Error (MAE) of 1.3313 and high internal validation metrics (R2 ​= ​0.9407, adjusted R2 ​= ​0.9329). External validation on a test set yields satisfactory results (R2 ​= ​0.9012, adjusted R2 ​= ​0.8436, CCC ​= ​0.9229). Docking analysis identifies compounds 111 and 112 as having the lowest binding affinity of −10.4 kJ/mol, characterized by specific molecular properties. Additionally, MD simulation provides insights into the dynamic behavior and interaction types of the protein-ligand complex, contributing to a deeper understanding of their stability and fluctuations.

Conclusion

The model validation parameters confirm the reliability and robustness of the model. The pharmacokinetics study validates the drug-likeness of the drug candidate through various parameters. The MD simulation sheds light on the dynamic behavior and interaction types of the protein-ligand complex, enhancing our understanding of their stability and fluctuations.
目标本研究的目标是利用从文献中获得的实验数据,创建一个值得信赖的定量结构-活性关系(QSAR)模型,该模型在治疗结肠癌方面几乎不会产生副作用,而且成本低廉。方法使用 ChemDraw 软件创建分子结构,然后使用 Spartan 14 软件对其进行优化,以生成量子化学描述符。使用特定的软件包进行数据预处理和数据分割。此外,还使用 Discovery Studio Visualizer、用于对接的 PyRx、用于药代动力学研究的 SwissADME 和用于分子动力学(MD)模拟的 Desmond 等软件工具进行了分析和验证。测试集的外部验证结果令人满意(R2 = 0.9012,调整后的 R2 = 0.8436,CCC = 0.9229)。Docking 分析确定 111 和 112 号化合物的结合亲和力最低,为 -10.4 kJ/mol,具有特定的分子特性。此外,MD 模拟还有助于深入了解蛋白质配体复合物的动态行为和相互作用类型,从而加深对其稳定性和波动性的理解。药代动力学研究通过各种参数验证了候选药物的药物相似性。MD 模拟揭示了蛋白质配体复合物的动态行为和相互作用类型,加深了我们对其稳定性和波动性的理解。
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引用次数: 0
Puerarin alleviates LPS-induced endothelial cells injury via SIRT1-mediated mitochondrial homeostasis signaling 葛根素通过 SIRT1 介导的线粒体平衡信号缓解 LPS 诱导的内皮细胞损伤
Pub Date : 2024-09-01 DOI: 10.1016/j.jhip.2024.08.004
Xing Chang , Meng Cheng , Ying Li , Xiuteng Zhou
Endothelial inflammation injury is a key mechanism that occurs in the pathological processes of various cardiovascular diseases. Puerarin (PUE) is an isoflavone compound with strong antioxidant properties and the main active component isolated from the rhizome of Pueraria lobata. PUE exhibits a good anti-atherosclerotic pharmacological effect, but there are few studies on the mechanism of its protective effect on endothelial cells. This study found that PUE could regulate to some extent the mitochondrial function of human umbilical vein endothelial cells (HUVECs) and reduce or inhibit lipopolysaccharide-induced inflammatory reactions and oxidative stress injury in HUVECs. Furthermore, the protective effect of PUE on HUVECs was closely related to the SIRT-1 signaling pathway. PUE increased the level of mitophagy and the activity of mitochondrial antioxidant enzymes by increasing SIRT-1 expression, reducing excessive production of ROS, and inhibiting expression of inflammatory factors and oxidative stress injury. Therefore, PUE may improve mitochondrial respiratory function and energy metabolism and increase the activity of HUVECs in the inflammatory state.
内皮炎症损伤是各种心血管疾病病理过程中的一个关键机制。葛根素(PUE)是从葛根根茎中分离出来的主要活性成分,是一种具有很强抗氧化性的异黄酮化合物。葛根素具有良好的抗动脉粥样硬化药理作用,但有关其对血管内皮细胞保护作用机制的研究却很少。本研究发现,葛根素能在一定程度上调节人脐静脉内皮细胞(HUVECs)线粒体功能,减轻或抑制脂多糖诱导的 HUVECs 炎症反应和氧化应激损伤。此外,PUE 对 HUVECs 的保护作用与 SIRT-1 信号通路密切相关。PUE通过增加SIRT-1的表达,减少ROS的过度产生,抑制炎症因子的表达和氧化应激损伤,从而提高线粒体吞噬水平和线粒体抗氧化酶的活性。因此,PUE 可改善线粒体呼吸功能和能量代谢,提高炎症状态下 HUVEC 的活性。
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引用次数: 0
Zebrafish as a rapid model system for early cardiotoxicity assessment of drugs 斑马鱼作为药物心脏毒性早期评估的快速模型系统
Pub Date : 2024-09-01 DOI: 10.1016/j.jhip.2024.09.002
Zonghao Lin , Xinru Wei , Yuanzheng Wei , Zongyu Miao , Huixin Ye , Meihui Wu , Xiangying Liu , Lei Cai , Chuqin Yu

Objective

There are some problems in the evaluation of drug cardiotoxicity in zebrafish, such as unsystematic indicators and weak sensitivity. This study aims to explore the advantages and disadvantages of various evaluation methods in rapid cardiotoxicity assessment, and to identify and establish representative and highly sensitive evaluation indicators.

Methods

Four typical cardiotoxic drugs (Doxorubicin, 5-Fluorouracil, Ibuprofen and Lidocaine) with different concentrations were selected to act on zebrafish embryos. The death, cardiac malformation, heart rate, blood flow and sinus venosus-bulbus arteriosus (SV-BA) distance of zebrafish in each group were observed and recorded by stereo microscopy. The behavioral changes of zebrafish after drug treatment were counted and analyzed using a zebrafish behavior recorder. Adult zebrafish were used to screen the cardiotoxic expressed genes, and the spatiotemporal expression stability and concentration-dose dependence of the specifically highly expressed genes were studied.

Results

All the 4 drugs can reduce the heart rate and blood flow velocity of zebrafish embryos to varying degrees, increase the SV-BA distance of zebrafish embryos, reduce the activity behavior of zebrafish embryos, and have different degrees of inhibitory effects on the cardiac function of zebrafish. Among the selected 12 genes expressed only in the heart, one and only CMLC1 showed high specific expression in the heart of zebrafish. However, doxorubicin did not affect the expression of CMLC1 gene in a concentration-dose dependent manner, and the other three drugs could significantly induce the up-regulation of CMLC1 gene expression.

Conclusion

Ethology is a faster and more sensitive method than the traditional cardiotoxicity evaluation indicators (heart rate, blood flow velocity, and SV-BA distance). Zebrafish have a small number of highly heart-specific expressed genes and are not suitable for assessing cardiotoxicity based solely on heart-specific expression of circulating mRNA.
目的斑马鱼药物心脏毒性评价存在指标不系统、灵敏度低等问题。方法选择四种不同浓度的典型心脏毒性药物(多柔比星、5-氟尿嘧啶、布洛芬和利多卡因)作用于斑马鱼胚胎。用体视显微镜观察和记录各组斑马鱼的死亡、心脏畸形、心率、血流量和静脉-大动脉窦(SV-BA)距离。使用斑马鱼行为记录仪对药物治疗后斑马鱼的行为变化进行计数和分析。结果 4种药物均能不同程度地降低斑马鱼胚胎的心率和血流速度,增加斑马鱼胚胎的SV-BA距离,减少斑马鱼胚胎的活动行为,对斑马鱼的心脏功能有不同程度的抑制作用。在筛选出的 12 个只在心脏表达的基因中,只有 CMLC1 在斑马鱼心脏有较高的特异性表达。结论与传统的心脏毒性评价指标(心率、血流速度和SV-BA距离)相比,选集是一种更快、更灵敏的方法。斑马鱼的心脏特异性表达基因较少,不适合仅根据循环 mRNA 的心脏特异性表达来评估心脏毒性。
{"title":"Zebrafish as a rapid model system for early cardiotoxicity assessment of drugs","authors":"Zonghao Lin ,&nbsp;Xinru Wei ,&nbsp;Yuanzheng Wei ,&nbsp;Zongyu Miao ,&nbsp;Huixin Ye ,&nbsp;Meihui Wu ,&nbsp;Xiangying Liu ,&nbsp;Lei Cai ,&nbsp;Chuqin Yu","doi":"10.1016/j.jhip.2024.09.002","DOIUrl":"10.1016/j.jhip.2024.09.002","url":null,"abstract":"<div><h3>Objective</h3><div>There are some problems in the evaluation of drug cardiotoxicity in zebrafish, such as unsystematic indicators and weak sensitivity. This study aims to explore the advantages and disadvantages of various evaluation methods in rapid cardiotoxicity assessment, and to identify and establish representative and highly sensitive evaluation indicators.</div></div><div><h3>Methods</h3><div>Four typical cardiotoxic drugs (Doxorubicin, 5-Fluorouracil, Ibuprofen and Lidocaine) with different concentrations were selected to act on zebrafish embryos. The death, cardiac malformation, heart rate, blood flow and sinus venosus-bulbus arteriosus (SV-BA) distance of zebrafish in each group were observed and recorded by stereo microscopy. The behavioral changes of zebrafish after drug treatment were counted and analyzed using a zebrafish behavior recorder. Adult zebrafish were used to screen the cardiotoxic expressed genes, and the spatiotemporal expression stability and concentration-dose dependence of the specifically highly expressed genes were studied.</div></div><div><h3>Results</h3><div>All the 4 drugs can reduce the heart rate and blood flow velocity of zebrafish embryos to varying degrees, increase the SV-BA distance of zebrafish embryos, reduce the activity behavior of zebrafish embryos, and have different degrees of inhibitory effects on the cardiac function of zebrafish. Among the selected 12 genes expressed only in the heart, one and only <em>CMLC1</em> showed high specific expression in the heart of zebrafish. However, doxorubicin did not affect the expression of <em>CMLC1</em> gene in a concentration-dose dependent manner, and the other three drugs could significantly induce the up-regulation of <em>CMLC1</em> gene expression.</div></div><div><h3>Conclusion</h3><div>Ethology is a faster and more sensitive method than the traditional cardiotoxicity evaluation indicators (heart rate, blood flow velocity, and SV-BA distance). Zebrafish have a small number of highly heart-specific expressed genes and are not suitable for assessing cardiotoxicity based solely on heart-specific expression of circulating mRNA.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"5 3","pages":"Pages 223-234"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ferroptosis: A prospective therapeutic target for radiotherapy- and chemotherapy-induced gastrointestinal inflammation 铁蛋白沉积:放疗和化疗引发的胃肠道炎症的前瞻性治疗靶点
Pub Date : 2024-08-13 DOI: 10.1016/j.jhip.2024.08.001
Siyu Han, Jingrui Zheng, Weijian Chen, Ke Nie

Ferroptosis is a unique mode of cell death driven by iron-dependent lipid peroxidation, and the process is regulated by a variety of cellular metabolic pathways, including redox homeostasis, iron processing, and lipid metabolism. It has been shown that radiotherapy- and chemotherapy-induced gastrointestinal (GI) inflammation exhibits the key features of ferroptosis, including iron deposition, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) inactivation and lipid peroxidation. In this paper, we found that ferroptosis plays an important role in radiotherapy- and chemotherapy-induced GI inflammation, and that elevating GSH levels, activating GPX4, inhibiting elevated levels of lipid peroxidation, and maintaining iron homeostasis significantly alleviated radiotherapy- and chemotherapy-induced GI inflammation. This suggests that ferroptosis may be a new target for the treatment of GI inflammation. In addition, we systematically summarize the potential mechanisms of traditional Chinese medicine (TCM) and its active ingredients in the treatment of GI inflammation, which may be effective in ameliorating radiotherapy- and chemotherapy-induced GI by acting on the key signaling pathways and mediators, such as Nrf2/HO-1, GSH/GPX4, polyunsaturated fatty acids (PUFAs), iron, and organic peroxides, which in turn inhibit the process of ferroptosis, and thereby effectively ameliorate the radiotherapy- and chemotherapy-induced GI inflammation. This finding provides a new potential approach for the treatment of such GI inflammation and demonstrates the potential value of TCM in modern medical treatment.

铁变态反应是由铁依赖性脂质过氧化驱动的一种独特的细胞死亡模式,该过程受多种细胞代谢途径的调控,包括氧化还原平衡、铁处理和脂质代谢。有研究表明,放疗和化疗引起的胃肠道(GI)炎症表现出铁质氧化的主要特征,包括铁沉积、谷胱甘肽(GSH)耗竭、谷胱甘肽过氧化物酶 4(GPX4)失活和脂质过氧化。在本文中,我们发现铁变态反应在放疗和化疗诱发的消化道炎症中起着重要作用,而提高谷胱甘肽水平、激活 GPX4、抑制脂质过氧化水平的升高以及维持铁的稳态能显著缓解放疗和化疗诱发的消化道炎症。这表明,铁氧化可能是治疗消化道炎症的一个新靶点。此外,我们还系统地总结了中药及其有效成分在治疗消化道炎症中的潜在机制,中药可能通过作用于关键信号通路和介质,有效改善放疗和化疗诱导的消化道炎症、Nrf2/HO-1、GSH/GPX4、多不饱和脂肪酸(PUFAs)、铁和有机过氧化物等关键信号通路和介质,进而抑制铁氧化过程,从而有效改善放疗和化疗引起的消化道炎症。这一发现为治疗此类消化道炎症提供了一种新的潜在方法,并证明了中医药在现代医学治疗中的潜在价值。
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引用次数: 0
Holistic integrative medicine declaration 整体综合医学宣言
Pub Date : 2024-08-07 DOI: 10.1016/j.jhip.2024.07.001
China Institute for Development Strategy of Holistic Integrative Medicine

Holistic integrative medicine, abbreviated as HIM, has been officially proposed since 2012. Its theoretical system has been continuously improved, and its practical methods have become increasingly diverse, becoming an inevitable choice and path for the medical development in the new era. This article demonstrates ten major propositions for HIM, elaborating on the connotation and extension of HIM from the perspectives of epistemology and methodology, in order to achieve the transformation and adaptive evolution of modern medicine.

整体整合医学,简称HIM,自2012年正式提出。其理论体系不断完善,实践方法日益多样,成为新时期医学发展的必然选择和必由之路。本文论证了HIM的十大命题,从认识论和方法论的角度阐述了HIM的内涵和外延,以实现现代医学的转型和适应性进化。
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引用次数: 0
Preparation of purine functionalized biochar and analysis of nephrotoxic substances in traditional Chinese medicine 嘌呤功能化生物炭的制备及中药中肾毒性物质的分析
Pub Date : 2024-07-23 DOI: 10.1016/j.jhip.2024.06.006
Yanhui Ge , Xinya Xu , Yuanru Zheng

In recent years, a growing lack of comprehension regarding the safety of traditional Chinese medicines (TCMs) has led to an escalating incidence of drug-induced organ damage, particularly kidney damage associated with TCM usage. This study focused on the development of purine-functionalized biochar and used to capture nephrotoxic substances in TCMs. The biochar was meticulously characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and elemental analysis. Subsequently, it was employed as a solid-phase extraction medium for capturing suspected nephrotoxic substances in TCMs. Results revealed that the functional biochar exhibited commendable selectivity for compounds with nephrotoxic effects, demonstrating its potential for effectively capturing nephrotoxic substances in TCMs. This research aimed to introduce an innovative method for monitoring potential nephrotoxic substances in large-scale TCMs, thereby contributing to the enhancement of the overall safety profile of traditional Chinese medicine.

近年来,由于对传统中药安全性的认识不足,药物引起的器官损伤,尤其是中药引起的肾脏损伤的发病率不断上升。本研究的重点是开发嘌呤功能化生物炭,用于捕捉中药中的肾毒性物质。利用扫描电子显微镜(SEM)、傅立叶变换红外光谱(FT-IR)、X 射线光电子能谱(XPS)和元素分析对生物炭进行了细致的表征。随后,将其用作固相萃取介质,以捕获中药中的可疑肾毒性物质。结果表明,功能性生物炭对具有肾毒性作用的化合物具有良好的选择性,表明其具有有效捕获中药中肾毒性物质的潜力。这项研究旨在引入一种创新方法来监测大型中药中潜在的肾毒性物质,从而有助于提高传统中药的整体安全性。
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引用次数: 0
Construction a six-gene prognostic model for hepatocellular carcinoma based on WGCNA co-expression network 基于 WGCNA 共表达网络构建肝细胞癌的六基因预后模型
Pub Date : 2024-06-01 DOI: 10.1016/j.jhip.2024.06.005
Tian Wang , Yu-Chun Fan , Lin-Li Zhang , Min-Yu Nong , Guang-Fei Zheng , Wan-Shuo Wei , Li-He Jiang

Objective

Currently, the incidence of hepatocellular carcinoma remains high, and the prognosis of patients is poor. Prognostic biomarkers are still worth exploring.

Methods

Based on The Cancer Genome Atlas (TCGA) database, the differentially expressed genes (DEGs) were screened. Subsequently, a modular analysis of these DEGs was performed using the weighted gene co-expression network analysis (WGCNA). A prognostic model for liver cancer patients was constructed employing the Cox proportional hazards model. Through univariate and multivariate Cox regression analyses, we developed a Cox proportional-hazards model specifically for hepatocellular carcinoma. Subsequently, International Cancer Genome Consortium (ICGC) cohort data were used to validate the accuracy of the Cox proportional-hazards model. Following this, we conducted further analyses of prognostic genes, encompassing functional enrichment analysis and survival analysis. Additionally, we utilized the BBcancer database to investigate whether these prognostic genes have the potential to serve as blood markers. Notably, in this six-gene prognostic model, we also analyzed the genes' drug susceptibility.

Results

Leveraging the candidate genes identified from the WGCNA analysis, we constructed a Cox proportional-hazards model with an AUC value greater than 0.7. This model incorporates HMMR, E2F2, WDR62, KIF11, MSH4, and KCNF1, revealing that patients with low expression levels of these genes had significantly better survival prognosis compared to those with high expression levels (P ​< ​0.05). The enrichment analysis revealed that these prognostic genes are enriched in pathways related to hepatitis B, hepatitis C, and hepatocellular carcinoma. Furthermore, we observed a strong association between HMMR, E2F2, WDR62, KIF11, MSH4, and KCNF1 with overall survival (OS) in hepatocellular carcinoma (HCC) patients, among which HMMR, E2F2, WDR62 and KIF11 genes were significantly differentially expressed in extracellular vesicles. Additionally, this six-gene prognostic model demonstrated sensitivity to drugs such as VX-680, TAE684, Sunitinib, S-Trityl-L-cysteine, Paclitaxel, and CGP-60474.

Conclusion

The Cox risk prognostic model based on HMMR, E2F2, WDR62, KIF11, MSH4, and KCNF1 represents a valuable tool for predicting the prognosis of HCC patients and may serve as a target for drug development. In particular, HMMR, E2F2, WDR62, and KIF11 have potential as blood biomarkers for hepatocellular carcinoma, though their precise biological functions require further exploration.

目的目前,肝细胞癌的发病率居高不下,且预后较差。方法基于癌症基因组图谱(TCGA)数据库,筛选差异表达基因(DEGs)。随后,利用加权基因共表达网络分析(WGCNA)对这些 DEGs 进行了模块化分析。利用 Cox 比例危险度模型构建了肝癌患者的预后模型。通过单变量和多变量 Cox 回归分析,我们建立了专门针对肝细胞癌的 Cox 比例危险度模型。随后,我们利用国际癌症基因组联盟(ICGC)队列数据验证了 Cox 比例危险度模型的准确性。之后,我们对预后基因进行了进一步分析,包括功能富集分析和生存分析。此外,我们还利用 BBcancer 数据库研究了这些预后基因是否有可能作为血液标记物。值得注意的是,在这个六基因预后模型中,我们还分析了这些基因对药物的敏感性。结果利用从 WGCNA 分析中发现的候选基因,我们构建了一个 AUC 值大于 0.7 的 Cox 比例危险模型。该模型纳入了 HMMR、E2F2、WDR62、KIF11、MSH4 和 KCNF1,结果显示,与高表达水平的患者相比,这些基因低表达水平的患者生存预后明显更好(P <0.05)。富集分析显示,这些预后基因富集在与乙型肝炎、丙型肝炎和肝细胞癌相关的通路中。此外,我们还观察到 HMMR、E2F2、WDR62、KIF11、MSH4 和 KCNF1 与肝细胞癌(HCC)患者的总生存期(OS)密切相关,其中 HMMR、E2F2、WDR62 和 KIF11 基因在细胞外囊泡中有显著差异表达。结论基于HMMR、E2F2、WDR62、KIF11、MSH4和KCNF1的Cox风险预后模型是预测HCC患者预后的重要工具,可作为药物开发的靶点。特别是,HMMR、E2F2、WDR62 和 KIF11 有可能成为肝细胞癌的血液生物标志物,但它们的确切生物学功能还需要进一步探索。
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引用次数: 0
期刊
Journal of Holistic Integrative Pharmacy
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