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Combining metabolomics and 16S rRNA sequencing to investigate the effects of fecal microbiota transplantation intervention in aging mice 结合代谢组学和 16S rRNA 测序研究粪便微生物群移植干预对衰老小鼠的影响
Pub Date : 2024-03-01 DOI: 10.1016/j.jhip.2024.04.007
Tianxin Zhu , Ling Yang , Zhizhong Luo , Jiqian He , Xuefeng Xu , Duosheng Luo

Aging is a complex physiological process, accompanied by metabolic and immune disorders leading to aging. The aging process yields dramatic alterations in the gut microbiota. However, there is limited evidence for a mechanistic role of the gut microbiota in aging processes. We conducted fecal microbiota transplantation from either young (4 months) or aged (22 months) donor mice into aged recipient mice (22 months) or young (4 months). Aged mice receiving young donor gut microbiota reversed aging-associated inflammation in serum and issues, and the behavioral characteristics with spontaneous activities, standing times, the number of falls, and the latency time in aged mice were alleviated. Conversely, young mice receiving aged donor gut microbiota promoted the development of inflammation, and the behavioral characteristics of aging were intensified. The relative abundance of Odoribacter, Flexispira, Veillonella, and Prevotellaceae_Prevotella were significantly enriched in aged mice, while changes were reversed in aged mice receiving young donor gut microbiota. The metabolites including indole acrylic acid, LPC (18:1/0:0), LPC (15:0/0:0), LPC (0:0/15:0) were up-regulated, and xanthine, inosine, allopurinol, N6-methyladenosine metabolites were down-regulated. After aged mice receiving young donor gut microbiota, these metabolite changes were reversed too. Analysis of the correlation between the microbiota, metabolites, and inflammatory cytokines showed indoleacrylic acid, LPC (18:1/0:0), LPC (15:0/0:0), and LPC (0:0/15:0) were negatively associated with Adlercreutzia, while positively correlated with Veillonella, Prevotellaceae_Prevotella, Streptococcus, and Odoribacter. 1-methylinosine, L-methyladenosine, allopurinol, and N6-methyladenosine were positively correlated with Desulfovibrio, and negatively correlated with Veillonella and Prevotellaceae_Prevotella. Indoleacrylic acid was negatively correlated with TGF-β. LPC (18:1/0:0), LPC (15:0/0:0), and LPC (0:0/15:0) were positively correlated with IL-10. 1-methylinosine, L-methyladenosine, N6-methyladenosine and inosine were negatively correlated with IL-6 and LPS. Our findings suggest that modulating the gut microbiome may be an appropriate treatment to promote healthy aging.

衰老是一个复杂的生理过程,伴随着导致衰老的代谢和免疫紊乱。衰老过程会导致肠道微生物群发生巨大变化。然而,关于肠道微生物群在衰老过程中的机理作用的证据却很有限。我们将年轻(4 个月)或年老(22 个月)的供体小鼠的粪便微生物群移植到年老(22 个月)或年轻(4 个月)的受体小鼠体内。接受年轻供体肠道微生物群的老年小鼠逆转了血清和问题中与衰老相关的炎症,老年小鼠的自发活动、站立时间、跌倒次数和潜伏时间等行为特征也得到了缓解。相反,接受老年供体肠道微生物群的年轻小鼠会促进炎症的发展,并加剧衰老的行为特征。在老年小鼠体内,Odoribacter、Flexispira、Veillonella 和 Prevotellaceae_Prevotella 的相对丰度显著增加,而在接受年轻供体肠道微生物群的老年小鼠体内,这种变化被逆转。吲哚丙烯酸、LPC(18:1/0:0)、LPC(15:0/0:0)、LPC(0:0/15:0)等代谢物上调,黄嘌呤、肌苷、别嘌呤醇、N6-甲基腺苷代谢物下调。老年小鼠接受年轻供体肠道微生物群后,这些代谢物的变化也发生了逆转。对微生物群、代谢物和炎症细胞因子之间相关性的分析表明,吲哚丙烯酸、LPC(18:1/0:0)、LPC(15:0/0:0)和 LPC(0:0/15:0)与阿德勒克鲁兹菌呈负相关,而与维氏菌、普雷沃特菌、链球菌和奥德菌呈正相关。1-甲基肌苷、L-甲基腺苷、别嘌呤醇和 N6-甲基腺苷与脱硫弧菌呈正相关,而与 Veillonella 和 Prevotellaceae_Prevotella 呈负相关。吲哚丙烯酸与 TGF-β 呈负相关。LPC(18:1/0:0)、LPC(15:0/0:0)和 LPC(0:0/15:0)与 IL-10 呈正相关。1-甲基肌苷、L-甲基腺苷、N6-甲基腺苷和肌苷与 IL-6 和 LPS 呈负相关。我们的研究结果表明,调节肠道微生物组可能是一种促进健康老龄化的适当治疗方法。
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引用次数: 0
Pharmacological underlying mechanisms of the anticancer effect of licorice: Bioinformatics and experimental verification 甘草抗癌作用的药理基础机制:生物信息学和实验验证
Pub Date : 2024-03-01 DOI: 10.1016/j.jhip.2024.04.006
Mengqi Liu , Lingping Fu , Hao Fu , Yu Chen , Mengxia Wu , Hanchun Liu

Purpose

Cancer is the second leading cause of human mortality and has rapidly become a major global issue. According to traditional Chinese medicine (TCM) theory, the primary pathogenesis of cancer is the deficiency of "vital Qi". Licorice (Gancao in Chinese, GC) one of the oldest and the most frequently used herbs for tonifying Qi, is commonly integrated with other Chinese medicines to treat cancer in TCM clinical practice. GC extract, or its chemical components, are often utilized in cancer treatment. However, the molecular mechanisms underlying GC's therapeutic effects on cancer remain unclear. Our current study aimed to elucidate these mechanisms from the perspective of network pharmacology and experimental validation.

Methods

We employed network pharmacology and bioinformatics to explore the anti-cancer mechanism, crucial targets, and kernel ingredients of GC. The significant targets and key ingredients (quercetin, glycyrrhetinic acid, and glucyrin) were substantiated using the Cancer Genome Atlas (TCGA) and Cell Counting Kit-8 (CCK-8) viability assay, respectively.

Results

Our findings identified eight critical targets and key ingredients (quercetin, glycyrrhetinic acid, glucyrin) and suggested that GC's anti-cancer effects are primarily associated with modulation of the immune system, signal transduction, cell cycle, and gene expression. The efficacy of quercetin, glycyrrhetinic acid, glucyrin against Human A549 lung cancer cells was confirmed.

Conclusion

This study comprehensively elucidates the mechanisms through which GC addresses cancer, leveraging network pharmacology and experimental validation. These insights contribute to identifying principal compounds and developing innovative drugs for cancer therapy.

目的癌症是导致人类死亡的第二大原因,并已迅速成为一个重大的全球性问题。根据传统中医理论,癌症的主要发病机理是 "元气 "不足。甘草是最古老、最常用的补气中药之一,在中医临床实践中通常与其他中药结合治疗癌症。甘草提取物或其化学成分常被用于癌症治疗。然而,GC 对癌症治疗作用的分子机制仍不清楚。本研究旨在从网络药理学和实验验证的角度阐明这些机制。结果我们发现了八个关键靶点和关键成分(槲皮素、甘草亭酸和葡萄糖苷),并认为 GC 的抗癌作用主要与免疫系统、信号转导、细胞周期和基因表达的调节有关。该研究利用网络药理学和实验验证,全面阐明了 GC 的抗癌机制。这些见解有助于确定主要化合物和开发用于癌症治疗的创新药物。
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引用次数: 0
Economic evaluation of isosorbide mononitrate sustained-release capsules for the treatment of angina pectoris 单硝酸异山梨酯缓释胶囊治疗心绞痛的经济评估
Pub Date : 2024-03-01 DOI: 10.1016/j.jhip.2024.04.003
Yuhang Liu , Jienan Zheng , Yeyou Xu , Shuli Zhang , Yueyun Li , Hui Zhang

Objective

Systematically evaluate the efficacy of (1) isosorbide mononitrate sustained-release capsules combined with conventional therapy and (2) conventional therapy alone in the treatment of angina pectoris and analyze their economic value to provide evidence and a reference for clinical medication and decision-making.

Methods

Randomized controlled trials on the efficacy of isosorbide mononitrate sustained-release capsules combined with conventional therapy and conventional therapy in the treatment of angina pectoris were searched and abstracted from major Chinese and English literature databases from August 26, 2003 to August 26, 2023, to calculate the rate of improvement in clinical symptoms using isosorbide mononitrate sustained-release capsules combined with conventional therapy (observation group) and using conventional therapy alone (control group). Review Manager 5.4 software was used for meta-analysis, and an economic evaluation was performed using cost-effectiveness analysis (CEA).

Results

The effectiveness rates for clinical symptom improvement were 95% in the observation group and 78% in the control group. According to the meta-analysis results, the efficiency of clinical symptom improvement in the observation group, which received the combination therapy with isosorbide mononitrate sustained-release capsules, was significantly better than that of the control group (OR ​= ​3.38, 95% CI: 2.28 to 4.99, P ​< ​0.001). The CEA indicated an incremental cost-effectiveness ratio of 434.12 yuan, and the sensitivity analysis results demonstrated that the evaluation outcomes were stable, suggesting a robust foundation for the study's conclusions.

Conclusions

Compared with conventional therapy alone, isosorbide mononitrate sustained-release capsules combined with traditional treatment have good efficacy and safety in the treatment of angina pectoris and have certain economic advantages.

目的系统评价(1)单硝酸异山梨酯缓释胶囊联合常规治疗和(2)单纯常规治疗治疗心绞痛的疗效,并分析其经济价值,为临床用药和决策提供证据和参考。方法检索并摘录2003年8月26日至2023年8月26日主要中英文文献数据库中有关单硝酸异山梨酯缓释胶囊联合常规疗法和常规疗法治疗心绞痛疗效的随机对照试验,计算单硝酸异山梨酯缓释胶囊联合常规疗法(观察组)和单纯常规疗法(对照组)临床症状改善率。结果 观察组临床症状改善的有效率为 95%,对照组为 78%。根据荟萃分析结果,接受单硝酸异山梨酯缓释胶囊联合治疗的观察组临床症状改善的有效率明显优于对照组(OR = 3.38,95% CI:2.28 至 4.99,P < 0.001)。CEA显示增量成本效益比为434.12元,敏感性分析结果显示评价结果稳定,表明研究结论具有坚实的基础。结论与单纯传统治疗相比,单硝酸异山梨酯缓释胶囊联合传统治疗心绞痛具有良好的疗效和安全性,并具有一定的经济优势。
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引用次数: 0
Danhong injection alleviates OGD-induced blood-brain barrier injury via VEGFR2/PI3K/AKT pathway based on network pharmacology and experimental evidence 基于网络药理学和实验证据的丹红注射液通过 VEGFR2/PI3K/AKT 通路缓解 OGD 诱导的血脑屏障损伤
Pub Date : 2024-03-01 DOI: 10.1016/j.jhip.2024.04.001
Yutong Zhang , Meixia Xie , Jiayin Liang , Li Li , Shumei Wang , Minghua Xian

Objective

Previous studies have shown that Danhong injection (DHI) has a protective effect on the blood-brain barrier (BBB) function after ischemic stroke. However, the role of DHI in protecting the integrity of the BBB after ischemic stroke through endothelial cells is still unclear. The purpose of this study is to explore the role and mechanism of DHI in protecting BBB by interfering with endothelial cells.

Methods

We used network pharmacology technology to determine the potential pathways and mechanisms of DHI in treating ischemic stroke through endothelial cells. On account of the network pharmacology results, we assessed the effects of DHI in oxygen-glucose deprivation (OGD) model of mouse brain-derived endothelial (bEnd.3) cells via MTT, and validated the molecular mechanisms of DHI improving BBB injury through Western blot.

Results

Network pharmacology analysis suggested that DHI may regulate the PI3K/AKT signaling pathway of endothelial cells in the treatment of ischemic stroke. Cellular experiments showed that DHI stimulates endothelial cell migration and reduces OGD-induced BBB damage via VEGFR2/PI3K/AKT pathway.

Conclusion

Network pharmacology analysis and cellular experiments have shown that DHI alleviated the BBB damage by activating the VEGFR2/PI3K/AKT signaling pathway on endothelial cells.

目的以前的研究表明,丹红注射液(DHI)对缺血性脑卒中后的血脑屏障(BBB)功能有保护作用。然而,丹红注射液通过内皮细胞保护缺血性脑卒中后血脑屏障完整性的作用尚不清楚。本研究的目的是探讨 DHI 通过干扰内皮细胞保护 BBB 的作用和机制。方法我们利用网络药理学技术确定了 DHI 通过内皮细胞治疗缺血性中风的潜在途径和机制。根据网络药理学结果,我们通过 MTT 评估了 DHI 在氧-葡萄糖剥夺(OGD)模型小鼠脑源性内皮细胞(bEnd.3)中的作用,并通过 Western blot 验证了 DHI 改善 BBB 损伤的分子机制。结果网络药理学分析表明,DHI 在治疗缺血性脑卒中中可能调节内皮细胞的 PI3K/AKT 信号通路。结论网络药理学分析和细胞实验表明,DHI通过激活内皮细胞的VEGFR2/PI3K/AKT信号通路减轻了BBB损伤。
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引用次数: 0
Corrigendum to “Analysis of clinical drug use and construction of pharmacy service model for children with Kawasaki disease based on integration concept” [J Holist Integr Pharm (2023) 133–139] 基于整合理念的川崎病儿童临床用药分析与药学服务模式构建》[J Holist Integr Pharm (2023) 133-139] 勘误表
Pub Date : 2024-03-01 DOI: 10.1016/j.jhip.2024.03.001
Huashen He , Yingyao Luo , Binghong Yu , Yingqiang Lai , Jinkun Zheng , Junfeng Ban
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引用次数: 0
Pharmacognostic studies on three species of Spermacoce 关于三种 Spermacoce 的药理研究
Pub Date : 2024-03-01 DOI: 10.1016/j.jhip.2024.03.002
Shan Fan, Wenfeng Weng, Shengguo Ji

To provide a scientific basis for identification of Spermacoce species, including Spermacoce remota Lamarck, Spermacoce exilis (L. O. Williams) C. D. Adams, and Spermacoce alata Aubl., the current study was carried out for pharmacognostical parameters. Roots, stems, and leaves of plants were collected for pharmacognostical studies involving source identification, microscopic evaluation, character observation, phytochemical screening, ultraviolet spectrum and molecular pharmacognosy analysis. S. remota, S. alata, and S. exilis belong to the same genus, and the morphology of the plants was similar. Powder microscopy showed the presence of fibers, needle crystal bundles, spiral vessels, and near spherical pollen grains in all the plants. Phytochemical investigation demonstrated that S. remota, S. alata, and S. exilis all contained glycosides, proteins and volatile oils. In addition, the extracts of S. alata and S. exilis revealed the presence of flavonoids and tannins. In this study, the ITS sequence of S. exilis was found for the first time which had been submitted to NCBI to obtain the GenBank registration number. The results of neighbor-joining phylogenetic tree showed that S. exilis, S. remota and S. alata could be distinguished accurately. The study will be beneficial to the identification, resource conservation and quality control of Spermacoce species.

为了给鉴定 Spermacoce(包括 Spermacoce remota Lamarck、Spermacoce exilis (L. O. Williams) C. D. Adams 和 Spermacoce alata Aubl.采集植物的根、茎和叶进行药理研究,包括来源鉴定、显微评价、特征观察、植物化学筛选、紫外光谱和分子药理分析。S. remota、S. alata 和 S. exilis 属于同一属,植物形态相似。粉末显微镜检查显示,所有植物都存在纤维、针状晶体束、螺旋器皿和近球形花粉粒。植物化学调查表明,S. remota、S. alata 和 S. exilis 都含有苷类、蛋白质和挥发油。此外,S. alata 和 S. exilis 的提取物还含有黄酮类化合物和单宁酸。本研究首次发现了 S. exilis 的 ITS 序列,该序列已提交给 NCBI 并获得 GenBank 注册号。邻接系统发生树的结果表明,S. exilis、S. remota和S. alata可以准确区分。该研究将有助于Spermacoce物种的鉴定、资源保护和质量控制。
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引用次数: 0
Combining single-cell RNA sequencing data and network pharmacology to explore the mechanism of action of Dayuan Yin in the treatment of acute lung injury 结合单细胞RNA测序数据和网络药理学探讨大元饮治疗急性肺损伤的作用机制
Pub Date : 2023-12-01 DOI: 10.1016/j.jhip.2024.01.002
Lei Zhang, Wei Zhu, Zepeng Zhang, Yu Huang

Background

This study aimed to analyze the usefulness of combined single-cell RNA sequencing data and network pharmacology in understanding the molecular regulation mechanism of Dayuan Yin (DYY) in acute lung injury (ALI).

Methods

The single-cell ALI dataset GSE224938 was acquired from the Gene Expression Database and cellular heterogeneity was examined using the Seurat software package. Differential expression analysis was conducted using the R software to identify genes with significant expression differences. The active constituents and therapeutic targets of DYY were acquired from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the protein-protein interaction (PPI) networks, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze the key targets. A visual network depicting the interaction between compounds, targets, and pathways was constructed, and the CytoNCA plug-in was utilized to identify core targets. The active component-core target relationship was validated using MOE, AutoDockTools, AutoDockVina, and other software. Finally, a preliminary experiment was conducted using the lipopolysaccharide-induced acute lung injury (ALI) rat model.

Results

In total, 5243 significantly differentially expressed genes were identified in ALI, and 260 genes were identified as DYY targets. Then, 81 target genes were identified at the intersection between drugs and diseases. The identified core target genes included PIK3R1, IL-1β, IL-6, ICAM1, and CCL2. GO analysis was mainly involved in cellular inflammatory response, dual regulation of cell apoptosis, and coordinated migration. KEGG analysis showed enrichment in inflammatory pathways. The major active components were well connected with IL-1β. DYY could significantly reduce the phosphorylation expression of PI3K, Akt, and NF-κBp65 in the lung tissue of ALI rats, and regulated the activation of related inflammatory cells.

Conclusions

We successfully screened the potential active ingredients of DYY for the treatment of ALI. In addition, in vivo experiments preliminarily verified the predictions of network pharmacology, showing that DYY can inhibit the PI3K/Akt/NF−КВ signaling pathway, reduce cytokine release and regulate the number of inflammatory cells, providing an alternative for ALI treatment.
本研究旨在分析单细胞RNA测序数据与网络药理学的结合对了解大元饮(DYY)在急性肺损伤(ALI)中的分子调控机制的意义。方法从基因表达数据库中获取单细胞ALI数据集GSE224938,采用Seurat软件包检测细胞异质性。采用R软件进行差异表达分析,找出表达差异显著的基因。从中药系统药理学(TCMSP)数据库中获取其有效成分和治疗靶点。随后,利用蛋白-蛋白相互作用(PPI)网络、基因本体(GO)和京都基因与基因组百科全书(KEGG)对关键靶点进行分析。构建了描述化合物、靶点和通路之间相互作用的视觉网络,并利用CytoNCA插件识别核心靶点。使用MOE、AutoDockTools、AutoDockVina等软件验证活动组件-核心目标关系。最后,采用脂多糖性急性肺损伤(ALI)大鼠模型进行初步实验。结果在ALI中共鉴定出5243个显著差异表达基因,其中鉴定出260个基因为DYY靶基因。然后,在药物与疾病的交叉点鉴定出81个靶基因。鉴定的核心靶基因包括PIK3R1、IL-1β、IL-6、ICAM1和CCL2。氧化石墨烯分析主要涉及细胞炎症反应、细胞凋亡的双重调控和协同迁移。KEGG分析显示炎症通路富集。主要活性成分与IL-1β有良好的联系。DYY可显著降低ALI大鼠肺组织中PI3K、Akt、NF-κBp65的磷酸化表达,调节相关炎症细胞的活化。结论我们成功筛选了DYY治疗ALI的潜在有效成分。此外,体内实验初步验证了网络药理学的预测,表明DYY可以抑制PI3K/Akt/NF−КВ信号通路,减少细胞因子释放,调节炎症细胞数量,为ALI治疗提供了一种替代方案。
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引用次数: 0
Research progress in the regulation of secondary metabolism in medicinal plants by MYB transcription factors MYB转录因子调控药用植物次生代谢的研究进展
Pub Date : 2023-12-01 DOI: 10.1016/j.jhip.2024.01.006
Xi Huang , Quan Yang , Hongyang Gao
MYB transcription factors (MYB TFs)are one of the largest families of transcription factors in plants, which are widely involved in various fields of plant growth and development, and play an important regulatory role in the biosynthesis of plant secondary metabolites. Most of the current studies on MYB transcription factors have focused on agricultural crops, and fewer studies have been conducted on medicinal plants. Therefore, this study reviews the research progress of plant MYB transcription factors in secondary metabolism of medicinal plants, which provides ideas and methods for better utilisation and development of medicinal plants.
MYB转录因子(MYB TFs)是植物中最大的转录因子家族之一,广泛参与植物生长发育的各个领域,在植物次生代谢产物的生物合成中发挥重要的调控作用。目前对MYB转录因子的研究大多集中在农作物上,对药用植物的研究较少。因此,本研究综述了药用植物MYB转录因子在药用植物次生代谢中的研究进展,为药用植物更好的利用和开发提供思路和方法。
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引用次数: 0
Vitamins strategies for psoriasis: An update on current scientific evidence 维生素治疗牛皮癣的策略:当前科学证据的更新
Pub Date : 2023-12-01 DOI: 10.1016/j.jhip.2024.01.005
Suyash Agnihotri , Jasleen Kaur , Priya Masand , Anurag , Vipan Kumar Parihar , Alok Sharma
Psoriasis is an aggressive chronic skin disorder that requires various therapies such as topical, oral, and occasionally, subcutaneous, or intravenous. In contrast, vitamins have more significant evidence in alteration to first-line therapies in the treatment of psoriasis. Vitamins such as fat-soluble and water-soluble supplements act as a secondary treatment that is given to reduce possible adverse effects from systematic medication, increase patient compliance, and consider affordable treatment costs. Here, the comparative study was conducted based on the data search from Pub Med, Google Scholar, Willy Library, etc., for both fat and water-soluble vitamins in psoriasis treatment first time. The present review summarizes the role of fat-soluble vitamins (A, D, E) and water-soluble vitamins (B2, B6, B12, and C) based therapies in psoriasis treatment and result highlights the efficiency of oral supplementation of vitamins in psoriasis and systematic inflammation. Further, clinical studies along with in-vitro and in vivo based investigations have been compiled in this review, which shows that vitamins effectively can manage psoriasis. Additionally, the present review consists of chemical identification of both fat and water-soluble vitamins by High Performance Liquid Chromatography. The role of vitamins therapies in psoriasis management is promising and can be further to give in new horizon for improving the treatment efficacy. This review could provide an insight into vitamins emerging therapy in the treatments of psoriasis.
牛皮癣是一种侵袭性慢性皮肤病,需要多种治疗方法,如局部、口服,偶尔也需要皮下或静脉注射。相比之下,维生素在银屑病治疗的一线疗法的改变中有更重要的证据。维生素(如脂溶性和水溶性补充剂)作为二级治疗,用于减少系统用药可能产生的不良反应,提高患者依从性,并考虑可负担的治疗费用。本文通过Pub Med、谷歌Scholar、Willy Library等网站的数据检索,首次对脂溶性维生素和水溶性维生素在银屑病治疗中的作用进行对比研究。本文综述了脂溶性维生素(A、D、E)和水溶性维生素(B2、B6、B12和C)在银屑病治疗中的作用,并强调了口服补充维生素对银屑病和全身炎症的疗效。此外,本综述汇编了临床研究以及体外和体内研究,表明维生素可以有效地治疗牛皮癣。此外,本文还对脂溶性维生素和水溶性维生素的高效液相色谱化学鉴定进行了综述。维生素治疗在银屑病治疗中的作用是有希望的,可以进一步为提高治疗效果提供新的视野。本综述为维生素在银屑病治疗中的应用提供了新的思路。
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引用次数: 0
Identifying candidate drugs based on transcriptional landscape associated with triple-negative breast cancer 基于与三阴性乳腺癌相关的转录景观确定候选药物
Pub Date : 2023-12-01 DOI: 10.1016/j.jhip.2023.12.001
Yuqin Lin , Yanghong Zhu , Xiang Li , Qi Chen , Guoyu Wu
Triple-negative breast cancer (TNBC) is a special type of breast cancer in which ER, PR and HER2 are all negative, characterized by high malignancy, strong invasiveness, and high recurrence rate. It is critical to develop novel drugs for improved therapies for triple-negative breast cancers. Here, we unveiled the transcriptional landscape associated with triple-negative breast cancer and identified candidate drugs using a comprehensive connectivity map. The candidate components could induce reverse expressions of the TNBC gene expression signature and trigger transcriptional reprogramming with a positive impact on modulating chemoresistance and the survival probability of breast cancer patients. Our study also provided an example of drug discovery using in silico drug screening followed by further validations, illustrating an effective computational drug discovery strategy.
三阴性乳腺癌(triple negative breast cancer, TNBC)是一种特殊类型的乳腺癌,其ER、PR、HER2均为阴性,具有恶性程度高、侵袭性强、复发率高的特点。开发新的药物来改善三阴性乳腺癌的治疗方法是至关重要的。在这里,我们揭示了与三阴性乳腺癌相关的转录景观,并使用综合连接图确定了候选药物。候选成分可诱导TNBC基因表达特征的反向表达并触发转录重编程,对调节乳腺癌患者的化疗耐药和生存率有积极影响。我们的研究还提供了一个使用计算机药物筛选进行药物发现的例子,随后进行了进一步的验证,说明了一种有效的计算药物发现策略。
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引用次数: 0
期刊
Journal of Holistic Integrative Pharmacy
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