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Volume 15 · Issue 11 · November 2025
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Review papers
Artificial intelligence guided Raman spectroscopy in biomedicine: Applications and prospects
Yuan Liu, Sitong Chen, Xiaomin Xiong, Zhenguo Wen, Long Zhao, Bo Xu, Qianjin Guo, Jianye Xia, Jianfeng Pei
J. Pharm. Anal. 2025. 15(11) 101271
https://doi.org/10.1016/j.jpha.2025.101271
拉曼光谱凭借其高灵敏度、非破坏性等优势,已成为生物制药分析与药物研发中不可或缺的重要工具。随着人工智能,特别是深度学习算法的快速发展,拉曼光谱在数据处理、特征提取和模型优化方面实现了质的飞跃,进一步拓展了其在生物医学领域的应用范围。人工智能引导的拉曼光谱技术广泛应用于药物结构表征、剂型分析、质量控制、成分鉴定及药物-生物分子相互作用研究等多个环节。此外,该技术也深刻改变了生物医学研究与临床诊断的模式,尤其在疾病早期诊断与治疗优化方面展现出巨大潜力。本文系统综述了多种人工智能方法——包括半监督学习、强化学习、迁移学习以及Transformer模型——在拉曼光谱解析中的关键作用。这些方法不仅推动了生物制药过程监控与临床诊断的智能化进程,也为疾病治疗策略和药品生产控制提供了全新的研究视角与技术支持。人工智能与拉曼光谱的深度融合,正持续为生物医学领域注入创新动力,具有广阔的发展前景。
Highlights
Raman's non-destructive, high-sensitivity drives biomedical/biopharmaceutical applications.
PLS/SVM remain key chemometric tools; ML/DL enhance analysis complexity & efficiency.
DL models (CNN, LSTM, GAN) improve pattern recognition & predictive accuracy.
Transformers enable big data processing/feature extraction, rising in Raman spectroscopy.
Mitochondrial membrane chromatography: Discovery of mitochondrial targeting modulators
Wu Su, Yu Kong, Hua Li, Yongyao Wang, Lizhuo Wang, Le Shi, Huaizhen He, Shengli Han, Hui Guo, Jiankang Liu, Jiangang Long
J. Pharm. Anal. 2025. 15(11) 101272
https://doi.org/10.1016/j.jpha.2025.101272
线粒体功能异常与衰老、神经退行性疾病、代谢综合征等密切相关,筛选线粒体靶向活性分子是相关疾病防治的关键。本文系统阐述线粒体膜色谱(MMC)技术的核心价值与应用进展:该技术通过将线粒体蛋白(含膜蛋白与基质蛋白)固定于载体制备固定相,无需纯化蛋白即可保留其天然构象与活性,整合高效液相色谱与受体药理学优势,解决传统方法靶向性差、效率低的难题。文中介绍MMC技术发展历程(物理吸附、化学键合、蛋白标签修饰等固定相制备方法),展示其在受体-配体相互作用研究、中药活性成分筛选等领域的应用,提出未来向多靶点、微型化发展及拓展至其他细胞器膜色谱技术的方向,为线粒体及其他细胞器靶向药物研发及中药现代化提供关键技术支撑。
Highlights
Proposed strategies for preventing and treating major chronic diseases through mitochondrial-targeted regulation.
Defined the concept of mitochondrial membrane chromography and detailed the protocol.
Summarized the applications of mitochondrial membrane chromatography.
Regulated cell death in age-related macular degeneration: Regulatory mechanisms and therapeutic potential
Le-Le Zhang, Jia-Mei Yu, Zhong-Xi Fan, Wen-Qi Xie, Liang Zou, Feiya Sheng
J. Pharm. Anal. 2025. 15(11) 101285
https://doi.org/10.1016/j.jpha.2025.101285
年龄相关性黄斑变性(AMD)是导致老年人不可逆视力丧失的主要疾病之一,目前临床治疗手段仍较为有限。研究表明,氧化应激、炎症反应及视网膜色素上皮损伤是推动AMD发生发展的关键病理因素。程序性细胞死亡在介导细胞应激、维持组织稳态以及促进疾病进展方面发挥核心作用,且与AMD的发生发展密切相关。本文系统综述了AMD中多种程序性细胞死亡的机制及其治疗潜力,涵盖凋亡、铁死亡、焦亡、坏死性凋亡等不同形式,详细阐述了各类细胞死亡调控通路在AMD病理进程中的作用,并探讨了针对这些通路的治疗策略,包括生物制剂、化学药物及天然产物等。文章进一步强调,靶向程序性细胞死亡具有显著的治疗潜力,有望为AMD的防治提供新的思路与药物靶点,具备重要的研究价值与应用前景。
Highlights
Age-related macular degeneration (AMD) has currently limited therapeutic options.
So far, the role of regulated cell death in AMD pathology has been neglected.
Apoptosis, ferroptosis, pyroptosis, necroptosis, and autophagy contribute to AMD.
Key elements in their pathways are promising therapeutic targets in AMD.
Recent advances in mass spectrometry-based bioanalytical methods for endogenous biomarkers analysis in transporter-mediated drug-drug interactions
Dang-Khoa Vo, Han-Joo Maeng
J. Pharm. Anal. 2025. 15(11) 101289
https://doi.org/10.1016/j.jpha.2025.101289
Highlights
Overview of potential endogenous transporters biomarkers and supporting evidence.
Summary of LC-MS(/MS) bioanalytical methods for quantifying endogenous biomarkers.
Selection of appropriate approaches for calibration curves and QC samples in biomarker quantification.
Summary of individual baseline levels of endogenous transporters biomarkers in biological fluids.
Small-molecule probes based on natural products: Elucidation of drug-target mechanisms in stroke
Xingyue Jin, Suyi Liu, Shujing Chen, Rui Han, Xingyi Sun, Mingyan Wei, Yanxu Chang, Lin Li, Han Zhang
J. Pharm. Anal. 2025. 15(11) 101290
https://doi.org/10.1016/j.jpha.2025.101290
本文聚焦天然产物(NPs)在卒中治疗新药研发中的重要作用。针对卒中药物开发中作用靶点识别这一关键挑战,基于NPs的小分子探针展现出独特优势。与传统探针相比,NPs探针凭借其丰富的结构多样性、良好的生物相容性及独特生物活性,克服了传统探针非特异性强、稳定性差与合成困难等不足,能够精确直接地探寻NPs活性小分子的相互作用蛋白靶点。本综述系统介绍了NPs小分子探针的特性,并详细探讨了其在卒中及其他疾病机制研究中的前沿应用。研究者期望这项工作能为揭示NPs活性小分子的作用机制提供新视角,进而加速其向卒中治疗候选药物的转化进程。
Highlights
Small-molecule probes based on natural products possess clear therapeutic efficacy and natural source properties.
Small molecule probes based on NPs can accurately and directly identify the interacting proteins of NPs.
Small-molecule probes based on NPs have been used for the discovery of therapeutic targets for a variety of diseases.
NPs-based small-molecule probes applied in stroke treatment offer insights into novel drug discovery.
Targeting proteostasis pathways for cancer therapy
Xiaofeng Dai, Ruohan Lyu, Guanqun Ge
J. Pharm. Anal. 2025. 15(11) 101287
https://doi.org/10.1016/j.jpha.2025.101287
蛋白质稳态失衡是驱动肿瘤发生的一个关键因素。虽然许多热休克蛋白家族成员抑制剂已进入临床试验阶段,但由于毒性等问题至今尚无获准临床应用的相关药物。本文通过分析HSP90抑制剂阻断肿瘤特征的分子机制,发现抑制HSP90可通过调节细胞蛋白质稳态,同时靶向癌症的多个关键特征。此外,本文通过建立蛋白质稳态与氧化还原稳态之间的内在关联提出低温常压等离子体(CAP)可以作为一种新型HSP90抑制剂治疗癌症并具有温和无毒副作用等优势的创新观点。最后,本文将HSP90抑制剂和CAP的治疗范围从癌症延伸至自身免疫病等其他炎症驱动性疾病。这些创新观点有助于推动现有疾病治疗模式的范式转移。
Highlights
Emphasizes the role of proteostasis in preventing carcinogenesis.
Attributes the cause of cancers to chronic inflammation.
Identifies intrinsic connections between proteostasis and redox homeostasis.
Proposes cold atmospheric plasma as a tool for maintaining proteostasis.
Extends the treatment spectrum of cold atmospheric plasma to autoimmune diseases.
Structure-based design of anticancer drugs based on β-elemene: Research foundations and development potential
Haiyi Chen, Yuntao Yu, Chenghong Hu, Lehuang Zhou, Zhe Wang, Odin Zhang, Yi Wang, Tian Xie
J. Pharm. Anal. 2025. 15(11) 101325
https://doi.org/10.1016/j.jpha.2025.101325
β-榄香烯是中药来源的重要抗癌活性成分,仅由碳氢元素构成,已被应用于多种癌症的临床治疗中。然而,β-榄香烯的理化性质和生物利用度较差,同时学界对于β-榄香烯发挥抗癌活性的具体靶标在结构层面仍无定论。本综述汇总并整理了已有的β-榄香烯抗癌机制研究,指出甲基转移酶样3蛋白(METTL3)有可能是β-榄香烯的抗癌靶点。以此蛋白作为案例,需要阐明β-榄香烯的受体-配体互作机制,并设计性质更为优良的衍生物。本文讨论了将基于结构的现代药物设计策略(SBDD)引入的可能性,涉及到传统的计算机辅助药物设计(CADD)技术如传统的基于分子对接的虚拟筛选和分子动力学模拟,及基于人工智能的药物设计(AIDD)技术如分子生成等。
Highlights
First systematic study of β-elemene’s anticancer mechanism via ligand-protein interactions.
Docking reveals novel insights for β-elemene modifications, proposed for the first time in academia.
AI-based molecular generation of β-elemene derivatives introduced, with preliminary examples provided.
CADD-driven optimization strategy for β-elemene remains applicable beyond METTL3 for other anticancer targets.
Recent trends in mesoporous carbon-based nanoplatforms for biomedical application
Wei Yang, Jinnian Ge, Mohan Jiang, Nan Zhang, Qinghe Yang, Kaisheng Nan, Qinfu Zhao, Long Wan, Xiaofan Wang
J. Pharm. Anal. 2025. 15(11) 101383
https://doi.org/10.1016/j.jpha.2025.101383
Highlights
Classification, synthesis methods and modification strategies of MCNs were expounded.
The physicochemical properties of MCNs and design strategies were highlighted.
MCNs-based nanoplatforms for tumor therapy and tumor theranostics were presented.
Antibacterial, biological detection and delivery of insoluble drugs were reviewed.
The challenges, prospects and clinical future development of MCNs were prospected.
Original articles
Revolutionizing antibiotic therapy: Polymyxin B and Fe2+-enriched liposomal carrier harness novel bacterial ferroptosis mechanism to combat resistant infections
Xiangrong Wei, Xinhui Cao, Chengyi Xu, Guangwei Shi, Hong Wang, Jinming Liu, Huiyang Li, Bingmei Yao, Yudong Zhang, Liqun Jiang
J. Pharm. Anal. 2025. 15(11) 101293
https://doi.org/10.1016/j.jpha.2025.101293
本研究针对当前日益严峻的细菌耐药性难题,提出一种“旧药新用”的创新策略,通过构建同时递送多黏菌素B(PMB)与Fe²⁺的脂质体载体(P/Fe@L-P),实现对多黏菌素耐药鲍曼不动杆菌的高效杀灭。与传统依赖LPS作用位点的抗菌机制不同,P/Fe@L-P在进入细菌后可协同促进Fenton反应,显著升高细菌内ROS与MDA水平,并下调Nrf2、GPX4等关键抗氧化蛋白,从而诱导铁死亡(ferroptosis)。研究显示,P/Fe@L-P对耐药菌株的MIC和MBC分别为54μM和192μM,较游离PMB(72μM和768μM)具有更强抑菌和杀菌能力。小鼠肺炎模型进一步验证了P/Fe@L-P在体内可显著降低肺部细菌负荷、改善组织损伤并提高存活率,治疗效果明显优于PMB。该工作不仅提供了一种突破耐药屏障的新型抗菌机制,也展示了通过递药系统激活传统抗生素潜力的可行路径,为抗生素创新研发与临床耐药感染治疗提供了新的重要思路。
Highlights
Liposomal co-delivery of polymyxin B & Fe2+ altered polymyxin B's bacterial interaction.
This liposome triggered ferroptosis, a novel bactericidal mode, in Acinetobacter baumannii.
The novel bactericidal mechanism enhanced efficacy against PMB-resistant Acinetobacter baumannii.
Caffeic acid alleviates myocardial ischemia-reperfusion injury by directly targeting Keap1N532/M550 and promoting its degradation
Ying Zhang, Huan Lan, Wenjuan Zhai, Lin Jiang, Xiaotong Xia, Fang Liu, Lin Zhang, Jinjun Wu, Zhongqiu Liu, Caiyan Wang
J. Pharm. Anal. 2025. 15(11) 101219
https://doi.org/10.1016/j.jpha.2025.101219
本研究首次揭示天然多酚化合物咖啡酸(CA)通过直接靶向并结合Keap1蛋白的N532和M550位点,促进其经p62依赖性自噬途径降解,进而激活Keap1/Nrf2信号通路,缓解心肌缺血再灌注损伤。研究利用细胞与动物模型证实,CA能显著减少氧化应激与炎症反应,增强抗氧化酶表达,改善心功能。通过晶体结构解析、分子动力学模拟及多种生物物理技术,明确了CA与Keap1的直接相互作用机制。此外,咖啡酸类似物绿原酸(CGA)也表现出类似的Keap1靶向降解能力。该研究为咖啡酸及其衍生物在心血管保护方面的临床应用提供了新的分子机制与结构基础。
Highlights
The complex structure of caffeic acid and Keap1Kelch domain was analyzed.
Caffeic acid directly targets Keap1 using multiple target confirmation techniques.
Caffeic acid promotes Keap1 degradation and inhibits myocardial ischemia-reperfusion injury.
Sulfonylation sites for adenine and its nucleosides/nucleotides
Xiaoyue Cheng, Pengcheng Li, Li Xu, Congcong Zhang, Qi Wang, Huiru Tang
J. Pharm. Anal. 2025. 15(11) 101258
https://doi.org/10.1016/j.jpha.2025.101258
磺酰化技术在生物化学研究中有着广泛的应用,但关于腺嘌呤及其核苷、核苷酸的磺酰化位点,学界却始终存在着诸多不一致和争议。本研究利用高分辨率质谱以及核磁共振波谱,对腺嘌呤及其甲基化衍生物、核苷、核苷酸与5-(N,N-二甲基氨基)萘-1-磺酰氯(DNS-Cl)和5-(N,N-二乙基氨基)萘-1-磺酰氯(DEANS-Cl)的磺酰化产物进行了全面而细致的分析。通过借助磺酰化诱导的化学位移变化以及二级质谱特征碎片离子,清晰地揭示了磺酰化位点。此外,研究者还合成了一种新型的磺酰化试剂——5-(N,N-二乙基亮氨酸氨基)萘-1-磺酰氯(DELANS-Cl),进一步探究了改变萘氨基团对磺酰化位点的潜在影响。经过一系列严谨的实验和分析发现:对于腺嘌呤,磺酰化试剂优先与N9H发生反应;对于核苷、AMP、ADP和ATP,磺酰化试剂优先与2'-OH发生反应;而对于那些2'-OH不存在的分子,如脱氧腺苷、dAMP,磺酰化试剂则优先与3'-OH发生反应。这一系列发现不仅为解决磺酰化位点的争议提供了明确的答案,也为未来相关领域的研究和应用奠定了坚实的基础。
Highlights
The sulfonylation sites were defined for adenine and its nucleosides/nucleotides.
N9H on imidazole ring was the major sulfonylation site for adenine.
2′-OH of ribose was main sulfonylation site for adenosine and its nucleotides.
3′-OH of deoxyribose was main sulfonylation site for 2′-deoxynucleosides/nucleotides.
Screening of glycan biomarkers for early detection of colorectal cancer based on novel isotope labeling relative quantitative method
Yuxuan Li, Zhenggen Piao, Songze Wang, Longhai Cui, Xinyan Li, Jinlong Ma, Chengqiang Han, Xi-Ling Li, Toufeng Jin, Jun Zhe Min
J. Pharm. Anal. 2025. 15(11) 101262
https://doi.org/10.1016/j.jpha.2025.101262
聚糖异常表达与疾病发生和发展密切相关,因此监测聚糖水平的变化对于阐明疾病机制和开发新的治疗策略至关重要。结直肠癌(CRC)是一种常见的胃肠道恶性肿瘤。然而,传统临床血清生物标志物的诊断准确性不足,导致患者在病情晚期才被确诊。鉴于此,本研究基于同位素质谱探针d0/d5-BOTC标记构建了聚糖相对定量分析新方法,并筛选了CRC患者血清和组织样本中差异性聚糖。结果发现CRC患者血清和组织样本中新型聚糖生物标志物H4N5F1SA、H5N4F、H5N4F3SA 和H5N4SA2在诊断CRC的阳性检测率高达90%以上。本研究为CRC的临床诊断提供了新的潜在生物标志物和策略。
Highlights
A novel method for differential glycans in CRC patients' serum and tissue was developed.
Seven glycans had a significant difference in the serum and tissue of CRC patients.
The sensitivity of H4N5F1SA, H5N4F, H5N4F3SA, and H5N4SA2 exceeds CEA for CRC diagnosis.
A novel strategy for early warning of CRC stages II and III was provided.
Obtain substance of anti-glioblastoma from Erigeron breviscapus through fragment-based target research (FBTR): An efficient strategy for pharmacology investigation and optimization of natural products
Chunguo Wang, Jinli Shi, Qinling Rao, Bingqing Shen, Canyu Su, Heng Chen, Zhixing Huang, Shuwei Jiang, Rongge He, Luni Xu, Muxuan Li, Yonggang Liu, Tao Ma, Yantong Xu, Xinqi Deng
J. Pharm. Anal. 2025. 15(11) 101366
https://doi.org/10.1016/j.jpha.2025.101366
天然产物(NPs)是创新药物研发的重要源泉。单体成分的靶标研究模式已经成熟,但是针对NPs复杂体系的靶标作用模式与机制解析研究,仍是亟待突破的关键科学问题。本研究建立了基于片段的靶标研究(FBTR)新策略,实现了NPs复杂体系中成分的共有靶标鉴定和药物优化研究。以灯盏细辛提取物(EBP)治疗胶质母细胞瘤(GBM)为范例,通过FBTR策略,最终获得了具有明确靶点的有效组分(EBPP)。EBPP不仅能通过靶向Fas相关死亡结构域蛋白(FADD)第105位半胱氨酸位点,高效诱导GBM免疫原性细胞死亡(ICD),还能显著延长GBM模型小鼠中位生存期。本研究证实了FBTR在NPs复杂体系的靶标作用模式和机制解析中的价值,并在推进NPs药物优化实现临床转化方面具有实用性。
Highlights
The FBTR approach was introduced in this study.
FBTR can be applied in exploring the function of natural products, revealing the target, and advancing drug optimization.
With FBTR, an optimized NPs named EBPP with definite target was obtained for glioblastoma treatment.
Signatures of proteomics and glycoproteomics revealed liraglutide ameliorates MASLD by regulating specific metabolic homeostasis in mice
Yuxuan Chen, Chendong Liu, Qian Yang, Jingtao Yang, He Zhang, Yong Zhang, Yanruyu Feng, Jiaqi Liu, Lian Li, Dapeng Li
J. Pharm. Anal. 2025. 15(11) 101273
https://doi.org/10.1016/j.jpha.2025.101273
代谢相关性脂肪性肝病(MASLD)与肥胖、2型糖尿病风险升高密切相关。利拉鲁肽(Lira)作为胰高血糖素样肽-1受体激动剂,已获FDA批准用于治疗糖尿病和肥胖症。尽管Lira具备明确的肝脏代谢改善作用,但其在MASLD中的深层机制,尤其是对关键糖基化病理轴的调控方式仍未明确。本研究利用定量蛋白质组学与位点分辨N-糖蛋白质组学揭示,Lira除调控蛋白表达外,在糖基化层面呈现更强且独立的效应,其对特定N-糖基化位点的影响显著高于对蛋白丰度的调节,并主要关联于氨基酸和碳水化合物代谢。结果表明,Lira通过重塑“代谢–糖基化”网络发挥作用,而蛋白变化则聚焦脂质代谢和纤维化,与糖基化形成互补机制。此外,本研究进一步设计了可延长给药间隔的Lira缓释水凝胶制剂,为提高依从性和优化临床应用提供了新的给药策略。本研究系统描绘了Lira的调控网络与作用靶标,为理解GLP-1RA类药物的肝脏作用提供新的视角,并为MASLD精准治疗策略提供关键科学依据。
Highlights
Comprehensive proteomics and glycoproteomics revealed MASLD mechanisms in HFD mice.
Liraglutide increased glycosylation, identifying 255 independent and impactful sites.
Liraglutide regulated amino acid and lipid metabolism, ferroptosis, and fibrosis.
Identified 21 signature molecules offered potential therapeutic targets.
Lira@Fib Gel improved delivery and efficacy for chronic metabolic disease management.
Dexamethasone palmitate-loaded sHDL nanodiscs: Enhanced efficacy and safety in allergic conjunctivitis
Jiawei Li, Pengyue Liu, Yue Zhang, Fan Yang
J. Pharm. Anal. 2025. 15(11) 101276
https://doi.org/10.1016/j.jpha.2025.101276
本研究开发了用于变应性结膜炎的sHDL纳米盘激素滴眼剂(DXP-sHDL)。地塞米松棕榈酸酯被稳定装载于约10nm的合成HDL盘状纳米结构中,形成澄清透明、可过滤灭菌、无需防腐剂且在低温长期稳定的滴眼剂,兼具安全性与产业化潜力。在小鼠过敏性结膜炎模型中,DXP-sHDL 显著延长眼表滞留时间、提升角膜渗透,并在远低于传统剂量下有效缓解红肿、瘙痒和分泌物。其作用机制包括抑制Th2型细胞因子与IgE,减少嗜酸性粒细胞浸润和肥大细胞脱颗粒,从而实现强效抗炎抗过敏。安全性优于市售激素滴眼液,显示出作为前节眼病创新递药平台的突出应用价值。
Highlights
The residence time of synthetic high-density lipoprotein nanodisc eye drops on the ocular surface of mice is prolonged.
The synthetic high-density lipoprotein nanodisc eye drops exhibit superior permeability performance in vitro.
The synthetic high-density lipoprotein nanodisc eye drops reduce the concentration of corticosteroids during administration.
The synthetic lipoprotein nanodisc eye drops are free of preservatives, exhibiting high safety and minimal side effects.
USP50-mediated NLRP3 deubiquitination enhances NLRP3 inflammasome activation to suppress HCC metastasis
Zhengyan Gong, Yuhong Li, Yixuan Nie, Shenhao Zhang, Xiaoyu Tang, Yu Hu, Tianfeng Yang, Man Zhu, Wenjuan Tang, Qi Su, Yingzhuan Zhan, Dongdong Zhang, Bingling Dai, Yanmin Zhang
J. Pharm. Anal. 2025. 15(11) 101380
https://doi.org/10.1016/j.jpha.2025.101380
本研究证实了NOD样受体热蛋白结构域蛋白3(NLRP3)具有抑制肝癌增殖转移的生物学功能。机制层面阐明,NLRP3通过与GSK3β结合,负向调控β-catenin信号通路,进而逆转上皮-间质转化(EMT)进程,最终发挥抗肝癌效应;β-catenin补救实验进一步验证,明确了NLRP3/GSK3β/β-catenin调控轴在肝癌发生发展中的作用。同时发现,泛素特异性肽酶50(USP50)在肝癌中低表达,其表达水平与患者不良预后显著相关。深入机制研究表明,USP50可通过特异性去除NLRP3蛋白K48位的多聚泛素链,提高其蛋白稳定性并增强其功能活化,进而正向调控NLRP3炎症小体的激活过程。本研究不仅系统揭示了NLRP3与USP50在肝癌中的关键调控作用及分子网络,为肝癌治疗提供了潜在新型靶点,更为临床开发针对性抗癌策略提供了重要的理论支撑与实验依据。
Highlights
USP50 interacts with NLRP3 at the PYD domain.
USP50 increases NLRP3 expression depending on its deubiquitinase activity.
NLRP3 negatively regulates β-catenin by binding with GSK3β in HCC.
USP50 inhibits HCC metastasis by activating NLRP3 inflammasome.
Ursolic acid ameliorates ocular surface dysfunction in dry eye via targeting EGFR/RAS/RAF/MAP2K1/MAPK1 pathway
Qinghe Zhang, Ke Yan, Yufei Lv, Qiuping Liu, Yi Han, Zuguo Liu
J. Pharm. Anal. 2025. 15(11) 101294
https://doi.org/10.1016/j.jpha.2025.101294
干眼(DE)是一种由多种因素引起、以眼表炎症为主要病理特征的疾病。熊果酸(UA)是一种具有显著抗炎特性的五环三萜类化合物。本研究评估了UA对干眼相关眼表功能障碍的治疗效果及其潜在机制。通过高渗应激模型和干眼动物模型,发现UA对细胞和动物整体水平具有保护作用。通过数据库挖掘和网络药理学分析,揭示了UA作用于干眼的核心靶点和信号通路,分子对接模拟进一步阐明了UA与其靶点之间的相互作用模式。进一步研究表明,UA通过调节EGFR/RAS/RAF/MAP2K1/MAPK1信号通路发挥治疗作用,其能改善炎症,有效修复角膜上皮,减轻干眼相关的眼表损伤。
Highlights
UA, a natural small molecule compound, is therapeutic potential for DE.
UA maintains homeostasis in HCEs under hyperosmotic stress.
UA promotes recovery of damaged ocular surfaces, alleviating DE in vivo.
UA mitigates lacrimal and meibomian gland dysfunction associated with DE.
UA exerts therapeutic effects on DE via modulation of the EGFR/RAS/RAF/MAP2K1/MAPK1 signaling pathway.
Gut microbiota-bile acid metabolic disorder involved in the cognitive impairments in epilepsy through HO-1 dependent ferroptosis
Xinyu Li, Jia Ji, Jing Li, Saisai Li, Qiang Luo, Maosheng Gu, Xin Yin, Meng Zhang, Hongbin Fan, Ruiqin Yao
J. Pharm. Anal. 2025. 15(11) 101291
https://doi.org/10.1016/j.jpha.2025.101291
本研究系统阐明了肠道菌群-胆汁酸代谢紊乱在癫痫及其认知障碍中的重要作用。靶向代谢组学分析显示,癫痫患者血清与脑脊液中的脱氧胆酸(DCA)显著升高,并与认知受损密切相关。结合16S核糖体RNA(16S rRNA)测序及小鼠模型,研究者证实癫痫诱导的肠道菌群失衡会加重包括DCA在内的次级胆汁酸(SBAs)代谢紊乱。来自健康小鼠的粪菌移植(FMT)能够纠正菌群和胆汁酸失衡,明显降低癫痫发作强度并改善认知表现。机制研究显示,DCA激活法尼醇X受体(FXR),上调血红素加氧酶1(HO-1)表达,从而诱导海马神经元铁死亡,加重癫痫病理过程。本研究首次从“肠道菌群-胆汁酸-神经元铁死亡”视角阐明了癫痫进展机制,并提出了“DCA-FXR-HO-1”轴作为潜在治疗靶点,为癫痫精准干预提供了全新思路。
Highlights
DCA is elevated in serum and CSF of epilepsy patients and correlates with cognitive impairment.
Gut microbiota dysbiosis links bile acid metabolism to ferroptotic neuronal death in epilepsy.
DCA activates FXR/Nrf2-HO-1 signaling to promote ferroptosis and neuronal injury.
Targeting the DCA-FXR pathway may help treat epilepsy and cognitive deficits.
Short communications
Time-specific study on the efficacy of stems and leaves of Arachis hypogaea L. targeting glycine/serine metabolism for insomnia treatment
Yin Wang, Yuling Huang, Guohua Wang, Ting Jiang, Shuwen Geng, Hongzhan Xu, Tingting Zhou, Wenjing Zhang
J. Pharm. Anal. 2025. 15(11) 101288
https://doi.org/10.1016/j.jpha.2025.101288
失眠症发病率高,危害性强,已成为全球重要的公共卫生问题,亟需安全有效的治疗手段。在自然界中一些植物具有“昼开夜合”的特性,这与人类的昼夜节律相一致。根据中医“天人相应”理论,这些“昼开夜合”的植物可能可以治疗失眠。本研究对具有“昼开夜合”特性的花生枝叶(PSL)开展一系列实验,采用UPLC-Q-TOF/MS对PSL成分进行了定性定量分析,并通过腹腔注射对氯苯丙氨酸(PCPA)建立了失眠大鼠模型,研究了PSL抗失眠疗效的时间特异性。代谢组学和转录组学分析显示甘氨酸/丝氨酸代谢与失眠症密切相关,且不同时间点服用PSL对失眠症的疗效以及甘氨酸/丝氨酸代谢水平存在显著差异——睡前服用抗失眠疗效最佳。本研究对失眠的病理生理特点具有重要意义,为优化“昼开夜合”植物(如PSL)在失眠治疗中的给药时间提供了科学依据。
Highlights
The timing of administration affects the hypnotic efficacy of Arachis hypogaea L., which exhibits diurnal opening and nocturnal closing characteristics.
Glycine and serine are potential insomnia biomarkers, showing similar trends across species and samples.
Arachis hypogaea L. time-specific regulation of glycine metabolism in the treatment of insomnia provides new ideas for the use of similar traditional Chinese tranquillizing medicine.
A DPAL method for the identification of the synergistic target of drugs
Dongyao Wang, Yuxiao Tang, Na Li, Chenghua Wu, Jianxin Yang, Mengpu Wu, Feng Lu, Yifeng Chai, Chenqi Li, Hui Shen, Xin Dong, Changquan Ling
J. Pharm. Anal. 2025. 15(11) 101351
https://doi.org/10.1016/j.jpha.2025.101351
华蟾素注射液是治疗肝癌的常用中药提取物,其主要有效成分蟾毒灵(Bufalin,B)、华蟾酥毒基(Cinobufagin,C)与脂蟾毒配基(Resibufogenin,R)组成的BCR组合,展现出显著的协同抗肝癌效应。然而,这一协同作用的分子靶点长期不明。本研究创新性运用DNA编程亲和标记(DPAL)技术,通过多组学分析与功能验证,成功锁定磷脂酰肌醇5-磷酸4-激酶2A(PIP4K2A)为BCR组合的特异性协同靶点。研究证实,BCR组合可通过结合PIP4K2A抑制其酶活性,调控脂质代谢通路,进而诱导肝癌细胞凋亡;而敲除PIP4K2A后,BCR的协同抗癌效应完全消失。该成果不仅揭示了华蟾素注射液协同抗癌的核心机制,更为中药复方协同靶点的筛选提供了高灵敏度、低干扰的DPAL技术方案,为中西医结合抗癌药物的研发提供了重要理论支撑与技术借鉴。
Highlights
A highly sensitive, low interference DPAL method for identifying the synergistic targets of drugs.
PIP4K2A is the synergistic target of the combination of Bufalin, Cinobufagin, and Resibufogenin.
PIP4K2A mediates the anti-HCC effects of Bufalin, Cinobufagin, and Resibufogenin synergism.
Butyrate-based ionic liquid for improved oral bioavailability and synergistic anti-colorectal cancer activity of glycyrol
Ziyu Wang, Xingyue Shi, Yikang Shu, Ran Gao, Ting Sun, Mingyue Wu, Mingxin Dong, Weiguo Wu, Ruili Ma, Daoquan Tang, Min Ye, Shuai Ji
J. Pharm. Anal. 2025. 15(11) 101359
https://doi.org/10.1016/j.jpha.2025.101359
甘草酚具有显著的抗结肠癌活性,但由于溶解度差,其口服生物利用度较低。本研究报道了一种用于口服递送甘草酚且具有抗结肠癌活性的离子液体,旨在提高其生物利用度并实现协同抗癌效果。首先,以具有抗结肠癌活性的丁酸为阴离子合成了四种离子液体,通过筛选发现其中的甜菜碱丁酸盐([BE][BA])能够显著提高甘草酚的口服生物利用度。机理研究表明,[BE][BA]能够增加甘草酚的溶解度,同时通过抑制MRP2来降低甘草酚的外排,从而促进其跨细胞吸收转运。另一方面,甘草酚与[BE][BA]在体外协同促进结肠癌细胞的凋亡,同时在裸鼠移植瘤模型中也展现出协同抗结肠癌效果。本研究为难溶性药物或天然产物的口服递送提供了新思路。
Highlights
Four new edible ionic liquids using butyrate as the anion were synthesized.
[BE][BA] increased oral bioavailability of glycyrol and other same type of compounds.
[BE][BA] enhanced solubility of glycyrol.
[BE][BA] promoted glycyrol absorption transport by inhibiting MRP2-mediated efflux.
Glycyrol and [BE][BA] had synergetic anti-colorectal cancer effect in vitro/in vivo.
近期阅读:
Journal of Pharmaceutical Analysis 2025年第10期
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Journal of Pharmaceutical Analysis(JPA,《药物分析学报(英文)》)创刊于2011年,由教育部主管,西安交通大学主办,是国内第一本有关药物分析的专业英文学术期刊,JPA 始终秉承服务国家重大战略需求、建设世界一流科技期刊的办刊宗旨,重点报道药物发现与药品全生命周期质量控制的新理论、新技术、新方法,临床精准用药,以及药物与生物、人工智能等交叉领域的技术方法方面的最新研究成果,为全球药物研发和药品质量控制提供高水平的国际学术交流平台,持续推动药物分析学科以及药学领域的快速发展。
JPA目前已组建一支以主编贺浪冲教授为核心的国际化的学术团队和专业的编辑出版团队,已实现编委国际化、稿源国际化、同行评议国际化、读者国际化和出版国际化。已被SCIE、PubMed、Scopus、DOAJ、中国科学引文数据库(CSCD)等多种重要国际和国内数据库和评价体系定为刊源。JPA连续7年入选“中国最具国际影响力学术期刊”。2019年入选“中国科技期刊卓越行动计划”重点期刊,2024年入选“中国科技期刊卓越行动计划二期”英文领军期刊。2024年影响因子 8.9,位于全球药理学和药学类学术期刊第14位(14/352),进入药学与药理学前4%,继续稳居于Q1区前列。2025年中科院1区,Top期刊。
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药物分析新技术、新方法,分析药理学,药物代谢与递送,中药与天然药物,生物传感,可视化分析,生物功能分析,生物技术药物,药物分析装备,人工智能应用
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编辑 | 李 蕾
校对 | 朱丹丹
审核 | 王梦杰、马维娜
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