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Exploring the therapeutic potential of Anoectochilus roxburghii in glucose and lipid metabolism disorder: From phenotypic effects to molecular mechanisms and network pharmacology 探索刺梨对糖脂代谢紊乱的治疗潜力:从表型效应到分子机制和网络药理学
IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2026-01-12 DOI: 10.1016/j.jpba.2026.117360
Wei Li , Yaqian Cheng , Tong Wu , Chenning Zhao , Qingsong Shao , Lanying Pan , Ying Zheng
Dysregulation of glucose and lipid metabolism has emerged as a leading cause of cardiovascular diseases worldwide. The current treatment for these diseases is often a combination of drugs. Despite the preference efficacy of combination therapies, adverse reactions have been frequently reported, such as gastrointestinal bleeding. Anoectochilus roxburghii (Wall.) Lindl., one of the traditional Chinese medicines, is recognized for its hypolipidemic and hypoglycemic effects. However, the exact therapeutic potential of A. roxburghii in glucose and lipid metabolism remains unsolved. By employing in vitro and in vivo experiments, this study evaluated the pharmacological activities of A. roxburghii and identified the primary active compounds involved in glucose and lipid metabolism. The results indicated that A. roxburghii can ameliorate dysregulation in glucose and lipid metabolism by promoting glycogen synthesis, and inhibiting gluconeogenesis and fatty acid oxidation. Using UHPLC-QE-MS, a total of 662 compounds were detected in the aqueous extract of A. roxburghii, and 769 were identified in the ethanol extract. Key ingredients such as morin and kaempferol participated in glucose metabolism, while kinsenoside and naringenin modulating lipid metabolism. Furthermore, A. roxburghii may potentially intervene in the insulin resistance signaling pathway by influencing TP53 protein expression, thereby modulating glucose metabolism process. This research provides evidence for the development and application of A. roxburghii as potential drugs in the treatment of glucose and lipid disordered diseases.
葡萄糖和脂质代谢失调已成为世界范围内心血管疾病的主要原因。目前对这些疾病的治疗通常是药物联合治疗。尽管联合治疗的疗效优先,但不良反应也经常被报道,如胃肠道出血。野牡丹(属)采用。中药之一,以其降血脂和降血糖的作用而闻名。然而,刺梨在葡萄糖和脂质代谢方面的确切治疗潜力仍未得到解决。本研究通过体外和体内实验,对刺梨的药理活性进行了评价,鉴定出参与糖脂代谢的主要活性化合物。结果表明,刺梨可通过促进糖原合成、抑制糖异生和脂肪酸氧化等途径改善糖脂代谢失调。采用UHPLC-QE-MS技术,在刺梨水提物中共检出662个化合物,在刺梨乙醇提物中共检出769个化合物。桑辣素和山奈酚等关键成分参与葡萄糖代谢,而人参皂苷和柚皮素调节脂质代谢。此外,刺梨可能通过影响TP53蛋白表达而潜在地干预胰岛素抵抗信号通路,从而调节葡萄糖代谢过程。本研究为刺梨作为治疗糖脂类疾病的潜在药物的开发和应用提供了依据。
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引用次数: 0
Integrated dual-molecular marker analysis with SSR and UPLC-Q-TOF/MS fingerprints technology reveal the interrelation of the molecule-metabolite in Morus alba L. leaves 基于SSR和UPLC-Q-TOF/MS指纹图谱技术的综合双分子标记分析揭示了桑树叶片中分子代谢物的相互关系
IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2026-01-12 DOI: 10.1016/j.jpba.2026.117359
Yuqing Tian , Pei Ma , Liang Wang , Bei Song , Jinghua Yang , Dan Qian , Wei Guo
Morus alba L. (M. alba) leaves, valued for their medicinal and edible properties, possess substantial economic and social importance. Notably, diverse germplasm resources of M. alba exhibit considerable variation in both metabolite composition and pharmacological activity. However, the interrelationships among genetic diversity, metabolites profiles, and pharmacological activity across different M. alba varieties remain insufficiently elucidated. This study aimed to construct simple sequence repeat (SSR) and ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) fingerprints, together with antipyretic clustering diagrams, for 69 different varieties of M. alba leaves, and analyze the correlations among their genetic structures, metabolite profiles, and antipyretic activities. In this study, 69 M. alba leaf samples representing different varieties were collected, and their antipyretic effects were evaluated using a rat pharmacodynamic model. SSR fingerprints were generated with TP-M13 SSR molecular markers to screen core primer pairs for variety identification. Simultaneously, metabolite fingerprints were established using UPLC-Q-TOF/MS with common peaks calibrated and compounds qualitatively identified by mass spectrometry. Finally, multivariate chemometric approaches were applied to integrate SSR data and UPLC-Q-TOF/MS fingerprint profiles, and antipyretic activity results for clustering and correlation analysis. The dominant M. alba varieties, Yantai 792, Zhesang 3, 8036, Fengyuan 1, Laiwugusang, Xiajingusang, Gaoqing 792, Zhesang 1 and Heizhenzhu exhibited the strongest antipyretic activities. In contrast, Guiyou, Danbaisang, and Dashi showed weaker effects and were clustered into a single category in the molecule-metabolite-efficacy clustering diagram, thereby indicating the substantial influence of varieties differences on genetic diversity, metabolite composition, and pharmacological activity. Pearson correlation analysis further confirmed significant correlations among genetic components, metabolites, and pharmacological effects. In addition, a core marker set comprising 7 SSR loci was identified, together with 8 key chemical markers including cryptochlorogenic acid, neochlorogenic acid, isoquercitrin, rutin, nicotiflorin, astragalin, salicylic acid, and umbelliferone. These findings help identify the “molecule-metabolite” dual molecular markers with the bias of antipyretic effects for M. alba leaves varieties, and provide valuable insights for refining the medicinal value of M. alba leaves and promoting the utilization of high-value resources.
桑叶因其药用和食用特性而受到重视,具有重要的经济和社会意义。值得注意的是,不同的白支霉种质资源在代谢物组成和药理活性方面都表现出相当大的差异。然而,遗传多样性、代谢物谱和药理活性之间的相互关系仍未得到充分阐明。本研究旨在构建69个不同品种白杨叶片的简单序列重复(SSR)和超高效液相色谱四极杆飞行时间质谱(UPLC-Q-TOF/MS)指纹图谱,并结合解热聚类图,分析其遗传结构、代谢物谱和解热活性之间的相关性。在本研究中,69 M。采用大鼠药效学模型对不同品种的白桦叶进行解热实验。利用TP-M13 SSR分子标记生成SSR指纹,筛选核心引物对进行品种鉴定。同时,采用UPLC-Q-TOF/MS建立代谢物指纹图谱,对共有峰进行了标定,并用质谱法对化合物进行了定性鉴定。最后,采用多元化学计量学方法对SSR数据、UPLC-Q-TOF/MS指纹图谱和解热活性结果进行聚类分析和相关分析。优势品种烟台792、浙桑3号、8036、凤源1号、莱乌古桑、下津古桑、高青792、浙桑1号和黑镇珠的解热活性最强。而贵油、丹白桑和大石药效较弱,在分子-代谢-药效聚类图中聚为一类,说明品种差异对遗传多样性、代谢物组成和药理活性的影响较大。Pearson相关分析进一步证实了遗传成分、代谢物和药理作用之间的显著相关性。鉴定出7个SSR位点组成的核心标记集,以及隐绿原酸、新绿原酸、异槲皮苷、芦丁、烟叶苷、黄芪甲苷、水杨酸、伞形花酮等8个关键化学标记。这些发现有助于在白叶品种中鉴定出具有解热作用偏倚的“分子-代谢物”双分子标记,为提炼白叶药用价值和促进高价值资源的利用提供有价值的见解。
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引用次数: 0
Identification of metabolites from the Himalayan herbal medicine Meconopsis integrifolia total flavonoids fraction in rats using UPLC-Q-exactive orbitrap-MS analysis 用uplc - q -高通量轨道谱-质谱法鉴定喜马拉雅草药绿绒蒿总黄酮大鼠代谢产物
IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2026-01-12 DOI: 10.1016/j.jpba.2026.117357
Enhui Ji , Yuan Liu , Yifan Tian , Limin Li , Pei Qun , Zhengming Yang , Chaoqin Ren , Yanfei Huang , Yongcang Zhang
Meconopsis integrifolia total flavonoids (MITF) have been identified as the hepatoprotective fraction of M. integrifolia, with its main components being flavonoid glycosides, along with lower levels of phenolic acids and alkaloids. Since flavonoid glycosides are poorly absorbed in vivo, metabolism serves as a crucial pathway for their biotransformation. However, the metabolism and material basis of pharmacological effects of MITF in vivo remain unknown. In this study, ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry was used to investigate the metabolic profiles of MITF. A total of 61 absorbed prototype compounds were identified, including 54 in feces (43 flavonoids, 8 phenolic acids, and 3 alkaloids), 8 in urine (2 flavonoids, 3 phenolic acids, 3 alkaloids), and 6 in plasma (2 flavonoids, 4 phenolic acids). Furthermore, 113 metabolites were characterized, including 64 in feces (38 flavonoids, 11 phenolic acids, 15 alkaloids), 46 in urine (17 flavonoids, 16 phenolic acids, 13 alkaloids), and 14 in plasma (5 flavonoids, 9 phenolic acids). The major metabolic pathways were dehydroxylation, hydroxylation, reduction, dehydrogenation, hydration, dehydration, methylation, sulfation, and glucuronidation. The results indicated that the biotransformation and absorption of flavonoids in vivo were limited. In contrast, phenolic acids and alkaloids were extensively absorbed. This research provides crucial insights into the metabolic fate of MITF in rats, thereby clarifying the pharmacologically active substances derived from M. integrifolia.

Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
综合Meconopsis integrifolia total flavonoids (MITF)是综合Meconopsis integrifolia的保肝成分,其主要成分为黄酮类苷,酚酸和生物碱含量较低。由于黄酮类苷在体内吸收较差,代谢是其生物转化的重要途径。然而,MITF在体内的代谢和药理作用的物质基础尚不清楚。本研究采用超高效液相色谱联用三重四极杆质谱法研究了MITF的代谢谱。共鉴定出61种吸收原型化合物,其中粪便54种(43种黄酮类化合物、8种酚酸类化合物和3种生物碱)、尿液8种(2种黄酮类化合物、3种酚酸类化合物、3种生物碱)和血浆6种(2种黄酮类化合物、4种酚酸类化合物)。共鉴定出113种代谢物,其中粪便64种(38种黄酮类化合物,11种酚酸,15种生物碱),尿液46种(17种黄酮类化合物,16种酚酸,13种生物碱),血浆14种(5种黄酮类化合物,9种酚酸)。主要代谢途径为去羟基化、羟基化、还原、脱氢、水化、脱水、甲基化、磺化和葡萄糖醛酸化。结果表明,黄酮类化合物在体内的生物转化和吸收是有限的。相反,酚酸和生物碱被广泛吸收。本研究为了解MITF在大鼠体内的代谢命运提供了重要的见解,从而阐明了来自整合芽孢杆菌的药理活性物质。数据可获得性支持本研究结果的数据可根据通讯作者的要求提供。由于隐私或道德限制,这些数据不会公开。
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引用次数: 0
A standard-free strategy for the differentiation of isomers and deep profiling of chemicalome in Chinese medicinal formulas 中药配方中异构体鉴别和化学组深度分析的无标准策略
IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2026-01-09 DOI: 10.1016/j.jpba.2026.117349
Ying-Shan Li , Xing-Ting Dong , Gui-Zhong Xin , Li-Fang Liu , Zi-Qi Shi
The precise differentiation of isomers is crucial for comprehensive mass spectrometry-based analysis of complex Chinese medicinal formulas (CMFs). To address this challenge, a standard-free strategy was proposed by integrating chromatographic behavior, mass spectrometric behavior, and quantum chemical calculations. Firstly, structural isomers and certain stereoisomers were differentiated based on characteristic fragment ions and calculated partition coefficient (clogP). For remaining indistinguishable isomers, fragment ions with significant intensity differences were identified, and 3D molecular structures of the precursor ions, product ions, and neutral loss fragments were constructed. The bond dissociation enthalpies (BDE) for critical fragmentation pathways were computed using density functional theory (DFT) and correlated with relative fragment ion abundances to achieve differentiation, following the principle that higher cleavage energies correspond to reduced fragmentation efficiency and lower product ion intensities. The methodology was validated using limited standards and the optimal collision energy (OCE) fitting. Using Qiangli Pipa syrup as a case, this integrated approach enabled the identification of 203 compounds, including 40 isomer groups comprising 27 structural isomers and 13 stereoisomers. This strategy overcomes the limitations of conventional methods that are typically restricted to specific structural classes, demonstrating robust capability for systematic isomer differentiation in CMFs.
同分异构体的精确鉴别是复杂中药复方综合质谱分析的关键。为了解决这一挑战,通过整合色谱行为、质谱行为和量子化学计算,提出了一种无标准策略。首先,根据特征碎片离子和计算的分配系数(clogP)区分结构异构体和某些立体异构体;对于其余难以区分的异构体,鉴定出强度差异显著的片段离子,构建前体离子、产物离子和中性损失片段的三维分子结构。利用密度泛函理论(DFT)计算了关键断裂途径的键解离焓(BDE),并与相对碎片离子丰度相关联,从而实现了区分,遵循更高的裂解能对应更低的断裂效率和更低的产物离子强度的原则。采用有限标准和最优碰撞能量拟合对方法进行了验证。以强力琵琶糖浆为例,该方法鉴定了203个化合物,包括40个异构体基团,27个结构异构体和13个立体异构体。该策略克服了传统方法通常局限于特定结构类的局限性,展示了CMFs系统异构体分化的强大能力。
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引用次数: 0
Three-dimensional high-performance liquid chromatographic determination of serine, threonine and allothreonine enantiomers in the d-amino acid oxidase deficient mice and rats. 三维高效液相色谱法测定d-氨基酸氧化酶缺陷小鼠和大鼠体内丝氨酸、苏氨酸和异苏氨酸对映体。
IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2026-01-08 DOI: 10.1016/j.jpba.2026.117348
Mai Oyaide, Takeyuki Akita, Chiharu Ishii, Yukiko Shimizu, Masashi Mita, Ryuichi Konno, Tadashi Okamura, Kenji Hamase

The amounts of the serine (Ser), threonine (Thr) and allothreonine (aThr) enantiomers were determined in tissues (cerebrum, cerebellum, pancreas, liver and kidney) and physiological fluids (plasma and urine) of rats and mice with deficiency of d-amino acid oxidase (DAO). DAO is an enzyme metabolizing d-amino acids in mammals and has been implicated in the pathophysiology of several diseases via the alteration of d-amino acids. To determine trace levels of the amino acid enantiomers, a three-dimensional (3D) HPLC system composed of reversed-phase, anion-exchange and chiral separations was designed and utilized. Prior to the 3D-HPLC analysis, the analytes were derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole to enhance the fluorescence detection sensitivity. By using the 3D-HPLC system, the tissues and physiological fluids of F344-Daoldao rats and B6DAO-/- mice (animals with the DAO deficiency) were analyzed. In both species, d-Ser levels were elevated in the absence of DAO activity except for the cerebrum. The amounts of d-Thr and d-aThr were increased in the cerebellum and kidney with the DAO deficiency while their amounts were almost the same in the other tissues and physiological fluids. These results indicated that the intrinsic d-Ser analogues were metabolized by DAO in mammals and further studies to clarify its physiological significance are expected.

测定了d-氨基酸氧化酶(DAO)缺乏大鼠和小鼠的组织(大脑、小脑、胰腺、肝脏和肾脏)和生理液体(血浆和尿液)中丝氨酸(Ser)、苏氨酸(Thr)和异素苏氨酸(aThr)对映体的含量。DAO是一种在哺乳动物体内代谢d-氨基酸的酶,并通过改变d-氨基酸参与多种疾病的病理生理。为了测定氨基酸对映体的痕量水平,设计并利用了由反相、阴离子交换和手性分离组成的三维高效液相色谱系统。在进行3D-HPLC分析之前,将分析物与4-氟-7-硝基-2,1,3-苯并恶二唑进行衍生化,以提高荧光检测灵敏度。采用3D-HPLC系统对f344 - DAO大鼠和B6DAO-/-小鼠(DAO缺乏症动物)的组织和生理体液进行分析。在这两个物种中,除大脑外,在没有DAO活性的情况下,d-Ser水平升高。d-Thr和d-aThr在DAO缺乏症患者的小脑和肾脏中含量升高,而在其他组织和生理体液中含量几乎相同。这些结果表明,内在的d-丝氨酸类似物在哺乳动物中被DAO代谢,需要进一步的研究来阐明其生理意义。
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引用次数: 0
Ease of analysis through unification: One gas chromatographic method for the chemical profiling of essential oils 统一易于分析:一种用于精油化学分析的气相色谱方法
IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2026-01-08 DOI: 10.1016/j.jpba.2026.117350
Dominik Kresnik, Bryan Bajor, Christian Steuer
The rising interest in essential oils (EOs) for their therapeutic, antibacterial, and antifungal properties has led to an increasing demand for high-quality products in both medicinal and industrial sectors. To meet these stringent quality requirements, robust, precise, and efficient analytical methods are essential. Gas chromatography (GC) remains the gold standard for EO analysis due to its sensitivity and resolution. Although numerous methods are available –primarily targeting similar analytes in varying combinations standardization remains a challenge, with protocols differing across ISO guidelines and international pharmacopoeias. In this study, Design of Experiments (DoE) was employed to optimize and harmonize existing GC methods, focusing on sample preparation and chromatographic parameters. A polar GC column (60 m length, 0.25 mm inner diameter, 0.25 µm film thickness) was selected for its ability to effectively separate 87 terpenes, sesquiterpenes, and related compounds commonly found in EOs. The optimized temperature gradient enabled complete separation within a 75-minute runtime, outperforming or matching existing methods in terms of resolution and reproducibility. Streamlined sample preparation protocols led to reduced solvent consumption and minimized sample requirements across all tested EOs. As a proof of concept, the final method was applied to 12 different essential oils, demonstrating comparable analytical performance and confirming its broad applicability and efficiency.
由于精油具有治疗、抗菌和抗真菌的特性,人们对精油的兴趣日益浓厚,这导致医药和工业部门对高质量产品的需求不断增加。为了满足这些严格的质量要求,稳健、精确和高效的分析方法是必不可少的。气相色谱法(GC)因其灵敏度和分辨率而成为EO分析的金标准。尽管有许多方法可用,但主要针对不同组合的类似分析物,标准化仍然是一个挑战,ISO指南和国际药典的协议不同。本研究采用实验设计(Design of Experiments, DoE)对现有的气相色谱方法进行优化和协调,重点关注样品制备和色谱参数。极性气相色谱柱(60 m长,0.25 mm内径,0.25 µm膜厚)能够有效分离EOs中常见的87种萜类、倍半萜类及相关化合物。优化后的温度梯度可以在75分钟内完成分离,在分辨率和重现性方面优于或匹配现有的方法。简化的样品制备方案减少了溶剂消耗,并将所有测试EOs的样品需求降至最低。作为概念验证,最后的方法被应用于12种不同的精油,展示了可比的分析性能,并证实了其广泛的适用性和效率。
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引用次数: 0
A readily interpretable rule involving multiple forms of pairwise molecule comparisons with applications for clinical make-decision of breast cancer management 一个容易解释的规则,涉及多种形式的两两分子比较与乳腺癌管理的临床决策应用
IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2026-01-07 DOI: 10.1016/j.jpba.2026.117347
Xin Huang , Jingyu Chen , Xinyu He
Cells of breast cancer (BC) can metastasize to lymph nodes or other organs and is the high leading cause of female cancer deaths. Efforts to improve the performance of early detection and precise treatment are urgent and important for BC management. In clinical application, compared with highly complex classification functions, precise, simple and biologically interpretable algorithms can strengthen the understanding of disease development and facilitate the personalization of therapeutic strategies. In this study, a novel readily interpretable decision rule involving multiple forms of molecular relationship (RI-MFR) was proposed for cancer clinical management applications. In RI-MFR, linear and nonlinear pairwise molecule comparisons were comprehensively analyzed by a joint probability mass function for the identification of top scoring pairs from high dimensional biomolecular data. Based on the selected few molecule pairs, accurate, readily interpretable decision rules were inferred to provide biological insight as to how classification was performed. RI-MFR can effectively eliminate the influence of sample variability caused by individual differences. RI-MFR was successfully employed to analyze changes in metabolic mechanisms during BC development based on genomics datasets and metabolic alterations before and after BC therapy using our metabolomic profiling. The experimental results indicated that genes and metabolites involving in the glycosphingolipid metabolism may be the crucial factors associated with BC development and contribute to the enhanced effectiveness of BC treatment. Compared with other algorithms, RI-MFR had the significantly better classification results with p-values < 0.05, which suggested it is a more useful tool to identify important bioinformation for clinical BC management.
乳腺癌细胞可以转移到淋巴结或其他器官,是女性癌症死亡的主要原因。努力提高早期发现和精确治疗的表现对BC的管理是迫切和重要的。在临床应用中,与高度复杂的分类功能相比,精确、简单且具有生物可解释性的算法可以加强对疾病发展的理解,促进治疗策略的个性化。在这项研究中,提出了一种新的易于解释的决策规则,涉及多种形式的分子关系(RI-MFR),用于癌症临床管理。在RI-MFR中,通过联合概率质量函数综合分析线性和非线性成对分子比较,从高维生物分子数据中识别得分最高的对。基于所选择的少数分子对,推断出准确,易于解释的决策规则,以提供关于如何进行分类的生物学见解。RI-MFR可以有效消除个体差异带来的样本变异性的影响。利用我们的代谢组学分析,RI-MFR成功地分析了BC发展过程中代谢机制的变化,基于基因组学数据集和BC治疗前后的代谢变化。实验结果表明,参与鞘糖脂代谢的基因和代谢物可能是与BC发展相关的关键因素,并有助于提高BC治疗的有效性。与其他算法相比,RI-MFR的分类结果明显更好,p值为<; 0.05,这表明RI-MFR是一种更有用的识别临床BC管理重要生物信息的工具。
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引用次数: 0
Pathophysiological impacts of particulate matter exposure on respiratory health and emerging biomarkers for early detection 颗粒物暴露对呼吸健康的病理生理影响和早期检测的新兴生物标志物
IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2026-01-06 DOI: 10.1016/j.jpba.2026.117339
Yen-Yi Lee , Guo-Ping Chang-Chien , Bo-Wun Huang , Balasubramanian Sriram , Sea-Fue Wang , Sakthivel Kogularasu , Meng-Chih Lin
Particulate matter (PM) is a significant and preventable environmental health hazard, closely associated with the initiation, progression, and exacerbation of respiratory diseases. The pathological effects of PM inhalation arise from the combined influence of its physicochemical properties and individual susceptibilities, triggering oxidative stress, inflammatory cascades, epithelial barrier disruption, and structural remodeling of lung tissue. This review synthesizes current knowledge on the compositional diversity and emission sources of PM, the underlying biological mechanisms of respiratory toxicity, and the emerging role of molecular biomarkers in early disease detection. Key biomarkers include inflammatory mediators such as IL-6 and TNF-α, oxidative stress indicators like 8-OHdG and MDA, epithelial injury markers including SP-D and CC16, and epigenetic regulators such as miRNA signatures and DNA methylation patterns. These biomarkers hold promise for identifying subclinical alterations in pulmonary function, enabling earlier intervention before irreversible damage occurs. However, progress is hindered by challenges in assay standardization, matrix-specific validation, and inter-individual variability. Advancing biomarker-based surveillance will require coordinated, multidisciplinary efforts integrating molecular biology, environmental toxicology, bioinformatics, and sensor technology. The integration of high-resolution biomarker science into environmental health frameworks offers transformative potential for predictive, preventive, and personalized strategies to mitigate the global burden of PM-related respiratory disease.
颗粒物(PM)是一种重大且可预防的环境健康危害,与呼吸系统疾病的发生、发展和恶化密切相关。PM吸入的病理效应是其理化性质和个体易感性的综合影响,引发氧化应激、炎症级联、上皮屏障破坏和肺组织结构重塑。本文综述了PM的组成多样性和排放源,呼吸毒性的潜在生物学机制以及分子生物标志物在早期疾病检测中的新作用。关键的生物标志物包括炎症介质如IL-6和TNF-α,氧化应激指标如8-OHdG和MDA,上皮损伤标志物如SP-D和CC16,以及表观遗传调节剂如miRNA特征和DNA甲基化模式。这些生物标志物有望识别肺功能的亚临床改变,从而在不可逆损伤发生之前进行早期干预。然而,在分析标准化、基质特异性验证和个体间可变性方面的挑战阻碍了进展。推进基于生物标志物的监测将需要协调、多学科的努力,整合分子生物学、环境毒理学、生物信息学和传感器技术。高分辨率生物标志物科学与环境卫生框架的整合为预测、预防和个性化策略提供了变革性潜力,以减轻pm相关呼吸系统疾病的全球负担。
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引用次数: 0
Revelation of metabolic pathways and potential targets associated with latent and active pulmonary tuberculosis via transcriptome and metabonomics analysis 通过转录组学和代谢组学分析揭示与潜伏性和活动性肺结核相关的代谢途径和潜在靶点
IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2026-01-06 DOI: 10.1016/j.jpba.2026.117340
Yourou Zhou , Yiwei Shang , Qikai Luo , Mengjiao Xue , Yan Liu , Yunguang Wang , Juan Jin , Lifang Sun
Tuberculosis (TB) is one of the world's top ten causes of mortality. Current diagnostic methods, primarily based on microbiology and Polymerase Chain Reaction (PCR), still lack the ability to accurately distinguish between latent and active TB, highlighting the urgent need for more precise diagnostic strategies. In recent years, transcriptomics and metabolomics have become increasingly popular in elucidating disease pathophysiology. In this study, we used an integrated multi-omics approach, combining non-targeted metabolomics and transcriptomics to examine blood samples from 39 clinical participants. Our results revealed that Valine, leucine and isoleucine biosynthesis, Linoleic acid metabolism and Purine metabolism were strongly associated with the progression of pulmonary tuberculosis (PTB) infection. Furthermore, we identified glycerophospholipid metabolism as a key pathway involved in PTB, and proposed ABCC6, ABCG1, and PLA2G4A as potential biomarkers for discriminating between active PTB and latent TB infection (LTBI).
结核病是世界十大死亡原因之一。目前主要基于微生物学和聚合酶链反应(PCR)的诊断方法仍然缺乏准确区分潜伏性结核病和活动性结核病的能力,因此迫切需要更精确的诊断策略。近年来,转录组学和代谢组学在阐明疾病病理生理方面越来越受欢迎。在这项研究中,我们使用综合多组学方法,结合非靶向代谢组学和转录组学来检查来自39名临床参与者的血液样本。结果表明,缬氨酸、亮氨酸和异亮氨酸的生物合成、亚油酸代谢和嘌呤代谢与肺结核(PTB)感染的进展密切相关。此外,我们确定甘油磷脂代谢是参与PTB的关键途径,并提出ABCC6, ABCG1和PLA2G4A作为区分活动性PTB和潜伏性TB感染(LTBI)的潜在生物标志物。
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引用次数: 0
An online rapid screening HPLC system establishing and applying discovered a new type of natural chemical ligand of the BRD4-BD1 from Hedyotis diffusa 建立并应用的在线快速筛选高效液相色谱系统发现了白花蛇舌草BRD4-BD1的一种新型天然化学配体
IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Pub Date : 2026-01-05 DOI: 10.1016/j.jpba.2026.117336
Lina Wang, Hong Wang, Shizhong Chen
Herein, we report an online high performance liquid chromatography (HPLC) for screening of the bromodomain-containing protein 4-first bromodomain (BRD4-BD1) ligands, leading to screen a new type of natural chemical ligand of the BRD4-BD1 from Hedyotis diffusa. The system was first established, validated, and then applied for rapid screening the ligands of BRD4-BD1 from Hedyotis diffusa. It was investigated using the positive ligand JQ1 in five aspects including the suitability, the specificity, the reproductivity, the limit of detection (LOD), and the saturability of this system. When it was been applied to screen BRD4-BD1 ligands from Hedyotis diffusa, one candidate ligand 1 was fished out. Then the ligand 1 was isolated and identified. And their interaction between the screened ligand 1 and the BRD4-BD1 was assay on the online system again and followed verified by the surface plasmon resonance (SPR) technique. The molecular docking was performed to the binding mode of ligand 1 with BRD4-BD1. The ligand 1 was found as a new type of natural ligand for BRD4-BD1 protein. In a conclusion, we have systemically demonstrated the feasibility of the online HPLC system screening method applying to screen the chemical ligand of the BRD4-BD1 in complex substance systems. Besides, the ligand 1 provided a potential new type of scaffold for chemical modification for BRD4-BD1 inhibitors in future.
本文报道了利用高效液相色谱(HPLC)在线筛选含溴结构域蛋白4-第一溴结构域(BRD4-BD1)配体的方法,从白花蛇形草中筛选出一种新型的天然化学配体BRD4-BD1。首先建立并验证了该系统,然后将其应用于白花蛇舌草BRD4-BD1配体的快速筛选。采用正配体JQ1对该体系的适宜性、特异性、可重复性、检出限(LOD)和饱和性等5个方面进行了考察。应用该方法筛选白花蛇舌草BRD4-BD1配体时,筛选出1个候选配体1。然后分离鉴定配体1。筛选到的配体1与BRD4-BD1的相互作用在在线系统上再次测定,随后用表面等离子体共振(SPR)技术进行验证。对配体1与BRD4-BD1的结合方式进行分子对接。配体1是BRD4-BD1蛋白的一种新型天然配体。综上所述,我们系统地论证了在线HPLC系统筛选方法用于复杂物质体系中BRD4-BD1化学配体筛选的可行性。此外,配体1为BRD4-BD1抑制剂的化学修饰提供了一种潜在的新型支架。
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Journal of pharmaceutical and biomedical analysis
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