JOURNAL OF MASS SPECTROMETRY
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2026
·Vol. 61
·期 8
·e70088
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IF 2.1
Liping Yang,Bingling Gao,Tao Yang,Liping Tang,Ying Kan,Keqi Sun,Peng Xiao
Dehydroepiandrosterone sulfate (DHEAS), a crucial steroid hormone for adrenal function and pubertal development, is highly associated with related diseases. This study aims to develop and validate an isotope dilution liquid chromatography tandem mass spectrometry (ID-LC–MS/MS)-based candidate reference measurement procedure (cRMP) for quantifying serum DHEAS. Serum samples were prepared by protein precipitation with acetonitrile and separated on a reversed phase column. Assay validation was conducted under the guidance of standard documents, including C62-A, EP6-A, EP10-A3, and C50-P endorsed by the Clinical and Laboratory Standards Institute (CLSI). The cRMP was established and proven to be highly specific without significant matrix effect and able to accurately quantify DHEAS in human serum. The intra-assay and inter-assay imprecision ranged from < 0.1 to 1.0% and from 1.0 to 1.1%, respectively. Trueness was assessed by recovery rate from 99.6 to 101.2%. The limit of detection (LoD) was 0.270 nmol/L, and the lower limit of the measuring interval (LLMI) was 12.1 nmol/L. A linear correlation ranged from 7.60 to 41 858 nmol/L was observed with a correlation coefficient > 0.999. R 2 value of linear regression analysis between this method and clinical immunoassays was ≥ 0.990. The relative expanded uncertainty was 1.5%–2.5% over the concentration range of 12.1–33 043 nmol/L. This study developed an ID-LC–MS/MS-based cRMP, which provided high specificity, trueness, and precision for serum DHEAS quantification, contributing to the DHEAS measurement standardization and traceability.
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PHYTOTHERAPY RESEARCH
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2026
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IF 8.1
Jing Li,Yang-Chi-Dung Lin,Hsi-Yuan Huang,Jihang Chen,Huali Zuo,Yun Tang,Hsien-Da Huang
Obesity is a major risk factor for type 2 diabetes. Some traditional Chinese medicine (TCM) compounds can improve obesity by increasing energy consumption. This study aimed to identify and verify TCM compounds that promote adipose thermogenesis to alleviate obesity via transcriptomic analysis, molecular docking, network pharmacology, and Connectivity Map (CMap) analysis. Thirty-six TCMs related to adipose tissue thermogenesis were first collected to generate transcriptomic data. Then a ranking method based on integrated transcriptomic data was used to select emodin from the TCM Da Huang for network pharmacology to explore its potential mechanisms and further experimental validation. CMap analysis of thermogenesis signature genes from ProFAT and GEO datasets identified triptolide as another compound for improving obesity through enhanced thermogenesis. In vitro experiments with 3T3-L1 cells and in vivo experiments with zebrafish were conducted. The results showed that both emodin and triptolide could upregulate the NAD + /NADH ratio, increase AMPK and SIRT1 expression, suppress lipid accumulation, and promote lipolysis, as verified by both in vitro and in vivo experiments. They also upregulated thermogenesis-related genes (e.g., UCP1, PGC1α, and PRDM16), lipolysis-related genes (e.g., PKA, ATGL, and HSL), mitochondrial biogenesis-related genes (e.g., NRF1, NRF2, and TFAM), and β-oxidation-related genes (e.g., CPT1α and CPT1β). Meanwhile, they downregulated lipogenesis-related genes such as FASN, SREBP1, and ACC. These results provide a basis for understanding the effects of emodin and triptolide on obesity. The findings highlight the effectiveness of combined screening approaches in exploring compounds with beneficial metabolic effects.
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MOLECULAR BIOLOGY REPORTS
·
2026
·Vol. 53
·期 1
·1218
·
IF 3.2
Li Feilong,Jiang Yingcun,Zhou Yang,Song Chao,Liu Zongchao,Fu Zhijiang
Osteoporosis is a major public health concern characterized by reduced bone mass and increased fracture risk, and Cyathulae Radix has been used in China for its prevention, yet its active constituents and mechanisms remain unclear. This study integrated network pharmacology with in vitro experiments to identify key bioactive components and underlying pathways. Using the TCMSP database, we screened the major compounds of Cyathulae Radix and, through intersection with osteoporosis-related targets from OMIM and GeneCards, obtained 29 overlapping genes. Subsequent protein–protein interaction network analysis via STRING revealed core targets including AKT1, TNF, IL-6, and MMP2 , among which quercetin emerged as a principal active component. To validate its effects, we employed H₂O₂ to induce oxidative damage in MC3T3 E1 pre-osteoblasts, and then treated cells with quercetin based on CCK8 and ROS assay results. The CCK8 assay showed that quercetin restored cell viability to near-normal levels. Quercetin treatment significantly improved cell proliferation and restored osteogenic differentiation, as shown by elevated alkaline phosphatase staining intensity, increased mineralized nodules in alizarin red staining, and markedly upregulated mRNA levels of RUNX2, OPN , and BMP-2 . Furthermore, quercetin attenuated oxidative stress by increasing SOD and GSH activities, decreasing MDA production, and activating the NRF2/HO-1/GPX4 antioxidant cascade, as confirmed by western blotting. Collectively, these results demonstrate that quercetin, a key constituent of Cyathulae Radix, exerts anti osteoporotic effects through both promoting osteogenesis and enhancing antioxidant defense, offering a mechanistic rationale for its clinical use against osteoporosis.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
·
IF 6.8
Yu Zhong,Licheng Zhang,Yiheng Deng,Qinghui Shao,Jiawei Liang,Gan Jiang,Qiuxing He
Ethnopharmacological relevance Annona squamosa L. (custard apple) is widely used in traditional folk medicine across tropical regions for treating inflammatory conditions and metabolic disorders. However, the antioxidant and anti-inflammatory potential of water-soluble polysaccharides from the edible pulp (WPAS) has not been previously investigated. Aim of the study To evaluate the antioxidant and anti-inflammatory activities of WPAS and to explore its potential mechanisms using integrated computational approaches and zebrafish models. Materials and methods The in vitro antioxidant capacity of WPAS was evaluated using DPPH radical- and hydroxyl radical-scavenging assays. DFT, network pharmacology, molecular docking, molecular dynamics simulation, QSAR, and PASS prediction were employed to characterize representative monosaccharide motifs that served as simplified structural proxies for WPAS and to generate exploratory hypotheses regarding potential interaction networks and inflammation-associated molecular markers. The in vivo anti-inflammatory effects were assessed in an LPS-induced zebrafish embryo inflammation model by evaluating ROS levels, neutrophil recruitment, inflammatory protein expression, and cytokine gene expression. Results WPAS exhibited concentration-dependent radical scavenging activity, with IC 50 values of 71.84 μg/mL for DPPH radicals and 804.6 μg/mL for hydroxyl radicals, indicating appreciable in vitro antioxidant potential, particularly against DPPH radicals. Monosaccharide-based computational analyses suggested MMP9-related interaction patterns within the in silico framework and indicated possible associations with pathway-related processes, including NF-κB, JAK-STAT, and PI3K-Akt-related processes. In LPS-challenged zebrafish embryos, WPAS exhibited favorable biosafety and significantly attenuated inflammatory responses in a dose-dependent manner, as evidenced by reduced intracellular ROS, decreased neutrophil infiltration, lowered protein levels of TNF-α, NF-κB p65, and MMP9, and downregulated mRNA expression of TNF-α, IL-1β, and IL-6. Conclusion This study provides the first evidence that WPAS exhibits antioxidant and anti-inflammatory activities. The protective effects observed in zebrafish were associated with reduced ROS production, decreased neutrophil recruitment, and changes in inflammatory marker levels, including NF-κB p65, TNF-α, and MMP9. These findings support the traditional use of Annona squamosa L. and highlight WPAS as a promising natural polysaccharide candidate for further investigation of its antioxidant and anti-inflammatory properties.
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MATERIALS & DESIGN
·
2026
·
IF 8.2
Ajing Wu,Wenxuan Wang,Rui Liu,Huifang Hao,Xiaochun Zheng,Mingxin Zhao,Haonan Chen,Yanchun Ma,Weiwei Kang,Ziliang Zheng
A synergistic nanoprobe enables precise, safe, non-radiative skeletal imaging. • Multi-targeting enables precise enrichment throughout the skeleton. • AA@TFN provides a versatile platform for bone disease diagnosis and monitoring. Early diagnosis of bone-related diseases remains a critical clinical challenge, attributable to persistent limitations in imaging accuracy and safety. While near-infrared Region II fluorescence (NIR-II FL) imaging confers substantial advantages for deep-tissue visualization, its clinical translation is hampered by the inadequate targeting specificity of conventional contrast agents. Here, we developed Au-Ag@Apo-Tf/-N 3 (AA@TFN), a synergistic targeting gold–silver nanocluster probe engineered with glutathione and azide functionalities, which achieved bone-specific enrichment via a hierarchical multi-targeting mechanism. AA@TFN first anchored to hydroxyapatite in the bone matrix through glutathione carboxyl-mediated chelation, then targeted transferrin receptors highly expressed in bone marrow, and finally endured macrophage-mediated uptake facilitated by azide-enhanced bone affinity. A synergistic targeting strategy enabled real-time, high-resolution NIR-II FL imaging across the complete skeleton, with enhanced probe enrichment at lesion sites driven by microenvironmental changes. AA@TFN enabled visualization of synovial inflammation in rheumatoid arthritis models and millimeter‑scale microlesions in multiple myeloma models. Furthermore, the probe exhibited excellent biocompatibility and favorable safety profiles, underscoring its strong translational potential. A versatile platform was established for the diagnosis of bone diseases and non-invasive monitoring of therapeutic efficacy. Download: Download high-res image (129KB) Download: Download full-size image
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2026
·
IF 4.1
Zhou Jiangshan,Zhang Shanyuan,Liu Mengfan,Wang Zhonghua,Zhou Zhi
Esophageal squamous cell carcinoma (ESCC) is a highly prevalent malignancy in China. Understanding its metabolic heterogeneity is of great significance for improving the precision of diagnosis and treatment. This study innovatively employed an adult zebrafish xenograft model, combining the spatial metabolomics and in situ derivatization method for fatty acid peroxidation products (FAPPs) based on air flow-assisted desorption electrospray ionization–mass spectrometry imaging (AFADESI-MSI) technology, to elucidate the metabolic patterns associated with ESCC and its differentiation grade. Spatial metabolomic data demonstrated that abundance alterations of glycerophospholipids and acetylated amino acids were statistically correlated with ESCC tumor formation. Levels of lysophospholipids and arachidonic acid-associated metabolites tended to increase with the progressive malignant differentiation of tumor lesions. Profiling of FAPPs showed elevated short- and medium-chain species accompanied by decreased long-chain counterparts in tumor-bearing zebrafish, which may be linked to tumor-initiated alterations in oxidative stress. Specifically, short- and medium-chain FAPPs were enriched in well-differentiated ESCC tissues, while long-chain FAPPs predominated in poorly differentiated tumors, suggestive of disparate lipid peroxidation patterns in ESCC cells at different differentiation stages. Furthermore, distinct signature metabolites were found to be specifically accumulated in the brain providing experimental clues that ESCC may remotely disturb the central nervous system metabolism of host animals. This research uncovers both tumor-induced and differentiation-dependent metabolic heterogeneity of ESCC, and validates whole-body MSI as a transformative approach to unravel tumor-host metabolic interactions. Graphical abstract
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Stem Cell Reviews and Reports
·
2026
·
IF 4.9
Lv Yan,Du Yongjun,Peng Zhi,Ma Chengjie,Li Zhenggang,Xu Rui,Hou Jianhong,Lu Sheng
Osteoporotic fracture is the most severe complication of osteoporosis, and impaired bone regeneration and delayed healing after fracture remain major clinical challenges. Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) may play a critical role in promoting bone regeneration after osteoporotic fracture. Enhancing their osteogenic potential and elucidating the underlying mechanisms may contribute to accelerated fracture healing. In this study, resveratrol-stimulated BMSC-derived EVs (Res-EVs) were isolated using differential centrifugation combined with ultracentrifugation. We found that compared with EVs secreted by BMSCs under normal culture conditions (Nor-EVs), Res-EVs significantly enhanced BMSCs osteogenic differentiation capacity. Analysis of miRNA sequencing data identified miR-19a-3p as significantly downregulated and PC-3p-83,608 as significantly upregulated. The reliability of the sequencing data was validated by qPCR results. By transfecting BMSCs with inhibitor and mimic of miR-19a-3p, we found that miR-19a-3p was a negative regulator of osteogenic differentiation. Bioinformatics prediction and dual-luciferase reporter assays confirmed that miR-19a-3p directly targets Raf1. Western blot results indicated that miR-19a-3p regulates osteogenic differentiation of BMSCs by targeting Raf1. In vivo experiments further demonstrated that Res-EVs treatment enhanced repair at osteoporotic fracture sites and increased the expression of RUNX2 and RAF1. Collectively, these findings indicate that Res-EVs promote bone regeneration at osteoporotic bone defect sites in rats, with the miR-19a-3p/Raf1 axis representing a potential underlying mechanism.
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ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Yanjiao Ding,Daogong Zhang,Jinye Li,Lei Xu,Haibo Wang
Hearing loss is a widespread global disability, commonly treated using dexamethasone (Dex). However, targeted delivery of Dex to the inner ear remains a significant challenge due to the blood-perilymph barrier (BLB), which limits its therapeutic efficacy. In this study, we aimed to develop a strategy to enhance Dex delivery to the inner ear and improve its treatment outcome by the noninvasive intranasal approach. Also, poly(ethylene glycol) (PEG)─liposomal nanoparticles were used as a drug carrier and loaded with Dex (PLN-Dex). For intranasal delivery, a thermosensitive hydrogel was fabricated by methylcellulose. The PLN-Dex nanocomposite was incorporated into the hydrogel to obtain PLN-Dex@Gel. PLN-Dex@Gel could be administrated intranasally and their transport pathway from olfactory mucosa to the cochlea was explored. In vivo magnetic resonance and fluorescence microscopy showed that drugs delivery into the olfactory mucosa reached the inner ear by dispersive transport via the brain. Interestingly, we found that beyond the cochlear duct, the cochlear axis may serve as a crucial pathway for the transportation of drugs from the brain to the inner ear. In guinea pig models of LPS-induced and noise-induced hearing loss, intranasal PLN-Dex@Gel treatment significantly reduced auditory brainstem response thresholds, ameliorated cochlear blood flow, and protected hair cells and synapses. Our findings underscore the potential of intranasal Dex delivery as a noninvasive and effective strategy for treating hearing loss. The target drug delivery to the inner ear, combined with the enhanced formulation of Dex-loaded liposomal hydrogels, offers promising prospects for future research in the treatment of inner ear disorders, with potential for clinical translation. This study expands the understanding of delivery route from nose to inner ear and suggests a method for utilizing intranasal administration as a strategy for treating hearing loss.
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NATURAL PRODUCT RESEARCH
·
2026
·
IF 1.8
Lin Zhang,Guanke Liu,Bingyang Zhang,Shiqing Song,Xiao Liu,Tie Yao,Feng Qiu,Feng Zhao
Two new secoiridoid glycosides, gentscaside A (1) and gentscaside B (2), were isolated along with three known compounds gentiopicroside (3), rindoside (4), gentiotrifloroside (5), from the Rhizomes of Gentiana scabra. The structures of the new compounds were determined by comprehensive NMR analysis, and their absolute configurations were determined on the basis of detailed spectroscopic analyses and acidic hydrolysis. The five compounds were evaluated for their anti-inflammatory activity (NO inhibitory activity in LPS-stimulated macrophages). Compounds 1, 4 and 5 showed significant inhibitory effects on LPS-induced NO release in RAW 264.7 cells. The IC50 values are 2.15 μM, 3.02 μM and 6.87 μM, respectively. Additionally, the potential anti-inflammatory mechanism of the active new compound 1 was explored.
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Acta Biomaterialia
·
2026
·
IF 10.4
Xiangrong Dai,Yi Liao,Rong Chen,Xuanxiang Jin,Jiajia Dong,Ying Tan,Xuru Jin
Nebulized inhalation represents an attractive approach for pulmonary drug delivery due to its non-invasiveness and direct lung targeting capability. However, the effectiveness of conventional inhaled formulations is limited by their inability to simultaneously evade mucociliary clearance and macrophage phagocytosis, leading to suboptimal lung retention and low bioavailability. To address these challenges, a series of ultra-small zwitterionic "camouflage" micelles, Distearoylphosphatidylethanolamine (DSPE)-block-poly ( N -methacryloyloxyethyl- N, N -dimethylammonium-α-N-methylcarboxybetaine) (CB) (D-PCB n ), were developed to synergize biomimetic targeting with enhanced mucosal penetration. The micelles feature a DSPE-based core structurally modeled after dipalmitoylphosphatidylcholine (DPPC), a key pulmonary surfactant lipid, enabling biomimetic alveolar targeting. Simultaneously, a carboxybetaine-derived corona facilitates robust hydration-mediated surface lubrication for efficient mucus penetration. Among the series, the optimized D-PCB 30 variant exhibited superior mucus-permeating capacity, enhanced pulmonary deposition, and high encapsulation efficiency for dexamethasone. In vivo evaluation in a murine model following aerosol administration demonstrated significantly improved lung accumulation, extended residence time, reduced systemic distribution, and enhanced anti-inflammatory efficacy. Transcriptomic analysis further indicated modulation of critical inflammatory pathways and reprogramming of macrophage polarization (M1 to M2 phenotype), corroborating the therapeutic benefits achieved through enhanced barrier penetration. These results demonstrate the potential of D-PCB n micelles as a promising inhalable nanoplatform for targeted treatment of lung diseases. Statement of Significance Delivering therapeutics to injured lungs is hampered by mucus barriers, rapid clearance, and immune sequestration. Here, we describe ultra-small, biomimetic zwitterionic micelles D-PCBMA n (D-PCB 30 ) that combine a DPPC-mimetic DSPE core with a carboxybetaine corona to create a “camouflage-and-lubricate” nanoplatform. D-PCB 30 exhibits a low critical micelle concentration (CMC), high drug loading, and stability upon nebulization, enabling deep mucus penetration, reduced macrophage uptake, and sustained pulmonary residence. When loaded with dexamethasone (DEX) and delivered by nebulization, D-PCB 30 increases local drug deposition while reducing systemic exposure, resulting in potent attenuation of LPS-driven inflammation, preservation of alveolar architecture, and diminished fibrotic remodeling. Mechanistically, transcriptomic profiling reveals suppression of TLR/MyD88/NF-κB inflammatory circuits and induction of tissue-repair programs, alongside a shift in macrophage phenotype toward resolution. With an encouraging biosafety profile and mitigated steroid side effects, D-PCB 30 represents a clinically promising strategy to overcome pulmonary barriers and to deliver targeted, effective therapies for acute inflammatory lung disease.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2026
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IF 5.2
Manxin Chen,Haiting Sun,Shunda Zhu,Hang Yu,Yungang Liu
Phenytoin is a long standing antiepileptic drug with confirmed teratogenicity and possible carcinogenicity. Phenytoin formed electrophilic metabolite and induced oxidative DNA damage in vitro , yet it was negative in genotoxicity assays in rodents following 1∼3 d exposure. We hypothesized that extended exposure durations from regular regimens may enhance its metabolic activation and genotoxicity. In this study, male C57BL/6J mice were administered with phenytoin by gastric gavage at 5∼20 mg/kg (b.w.)/d for 7 d (5 mice in each group), then a comet assay with isolated hepatocytes, a Western blot assay of hepatic γ-H2AX (indicating double-strand DNA breaks), and a micronucleus test in the bone marrow polychromatic erythrocytes were performed. Positive results were observed in the above genotoxicity assays with phenytoin at 10 and/or 20 mg/kg/d doses, evidencing its DNA-breaking and chromosome-damaging effect. The protein levels of hepatic Cyp2c38, Cyp2c39, Cyp3a11, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) (both receptors transcriptionally regulating Cyp2c enzymes) were all increased in the 10 and/or 20 mg/kg/d phenytoin groups. Additionally, co-exposure of 1-aminobenzotriazole (100 mg/kg/d, a wide-spectrum Cyp inhibitor) blocked the genotoxic effects and phenytoin-induced Cyp2c38, 2c39 and CAR protein expression. In a mouse hepatocarcinoma (Hepa1-6) cell line, phenytoin alone induced micronucleus weakly, however, dexamethasone (DEX, 0.1 μM, a Cyp2c inducer) obviously potentiated the effect, which could be further blocked by sulfaphenazole (50 μM, a Cyp2c inhibitor). This study suggests that following 7-d oral administration phenytoin could be genotoxic in mice (potency being close to N -nitrosodiethylamine), which requires metabolic activation, possibly by Cyp2c enzymes.
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ACS Applied Polymer Materials
·
2026
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IF 5.2
Yaqi Zhang,Shiyao Liu,Hongman Xu,Jiahui Wu,Ruquan Zhang,Yongzhen Tao
Polyanionic polysaccharide-based hydrogels were developed as multistimuli-responsive drug carriers. Methacrylated pullulan (MP) acted as a thinner and rigidity regulator. Carboxymethylated-methacrylated xanthan gum (CMMXG) provided negative charges, ionic conductivity, and viscoelasticity. The cumulative ciprofloxacin hydrochloride (CPFXH) release mass dropped dramatically, whether the hydrogel was set at the anode or cathode with a potential of 3 V, due to irreversible electrochemical oxidation. Hydrogels with lower drug-loading amounts exhibited higher release efficiency when an electric stimulus was applied in the initial 5 h. A high CPFXH-loading amount led to rapid diffusion and quick electrochemical oxidation. For CMMXG3-MP7.5-CPFXH1680-LAP, the CPFXH release efficiency ratio of 3 to 0 V decreased from 1.33 ± 0.43 to 1.01 ± 0.06 over a duration of 0.5 ∼ 2 h, further indicating that the encouraged release and electrochemical degradation occurred simultaneously. The CPFXH release efficiency in phosphate buffer saline (pH = 7.4) was 1.5 times higher than that in simulated gastric fluid (pH = 1.2), and the CPFXH diffusion coefficient with loading weight was 6 times higher than that without loading, indicating that it was sensitive to pH and compressive force. The hydrogels exhibited electric, pH, and mechanical stimuli-responsiveness due to the presence of charged groups along the chains and viscoelasticity with robustness enough to respond and withstand compressive loading.
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危险品化学品经营许可证（带存储）