Nature Communications
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2025
·Vol. 16
·期 1
·1-20
·
IF 15.7
Zhang Zehong,Wan Qianyi,Zhu Yuedan,Ye Jinbao,Fu Fang,Fan Xinxin,Chen Haiou,Ren Gang,Jiang Wei,Guo Xiaoxin,Zhou Juanyu,Yan La,Yan Jinhua,Liu Xingzhu,Yuan Yu,Chen Yi,Chen Haiyang
Intestinal stem cell (ISC) aging diminishes the regenerative capacity of the intestinal epithelia, but effective therapeutic strategies to counteract human ISC aging remain elusive. Here, we find that the synthesis of α-lipoic acid (ALA) is reduced in old human small intestine. Notably, ALA supplementation inhibits ISC aging and decreases the number of atypical Paneth cells in old human intestinal organoids and in old mouse small intestines. Importantly, we discern that the effect of ALA on mitigating ISC aging is contingent upon the presence of Paneth cells. Inhibiting the mTOR pathway in Paneth cells with ALA or rapamycin significantly increases cyclic ADP ribose (cADPR) secretion and decreases Notum secretion, which, in turn, enhances ISC functions. In this work, our findings substantiate the role of ALA in inhibiting human ISC aging and present a potential therapeutic approach for managing age-related human intestinal diseases.
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Crystals
·
2025
·Vol. 15
·期 6
·512
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IF 2.4
Shixin Fan,Wenling Zheng,Shizhao Ren,Wangchuan Xiao,Fenghua Chen,Rongrong Xue
Amorphous solid dispersion (ASD) technology is popularly used for enhancing the solubility of poorly water-soluble drugs. Drug molecules in ASDs can be dispersed in the form of either amorphous (AASD) or molecular (MASD) forms. The boundary between AASDs and MASDs (A–M boundary) is defined as the drug concentration at which the existence of MASDs obviously influences the physicochemical properties of ASDs. In this work, fluorescence spectroscopy based on the aggregation-caused quenching (ACQ) phenomenon was used to determine the A–M boundary of curcumin (CUR) ASDs prepared via neat ball milling. The relationship between the fluorescence intensity and the loading of CUR in the sample is consistent with the Stern–Volmer equation. For the CUR ASDs with PVP, the samples with CUR loading below 10% show significantly increased fluorescence and have a higher solubility (~178 μg·mL−1), suggesting the A–M boundary is around 10%. Similar A–M boundaries around 10% were also observed for CUR ASDs with PVPVA, Soluplus, HPMC, and HPMCAS. It is of great significance to define the A–M boundary of ASDs for guiding pharmaceutical ASD formulas by balancing drug loading, stability, and solubility.
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Crystals
·
2025
·Vol. 15
·期 4
·323
·
IF 2.4
Wenling Zheng,Junni Ke,Kaerdun Liu,Rongrong Xue,Fenghua Chen
Spray drying of poorly water-soluble drugs in organic solvents is a mature process in the preparation of drugs amorphous solids dispersions (ASDs). The use of organic solvents is under increasing environmental protection and safety pressure and restricts the application of advanced polymers as proteins which are usually insoluble and unstable in organic solvents. Aqueous solution spray drying technology is a candidate method for preparing ASDs without the use of organic solvents. Increasing temperature and adding volatile additives can improve the solubility of poorly water-soluble drugs in water without introducing additional components and energy needed. In this work, ammonia assisted aqueous solution spray drying method was successfully used to prepare various ASDs of indomethacin (25%) with synthetic polymers as polyvinylpyrrolidone and proteins as β-lactoglobulin, lactalbumin hydrolysate, bovine serum albumin, with high yields, special micro golfs morphology, precise compositions and longtime stabilities, compared to high-temperature aqueous solution spray drying method. ASDs with lactalbumin hydrolysate and bovine serum albumin show better dissolution profiles than other ASDs. Aqueous solution spray drying is easily extended to prepare the ASDs of sulfamerazine and celecoxib, providing a possibility to avoid the use of organic solvents in advanced ASDs preparations via spray drying.
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ANALYTICA CHIMICA ACTA
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2015
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IF 4.513
Qing Wang,Mao Ye,Li Xu,Zhi-guo Shi
A mixed-mode chromatographic packing material, C18 and diol groups modified silica (C18-Diol), was prepared with controllable hydrophobicity and hydrophilicity . It demonstrated excellent aqueous compatibility and stability in aqueous mobile phase ; compared to the traditional C18 column, improved peak shape of basic analytes was also obtained. Additionally, it exhibited both reversed-phase liquid chromatographic (RPLC) and hydrophilic interaction chromatographic (HILIC) performance; the analyte separation scope was thus enlarged, demonstrated by simultaneous separation of twenty acids, bases and neutrals. More interestingly, a novel on-line two-dimensional liquid chromatography on the single column (2D-LC-1C) was established by modifying the high performance liquid chromatographic instrument only with the addition of an extra six-port two-position valve. The early co-eluted components of the extract of Lonicera japonica on the 1st-dimension (RPLC) were collected for the online re-injection to the 2nd-dimension (HILIC) by conveniently varying the mobile phase components. Six more peaks were obtained. The established system was simple, easy operation and low cost, which had advantages in analyzing complicated samples.
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FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Longyan Yang,Ruili Yin,Ziyu Shan,Anqi Feng,Kun Li,Yan Wang,Ke Yu,Yongsong Xu,Lin Mao,Jianan Lang,Baoyu Zhang,Dong Zhao
Aims Overweight and obesity are closely associated with hyperuricemia (HUA). However, the effect of obesity-induced adipokine on the level of serum uric acid (UA) has not been fully elucidated. This study aimed to determine the role of adipokine in the pathogenesis of HUA. Methods Omental adipose tissues from HUA patients with obesity were collected for data- independent acquisition (DIA) proteomics analysis, and the secreted protein angiopoietin-like protein (ANGPTL2) was identified and further validated via Western blot and ELISA. Angptl2 knockout (ko) and adipocyte-specific ANGPTL2 overexpression mice were generated to establish HUA models. HK2 cells and primary renal tubule epithelial cells (RTECs) were applied to induce HUA cell model and treated with recombinant human ANGPTL2 or supernatants derived from C3H10 cells differentiated into adipocytes. Result ANGPTL2 levels were significantly elevated in the omental adipose tissue from HUA with obesity patients compared to control participants. Circulating ANGPTL2 levels were also increased, and positively correlated with serum UA levels, especially in male participants. Plasma UA levels were significantly decreased in Angptl2 ko mice, coinciding with up-regulated expression of ATP binding cassette subfamily G member 2 (ABCG2) and down-regulated glucose transporter 9 (GLUT9) in renal tissue. However, plasma UA levels were significantly increased, accompanied by decreased ABCG2 expression and enhanced GLUT9 expression after adipocyte-specific ANGPTL2 overexpression. Furthermore, adipocyte- derived ANGPTL2 increased UA level in cell supernatants through the inhibition of protein kinase B (AKT)/ABCG2 signaling in RTECs and HK2 cells. Conclusion Adipokine ANGPTL2 levels were significantly elevated in HUA patients with obesity. Circulating ANGPTL2 concentrations were independently associated with serum UA levels, particularly in obese males. Adipocyte-secreted ANGPTL2 promoted the level of UA through AKT/ABCG2 signaling in renal tubular cells. These findings establish ANGPTL2 as a critical adipokine linking obesity to hyperuricemia and suggest its potential as a novel therapeutic target for HUA.
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ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2025
·
IF 11.3
Shirong Li,Junwen Ding,Zihan Liu,Jinjin Jia,Qian Zhao,Peijie Li,Han Zhang,Guibai Li,Langming Bai,Heng Liang
Environmental organic micropollutants in aquatic systems pose a threat to human health. Conventional nanofiltration membranes struggle with micropollutant removal due to inadequate steric hindrance and unfavorable interactions. This study focused on regulating micropollutant interfacial partitioning by constructing an enhanced separation interface for nanofiltration membranes. Three types of amino acids were introduced into interfacial polymerization to fabricate the amino acid-modified nanofiltration membranes. Molecular dynamics (MD) simulations and density functional theory (DFT) calculations revealed how amino acids regulate monomer diffusion and enable in situ chemical modification. Membrane performance evaluations showed an improved micropollutant removal by the modified membranes. Notably, the rejection of the modified membrane for neutral and positively charged micropollutants can reach up to twice that of the control membrane. The micropollutant interfacial partitioning behavior was elucidated through quartz crystal microbalance with dissipation (QCM-D) measurements and calculation analysis, demonstrating the effectiveness of interface-facilitated micropollutant removal. Additionally, the modified membrane also exhibited enhanced antifouling properties, mitigating the negative impact of the fouling layer on the micropollutant rejection. This study advances our understanding of the regulatory mechanisms governing micropollutant interfacial partitioning on nanofiltration membranes and proposes a simple yet effective strategy for removing organic micropollutants in environmental water treatment.
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Food Science & Nutrition
·
2025
·Vol. 13
·期 12
·e71310
·
IF 3.8
Fan Cao,Hua Wu,Zhen He,Mengxin Di,Bin Liu,Zhenwei Chen,Jieming Xie,Yonghong Zhang,Xinhua Ma
Melia azedarach L., also known as the chinaberry tree, has long been used in traditional medicine to treat inflammatory conditions. In this study, we preliminarily investigated the anti-inflammatory effect of 21 α -methylmelianol (MMN), a tirucallane-type triterpenoid isolated from M. azedarach , in lipopolysaccharide (LPS)-mediated RAW264.7 macrophages in vitro and in a dextran sodium sulfate (DSS)-stimulated ulcerative murine colitis model in vivo. MMN reduced LPS-stimulated nitric oxide production without inducing cytotoxicity. It significantly attenuated LPS-induced protein expression of reactive oxygen species and effectively suppressed the production of pro-inflammatory factors, including tumor necrosis factor-alpha (TNF- α ), interleukin (IL)-6, and IL-1 β . In addition, mechanistic investigations showed that MMN inhibited signal transduction and activator of STAT3 phosphorylation and activation of nuclear factor κ B (NF- κ B). In mice with DSS-induced colitis, MMN attenuated DSS-mediated pathological manifestations, including colon shortening, body weight loss, and histopathological alterations. Its in vivo effects were associated with the regulation of pro- and anti-inflammatory cytokine levels through suppression of the NF- κ B signaling cascade and downstream inflammatory pathways. Collectively, these findings provide compelling evidence of the anti-inflammatory properties of MMN and highlight its therapeutic potential for the management of inflammatory disorders.
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BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Wenhao Zhou,Yijie Cai,Xilei Wang,Yijun Tu,Jiejuan Jiang,Jianqing Yu
Alantolactone (AL) and isoalantolactone (IAL) are the bioactive components of Inula racemosa Hook. f. and constitute a significant portion in this herb. These two compounds are widely utilized in pharmaceuticals, cosmetics, agriculture and other fields due to their extensive biological activities, exhibiting remarkable market potential. However, their current acquirement remains primarily reliant on traditional Chinese medicine, which makes it necessary to optimize the extraction process. Additionally, the minor components, particularly sesquiterpenes, are often overlooked due to the high contents of AL and IAL, which makes their chemical components still unclear. This study developed an HPLC detection method and optimized an ultrasound-assisted extraction process with response surface methodology (RSM), achieving optimal parameters: liquid-solid ratio of 15.34: 1, 88.92 % ethanol, and 49.21 °C. Furthermore, to identify the minor components, a novel combination of Feature-based Molecular Networking (FBMN), Network Annotation Propagation (NAP), and ClassyFire was employed. The results revealed that the minor sesquiterpenes still accounted for a high proportion. Systematic separation yielded 22 sesquiterpenes, including three novel compounds ( 1 – 3 ) and 19 known ones ( 4 – 22 ). Biological evaluation demonstrated that some compounds exhibited stronger cytotoxicity than AL and IAL against HepG2, SKOV3 and HeLa cells, and compound 14 showed the best cytotoxicity via apoptosis induction. Moreover, four compounds exhibited synergistic effects with cisplatin (CDDP) on SKOV3 cells. Compounds 14 and 15 displayed potent anti-inflammatory effects with IC 50 < 3 μM. These findings indicated that the neglected part still contain bioactive sesquiterpenes, deserving for further exploration.
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International Journal of Nanomedicine
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2025
·
IF 6.5
Qiao Zeng,Jie Chen,Han Zhang,Wenying Yu,Haonan Xu,Qiao Wang,Zhan Tang
Purpose To develop everolimus-loaded nanosuspensions (EV-sus) for the in vitro and in vivo corneal neovascularization (CNV) treatment.Results Everolimus was encapsulated into nanosuspensions using a solvent volatilization technique. The developed nanosuspensions exhibited a drug concentration of 0.96 mg·mL−1, an average particle size of 141.0 ± 1.0 nm, and a zeta potential of −12.2 ± 0.4 mV. C6-labeled EV-sus uptake by Human Corneal Epithelial Cells-Transformed (HCE-T) was time-dependent, energy-dependent, and involved multiple endocytic pathways, including caveolae- and lipid raft-mediated endocytosis, clathrin-mediated endocytosis, and caveolae-mediated endocytosis. The nanosuspensions exhibited efficacy in inhibiting VEGF-induced proliferation, migration, and tube formation in Human Umbilical Vein Endothelial Cells (HUVECs). According to RT-qPCR, the in vivo CNV model showed that EV-sus effectively reduced neovascularization, decreased vascular length and area, and diminished the expression of IL-1, IL-6, MMP-9, VEGF, and TNF-α. Additionally, the rabbit eye irritation test confirmed the safety and tolerability of the formulation.Conclusion These findings indicate that EV-sus might be an effective therapy for corneal neovascularization. The formulation exhibits excellent biocompatibility, efficient cellular uptake, and robust anti-angiogenic activity, suggesting its suitability for ocular administration and the potential to mitigate CNV progression with minimal irritation.
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TALANTA
·
2025
·
IF 6.1
Jingbo Sun,Liushunhao Chen,Hongchen Li,Chen Xu,Dong Xu,Jiali Ren
Biological staining is essential for imaging, functional investigation, and disease diagnostics. In this research, innovative green-emissive carbon dots (G-CDs) were hydrothermally prepared from 1,2,4-triaminobenzene and ascorbic acid (AA) and further explored for versatile imaging of mammalian cells, plant cells, and microorganisms. The G-CDs, exhibiting fluorescence enhancement, outperform conventional dyes in terms of staining efficiency and specificity across various biological systems. For mammalian cells (SH-SY5Y, Hep3B, and HEK293), the G-CDs can stain both the nuclei and nucleoli in 10 min via a micropinocytic endocytosis approach, with the latter brighter. Fluorescence enhancement was greater for RNA than for DNA. Interestingly, for plant cells, only cell walls were stained, because positive charges on G-CDs enable strong adsorption onto the negatively charged cell walls, thereby hindering their further entry. G-CDs can stain cell walls and nuclei for fungi (including Aspergillus flavus and Aspergillus niger ), and cell walls and nucleoids for bacteria ( Bacillus subtilis and Escherichia coli ). The targeted staining arises from both the binding of G-CDs to DNA, RNA, pectin, peptidoglycan, and cellulose, and fluorescence enhancement due to surface passivation inhibiting rotation and vibration of functional groups. Electrostatic interactions, coordination, hydrogen bonding, and amidation collectively account for the interactions between G-CDs and these biomolecules . Finally, their practical applications in leucorrhea examinations demonstrated their capability to differentiate between bacterial and fungal vaginosis, highlighting their potential in clinical diagnostics.
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