MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 3
·1-10
·
IF 6.232
Zhao Yu,Pang Bo,Chen Jie,Xiao Lizhi,Liu Hou,Lian Wenhui,Sun Tianxia,Jiang Yingnan,Lin Quan
Doubly charged pH-responsive core/shell hydrogel nanoparticles with green fluorescence were prepared and were shown to be viable bioprobes for active targeting tumor tissue and imaging of cancer cells. Via emulsionfree copolymerization hydrogel nanoparticles as VANPs were prepared, the core of which was polystyrene (Ps) and the shell was comprised of strongly positive electrolyte (ar-vinylbenzyl)trimethylammonium (VBTAC) with weak negative electrolyte acrylic acid (AA). Through conventional amidation, the shell was conjugated with cell-specific folic acid (FA), denoted as VANPs-FA. Then, negatively charged sulfonated 9,10-distyrylanthracene derivatives (SDSA) based on aggregation induced emission (AIE), was binding tightly to positively charged VBTAC of VANPs-FA shell. The prepared double charged fluorescent core/shell hydrogel nanoparticles abbreviated as VANPs-FS, showed excitation/emission wavelengths at ~420/528 nm. Dynamic light scattering (DLS) measurements were performed to determine the size and surficial zeta potential of VANPs-FS. Under proper ratio of VBTAC to AA, the VANPs-FS was stable (~ 64.63 nm, −20.2 mV) at high pH (> 7), started to aggregate (~ 683.0 nm, −3.2 mV) at pH around 6, and can redispers at low pH (< 5). The MTT analysis proved that VANPs-FS had good biocompatibility and low cytotoxicity. The targeting effectiveness of VANPs-FS was confirmed by confocal laser scanning microscopy (CLSM).
Detailed synthetic route of VANPs-FS (top) and schematic cancer tumor-target aggregation of pH-sensitive VANPs-FS with enhanced retention and rapid cancer cell imaging (bottom).
研究领域:
纳米技术
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癌症研究
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生物医学工程
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材料科学
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DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Bin Hu,Jiani Liu,Chengwen Deng,Youmei Xing,Min Gong,Zhen Wu,Guojie Wang
Stimuli-responsive surfactants have garnered significant attention as promising candidates for diverse applications in efficient oil recovery, programmable all-liquid devices, and microreactors owing to their dynamic interfacial self-assembly behavior under specific triggers. However, contemporary applications of stimuli-responsive surfactants remain constrained within monofunctional paradigms, significantly impeding their integration into advanced multifunctional manufacturing. Here, an interesting pH-responsive gemini surfactant is reported that can dynamically switch between gemini (GTL, pH ≥ 8.0) and single-chain (TL + , pH ≤ 6.0) conformation, facilitating adaptive functionalities spanning reversible oil/water separation, structured liquid, 3D printing, and thermal insulative aerogels. As triggered by CO 2 /Ar, GTL acts as a smart emulsifier, achieving efficient oil/water separation over 10-cycle reusability. The electrostatic co-assembly of TL + and sulfated cellulose nanocrystals (CNC-OSO 3 − ) at the oil-water interface drives a jammed film, yielding a reconfigurable all-liquid structure. Furthermore, TL + /CNC-OSO 3 − -stabilized emulsions exhibit self-supporting properties, enabling dual functionality as 3D-printable inks for complex patterning in air/oil baths, and as advanced precursors for thermal insulative aerogels. Density functional theory calculations reveal the pH-dependent adsorption of GTL at the oil-water interface and the co-assembly of TL + /CNC-OSO 3 − driven by abundant non-covalent interactions. This pH-responsive surfactant addresses the critical demand for multifunctional manufacturing, establishing an adaptive paradigm for next-generation smart materials.
研究领域:
化学工程
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材料科学
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软物质物理
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胶体与界面科学
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纳米技术
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DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2026
·
IF 4.1
Zihan Li,Boxuan Xie,Xilei Liu,Zihan He,Zhongwei Zhang,Jianming Zhou,Tong Zhou,Huai Wang
As the most frequently occurring cancer worldwide, lung cancer is notoriously diagnosed at advanced stages, resulting in high mortality rates. The primary factor underlying this persistent global health burden remains tobacco consumption. Nicotine, a key component of cigarette smoke, is one of the major contributing factors to the development of lung cancer, but the molecular mechanisms remain incompletely elucidated. α7-nAChR, β2-AR, and HGF/c-Met are known to contribute to lung cancer development, respectively. However, the specific signaling cascade through which they interact in nicotine-induced malignancy is unclear. In this study, using CCK-8 assays across a range of concentrations (0–5 μM), we determined that 1 μM nicotine treatment for 48 h optimally enhances A549 cell proliferation, establishing this condition for subsequent experiments. This study uncovers nicotine’s role in driving malignant behaviors including proliferation, migration, and invasion in nonsmall cell lung cancer A549 cells. Notably, nicotine potently stimulated migration and invasion, accompanied by upregulation of Cyclin D1 and MMP-2, and downregulation of BAX, BAD, and Caspase-3. Mechanistically, nicotine induced synergistic engagement of α7-nAChR and β2-AR, leading to activation of the HGF/c-Met/PI3K/AKT axis and enhancing the secretion of both HGF and MMP-2. Importantly, we reveal a previously unrecognized bidirectional regulatory loop between α7-nAChR and β2-AR that functionally converges on the HGF/c-Met axis, which acts as a critical signaling hub to drive the downstream PI3K/AKT pathway and facilitate tumor progression. Our findings provide the first evidence of a coordinated α7-nAChR/β2-AR interface regulating HGF/c-Met signaling that orchestrates both intracellular signaling and extracellular secretory programs in nicotine-promoted lung cancer progression. This offers innovative insights for identifying potential antitumor therapeutic targets and presents novel perspectives for the prevention and clinical management of lung cancer, particularly in smokers with nonsmall cell lung cancer.
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DOI
PubMed
高影响因子
Cell Death & Disease
·
2017
·Vol. 8
·期 10
·e3095
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IF 5.965
Xu Junjie,Zheng Longbo,Chen Jiang,Sun Yin,Lin Hui,Jin Ren-an,Tang Minyue,Liang Xiao,Cai Xiujun
Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2 α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2 α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2 α , increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2 α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
·
2019
·Vol. 9
·期 1
·1-10
·
IF 4.011
Sun Juan,Zhang Zonghuai,Gong Yansheng,Wang Huanwen,Wang Rui,Zhao Ling,He Beibei
The development of highly active and cost-effective catalysts based on noble metal free oxygen electro-catalysis is critical to energy storage and conversion devices. Herein, we highlight a plasma-treated Bi 0.1 (Ba 0.5 Sr 0.5 ) 0.9 Co 0.8 Fe 0.2 O 3−δ perovskite (denoted as P-Bi 0.1 BSCF) as a promising catalyst for oxygen evolution reaction (OER) in alkaline media. H 2 /Ar plasma engraving could significantly increase electrochemically active O 2 2− /O − concentration and tune the electronic structure of Co ions efficiently, and consequently tailor the intrinsic electrocatalytic ability for OER. Of note, P-Bi 0.1 BSCF, with unique crystalline core/amorphous shell structure, exhibits an enhanced intrinsic OER activity and higher stability than the noble metal IrO 2 catalyst, which outperforms most of the reported perovskite catalysts. The present work provides new insights into exploring efficient catalysts for OER, and it suggests that, in addition to the extensively applied for surface treatment of various catalysts such as carbons and metal oxides, the plasma engraved perovskite materials also exhibits great potential as precious metal-free catalysts.
研究领域:
材料科学
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电化学
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催化
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能源存储与转换
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2017
·
IF 2.981
Jie Wu,Xue Li,Wencheng Wan,Qiaohong Yang,Weifeng Ma,Dan Chen,Jiangmiao Hu,C.-Y.Oliver Chen,Xiaoyong Wei
Ethnopharmacological relevance Dendrobium . chrysotoxum Lindl is a commonly used species of medicinal Dendrobium which belongs to the family of Orchidaceae , locally known as “Shihu” or “Huangcao”. D. chrysotoxum Lindl is widely known for medicinal values in traditional Chinese medicine as it possesses anti-inflammatory, anti-hyperglycemic induction, antitumor and antioxidant properties. Study aim To characterize the interaction between gigantol extracted from D. chrysotoxum Lindl and the AR gene, and determine gigantol's efficacy against cataractogenesis . Materials and methods Human lens epithelial cells (HLECs) were induced by glucose as the model group. Reverse transcription polymerase chain reaction (RT-PCR) was used to assess AR gene expression. Then, the mode of interaction of gigantol with the AR gene was evaluated by UV–visible spectroscopy, atomic force microscope (AFM) and surface-enhanced Raman spectroscopy (SERS). The binding constant was determined by UV–visible. Results Gigantol depressed AR gene expression in HLECs. UV–visible spectra preliminarily indicated that interaction between the AR gene and gigantol may follow the groove mode, with a binding constant of 1.85×10 3 L/mol. Atomic force microscope (AFM) data indicated that gigantol possibly bound to insert AR gene base pairs of the double helix. Surface-enhanced Raman spectroscopy (SERS) studies further supported these observations. Conclusion Gigantol extracted from D. chrysotoxum Lindl not only has inhibitory effects on aldose reductase, but also inhibits AR gene expression. These findings provide a more comprehensive theoretical basis for the use of Dendrobium for the treatment of diabetic cataract.
研究领域:
药理学
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民族药理学
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分子生物学
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糖尿病研究
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眼科
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Chunlan Tang,Zhiling Fang,Donghui Chu,Lulu Zhang,Yuqing Tang,Jinyue Zhou,Rui Fang,Jiaming Ying,Fang Wang,Yuping Zhou,Chunshuang Xu,Qinwen Wang
Alzheimer’s disease (AD) is a common and serious neurodegenerative disease in the elderly; however, the treatment of AD is still lacking of rational drugs. In this paper, the active constituents and targets of the self-developed Chinese medicine Formula 9002A in the treatment of AD were investigated from three aspects: pharmacodynamics based on cell and animal experiments, network pharmacology analysis, and pharmacokinetic analysis. A total of 124 compounds were screened in Formula 9002A, and four constituents including salidroside, gastrodin, niacinamide, and umbelliferone were screened as potential active components for the treatment of AD by network pharmacology. Among them, salidroside and gastrodin showed higher relevance with AD targets, such as ESR1 and AR. The pharmacokinetic study showed that they could be absorbed and identified in plasma; the half-life and mean residence times of salidroside and gastrodin in plasma were nearly increased 2-fold by the administration of Formula 9002A compared with those by the administration of a monomer, indicating the extended action time of active compounds in vivo . Formula 9002A exerted the efficacy in the treatment of AD mainly by regulating APP, GSK3β, ESR1, and AR targets based on the anti-β-amyloid protein deposition, anti-oxidation and anti-apoptosis pathways. Two genes enriched in Alzheimer’s disease pathway, APP and GSK3β, were further validated. The experiments also demonstrated that Formula 9002A could downregulate APP and GSK3β protein expression in the model mice brain and improved their cognitive ability. In summary, Formula 9002A has the characteristics of multiple targets and multiple pathways in the treatment of AD, and salidroside and gastrodin might be the main active constituents, which could provide a foundation for further research and application.
研究领域:
神经学
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药理学
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中医药
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网络药理学
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药代动力学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Yaqi Wang,Ping Shu,Mei Lv,Yonghao Xing,Haoran Zhang,Xiaojing Yan,Bo Wang,Tingting Huang,Minfeng Fang
Farfarae Flos and its honey-processed product are used to treat respiratory diseases; yet their active components and therapeutic targets remained unclear. Herein, we developed an integrated strategy combining receptor chromatography and mice models to screen and evaluate active components in both raw and honey-processed Farfarae Flos. We focused on three key receptors,β 2 -AR, CysLT 1 R, and M 3 R, known to be involved in antitussive, anti-inflammatory, and expectorant activities. These receptors were immobilized onto silica gels to construct affinity columns. Using these columns, we identified the bioactive compounds in both forms of Farfarae Flos. The results revealed an identical set of target-specific compounds across raw and honey-processed samples: chlorogenic acid (CGA) and caffeic acid (CA) targeted β 2 -AR; CGA and rutin bound to CysLT 1 R; and CGA along with isochlorogenic acids A, B, and C interacted with M 3 R. Notably, the interactions of rutin with CysLT 1 R and isochlorogenic acids A, B, and C with M 3 R are reported for the first time. These findings indicate that both raw and honey-fired Farfarae Flos share the same material basis for their antitussive, anti-inflammatory, and expectorant effects, with no significant alteration in pharmacological efficacy due to honey processing. Furthermore, the binding affinities of the bioactive compounds for the receptors correlated well with the molecular docking-predicted binding energies of the corresponding compound-receptor complexes. To our knowledge, this study represents the first target-centric comparative analysis of raw and processed Farfarae Flos. It establishes a generalizable framework for investigating processing-induced changes in herbal pharmacology and provides empirical evidence connecting metabolomic profiles to clinical efficacy.
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PubMed
高影响因子
MOLECULAR MEDICINE
·
2025
·Vol. 31
·期 1
·1-17
·
IF 6.4
Liu Jing,Li Wenqi,Jiao Ran,Liu Zhigang,Zhang Tiantian,Chai Dan,Meng Lingxin,Yang Zhongyi,Liu Yuming,Wu Hongliang,Gu Xiaoting,Li Xiaohe,Yang Cheng
Background Cardiac fibrosis is significant global health problem, which is associated with numerous cardiovascular diseases, and ultimately leads to the progression to heart failure. β-adrenergic receptor (β-AR) overactivation play a role in the development of cardiac fibrosis. Miglustat (Mig) has shown anti-fibrosis effects in multiple fibrotic diseases. However, it is unclear whether and how Mig can ameliorate cardiac fibrosis induced by β-AR overactivation. Methods In vivo, mice were injected with isoproterenol (ISO) to induce cardiac fibrosis and treated with Mig. In vitro, primary cardiac fibroblasts were stimulated by ISO and treated with Mig. Levels of cardiac fibrosis, cardiac dysfunction, activation of cardiac fibroblasts were evaluated by real-time polymerase chain reaction, western blots, sirius red staining, immunohistochemistry staining and echocardiography. Through GEO data and knockdown UDP-glucose ceramide glycosyltransferase (UGCG) in primary cardiac fibroblasts, whether Mig alleviates cardiac fibrosis by targeting UGCG was explored. Results The results indicated that Mig alleviated ISO-induced cardiac dysfunction. Consistently, Mig also suppressed ISO-induced cardiac fibrosis. Moreover, Mig attenuated ISO-induced cardiac fibroblasts (CFs) activation. To identify the protective mechanism of Mig on cardiac fibrosis, several classical β-AR downstream signaling pathways, including ERK, STAT3, Akt and GSK3β, were further analyzed. As expected, ISO activated the ERK, STAT3, Akt and GSK3β in both CFs and mouse hearts, but this effect was reversed pretreated with Mig. Besides, Mig ameliorates ISO-induced cardiac fibrosis by targeting UDP-glucose ceramide glycosyltransferase (UGCG) in CFs. Conclusions Mig ameliorates β-AR overactivation-induced cardiac fibrosis by inhibiting ERK, STAT3, Akt and GSK3β signaling and UGCG may be a potential target for the treatment of cardiac fibrosis.
研究领域:
心血管疾病
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
TOXICOLOGY IN VITRO
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2021
·
IF 3.5
Shuyu Ouyang,Dachuan Zhang,Tengfei Zhu,Shuting Yu,Wunier,Qian-Nan Hu,Yingying Le
β 2 -adrenoceptor (β 2 AR) agonists can stimulate skeletal muscle growth. Their illegal use in food-producing animals, human athletes and bodybuilders causes adverse health effects. In the present study, we developed 3D-QSAR models for predicting the activity of chemicals which can stimulate skeletal muscle growth through β 2 AR. The activity of 25 β 2 AR agonist s was measured by β 2 AR-cAMP response element (CRE) –luciferase (Luc) reporter assay. The 3D-QSAR models were built using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models displayed high external predictability (R 2 0.996 and 0.992, respectively) and good statistical robustness, and revealed that electrostatic effects were the most prominent forces influencing the activity of β 2 AR agonists. The CoMFA and CoMSIA contour plots provided clues regarding the main chemical features responsible for the activity variations and also resulted in predictions which correlate very well with the observed activity. In vitro study with differentiated myotubes showed that the potency orders of β 2 AR agonists in activating the β 2 AR-CRE-Luc reporter and in upregulating CREB target genes related to muscle growth were consistent. These 3D-QSAR models provide tools for predicting the activity of chemicals which might be illegally used in livestock or humans to stimulate skeletal muscle growth.
研究领域:
药理学
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分子生物学
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生物信息学
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毒理学
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2023
·
IF 5.6
Wenkai Zhang,Li Kong,Zhen Zhong,Lezhen Lin,Jingen Li,Guodong Zheng
To investigate the molecular mechanism of short chain fatty acids (SCFAs) on promoting fatty acid β-oxidation and browning in 3T3-L1 adipocytes. SCFAs significantly reduced lipid accumulation in 3T3-L1 adipocytes. In addition, via increasing the expression of Tfam and Nrf1, SCFAs enhanced mitochondrial biogenesis. According to the results of qPCR analysis, the expression levels of fatty acid β-oxidation genes ( PPARα , CPT1α , ACOX1 ) were up-regulated by SCFAs. Moreover, SCFAs treatment increased the genes and proteins expression of brown adipocyte-specific factors such as PRDM16, PGC-1α, and UCP-1, as well as up-regulated the genes expression of beige adipocytes markers ( Tmem26 , Tbx1 , CD137, and Cited1) . Furthermore, the effects of β3-AR and AMPK antagonist were reversed by SCFAs. In conclusion, SCFAs promote fat β-oxidation and browning of adipocytes through β3-AR/AMPKα signaling pathway, thereby reducing fat accumulation in 3T3-L1 adipocytes. Therefore, SCFAs may be a helpful supplement to combat obesity.
研究领域:
分子生物学
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细胞生物学
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代谢
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营养学
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高影响因子
危险品化学品经营许可证（带存储）