BRITISH JOURNAL OF PHARMACOLOGY
·
2025
·
IF 7.7
Yiling Mei,Xudong Chen,Si Shi,Wante Lin,Zhenfeng Cheng,Xiaoxi Fan,Wenqi Wu,Jibo Han,Weijian Huang,Bozhi Ye,Shanshan Dai
Background and Purpose Myocardial dysfunction is a significant complication associated with sepsis. However, there are currently no specific and effective treatments available. Inhibiting gasdermin D (GSDMD)-mediated pyroptosis has shown promise in mitigating sepsis-induced myocardial dysfunction. The GSDMD inhibitor Y2 (GI-Y2) has been demonstrated to directly bind to GSDMD. Nonetheless, it remains uncertain whether GI-Y2 offers a cardioprotective effect in the context of sepsis-induced myocardial dysfunction. Experimental Approach A mouse model of sepsis was created using lipopolysaccharide (LPS), caecal ligation and puncture. Following treatment with GI-Y2 or macrophage membrane-encapsulated GI-Y2 nanoparticles (GI-Y2@MM-NPs), myocardial dysfunction and pyroptosis levels in heart tissues were assessed. Transcriptome sequencing revealed the molecular mechanism of GI-Y2 in treating septic cardiomyopathy. Key Results We observed that GI-Y2 alleviated myocardial dysfunction and attenuated cardiac inflammation in mice induced by LPS, caecal ligation and puncture. GI-Y2 reduced macrophage pyroptosis and attenuated macrophage-mediated cardiomyocyte injury induced by LPS/nigericin. Concurrently, we confirmed the protective effect of GI-Y2 against LPS-induced cardiac dysfunction was abolished in the absence of GSDMD. Additionally, GI-Y2 attenuated the mitochondrial damage induced by LPS by inhibiting GSDMD in the mitochondria. Furthermore, we developed GI-Y2@MM-NPs to enhance the targeting capability of GI-Y2 towards macrophages in heart tissues and demonstrated its protective effect in vivo . Conclusion and Implications These findings indicate that GI-Y2 alleviates septic myocardial injury and dysfunction by specifically targeting GSDMD, thereby inhibiting GSDMD-mediated pyroptosis and mitochondrial damage. Both GI-Y2 and GI-Y2@MM-NPs may serve as promising therapeutic options for addressing septic myocardial dysfunction. Graphical
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Daoqing Fan,Shuai Qin,Chuanping Li,Yujia Ren,Lilin Hao,Hengqian Zhang,Jiawen Han,Jingyu Hou,Juan Wang,Shaojun Dong
Rational design of high-performance nanozymes with multiple enzyme-mimicking activities for biochemical sensing is one of the most promising directions in this area. D-PA is a kind of S-containing pharmaceutical for treating various diseases; the side effects caused by its unreasonable intake/residual have posed severe threats to human health and the living environment, making its accurate analysis gradually significant. However, most previous works exhibited the drawbacks of complicated synthesis of nanomaterials, unreliable single-modal results, and limited portable sensing ability. Herein, we prepared a low-cost MoCu-2MI MOF nanozyme via a simple hydrothermal method and revealed its excellent peroxidase/laccase dual-enzyme-mimicking properties that might benefit from a bimetallic valence modulation strategy via multifaceted experiments (EIS, EPR, ROS probes, and Michaelis-kinetic tests). Initially, MoCu-2MI MOF worked as a POD mimic and catalyzed the oxidation of TMB into blue-colored Ox-TMB. By synergistically harnessing the visual/photothermal effect of Ox-TMB and the effective reduction and ROS-scavenging abilities of D-PA, we constructed the first colorimetric-RGB-photothermal trimodal D-PA sensor with the assistance of portable devices, bringing evidently strengthened cost-effectiveness, reliability, and portable sensing ability. The LODs for D-PA under the three modes were 0.24, 7.88, and 7.98 μM, which could compete with most previous works. Moreover, the trimodal sensor presented satisfactory applicability in human serum and milk samples. More surprisingly, taking 2,4-DP as the model target (LOD = 0.11 μM), we further achieved the visual analysis of phenolic pollutants based on the excellent LAC-like activity of MoCu-2MI MOF. This work not only offered an effective approach for the exploration and controllable modulation of nanozymes with multiple enzyme-like properties but also opened up unique horizons for the design of multimodal portable biosensors.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL THERMODYNAMICS
·
2016
·
IF 2.196
Dandan Han,Yumin Liu,Xiaona Li,Teng Zhang,Zhenfang Li,Shichao Du,Mingxia Guo,Shijie Xu,Bo Yu,Baohong Hou,Junbo Gong
The solubility of calcium d -pantothenate in (water + methanol) mixtures and the effect of β -alanine on the solubility of calcium d -pantothenate in a constant mole ratio of methanol and water was measured from 263.15 K to 303.15 K by the HPLC analysis method ( P = 0.1 MPa). The solubility of calcium d -pantothenate increased with increasing temperature in all the mixtures at constant composition. Besides, it also increased with mole fraction of water in (water + methanol) mixtures at a constant temperature. Additionally, the solubility of calcium d -pantothenate was enhanced by β -alanine at a given temperature. The experimental solubility in (water + methanol) mixtures was correlated by the modified Apelblat equation, the ternary NRTL equation and Solubility-Polarity Model. The Apelblat equation, the quaternary NRTL equation and the Cohn equation were adopted to correlate the experimental solubility in the (water + methanol + β -alanine) mixtures. Worthwhile, the quaternary NRTL equation was first applied to correlating the quaternary solid-liquid equilibrium. It turned out that all the selected models give good performance on solubility prediction.
✓ 已验证
产品关联
DOI
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 16
·期 2
·1298-1306
·
IF 1.692
Yuyan Liang,Hai Niu,Limei Ma,Dan Du,Li Wen,Qing Xia,Wen Huang
Coreopsis tinctoria (snow chrysanthemum) has been reported to exert antihyperlipidemic effects. The present study aimed to identify the active compounds of Coreopsis tinctoria and to investigate the molecular mechanisms underlying its effects on lipid dysregulation by measuring lipid levels, reactive oxygen species, lipid peroxidation and fatty acid synthesis. The present results demonstrated that snow chrysanthemum aqueous extracts significantly reduced serum lipid levels and oxidative stress in vivo. The main compounds that were isolated were identified as flavanomarein (compound 1) and eriodictyol 7‑O‑β‑D glucopyranoside (compound 2). Compounds 1 and 2 demonstrated potent antioxidative properties, including free radical scavenging activity, inhibition of lipid peroxidation, as well as lipid‑lowering effects in human HepG2 hepatocellular carcinoma cells treated with free fatty acids (FFAs). Compound 2 was revealed to suppress the elevation of triglyceride levels and inhibit lipid peroxidation following FFA treatment. In addition, it was demonstrated to significantly reduce intracellular levels of reactive oxygen species and improve the mitochondrial membrane potential and adenosine triphosphate levels, thus protecting mitochondrial function in FFA‑treated HepG2 cells. Furthermore, compound 2 markedly suppressed the protein expression levels of disulfide‑isomerase A3 precursor and fatty acid synthase, thus suppressing FFA‑induced lipogenesis in HepG2 cells. In conclusion, the present study identified compound 2 as one of the main active compounds in Coreopsis tinctoria responsible for its lipid‑lowering effects. Compound 2 was revealed to possess antihyperlipidemic properties, exerted via reducing oxidative stress, protecting mitochondrial function and suppressing lipogenesis.
研究领域:
药理学
·
生物化学
·
分子生物学
·
植物科学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2026
·
IF 2.5
Hai Huang,Liwei Guo,Hansong Sun,Yunhong Liu,Jun Zhang,Weijie Tang,Xiaodong Xia,Yu Wang,Ni Chen,Dong Lv,Jing Yang
Objective To investigate the mechanism of action of saikosaponin D (SSD) on bladder cancer (BCa) and evaluate its synergistic antitumor efficacy with the chemotherapeutic agent gemcitabine (GEM). Methods MTT, colony formation, Transwell, and scratch wound healing assays detected SSD's effects on the proliferation, invasion, and migration of RT112 and T24 cells. Specific inhibitors identified cell death mode. Western blotting, immunohistochemistry, and flow cytometry verified ferroptosis-related protein expression and oxidative stress. Network pharmacology predicted core pathways, validated by examining PI3K/AKT pathway activity. Animal models evaluated the synergistic effect of SSD and GEM. Results In vitro, SSD dose-dependently inhibited the BCa cells proliferation, invasion, and migration, and upregulating E-cadherin whilst downregulating N-cadherin, Vimentin, and Snail. The effects were blocked by the ferroptosis inhibitor Fer-1. Network pharmacology identified the PI3K/AKT pathway as a core target. Moreover, SSD regulated the GPX4/SLC7A11/ACSL4, suppressed PI3K/AKT phosphorylation, and triggered lipid peroxidation and reactive oxygen species accumulation, partially reversed by a PI3K-specific phosphopeptide agonist. In vivo, SSD inhibited tumor growth, and its combination with GEM showed superior efficacy. The combination therapy most effectively downregulated SLC7A11, GPX4, Vimentin, N-cadherin and Snail, while upregulating the ACSL4 and E-cadherin. Conclusion SSD inhibits the malignant phenotype of BCa by targeting PI3K/AKT to trigger ferroptosis. Its synergistic effect with GEM from the dual mechanisms of ferroptosis sensitization and epithelial-mesenchymal transition inhibition, providing an innovative combination strategy based on natural product active ingredients to overcome bladder cancer chemoresistance.
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Da-Yuan Wang,Jing Li,Xiao-Han Tian,Siyu Zhang,Yao Chen,Feihe Ma,Henk.J. Busscher,Jing Shen,Linqi Shi
Light-activatable CO-generating molecules such as 3-hydroxyflavone (3-HF) derivates, are water-insoluble, which limits their applicability for infectious biofilm control. Here, a 3-HF-modified type of D-alanine (3-HFD) was coupled with hexadecyltrimethylammonium-bromide (CTAB) to self-assemble into water-suspensible, hydrophilic nanoparticles. Self-assembled 3-HFD nanoparticles did not generate CO upon visible-light irradiation, but dynamically disassembled upon metabolic-incorporation in bacterial cell-wall peptidoglycan of Gram-positive and Gram-negative periodontal pathogens, leaving molecular 3-HFD inside the cell-wall that generated CO upon visible-light irradiation. In vitro , visible-light irradiation of aerobic Staphylococcus aureus and anaerobic Porphyromonas gingivalis biofilms in presence of 3-HFD nanoparticles yielded CO-generation with strong antibiofilm activity under atmospheric oxygen conditions and in a nitrogen atmosphere. 3-HFD nanoparticles were subsequently applied for treatment of ligature-induced periodontitis in specific-pathogen-free rats with P. gingivalis inoculated, periodontal pockets. Irrigation with nanoparticle suspensions and visible-light irradiation of P. gingivalis infected periodontal pockets was demonstrated to yield in-pocket CO-generation. CO-generation improved bone-regeneration, modulated macrophages to attenuate immune-inflammation and reduced P. gingivalis colony-forming-unit counts, while hardly affecting total colony-forming-unit counts. This points to selective elimination of CO-susceptible pathogens and restoration of a healthy periodontal microbiome, as confirmed using 16S rRNA microbiome analyses. Herewith, an effective, non-surgical and non-antibiotic based three-in-one CO-based treatment of periodontitis is proposed.
✓ 已验证
产品关联
DOI
高影响因子
Nutrients
·
2025
·Vol. 17
·期 20
·3298
·
IF 5
Bingsi Li,Yuxuan Gu,Libing Zhou,Rui Chen,Yiwei Liu,Zexuan Wan,Ziyi Liang,Yukang Wang,Renlei Ji,Zhian Liu
Background/Objective: Cellular senescence is increasingly recognized as a key mechanism underlying sarcopenia, an age-related muscle disorder with no effective therapeutic. 6,4′-Dihydroxy-7-methoxyflavanone (DMF), a flavonoid isolated from Dalbergia odorifera T. Chen, has shown anti-senescence potential. This study aimed to investigate the protective effects of DMF against myoblasts senescence and elucidate the underlying molecular mechanisms. Method: A cellular model of senescence was established in C2C12 myoblasts using D-galactose (D-gal). The effects of DMF pretreatment were evaluated by assessing senescence phenotypes, myogenic differentiation, and mitochondrial function. The role of Sirtuin3 (SIRT3) was confirmed using siRNA-mediated knockdown. Results: DMF Pre-treatment effectively attenuated D-gal-induced senescence, as indicated by restored proliferation, reduced senescence-associated β-galactosidase activity, decreased DNA damage, and the downregulation of p53, p21Cip1/WAF1and p16INK4a. Furthermore, DMF rescued myogenic differentiation capacity, enhancing the expression of Myoblast determination protein 1, Myogenin, Myosin heavy chain and Muscle-specific regulatory factor 4, and promoting myotube formation. Mechanistically, DMF was identified as a SIRT3 activator. It enhanced SIRT3 expression and activity, leading to the deacetylation and activation of the mitochondrial antioxidant enzyme superoxide dismutase 2. This consequently reduced mitochondrial reactive oxygen species, improved mitochondrial membrane potential and ATP production, and suppressed the NF-κB pathway by inhibiting IκBα phosphorylation and p65 acetylation/nuclear translocation. Crucially, all the beneficial effects of DMF—including oxidative stress reduction, mitochondrial functional recovery, anti-inflammatory action, and ultimately, the attenuation of senescence and improvement of myogenesis—were abolished upon SIRT3 knockdown. Conclusions: Our findings demonstrate that DMF alleviates myoblasts senescence and promotes myogenic differentiation by activating the SIRT3-SOD2 pathway, thereby reducing oxidative stress and NF-κB-driven inflammation responses. DMF emerges as a promising therapeutic candidate for sarcopenia.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.5
Lu Wang,Chunyan Lu,Shugang Li,Tong Wu,Xiaomeng Ren,Shuang Song,Chunqing Ai
Aging is a multifactorial biological process in which chronic inflammation and oxidative stress are central to the development of age-related disorders, including neurodegenerative decline. Fucoidan, a sulfated polysaccharide extracted from brown algae, has well-documented anti-inflammatory and antioxidant effects, and therefore has the potential to be a neuroprotective agent against cognitive impairment associated with aging. In the present study, the major fucoidan fraction (LJF-2) isolated from Laminaria japonica was examined for its neuroprotective properties in a D-galactose induced aging mouse model. Oral administration of LJF-2 for 8 weeks significantly improved spatial learning and memory and suppressed neuroinflammatory responses and oxidative stress while significantly reducing the activation of astrocytes and microglia. These neuroprotective effects were linked to the regulation of key proteins involved in neuronal protection and synaptic function, such as neprilysin and synapsin, by cAMP response element-binding protein signaling. Furthermore, LJF-2 significantly remodeled the gut microbiota through a reduction in the abundance of the Bacteroidota, Proteobacteria, and several putative pathogenic genera, which enhanced the intestinal barrier integrity and modified the microbial metabolite profiles, especially those associated with tryptophan metabolism. Fecal microbiota transplantation experiments further confirmed the role of the gut microbiota modulated by LJF-2 in mediating its neuroprotective effects through reduction of oxidative stress and inflammation. Collectively, these findings suggest that LJF-2 may be a promising therapeutic approach to address the aging-related cognitive decline by modulating the gut–brain axis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Hanyu Wang,Yukun Ouyang,Wenjing Zou,Xingchong Liu,Haimin Li,Ruonan Zhou,Xian Peng,Xiaoli Gong
Perovskite defect passivation with molecule doping shows great potential in boosting the efficiency and stability of perovskite solar cells (PSCs). Herein, an efficient and low-cost bifunctional Lewis base additive d-tryptophan is introduced to control the crystallization and growth of perovskite grains and passivation defects. It is found that the additive doped in the solution precursors could retard crystal growth by increasing activation energy, resulting in improved crystallization of large grains with reduced grain boundaries, as well as inhibiting ion migration and PbI2 aggregation. As a result, the PSCs incorporated with d-tryptophan additives achieve an improved power conversion efficiency from 18.18 to 21.55%. Moreover, the d-tryptophan passivation agent improves the device stability, which retains 86.85% of its initial efficiency under ambient conditions at room temperature after 500 h. This work provides Lewis base small-molecule d-tryptophan for efficient defect passivation of the grain boundaries toward efficient and stable PSCs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Wen-long Zhao,Di Xu,Jun-song Wang
Aldose reductase (AR) is an important enzyme involved in the reduction of various aldehyde and carbonyl compounds, including the highly reactive and toxic 4-hydroxynonenal (4-HNE), which has been linked to the progression of various pathologies such as atherosclerosis , hyperglycemia , inflammation, and tumors. AR inhibitors have potential therapeutic benefits for these diseases by reducing lipid peroxidation and mitigating the harmful effects of reactive aldehydes. In this study, we found that torachrysone-8- O -β- d -glucoside (TG), a natural product isolated from Polygonum multiflorum Thunb., functions as an effective inhibitor of AR, exhibiting potent effects in clearing reactive aldehydes and reducing inflammation. TG up-regulated the mRNA levels of several antioxidant factors downstream of NRF2, especially glutathione S-transferase (GST), which is significantly increased, thus detoxifying 4-HNE by facilitating the conjugation of 4-HNE to glutathione, forming glutathione-4-hydroxynonenal (GS-HNE). By employing a combination of molecular docking, cellular thermal shift assay, and enzyme activity experiments, we demonstrated that TG exhibited strong binding affinity with AR and inhibited its activity and blocked the conversion of GS-HNE to glutathionyl-1,4-dihydroxynonene (GS-DHN), thereby preventing the formation of protein adducts and inducing severe cellular damage. This study provides novel insights into the anti-inflammatory mechanisms of AR inhibitors and offers potential avenues for developing therapeutic strategies for AR-related pathologies. Our findings suggest that TG, as an AR inhibitor, may hold promise as a therapeutic agent for treating conditions characterized by excessive lipid peroxidation and inflammation. Further investigations are needed to fully explore the clinical potential of TG and evaluate its efficacy in the treatment and management of these complex diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DNA AND CELL BIOLOGY
·
2020
·Vol. 39
·期 3
·355-367
·
IF 3.314
Jiuwei Zhang,Yaodong Chen,Jing Lin,Ruimei Jia,Tingting An,Tianxiu Dong,Yu Zhang,Xiuhua Yang
Hepatocellular carcinoma (HCC), the sixth most common malignancy worldwide, is characterized by a dismal prognosis due to high recurrence and metastasis rates. Thus, the need for the development of novel chemotherapeutic drugs is urgent. Cyclovirobuxine D (CVB-D), a steroidal alkaloid extracted from Buxus microphylla that has been extensively used to relieve the symptoms of cardiovascular diseases, has shown promising antineoplastic effects in recent studies. However, the therapeutic effects and underlying mechanisms of CVB-D on HCC remain largely unelucidated. This study experimentally indicated that CVB-D can repress HCC cell proliferation by arresting the cell cycle in G2 phase and can facilitate apoptosis. In addition, the migratory and invasive capabilities of HCC cells were noticeably attenuated by a nonlethal dose of CVB-D, and this attenuation was correlated with the inhibition of epithelial–mesenchymal transition (EMT). Moreover, in vivo, CVB-D displayed excellent anticancer effects in HCC tumor-bearing nude mice. Regarding the molecular mechanisms of CVB-D activity, decreased Slug expression was determined to be associated with the aforementioned anti-HCC functions of this extract, which might be regulated by epidermal growth factor receptor (EGFR) through the focal adhesion kinase (FAK)-associated PI3K/AKT and MEK/ERK1/2 signaling pathways. Collectively, our results revealed the suppressive effects of CVB-D on progressive behaviors of HCC, including proliferation, migration, invasion, and EMT, in addition to its outstanding proapoptotic effects, which were correlated with the inhibition of the EGFR-FAK-AKT/ERK1/2-Slug signaling pathway. These discoveries provide an experimental and theoretical foundation for the use of CVB-D as a promising candidate for HCC therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Rongkang Hu,Ruiguo Cui,Qingyun Tang,Dongming Lan,Fanghua Wang,Yonghua Wang
The mechanism of active site loops of Streptomyces phospholipase D (PLD) binding to the lipid–water interface for catalytic reactions still remains elusive. A flexible loop (residues 376–382) in the active site of Streptomyces klenkii PLD (SkPLD) is conserved within PLDs in most of the Streptomyces species. The residue Ser380 was found to be essential for the enzyme’s adsorption to the interface and its substrate recognition. The S380V mutant showed a 4.8 times higher catalytic efficiency and nearly seven times higher adsorption equilibrium coefficient compared to the wild-type SkPLD. The monolayer film technique has confirmed that the substitution of Ser380 with valine in the loop exhibited positive interaction between the enzyme and PCs with different acyl chain lengths. The results of the interfacial binding properties indicated that the S380V mutant might display suitable phosphatidylserine synthesis activity. The present study will be helpful to explain the role of residue 380 in the active site loops of Streptomyces PLD.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）