Cell Death & Disease
·
2018
·Vol. 9
·期 7
·1-16
·
IF 5.638
Wang Zhe,Zhao Simeng,Song Lihua,Pu Yuzhi,Wang Qiang,Zeng Guangzhi,Liu Xing,Bai Ming,Li Shao,Gao Fabao,Chen Lijuan,Wang Chen,Tan Ninghua
Rubiaceae-type cyclopeptides (RAs) are a type of plant cyclopeptides from the Rubia that have garnered significant attention owing to their unique bicyclic structures and amazing antitumour activities. Our recent work has shown that RAs suppress inflammation and angiogenesis and induce apoptosis. However, the underlying mechanism and targets remained unknown. Nuclear factor κB (NF-κB) signaling pathway plays a critical role in these biological processes, prompting us to investigate whether and how RAs affect this pathway. By screening compound libraries using NF-κB-dependent luciferase reporter, we observed that RA-V is the best NF-κB inhibitor. Further experiments demonstrated that RA-V interrupted the TAK1–TAB2 interaction and targeted TAK1 in this pathway. Moreover, RA-V prevented endotoxin shock and inhibited NF-κB activation and tumor growth in vivo. These findings clarify the mechanism of RA-V on NF-κB pathway and might account for the majority of known bioactivities of RA-V, which will help RA-V develop as new antiinflammatory and antitumour therapies.
研究领域:
药理学
·
免疫学
·
癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Mingyu Liu,Zhixing Lai,Lijun Zhu,Xin Ding,Xiyang Tong,Zhen Wang,Qirui Bi,Ninghua Tan
At present, oral chemotherapy showing the advantages of non-invasiveness, convenience, and high patient compliance, is gradually replacing traditional intravenous chemotherapy to treat patients with cancer. RA-XII, a unique natural cyclopeptide , exhibits various biological activities , such as anti-tumor, anti-angiogenic, and anti-metastatic activities. Designing an orally available formulation of RA-XII is of great importance in the development of clinically useful anticancer agents . However, RA-XII shows low oral bioavailability in rats due to its poor solubility and low permeability. To overcome these limitations, in this work, a natural deep eutectic solvent (NADES) was designed to efficiently deliver RA-XII by oral administration. A novel NADES composed of betaine and mandelic acid in the molar ratio of 1:1 (Bet-Man NADES) was successfully prepared based on a binary phase diagram of Bet and Man. Acute toxicity studies indicated that Bet-Man NADES was well tolerated with acceptable toxicity. In Bet-Man NADES solutions, the solubility of RA-XII was increased by up to 17.54-fold, and the diffusion and permeability of RA-XII carried out in a Franz cell was also significantly improved 10.35 times. In terms of biopharmaceutical classification this is translated into a change for RA-XII from class IV to class II systems. More importantly, Bet-Man NADES was transferred into the solid formulation by the inclusion of a polymer, and amorphous solid dispersions based on Bet-Man NADES (PVP K30/NADES/RA-XII, ASDs) were successfully prepared to improve uniformity, apparent solubility, dissolution, and cytotoxicity in vitro. Consequently, the oral bioavailability of RA-XII in NADES solutions and ASDs was enhanced by approximately 11.58 and 7.56 times compared with that of pure RA-XII in 0.5% CMC Na. Thus, it can be seen that a natural deep eutectic solvent and its modified amorphous solid dispersions are appropriate novel strategies for improving dissolution rate and bioavailability of poor soluble natural products such as RA-XII.
研究领域:
药剂学
·
肿瘤学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYHEDRON
·
2025
·
IF 2.6
Keliang Wan,Lifeng Tan
Double-stranded RNA determines and regulates many biological processes in cells, plays a vital role in cell information transmission and gene regulation, and is a key target for the treatment of certain diseases. Here, we synthesized and characterized two novel ruthenium(II) complexes [Ru(phen) 2 ( o -CNPIP)] 2+ (Ru 1 ) and [Ru(phen) 2 ( o -CH 3 PIP)] 2+ (Ru 2 , phen = 1,10-phenanthroline, o -CNPIP = (2-(4-cyanodipyrido)-imidazo-[4,5- f ][1,10]-phenanthroline, o -CH 3 PIP = 2-(4-methyl)-imidazo-[4,5- f ][1,10]-phenanthroline). The interaction of the two Ru (II) complexes with double-stranded RNA poly(rA)•poly(rU) under dilute solution and molecular crowding conditions was studied by various spectroscopic methods and viscosity measurements. The results of UV–vis absorption spectroscopy and steady-state emission spectroscopy studies show that Ru 1 showed stronger binding and stabilizing ability to poly(rA)•poly(rU) and the binding affinity of Ru 1 and Ru 2 to poly(rA)•poly(rU) was weakened under molecular crowding conditions. Subsequently, the results of circular dichroism spectroscopy studies, thermal denaturation measurements and viscosity measurements also confirmed the results of our UV–vis absorption spectroscopy and steady-state emission spectroscopy studies. The results also showed that the two Ru(II) complexes bind, stabilize and perturb the structure of poly(rA)•poly(rU) by intercalation under dilute solution and molecular crowding conditions. In addition, it was found that the strength of these abilities was closely related to the binding affinity of the Ru(II) complexes to poly(rA)•poly(rU) by comparing the results of these studies. Furthermore, the thermodynamic parameters for the binding of Ru(II) complexes to poly(rA)•poly(rU) under the two conditions indicate that the binding process is spontaneous, is an enthalpy-driven process, and that hydrogen bonding serves as the dominant force. The purpose of this work is to explore the substituent effect of Ru(II) complexes and the effect of solution environment on the ability of Ru(II) complexes to bind and stabilize poly(rA)•poly(rU). Some insights resulting from this work are expected to facilitate the design of highly selective double-stranded RNA binders based on Ru(II) complexes. Interestingly, the phosphorescence intensity of Ru 2 after binding to poly(rA)•poly(rU) is significantly higher than that of Ru 1 under both solution conditions, with even stronger phosphorescence emission observed under molecular crowding conditions. This indicates that Ru 2 possesses the potential to serve as a nucleic acid luminescent probe for nucleic acid imaging in biological cells. To enhance its luminescent properties and specific binding capacity, further structural modification of Ru 2 is essential, which will be one of the key focuses of our future research efforts.
研究领域:
无机化学
·
生物无机化学
·
核酸化学
·
分子光谱学
·
生物物理化学
✓ 已验证
DOI
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2022
·
IF 3.191
Zhen Yang,Rui Han,Hongqing Yin,Jingfang Li,Ying Cao,Ruoxi Guo,Yuanyuan Sheng,Lili Song,Yanjun Zhang
Interstitial lung disease (ILD) is the most common complication of rheumatoid arthritis (RA), which highly increases the morbidity and mortality of RA. Lycopodii herba (SJC) has been used as a widespread traditional Chinese medicine to treat RA and the related complications for more than 500 years. However, its therapeutic effect on RA-ILD and related mechanisms are not clear. The purpose of this work was to confirm the efficacy of SJC for RA-ILD and clarify its mechanism. In this study, we first determined the efficacy of SJC on RA-ILD. Then, 15 potential biomarkers of SJC were identified by metabolomics in rat serum, which were mainly associated with ether lipid metabolism and arachidonic acid metabolism. 21 pathways were related to SJC by network pharmacology . Combined with the results of metabolomics and network pharmacology and real-time PCR (RT-PCR) validation, the mechanism of SJC for RA-ILD may be related to the Ras signaling pathway and PI3K-Akt signaling pathway by regulating the expression of PLA2G1B and PI3KCA. This work preliminary confirmed the preventive and therapeutic effects of SJC on RA-ILD and elucidated the mechanism from the metabolic perspective.
✓ 已验证
DOI
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Xiyue Duan,Kepeng Hu,Jiawei Wang,Xiaozhao Wang,Xiaojun Long,Weiming Lin,Chengwei Wu,Wenjian Weng,Zhangfa Song,Kui Cheng
The imbalance of macrophage polarization between M1 and M2 phenotypes in rheumatoid arthritis (RA) results in a persistent inflammatory cascade. Activating M2 anti-inflammatory polarization, which remove excess extracellular matrix (ECM) via phagocytosis, represents a potential therapeutic target for RA. This study introduces Col/Cs@ECM microspheres, a novel drug delivery system designed for macrophage recognition via a tailored ECM surface, enhancing phagocytic efficiency and accumulation. Moreover, the Col/Cs@ECM microspheres are composed of biocompatible and fully degradable materials, ensuring their safety profile within the physiological environment. Following cell phagocytosis, the collagen/chitosan (Col/Cs) core release the drug (Dexamethasone, Dex) intracellularly to inhibit M1 polarization by inhibiting the NF-κB signaling pathway and to facilitate M2 polarization. This macrophage targeted and intracellular release approach offers a significant advantage over traditional medications by reducing systemic side effects and improving the therapeutic index. The strategy prompts macrophages to express anti-inflammatory cytokines like IL-10 while suppressing pro-inflammatory cytokines such as TNF-α, thereby remodeling the immune microenvironment. Additionally, the specially engineered ECM shell of the microspheres extends the anti-inflammatory response by prolonging macrophage lifespan, a feature that is not present in conventional treatments. This results in improved treatment outcomes in an in vivo RA animal model. This research presents a possible intracellular anti-inflammatory treatment approach for rheumatoid arthritis injection therapy with the potential to outperform existing treatments in terms of efficacy and safety.
研究领域:
生物医学工程
·
免疫治疗
·
药物递送系统
·
风湿病学
·
细胞生物学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOCHEMICAL ANALYSIS
·
2025
·
IF 2.6
Jing Xu,Yulong Zhu,Yi Wei,Peirong Gan,Shilin Xia,Ya Li,Xiaoman Jiang,Yan Wang,Hong Wu
Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily manifests with symptoms such as heat and toxin. However, the key components and molecular mechanisms of Zhizi Baipi decoction (ZBD) in the treatment of RA are still unclear. Objectives The study aimed to explore the mechanism of action of ZBD for treating RA through ingredient analysis, network pharmacology, and experimental validation. Material and Methods The chemical constituents of ZBD were identified by ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MS E ). Additionally, the active ingredients of ZBD treating RA were screened by network pharmacology and using molecular docking to verify the binding energy of the active ingredients and ZBD's targets. Then we elucidated ZBD's mechanism of action on collagen-induced arthritis (CIA) model rats. Subsequently, experimental validations were used to validate the findings of network pharmacology. Results A total of 84 chemical constituents was identified by UPLC-Q-TOF-MS E . The results of network pharmacology indicated that ZBD could exert its therapeutic effect on RA through the vascular endothelial growth factor (VEGF) pathway. Molecular docking revealed a strong binding capacity between the target KDR and the active ingredients. Additionally, we quantified the five active ingredients of ZBD. In vivo experiments demonstrated that ZBD inhibited synovial angiogenesis and alleviated the occurrence and progression of RA. Conclusion Overall, ZBD has a significant therapeutic effect on RA. The results of qualitative analysis, network pharmacology, molecular docking, and in vivo experiments indicated that the main active components of ZBD could modulate the VEGF pathway to treat RA.
研究领域:
药理学
·
免疫学
·
分子生物学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Abudureheman Bahatibieke,Jianming Zhao,Danping Fan,Zixiang Zhou,Junfei Li,Xing Wang,Hongyan Zhao,Tianyang Wang,Ziyuan Fang,Yajie Xie,Cheng Huang,Cheng Xiao,Yudong Zheng
Rheumatoid arthritis (RA) is a common autoimmune joint disease characterized by persistent synovial inflammation and cartilage damage. The current clinical treatments primarily utilize drugs such as triptolide (TP) to address inflammation, yet they are unable to directly repair damaged cartilage. Furthermore, the persistent inflammation often undermines the effectiveness of traditional cartilage repair strategies, preventing them from achieving optimal outcomes. To tackle this challenge, this study successfully developed a drug-loaded polyurethane hydrogel-oriented porous scaffold, designed to address persistent inflammation and facilitate cartilage repair under RA conditions. A drug-loaded hydrogel was formed via solvent-induced polyurethane-gelatin, resulting in the scaffold TP@GSPU. The sea-island micelle structure of TP@GSPU enables efficient loading of TP. The release of TP in the in vivo environment regulates the expression of inflammatory factors in macrophages, thereby improving the inflammatory microenvironment within the joint cavity. Additionally, the gelatin component of the scaffold provides robust support for cartilage regeneration. The efficacy of the TP@GSPU in regulating the inflammatory microenvironment and facilitating cartilage repair under RA conditions, which was demonstrated through cartilage damage repair experiments conducted in a rat collagen-induced arthritis (CIA) model. The design scheme of this material offers a potential approach to cartilage repair in the conditions of RA.
研究领域:
医学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2026
·
IF 6.1
Li Jiang,Luna Shen,Shuting Fang,Fangyuan Sun,Guizhong Xin,Lifang Liu,Jiayi Zheng
An integrated multi-level analytical framework was developed to characterize glutamine metabolic remodeling associated with RA-ILD. • Multi-matrix metabolomics revealed compartment-specific redistribution of glutamine-related amino acids. • [α- 15 N] glutamine tracing in vitro identified intracellular fibrotic redirection toward serine/glycine biosynthesis. • CTSs modulated intestinal transporters and suppressed the ATF4-associated serine/glycine program. Background Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe complication with limited therapeutic options, characterized by destructive joint lesions and pulmonary fibrosis involving excessive collagen deposition. Glutamine metabolism supplies precursors for collagen-related amino acid biosynthesis, which drives the fibrotic remodeling process, but its cross-organ redistribution and pathway-specific utilization remain difficult to resolve using conventional metabolomic readouts. An analytical strategy capable of integrating quantitative multi-matrix profiling with isotope-resolved nitrogen tracing is therefore needed to characterize alterations in glutamine-related amino acid metabolism associated with RA-ILD and its pharmacological modulation. Results We established a complementary analytical framework in which 3-trimethylsilyl-1-propanaminium chloride (TSPC) derivatization-assisted UPLC-QqQ-MS/MS targeted metabolomics and intestinal amino acid transporter profiling were applied to an RA-ILD rat model, while [α- 15 N] glutamine tracing was independently performed in a TGF-β1-induced fibrotic cell model to examine pathway-specific glutamine nitrogen utilization. The validated method enabled sensitive quantification of glutamine-related amino acids in serum, lung tissue, and cells. In RA-ILD rats, cross-matrix profiling revealed a compartment-dependent disturbance of glutamine-related amino acid distribution, characterized by pulmonary accumulation coupled with altered circulating availability. Clematis triterpenoid saponins (CTSs) partially normalized this metabolic imbalance and were associated with coordinated regulation of intestinal glutamine transporters. Stable-isotope tracing in a fibrotic cell model further showed preferential incorporation of glutamine-derived nitrogen into the serine-glycine axis, which was supported by increased expression of ATF4-associated serine-glycine biosynthetic enzymes in lung tissue. CTSs treatment attenuated the corresponding lung transcriptional alterations. Significance Together, in vivo multi-matrix metabolomics characterized systemic glutamine-related metabolic redistribution and its response to CTSs in RA-ILD, whereas complementary in vitro isotope tracing provided pathway-level evidence for preferential glutamine-derived nitrogen utilization through the serine-glycine axis under fibrotic stimulation. Such a complementary framework also provides a transferable analytical strategy for investigating cross-organ diseases and multi-level interventions of traditional Chinese medicines. Download: Download high-res image (371KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
PHARMACEUTICAL BIOLOGY
·
2019
·
IF 2.492
Chunfang Zhang,Wenfeng Zhang,Rongyu Shi,Bangyi Tang,Shicheng Xie
Context: Adlay seed [Job’s tears, Coix lachryma-jobi L. var. ma-yuen Stapf (Poaceae)] is a Traditional Chinese Medicine, which has been investigated to treat inflammatory diseases and rheumatism.Objective: This study evaluates the ameliorative effects of adlay seed extract (ASE) in a complete Freund’s adjuvant (CFA)-induced rheumatoid arthritis (RA) rats.Materials and methods: The RA Sprague–Dawley rat model was induced and randomly divided into six groups with or without ASE treatment (50, 100 or 200 mg/kg). After 28 d administration, the symptoms, biochemical parameters and molecular mechanisms were investigated.Results: The values of paw oedema, PGE2 and MMP-3 decreased from 1.46 ± 0.04 to 0.66 ± 0.07 cm3, from 126.2 ± 11.48 to 79.71 ± 6.8 pg/mL and from 142.7 ± 8.36 to 86.51 ± 5.95 ng/mL, respectively; the values of body weight increased from 177.25 ± 5.94 to 205 ± 6.52 g in HASE group. In addition, treatment of ASE reduced the levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, MCP-1), and increased the activities of antioxidant enzyme (GSH-Px, SOD, and CAT). Furthermore, ASE could suppress the mRNA expression of COX-2 and CHI3L1 and improve the mRNA expression of CAT and GPx-1 in ankle tissues of RA rats.Discussion and conclusions: For the first time, our results indicated ASE exerts anti-RA effects via inhibiting pro-inflammatory factors and alleviating oxidative stress. Our finding sheds light on the research and development of anti-RA functional foods from adlay seed.
研究领域:
药理学
·
免疫学
·
中医药
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Molecular Catalysis
·
2021
·
IF 5.062
Shiyu Wei,Yafei Liu,Jieyu Zhou,Guochao Xu,Ye Ni
Two enantiocomplementary Baeyer-Villiger monooxygenases Ra BVMO and Am BVMO were identified by genome mining for the asymmetric sulfoxidation. Both recombinant BVMOs have optimal pH of 9.0 and temperature of 35 °C. The half-lives of Ra BVMO and Am BVMO at 30 °C were 24.4 and 24.6 h. Ra BVMO and Am BVMO exhibited broad substrate spectrum and could catalyze the oxidization of various compounds including fatty ketones, cyclic ketones, and thioethers. Kinetic parameters analysis revealed that both Ra BVMO and Am BVMO displayed higher catalytic efficiency toward thioanisole than cyclohexanone. As much as 50 mM thioanisole could be completely oxidized by Am BVMO and Ra BVMO with 99% ( R ) and 95% ( S ), respectively. Molecular docking analysis further provides evidence for the complementary enantioselectivity of Ra BVMO and Am BVMO. Our results demonstrate the potential application of the two novel BVMOs in asymmetric synthesis of sulfoxides.
研究领域:
生物化学
·
酶学
·
有机化学
✓ 已验证
DOI
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 23
·8475
·
IF 4.927
Lanxin Bao,Jing Ye,Nannan Liu,Yubao Shao,Wenhao Li,Xuefei Fan,Dahai Zhao,Hongzhi Wang,Xiaoyu Chen
Interstitial lung disease associated with rheumatoid arthritis (RA-ILD) can lead to interstitial fibrosis and even lung failure as a complication of rheumatoid arthritis (RA), and there is currently no effective treatment and related basic research. Studies have found that resveratrol (Res) can improve the progression of RA by regulating autophagy, and increasing evidence supports the connection between autophagy and common interstitial lung disease (ILD). We explored changes in autophagy levels in fibrotic lungs in RA-ILD and found that the level of autophagy is enhanced in the early stage but inhibited in the late stage. However, resveratrol treatment improved the level of autophagy and reversed the inhibition of autophagy, and attenuated fibrosis. We created corresponding cell models that exhibited the same phenotypic changes as animal models; under the effect of resveratrol, the level of fibrosis changed accordingly, and the fusion process of lysosomes and autophagosomes in autophagy was liberated from the inhibition state. Resveratrol effects were reversed by the addition of the late autophagy inhibitor chloroquine. These results suggest that resveratrol attenuates pulmonary fibrosis, increases autophagic flux, and modulates the autophagy–lysosome pathway, and particularly it may work by improving the formation of autophagic lysosomes, which may be an effective treatment for induced RA-ILD.Keywords:RA-ILD;resveratrol;autophagy;fibrosis;P62/SQSTM1
研究领域:
药理学
·
免疫学
·
肺病学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF LUMINESCENCE
·
2025
·
IF 3.6
Zihao Han,Zhihao Jiang,Jianwei Dao,Tiqun Wei,Zhenglin Jiang,Zhicheng Lv,Liang Yang
To advance artificial-light plant cultivation and high-performance white light-emitting diodes (LEDs), a phosphor combining excellent luminous thermal stability with superior luminescence is essential. In this work, the high-thermal-stability Ca 3 Bi(PO 4 ) 3 (CBPO): Eu 3+ red phosphors were successfully synthesized via high-temperature solid-state method. The performance of LEDs fabricated with the phosphors is enhanced in the far-red light region. When combined with commercial blue and green phosphors, the resulting white LEDs achieve high color rendering index (R a = 90.3) and low correlated color temperature (CCT = 4898 K). Upon near-ultraviolet (n-UV) excitation, the CBPO: Eu 3+ phosphors exhibit bright red emission at 615 nm, achieving optimal performance at a doping concentration of 0.24. At temperature of 423 K (150 °C), the luminescence intensity of the CBPO: 0.24Eu 3+ phosphor retained 71.9% of room-temperature value, demonstrating its good luminous thermal stability. The fabricated red LEDs with high color purity and spectral characteristics closely matching the absorption properties of plant photosensitive receptor proteins, enhance photosynthetic efficiency and underscore their substantial application potential in plant growth. The fabricated white LEDs can emit bright white light, with R a and R 9 values of 90.3 and 62, which are significantly higher than the standard R a (80) and R 9 (30) of commercial phosphors. We conducted a plant growth experiment in the laboratory, demonstrating that the fabricated red LEDs effectively supplement plant illumination and promote growth. These results demonstrate that the prepared CBPO: Eu 3+ red phosphors hold significant potential for applications in both plant growth lighting and white LEDs.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）