Small
·
2025
·
IF 12.1
Xianquan Feng,Yan Zhang,Wanjing Lin,Jing Li,Fei Wu,Qingyu Lu,Hongtao Song,Hao Zhang,Fenghua Lan,Jun Lu
The efficacy of immunotherapy in triple-negative breast cancer (TNBC) is significantly hindered by its low immunogenicity and immunosuppressive tumor microenvironment. Non-invasive photodynamic therapy (PDT) is increasingly recognized as a potential immunotherapeutic stimulant in the treatment of TNBC. However, photodynamic immunotherapy is constrained by tumor hypoxia and excessive inflammation suppression during the course of treatment. Herein, a simple and efficacious biomedicine is formulated to overcome adverse influences by amplifying photodynamic immunotherapy, thereby stimulating the systemic immune response. Specifically, the approach targeted tumor delivery by employing specific agents such as the photosensitizer (verteporfin), the hypoxic ameliorator (atovaquone), and the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) signaling blocker (celecoxib). More importantly, the biomedicine effectively ameliorated hypoxia and inhibited COX-2/PGE2 signaling, thereby amplifying PDT-induced immunogenic cell death. This, in turn, enhanced the efficacy of photodynamic immunotherapy and triggered a robust immune response cascade. Notably, the self-amplifying photodynamic biomedicine significantly inhibited primary tumors, distal tumors, lung metastases, and post-operative recurrence while maintaining high biocompatibility. To sum up, the work provides a viable cascade stimulation approach and an efficient biomedical nanoplatform, offering a novel strategy for photodynamic immunotherapy of TNBC in the clinic.
研究领域:
肿瘤学
·
免疫学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IMMUNOBIOLOGY
·
2024
·
IF 2.5
Min Li,Wenjia Tong,Chao Dai,Guoping Lu,Danqun Jin,Fang Deng
Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-κB signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-κB P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF-κB. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition.
研究领域:
免疫学
·
肾病学
·
炎症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2019
·Vol. 7
·期 3
·949-958
·
IF 1.747
Yaqiong Zhang,Ming Li,Hang Gao,Bo Wang,Xu Tongcheng,Boyan Gao,Liangli (Lucy) Yu
In this study, a new red sorghum variety (Ji Liang No. 1) was investigated for its triacylglycerol (TAG) and fatty acid profiles, carotenoid and tocopherol compositions, total phenolic, total flavonoid and phenolic acid contents, and antioxidant and anti-inflammatory properties. A total of 17 TAGs were identified in the red sorghum oil. Linoleic and oleic acids were the primary fatty acids, contributing more than 80% of the total fatty acids. β-Carotene was the primary carotenoid at a level of 26.14 μg/g. α-, γ-, and δ-tocopherols were at levels of 0.19, 4.08, and 0.10 μg/g, respectively. Moreover, acetone–water (60:40, v/v) extract of the red sorghum exhibited the greatest total phenolic content of 2.77 mg GAE/g and total flavonoid content of 5.44 mg RE/g. The extract had scavenging capacities against DPPH, ABTS + , and peroxyl radicals and suppressed LPS stimulated IL-1β, IL-6, and COX-2 mRNA expressions in a dose-dependent manner. Ferulic, p -coumaric, isoferulic, and p -hydroxybenzoic acids were found in the red sorghum, with ferulic acid as the predominant phenolic acid and mostly in an insoluble bound form. These data indicated a potential utilization of the red sorghum in health-promoting functional food or supplemental products.
研究领域:
农业
·
食品科学
·
营养学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Jiawei Zuo,Shi-Meng Wang,Xia Jiang,Mengxin Cao,Ziwen Zhang,Tianlu Shi,Hua-Li Qin,Wenjian Tang
Acute kidney injury (AKI) is associated with a strong inflammatory response, and inhibiting the response effectively prevents or ameliorates AKI. A series of novel arylpropionic esters were designed, synthesized and evaluated their biological activity in LPS-stimulated RAW264.7 cells. Novel arylpropionic esters bearing multi-functional groups showed significant anti-inflammatory activity, in which, compound 13b exhibited the most potent activity through dose-dependent inhibiting the production of nitric oxide (NO, IC 50 = 3.52 μM), TNF-α and IL-6 (84.1% and 33.6%, respectively), as well as suppressing the expression of iNOS, COX-2 and TLR4 proteins. In C57BL/6 mice with cisplatin-induced AKI, compound 13b improved kidney function, inhibited inflammatory development, and reduced pathological damage of kidney tissues. In brief, this arylpropionic ester scaffold may be developed as anti-inflammatory agents.
研究领域:
药理学
·
药物化学
·
炎症研究
·
肾脏生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2019
·Vol. 393
·期 6
·967-978
·
IF 2.058
Rong Rong,Zhang Rui-zhen,Wang Xin,Dan Yu-han,Zhao Yun-li,Yu Zhi-guo
R -/ S -2-(2-hydroxypropanamido) benzoic acid ( R -/ S -HPABA), marine-derived anti-inflammatory antiplatelet drugs, were initially synthesised in our group. However, preliminary research showed that R -/ S -HPABA were eliminated rapidly because of extensive hydroxylation metabolism of phenyl ring in vivo. In order to reduce significant hydroxylation metabolism to improve pharmacological activity and bioavailability, trifluoromethyl group was incorporated into R -/ S -HPABA to synthesise R -/ S -2-(2-hydroxypropanamido)-5-trifluoromethyl benzoic acid ( R -/ S -HFBA), respectively. The purposes of this study were to report the synthesis of R -/ S -HFBA and compare the anti-inflammatory antiplatelet effect and pharmacokinetic properties of R -/ S -HFBA with those of R -/ S -HPABA. Carrageenan-induced rat paw edema assay was used for the evaluation of the anti-inflammatory activity. R -/ S -HFBA showed better results in inhibiting edema and were able to prolong the anti-inflammatory effect after carrageenan injection. The antiplatelet aggregation activity of R -/ S -HFBA and R -/ S -HPABA was studied on arachidonic acid-induced platelet aggregation of rabbit platelet-rich plasma. The aggregation inhibition rate of R- / S -HFBA was significantly ( p < 0.05) higher than that of R- / S -HPABA, respectively. Molecular docking study revealed that R -/ S -HFBA possess more potent binding affinity with COX-1/COX-2 than R -/ S -HPABA, respectively, and that the presence of trifluoromethyl group leads to increase in activity of R -/ S -HFBA. R -/ S -HFBA also afford more favorable pharmacokinetic properties than R- / S -HPABA, respectively, such as higher C max , larger AUC 0-∞ , and longer t 1/2 , which, as expected, are more metabolically stable.
研究领域:
药理学
·
药物化学
·
药物设计
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Ziwen Wang,Dongdong Wang,Jiaxuan Fang,Zixin Song,Jiman Geng,Jianfei Zhao,Yifan Fang,Changtao Wang,Meng Li
In this study, an ultrasonic-assisted natural deep eutectic solvent (NaDES) was used to extract flavonoids from Perilla frutescens (L.) Britt. leaves. Of 10 tested NaDESs, that comprising D-(+)-glucose and glycerol exhibited the best total flavonoid extraction rate. Response surface methodology (RSM) was used for extraction modeling and optimization, and the total flavonoid content reached 87.48 ± 1.61 mg RE/g DW, which was a significant increase of 5.36% compared with that of 80% ethanol extraction. Morphological changes in P. frutescens leaves before and after extraction were analyzed by scanning electron microscopy (SEM), and the mechanism of NaDES formation was studied by Fourier transform infrared (FT-IR) spectroscopy. Furthermore, 10 flavonoids were identified by UPLC-Q-TOF-MS. In addition, the NaDES extract had better biological activity according to several antioxidant, cyclooxygenase-2 (COX-2) and hyaluronidase (Hyal) inhibition experiments. Moreover, the stability test revealed that the total flavonoid loss rate of the NaDES extract after four weeks was 37.75% lower than that of the ethanol extract. These results indicate that the NaDES can effectively extract flavonoids from P. frutescens leaves and provide a reference for further applications in the food, medicine, health product and cosmetic industries.
研究领域:
药理学
·
分析化学
·
食品科学
·
医学
·
化妆品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Feng Yunhui,Mei Liyan,Wang Maojie,Huang Qingchun,Huang Runyue
18β-Glycyrrhetinic acid (18β-GA), an active component from Glycyrrhiza glabra L. root (licorice), has been demonstrated to be able to protect against inflammatory response and reduce methotrexate (MTX)-derived toxicity. This study was therefore designed to test the therapeutic possibility of 18β-GA on rheumatoid arthritis (RA) and to explore the underlying mechanism. LPS or TNF-α-induced inflammatory cell models and collagen-induced arthritis (CIA) animal models were applied in this study. Real-time quantitative PCR (RT-qPCR) was used to measure the mRNA levels of various cytokines and FOXO family members. The protein levels of molecules in the MAPK/NF-κB signaling pathway were analyzed using western blot. The cell proliferation assay and colony-forming assay were used to test the influence of 18β-GA on cell viability. The cell apoptosis assay and cell cycle assay were performed to detect the effect of 18β-GA on cell proliferative capacity by using flow cytometry. Hematoxylin and eosin (H&E) staining was performed to evaluate pathological changes after drug administration. The enzyme-linked immunosorbent assay (ELISA) was carried out for the detection of cytokines in serum. In vitro, we found that 18β-GA decreased the mRNA levels of IL-1β, IL-6, and COX-2 by inhibiting the MAPK/NF-κB signaling pathway in MH7A and RAW264.7 cell lines. Moreover, 18β-GA was able to suppress cell viability, trigger cell apoptosis, and G1 phase cell cycle arrest in our in vitro studies. 18β-GA dramatically enhanced the mRNA level of FOXO3 in both TNF-α- and LPS-induced inflammation models in vitro. Interestingly, after analyzing GEO datasets, we found that the FOXO3 gene was significantly decreased in the RA synovial tissue as compared to healthy donors in multiple microarray studies. In vivo, 18β-GA exhibited a promising therapeutic effect in a collagen-induced arthritis mouse model by alleviating joint pathological changes and declining serum levels of TNF-α, IL-1β, and IL-6. Finally, we observed that 18β-GA administration could mitigate liver damage caused by collagen or MTX. Collectively, the current study demonstrates for the first time that 18β-GA can inhibit inflammation and proliferation of synovial cells, and the underlying mechanism may be associated with its inhibition of MAPK/NF-κB signaling and promotion of FOXO3 signaling. Therefore, 18β-GA is expected to be a new drug candidate for RA therapy.
研究领域:
药理学
·
免疫学
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2023
·
IF 3.9
Qingqing Du,Xiaoyun Wu,Kai Ma,Weiwei Liu,Panwen Liu,Toshihiko Hayashi,Kazunori Mizuno,Shunji Hattori,Hitomi Fujisaki,Takashi Ikejima
Type 2 diabetes (T2DM) is induced by the abundance of glucose and lipids , which causes glucolipotoxicity to the pancreatic β-cells. Silibinin is a natural flavonoid possessing the regulatory activity on insulin production and therapeutic activity in diabetic mice; however, its effect on glucolipotoxicity is not fully explained. This in vitro study investigates the effects of silibinin on palmitic acid (PA) and high glucose (HG)-induced cell loss and ferroptosis of rat insulinoma INS-1 cells. In the cells treated with PA and HG, expressions of glucose transporter 4 (Glut4) and carnitine acyltransferase I (CPT1) for β-oxidation of fatty acids are reduced. Mitochondria are the metabolic organelles for glucose and fatty acids. The mitochondrial membrane potential (MMP) and ATP production were decreased, while the ROS level was elevated in the cells treated with PA and HG, indicating an induction of mitochondrial disorder . Cell loss was partially rescued by ferroptosis inhibition, suggesting an involvement of ferroptosis in the cells treated with PA and HG. More importantly, the increases in total iron, lipid ROS, MDA and COX-2, and the decrease in ferroptosis inhibitory molecules GSH, GPX4 and FSP1 appeared in the cells treated with PA and HG, confirming the occurrence of ferroptosis. Moreover, PINK1/parkin-mediated mitophagy , a vital process for selective elimination of damaged mitochondria, was blocked. Interestingly, silibinin rescued the mitochondria, restricted the ferroptosis and restored the mitophagy. By using the pharmacological stimulator and inhibitor of mitophagy, and si-RNA transfection to silence PINK1 expression, silibinin's protective effect against ferroptosis caused by PA and HG treatment was found to depend on mitophagy. Collectively, our current study reveals the new mechanisms for the protection of silibinin against the injury of INS-1 cells treated with PA and HG, elucidates the participation of ferroptosis in glucolipotoxicity, highlighting the involvement of mitophagy in defense against ferroptotic cell death.
研究领域:
糖尿病
·
细胞生物学
·
药理学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2022
·Vol. 57
·期 24
·11317-11331
·
IF 4.682
Hao Dule,Zhang Zheng,Cheng Yu,Cheng Long,Ji Yuanhui
An increasing number of studies have demonstrated that inflammation has a close correlation with multiple stages of tumor development, including tumor initiation, promotion, and migration. Cyclooxygenase-2 (COX-2), which is overexpressed in inflammation, has also been found to be overexpressed in several types of cancer. Some anti-inflammatory drugs have been shown to have potential effects on the inhibition of tumor pathogenesis and development. Among them, non-steroidal anti-inflammatory drugs (NSAIDs) play a role by inhibiting the overexpression of COX-2 with low price and few side effects. In this work, ibuprofen was linked to an amphiphilic polymer mPEG-PLA via disulfide bond to form a polymeric prodrug molecule with reductive sensitivity. The amphiphilic molecule can self-assemble into nanoparticles in an aqueous solution and encapsulate hydrophobic drug, doxorubicin, into the core. Electrostatic potential analysis and weak interaction analysis showed different weak interactions, including hydrogen bonds and π-π stackings, are the driving force of the formation of the complex system between doxorubicin and polymeric prodrug molecules. These quantitative calculations were helpful to understand the formation mechanism of prodrug polymeric carriers. Characterization methods such as TEM and DLS proved that mPEG-PLA- s -IHE/DOX (PDC/DOX) micelles had an excellent uniform nanostructure, and in vitro drug release experiments showed superior sustained-release and reductive environment-dependent release of this drug. More importantly, in vitro cytotoxicity and cell uptake studies showed that the PDC/DOX micelles induced apoptosis of A549 lung cancer cell lines. This study demonstrates the advantage of combining NSAIDs with chemotherapy agents in the treatment of lung cancer, which provides a feasible and novel polymer delivery system, and a reasonable explanation of formation mechanism. Graphical Abstract
研究领域:
药学
·
材料科学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Jie Liu,Ailing Hui,Jinghe Wang,Qingfeng Hu,Shengnan Li,Yuanli Chen,Zeyu Wu,Wencheng Zhang
Neuroinflammation is considered as an important pathological mechanism in neurodegenerative diseases. The natural isoquercitrin (IQ) was reported to have potential anti-neuroinflammatory activity. The acylation of glycoside in IQ enhanced its hydrophobicity, which was expected to enhance the protective effect against inflammation. In this study, three carboxylic acids with anti-neuroinflammatory effects including cinnamic acid, ibuprofen (IBU) and acetylsalicylic acid were introduced into the 6''-OH of IQ through the corresponding vinyl esters intermediates ( 8a-8c ). Ultimately, the acylated IQ derivatives (Compound 9a-9c ) were obtained with 35–42% yields using immobilized lipase Novozym 435 as catalyst. Subsequently, their anti-neuroinflammatory activities were evaluated in lipopolysaccharide (LPS)-induced BV2 cells. Compound 9b improved cell viability in the range of ≤50 μM and significantly decreased NO, PGE 2 production and TNF-α, IL-1β release and oxidative stress level with a concentration-dependent manner. Also, it could downregulate iNOS, COX-2, TNF-α and IL-1β expression levels, approximately 40% reduction were achieved when 15 μM compound 9b was employed. In addition, compound 9b resisted phosphorylation and degradation of IkBαs, suppressing the activation of NF-κB signaling pathway, exhibiting excellent neuroinflammatory inhibition. Moreover, the administration of compound 9b (30, 60 mg/kg) alleviated behavioral disorders and neuronal damages in LPS-induced neuroinflammatory mice. Meanwhile, the decreased TNF-α, IL-1β release, expression and the inhibited glial cells activation were obtained in compound 9b -treated group, which was superior to that of IQ or IBU. Overall, these findings demonstrated that compound 9b , formed by the introduction of ibuprofen into IQ, can serve as a novel promising therapeutic agent for anti-neuroinflammation.
研究领域:
药理学
·
神经科学
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-29
·
IF 10.6
Yu Xiao-Jun,Zhao Yuan-Ting,Abudouaini Haimiti,Zou Peng,Li Tian-Qi,Bai Xiao-Fan,Wang Shan-Xi,Guan Jian-Bin,Li Meng-wei,Wang Xiao-dong,Wang Ying-guang,Hao Ding-Jun
Methods Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1β. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. Results CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1β, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). Conclusion The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs. Graphical Abstract Molecular mechanism of GCA targeting CFIm25 in NP cells to promote regeneration of degenerated intervertebral disc NP
研究领域:
生物医学工程
·
再生医学
·
组织工程
·
分子生物学
·
细胞生物学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Kun Hu,Yongjin Sun,Jie Wang,Shaojun Wu,Jie Ren,Dan Su,Lidan Tang,Jinhong Gong,Hufeng Fang,Shan Xu,Hao Yang
Hepatocyte lipid accumulation in type 2 diabetes mellitus (T2DM) promotes the development of metabolic dysfunction-associated steatosis liver disease (MASLD), whereas no specific drug treatment is available. Pinocembrin assists in the treatment of many diseases, however, little is known about its protective effect on hepatic lipid metabolism disorders induced by T2DM. In this study, the ameliorative effects of pinocembrin on T2DM-induced hepatocyte lipid accumulation were investigated by in vitro experiments combined with a comprehensive analysis strategy of network pharmacology and molecular docking. High glucose and free fatty acid co-cultured HepG2 cell line was used. The results indicated that pinocembrin reduced lipid deposition by modulating the release of Cyclooxygenase-2 (COX-2)-mediated inflammatory factors and improving insulin resistance (IR) in HepG2 cells. Overall, the findings of this study suggested that pinocembrin ameliorated lipid accumulation and IR in vitro , and thus may be a potential therapeutic agent for the treatment of T2DM-induced hepatic steatosis.
研究领域:
药理学
·
细胞生物学
·
代谢学
·
糖尿病研究
✓ 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）