JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2025
·Vol. 44
·期 1
·321
·
IF 12.8
Lei Yu,Bai Yaowei,Bai Xiatong,Sun Bo,Zhu Licheng,Wu Wenlong,Su Yang,Zhang Hongsen,Wang Yingliang,Zheng Chuansheng
Background and aims Radiofrequency ablation (RFA) is an effective treatment for hepatocellular carcinoma (HCC), but incomplete ablation and recurrence of residual tumors remain significant challenges, partly due to local inflammation and elevated COX-2 levels in the tumor microenvironment. This study aims to investigate the potential of combining celecoxib, a COX-2 inhibitor, with anti-PD-1 monoclonal antibody (αPD-1) to enhance anti-tumor efficacy and activate immune responses. Methods In vitro, ELISA was used to assess the effects of radiofrequency heat treatment and celecoxib on PGE 2 secretion by Hepa1-6 cells. Scanning electron microscopy, flow cytometry, and CCK-8 assays were employed to evaluate the function and cytotoxic activity of NK92 cells against Hepa1-6 cells. In vivo, orthotopic HCC mice were divided into five groups to evaluate tumor volume, pathology, and survival. The role of celecoxib in the COX-2/PGE 2 /NK cell axis and its impact on NK cell immune function were investigated. Results In vitro experiments showed that celecoxib reversed PGE 2 -mediated suppression of NK cell function and cytotoxic activity against HCC cells by inhibiting PGE 2 secretion. In vivo, orthotopic HCC mice treated with celecoxib and αPD-1 exhibited significantly reduced tumor volumes, attenuated the infiltration and activation of NK cells, and prolonged survival compared to control groups. The combination therapy also demonstrated a notable abscopal-like effect, inhibiting metastatic tumor growth and activating systemic immunity. Conclusions Taken together, these findings suggest that celecoxib combined with αPD-1 represents a promising strategy for treating residual HCC after RFA, with enhanced anti-tumor effects and good safety. Graphical abstract
研究领域:
肿瘤学
·
免疫治疗
·
分子生物学
·
癌症免疫学
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2020
·
IF 4.873
Liu Tang,Xiao-Lei Li,Zi-Xin Deng,Yao Xiao,Ya-Hong Cheng,Jing Li,Hong Ding
Conjugated linoleic acid (CLA), commonly found in beef, lamb and dairy products, has been reported to exhibit anti-inflammatory and antipruritus effects and to inhibit the release of chemical mediators such as histamine and eicosanoid in laboratory rodents. The chief objective of the study is to assess the efficacy of CLA on atopic dermatitis (AD) in mice and to explore possible mechanisms with CLA treatments . To develop a new therapy for AD, the anti-AD potential of CLA was investigated by inducing AD-like skin lesions in mice using 2,4-dinitrofluorobenzene. We evaluated dermatitis severity; histopathological changes; serum levels of T helper (Th) cytokines (interferon-γ, interleukin-4); changes in protein expression by western blotting and immunohistochemistry staining for cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), toll like receptor 4 (TLR-4), myeloid differentiation factor 88 (MyD88), nuclear factor-κB (NF-κB) and tumor necrosis factor α (TNF-α); and production of the proinflammatory lipid mediators, such as prostaglandin E 2 and leukotriene B4 , in the skin lesions. Treatment with CLA ameliorated the development of AD-like clinical symptoms and effectively inhibited epidermal hyperplasia and infiltration of mast cells and CD4 + T cells in the AD mouse skin. Total serum immunoglobulin E levels and the expression levels of Th1/Th2 cytokines and lipid mediators in dorsal skin were dramatically suppressed by CLA. Furthermore, CLA down-regulated the expressions of COX-2, 5-LOX, TLR4, MyD88, NF-κB and TNF-α. Taken together, our findings demonstrate the potential usefulness of CLA as an anti-inflammatory dietary supplement or drug for the prevention and management of AD skin diseases by modulating the COX-2/5-LOX and TLR4/MyD88/NF-κB signaling pathways .
研究领域:
免疫学
·
药理学
·
皮肤科
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2024
·
IF 4.2
Haocong Zhang,Liangbi Xiang,Hong Yuan,Hailong Yu
Spinal cord injury (SCI) is a severe central nervous system injury and microglia are major participants in neuroinflammation after injury. ADP-ribosylation factor-like GTPase 11 (ARL11) is a GTP-binding protein. Whether ARL11 is involved in the SCI progression is unknown. In the impactor-induced moderate SCI mouse model, ARL11 protein and mRNA expression were significantly increased in the injury site. LPS (100 ng/mL) and IFN-γ (20 ng/mL) were incubated with BV2 cells (immortalized mouse microglial cell line) to drive them into an M1-like phenotype. ARL11 up-regulation was also observed in activated microglia in SCI mice and LPS and IFN-γ treated BV2 cells. Basso Mouse Scale scores and inclined plate test revealed that ARL11 deletion promoted motor function recovery in SCI mice. Pathological examination showed ARL11 knockdown reduced spinal cord tissue damage, increased neuron numbers, and inhibited neuronal apoptosis in SCI mice. ARL11 knockdown notably inhibited IL-1β and IL-6 production in vivo and in vitro. Furthermore, ARL11 deletion significantly inhibited iNOS protein and mRNA expression in vivo and in vitro, and COX-2 expression in vivo . Mechanism studies revealed that ARL11 silencing decreased phosphorylated ERK1/2 protein expression. Additionally, ELF1 knockdown significantly inhibited ARL11 protein and mRNA expression in vitro . ELF1 acted as a transcription activator in regulating ARL11 expression by binding to the promoter. In conclusion, ARL11 knockdown protects neurons by inhibiting M1 microglia-induced neuroinflammation, thereby promoting motor functional recovery in SCI mice. This may occur in part under the regulation of ELF1. Our study provides a new molecular target for SCI treatment.
研究领域:
神经科学
·
炎症
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yongfang Sun,Jinmei Xie,Canzheng Wang,Shaoxue Qin,Kun Ren,Dongmei Wang,Yingni Pan,Shumeng Ren,Xiaoqiu Liu
Curcumae wenyujin Rhizoma (CWR) is extensively implemented in clinical practice for treating primary dysmenorrhea (PD) resulting from qi stagnation and blood stasis. However, the development of CWR-derived polysaccharides remains poorly investigated. In this study, the polysaccharide CWP-3 was isolated from CWR, and structurally characterized through FT-IR, HPLC, GC–MS, and NMR, which identified it as an RG-I-type pectin polysaccharide with a molecular weight of 423.6 kDa. CWP-3 consists of the monosaccharides Rha, GalA, Gal, and Ara (25.7: 28.6:42.8:2.9). The main backbone consisted of alternating 1,2-linked Rha p and 1,4-linked GalA p residues, with Gal and Ara forming the side chains, respectively. SEM revealed a porous, sheet-like morphology, while Congo Red staining and AFM analyses confirmed a triple helix structure with a height of 3.37 nm, and TG-DSC analysis indicated good thermal stability. In a mouse model of PD, 160 mg/kg CWP-3 reduced writhing by 70.3 %, prolonged coagulation time by 37.5 %, restored uterine and hepatic indices, and decreased AST, ALT, D2D, TXB2, IL-6, IL-1β, and TNF-α, while normalizing PGF₂α/PGE₂ levels. These results indicate that CWP-3 exerts blood-activating and analgesic effects through cytokine-mediated COX-2 suppression, suggesting its potential as a therapeutic candidate for PD with qi stagnation and blood stasis.
研究领域:
药理学
·
生物化学
·
药物化学
·
妇科学
·
结构生物学
·
多糖研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Meng Chen,Yonglu Li,Xin Yu,Yaxuan Wang,Wen Chen,Xiang Ye,Yangyang Liu,Yong Jiang,Xiaodong Zheng
Tetrastigma hemsleyanum Diels et Gilg, a rare herbal plant native to China, possesses high medicinal value. More researches have focused on the flavones in the tubers of Tetrastigma hemsleyanum whereas polysaccharides attract few attentions. In this study, a purified polysaccharide (TTP-1) with the average molecular weights of 478.33 kDa was extracted from Tetrastigma hemsleyanum and conducted multiple analysis to identify its structural information. In vitro , TTP-1 could suppress the inflammation, cytotoxicity, genotoxicity, mitochondrial dysfunction and oxidative damage induced by LPS in RAW264.7 cells. Meanwhile, TTP-1 could attenuate inflammation via COX-2, iNOS, MAPKs pathways and ameliorate oxidative damage through Nrf2-Keap1, Sirt1-FoxO1 pathways in RAW264.7 cells. In vivo , the inflammation induced by LPS triggered the suppression of survival ratio and growing development, as well as the restrain of athletic ability in Caenorhabditis elegans . The treatment of TTP-1 reversed the situation induced by LPS. In a word, TTP-1 could ameliorate LPS-induced inflammation both in vitro and in vivo .
研究领域:
药理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2016
·
IF 5.671
Wei Kevin Zhang,Hong-Wei Gu,Xiao-Jun Li,Yu-Sang Li,He-Bin Tang,Gui-Hua Tian,Hong-Cai Shang
Nano-carriers, especially lipid nanoparticles have been used widely in “a good manner”, for instance in the treatment of cancer , by enhancing the targetability and reducing required dose. Here in the contrary, we presented a new possibility: nanoDEN, a nanoparticle-packed “bad guy”, which is more effective and efficient in generating liver tumor in mice. We have shown that nanoDEN, same as diethylnitrosamine (DEN), induced overexpression of multiple pivotal factors (including COX-2, β-catenin and PCNA) during oncogenesis. Moreover, nanoDEN increased the apoptosis of liver cells compared with DEN alone. This apoptotic effect of nanoDEN is more efficient on normal cells than on cancer cells . Taken into consideration the fact that there are endogenous nanoparticles naturally formed inside our body, our research enlarged our views of all the aspects of oncogenic chemicals, while also established a better method of producing animal model of liver cancer, which has future investigational and therapeutical potential.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
·
2022
·Vol. 306
·期 1
·115-125
·
IF 2.493
Zhu Bo,Chen Yumei,Guo Min,zhang Chenhui,Huang Lingxiao,Pan Qiangwei,Lin Tao,Lu Yiyi,Shen Xiaolu,Zhang Hongping
Purpose Adenomyosis is a common gynecological disease, but its pathogenesis and treatment options are not yet completely clear. This study aimed to investigate the analgesic effect of berberine on tamoxifen-induced neonatal mouse adenomyosis and its curative effects on the disease. Methods The mouse adenomyosis model was established in neonatal female mice via oral administration of tamoxifen suspended solution. Adenomyosis mice were given berberine by intraperitoneal injection with the dosage of 5, 10, and 20 mg/kg body weight, respectively, at 17 weeks after birth. The pain sensation of the mice was evaluated by hotplate and tail-flick tests. The mRNA levels of gene expression were detected by RT-qPCR. The protein expression was analyzed by ELISA and Western blot. Results Berberine reduced the uterine weight, suppressed the myometrial infiltration of ectopic endometrium, improved the hotplate and tail-flick latency of the adenomyosis mice. Mechanistically, berberine downregulated the expression of genes related to pain and inflammation, such as TRPV1, COX-2, VEGF and OTR, impaired the inflammatory response at the DRG site, and inhibited the expression of TLR4 in DRG and uterine tissues. Conclusions Berberine attenuates hyperalgesia and exhibits analgesic and therapeutic effects on adenomyosis mice.
研究领域:
药理学
·
妇科学
·
疼痛研究
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Runan Zhao,Shumeng Hu,Zhehao Yang,Tao Chen,Xuesong Chi,Di Wu,Wenjun Wang,Donghong Liu,Beiwei Zhu,Jiangning Hu
Gastric ulcers, often caused by factors such as ethanol consumption and Helicobacter pylori infection, present significant treatment challenges due to the limited efficacy and adverse effects of current therapies. This study aimed to develop a nanoscale quercetin (Qu) delivery system using folic acid (FA)-functionalized cyclodextrin-based metal–organic frameworks (CD-MOFs), termed Qu@FA-CMOF nanoplatforms, to enhance therapeutic outcomes for acute gastric ulcers. The FA modification endowed the nanoplatforms with targeted delivery capabilities, improving cellular uptake and facilitating the sustained release of Qu. Comprehensive in vitro and in vivo evaluations demonstrated that Qu@FA-CMOF significantly attenuated gastric tissue injury, reduced oxidative stress, and suppressed inflammation by modulating the Nrf2/HO-1 and COX-2/NF-κB signaling pathways. Furthermore, the nanoplatform exhibited potent anti-apoptotic effects through regulation of the Bax/Bcl-2 pathway, and showed favorable biocompatibility with no significant toxicity observed in major organs. These findings highlight the potential of Qu@FA-CMOF nanoplatforms as a safe and effective therapeutic strategy for ethanol-induced gastric injury, offering a promising avenue for future nanomedicine-based therapies in gastric ulcer treatment.
研究领域:
药学
·
纳米技术
·
胃肠病学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Chemical Biology & Drug Design
·
2024
·Vol. 103
·期 1
·e14437
·
IF 3.2
Junde Xu,Keshuang Tang,Zhiran Ju
The adverse effects caused by nonselective and selective cyclooxygenase-2 (COX-2) inhibitors remain a challenge for current anti-inflammatory medications. A balanced inhibition of COX-1/−2 represents a promising strategy for the development of novel COX-2 inhibitors. In this study, we present the design and synthesis of a novel series of firocoxib analogues incorporating an amide bond to facilitate essential hydrogen bonding with amino residues in COX-2. The synthesized analogs were evaluated for their inhibitory activity against both COX-1 and COX-2 enzymes. Among them, compound 9d demonstrated potent and balanced inhibition. Inhibition of COX enzymes by 9d in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages resulted in the suppression of the NF- κ B signaling pathway to reduced expression of pro-inflammatory factors such as inducible nitric oxide synthase (iNOS), COX-2, nitric oxide (NO), and reactive oxygen species (ROS). The remarkable in vitro anti-inflammatory activity exhibited by 9d positions it as a promising candidate for further development as a novel lead compound for inflammation treatment.
研究领域:
药理学
·
药物化学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
FITOTERAPIA
·
2024
·
IF 2.5
Ren-Fen Ma,Qian Wu,Yin-Po Pan,Hu Liu,Xin-Cheng Zhuang,Hua Zhang
The Euphorbia plants are famous for their diterpenoid constituents with diverse structures and broad biological activities. Herein, the discovery of 15 ingenane diterpenoids including 10 previously unreported ones ( 1 − 10 ) from Euphorbia antiquorum was presented. Structures of the undescribed compounds were established via detailed spectroscopic analyses. Meanwhile, a preliminary anti-inflammatory screening revealed that compound 6 showed significant inhibitory activity against the production of nitric oxide, as well as downregulated the expression of COX-2 and IL-6, in lipopolysaccharide-stimulated RAW264.7 macrophages. Further mechanistical exploration revealed that compound 6 could exert its anti-inflammatory effect by inhibiting NF-κB and activating Nrf2 signaling pathways.
研究领域:
药理学
·
化学
·
免疫学
·
植物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yan Du,Yu-lang Chen,Ying Zhang,Yan-lin Zhao,Zhong Huang,Peng Jin,Shuai Ji,Dao-Quan Tang
Ethnopharmacological relevance Mulberry ( Morus alba L.) leaf is a well-known herbal medicine in China for thousands of years. Mulberry leaf can regulate arachidonic acid (ARA) metabolism disorder in obesity and type 2 diabetes mellitus. However, the active ingredients involved in this process are still unclear. Aim of study To explore the potential active ingredients in mulberry leaf against ARA metabolism disorder. Materials and methods In this research, an efficient method combining affinity ultrafiltration, molecular docking, and network pharmacology was developed and applied to explore cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors from mulberry leaf. Results A total 17 potential inhibitors were screened by affinity ultrafiltration assay and identified by high resolution mass spectrometry. In addition, 8 bioactive ingredients were obtained after re-evaluated by molecular docking and network pharmacology, and their inhibitory activities on COX-2 and 5-LOX were confirmed by in vitro inhibitory assays. The results of cell experiments showed that the expressions of COX-2 and 5-LOX were significantly suppressed by neochlorogenic acid, rutin, isoquercetin, and (−)-syringaresinol-4-O-glucoside. Conclusion Neochlorogenic acid, rutin, isoquercetin, and (−)-syringaresinol-4-O-glucoside may be the potential material basis of mulberry leaf in the regulation of ARA metabolism of obesity and type 2 diabetes mellitus.
研究领域:
药理学
·
分析化学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2014
·Vol. 9
·期 6
·e98513
·
IF 3.534
Xi-E Zhen,Ming Zong,Sai-Nan Gao,Yong-Gang Cao,Lei Jiang,Shu-Xin Chen,Kuan Wang,Shi-Qin Sun,Hai-Sheng Peng,Yu-Hua Bai,Sen Li
The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa. To address this problem, we synthesized a derivative form of ASP, prepared by modification of ASP with nano-hydroxyapatite (a kind of inorganic particle containing Ca 2+ ). The derivative was named Ca-ASP. Structural study showed that Ca-ASP was a kind of carboxylate containing intramolecular hydrogen bonds. Rats given a high dose of Ca-ASP (5 mmol per kg body weight) showed similar anti-thrombotic activity as those given the same dose of ASP, but had much lower gastric mucosal damage than ASP (UI: 2 versus UI: 12.5). These rats also showed reduced expression of COX-2, but their COX-1 expression was similar to that of control rats, but significantly higher than that of ASP-administered rats. Furthermore, the level of prostaglandin E2 (PGE2) was up-regulated in Ca-ASP-administered rats compared to ASP-administered rats. Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.
研究领域:
药学
·
药物化学
·
药理学
✓ 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）