CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Li Qiao,Xue-Tian Qian,Yi-Gang Zhang,Xia-Feng Peng,Qi Liu,Shi-Qi Chang,Chang Cui,Feng Zhang,Shu-Kui Wang,Ning-Ping Huang
A novel Eudragit S100-coated and mannose-modified liposome enables colon-specific and macrophage-targeted siRNA delivery. EML/siRNA exhibit excellent stability, biocompatibility, and efficient intracellular delivery siRNA. • The nanocarrier protects TNF-α siRNA from Gastrointestinal (GI) degradation and achieves responsive release in the colon. • Treatment in IBD models significantly downregulates pro-inflammatory cytokines and promotes tissue repair. • The platform provides a targeted and improved therapeutic strategy for precise IBD management. Inflammatory bowel disease (IBD) is a chronic and clinically important intestinal disorder with rapidly rising global incidence and prevalence. While biological therapies targeting tumor necrosis factor-alpha (TNF-α), a key cytokine in IBD pathogenesis, have shown clinical efficacy, their use is often limited by systemic adverse effects. RNA interference (RNAi) offers a promising strategy for precise gene silencing, yet its therapeutic application is constrained by the poor stability and inefficient in vivo delivery of small interfering RNA (siRNA). To overcome these challenges, we developed a macrophage-targeted, colon-specific liposomal system for delivering TNF-α siRNA. The liposomes were functionalized with mannose to selectively engage the mannose receptor (MR, CD206), highly expressed on macrophages, and coated with Eudragit S100 (ES100), a pH-responsive polymer that shields siRNA from gastrointestinal degradation and enables site-specific release in the colon. The resulting ES100-coated, mannose-modified liposomes (EML/siRNA) demonstrated enhanced cellular uptake and efficient siRNA delivery to macrophages both in vitro and in vivo. In animal models of IBD, treatment with EML/siRNA significantly downregulated pro-inflammatory cytokine, alleviated intestinal inflammation, and promoted mucosal tissue repair, as evidenced by histopathological analysis. This study introduces a dual-functional nanotherapeutic platform that combines targeted RNAi-mediated TNF-α silencing with colon-specific delivery and mucosal protection, offering a promising and refined therapeutic strategy for IBD. Download: Download high-res image (159KB) Download: Download full-size image
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高影响因子
MICROCHEMICAL JOURNAL
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2025
·
IF 5.1
Tiantian Wang,Yanli Zhou,Lantao Liu,Hui Dong,Yinghan Xu,Yidan Sun,Yaocun Yue,Jiaqing Tian,Maotian Xu
Abnormal Tumor necrosis factor-α (TNF-α) levels in serum are closely linked to Alzheimer's disease onset, progression, and severity. Highly sensitive and specific detection of TNF-α offers a key biomarker for early diagnosis and disease evaluation, providing significant clinical value for improved disease management. In this study, an iridium complex [(piq)₂Ir(dpppy)] containing a cyclometalated ligand was used as a novel and highly efficient electrochemiluminescence (ECL) luminophore to construct an ultrasensitive electrochemical biosensor for the detection of TNF-α. First, the TNF-α antibody was immobilized in the microplate reactor, and a quasi-specific sandwich immunoassay was performed. Subsequently, aptamers modified with silver nanoparticles-which were in-situ generated on the C-rich sequence-modified aptamer, captured the TNF-α antigen. After dissociation with nitric acid, the solution containing Ag + was transferred to the electrode surface modified with the cyclometalated iridium complex for ECL signal detection. The constructed immunosensor not only exhibited a wide linear range of 0.001 ng mL −1 –100 ng mL −1 , but also showed excellent recovery in human serum samples, ranging from 98.6 % to 101.7 %, with a relative standard deviation of 0.66 %–3.8 %. This strategy not only enhanced the detection sensitivity due to the efficient performance of the iridium complex in the 3 LCπ − π* state, but also this strategy of this biosensor effectively maintained the specificity and stability.
研究领域:
生物化学
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生物传感器
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免疫学
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电化学
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医学诊断
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高影响因子
Heliyon
·
2024
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IF 3.4
Fanzhuo Zeng,Anqi Chen,Wei Chen,Shuai Cheng,Sen Lin,Rongcheng Mei,Xifan Mei
Background Spinal cord injury (SCI) is a serious and difficult to treat traumatic disease of the central nervous system. Spinal cord injury causes a variety of detrimental effects, including neuroinflammation and ferroptosis, leading to chronic functional impairment and death. Recent studies have shown that microglia/macrophages (M/Ms) at the injury site remain primarily in the pro-inflammatory state, which is detrimental to recovery. However, information on the factors behind pro-inflammatory polarization skew in the injured spinal cord remains unclear. In this study, we found that Tumor Necrosis Factor-α(TNF-α) ablation protected after SCI by suppressing neuroinflammation and ferroptosis. Though using TNF-α knock out mice (TNF−/−), we induced downregulation of TNF-α in M/Ms and further investigated its effect on SCI outcome. In TNF−/− mice, significant behavioral improvements were observed as early as 7 days after injury. We showed that TNF-α inhibition promote injury-mediated M/Ms polarization from pro-inflammatory to anti-inflammatory phenotype in vivo. Furthermore, accumulated iron in M/Ms after SCI increased the expression of TNF-α and the population of M/Ms to pro-inflammatory phenotype. Moreover, zinc supplement reduced the secondary damage caused by iron overload. In conclusion, we found that knock out of TNF-α promotes recovery of motor function after spinal cord injury in mice by inhibiting ferroptosis and promoting the shift of macrophages to an anti-inflammatory phenotype, indicating that there is great potential for this therapy to SCI.
研究领域:
神经科学
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免疫学
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药理学
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细胞生物学
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PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
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2020
·Vol. 40
·期 11
·1526-1533
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IF 2.997
Yalei Yu,Youyou Zhang,Jie Zhang,Chuhuai Guan,Liang Liu,Liang Ren
Cantharidin is of high medicinal value but has strong toxicity. Nowadays, multiple research has focused on the mechanism of its antitumor activity while research on toxicological profiles associated with cantharidin poisoning is still limited. Its hepatotoxicity has attracted attention recently for the crucial role of the liver in detoxification. Here, we aim to find a potential mechanism for cantharidin-induced acute hepatotoxicity with a view to assisting subsequent research or clinical use or detoxification. Twenty-one male Sprague-Dawley rats were randomly divided into control, low-dose (1.34 mg/kg) and high-dose (2.67 mg/kg) cantharidin exposure groups. We used hematoxylin-eosin to observe pathological changes and used immunofluorescent staining, western blotting and real-time quantitative polymerase chain reaction to detect the expression of the markers. The main pathological changes in livers of cantharidin-treated rats were necrosis, inflammatory infiltration and hemorrhage. We found coexpression of tumor necrosis factor alpha (TNF-α), IkappaB kinase-alpha (IKK-α) and caspase3 by immunofluorescent staining in livers of cantharidin-treated rats. Compared with the control, the levels of TNF-α, IKK-α and caspase3 increased significantly in the experimental groups ( P < .05). The ratio of B-cell lymphoma-2 (Bcl-2)/Bax increased in the low-dose group but decreased in the high-dose group ( P < .05). Cantharidin exposure raised IKK-α mRNA and caspase3 mRNA levels ( P < .05). In conclusion, the participation of TNF-α, IKK-α, Bcl-2, Bax and caspase3 uncovered a novel mechanism underlying cantharidin-induced acute hepatotoxicity, and the mechanism needs to be studied further.
研究领域:
药理学
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毒理学
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分子生物学
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PubMed
高影响因子
Chemical Biology & Drug Design
·
2015
·Vol. 86
·期 4
·753-763
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IF 2.485
Jianpeng Feng,Bing Xiao,Wenbo Chen,Ting Ding,Lingfeng Chen,Pengtian Yu,Fengli Xu,Huajie Zhang,Zhiguo Liu,Guang Liang
We previously reported a symmetric monocarbonyl analog of curcumin (MACs), C66, which demonstrated potential anti-inflammatory activity and low toxicity. In continuation of our ongoing research, we designed and synthesized 34 asymmetric MACs based on C66 as a lead molecule. A majority of the C66 analogs effectively inhibited LPS induction of TNF- α and IL-6 expression. Additionally, a preliminary SAR was conducted. Furthermore, active compounds 4a11 and 4a16 were found to effectively reduce the W/D ratio in the lungs and the protein concentration in the bronchoalveolar lavage fluid (BALF). Meanwhile, a histopathological examination indicated that these two analogs significantly attenuate tissue injury in the lungs with LPS-induced ALI rats. 4a11 and 4a16 also inhibited mRNA expression of several inflammatory cytokines, including TNF- α , IL-6, IL-1 β , COX-2, ICAM-1 and VCAM-1, in the Beas-2B cells after LPS challenge. Altogether, the data exhibit a series of new C66 analogs as promising anti-inflammatory agents for the treatment of LPS-induced ALI.
研究领域:
药理学
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合成化学
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免疫学
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PubMed
高影响因子
International Journal of Pharmaceutics-X
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2026
·
IF 7.9
Sai Gao,Ruili Yin,Jingxuan Shi,Zhuang Miao,Longyan Yang,Dong Zhao
Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation and cytokine-driven immune activation, in which TNF-α plays a central pathogenic role. We developed a layered hydrated silk fibroin (SF) microneedle system (ETA@Hyd MN) with SF tips loaded with etanercept (ETA, a TNF-α inhibitor for psoriasis), for local cutaneous delivery to reduce systemic exposure and rapidly dissolving polyvinyl alcohol (PVA) bases that facilitate retention of the SF tips within the skin. Hydration markedly slowed ETA release, with approximately 80% released at 48 h compared with approximately 75% released within 1 h from microneedles without hydration. In HaCaT cell scratch assays, release media from ETA@Hyd MN attenuated the accelerated wound closure response, resulting in a greater remaining scratch width than that in the model group at 48 h. In an IMQ-induced psoriasis-like mouse model, ETA@Hyd MN improved clinical symptoms, reduced PASI scores, alleviated spleen enlargement, and suppressed epidermal hyperplasia and TNF-α/IL-6 expression. These results demonstrate that ETA@Hyd MN enables sustained ETA release and effectively suppresses inflammation, highlighting its potential for treating inflammatory skin diseases. Download: Download high-res image (190KB) Download: Download full-size image
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CHEMICAL ENGINEERING JOURNAL
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2026
·
IF 12.5
Jianan Chen,Tong Xing,Jialei Song,Hang Zhang,Shaotian Fu,Lizhi Jiang,Yiqi Xu,Lei He,Huatao Liu,Hailong Ma,Xin Wang,Tangjun Zhou,An Qin,Peixiang Ma,Jie Zhao
The inflammatory environment mediated by TNF-α in the intervertebral disc can reduce the transfection efficiency of LNPs. • Engineered fibroblasts overexpressing TNF-α antibodies exhibit resistance to the decline in proliferation ability and activity induced by the inflammatory microenvironment. • Engineered fibroblasts rescue the inflammatory phenotype and ameliorate ECM homeostasis of degenerated nucleus pulposus cells in IVDD models in vitro and in vivo. Lumbar intervertebral disc degeneration (IVDD) is a prevalent degenerative condition lacking effective early-stage treatments. While fibroblast cell therapy and mRNA therapeutics represent promising approaches, their efficacy is limited by the inflammatory microenvironment of degenerated discs, which affects the delivery efficiency and compromises cell viability and gene delivery. To overcome these challenges, we developed an LNP-mRNA-engineered fibroblast strategy, utilizing fibroblasts as a “Trojan horse” for targeted mRNA delivery. In IVDD progression, inflammatory factors, particularly TNF-α, accumulate and exacerbate degeneration. Engineered fibroblasts mitigates TNF-α-induced senescence and proliferation arrest in inflammatory conditions, counteracts nucleus pulposus inflammation, and restores extracellular matrix production. In a rat IVDD model, engineered fibroblasts significantly improved disc height and showed superior therapeutic effects compared to naive fibroblasts. These results highlight the dual therapeutic mechanism of our approach, i.e. combining cell therapy with mRNA delivery, and its clinical potential in the treatment of IVDD. Download: Download high-res image (105KB) Download: Download full-size image
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高影响因子
Evidence-based Complementary and Alternative Medicine
·
2013
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IF 1.722
Huiqing Lv,Xiaoping Zhang,XueZhi Chen,Zhijun Xie,Changfeng Hu,Chengping Wen,Kezhi Jiang
Background. Ficus pandurata H. (Moraceae) is widely used in traditional Chinese medicine as a healthy food condiment or a medicine for treatment of various diseases including inflammation. Objective. The purpose of the present study is to investigate the phytochemical compositions and antioxidant and anti-inflammatory activities of crude water (FPW) and ethanolic extracts (FPE) from Ficus pandurata H. Methods. Phytochemical compositions were identified by a high-performance liquid chromatography-electrospray ionization-mass spectrometry method (HPLC-ESI-MS). The antioxidant activities were evaluated by diphenylpicrylhydrazyl (DPPH) and hydroxyl radical assays, and the anti-inflammatory activities were evaluated by paw edema and levels of inflammatory mediator TNF-α and PGE2 in monosodium urate (MSU) crystal-induced rats. Results. Six compounds were identified by HPLC-MS method, and abundance of phenolics was found in FPE. The FPE showed concentration-dependent-significant scavenging of DPPH and hydroxyl radicals with IC50 values 118.4 and 192.9 μg/mL, respectively. The FPE treatment significantly inhibited the paw edema and the production of TNF-α and PGE2 in MSU crystal-induced rats. Conclusion. The FPE exerted stronger antioxidant and anti-inflammatory activities which may be attributed to its high phenolic content.
研究领域:
药理学
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植物化学
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传统医学
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PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
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2026
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IF 3.1
Weizuo Liao,Yuxuan Xiao,Qunying Leng,Xinxin Yin,Ziyin Li,Junfeng Deng,Shixiong Zheng,Ruixue Liu,Biao Chen,Shiwei Li,Qiang Niu,Xingfen Yang,Zhini He
A TNF-α-induced inflammatory model using the human keratinocyte HaCaT cell line was developed and validated as an alternative in vitro method for evaluating the anti-inflammatory potential of cosmetic ingredients. In comparison with the conventional lipopolysaccharide (LPS)–stimulated RAW264.7 murine macrophage model, the HaCaT-based system demonstrated enhanced sensitivity, detecting significant cytokine inhibition at concentrations up to 1000-fold lower for certain actives. The model reliably distinguished established anti-inflammatory agents (ectoine, troxerutin, and dipotassium glycyrrhizinate) from non-active controls (glycerin, butanediol, and propylene glycol) through the suppression of interleukin-6 (IL-6). Notably, the HaCaT model also identified a potential pro-inflammatory shift at high concentrations of some active ingredients—an effect not observed in the RAW264.7 system. Multi-laboratory verification using the novel cosmetic ingredient β-nicotinamide mononucleotide (NMN) confirmed both the anti-inflammatory activity of NMN and the high reproducibility of the assay. These results support the TNF-α-HaCaT model as a sensitive, human-relevant, and reproducible alternative for screening cosmetic ingredients, contributing to the growing toolbox of nonanimal methods for safety and efficacy assessment.
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PubMed
高影响因子
Thoracic Cancer
·
2026
·Vol. 17
·期 17
·e70383
·
IF 2.6
Kairui Zhu,Yulong Mu,Zhenguo Su,Zhen Yue,Dongyang Wu,Guiwu Qu,Chenyang Jiang,Qing Li,Youjie Li,Ning Xie
Background Pyroptosis-related signaling contributes to lung adenocarcinoma (LUAD) progression and prognosis. Apigenin (AP) has anti-inflammatory and cytoprotective properties, but its effects on pyroptosis-associated signaling in injured LUAD cells remain unclear. Methods A549 cells were treated with carbonyl cyanide m -chlorophenyl hydrazone (CCCP) and ferrous sulfate (FeSO 4 ) to establish a cellular injury model. Cell morphology, Cell Counting Kit-8 signals, and pyroptosis-associated proteins were assessed after AP treatment. Network pharmacology, molecular docking, molecular dynamics simulations, and analyses of The Cancer Genome Atlas and Gene Expression Omnibus datasets were used to prioritize candidate targets, characterize pyroptosis-related genes, and develop a prognostic signature. Results CCCP/FeSO 4 reduced CCK-8 signals and induced morphological injury, whereas AP partially reversed these changes. AP also reduced alterations in GSDMD-N, caspase-1, IL-1β, TNF-α/NF-κB pathway proteins, AIM2, and ASC. TNF was prioritized as a candidate target, and computational analyses predicted a potentially stable AP–TNF interaction without demonstrating direct binding. Bioinformatic analyses identified distinct pyroptosis-related LUAD subgroups and generated a prognostic signature that stratified survival in training and external validation cohorts. AIM2 was additionally prioritized as a LUAD- and stress-associated candidate. Conclusion AP attenuated CCCP/FeSO 4 -induced injury and pyroptosis-associated molecular changes in A549 cells, potentially through TNF-α/NF-κB and AIM2-related signaling. Further mechanistic validation is required.
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高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Shuaishuai Chen,Weina Xue,Zhongxiu Wu,Dingyan Lu,Lin Zheng,Meng Zhou,Yongjun Li,Yonglin Wang,Ting Liu
Objective: The total flavonoids of Periploca forrestii Schltr. (TFPF) exhibit notable anti-rheumatoid arthritis (RA) properties, highlighted by their inhibitory action on TNF-α. This study investigates the specific compounds of TFPF responsible for TNF-α inhibition and delineates their mechanism of action.Methods: L929 cells and luciferase-based assays were used to assess anti-TNF-α activity. Additionally, MH7A cells and Wistar rats were employed to establish in vitro and in vivo models of RA. Chemical chromatography, thermal proteome profiling (TPP), molecular docking, surface plasmon resonance (SPR), cellular thermal shift assays (CETSA), drug affinity responsive target stability tests (DARTS), and transcriptomic analysis were used to study the potent molecules of TFPF and their protein targets and pathways. H&E staining, immunofluorescence staining, ELISA, and Western blot were employed for pharmacodynamic and mechanism studies of these potent molecules.Results: TFPF mitigated cellular injury in L929 cells and inhibited luciferase expression, both of which were induced by TNF-α. Among the eight compounds identified, quercetin exhibited the most potent anti-TNF-α activity. Quercetin improved cellular injury and reduced the cell apoptosis rate in L929 cells treated with TNF-α. TPP revealed the interaction between quercetin and TNF-α, which was verified by molecular docking, SPR, CETSA, and DARTS assays. Transcriptomic analysis highlighted the TNF signaling pathway, suggesting that quercetin may target TNF-α to inhibit the activation of the NF-κB signaling pathway. Quercetin inhibited luciferase expression, suppressed the phosphorylation of IκBα and p65, blocked p65 nuclear translocation, and reduced the mRNA expression of COX-2, INOS, IL-6, and IL-1β. Moreover, quercetin decreased inflammation and joint damage in RA.Conclusion: Quercetin, a compound of TFPF, interacts with and inhibits the activity of TNF-α, thereby suppressing the TNF-α/NF-κB signaling pathway and alleviating the symptoms of RA. These findings position quercetin as a promising TNF-α inhibitor for the treatment of RA.
研究领域:
药理学
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免疫学
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分子生物学
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PubMed
高影响因子
ACS Omega
·
2020
·
IF 2.87
Donghong Liu,Jia Liu,Chao Li,Wei Li,Wei Wang,Jie Liu
Gene therapy is an emerging therapeutic strategy used in clinics. Ultrasound-mediated gene transfection possesses great potential as a secure and available approach for gene delivery. However, transfection efficiency and targeting ability remain challenging. In this study, we developed a kind of ultrasound-aided and targeting nanoparticles for microRNA delivery. These nanoparticles carrying nucleic acids were prepared with cationic poly-(amino acid) encapsulated with perfluoropentane. The formulated nanoparticles were stabilized with negatively charged PGA–PEG–RGD peptide coating. Ultrasound imaging and specific gene transfection using this nanocarrier could be implemented simultaneously. Upon treatment with ultrasound irradiation, phase transition was induced in the nanoparticles and they generated acoustic cavitation, resulting in enhanced gene transfection against the endothelial cells. With the overexpression of miR-181b loaded by the nanoparticles, the TNF-α-stimulated endothelial cells were effectively rescued from the inflammatory state through the protection of cell viability and suppression of cell adhesion.
研究领域:
生物医学工程
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分子生物学
·
基因治疗
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DOI
PubMed
高影响因子
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