JOURNAL OF APPLIED TOXICOLOGY
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2026
·
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
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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 ETHNOPHARMACOLOGY
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2025
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IF 5.4
Chao-Yue Sun,Wan-Qing Li,Jing-Wen Lu,Ao-Yue Zhang,Qing-Xia Chu,Li Tang,Wei Gao,Jin-Jie Cai,Ying Lu,Dong Liu
Ethnopharmacological relevance Ampelopsis grossedentata (AG) is a popular folk tea that has been used in China for more than 1000 years. It is noteworthy that AG is widely recognized for preventing alcohol hangover in folk, and its protective effects on alcohol-induced hepatic steatosis have been demonstrated. Aim of the study Alcohol overconsumption can induce acute duodenal injury (ADI) that lacks effective therapeutic strategies. This study investigated the gastrointestinal protective effects of AG on alcoholic ADI in mice. Materials and methods AG extract was chemically characterized by HPLC analysis. Institute of Cancer Research (ICR) mice were pre-administered AG extract via gavage, and then subjected to an ethanol-induced ADI. After treatment, duodenal tissues were stained with hematoxylin and eosin (H&E), and cell apoptosis was detected by TUNEL staining and immunofluorescence. Untargeted metabolomics was employed to identify the differentially expressed metabolites, and the gene expressions of duodenal tissues were determined using RNA sequencing, immunofluorescence, immunohistochemistry, and western blotting. Results Acute ethanol administration caused severe duodenal damage, characterized by necrosis and shedding of duodenal villi, hemorrhagic injury, mucosal edema, and disruption of intestinal barrier in mice, which was improved by the pre-treatment with AG extract. Notably, administration of AG aqueous extract suppressed ethanol-induced duodenal villous apoptosis in mice by inhibiting caspase-3/7. In addition, untargeted metabolomics data showed AG extract improved ethanol-induced disruption of amino acid biosynthesis and metabolism, and increased the levels of amino acids, such as L-serine, L-histidine, L-leucine, L-glutamine and L-tryptophan. RNA sequencing analysis revealed that ethanol intake activated TNF, IL-17, MAPK and apoptosis pathways, and these pathways were inhibited by AG extract pre-treatment. Immunofluorescence and immunohistochemistry results showed AG extract reduced the expressions of TNF-a, FADD, TRADD, RIPK1 and caspase-8 activity in duodenal tissue in ethanol-fed mice. In addition, western blotting data showed that pre-treatment with AG extract suppressed ethanol-induced activation of IL-17 and MAPK pathways. Conclusion In conclusion, pre-treatment with AG inhibited ethanol-induced apoptosis of duodenal villi, disruption of intestinal barrier and amino acids metabolic disturbance. AG extract inhibited the TNF-a/FADD/caspase-8 and IL-17/MAPK signaling pathways. These findings highlight the gastrointestinal protective effects of AG extract against alcoholic ADI, and support its application as a duodenal protectant in drug development and dietary supplements.
研究领域:
药理学
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民族药理学
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胃肠病学
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分子生物学
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代谢组学
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免疫学
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高影响因子
Journal of Inflammation Research
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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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高影响因子
ACS Omega
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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
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基因治疗
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高影响因子
Journal of Inflammation Research
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2025
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IF 4.1
Siyue Bo,Xiaotong Wang,Jiani Qian,Guoqiang Ma,Zheng Ying,Duanmin Hu,Chunyan Hou,Junfeng Ma,Longjiang Xu,Shuang Yang
Background Ulcerative colitis (UC) disrupts the colon’s protective mucus layer, exposing the epithelium to bacteria and triggering inflammation. This barrier, crucial for intestinal health, depends on complex glycosylation, notably sialic acid modifications. However, the precise role of sialic acid acetylation and the enzyme SIAE (sialic acid acetylesterase) in UC pathogenesis remains unclear. This study investigates the role of glycosylation changes, specifically sialic acid de-acetylation, in UC progression.Methods Tissue samples were obtained from patients with ulcerative colitis (UC) and colorectal cancer at the Second Affiliated Hospital of Soochow University. HT-29 cells were utilized to investigate the molecular mechanisms of SIAE in UC pathogenesis. Mass spectrometry was performed to analyze differences in protein and glycoprotein expression. Western blot (WB) and immunohistochemistry (IHC) were used to examine SIAE protein expression changes during inflammation. Furthermore, polymerase chain reaction (PCR) and immunofluorescence were employed to determine the effects of SIAE on sialic acid levels and mucosal immunity.Results In this study, we characterized proteins and glycoproteins from patient tissues with UC, finding that sialic acid acetylesterase (SIAE) is upregulated in UC. HT-29 cells exposed to TNF-α induced an inflammatory response with a 5-fold increased expression of SIAE and NEU1 when TNF-α was at a concentration of 100 ng/mL. Mass spectrometry analysis revealed a reduction in acetylation on glycans and glycoproteins, while confocal microscopy confirmed a decrease in sialic acid on the cell surface. Gene expression analysis showed that CDH1, CTNND1, and ITGA8 were significantly downregulated in HT-29 cells stimulated by TNF-α, suggesting a reduction in cell-cell adhesion. SNA lectin-confocal microscopy revealed a reduction of sialic acid on HT-29 cells in TNF-α-induced UC cell models.Conclusion This study demonstrates that SIAE is significantly upregulated in ulcerative colitis (UC) tissues and TNF-α-stimulated HT-29 cells, leading to a marked reduction in sialic acid acetylation and cell surface sialic acid levels. These changes correlate with decreased expression of cell adhesion molecules, suggesting a disruption of the mucosal barrier integrity. Consequently, SIAE-mediated sialic acid de-acetylation emerges as a critical factor in UC pathogenesis, potentially serving as both a valuable biomarker and a promising therapeutic target.
研究领域:
医学
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分子生物学
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免疫学
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高影响因子
Chemical Biology & Drug Design
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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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高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2025
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IF 4
Xiangxuan Feng,Yaohui Wang,Yifan Wang,Jun Ren
The dysregulated overproduction of pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) is a hallmark of severe inflammatory diseases. Extracorporeal blood purification offers a promising therapeutic strategy, but current adsorbents often lack the specificity required for precise intervention. This study reports the development of a bispecific nanobody (bsNb)-based immunoadsorbent for the simultaneous and specific removal of IL-6 and TNF-α. The functional bsNb, produced in a prokaryotic system via tandem fusion, was covalently immobilized on Sepharose CL-6B matrix to prepare the affinity adsorbent. Comprehensive characterization confirmed its high saturation adsorption capacity (6.9 mg/mL for IL-6 and 2.2 mg/mL for TNF-α) and rapid binding kinetics. In a simulated hemoperfusion system using human serum, the adsorbent achieved removal efficiencies exceeding 85% for both cytokines across a range of pathophysiological concentrations. Crucially, the bsNb adsorbent effectively captured both targets simultaneously from a complex serum matrix. This work highlights the significant potential of bispecific nanobodies as robust and selective ligands for preparing targeted immunoadsorbents. The developed platform represents a superior alternative to non-specific adsorbents, paving the way for more precise and effective extracorporeal therapies against cytokine-driven inflammatory disorders.
研究领域:
免疫学
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生物医学工程
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炎症治疗
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纳米生物技术
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高影响因子
PHYTOMEDICINE
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2026
·
IF 11.3
Benlu Chen,Hongduo Lu,Jiayu Gan,Yunhao Hu,Zhiwen Chen,Changbo Cheng,Yang Liu,Yangwenxiang Wei,Yuehui Zhou,Yuxuan Xue,Yuhao Liu,Chi Zhou,Yinuo Fan,Zhenqiu Chen
CSA ameliorates estrogen-deficient osteoporosis without hepatotoxicity or nephrotoxicity. • CSA bidirectionally inhibits osteoclastogenesis and promotes osteogenesis. • CSA directly targets TNF-α to restore bone coupling balance. • CSA upregulates MIRO1 and promotes mitochondrial transfer from osteoblasts to osteoclasts. Background Oestrogen-deficient osteoporosis features an imbalanced bone formation–resorption coupling with excessive osteoclast activation and impaired osteoblast function. Compounds that bidirectionally regulate bone metabolism remain rare among natural small molecules. Cajaninstilbene acid (CSA) from Cajanus cajan leaves exerts regulatory effects on bone metabolism and anti-inflammatory activity, but its mechanism in restoring bone homeostasis via intercellular mitochondrial transfer remains unclear. Purpose To investigate the therapeutic effect of CSA on oestrogen-deficient osteoporosis and reveal its molecular mechanism by targeting TNF-α-mediated mitochondrial transfer to rebalance osteogenesis and osteoclastogenesis. Materials Ovariectomised (OVX) mice were used as the estrogen-deficient osteoporosis model and treated with Cajaninstilbene Acid (CSA) for 6 weeks. Bone microstructure and metabolism were evaluated by micro-computed tomography (micro-CT), histological staining and immunohistochemistry (IHC). Primary bone marrow macrophages (BMMs) and bone marrow mesenchymal stem cells (BMSCs) were cultured for osteoclastic and osteogenic differentiation. Differentiation was assessed by tartrate-resistant acid phosphatase (TRAcP), alkaline phosphatase (ALP) and alizarin red staining (ARS). Key targets were screened by transcriptomic analysis and validated by molecular docking and surface plasmon resonance (SPR). Mitochondrial transfer and activity were observed by co-culture, fluorescence labelling and JC-1 staining. Protein and gene expression were determined by Western blot (WB) and quantitative real-time polymerase chain reaction (qPCR). Results CSA significantly increased bone mineral density and improved trabecular microarchitecture in OVX mice without obvious hepatorenal toxicity. In vitro, CSA dose-dependently suppressed RANKL-induced osteoclastogenesis by downregulating NFATc1 and CTSK, while enhancing osteoblast differentiation by upregulating RUNX2, OCN and OPG. Mechanistically, CSA directly bound and inhibited TNF-α, upregulated the mitochondrial transporter MIRO1, and restored mitochondrial transfer from osteoblasts to osteoclasts, reversing the disrupted bone coupling balance. Conclusion CSA bidirectionally inhibits bone resorption and promotes bone formation by blocking TNF-α signalling and restoring MIRO1-mediated mitochondrial transfer, effectively ameliorating oestrogen-deficient osteoporosis. This study provides pharmacological support and novel mechanistic insights for CSA as a promising natural candidate for osteoporosis treatment. Download: Download high-res image (189KB) Download: Download full-size image
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高影响因子
POLYMER TESTING
·
2026
·
IF 6.4
Mei Yin,Jiamei Luo,Minqiang Jiang,Yong Liu,Youwei Zhang,Hui Zhang,Jianyong Yu
The widespread use of highly integrated smart electronic devices has led to serious electromagnetic pollution, making electromagnetic interference (EMI) shielding materials a crucial solution for controlling electromagnetic radiation. This study utilizes electrostatic self-assembly between negatively charged Co/C@TNF felts and positively charged cetyltrimethylammonium bromide (CTAB) functionalized multiwall carbon nanotubes (fMWNT) to construct a unique three-dimensional (3D) structure within epoxy resin (EP). Due to electrostatic interactions, fMWNT were uniformly loaded on Co/C@TNF felts. These well-dispersed fMWNT serve as bridges, connecting adjacent Co/C@TNF felts and EP, forming a more efficient conductive network, thereby obtaining composites with enhanced mechanical properties and superior EMI shielding effectiveness (EMI SE). The optimized EMI SE of xfMWNT/Co/C@TNF-EP composites reached 54.4 dB, which was 19.3% higher than that of pure Co/C@TNF-EP. Additionally, the flexural properties of the xfMWNT/Co/C@TNF-EP composites were also markedly enhanced, with a flexural strength of 164.40 MPa.
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高影响因子
ACS Sensors
·
2026
·
IF 10.9
Zhenghan Shi,Liya Ding,Li-ang Zhou,Ye Liu,Yuhang Wang,Yi Xu,Yunrui Cao,Zhinong Jiang,Qingjun Liu
Tumor necrosis factor-α (TNF-α) is an important inflammatory cytokine whose rapid and quantitative detection is essential for disease diagnosis and monitoring. However, conventional methods are often limited by bulky instrumentation and are not well suited for analysis in complex biological environments. Herein, a portable CRISPR/Cas12a-based aptasensor system was developed for detection of TNF-α by integrating aptamer recognition, Cas12a trans-cleavage signal amplification, and a miniaturized fluorescence detection device. An aptamer for TNF-α was designed to regulate the accessibility of the target sequence to the CRISPR RNA (crRNA), and the resulting change in Cas12a activity was converted into fluorescence signals. The portable device integrated light-emitting diode (LED) excitation and photodiode-based detection, with modulated signals wirelessly transmitted to a smartphone for readout. The aptasensor showed concentration-dependent responses, and the inhibition rate exhibited a linear relationship with TNF-α concentration. The applicability of the system was validated in cell culture supernatants and cervical tissue samples, including tumor and adjacent normal tissues. Distinct TNF-α levels were observed between these samples, showing good agreement with enzyme-linked immunosorbent assay (ELISA) results. This portable CRISPR/Cas12a aptasensor system provides a practical approach for point-of-care TNF-α detection and extends CRISPR-based sensing to protein biomarkers.
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JOURNAL OF CELLULAR BIOCHEMISTRY
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2017
·Vol. 119
·期 2
·1501-1510
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IF 3.085
Qing Wang,Pu Wang,Hong Zhou,Yan Hu,Chengshen Xie,Fei Gao,Ningjie Ma,Haoli Hou,Hao Zhang,Lijia Li
DNA methylation plays a crucial role in lots of biological processes and cancer. 5-azacytidine (5-AC), a DNA methylation inhibitor, has been used as a potential chemotherapeutic agent for cancer. In this study, we used 5-AC treatment to investigate whether DNA methylation was involved in regulation of programmed cell death (PCD) in mouse embryo fibroblast NIH-3T3 cells which could undergo PCD after treatment with TNF-α and cycloheximide (CHX). The results showed that the genomic DNA of NIH-3T3 cells was hypermethylated during PCD induced by TNF-α and CHX, and 5-AC might prevent this PCD process. However, treatment with the other three DNA methylation inhibitors, 5-aza-deoxycytidine, 6-thioguanine and RG108, did not interfere with the NIH-3T3 cell PCD process. Additionally, knockdown of DNMT1 did not affect the apoptosis process. The present results and observations indicated that 5-AC specifically inhibited the NIH-3T3 apoptosis process via a genomic DNA methylation-independent pathway. During the TNF-α and CHX-inducing apoptosis process, the PCD related BCL-2 family proteins were significantly down-regulated. Furthermore, after the small interference RNA-mediated knockdown of BCL-XL, one of the BCL-2 family proteins, 5-AC did not inhibit the apoptosis process, suggesting that 5-AC inhibited the PCD process induced by TNF-α and CHX by affecting the anti-apoptotic protein BCL-XL.
研究领域:
癌症研究
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细胞生物学
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表观遗传学
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高影响因子
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