Cell Reports
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2025
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IF 6.9
Kangtai Xu,Xuefei Liu,Qian Zeng,Yaqi Liu,Leyan Shan,Luyao Ji,Yifei Wu,Jiawei Wu,Yiming Chen,Yitong Li,Songqiang Huang,Changyu Jiang,Xin Hong,Chaoran Wu,Zilong Wang
Chronic itch is a devastating clinical condition, and its central mechanisms remain poorly understood. We reported that spinal cannabinoid receptor type 2 (CB 2 R) activation exerts antipruritic effects and that itch escalates in mice lacking Cnr2 in mouse models of dermatitis and psoriasis. In the spinal cord, CB 2 R is mainly expressed in microglia, and microglial ablation or inhibition attenuated chronic itch, suggesting that microglial activation contributes to chronic itch. Particularly, conditional Cnr2 deletion in microglia also exacerbated chronic itch in mice. Single-cell RNA sequencing and molecular mechanistic studies suggest that CB 2 R activation reprogrammed microglia by inducing anti-inflammatory suppressor of cytokine signaling 3 (SOCS3) and reducing itch-related p38 and signal transducer and activator of transcription 1 (STAT1) phosphorylation. Finally, CB 2 R activation suppressed neuronal excitability and synaptic transmission in gastrin-releasing peptide (GRP)/GRP receptor (GRPR) interneurons and ascending projection neurons by inhibiting microglia-derived cytokines. These findings demonstrate that microglial activation contributes to chronic itch, while CB 2 R activation in microglia alleviates chronic itch via neuro-immune interactions.
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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DOI
PubMed
高影响因子
ACS Sensors
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2020
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IF 7.333
Dan Sun,Weiqing Xu,Chongyang Liang,Wei Shi,Shuping Xu
High-efficiency induction of bone marrow mesenchymal stem cells (BMSCs) to osteogenic differentiation in vitro can help solve a series of bone diseases such as bone injury, fracture repair, and osteoporosis. In order to explore the optimal conditions for different chemical inducers to promote BMSCs differentiation and the possible differentiation mechanisms, we developed a smart nanoprobe that can achieve in situ alkaline phosphatase (ALP) activity detection during osteogenic differentiation in cells. The smart nanoprobe (Au@BCIP) was designed as the surface decoration of gold nanoparticles (AuNPs) with 5-bromo-4-chloro-3-indolyl phosphate (BCIP). The nanoprobe was co-cultured with differentiated BMSCs at different stages to monitor ALP activity based on an ALP-catalyzed hydrolysis reaction with BCIP as a substrate. The product can be quickly oxidized by dissolved oxygen to obtain a Raman-active species (5,5′-dibromo-4,4′-dichloro-1H,1H-[2,2′] biindolylidene-3,3′-dione). The SERS sensitivity was greatly improved by resonating the excitation wavelength of 632.8 nm. It is a new strategy for tracing bone disease-related ALP activity in an in vivo model with high sensitivity and selectivity and non-invasion. By using this nanoprobe, osteogenic differentiation of cells under osteogenic supplements was assessed and the p38 MAPK signaling pathway for osteogenic differentiation was experimentally evidenced, which are of significance for understanding BMSCs and regulating their osteogenic differentiation process.
研究领域:
生物医学工程
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细胞生物学
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骨科医学
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DOI
PubMed
高影响因子
Journal of Applied Biomedicine
·
2023
·Vol. 21
·期 4
·193-199
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IF 1.3
Hongji Wang,Lisha Chen,Juping Xing,Xiangchao Shi,Changshui Xu
Naringin inhibits inflammation and oxidative stress, the P2 purinoreceptor X4 receptor (P2X4R) is associated with glial cell activation and inflammation, the purpose of this study is to investigate the effects of naringin on P2X4 receptor expression on satellite glial cells (SGCs) and its possible mechanisms. ATP promoted the SGC activation and upregulated P2X4R expression; naringin inhibited SGC activation, decreased expression of P2X4R, P38 MAPK/ERK, and NF-κB, and reduced levels of Ca2+, TNF-α, and IL-1β in SGCs in an ATP-containing environment. These findings suggest that naringin attenuates the ATP-induced SGC activation and reduces P2X4R expression via the Ca2+-P38 MAPK/ERK-NF-κB pathway.
研究领域:
神经科学
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药理学
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细胞生物学
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炎症研究
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DOI
PubMed
高影响因子
TOXICOLOGY
·
2024
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IF 4.8
Linjing Xu,Huan Liu,Yifeng Rang,Lizi Zhou,Xukai wang,Yinhuan Li,Chunhong Liu
Nonylphenol (NP) and octylphenol (OP) are environmental contaminants with potential endocrine disrupting effects. However, there is limited research on the mechanisms and intervention of combined NP and OP exposure-induced neurotoxicity. This study aims to explore the cytotoxicity of combined NP and OP exposure and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. In present study, LBP (62.5, 125 and 250 µg/mL) were applied to intervene rat adrenal pheochromocytoma (PC-12) cells treated with combined NP and OP (NP: OP = 4:1, w/w; 1, 2, 4 and 8 µg/mL). The results showed that NP and OP induced oxidative stress, disrupted the 5-hydroxytryptamine (5-HT) and cholinergic systems in PC-12 cells. Additionally, they activated the p38 protein kinase (p38) and suppressed the expression of silent information regulation type 1 (SIRT1), monoamine oxidase A (MAOA), phosphorylated cyclic-AMP response binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase receptor type B (p-TrkB). However, N-acetyl-L-cysteine (NAC) treatment counteracted the changes of signalling molecule p38, SIRT1/MAOA and CREB/BDNF/TrkB pathways-related proteins induced by NP and OP. LBP pretreatment ameliorated combined NP and OP exposure-induced oxidative stress and neurotransmitter imbalances. Furthermore, the application of LBP and administration of a p38 inhibitor both reversed the alterations in the signaling molecule p38, as well as the proteins associated to the SIRT1/MAOA and CREB/BDNF/TrkB pathways. These results implied that LBP may have neuroprotective effects via p38-mediated SIRT1/MAOA and CREB/BDNF/TrkB pathways.
研究领域:
毒理学
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神经科学
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药理学
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环境科学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2021
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IF 9.381
Fei He,Shihai Zhang,Yanan Li,Xia Chen,Zhenyun Du,Chenghao Shao,Kan Ding
The fruit of Lycium ruthenicum Murr is used as traditional medicine and functional food . Previously we reported that one RG-I pectin from this fruit might inhibit pancreatic cancer cells growth. We further hypothesized that there might be other type of polysaccharides in this fruit also have anti-tumor effect. Here, we showed novel structure of a homogeneous polysaccharide named LRP1-S2 from this fruit and its anti-pancreatic cancer effect. Structure analyses suggested that LRP1-S2 was a novel arabinogalactan with the molecular weight ( Mw ) of 17.0 kDa. Bioactivity test showed that LRP1-S2 might attenuate the proliferation of pancreatic cancer cells in vitro and in vivo without significant cytotoxicity to normal pancreatic HPDE6-C7 cells and LO2 liver cells. Mechanism study indicated that it might induce apoptosis of BxPC-3 by inactivating P38 MAPK/NF-κB and GSK-3β/β-Catenin signaling pathways . These results suggested that LRP1-S2 could be a potential anti-tumor leading compound for functional food and new drug development. Chemical compounds arabinogalactan, pectin, galactan , arabinan , RN-1, HH1-1, LRP1-S2, LRP3-S1.
研究领域:
药理学
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癌症研究
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分子生物学
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植物学
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DOI
PubMed
高影响因子
CELLULAR SIGNALLING
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2020
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IF 3.968
Yan Lin,Moussa Harouna Koumba,Suxuan Qu,Dongxu Wang,Lianjie Lin
Ulcerative colitis-associated colorectal cancer (UC-CRC) is the most serious complication of ulcerative colitis (UC). Nuclear factor of activated T cells 3 (NFATc3) is participated in inflammation and cancer. In this study, we investigated the effects of NFATc3 on experimental UC-CRC in vivo and in vitro , and explored the underlying mechanisms. Administration of azoxymethane (AOM) and dextran sulfate sodium (DSS) induced UC-CRC model in C57BL/6 mice. Body weight was monitored weekly. Colon tissues were harvested at week 14. We examined changes in the histopathology, inflammatory cytokines, carcinogenesis factors, and epithelial-mesenchymal transition (EMT) markers in colon tissues. We found that NFATc3 expression was significantly up-regulated in AOM/DSS treated mice compared with control. Mice lacking NFATc3 showed decreased tumor number and size, decreased mucosal damage, and increased survival rate. Moreover, down-regulation of NFATc3 could inhibit the proliferation and EMT of UC-CRC, decrease the levels of pro-inflammatory cytokines, reduce the colonic infiltration by neutrophils and macrophages, and suppress the activation of P38 and JNK signal pathway in mice . In In vitro experiments, silencing NFATc3 suppressed the proliferation and EMT of CRC cells, and reduced the activation of P38 and JNK. In addition, miR-370-3p could bind to NFATc3. Down-regulation of miR-370-3p promoted proliferation and EMT of CRC cells, while silencing NFATc3 could reverse these effects. In conclusion, NFATc3 was involved in the pathogenesis of experimental UC-CRC and NFATc3 knockdown ameliorated experimental UC-CRC progression via the inhibition of inflammatory responses and EMT. NFATc3 mediated the inhibitory effects of miR-370-3p on CRC cells proliferation and EMT. Targeting NFATc3 may be effective in treating UC-CRC.
研究领域:
癌症生物学
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免疫学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
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2022
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IF 3.973
Xiaoying He,Jiali Wang,Qian Wang,Jing Liu,Xi Yang,Lingjuan He,Haihong Hu,Su Zeng,Lushan Yu,Yunqing Qiu,Yan Lou
Hand-foot syndrome (HFS) is a major adverse reaction to capecitabine (CAP). The exact pathogenesis of this disease remains unclear. In this study, metabolomics combined with cell RNA sequencing was used to study the mechanisms of CAP-induced HFS. The murine model of HFS was constructed by intragastric administration of CAP or its metabolites. Quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to verify the mechanisms. Metabolomics showed the phosphatidylinositol signaling pathway and amino acid and fatty acid metabolism to be the major metabolic alterations related to the occurrence of HFS. Transcriptomics profiles further revealed that the cytokine–cytokine receptor interaction, IL17 signaling pathway, Toll-like receptor signaling pathway, arachidonic acid metabolism, MAPK signaling pathway, and JAK-STAT3 signaling pathway were the vital steps in skin toxicity induced by CAP or its metabolites. We also verified that the inflammation mechanisms were primarily mediated by the abnormal expression of interleukin (IL) 6 or IL8 and not exclusively by COX-2 overexpression. Finally, the P38 MAPK, NF-κB, and JAK-STAT3 signaling pathways, which mediate high levels of expression of IL6 or IL8, were identified as potential pathways underlying CAP-induced HFS.
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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免疫学
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生物化学
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DOI
PubMed
高影响因子
Environment & Health
·
2026
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IF 6.3
Shiyin Zhong,Qiongli Zhou,Jirui Yang,Zhimin Zhang,Xueting Chai,Jinghao Luo,Xin Zhang,Jingjing Liu,Yangzong Yixi,Lei Shi,Xuhong Chang,Hui Wang
Manganese (Mn) is an essential trace element, but increasing industrial and agricultural use has led to elevated levels of environmental Mn levels. Chronic overexposure to Mn can cause a Parkinson’s-like neurodegenerative disorder; however, the underlying mechanisms remain incompletely understood. This study combined in vitro and in vivo models to investigate the role of the cGAS–STING/NLRP3 axis in regulating the p38 MAPK/NF–κB pathway in the process of Mn-induced Tau aggregation leading to neurotoxicity. Our results demonstrated that MnCl2 exposure significantly activated both the cGAS–STING/NLRP3 signaling axis and the p38 MAPK/NF–κB pathway, accompanied by increased Tau expression. Genetic ablation of cGAS, STING, or NLRP3 attenuated Mn-induced Tau upregulation, indicating that the cGAS–STING/NLRP3 signaling axis mediates Tau expression. RNA-seq analysis further revealed that the decreased Tau expression in knockout cells is associated with the MAPK/NF–κB signaling pathway. Pharmacological inhibition of p38 MAPK or NF–κB markedly downregulated cGAS–STING signaling, inflammatory cytokine release, and phosphorylated Tau (p-Tau) levels. Moreover, we observed colocalization and interaction among p-p38, p-p65, and p-Tau. Overall, these findings reveal that Mn activates the cGAS–STING/NLRP3 signaling axis regulated by the p38 MAPK/NF–κB pathway, driving pathological Tau aggregation.
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高影响因子
BMC Medicine
·
2025
·Vol. 23
·期 1
·1-16
·
IF 8.3
Li Yinyan,Yang Sizu,Jiang Feng,Luo Siqi,Liang Jinlong,Jiang Linrui,Chen Zhixuan,Chen Xin,Yang Jie
Background Influenza A virus (IAV) is a major cause of seasonal and global pandemics, posing serious health risks. Repositioning approved drugs offers an efficient antiviral strategy, particularly as calcium (Ca 2 ⁺) is crucial for IAV infection, making Ca 2 ⁺ channel blockers (CCBs) promising candidates for antiviral agents. Methods The in vitro antiviral activity of cilnidipine was evaluated using MTT assays, qRT-PCR, plaque assays, and western blotting. Mechanistic studies involved time-of-addition, viral internalization, pseudovirus neutralization, and HA (hemagglutinin) syncytium assays. For in vivo analysis, BALB/c mice were intranasally infected to evaluate the effects of cilnidipine on viral titer, lung index, pulmonary inflammatory mediators, and survival rate. Results In vitro, cilnidipine exhibits antiviral activity against IAV during the early stages of infection. It disrupts clathrin- and caveolin-mediated endocytosis to inhibit the internalization of IAV and interacts with the viral HA2 subunit to impede virus membrane fusion. Additionally, cilnidipine suppresses the PI3K-AKT and p38 MAPK pathways activated by IAV infections. In vivo, cilnidipine reduces virus titers and lung index, ameliorates lung pathology, and inhibits pulmonary inflammatory mediator expression, improving survival rates. Conclusions These findings highlight the promising anti-IAV properties of cilnidipine both in vitro and in vivo, suggesting its potential as a clinical agent for emergencies against influenza outbreaks.
研究领域:
病毒学
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药理学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Jinping Wang,Jianmin Wu,Zishen Lin,Ning Ma,Zhaoyue Men,Chao Zhang,Xi Ma,Hongyu Zheng
The invasion of pathogens derived from diet or the environment triggers intestinal inflammation, which is a result of the host intestinal barrier damage and immune dysfunction, such as the decrease of host defense peptides (HDPs) and inhibition of cell proliferation. Herein, the siRNA interference demonstrated that a critical lysozyme, which was mainly induced by dietary supplementations of sodium butyrate and forskolin, improved cell proliferation by inhibiting p38 MAPK and JNK signaling pathways and reinforced the intestinal barrier. Moreover, we established a mouse model of intestinal inflammation with Citrobacter rodentium ( C. rodentium ). It was found that NaBu and FSK stimulated intestinal epithelial proliferation to repair barrier damage, and performed stronger disease resistance to C. rodentium infection on account of the lysozyme upregulation in colon. Therefore, this study revealed that NaBu and FSK prevented or alleviated the development of foodborne infections by promoting lysozyme expression, which may be mediated by the effect of lysozyme on promoting cell proliferation and improving barrier function.
研究领域:
胃肠病学
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免疫学
·
分子生物学
·
微生物学
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Dalin Sun,Dong Xing,Dandan Wang,Yuanyuan Liu,Bin Cai,Weimin Deng,Qinglin Hu,Wenjun Ma,Baofang Jin
Background: Chronic non-bacterial prostatitis (CNP), one of the most common chronic diseases in urology, leads to pain in the prostate and dysuria, critically affecting the physical or mental health of patients. However, there are no standard treatment approaches for the treatment of CNP in the clinic. Although the clinical application of Bushen Daozhuo granule (BSDZG) offers hope to CNP patients in China, the mechanisms of BSDZG in treating CNP are still not entirely clear. Hence, we aimed to investigate the novel therapeutic mechanisms of BSDZG on CNP. Methods: In this study, we first assayed the prostate index of rats and then determined the anti-inflammatory and anti-apoptotic effects of BSDZG on CNP in vivo and in vitro by employing ELISA kits and TUNEL staining. Next, we investigated whether the anti-inflammatory and anti-apoptotic mechanisms of BSDZG on prostate protein-induced rats and lipopolysaccharide (LPS) induced RWPE-1 cells were related to the AKT, p38 MAPK, and NF-κB pathways with the help of Western blot. Finally, the influence of BSDZG on the interaction between the p38 MAPK and NF-κB pathway in LPS-induced RWPE-1 cells was explored by adopting dehydrocorydaline (DHC, p38 MAPK activator) with the help of ELISA kits and Western blot. Results: In vivo , BSDZG effectively reduced the prostate index. In vivo and in vitro , BSDZG dramatically declined the level of two pro-inflammatory cytokines, TNF-α and IL-1β, as well as the apoptosis rate. Moreover, in vivo and in vitro , BSDZG memorably upregulated the expression level of p-AKT, and substantially downregulated the expression level of p-p38 MAPK and NF-κB2. The activation of p38 MAPK significantly reversed the moderation effects of BSDZG on the level of TNF-α and IL-1β, as well as the expression level of p-p38 MAPK and NF-κB2 in vitro . Conclusion: To sum up, the in vivo and in vitro therapeutic mechanisms of BSDZG on CNP were reflected as the anti-inflammation and anti-apoptosis that was formed by inhibiting the level of pro-inflammatory cytokines, TNF-α and IL-1β, to regulate the AKT, p38 MAPK, and NF-κB pathways, and the anti-inflammatory effect of BSDZG was realized by suppressing the p38 MAPK pathway to inhibit the downstream NF-κB pathway.
研究领域:
泌尿外科
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药理学
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Pengchen Chen,Yali Song,Li Tang,Zhuolin Qiu,Junhui Chen,Siyu Xia,Ashok Iyaswamy,Jing Cai,Yan Sun,Chuanbin Yang,Jigang Wang
Tri (2-Ethylhexyl) phosphate (TEHP), widely used as a fire retardant and plasticizer, has been commonly found in the environment. Its potential health-related risks, especially reproductive toxicity, have aroused concern. However, the potential cellular mechanisms remain unexplored. In this study, we aimed to investigate the molecular mechanisms underlying TEHP-caused cell damage in Sertoli cells, which play a crucial role in supporting spermatogenesis. Our findings indicate that TEHP induces apoptosis in 15P-1 mouse Sertoli cells. Subsequently, we conducted RNA sequencing analyses, which suggested that ER stress, autophagy, and MAPK-related pathways may participate in TEHP-induced cytotoxicity. Furthermore, we demonstrated that TEHP triggers ER stress, activates p38 MAPK, and inhibits autophagy flux. Then, we showed that the inhibition of ER stress or p38 MAPK activation attenuates TEHP-induced apoptosis, while the inhibition of autophagy flux is responsible for TEHP-induced apoptosis. These results collectively reveal that TEHP induces ER stress, activates p38, and inhibits autophagy flux, ultimately leading to apoptosis in Sertoli cells. These shed light on the molecular mechanisms underlying TEHP-associated testicular toxicity.
研究领域:
毒理学
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生殖生物学
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分子生物学
·
细胞生物学
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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）