Journal of Applied Biomedicine
·
2023
·Vol. 21
·期 4
·193-199
·
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
·
药理学
·
细胞生物学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
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
·
癌症研究
·
分子生物学
·
植物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2022
·
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
·
毒理学
·
分子生物学
·
免疫学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Environment & Health
·
2026
·
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.
✓ 已验证
产品关联
DOI
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
·
药理学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Cheng Cao,Mubin Sun,Jiabao Li,Zhenyu Yuan,Yuwei Gu,Yufan Shao,Lisheng Wang,Xiaohua Jin,Yijie Cheng,Bo Fan
Urate transporter 1 (URAT1, encoded by SLC22A12 ) is a key mediator of renal urate reabsorption and an important pharmacological target for urate-related disorders. Sodium butyrate (BuNa), a gut microbiota derived short-chain fatty acid, has been implicated in host metabolic regulation, but its role in renal urate transport remains unclear. Here, using molecular docking, cellular thermal shift assays, immunoprecipitation-mass spectrometry and multi-omics analyses, we identified free fatty acid receptor 2 (FFAR2) as a direct target of BuNa in renal proximal tubular HK2 cells . BuNa binding upregulated FFAR2 and promoted URAT1 expression and urate uptake via an FFAR2-dependent pathway. Mechanistically, BuNa/FFAR2 signaling acts via GNAQ to activate PLCβ, generating diacylglycerol and engaging a PKC-dependent p38 MAPK/ELK1 cascade that upregulates arrestin beta 2 (ARRB2). ARRB2 directly binds to IκB, preventing its phosphorylation-dependent degradation, thereby stabilizing IκB and inhibiting NF-κB nuclear translocation. Within the SLC22A12 promoter, NF-κB (RELA/p50) and hepatocyte nuclear factor 1 beta (HNF1β) compete for overlapping binding sites. By blocking NF-κB nuclear entry, BuNa relieves this competition, permitting HNF1β-driven SLC22A12 transcription. Thus, BuNa enhances URAT1-mediated urate reabsorption in HK2 cells via an FFAR2/GNAQ/p38 MAPK/ELK1/ARRB2 axis that stabilizes IκB, suppresses NF-κB, and relieves the competitive binding between NF-κB and HNF1β on the SLC22A12 promoter. These findings establish a previously unrecognized gut microbiota–kidney axis linking microbial BuNa to renal urate homeostasis through a novel transcriptional regulatory circuit.
✓ 已验证
产品关联
DOI
高影响因子
NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 2
·80
·
IF 4.5
Lu Xuefei,Xu Kai,Zhou Zhenyu,Ding Gaonan,Zhang Yuan,Liang Yongwen,Zhou Jiahui,Jia Minglu,Zhang Yitang,Shen Li,Li Hualing
Alzheimer’s disease (AD) is a progressive neurodegenerative disease for which no effective clinical therapies currently exist. The neuroprotective potential of Chaetoglobosin F (CF), a fungal secondary metabolite, was investigated in this study using a Caenorhabditis elegans ( C. elegans ) model of AD that are transgenic nematodes expressing amyloid-beta (Aβ). Key parameters evaluated included paralysis rate, lifespan, motor and cognitive functions, Aβ plaque aggregation, intracellular reactive oxygen species (ROS), and autophagosome formation. The transcriptional levels of genes were examined by real time PCR. Results showed that treatment with CF significantly delayed paralysis, extended lifespan, and ameliorated Aβ-induced deficits in locomotion and chemotaxis. CF markedly reduced Aβ plaque accumulation, suppressed intracellular ROS levels, and promoted autophagosome formation. Furthermore, CF had potent inhibitory effects on acetylcholinesterase (AChE) activity. These beneficial effects were correlated with the upregulation of crucial genes, including daf-16 , skn-1 , pmk-1 , mtl-1 , unc-51 , bec-1 , lgg-1 , sod-1 and sod-3 , which confirmed the improving antioxidant defenses and autophagy. Our findings demonstrate that CF confers strong neuroprotection against Aβ-induced toxicity in C. elegans by co-regulating oxidative stress and autophagy through the Insulin/IGF-1 (IIS) and p38 MAPK signaling pathways. These results suggest that CF is a promising natural compound for further investigation as a potential therapeutic agent for AD. Graphical
✓ 已验证
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
·
免疫学
·
分子生物学
·
微生物学
✓ 已验证
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
·
药理学
·
分子生物学
·
炎症研究
✓ 已验证
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
·
生殖生物学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Shengqi Zang,Can Xiao,Maodian He,Bo Chen,Bingyao Liu,Shuai Yi,Lei Wang,Junxia Li,Xiaolei Shi,Shoushan Bu,Lei Jin
Biomimetic surface modification of scaffolds with osteoinductive molecules is a promising strategy for improving the bioactivity of scaffold and stimulating stem cell signals in bone tissue engineering. Zirconia (ZrO 2 ) offers excellent mechanical properties and biocompatibility, but its bio-inert nature hinders its use in bone regeneration applications. Recombinant human bone morphogenetic protein 7 (rhBMP-7) and arginine-glycine-aspartate (RGD) peptide were investigated for their potential use as surface-modifying biomolecules on the ZrO 2 scaffold. Our results showed that human dental pulp stem cells (hDPSCs) were induced to osteogenic differentiation by rhBMP-7 and RGD in a dose-dependent manner. Significantly enhanced alkaline phosphatase activity and up-regulated expression of osteogenic genes in hDPSCs were associated with rhBMP-7 and RGD grafting onto the ZrO 2 scaffold. Western blot analysis revealed that rhBMP-7 and RGD grafting led to activation of the SMAD1/5, p38 MARK, and ERK signaling pathways during hDPSCs differentiation. After 4 and 8 weeks of transplantation, the hDPSCs-seeded ZrO 2 -RGD-BMP-7 scaffold facilitated osteogenic differentiation and enhanced in vivo bone formation in critical-sized calvarial bone defects. The results support the simultaneous use of rhBMP-7 and RGD as surface-modifying biomolecules and hDPSCs as a source of osteogenic stem cells in conjugation with ZrO 2 -based porous scaffold for bone tissue engineering.
研究领域:
组织工程
·
生物材料
·
干细胞生物学
·
骨再生
✓ 已验证
产品关联
DOI
高影响因子
REPRODUCTIVE TOXICOLOGY
·
2025
·
IF 2.8
Cheng Cheng,Yanfan Cui,Yujie Wang,Jingfeng Huang,Jiale Ma,Tao Luo,Wen Chen
Microplastics and nanoplastics (MNPs) are widespread in the environment and have male reproductive toxicity. However, toxic interventions involving MNPs have not been extensively examined. In this investigation, we explored the elimination capacity of magnetic nano-Fe 3 O 4 on polystyrene microplastics and nanoplastics (PS-MNPs) of different sizes. This study also investigated whether magnetic nano-Fe 3 O 4 could alleviate the toxicity of PS-MNPs in spermatogonial GC-1 cells. After coprecipitation by magnetic nano-Fe 3 O 4 in ddH 2 O, the removal rates of polystyrene microplastics (PS-MPs, 4 and 10 μm) are much higher than those of PS-NPs (25 nm, 100 nm, and 500 nm). The removal rate of the PS-NPs dramatically enhanced in the salt ion solutions. In addition, 25-nm, 100-nm, 500-nm, and 4-µm PS-MNPs penetrated GC-1 cells. Nevertheless, exclusively 25-nm PS-NPs decreased cell viability, elevated reactive oxygen species, disrupted the mitochondrial membrane potential, and induced apoptosis and inflammation through the P38/MAPK and Nrf2/HO-1 signaling pathways in GC-1 cells. Interestingly, magnetic nano-Fe 3 O 4 alleviated these harmful impacts of the 25-nm PS-NPs on the GC-1 cells. In conclusion, we demonstrated the toxicity of PS-NPs in GC-1 cells and provided a viable way to alleviate their toxicity.
研究领域:
环境毒理学
·
纳米技术
·
生殖生物学
·
材料科学
·
细胞生物学
✓ 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）