ENVIRONMENTAL TOXICOLOGY
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2022
·Vol. 37
·期 7
·1551-1562
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IF 4.109
Dan Song,Yuan Liu,Yaxin Yao,Feng Liu,Wenjing Tao,Xiaolong Zhou,Runsheng Li,Xiaowei Zhang,Xiangchen Li
The aim of this study was to assess the protective effect and potential mechanism of melatonin against bisphenol A (BPA)-induced apoptosis and oxidative damage in FLK-BLV cells. The results showed that BPA reduced cell viability in a dose- and time-dependent manner, caused cell shrinkage and induced oxidative stress and apoptosis in FLK-BLV cells, which were effectively reversed by melatonin. In addition, BPA caused autophagy flux impairment, which was confirmed by the increased of LC3-II and p62 levels, whereas melatonin treatment effectively reduced p62 levels under BPA treatment, and reversed apoptosis-related protein expression patterns caused by BPA. However, inhibition of autophagy by CQ partially abolished the protective effect of melatonin on apoptosis, suggesting that melatonin against BPA-induced oxidative injury and apoptosis by activating autophagy pathway. Moreover, we found that melatonin inhibited BPA-induced the activation of p38 MAPK, which was comparable to SB203580 pretreatment, and companied by the activation of autophagy and decreases of apoptosis when compared to BPA alone, indicating that melatonin protected against BPA-induced apoptosis partially through the p38 MAPK-autophagy pathway. In conclusion, these results suggest that melatonin may prevent BPA-induced FLK-BLV cell damage by inhibiting p38/MAPK signaling pathway and activating autophagy, and it could be a potential therapeutic compound in preventing BPA-induced cell damage.
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FOOD AND CHEMICAL TOXICOLOGY
·
2019
·
IF 3.775
Tongtong Shen,Yufan Miao,Chenchen Ding,Wentao Fan,Shuhui Liu,Yanan Lv,Xiaona Gao,Marthe De Boevre,Liping Yan,Sheila Okoth,Sarah De Saeger,Suquan Song
Zearalenone (ZEA) can widely contaminate crops and agricultural products. The ingestion of ZEA-contaminated food or feed affects the integrity and functions of the intestines. In this study, we aimed to find the potential protective mechanism against ZEA ingestion. We found that ZEA induced cell death in IPEC-J2 cells. Meanwhile, the cytoprotective autophagy was activated in ZEA-treated cells. Further studies demonstrated that a p38/MAPK inhibitor down-regulated autophagy and increased cell death compared to those of the controls. Furthermore, ZEA could induce the accumulation of ROS , and eliminating ROS with NAC resulted in a decline in cell death, p38/MAPK phosphorylation, and the expression of LC3-II compared to those of ZEA-group. In addition, cytochrome P450 reductase (CYPOR) was significantly increased in ZEA-treated cells compared to that in the controls, and an inhibitor of CYPOR decreased ROS levels and mitigated cell death compared to those of the ZEA-group. More importantly, we found that blocking both p38/MAPK signalling and autophagy could enhance CYPOR expression and elevate ROS levels. Overall, our study indicated that the p38/MAPK pathway could activate protective autophagy in response to the CYPOR-dependent oxidative stress that was induced by ZEA in IPEC-J2 cells.
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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
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分子生物学
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微生物学
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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
·
分子生物学
·
炎症研究
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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
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细胞生物学
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JOURNAL OF NANOPARTICLE RESEARCH
·
2013
·Vol. 15
·期 12
·1-11
·
IF 2.175
Li Zhi,Zhang Fei-long,Wang Zhiyuan,Pan Li-li,Shen Ying-ying,Zhang Zhen-zhong
The photocytotoxicity of water-dispersed 100–300 nm fullerene amino acid derivatives nanoparticles was studied. The nanoparticle solution of fullerene derivatives, l -phenylalanine (C60-phe) and glycine (C60-gly), suppressed the in vitro growth of MCF-7 cells lines, induced cancer cells apoptosis, and caused a perturbation of the cell cycle. These nanoparticle solutions increased intracellular reactive oxygen species after irradiation. C60-phe or C60-gly upregulated the expression of phosphorylated (p)p38 mitogen-activated protein kinase (MAPK). N -Acetyl- l -cysteine significantly depressed the composite-induced activation of p38MAPK, and the kinase inhibitor SB203580 significantly prevented C60 derivative-induced cell apoptosis. This study revealed that p38MAPK is activated by C60 nanoparticles through triggering reactive oxygen species generation, leading to cancer cell injuries.
研究领域:
纳米技术
·
癌症生物学
·
细胞生物学
·
药理学
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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.
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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
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ACTA PHARMACOLOGICA SINICA
·
2022
·Vol. 43
·期 9
·2289-2301
·
IF 7.169
Su Xue-ling,Wang Shu-hui,Komal Sumra,Cui Liu-gen,Ni Rui-cong,Zhang Li-rong,Han Sheng-na
Connexin 43 (Cx43) is the most important protein in the gap junction channel between cardiomyocytes. Abnormalities of Cx43 change the conduction velocity and direction of cardiomyocytes, leading to reentry and conduction block of the myocardium, thereby causing arrhythmia. It has been shown that IL-1β reduces the expression of Cx43 in astrocytes and cardiomyocytes in vitro. However, whether caspase-1 and IL-1β affect connexin 43 after myocardial infarction (MI) is uncertain. In this study we investigated the effects of VX765, a caspase-1 inhibitor, on the expression of Cx43 and cell-to-cell communication after MI. Rats were treated with VX765 (16 mg/kg, i.v.) 1 h before the left anterior descending artery (LAD) ligation, and then once daily for 7 days. The ischemic heart was collected for histochemical analysis and Western blot analysis. We showed that VX765 treatment significantly decreased the infarct area, and alleviated cardiac dysfunction and remodeling by suppressing the NLRP3 inflammasome/caspase-1/IL-1β expression in the heart after MI. In addition, VX765 treatment markedly raised Cx43 levels in the heart after MI. In vitro experiments were conducted in rat cardiac myocytes (RCMs) stimulated with the supernatant from LPS/ATP-treated rat cardiac fibroblasts (RCFs). Pretreatment of the RCFs with VX765 (25 μM) reversed the downregulation of Cx43 expression in RCMs and significantly improved intercellular communication detected using a scrape-loading/dye transfer assay. We revealed that VX765 suppressed the activation of p38 MAPK signaling in the heart tissue after MI as well as in RCMs stimulated with the supernatant from LPS/ATP-treated RCFs. Taken together, these data show that the caspase-1 inhibitor VX765 upregulates Cx43 expression and improves cell-to-cell communication in rat heart after MI via suppressing the IL-1β/p38 MAPK pathway.
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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
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纳米技术
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生殖生物学
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材料科学
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细胞生物学
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高影响因子
ORAL DISEASES
·
2024
·
IF 2.9
Yifei Deng,Junhong Xiao,Xin Huang,Zhengguo Cao
Objective Inflammatory stimuli compromise the differentiation potency of human periodontal ligament cells (hPDLCs). Macrophage-derived exosomes (M-Exo) play a role in several aspects of cellular activity. This study investigated how M-Exo contributes to the osteo-/cementogenic differentiation of hPDLCs under inflammation and the mechanism involved. Methods M-Exo was identified by transmission electron microscopy, western blotting (WB), and dynamic light scattering. The internalization of M-Exo by hPDLCs was observed. After M-Exo treatment, the osteo-/cementogenic markers were detected by RT-qPCR and WB, and alkaline phosphatase (ALP) activity by ALP staining. Tumor necrosis factor alpha (TNF-ɑ) was applied to simulate inflammation. The rescue effect of M-Exo on TNF-ɑ-suppressed differentiation was validated. The p38 MAPK pathway activity was tested and a specific inhibitor was applied to explore the mechanism. Results M-Exo was successfully isolated, identified and internalized by hPDLCs. M-Exo enhanced the osteo-/cementogenic differentiation of hPDLCs, as indicated by upregulated osteo-/cementogenic markers and elevated ALP activity. Moreover, TNF-ɑ inhibited the differentiation capabilities of hPDLCs, on which M-Exo showed a rescue effect. M-Exo activated the p38 MAPK pathway and SB203580 attenuated its promotion effect. Conclusion This study showed that M-Exo ameliorated the TNF-ɑ-suppressed osteo-/cementogenic differentiation of hPDLCs partly through the p38 MAPK pathway.
研究领域:
牙科研究
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细胞生物学
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炎症
·
组织工程
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International Journal of Nanomedicine
·
2024
·
IF 6.6
Xiaojie Yan,Xueying Zhao,Mingde Fan,Wenfu Zheng,Guanxiong Zhu,Bin Li,Le Wang
Background Dihydroartemisinin (DHA) has emerged as a promising candidate for anticancer therapy. However, the application of DHA in clinics has been hampered by several limitations including poor bioavailability, short circulation life, and low solubility, significantly restricting its therapeutic efficacy and leading to notable side effects during the treatment.Purpose We present DHA-loaded zeolitic imidazolate framework-8 (D-ZIF) with controllable and targeted DHA release properties, leading to enhanced antitumor effects while reducing potential side effects.Methods D-ZIF was prepared by one-pot synthesis method using methylimidazole (MIM), Zn(NO3)2•6H2O and DHA. We characterized the physical and chemical properties of D-ZIF by TEM, DLS, XRD, FT-IR, and TG. We measured the drug loading efficiency and the cumulative release of DHA in different pH conditions. We evaluated the cytotoxicity of D-ZIF on renal cell carcinoma (RCC786-O), glioma cells (U251), TAX-resistant human lung adenocarcinoma (A549-TAX) cells by CCK8 in vitro. We explored the possible antitumor mechanism of D-ZIF by Western blot. We evaluated the biocompatibility and hemolysis of D-ZIF and explored the in vivo antitumor efficiency in mice model by TUNEL testing and blood biomarker evaluations.Results D-ZIF showed rhombic dodecahedral morphology with size of 129±7.2 nm and possessed a noticeable DHA encapsulation efficiency (72.9%). After 48 hours, D-ZIF released a cumulative 70.0% of the loaded DHA at pH 6.5, and only 42.1% at pH 7.4. The pH-triggered programmed release behavior of D-ZIF could enhance anticancer effect of DHA while minimizing side effects under normal physiological conditions. Compared with the free DHA group with 31.75% of A549-TAX cell apoptosis, the percentage of apoptotic cells was approximately 76.67% in the D-ZIF group. D-ZIF inhibited tumor growth by inducing tumor cell apoptosis through the mechanism of ROS production and regulation of Nrf2/HO-1 and P38 MAPK signaling pathways. D-ZIF showed potent effects in treating tumors with high safety in vivo.Conclusion This pH-responsive release mechanism enhanced the targeting efficiency of DHA towards tumor cells, thereby increasing drug concentration in tumor sites with negligible side effects. Herein, D-ZIF holds great promise for curing cancers with minimal adverse effects.
研究领域:
药学
·
癌症研究
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纳米技术
·
生物医学工程
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高影响因子
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