CTS-Clinical and Translational Science
·
2020
·Vol. 14
·期 5
·2075-2084
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IF 3.373
Hongtao He,Kuangyuan Qiao,Chao Wang,Wuhan Yang,Zhuo Xu,Zhilei Zhang,Yuming Jia,Chong Zhang,Li Peng
Hydrazinocurcumin (HZC), a synthetic derivative of curcumin (CUR), has been documented to show anticancer potential in impeding tumor growth in several cancers, including hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms remain unclear. This study aimed to explore the function and underlying mechanisms of HZC on HCC cells, which may involve the p38 mitogen activated protein kinase (MAPK) pathway. HZC was first purified and identified. HepG2 cells were then subjected to treatment with HZC or CUR of different concentrations and p38 MAPK signaling inhibitor (SB203580) to verify their effects on HCC cell apoptosis and proliferation. Furthermore, the functional relevance between HZC and the p38 MAPK pathway in HCC was examined. It was observed that 40 μM HZC exhibited the best pro-apoptosis effect in HCC cells. HZC was found to inhibit HCC cell proliferation and promote apoptosis, the effect of which was stronger than 5-fluorouracil (5-FU). More importantly, the anti-oncogenic effect of HZC and 5-FU was implicated with activation of the p38 MAPK pathway. In vivo experimental results showed that HZC inhibited tumor growth more effectively than 5-FU through the p38 MAPK pathway. These results provide evidence that HZC exerted anti-oncogenic and pro-apoptosis effects in HCC cells through activation of the p38 MAPK pathway.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Mengmeng Yang,Yuxuan Lu,Shufan Jin,Wanqiu Liu,Miaoshi Yao,Zhiwei Jiang,Yachun Shu
Aim of the study This study investigated the mechanism by which the Postoperative Tongqi Formula (PTQF) treats postoperative ileus (POI) through regulation of the p38 MAPK signaling pathway, Zona occludens 1 (ZO-1) protein, and metabolism. Methods The primary components of PTQF were characterized using UHPLC-Q-TOF-MS/MS. The identified compounds subsequently employed network pharmacology to predict the signaling pathways associated with the inflammatory phase of POI. The anti-inflammatory effects of PTQF were evaluated in vitro using RAW264.7 cells. A rat model of POI was used to assess efficacy based on the spleen index and charcoal powder propulsion rat in the small intestine. Furthermore, pathological damage to the small intestine was analyzed using hematoxylin and eosin (HE) staining as well as immunofluorescence to evaluate ZO-1 protein expression. Inflammatory cytokine levels were quantified using enzyme-linked immunosorbent assay (ELISA). Subsequently, Western blot analysis was performed to examine the p38 MAPK signaling pathway. Finally, a metabolomics approach was employed to analyze serum samples to identify potential metabolic pathways. Results A total of 130 chemical constituents were identified in PTQF. Following the network pharmacology analysis of these compounds, the p38 MAPK signaling pathway was chosen for further investigation. In vitro , PTQF effectively inhibited inflammatory responses in RAW264.7 cells. Results from the spleen index and charcoal powder propulsion rate indicated that PTQF alleviated the inflammatory phase of POI in rats by mitigating systemic and intestinal inflammation. This was supported by reduced levels of inflammatory factors, modulation of ZO-1 protein expression, and a decrease in p38 MAPK phosphorylation levels. Furthermore, serum metabolomics revealed nine differential metabolites linked to intestinal inflammation. Conclusion PTQF mitigates inflammation and intestinal damage in POI rats by modulating inflammatory factors, ZO-1 protein expression, the p38 MAPK signaling pathway, and metabolic disturbances.
研究领域:
药理学
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分子生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BEHAVIOURAL BRAIN RESEARCH
·
2020
·
IF 2.977
Yuan-Jian Song,Yue Shi,Miao-Miao Cui,Man Li,Xiang-Ru Wen,Xiao-Yan Zhou,He-Qing Lou,Yu-Lan Wang,Da-Shi Qi,Man Tang,Xun-Bao Zhang
Cerebral ischemia/reperfusion (I/R) injury is a leading cause of learning and memory dysfunction. Hydrogen sulfide (H 2 S) has been shown to confer neuroprotection in various neurodegenerative diseases, including cerebral I/R-induced hippocampal CA1 injury. However, the underlying mechanisms have not been completely understood. In the present study, rats were pretreated with SAM/NaHS (SAM, an H 2 S agonist, and NaHS, an H 2 S donor) only or SAM/NaHS combined with CaM (an activator of CaMKII) prior to cerebral ischemia. The Morris water maze test demonstrated that SAM/NaHS could alleviate learning and memory impairment induced by cerebral I/R injury. Cresyl violet staining was used to show the survival of hippocampal CA1 pyramidal neurons. SAM/NaHS significantly increased the number of surviving cells, whereas CaM weakened the protection induced by SAM/NaHS. The immunohistochemistry results indicated that the number of Iba1-positive microglia significantly increased after cerebral I/R. Compared with the I/R group, the number of Iba1-positive microglia in the SAM/NaHS groups significantly decreased. Co-Immunoprecipitation and immunoblotting were conducted to demonstrate that SAM/NaHS suppressed the assembly of CaMKII with the ASK1-MKK3-p38 signal module after cerebral I/R, which decreased the phosphorylation of p38. In contrast, CaM significantly inhibited the effects of SAM/NaHS. Taken together, the results suggested that SAM/NaHS could suppress cerebral I/R injury by downregulating p38 phosphorylation via decreasing the assembly of CaMKII with the ASK1-MKK3-p38 signal module.
研究领域:
神经科学
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药理学
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神经保护
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信号转导
✓ 已验证
DOI
PubMed
高影响因子
Future Science OA
·
2025
·
IF 2.1
Chunyang Wei,Xiaoying Liu,Zhuang Miao,Hua Zhang,Yanfu Wang,Guoxian Qi
Aim The primary objective of this study is to investigate the impact of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), on the process of vascular smooth muscle cell (VSMC) senescence.Methods Rat arterial VSMCs were cultured with angiotensin II to establish a model of premature senescence. The effects of TWEAK and Fn14 on senescent VSMCs were evaluated. Additionally, the role of p38 phosphorylation pathway in the effect of TWEAK on VSMCs senescence was assessed.Results Expressions of TWEAK and Fn14 were significantly elevated in senescent VSMCs. TWEAK activated the p38 phosphorylation pathway and promoted the SA-β-gal staining and P53 expression.Conclusion These preliminary findings suggest that the TWEAK/Fn14 axis may play a crucial role in promoting VSMC senescence.
研究领域:
心血管研究
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细胞信号传导
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Li Wang,Tao Gu,Chunguang Yu,Yingying Gao,Tingting Xuan,Kaichun Shen,Guowei Wang,Zhenhai Wang
Kaempferol (Kae) is a flavonoid that has antioxidant, anti-inflammatory and neuroprotective effects. In recent years, there have been increasing reports on viral infection-induced Guillain-Barré syndrome (GBS) with high rates of disability and fatality. Therefore, in order to search for effective peripheral nerve injury repair drugs, we used rats with experimental autoimmune neuritis (EAN) as the typical animal model for GBS, and implemented Kae treatment intervention on EAN rats. Real-time quantitative polymerase chain reaction (qPCR), western blotting (WB) and immunofluorescence (IF) were utilized to detect the changes of inflammatory factors and signaling pathway proteins in peripheral nerve of rats. The impact of Kae on peripheral nerve damage in EAN rats was evaluated in multiple dimensions by clinical symptom score and neuroelectrophysiology examination, and the protective impact and mechanism of Kae on peripheral nerve injury were revealed. Our results showed that Kae increased the expression of sciatic myelin basic protein (MBP), decreased the expression of peripheral nerve macrophage infiltration and inflammatory cytokines, including TNF-α, IL-1β and IL-6, and down-regulated the expression levels of TNFR1. Additionally, it suppressed the activation of the JNK and p38 pathways. It can alleviate sciatic nerve symptoms and pathological injury in EAN rats. Therefore, we believe that Kae can be used as an adjunct drug in the treatment of GBS.
研究领域:
药理学
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神经科学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2025
·Vol. 57
·期 12
·1983
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IF 3.4
Rongjuan Wei,Tao Zhong,Ke Deng,Xianglong Zhang,Dongping Li,Meiling Chen,Ping Chang,Peng Wu,Zhanguo Liu
Gut microbiota plays an important role in orchestrating the host immune response. We previously reported that gut microbiota-derived rhamnose enhances the phagocytosis of macrophages, upon which we further asked whether rhamnose has modulatory effects on inflammation. Here, we show that, in an LPS-induced endotoxic mouse model, plasma rhamnose levels are increased. This bacteria-derived sugar alone does not impact inflammatory cytokine homeostasis or cause organ damage. In contrast, it is able to alleviate endotoxin-induced systemic inflammation and organ damage. Mechanistically, in macrophages in vitro , rhamnose binds to the V39, D40, and T101 sites of carcinoembryonic antigen-associated cell adhesion molecule 1 (CEACAM1), subsequently promoting the interaction between CEACAM1 and galectin 9 (LGALS9), which increases the protein level of dual-specificity protein phosphatase 1 (DUSP1). This inhibits p38 phosphorylation and thus attenuates the LPS-triggered expressions of proinflammatory factors. Collectively, our results suggest that rhamnose signals via the CEACAM1/LGALS9-p38 axis, which suppresses endotoxemia-associated inflammation, and that rhamnose is a candidate anti-inflammatory agent for the control of infection-induced organ damage.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2024
·
IF 2.7
Qianqian Wang,Yaqian Yang,Pengfei Li,Ruoyun Dong,Chenhao Sun,Guanling Song,Yan Wang
Titanium dioxide nanoparticles (TiO 2 NPs) can cause apoptosis in TM4 cells; however, the underlying mechanism has not been entirely elucidated. The purpose of this study was to investigate the effects of TiO 2 NPs on ROS, Ca 2+ level, p38/AKT/mTOR pathway, and apoptosis in TM4 cells and to evaluate the role of Ca 2+ in p38/AKT/mTOR pathway and apoptosis. After exposure to different concentrations (0, 50, 100, 150, and 200 μg/mL) of TiO 2 NPs for 24 h, cell viability, ROS, Ca 2+ level, Ca 2+ -ATPase activity, p38/AKT/mTOR pathway-related proteins, apoptosis rate, and apoptosis-related proteins (Bax, Bcl-2, Caspase 3, Caspase 9, and p53) were detected. The ROS scavenger NAC was used to determine the effect of ROS on Ca 2+ level. The Ca 2+ chelator BAPTA-AM was used to evaluate the role of Ca 2+ in p38/AKT/mTOR pathway and apoptosis. TiO 2 NPs significantly inhibited cell viability, increased ROS level, and elevated Ca 2+ level while suppressing Ca 2+ -ATPase activity. TiO 2 NPs regulated the p38/AKT/mTOR pathway via increasing p-p38 level and decreasing p-AKT and p-mTOR levels. TiO 2 NPs significantly enhanced the apoptosis. NAC attenuated Ca 2+ overload and reduction in Ca 2+ -ATPase activity caused by TiO 2 NPs. BAPTA-AM alleviated TiO 2 NPs-induced abnormal expression of p38/AKT/mTOR pathway-related proteins. BAPTA-AM assuaged the apoptosis caused by TiO 2 NPs. Altogether, this study revealed that TiO 2 NPs elevated intracellular Ca 2+ level through ROS accumulation. Subsequently, the heightened intracellular Ca 2+ level was observed to exert regulation over the p38/AKT/mTOR pathway, ultimately culminating in apoptosis. These results provides a complementary understanding to the mechanism of TiO 2 NPs-induced apoptosis in TM4 cells.
研究领域:
纳米技术
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细胞生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2014
·
IF 2.61
Xiaokang Zhu,Mingdong Jiang,Erqun Song,Xiaoji Jiang,Yang Song
Ultraviolet B (UVB) radiation causes oxidative damage and inflammation, and ultimately increases the risk of skin carcinogenesis. Selenium is an essential trace element, previous studies indicated selenium deficiency impairs tissue antioxidant capacity in different experimental models. However, the synergistic effect of selenium deficiency and UVB radiation on skin damage is not clear. In the current study, our data revealed selenium deficiency resulted in further increases of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS) and phosphorylated H2AX levels, decreases of GSH level and antioxidant enzyme activities in UVB-irradiated mice. Selenium deficiency also exacerbated UVB-induced cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 mRNA expressions. Mechanism studies indicated that UVB-induced p38 signaling was further elevated in the skin of mice maintained with selenium deficiency diet, compared with those maintained with selenium adequate diet. Our investigation suggested that selenium deficiency diet weakens the antioxidant capacity of UVB-irradiated mice skin, which sensitizes to UV radiation-induced oxidative damage and inflammation.
研究领域:
皮肤病学
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分子生物学
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营养学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL SCIENCES
·
2022
·
IF 3.578
Qingxin Song,Shanxin Peng,Fengyuan Che,Xiaosong Zhu
Ferroptosis is implicated in various tumors, including glioblastoma. Artesunate (ART), an anti-malarial drug, exerted antitumor properties in several cancer types. However, the role of ferroptosis in the inhibiting effect of artesunate on glioblastoma remains unclear. The purpose of this study was to investigate the effects of ART on the ferroptosis of glioblastoma and to elucidate the underlying mechanisms. We found that ART inhibited the proliferation of glioblastoma cells in vitro and glioblastoma tumorigenesis in vivo . Characteristic changes of ferroptosis were observed in ART group, including GSH depletion, lipid peroxidation and iron overload. Meanwhile, the protein level of GPX4 were lower in ART group than that in control group. Ferrostatin-1, a ferroptosis inhibitor, could rescue the cell death induced by ART in U251 cells. Further examination of the mechanism revealed that the effect of ART on ferroptosis was partially governed by regulating iron homeostasis and p38 and ERK signaling pathway. These findings support that ART triggers ferroptosis in glioblastoma and might be a potential therapeutic agent for glioblastoma treatment.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Zheng Zhao,Xue Yang
Paraquat (PQ) poisoning leads to irreversible fibrosis in the lungs with high mortality and no known antidote. In this study, we investigated the effect of the SET and MYND domain containing 2 (SMYD2) on PQ-induced pulmonary fibrosis (PF) and its potential mechanisms. We established an in vivo PQ-induced PF mouse model by intraperitoneal injection of PQ (20 mg/kg) and in vitro PQ (25 μM)-injured MLE-12 cell model. On the 15th day of administration, tissue injury, inflammation, and fibrosis in mice were evaluated using various methods including routine blood counts, blood biochemistry, blood gas analysis, western blotting, H&E staining, ELISA, Masson staining, and immunofluorescence. The findings indicated that AZ505 administration mitigated tissue damage, inflammation, and collagen deposition in PQ-poisoned mice. Mechanistically, both in vivo and in vitro experiments revealed that AZ505 treatment suppressed the PQ-induced epithelial-mesenchymal transition (EMT) process by downregulating GLI pathogenesis related 2 (GLIPR2) and ERK/p38 pathway. Further investigations demonstrated that SMYD2 inhibition decreased GLIPR2 methylation and facilitated GLIPR2 ubiquitination, leading to GLIPR2 destabilization in PQ-exposed MLE-12 cells. Moreover, rescue experiments conducted in vitro demonstrated that GLIPR2 overexpression eliminated the inhibitory effect of AZ505 on the ERK/p38 pathway and EMT. Our results reveal that the SMYD2 inhibitor AZ505 may act as a novel therapeutic candidate to suppress the EMT process by modulating the GLIPR2/ERK/p38 axis in PQ-induced PF.
研究领域:
药理学
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毒理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Marine Drugs
·
2022
·Vol. 20
·期 2
·110
·
IF 6.085
Chunlei Li,Sirui Zhang,Jianhua Zhu,Weijuan Huang,Yuanyuan Luo,Hui Shi,Dongbo Yu,Liguo Chen,Liyan Song,Rongmin Yu
Colorectal carcinoma (CRC) is one of the major causes of cancer-related incidence and deaths. Here, we identified a novel antitumor peptide, P6, with a molecular weight of 2794.8 Da from a marine Chinese medicine,Arca inflataReeve. The full amino acid sequence and secondary structure of P6 were determined by tandem mass de novo sequencing and circular dichroism spectroscopy, respectively. P6 markedly inhibited cell proliferation and colony formation, and induced apoptosis in CRC cells. Mechanistically, transcriptomics analysis and a serial functional evaluation showed that P6 induced colon cancer cell apoptosis through the activation of the p38-MAPK signaling pathway. Moreover, it was demonstrated that P6 exhibited antitumor effects in a tumor xenograft model, and induced cell cycle arrest in CRC cells in a concentration-dependent mode. These findings provide the first line of indication that P6 could be a potential therapeutic agent for CRC treatment.Keywords:Arca inflata;antitumor peptide;apoptosis;MAPK signaling;calmodulin;colorectal cancer
研究领域:
肿瘤学
·
药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2020
·
IF 3.723
Meihui Chen,Dan Luo,Jiheng Zhan,Yu Hou,Shudong Chen,Xing Li,Dingkun Lin
Bone mesenchymal stem cells (BMSCs) are a well-known donor graft source due to their potential for self-renewal and differentiation into multi-lineage cell types, including osteoblasts that are critical for fracture healing. Fasudil (FAS), a Rho kinase inhibitor, has been proven to induce the differentiation of bone marrow stem cells (BMSCs) into neuron-like cells. However, its role in the osteogenesis of BMSCs remain uncertain. Herein, we for the first time studied the effects of FAS on osteogenic differentiation in a mouse fracture model and further explored the involved mechanisms in mouse BMSCs. The results showed that FAS stimulated bone formation in the fracture mouse model. Additionally, at 30 μM, FAS significantly promotes alkaline phosphatase activity, mineralization, and the expression of osteogenic markers COL-1, RUNX2 and OCN in murine BMSCs. Blocking of P38 by SB202190 significantly reversed the effects of FAS, in vitro, suggesting that P38, but not ERK or JNK activation is required for FAS-induced osteogenesis. Collectively, our results indicate that FAS may be a promising agent for promoting fracture healing.
研究领域:
干细胞生物学
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药理学
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骨科学
✓ 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）