Cell Death & Disease
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2022
·Vol. 13
·期 9
·1-9
·
IF 9.685
Bi Jianbin,Zhang Jia,Ke Mengyun,Wang Tao,Wang Mengzhou,Liu Wuming,Du Zhaoqing,Ren Yifan,Zhang Shuqun,Wu Zheng,Lv Yi,Wu Rongqian
Heat shock proteins (HSPs) depletion and protein misfolding are important causes of hepatocyte death and liver regeneration disorder in liver injury. HSF2BP, as its name implies, is a binding protein of HSF2, but the specific role of HSF2BP in heat shock response (HSR) remains unknown. The aim of this study is to identify the role of HSF2BP in HSR and acute liver injury. In this study, we found that HSF2BP expression increased significantly within 24 h after APAP administration, and the trend was highly consistent with that of HSP70. hsf2bp - KO and hsf2bp - TG mouse models demonstrated HSF2BP reduced hepatocyte death, ameliorated inflammation, and improved liver function in APAP- or D-GalN/LPS- induced liver injury. Meanwhile, a significant increase of the survival rate was observed in hsf2bp - TG mice after APAP administration. Further studies showed that HSF2BP upregulated the expression of HSF2 and HSP70 and inhibited the activation of Jnk1/2 and P38 MAPK. Additionally, HSP70 siRNA pretreatment abolished the effect of HSF2BP on the MAPK pathway in APAP-treated hepatocytes. The results reveal that HSF2BP is a protective factor in acute liver injury, and the HSF2BP/HSP70/MAPK regulatory axis is crucial for the pathogenesis of liver injury. HSF2BP is a potential therapeutic target for liver injury.
研究领域:
分子生物学
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医学
·
肝脏研究
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DOI
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2017
·Vol. 233
·期 9
·6714-6721
·
IF 4.08
Haihong Zhou,Congli Jin,Lili Cui,Huaijie Xing,Jun Liu,Wang Liao,Haojie Liao,Yangsheng Yu
This study aimed to investigate whether HMGB1 (high mobility group box-1 protein) and receptor for advanced glycation end products (RAGE) were involved in the irradiation-induced endothelial barrier damage and their mechanism. We constructed the damage model of endothelium barrier model with bEnd.3 cells. The permeability of endothelial barrier was detected by sodium fluorescein (Na-F) permeation test, and the irradiation dose which could induce permeability transition was determined by being exposed to different irradiation doses (5, 10, 15, 20 Gy). MTT assay was applied to detect cell viability under different concentrations of HMGB1 , glycyrrhizic acid (GA, a specific inhibitor of HMGB1 ), and FPS-ZM1 (a blood-brain-barrier permeant blocker of RAGE V domain-mediated ligand binding). The expression of HMGB1 , RAGE, and related molecules involved in MAPK signaling pathway, MMP-2, MMP-9, ZO-1, and claudin 5 of differently treated groups were measured by qRT-PCR, western blot, and immunofluorescence. Cells possessed stable endothelial barrier function on 4–7 days after seeded on transwell plates. The permeability of endothelial barrier would change under at least 10 Gy radiation. Both radiation and HMGB1 treatment alone could improve the permeability. After irradiation, the expressions of HMGB1 and RAGE increased and MAPK signal pathway was activated. Meanwhile, MMP-2 and MMP-9 were overexpressed, while the expression of tight junction proteins ZO-1 and claudin 5 was decreased. Radiation could activate MAPK signaling pathway through promoting the expression of HMGB1 and RAGE, which further led to endothelial barrier injury and changed its permeability.
研究领域:
细胞生物学
·
分子生物学
·
医学研究
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产品关联
DOI
PubMed
高影响因子
BONE
·
2025
·
IF 3.6
Zhen Guo,Yiwen Huang,Xiaowei Wang,Yi Han,Ang Li,Yiyang Qu,Lin Chen,Meihang Du,Yiming Zhang,Yuanzhi Xu
The accumulation of reactive oxygen species (ROS) within cells regulates the formation and function of osteoclasts, which is crucial therapeutic target for the treatment of osteoporosis. Ergothioneine (EGT) is a rare amino acid with strong antioxidant and anti-inflammatory properties. However, its application on osteoporosis has not been reported. In this study, we investigated the effects of EGT on osteoclastogenesis in vitro and in ovariectomized (OVX) mice. The results revealed that EGT could suppress RANKL-induced podosome belt formation and osteoclast development in vitro, while reducing intracellular ROS levels by upregulating key antioxidant enzymes, including HO-1 and Catalase. EGT was also found to downregulate the expression of critical osteoclast-specific proteins such as Trap, c-Fos, and Ctsk through attenuation of MAPK signaling. The potential of EGT to protect against trabecular bone loss in OVX mice was further demonstrated by micro-CT imaging, possibly by reducing osteoclast numbers shown by histological outcomes. These findings together highlighted the potential value of EGT as a novel tool for treating osteoporosis through its ability to suppress osteoclastogenesis and mitigate the accumulation of intracellular ROS.
研究领域:
医学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Biomedicines
·
2023
·Vol. 11
·期 9
·2442
·
IF 4.7
Eun-Young Choi,Eun-Ji Han,Su-Ji Jeon,Sang-Woo Lee,Jun-Mo Moon,Soo-Hyun Jung,Ji-Youn Jung
Oral cancer is a malignant tumor that primarily affects areas such as the lips, tongue, buccal mucosa, salivary gland, and gingiva and has a very high malignancy. Piperlongumine (PL), isolated from long pepper (Piper longumL.), is a natural alkaloid with pharmacological effects, such as anti-inflammatory and anti-atherosclerotic effects. The effect and mechanism of PL in oral cancer cell lines has not been explored. Therefore, this study aimed to investigate the mechanism of anticancer effects of PL in the human oral cancer cell lines MC-3 and HSC-4 in vitro. This study demonstrated that PL inhibits cell proliferation by inducing apoptosis and autophagy in human oral cancer cell lines, which was confirmed by the levels of apoptosis- and autophagy-related proteins through Western blotting. Moreover, the pharmacological blockade of autophagy activation by hydroxychloroquine (HCQ), an autophagy inhibitor, significantly improved PL-induced apoptosis in MC-3 cells, suggesting a cytoprotective effect. In addition, activation of the mitogen-activated protein kinase (MAPK) signaling pathway contributed to PL-induced apoptosis. Collectively, the study suggested that combining an autophagy inhibitor with PL treatment can exert effective anticancer properties in oral cancer cells by inducing apoptosis and cytoprotective autophagy via the JNK-mediated MAPK pathway.Keywords:piperlongumine;oral cancer;apoptosis;autophagy;MAPK pathway;anti-cancer agent
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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DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 9
·3687
·
IF 4.6
Changli Fu,Mingjin Wang,Yuan Lu,Jie Pan,Yueting Li,Yongjun Li,Yonglin Wang,Aimin Wang,Yong Huang,Jia Sun,Chunhua Liu
AlthoughPolygonum orientaleL. (PO) has a beneficial effect on treatment of myocardial ischemia (MI), its mechanism remains unclear. This study aimed to explore the pharmacological mechanism of PO against MI through MAPK signaling pathways. Firstly, the therapeutic effect of PO was evaluated for treatment of MI mice. Using Western blot and immunohistochemistry, the influence of PO on MAPK signaling pathways and cell apoptosis was investigated. Subsequently, one key pathway (ERK) of MAPK signaling pathways was screened out, on which PO posed the most obvious impact. Finally, an inhibitor of ERK1/2 was utilized to further verify the regulatory effect of PO on the MAPK/ERK signaling pathway. It was found that PO could reduce the elevation of the ST segment; injury of heart tissue; the activity of LDH, CK, NOS, cNOS and iNOS and the levels of NO, BNP, TNF-α and IL-6. It is notable that PO could significantly modulate the protein content of p-ERK/ERK in mice suffering from MI but hardly had an effect on p-JNK/JNK and p-p38/p38. Additionally, the expressions of bax, caspase3 and caspase9 were inhibited in heart tissue in the PO-treated group. To evaluate whether ERK1/2 inhibitor (PD98059) could block the effect of PO on treatment of MI, both PO and PD98059 were given to mice with MI. It was discovered that the inhibitor indeed could significantly reverse the regulatory effects of PO on the above indicators, indicating that PO could regulate p-ERK/ERK. This study provides experimental evidence that PO extenuates MI injury, cardiomyocyte apoptosis and inflammation by activating the MAPK/ERK signaling pathway.Keywords:Polygonum orientaleL.;myocardial ischemia;MAPK signaling pathway
研究领域:
药理学
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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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
·
营养学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Sun Xiaoxi,Huang Bing,Pan Yuping,Fang Jinhua,Wang Hefeng,Ji Yanru,Ling Yingchen,Guo Pei,Lin Jiangguo,Li Quhuan,Fang Ying,Wu Jianhua
Activation of integrins is crucial for recruitment of flowing leukocytes to inflammatory or injured vascular sites, but their spatiotemporal characteristics are incompletely understood. We discovered that β2-integrin activation over the entire surface of neutrophils on immobilized P-selectin occurred via mitogen-activated protein kinase (MAPK) or non-MAPK signaling with a minute-level timescale in a force-dependent manner. In flow, MAPK signaling required intracellular Ca2+ release to activate integrin within 2 min. Integrin activation via non-MAPK signaling occurred first locally in the vicinity of ligated P-selectin glycoprotein ligand-1 (PSGL-1) within sub-seconds, and then over the entire cell surface within 1 min in an extracellular Ca2+ influx-dependent manner. The transition from a local (but rapid) to global (but slow) activation mode was triggered by ligating the freshly activated integrin. Lipid rafts, moesin, actin, and talin were involved in non-MAPK signaling. Fluid loads had a slight effect on local integrin activation with a second-level timescale, but served as enhancers of global integrin activation.
研究领域:
免疫学
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细胞生物学
·
生物物理学
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产品关联
DOI
PubMed
高影响因子
Cell Reports
·
2025
·
IF 6.9
Zaoqu Liu,Yuhao Ba,Dan Shan,Xing Zhou,Anning Zuo,Yuyuan Zhang,Hui Xu,Shutong Liu,Benyu Liu,Yanan Zhao,Siyuan Weng,Ruizhi Wang,Jinhai Deng,Peng Luo,Quan Cheng,Xin Hu,Shuaixi Yang,Fubing Wang,Xinwei Han
Cancer-associated fibroblasts (CAFs) display significant functional and molecular heterogeneity within the tumor microenvironment, playing diverse roles in cancer progression. Employing single-cell RNA sequencing data of colorectal cancer (CRC), we identified a subset of matrix CAFs (mCAFs) as a critical subtype that secretes THBS2, a molecule linked to advanced cancer stages and poor prognosis. Spatial transcriptomics and multiplex immunohistochemistry revealed clear spatial colocalization between THBS2-producing mCAFs and tumor cells. Mechanically, CAF-secreted THBS2 binds to CD47 on tumor cells, triggering the MAPK/ERK5 signaling pathway, which enhances tumor progression. The tumor-promoting role of THBS2 was further validated using fibroblast-specific THBS2 knockout mice, patient-derived organoids, and xenografts. Moreover, the transcription factor CREB3L1 was identified as a regulator of the transformation of normal fibroblasts into THBS2-producing mCAFs. These findings underscore the pivotal role of THBS2 in CRC progression and highlight the therapeutic potential of targeting the THBS2-CD47 axis and CREB3L1 in CRC.
研究领域:
肿瘤学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2025
·
IF 4.3
Jinhua Yan,Chenxi Feng,Hanmei Zhang,Ting Luo,Haiyang Chen,Haiou Chen
Introduction Intestinal stem cells (ISCs) possess the ability to self-renew and differentiate, which is essential for maintaining intestinal tissue homeostasis. However, their functionality significantly declines with age, leading to diminished tissue regeneration and an increased risk of age-associated diseases. Methods This study investigates the effects of Dapagliflozin (DAPA), a novel insulin sensitizer and SGLT2 inhibitor, on aging ISCs using the Drosophila melanogaster model. Our findings demonstrate that DAPA can inhibit the MAPK signaling pathway, as confirmed by network pharmacology analysis and molecular docking experiments. Results DAPA ameliorates ISC aging, improves intestinal function (including enhanced fecal excretion, restored intestinal barrier integrity and acid-base balance), and enhances healthspan. These results highlight the potential of DAPA as an anti-aging therapeutic agent. Discussion This study provides new evidence for the application of DAPA as an anti-aging treatment.
研究领域:
细胞生物学
·
分子生物学
·
药物学
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产品关联
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
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Genetics
·
2023
·
IF 3.7
Bin Wang,Yukun Wang,Xiao Yuan,Yuanyuan Jiang,Yunna Zhu,Xinmiao Kang,Jinming He,Yanhui Xiao
Planting aromatic plant might be a promising strategy for safely utilizing heavy metal (HM)-contaminated soils, as HMs in essential oil could be completely excluded using some special technologies with ease. Clove basil ( Ocimum gratissimum L.) is an important aromatic plant used in essential oil production. Improving cadmium (Cd) tolerance in clove basil can increase its production and improve the utilization efficiency of Cd-contaminated soils. However, the lack of genomic information on clove basil greatly restricts molecular studies and applications in phytoremediation. In this study, we demonstrated that high levels of Cd treatments (0.8, 1.6 and 6.5 mg/L) significantly impacted the growth and physiological attributes of clove basil. Cd contents in clove basil tissues increased with treatment concentrations. To identify Cd stress-responsive genes, we conducted a comparative transcriptomic analysis using seedlings cultured in the Hoagland’s solution without Cd ion (control) or containing 1.6 mg/L CdCl 2 (a moderate concentration of Cd stress for clove basil seedlings). A total of 104.38 Gb clean data with high-quality were generated in clove basil under Cd stress through Illumina sequencing. More than 1,800 differential expressed genes (DEGs) were identified after Cd treatment. The reliability and reproducibility of the transcriptomic data were validated through qRT-PCR analysis and Sanger sequencing. KEGG classification analysis identified the “MAPK signaling pathway,” “plant hormone signal transduction” and “plant-pathogen interaction” as the top three pathways. DEGs were divided into five clusters based on their expression patterns during Cd stress. The functional annotation of DEGs indicated that downregulated DEGs were mainly involved in the “photosynthesis system,” whereas upregulated DEGs were significantly assigned to the “MAPK signaling pathway” and “plant-pathogen interaction pathway.” Furthermore, we identified a total of 78 transcription factors (TFs), including members of bHLH, WRKY, AP2/ERF, and MYB family. The expression of six bHLH genes, one WRKY and one ERF genes were significantly induced by Cd stress, suggesting that these TFs might play essential roles in regulating Cd stress responses. Overall, our study provides key genetic resources and new insights into Cd adaption mechanisms in clove basil.
研究领域:
植物学
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环境科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2023
·
IF 5.3
Jing Zhao,Meini Le,Jie Li,Qiong Huang,Haocong Chen,Wenyi Zhang,Huiwen Mao,Qing Sun,Aiguo Li,Yingmin Zhao,Lingling Yu,Mingjiang Yi,Jie Wang,Xinyuan Li,Guangming Zhang,Jun Ma,Xiaohua Dong
Hypoxic-ischemic encephalopathy (HIE) is an important factor leading to permanent damage of central nervous system (CNS) and even neonatal death . Long non-coding RNAs (lncRNAs) has been shown to get involved in the pathogenesis of nervous system diseases . LINC00938 is an intergenic lncRNA which is reported to be involved in neurodegenerative disease . However, the potential role of LINC00938 in nerve injury of neonatal HIE is undetermined. Here, we found that the expression of LINC00938 in the whole blood of neonates with HIE was downregulated compared with the non-HIE group. Functional study revealed that the expression of LINC00938 was significantly decreased in oxygen-glucose deprivation (OGD)-induced SH-SY5Y. Knockdown of LINC00938 induced the neural cell apoptosis by increased the protein level of Bax, Cleaved-Caspase3 and decreased the expression of Bcl-2. In addition, overexpression of LINC00938 prevented the apoptosis of SH-SY5Y from OGD injury. RNA-seq analysis showed that MAPK signaling was involved in the anti-apoptosis function of LINC00938. LINC00938 knockdown induced the activation of c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and inhibited the activation of ERK signaling. However, LINC00938 play neuroprotective role in OGD-induced SH-SY5Y by suppression the phosphorylation of JNK and p38 MAPK rather than regulation of ERK signaling pathway . Further analyses illustrated that the cell apoptosis of neuronal cell was dependent on the elevation of reactive oxygen species (ROS) and result in mitochondria dysfunction in LINC00938 knockdown SH-SY5Y. Pretreated with ROS inhibitor N -acetylcysteine amide (NACA) dramatically suppressed LINC00938 knockdown induced oxidative stress and mitochondria dysfunction which induced cell apoptosis. In addition, NACA treatment significantly reduced the expression of p-JNK and p-p38 in OGD-induced SH-SY5Y. Furthermore, overexpression of LINC00938 displayed a notably neuroprotective effect by suppress central nervous system cell apoptosis via alleviating oxidative stress in CoCl 2 -induced hypoxic HIE model of zebrafish. Taken together, these results suggested that LINC00938 can act as a neuroprotective factor to inhibit oxidative stress and apoptosis of CNS under HIE conditions.
研究领域:
神经科学
·
分子生物学
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儿科
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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）