BONE
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2025
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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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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2023
·Vol. 52
·期 6
·1-11
·
IF 5.4
Su-Ji Jeon,Eun-Young Choi,Eun-Ji Han,Sang-Woo Lee,Jun-Mo Moon,Soo-Hyun Jung,Ji-Youn Jung
Piperlongumine (PL) is an amide alkaloid with diverse pharmacological effects against cancer, bronchitis and asthma; however, research on its efficacy against melanoma is lacking. The present study investigated the anticancer effects of PL on A375SM and A375P human melanoma cells. PL decreased the survival rate of A375SM and A375P cells, as shown by MTT assay, increase of apoptotic cells by DAPI staining. And PL induced apoptosis by decreasing the expression of the anti‑apoptotic protein Bcl‑2 and increasing that of the pro‑apoptotic proteins cleaved‑PARP and Bax. PL also induced apoptosis in A375SM and A375P cells via the MAPK pathway, increasing expression of the MAPK pathway proteins, phosphorylated‑(p‑ERK), p‑JNK p‑p38. These proteins were confirmed by western blot. In addition, A375SM and A375P cells treated with PL showed an increased number of acidic vesicular organelles by acridine orange staining. Also, autophagy induced by the expression of 1A/1B‑light chain 3, Beclin 1and mTOR was investigated through western blot. When PL was applied following treatment with autophagy inhibitors 3‑methyladenine and hydroxychloroquine, autophagy exhibited a cytoprotective effect against apoptosis in MTT assay. Pretreatment of A375P cells with the ERK inhibitor PD98059 and the JNK inhibitor SP600125 followed by treatment with PL confirmed that apoptosis and autophagy were mediated via the MAPK/ERK pathway by western blot. In summary, the present study provided empirical evidence supporting the anticancer effects of PL on human melanoma cells and indicated the potential of PL as a treatment for melanoma.
研究领域:
肿瘤学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
Lipids in Health and Disease
·
2025
·Vol. 24
·期 1
·1-15
·
IF 4.2
An He,Cheng Dong-liang,Xia Xian-ru,Li Xian-dong,Ruan Zhi-hua,Peng Chun-yan
Background Dyslipidemia has been extensively documented as a key driver of cardiovascular pathology. Regulating lipid homeostasis holds promise for treating atherosclerosis (AS). Although the protein phosphatase 2 catalytic subunit beta (PPP2CB) is involved in post-transcriptional gene regulation, its role in AS-associated dyslipidemia is not well understood. Methods The study included both human participants and animal models. The following techniques were employed: cell culture, extraction of exosomes, preparation of pooled hyperlipidemic serum (HS), transfection, western blotting, immunofluorescence staining, quantitative reverse transcription polymerase chain reaction (qRT-PCR), co-immunoprecipitation, low-density lipoprotein cholesterol (LDL-C) uptake assay, biochemical assays, assessment of aortic atherosclerotic lesions, as well as statistical analysis. Results This study identified a marked upregulation of PPP2CB expression in peripheral blood leukocytes of AS patients, artery plaque of ApoE −/− mice given a high-fat diet, and hepatic cells exposed to hyperlipidemic stimuli. Overexpression of PPP2CB in hepatic cells exacerbated lipid accumulation and low-density lipoprotein uptake, whereas silencing PPP2CB mitigated this effect. Immunofluorescence co-localization and co-immunoprecipitation analysis confirmed a direct interaction between PPP2CB and lectin-like oxidized LDL receptor-1 (LOX-1). Notably, PPP2CB manipulation disrupted hyperlipidemia-induced LOX-1 expression. Additionally, PPP2CB-mediated lipid dysregulation was linked to the activation of the LOX-1/ mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) signaling cascade. Conclusions These results unveil PPP2CB as a novel lipid regulator in the progression of pathological AS and highlight its involvement in signaling regulation during abnormal lipid metabolism. PPP2CB could be considered a promising candidate for biomarker development and therapeutic intervention in AS.
研究领域:
生物学
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医学
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药理学
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DOI
PubMed
高影响因子
Cell Death & Disease
·
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
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肝脏研究
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DOI
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 16
·6014
·
IF 4.6
Shanbin Chen,Dong Zhao,Chunguang Luan,Jia Zheng,Wei Liu,Zheng Feng,Ruiqi Luo,Xinglin Han,Deliang Wang
Ferulic acid (FA) is a bioactive compound found in traditional Chinese herbal medicine; for example, it is present in Xinjiang Ferula, but also in strong-flavor Chinese baijiu. FA has been shown to play a crucial role in treating oxidative stress, skin whitening, and eye diseases. In this study, the potential role of FA as a means of inducing apoptosis and inhibiting colon cancer induced by the transplantation of CT26 cells was investigated. The results show that FA adjuvant treatment caused an upregulation in the expression of genes related to autophagy while simultaneously suppressing the expression of inflammatory response elements and improving the bodyweight, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST) in vivo. Furthermore, FA inhibited the proliferation of CT26 cells and induced apoptosis, specifically by activating the phosphorylation of ERK and JNK to enhance the essential proteins BCL-2 and BAX in the apoptosis pathway. These results suggest that FA could be a promising auxiliary therapeutic agent for the treatment of colon cancer. Further research is needed to better understand the mechanisms underlying the beneficial effects of FA and its synergistic effects with other compounds.Keywords:ferulic acid;apoptosis;autophagy;MAPK pathway
研究领域:
药理学
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肿瘤学
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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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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
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分子生物学
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药物学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
·
2025
·
IF 3.8
Jiajia Chen,Huanle Liu,Yanfang Fu,Xiaolan Chen,Shiqin Zhang,Yongqi Yang,Shengwen Li,Guixiang Wang,Tian Lan
Background Chronic liver inflammation is a major cause of death in patients with liver fibrosis and cirrhosis, which pose a serious health threat worldwide, and there is no effective anti-hepatic fibrosis drug. Kaempferol (KA), a flavonoid polyphenol extracted from many edible plants and traditional Chinese medicine, has been reported to possess anti-inflammatory, antioxidant, and antitumor activities and has an ameliorating effect on liver fibrosis or other fibroproliferative diseases. However, the specific regulatory mechanism of KA-reversed macrophage M1 polarization is still obscure. This study aimed to investigate the protective effects of KA on carbon tetrachloride (CCl 4 )-induced liver fibrosis in mice through M1 polarization. Methods C57BL/6 mice were intraperitoneally injected with CCl 4 twice weekly to induce liver fibrosis. Male mice were randomly divided into four groups (n = 5): the oil group, the CCl 4 group, the low-dose KA-treatment CCl 4 group (50 mg/kg/d KA), and the high-dose KA-treatment CCl 4 group (100 mg/kg/d KA). An equal amount of solvent was given to each group by intraperitoneal injection. Results The results indicated that KA decreased liver pathologic changes, hepatic macrophage recruitment, and serum alanine aminotransferase (ALT) levels. Notably, it reduced the activation of M1-type macrophages in the liver. The expression of proinflammatory cytokines and genes associated with M1 macrophages, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and inducible nitric oxide synthase (iNOS), was also decreased. The core targets, signaling pathways, and possible mechanisms related to the M1 polarization of KA were analyzed by network pharmacology and molecular docking. Further analysis revealed that KA regulated MAPK/NF-κB signaling pathways. Finally, the results indicated that KA regulates M1 macrophage activation by modulating the MAPK/NF-κB signaling pathways. Conclusions This study revealed that KA ameliorated liver injury, inflammation, and fibrosis by inhibiting macrophage M1 polarization through the MAPK/NF-ҡB signaling pathway, highlighting KA as a potential novel agent for the prevention and treatment of liver fibrosis.
研究领域:
药理学
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肝脏病学
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分子生物学
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DOI
PubMed
高影响因子
CTS-Clinical and Translational Science
·
2020
·Vol. 14
·期 5
·2075-2084
·
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
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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
·
药理学
·
细胞生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Ruoting Xian,Hongyi Xian,Hao Dong,Jiating Lin,Xianxian Zhuang,Yue Zou,Qinkai Xie,Youde Liang,Shaobing Li
Repair and regeneration of oral and maxillofacial tissue defects remain significant challenges, mainly due to the limitations of existing treatment approaches. Conventional methods such as transplantation, tissue scaffolds, growth factors, and stem cell therapies often face obstacles, including donor shortages, insufficient vascularization, and safety concerns. There is an urgent need for innovative therapeutic strategies to effectively promote vascular regeneration while minimizing complications. Black phosphorus nanosheets (BPNSs) and hydrogels present significant advantages and broad application potential as tissue regeneration carriers due to their biocompatibility, degradability, and controlled drug release properties. By combining various characterization techniques and detection methods, we conducted a thorough analysis of BPNSs and gelatin methacryloyl (GelMA) scaffolds loaded with BPNSs (BP-GelMA). The results indicate that this study successfully prepared BPNSs with uniform size, good dispersion, and intact structure. Moreover, the BP-GelMA composite demonstrated excellent swelling behavior and structural stability while effectively enabling the controlled release of BPNSs. This study investigated the angiogenic effects of BP-GelMA at concentrations of 0, 12.5, and 25.0 μg/mL. In vitro experiments showed that BP-GelMA significantly enhanced endothelial cell proliferation, migration, and tube formation. In vivo results demonstrated that 12.5 μg/mL and 25.0 μg/mL BP-GelMA did not induce significant developmental toxicity in zebrafish and effectively promoted neovascularization. RNA-Seq analysis revealed that BP-GelMA activates angiogenesis-related biological processes. Mechanistic studies identified PEAK1 as a central regulator, driving vascular formation through activation of the MAPK signaling pathway. These findings highlight the potential of BP-GelMA as a therapeutic strategy for promoting angiogenesis and underscore the importance of optimizing BP-GelMA concentrations to achieve maximum therapeutic efficacy and safety in clinical applications.
研究领域:
生物材料学
·
再生医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）