INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yan-Xia Li,Zhong-Fei Zhang,Yu-Meng Wu,Le Shi,Hui-Xian Shen,Navindra P. Seeram,Hang Ma,Yong-Ming Lu
Ashwagandha ( Withania somnifera ) is a well-known medicinal plant, with polysaccharides recognized as key bioactive constituents. In this study, we isolated a neutral polysaccharide, AP-1, from ashwagandha roots and elucidated its structure. AP-1 has a molecular weight of 9.21 kDa and is primarily composed of mannose, glucose, and galactose in a molar ratio of 0.1:1.5:1. Spectroscopic analyses revealed that AP-1's backbone consists of 1,4-α-Glc p and 1,3-α-Gal p , with branching at the C-6 of 1,4,6-α-Glc p and C-4 of 1,3,4-α-Gal p positions. The immunostimulatory activity of AP-1 was evaluated in murine macrophage RAW264.7 cells. AP-1 significantly enhanced macrophage immune responses, promoted M1-type polarization, and activated the NF-κB signaling pathway. It increased the production and mRNAs expression of pro-inflammatory mediators including nitric oxide, oxygen species, tumor necrosis factor, interleukins-1β and -6, and upregulated the M1 surface biomarker CD86. These findings highlight the potential of AP-1 as a promising bioactive ingredient for functional foods targeting immune enhancement.
研究领域:
药用植物学
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免疫学
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生物化学
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DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2023
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IF 7.31
Hongwei Shi,Liang Duan,Ying Lan,Quan He,Peng Pu,Heng Tang
Pirarubicin (THP) is one of the classic chemotherapy drugs for cancer treatment. It is often clinically limited because of its cardiotoxicity. The occurrence and development of THP-mediated chemotherapy-related cardiotoxicity (CRC) may be reversed by RING finger protein 10 (RNF10). This study was performed with the aim of evaluating the inhibitory effect of RNF10 on THP-mediated CRC and its molecular mechanism. In vivo, we found that the expression of RNF10 decreased in THP-induced CRC rats, accompanied by Meox2 inhibition and AP-1 activation, resulting in increased cardiomyocyte apoptosis. After small interfering RNA (siRNA) and lentivirus transfection (Lv) of RNF10 in vitro, the expression of RNF10, Meox2, and AP-1 proteins and the degree of cardiomyocyte apoptosis were detected. We found that overexpression of RNF10 in H9C2 cardiomyocytes significantly promoted Meox2 and inhibited AP-1, alleviated apoptosis, and showed further inhibitory activity on THP-induced cardiomyocyte toxicity. Silencing RNF10 showed the opposite result. Our study showed that RNF10 inhibited THP-induced CRC through the activity of Meox2 and AP-1 proteins. RNF10 may be the next drug target for the treatment of CRC and other related cardiovascular diseases.
研究领域:
肿瘤学
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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
TOXICOLOGY LETTERS
·
2022
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IF 4.271
Yishuang Luo,Jinyu Kang,Jia Luo,Zheng Yan,Shengtao Li,Zhuoheng Lu,Yufei Song,Xie Zhang,Julin Yang,Aiming Liu
The development of cholestatic liver injury (CLI) involves inflammation, but the dominant pathway mediating the chemotaxis is not yet established. This work explored key signaling pathway mediating chemotaxis in CLI and the role of Kupffer cells in the inflammatory liver injury. Probe inhibitors T-5224 (100 mg/kg) for AP-1 and C188–9 (100 mg/kg) for STAT3 were used to validate key inflammatory pathways in alpha-naphthylisothiocyanate (ANIT, 100 mg/kg)-induced CLI. Two doses of GdCl 3 (10 mg/kg and 40 mg/kg) were used to delete Kupffer cells and explore their role in CLI. Serum and liver samples were collected for biochemical and mechanism analysis. The liver injury in ANIT-treated mice were significantly increased supported by biochemical and histopathological changes, and neutrophils gathering around the necrotic loci. Inhibitor treatments down-regulated liver injury biomarkers except the level of total bile acid . The chemokine Ccl2 increased by 170-fold and to a less degree Cxcl2 by 45-fold after the ANIT treatment. p-c-Jun and p-STAT3 were activated in the group A but inhibited by the inhibitors in western blot analysis . The immunofluorescence results showed AP-1 not STAT3 responded to inhibitors in ANIT-induced CLI. With or without GdCl 3 , there was no significant difference in liver injury among the CLI groups. In necrotic loci in CLI, CXCL2 colocalized with hepatocyte biomarker Albumin, not with the F4/80 in Kupffer cells. Conclusively, AP-1 played a more critical role in the inflammation cascade than STAT3 in ANIT-induced CLI. Hepatocytes, not the Kupffer cells released chemotactic factors mediating the chemotaxis in CLI.
研究领域:
肝病学
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免疫学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
NEUROTOXICITY RESEARCH
·
2016
·Vol. 31
·期 2
·259-268
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IF 3.14
Zhang Yaqiong,Gao Lingyue,Cheng Zhihua,Cai Jiayi,Niu Yixuan,Meng Weihong,Zhao Qingchun
Impaired hippocampal neurogenesis and neuroinflammation are involved in the pathogenesis of radiation-induced brain injury. Kukoamine A (KuA) was demonstrated to have neuroprotective effects through inhibiting oxidative stress and apoptosis after whole-brain irradiation (WBI) in rats. The aim of this study was to investigate whether administration of KuA would prevent radiation-induced neuroinflammation and the detrimental effect on hippocampal neurogenesis. For this study, male Wistar rats received either sham irradiation or WBI (30 Gy single dose of X-rays) followed by the immediate injection of either KuA or vehicle intravenously. The dose of KuA was 5, 10, and 20 mg/kg, respectively. The levels of pro-inflammatory cytokines were assayed by ELISA kits. The newborn neurons were detected by 5-bromo-2-deoxyuridine (BrdU)/neuronal nuclei (NeuN) double immunofluorescence. Microglial activation was measured by Iba-1 immunofluorescence. The expression of Cox-2 and the activation of nuclear factor κB (NF-κB), activating protein 1(AP-1), and PPARδ were evaluated by western blot. WBI led to a significant increase in the level of TNF-α, IL-1β, and Cox-2, and it was alleviated by KuA administration. KuA attenuated microglial activation in rat hippocampus after WBI. Neurogenesis impairment induced by WBI was ameliorated by KuA. Additionally, KuA alleviated the increased translocation of NF-κB p65 subunit and phosphorylation of c-jun induced by WBI and elevated the expression of PPARδ. These data indicate that KuA could ameliorate the neuroinflammatory response and protect neurogenesis after WBI, partially through regulating the activation of NF-κB, AP-1, and PPARδ.
研究领域:
神经科学
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放射生物学
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药理学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2024
·
IF 5.3
Yu-Xin Jiao,Yan-Mei Zhou,Zi-Wen Zhou,Yong He,Shan Liu,Xue-Ting Xu,Kunmei Ji,Jia-Jie Chen
Activation of immunoglobulin E (IgE)-associated mast cells (MCs) triggers the onset of pro-inflammatory signals associated with type I allergic diseases. Although histone acetylation changes have been associated with inflammatory diseases, the impact of lysine-acetyltransferase (KAT) inhibitors on IgE-mediated MCs function is unclear. Potential anti-allergic effects of the KAT6A inhibitor WM-1119 on IgE-mediated MCs activation and allergic inflammation were examined in this study. WM-1119 was observed to reduce IgE-mediated degranulation in rat basophilic leukemia-2H3 cells (RBLs) and murine bone marrow-derived mast cells (BMMCs), as demonstrated by reduced the release of β-hexosaminidase (β-hex) or histamine (HA) and decreased inflammatory cytokines. Additionally, WM-1119 attenuated allergic responses in IgE-induced passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) mice. No WM-1119 effects on histamine-induced hypothermia in mice were observed. Mechanically, WM-1119 reduced levels of histone H3 lysine 14 acetylation (H3K14ac) and H3K27ac, while also reducing IgE-induced MAPK or NF-κB activity. Moreover, WM-1119 reduced activator protein-1 (AP-1) activity in a manner involving inhibition of c-Fos transcription and translation together with decreased AP-1 binding of its downstream promoters. KAT6A knockdown in MCs also reduced AP-1 activity by inhibiting c-Fos expression. H3K14ac enrichment in the Fos promoter was observed, indicating that H3K14ac may regulate c-Fos expression. In conclusion, KAT6A inhibition or knockdown was shown to reduce IgE-mediated MCs activation and allergic inflammation through a mechanism involving changes in c-Fos expression and downstream AP-1 activity consequent to down-regulation of histone acetylation. KAT6A inhibition may represent a new treatment strategy for suppressing MCs in treating allergic diseases.
研究领域:
免疫学
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表观遗传学
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药理学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2025
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IF 8
Ziyi Shen,Simeng Zhou,Yaru Zhang,Yuan Zhang,Hongyan Wang,Daxiang Li,Yijun Wang,Zhongwen Xie,Huifang Ge
Large-leaf yellow tea protein-derived oligopeptides (TPP) contain a substantial number of antioxidant peptides that facilitate skin damage repair and may be employed to mitigate skin photoaging. However, the potential alleviating mechanism by which TPP alleviates skin photoaging damage remains insufficiently understood. This study investigated the in vitro antioxidant capacity and cell migration-promoting ability of TPP. Additionally, it utilized ultraviolet (UV)-exposed and intrinsically aged ICR mice, which exhibit signs of skin aging, to assess the effects of an 8-week oral TPP intervention. The findings indicate that TPP exhibits potent free radical scavenging properties, which mitigate oxidative damage in Raw264.7 cells and promote the migration of NIH/3 T3 cells. TPP intervention significantly ameliorates oxidative stress and skin inflammation symptoms in UV-induced skin photoaging damage by restoring the activity of endogenous antioxidant enzymes and suppressing the mRNA expression of pro-inflammatory cytokines, including IL-1β , IL-6 , and TNF-α ., as well as inhibiting the MAPK/AP-1/MMP9 signaling pathways. This study proposes that TPP is a viable plant protein-derived nutritional supplement for the prevention of UV-induced skin photoaging damage.
研究领域:
营养科学
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皮肤科学
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分子生物学
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食品科学
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药理学
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产品关联
DOI
PubMed
高影响因子
INFLAMMATION
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2025
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IF 5
Deng Qirui,Liu Xinyan,Wen Xiujuan,Huang Hao,Tang Hongfeng
The aim of this study was to investigate how ultraviolet B (UVB) light regulates AP-1 expression via the β2-adrenergic receptor (β2-AR) in epidermal keratinocytes, which in turn regulates melanin synthesis in melanocytes, thereby modulating downstream melanin production in skin hair follicles and altering mouse skin color. We established a UV-irradiated mouse model to investigate the effects of UV radiation on changes in skin color. By measuring changes in the expression of genes related to cutaneous sympathetic nerves, norepinephrine synthesis and melanin synthesis, we investigated the relationship between β2-AR expression and cutaneous melanogenesis and determined the localization of β2-AR in cells. The results of the siRNA-mediated transfection of keratinized cells with downregulated β2-AR expression were further verified in vitro. Our results suggest that UVB alters the color of the dorsal skin in mice by activating the AP-1/IL-6 pathway, which triggers the sympathetic release of norepinephrine, thereby increasing β2-AR expression in keratinocytes. Overall, our study improves the current understanding of how UVB light influences skin color changes and highlights the complex interplay between ultraviolet radiation and skin physiology.
研究领域:
皮肤病学
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分子生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Human Cell
·
2024
·
IF 3.4
Cao Yue,Xing Ruixian,Li Qiushi,Bai Yang,Liu Xuewen,Tian Buxian,Li Xin
Reperfusion after cerebral ischemia leads to secondary damage to the nervous system, called cerebral ischemia/reperfusion injury (CIRI). The blood–brain barrier (BBB) consists of endothelial cells and tight junction (TJ) proteins, and its disruption aggravates CIRI. Two GSE datasets identified Tissue Factor Pathway Inhibitor 2 (TFPI2) as a differentially upregulated gene (Log2FC > 1, p < 0.01) in the cerebral cortex of ischemic rats, and TFPI2 affects angiogenesis of endothelial cells. Moreover, genes (c-Jun, c-Fos, FosL1) encoding subunits of Activator Protein-1 (AP-1), a transcription factor involved in IRI, were highly expressed in ischemic samples. Thus, the effects of the AP-1/TFPI2 axis on CIRI were explored. We determined increased TFPI2 expression in the cerebral cortex of rats receiving middle cerebral artery occlusion (MCAO) for 90 min and reperfusion (R) for 48 h. Then AAV2-shTFPI2 particles (5 × 10 10 vg) were injected into the right lateral ventricle of rats 3 weeks before MCAO/R. TFPI2 knockdown decreased infarct size and neuronal injury in ischemic rats. It improved BBB integrity, demonstrated by reduced FITC-dextran leakage in brain tissues of MCAO/R-operated rats. Furthermore, it increased the expression of TJ proteins (Occludin, Claudin-5, TJP-1) in the cerebral cortex of rats with CIRI. Consistently, we found that TFPI2 knockdown mitigated cell damage in mouse endothelial bEND.3 cells with oxygen and glucose deprivation (ODG) for 6 h and reoxygenation (R) for 18 h (OGD/R) treatment. High co-expression of c-Jun and c-Fos significantly elevated TFPI2 promoter activity. c-Jun knockdown inhibited TFPI2 expression in OGD/R-treated bEND.3 cell. Collectively, our findings demonstrate that inhibition of the AP-1/TFPI2 axis alleviates CIRI.
研究领域:
神经科学
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分子生物学
·
细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Communications Biology
·
2024
·Vol. 7
·期 1
·1-15
·
IF 5.2
Gong Ting-Ting,Liu Fang-Hua,Xiao Qian,Li Yi-Zi,Wei Yi-Fan,Xu He-Li,Cao Fan,Sun Ming-Li,Jiang Feng-Li,Tao Tao,Ma Qi-Peng,Qin Xue,Song Yang,Gao Song,Wu Lang,Zhao Yu-Hong,Huang Dong-Hui,Wu Qi-Jun
Platinum-based chemotherapy remains one of the major choices for treatment of ovarian cancer (OC). However, primary or acquired drug resistance severely impairs their efficiency, thereby causing chemotherapy failure and poor prognosis. SH3 domain containing ring finger 2 (SH3RF2) has been linked to the development of cancer. Here we find higher levels of SH3RF2 in the tumor tissues from cisplatin-resistant OC patients when compared to those from cisplatin-sensitive patients. Similarly, cisplatin-resistant OC cells also express higher levels of SH3RF2 than normal OC cells. Through in vitro and in vivo loss-of-function experiments, SH3RF2 is identified as a driver of cisplatin resistance, as evidenced by increases in cisplatin-induced cell apoptosis and DNA damage and decreases in cell proliferation induced by SH3RF2 depletion. Mechanistically, SH3RF2 can directly bind to the RNA-binding protein mRNA processing factor (RBPMS). RBPMS has been reported as an inhibitor of cisplatin resistance in OC. As a E3 ligase, SH3RF2 promotes the K48-linked ubiquitination of RBPMS to increase its proteasomal degradation and activator protein 1 (AP-1) transactivation. Impairments in RBPMS function reverse the inhibitory effect of SH3RF2 depletion on cisplatin resistance. Collectively, the SH3RF2-RBPMS-AP-1 axis is an important regulator in cisplatin resistance and inhibition of SH3RF2 may be a potential target in preventing cisplatin resistance.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Mingliang Zhang,Weihao Zhu,Hongfei Liu,Kaihua Pan,Qian Li,Qian Zhu,Yanni Huang,Changchang Wang,Junqiang Hu,Mingli Jiang,Xin Yan,Qing Hong
Acetaminophen (APAP), an analgesic and antipyretic drug, is commonly detected in wastewater treatment plant (WWTP) effluents, surface water, and soil, indicating its status as an emerging environmental contaminant. In this study, we isolated a bacterium, Pseudomonas taiwanensis AP-1, capable of completely mineralizing APAP and utilizing it as the sole carbon source for growth. A newly identified metabolite, γ-glutamyl-4-aminophenol (γ-G4AP), was reported for the first time in the degradation of APAP by strain AP-1. Two amidases (ApaH1 and ApaH2), responsible for the conversion of APAP to 4-aminophenol (4-AP), were identified through a combination of genomic comparison, heterologous expression, and gene knockout. Notably, ApaH1 played a pivotal role in the degradation of APAP by strain AP-1. The catalytic triad of ApaH1 (K82-S161-S185) and ApaH2 (K85-S160-S184) were identified as by molecular docking and site-directed mutagenesis. Additionally, a gene cluster apd for the metabolism of 4-AP was also successfully identified in strain AP-1, consisting of the aniline dioxygenase gene cluster apdBCD1D2EF and the BT catabolic gene apdGH . Interestingly, the 4-AP metabolic gene cluster apd was highly conserved among other Pseudomonas strains capable of APAP degradation. Our results provide new insights into the mechanism of APAP biodegradation and strain AP-1 may be a promising bacterium for the bioremediation of APAP pollutions.
研究领域:
环境科学
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微生物学
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药物代谢
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产品关联
DOI
PubMed
高影响因子
Drug Metabolism and Pharmacokinetics
·
2013
·
IF 2.071
Qiuxia Chen,Yicong Bian,Su Zeng
Caco-2 is a widely used cell model in drug absorption and P-glycoprotein (P-gp,MDR1) substrate identification. Long term vinblastine treatment of Caco-2 cells could increase the expression of P-gp, thus, the vinblastine resistant Caco-2 (Caco-2 vbl) cells can be used as a rapid and sensitive alternative model in identifying P-gp substrates. The mechanism of P-gp induction in this model is not clear, this study was therefore intended to clarify the possible factors involved in P-gp up- regulation in Caco-2 vbl cells. Since vinblastine is the inducer of both activator protein-1 (AP-1) and nuclear factor kappa B(NF-κB), we investigated the role of AP-1 and NF-κB in regulation of MDR1 gene expression. Our results indicated that the AP-1 and NF-κB luciferase activity was higher in Caco-2 vbl cells than that in Caco-2 cells by reporter gene assay. The mRNA expression of AP-1 subunit c-Jun and NF-κB was increased in Caco-2 vbl cells. The c-Jun inhibitor SP600125 and NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) suppressed the expression of MDR1 mRNA in Caco-2 vbl cells. In conclusion, this study provides the evidence that AP-1 and NF-κB are involved in the P-gp induction in Caco-2 vbl cells.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2026
·
IF 7
Tianyi Xu,Qilei Yang,Yue Peng,Congcong Xie,Huimin Yu
Rheumatoid arthritis (RA) therapy demands agents that are both effective and safe, yet many natural products with promising bioactivity, such as curcumin, face major translational challenges due to poor solubility and bioavailability. To overcome these limitations, we designed and synthesized a series of dual-functional curcumin-borneol prodrugs via a succinate ester linkage, including the parent ester (CBS), its water-soluble sodium salt (CBS-Na), and a disubstituted analog (DCBS), to enhance delivery and synergize therapeutic action. These derivatives markedly improved cellular uptake and nuclear localization, potently scavenged reactive oxygen species, and effectively suppressed the MAPK/AP-1 signaling axis by inhibiting ERK and p38 phosphorylation and c-Fos expression, leading to downregulation of matrix metalloproteinase MMP9 and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). In a collagen-induced arthritis rat model, the derivatives demonstrated superior efficacy over native curcumin in alleviating joint inflammation and destruction, while exhibiting an excellent safety profile, thus representing a novel and promising therapeutic strategy for RA.
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DOI
PubMed
高影响因子
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