JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
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2024
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IF 4.9
Lu Wang,Wanyue Sang,Yi Jian,Yafan Han,Feifei Wang,Subinuer Wubulikasimu,Li Yang,Baopeng Tang,Yaodong Li
Objectives To investigate the role and mechanism of MAPK14/AIFM2 pathway in Ang II-induced atrial fibrillation in rats. Methods A rat model of AF was established for in vivo experiments and HL-1 cells were treated with Ang II to develop an in vitro model. In addition, HL1 cells overexpressing AIFM2 (oeAIFM2) were constructed. SB203580 was used to inhibit the expression of MAPK14. The role of MAPK14 in Ang II-AF model was investigated by in vivo electrophysiological examination and molecular biology tests. The role of MAPK14 / AIFM2 pathway on AF induced by Ang II was explored in vitro. Results MAPK14 and AIFM2 were significantly up-regulated in AF induced by Ang II (all P < 0.05). In vivo experiments indicated that inhibition of MAPK14 down-regulated AIFM2, improved atrial electrical conduction, AF inducibility and durations, and alleviated the structural and functional damage of heart and mitochondria (all P < 0.05). Both in vivo and in vitro tests showed that the MAPK14/AIFM2 pathway prevented Ang II-induced AF via regulating mitophagy-dependent apoptosis. Conclusions Inhibition of the MAPK14/AIFM2 pathway improved Ang II-induced AF by inhibiting mitophagy-dependent apoptosis.
研究领域:
心血管病学
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分子生物学
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DOI
PubMed
高影响因子
Genes & Genomics
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2026
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IF 1.7
Ou Yuyang,Chen Chen,Wang Ziyi,Zhu Xi,Luo Yaoxing,Li Shulin,Li Dan
Background Intracerebral hemorrhage (ICH) is a primary non-traumatic parenchymal hemorrhage of the brain with a high mortality and disability rate. Acupuncture has been proved to alleviate neurological deficits after ICH. Objective Our previous study found that UBL4A is up-regulated in the ICH rat treated with acupuncture, and may be a potential molecular target for acupuncture treatment of ICH. However, the molecular mechanism behind UBL4A is unclear. Methods UBL4A knockdown was conducted in ICH rats with acupuncture treatment to explore its role in the therapeutic effects of acupuncture on ICH. In vitro, the effects of UBL4A on heme-induced neuronal injury were evaluated using E18 rat embryonic primary cortical neurons. Proteomic experiments were used to verify the regulatory relationship between UBL4A and MAPK14. Results UBL4A knockdown has opposite effects to the therapeutic effects of acupuncture on ICH, including increasing corner turn score, brain water content and the number of degenerated and apoptotic neuron in ICH rats. UBL4A knockdown increased the level of ROS, OPA1-S/L, p-MAPK14 and mitochondrial Drp1, and decreased mitochondrial membrane potential, ATP level and MFN2 level in rat brain tissue. In vitro, UBL4A overexpression reduced ROS level and mitochondrial membrane potential and inhibited the activation of the MAPK14/Drp1 signaling pathway. Co-IP verified the binding of UBL4A and MAPK14, and MAPK14 overexpression reversed the effect of UBL4A on hemin-induced neuronal apoptosis and ROS level. Conclusion Our study confirms that UBL4A is involved in the therapeutic effect of acupuncture on ICH, and affects mitochondrial damage and oxidative stress through MAPK14 ubiquitination. Graphical abstract UBL4A participates in the therapeutic effect of acupuncture on cerebral hemorrhage and regulates mitochondrial function through MAPK14.
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PubMed
高影响因子
PHYTOMEDICINE
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2026
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IF 11.3
Zhuorui Li,Ningbo Zhang,Limei Dai,Xiangzhen Meng,Jiaqi Huang,Qingwen Hei,Zhinan Mei,Hui Xiong
Bairesi Pills promote repigmentation in hydroquinone-induced vitiligo mice. • Bairesi Pills reduce hippuric acid levels and restore gut-skin axis homeostasis. • Bairesi Pills and their active constituents including piperine and quercitrin, enhance melanogenesis through modulation of the MAPK14/β-catenin pathway. Background Bairesi Pills is a traditional Uyghur medicinal formula prescribed for vitiligo. However, its bioactive constituents and specific pharmacological mechanisms remain to be fully elucidated. Purpose This study aims to elucidate the underlying mechanisms and identify the active constituents of Bairesi Pills in the treatment of vitiligo. Methods A hydroquinone-induced vitiligo mouse model was established to evaluate the effects of Bairesi in vivo. Serum untargeted metabolomics and gut microbiome analyses were integrated to identify key differential metabolites and explore the association between gut dysbiosis and skin depigmentation. In vitro, melanocyte oxidative injury models were established using H₂O₂ or hippuric acid. Transcriptome sequencing was performed to screen differentially expressed genes and related signaling pathways. MAPK14 overexpression and pharmacological inhibition were further used to verify the effects and mechanisms of Bairesi and its active constituents in alleviating hippuric acid-induced oxidative stress. Results In vivo, Bairesi ameliorated oxidative stress and promoted pigment deposition in vitiligo-like mice, which was associated with enhanced intestinal mucus barrier integrity, reshaped gut microbiota, and reduced hippuric acid accumulation. In vitro, H₂O₂ or hippuric acid induced oxidative injury and MAPK activation in melanocytes, whereas Bairesi, piperine, and quercitrin suppressed MAPK14 activation, alleviated oxidative stress, and restored melanin synthesis, but these protective effects were attenuated by MAPK14 overexpression. Conclusion Bairesi Pills ameliorates vitiligo-like depigmentation by reshaping the gut microbiota–metabolite profile, reducing hippuric acid accumulation, and reversing HA-induced oxidative stress through inhibition of MAPK14 phosphorylation. Download: Download high-res image (219KB) Download: Download full-size image
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DOI
高影响因子
Food Frontiers
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2025
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IF 6.9
Peng Han,Bo Wang,Luyang Han,Yanbo Zhu,Jiawei Dong,Yuekang Xu,Xiaoying Liu,Jinyao Li
Zanthoxylum ailanthoides , a medicinal and edible plant, was mostly used as medicinal materials or spices, in which 7-demethylsuberosin (7-Dem) was identified as active component, but its function and mechanism on dendritic cells (DCs) are not clear. The objective of this study was to explore the effect and mechanism of 7-Dem on the maturation and function of DCs in the treatment of rheumatoid arthritis. The impact of 7-Dem on DCs was assessed using flow cytometry and ELISA. Agonists of the Toll-like receptor pathway and cytochalasin D were employed to validate the pathway affected by 7-Dem. Furthermore, molecular docking, network pharmacology, Western blotting, and CETSA were used to explore the targets of 7-Dem. The immunomodulatory effects of 7-Dem were examined using the adjuvant-induced arthritis (AIA) mouse model. The results showed that 7-Dem did not damage the viability of DCs at doses below 10 µM but suppressed the maturation of DCs induced by lipopolysaccharide in vitro and in vivo , enhanced phagocytosis, and restrained migration. DCs exhibited an impaired stimulation of CD4 + T cell proliferation and restored the imbalance of CD4 + T cell subtypes after treatment with 7-Dem. At molecular levels, 7-Dem inhibited the maturation of DCs induced by agonists and decreased the expression of TRAF6, not TRAF3. Furthermore, 7-Dem improved the thermal stability and reduced the phosphorylation of MAPK14. In vivo , 7-Dem alleviated joint inflammation with restored imbalance of T cell subtypes. In conclusion, 7-Dem inhibits the maturation and function of DCs by targeting MAPK14 and inhibiting the phosphorylation of MAPK14, which thereby restores immune tolerance and alleviates inflammation in the AIA joints.
研究领域:
生药学
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免疫学
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天然产物研究
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分子生物学
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风湿病学
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功能食品
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民族药理学
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DOI
高影响因子
Life Science Alliance
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2024
·Vol. 7
·期 4
·e202302375
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IF 3.3
Jialing Bao,Yunlin Tang,Yebo Chen,Jiangyan Jin,Xue Wang,Guozhen An,Lu Cao,Huarui Zhang,Gong Cheng,Guoqing Pan,Zeyang Zhou
Microsporidia are difficult to be completely eliminated once infected, and the persistence disrupts host cell functions. Here in this study, we aimed to elucidate the impairing effects and consequences of microsporidia on host DCs. Enterocytozoon hellem, one of the most commonly diagnosed zoonotic microsporidia species, was applied. In vivo models demonstrated that E. hellem-infected mice were more susceptible to further pathogenic challenges, and DCs were identified as the most affected groups of cells. In vitro assays revealed that E. hellem infection impaired DCs’ immune functions, reflected by down-regulated cytokine expressions, lower extent of maturation, phagocytosis ability, and antigen presentations. E. hellem infection also detained DCs’ potencies to prime and stimulate T cells; therefore, host immunities were disrupted. We found that E. hellem Ser/Thr protein phosphatase PP1 directly interacts with host p38α (MAPK14) to manipulate the p38α(MAPK14)/NFAT5 axis of the MAPK pathway. Our study is the first to elucidate the molecular mechanisms of the impairing effects of microsporidia on host DCs’ immune functions. The emergence of microsporidiosis may be of great threat to public health.
研究领域:
免疫学
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微生物学
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病理学
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DOI
PubMed
高影响因子
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