LIFE SCIENCES
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2024
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IF 5.2
Kai Yang,Xiaoxiao Yu,Zihao Guo,Zhihao Fang,Hongyu Zhang,Wanyangchuan Zhang,Changxu Liu,Yanchao Ji,Zhichao Dong,Qiang Gu,Jiahao Yao,Chang Liu
Aims Non-alcoholic fatty liver disease (NAFLD) has risen as a significant global public health issue, for which vertical sleeve gastrectomy (VSG) has become an effective treatment method. The study sought to elucidate the processes through which PIM1 mitigates the advancement of NAFLD. The Pro-viral integration site for Moloney murine leukemia virus 1 (PIM1) functions as a serine/threonine kinase. Bioinformatics analysis revealed that reduced PIM1 expression in NAFLD. Methods To further prove the role of PIM1 in NAFLD, an in-depth in vivo experiment was performed, in which male C57BL/6 mice were randomly grouped to receive a normal or high-fat diet for 19 weeks. They were operated or delivered the loaded adeno-associated virus which the PIM1 was overexpressed (AAV-PIM1). In an in vitro experiment, AML12 cells were treated with palmitic acid to induce hepatic steatosis. Key findings The results revealed that the VSG surgery and virus delivery of mice alleviated oxidative stress, and apoptosis in vivo. For AML12 cells, the levels of oxidative stress, apoptosis, and lipid metabolism were reduced via PIM1 upregulation. Moreover, ML385 treatment resulted in the downregulation of the NRF2/HO-1/NQO1 signaling cascade, indicating that PIM1 mitigates NAFLD by targeting this pathway. Significance PIM1 alleviated mice liver oxidative stress and NAFLD induced by High-fat diet by regulating the NRF2/HO-1/NQO1 signaling Pathway.
研究领域:
肝病学
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分子生物学
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病理学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
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2026
·Vol. 78
·期 3
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IF 3.7
Wang Heng,Wang Yiying,Zhang Ronghao,Zhang Xing,Wang Mengjie,He Shijun,Wang Xiaoyu,Kadowaki Makoto
ObjectivesThe present study explored whether allyl isothiocyanate from the traditional Chinese medicine mustard seed, ameliorated the arthritis by modulating immune cell responses, particularly by inhibiting mast cell activation and the Pim1 pathway.MethodsMicro-CT, hematoxylin and eosin staining, and flow cytometry were performed to evaluate pathological changes in collagen-induced arthritis mice. To investigate the mechanism underlying allyl isothiocyanate-mediated mast cells activation, degranulation, intracelluar calcium measurement, RNA sequencing, real-time polymerase chain reaction and western blotting were carried out.Key findingsAllyl isothiocyanate reduced the number of mast cells in the ankle joints of collagen-induced arthritis mice, and it inhibited the degranulation of mouse bone marrow-derived mast cells and RBL-2H3. RNA sequencing revealed that allyl isothiocyanate significantly inhibited Pim1 expression. Additionally, it inhibited the expression of Pim1, p-STAT5, p-AKT and c-myc in RBL-2H3 and RAW264.7 cells and the ankle joints of collagen-induced arthritis mice. Adoptive transfer of mouse bone marrow-derived mast cells early in collagen-induced arthritis exacerbated joint inflammation, which was similarly inhibited by allyl isothiocyanate.ConclusionThese findings support mast cell as a major cellular target of AITC in CIA and suggest that Pim1-related signaling contributes to AITC-mediated suppression of mast cell activation.
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高影响因子
Research
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2026
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IF 12.9
Zepeng Su,Yipeng Zeng,Qibo Li,Jinteng Li,Guan Zheng,Weihao Zhang,Zipeng Xiao,Zibin Chen,Yangfeng Lin,Ziqian Liu,Yanfeng Wu,Jiajie Lin,Wenhui Yu,Zhongyu Xie
Inflammatory arthritis, mainly including rheumatoid arthritis (RA) and ankylosing spondylitis (AS), is a group of chronic progressive autoimmune diseases that destroy joints. T helper 17 (Th17) cells are extensively involved in the joint inflammation as well as bone and cartilage destruction of these diseases. Previously, proviral integration site for Moloney-murine leukemia virus 1 (Pim1) was reported to be involved in various autoimmune diseases by mediating the proinflammatory effects of T cells. However, the pathological effect and the therapeutic potential of Pim1 in inflammatory arthritis remain elusive. The present study demonstrated that Pim1 expression was elevated in CD4 + T cells locally and systemically in patients with RA or AS and in 2 mice models of inflammatory arthritis. Conditional knockdown of Pim1 in CD4 + T cells (Pim1 cKO) or using the Pim1 inhibitor AZD1208 alleviated the development of inflammatory arthritis in association with decreasing the proportion of Th17 cells. In vitro experiments involving inhibition and overexpression confirmed the promoting effect of Pim1 on Th17 cell differentiation. Mechanistically, Pim1 phosphorylated mitochondrial calcium uptake protein 1 to increase mitochondrial calcium influx, which subsequently activated mitochondrial oxidative phosphorylation and promoted Th17 cell differentiation. Through molecular docking and dynamic simulation, nilotinib, a Food-and-Drug-Administration-approved drug, was identified as a selective substitute for the currently clinically nonapproved Pim1 inhibitors, which impeded Th17 cell differentiation and was well tolerated during the treatment of Pim1 cKO mice and 2 inflammatory arthritis mouse models. Our study contributes to a better understanding of the mechanism through which Pim1 promotes Th17 cell differentiation and advances the clinical application of Pim1 as an effective target for treating inflammatory arthritis.
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PubMed
高影响因子
Journal of Functional Foods
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2022
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IF 5.223
Bo Jiang,Xinsheng Fu,Qichuan Zhang,Yunfei Du
Dioscin (DS) is a natural compound with inhibitory effects on multiple cancer types and we explored the mechanism driving the antagonizing effect of DS on osteosarcoma (OS). OS cell lines were treated with DS and microRNAs (miRs) responding to DS treatment were determined. Effects of DS on viability, apoptosis, metastasis, and miR-16-5p/HuR/Pim1 pathway activity were assessed. MiR-16-5p was inhibited before DS treatment to confirm its central role in anti-OS effects of DS. The conclusion derived from in vitro assays was verified with a mouse model. DS suppressed viability, invasion and migration, while induced apoptosis in OS cells. Moreover, the compound also induced the expression of miR-16-5p, contributing to the inhibition of HuR/Pim1 pathway. The inhibited expression of miR-16-5p counteracted the anti-OS function of DS, which was also validated in mice. Anti-OS effects of DS depended on the induction of miR-16-5p, making the compound a promising adjuvant agent for treating OS.
研究领域:
肿瘤学
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分子生物学
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药理学
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高影响因子
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