FREE RADICAL BIOLOGY AND MEDICINE
·
2026
·
IF 8.2
Lili Hao,Wenjie Zhang,Xiaoting Peng,Yujia Bai,Cheng Tian,Yiwen Zhang,Di Li,Zhihui Feng,Baoshan Xu,Qiong Xu
Disordered osteogenic potential in bone marrow mesenchymal stem cells (BMSCs) is a hallmark of inflammatory jaw diseases. Recent studies suggest that inflammatory stimulating disrupts energy metabolism during BMSC osteogenesis. However, the impact of key metabolites on BMSC ossification remains unclear. In this study, a comprehensive targeted metabolomic analysis was performed during BMSC osteogenic differentiation, with and without inflammatory stimulation induced by lipopolysaccharide (LPS). We identified a significant downregulation of spermidine (SPD), along with methylated purines and pyrimidines, in the inflammatory environment. Exogenous SPD supplementation enhanced BMSC osteogenesis and increased N6-methyladenosine (m 6 A) methylation. Mechanistically, SPD elevated S-adenosylmethionine (SAM) levels and upregulated the methyltransferases METTL3 and METTL14. Similarly, betaine, a promoter of SAM synthesis, increased m 6 A methylation and improved BMSC osteogenic potential. In contrast, the METTL3/METTL14 inhibitor S-adenosylhomocysteine (SAH) reduced m 6 A methylation and negated SPD's osteogenic effects. This suggests that SPD enhances BMSC osteogenesis through m 6 A methylation regulation. Furthermore, SPD activated autophagy in BMSCs, while SAH inhibited SPD-induced autophagy. Notably, treatment with rapamycin (Rap), an autophagy inducer, restored both autophagy and osteogenic differentiation impaired by SAH. In vivo , SPD supplementation enhanced m 6 A methylation and facilitated bone regeneration in a rat model of inflammatory mandibular defects. In conclusion, this study demonstrates that SPD promotes the osteogenic potential of BMSCs through an m 6 A methylation–autophagy axis under inflammatory conditions, providing a novel therapeutic approach for inflammatory jaw diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2026
·Vol. 22
·期 3
·1542
·
IF 10
Yini Li,Tongtong Tian,Qian Yu,Huiqin Jiang,Te Liu,Hao Wang,Ran Huo,Chenzheng Gu,Yu Liu,Ying Zhao,Chunyan Zhang,Yan Zhou,Jiyan Wang,Lin Ding,Chuyu Wang,Xinyi He,Wei Guo,Wenjing Yang,Beili Wang
Dietary intervention provides a novel approach for cancer therapy. Elaidic acid (EA), which accounts for 80-90% of total trans fatty acids in foods, has recently been found to exert anti-tumor effects. However, the biological functions and underlying mechanisms of EA remain elusive in hepatocellular carcinoma (HCC). In this study, targeted fatty acid metabolomics demonstrated that among 44 types of fatty acids, the concentration of EA decreased most significantly when comparing plasma from HCC patients with plasma from healthy people. Through in vivo assays using HCC orthotopic and xenograft mouse models, we further revealed that dietary EA attenuates HCC growth. Notably, when gut microbiota was depleted using a cocktail of antibiotics, the anti-tumor effect of EA was diminished, confirming that EA suppresses HCC tumor growth by modulating gut microbiota. Mechanistically, analysis of 16S ribosomal RNA sequencing showed that dietary EA markedly increases the abundance of intestinal Ligilactobacillus murinus (L. murinus) . Subsequent untargeted metabolomic sequencing analysis further demonstrated that dietary EA drives the production of L. murinus -derived spermidine (SPD), which attenuates HCC growth in vitro as well as in vivo . The observed impact correlated with the phosphorylation of p38 MAPK and the upregulation of biomarkers pertinent to apoptosis and proliferation, including tumor protein 53, bcl-2-associated X protein, and cysteine-requiring aspartate protease 3. Taken together, our findings highlight the important role of intestinal L. murinus -derived SPD in EA-mediated HCC suppression, thereby offering a promising dietary strategy for HCC treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW PHYTOLOGIST
·
2026
·
IF 8.7
Lele Chu,Xiangming Shang,Bachar Dahro,Xi Zeng,Wenqiang Hu,Chunlong Li,Ji-Hong Liu
Summary Ethylene exerts a divergent role in modulating plant organ abscission. Spermidine (Spd) shares a common precursor for de novo biosynthesis with ethylene, but the antagonistic role between them in the regulation of plant organ abscission remains largely elusive. Here, RNA-sequencing of abscission zones from ethylene-treated sweet orange ( Citrus sinensis L.) fruit led to the identification of two ethylene-responsive factors (ERFs), CsERF113 and CsERF7. CsERF113 functioned in promoting fruit abscission and suppressed Spd accumulation, whereas CsERF7 exhibited an opposite trend. CsERF113 and CsERF7 were verified to act as a transcriptional repressor or an activator of CsSAMDC1 / 2 / 3 encoding S -adenosylmethionine decarboxylase (SAMDC), an enzyme responsible for Spd biosynthesis, by binding directly to their promoters in an ethylene-dependent manner. Moreover, CsSAMDC1 / 2 / 3 functioned to inhibit fruit abscission by promoting Spd synthesis. Interestingly, CsERF7 and CsERF113 transcriptionally repressed each other to modulate the ethylene-mediated downregulation of CsSAMDC1 / 2 / 3 , forming an antagonistic regulatory circuit that could be negatively orchestrated by exogenous Spd. Taken together, our results uncover that CsERF113 and CsERF7 integrate the ethylene signal to antagonistically regulate CsSAMDC1 / 2 / 3 -mediated synthesis of Spd and fruit abscission. This study provides important insights into understanding the molecular mechanisms by which ethylene and Spd antagonize to modulate fruit abscission.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Shixiong Zhang,Xinjing Mao,Liping Chang,Mengnan Li,Cong Wei,Hongrong Li,Xiaogang Shen,Kunxu Niu,Runtao Zhang,Yuning Jiang,Xuan Lu,Yahui Song,Liangxing Zhou,Lini Gao,Zhiqin Zhao,Liying Niu,Qian Yang,Yunlong Hou,Yiling Wu
Ethnopharmacological relevance Bazi Bushen Capsule (BZBS), a traditional Chinese medicine formulation composed of multiple bioactive herbal components, has been validated in multicenter randomized double-blind controlled trials for its potent anti-aging properties. Previous studies from our group have demonstrated that BZBS effectively restores gut microbiota homeostasis and attenuates the impairment of intestinal barrier function, thereby ameliorating age-related cognitive decline. However, the specific molecular mechanisms by which BZBS modulates key microbial-metabolite networks to delay brain aging remain poorly understood and warrant further investigation. Aim of the study This study aims to elucidate the key microbiota-metabolite networks through which BZBS improves cognitive function and delays brain aging in senescence-accelerated mouse-prone 8 (SAMP8) mice. Materials and methods Eight-week-old male SAMP8 mice were used as experimental models, randomly divided into Model, BZ-low (0.5 g/kg/d BZBS), BZ-high (1 g/kg/d BZBS), and RAPA (2 mg/kg/d rapamycin) groups. Senescence-accelerated mouse resistant 1 (SAMR1) mice served as the control group. Cognitive function was assessed using the Barnes Maze test and the three-chamber social test. The structural damage and pathological changes in the brain tissue were evaluated through transcranial Doppler, micro-computed tomography, Nissl staining, and Western blot analysis. Next, the intestinal barrier function was detected by hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and immunofluorescence (IF) staining. Characteristic bacteria were identified by 16S rRNA sequencing, and metabolomic profiling was performed using non-targeted metabolomics. Akkermansia muciniphila (Akk) was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate its contribution to intestinal barrier function. Results The study revealed that BZBS therapy not only enhances cognitive capabilities but also restores the intestinal barrier function. Akk was identified as a key regulatory agent mediating the therapeutic effects of BZBS. BZBS administration significantly increased the abundance of Akk and modulated its metabolite profile, particularly components associated with spermidine, thereby reinforcing the intestinal barrier and mitigating age-related cognitive decline. Furthermore, this study demonstrated that Akk, administered via fecal microbiota transplantation, alleviated dextran sulfate sodium (DSS)-induced colitis.. Conclusion The results showed that BZBS capsule, a traditional Chinese medicine, may delay brain aging in SAMP8 mice by modulating Akk and its spermidine production.
研究领域:
民族药理学
·
微生物组学
·
代谢组学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Metabolism
·
2025
·
IF 30.9
Xiaohui Zhang,Zhongliang Nie,Shuang Wang,Yuxi Ma,Dan Han,Ting Hu,Liu Liu,Liying Men,Tao Zhang,Xiaoting Wu,Xu Li,Sheng Hu,Meng Yuan,Liu Liu,Chaoqun Wang,Ping Xu,Limin Xiang,Jiao Liu,Yong Zhang,Dahai Zhu,Hehua Lei,Limin Zhang,Xiangpan Li,Yanxia Zhao,Wei Yan
Radiotherapy reduces the risk of cancer recurrence and death, but the fact that it's accompanied by multiple side effects including muscle fibrosis and weakness, seriously affects the life quality of patients. However, the underlying mechanism is poorly defined. Here, we identify that cancer cells secrete more spermidine synthase (SRM) enzyme through small extracellular vesicles to trigger skeletal muscle weakness upon radiotherapy. Mechanistically, irradiation-triggered arachidonic acid (ArA) accumulation elevates the ISGylation of the SRM protein, facilitating SRM packaging into extracellular vesicles from the primary tumor. Circulating SRM results in spermidine accumulation in skeletal muscle and type I collagen fiber biosynthesis in an eIF5A-dependent manner. However, losartan treatment blocks the ISGylation of SRM and its subsequent secretion. Collectively, our findings determine that ArA functions in concert for circulating SRM secretion upon radiotherapy, which aggravates skeletal muscle fibrosis through rewiring polyamine metabolism, shedding light on the alleviation of radiotherapy-mediated muscle weakness when combined with losartan treatment.
研究领域:
肿瘤学
·
生物化学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxics
·
2025
·Vol. 13
·期 10
·822
·
IF 4.1
Guangchao Yu,Ming Wei,Zhipeng Wang,Lian Jia,Yue Qu
This study aims to investigate the role of exogenous spermidine (Spd) in mitigating the adverse effects of cadmium (Cd) stress on the growth and development of cucumber (Cucumis sativus). The cucumber cultivar “Xintaimici” was used as the experimental material, and a hydroponic experiment was carried out. Based on a baseline Cd concentration of 10 mg·L−1, Spd was supplemented at concentrations of 0.05, 0.1, 0.2, 0.4, and 0.5 mM, resulting in seven treatment groups: control group (CK), S0 group (Cd-only treatment, 10 mg·L−1Cd + 0 mM Spd), S1+ Cd group (10 mg·L−1Cd + 0.05 mM Spd), S2+ Cd group (10 mg·L−1Cd + 0.1 mM Spd), S3+ Cd group (10 mg·L−1Cd + 0.2 mM Spd), S4+ Cd group (10 mg·L−1Cd + 0.4 mM Spd), and S5+ Cd group (10 mg·L−1Cd + 0.5 mM Spd). This study analyzed the regulatory effects of Spd on the growth and development, antioxidant capacity and cadmium accumulation characteristics of cucumber seeds and seedlings. It was found that cadmium stress significantly inhibited their growth process and led to a decline in multiple physiological indicators. Under a Cd concentration of 10 mg·L−1, the application of 0.2 mM Spd significantly improved these parameters. During the seedling stage, the application of 0.2 mM Spd under Cd stress significantly enhanced the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), as well as the content of soluble proteins, while significantly reducing malondialdehyde (MDA) levels. Cd content analysis revealed that 0.2 mM Spd promoted Cd accumulation in roots while suppressing its translocation to young leaves, thereby reducing Cd accumulation in aboveground tissues. Gene expression analysis demonstrated that this treatment significantly upregulated the expression levels of the phytochelatin synthase gene (CsPCS1) and the gene associated with reduced glutathione synthesis (CsGSHS). In conclusion, the exogenous application of 0.2 mM Spd effectively alleviates oxidative damage and osmotic stress induced by Cd stress in cucumber, promotes plant growth, and significantly enhances Cd tolerance.
研究领域:
植物生理学
·
环境毒理学
·
分子生物学
·
重金属胁迫
·
作物科学
·
抗氧化代谢
·
植物营养
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Metabolism
·
2024
·
IF 27.7
Li Zhang,Hao-li Wang,Ya-fang Zhang,Xin-tao Mao,Ting-ting Wu,Zhi-hui Huang,Wan-jun Jiang,Ke-qi Fan,Dan-dan Liu,Bing Yang,Mei-hui Zhuang,Guang-ming Huang,Yinming Liang,Shu Jeffrey Zhu,Jiang-yan Zhong,Guang-yin Xu,Xiao-ming Li,Qian Cao,Yi-yuan Li,Jin Jin
Irritable bowel syndrome with diarrhea (IBS-D) is a common and chronic gastrointestinal disorder that is characterized by abdominal discomfort and occasional diarrhea. The pathogenesis of IBS-D is thought to be related to a combination of factors, including psychological stress, abnormal muscle contractions, and inflammation and disorder of the gut microbiome. However, there is still a lack of comprehensive analysis of the logical regulatory correlation among these factors. In this study, we found that stress induced hyperproduction of xanthine and altered the abundance and metabolic characteristics of Lactobacillus murinus in the gut. Lactobacillus murinus -derived spermidine suppressed the basal expression of type I interferon (IFN)-α in plasmacytoid dendritic cells by inhibiting the K63-linked polyubiquitination of TRAF3. The reduction in IFN-α unrestricted the contractile function of colonic smooth muscle cells, resulting in an increase in bowel movement. Our findings provided a theoretical basis for the pathological mechanism of, and new drug targets for, stress-exposed IBS-D.
研究领域:
胃肠病学
·
免疫学
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Hang Ren,Peng Wang,Hanwen Huang,Junshen Huang,Yuheng Lu,Yanfeng Wu,Zhongyu Xie,Youchen Tang,Zhaopeng Cai,Huiyong Shen
Titanium (Ti) and its alloys have been widely employed in the treatment of orthopedics and other hard tissue diseases. However, Ti-based implants are bioinert and suffer from bacterial infections and poor osseointegration in clinical applications. Herein, we successfully modified Ti with a porous N-halaminated spermidine-containing polymeric coating (Ti-SPD-Cl) through alkali-heat treatment, surface grafting and chlorination, and it has both excellent antibacterial and osteogenic abilities to significantly enhance osseointegration. The as-obtained Ti-SPD-Cl contains abundant N–Cl groups and demonstrates effective antibacterial ability against S. aureus and E. coli. Meanwhile, due to the presence of the spermidine component and construction of a porous hydrophilic surface, Ti-SPD-Cl is also beneficial for maintaining cell membrane homeostasis and promoting cell adhesion, exhibiting good biocompatibility and osteogenic ability. The rat osteomyelitis model demonstrates that Ti-SPD-Cl can effectively suppress bacterial infection and enhance bone–implant integration. Thus, Ti-SPD-Cl shows promising clinical applicability in the prevention of orthopedic implant infections and poor osseointegration.
研究领域:
材料科学
·
生物材料
·
骨科
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2020
·
IF 4.831
Xin Yang,Mohan Zhang,Yuhua Dai,Yuchao Sun,Yahyah Aman,Yuying Xu,Peilin Yu,Yifan Zheng,Jun Yang,Xinqiang Zhu
Aging is the primary driver of various diseases, including common neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Currently there is no cure for AD and PD, and the development of novel drug candidates is demanding. Spermidine is a small anti-aging molecule with elimination of damaged mitochondria via the process of mitophagy identified as a molecular mechanism of action. Here, we show that spermidine inhibits memory loss in AD worms and improves behavioral performance, e.g., locomotor capacity, in a PD worm model, both via the PINK1-PDR1-dependent mitophagy pathway. Additionally, spermidine delays accelerated aging and improves healthspan in the DNA repair-deficient premature aging Werner syndrome (WS) worm model. While possible intertwined interactions between mitophagy/autophagy induction and DNA repair by spermidine are to be determined, our data support further translation of spermidine as a possible therapeutic intervention for such diseases.
研究领域:
生物学
·
医学
·
神经科学
·
衰老研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Jing Tang,Jianming Li,Guo Li,Haitao Zhang,Ling Wang,Dai Li,Jinsong Ding
Idiopathic pulmonary fibrosis is a progressive, fatal lung disease with poor survival. The advances made in deciphering this disease have led to the approval of different antifibrotic molecules, such as pirfenidone and nintedanib. An increasing number of studies with particles (liposomes, nanoparticles [NPs], microspheres, nanopolymersomes, and nanoliposomes) modified with different functional groups have demonstrated improvement in lung-targeted drug delivery. In the present study, we prepared, characterized, and evaluated spermidine (Spd)-modified poly(lactic-co-glycolic acid) (PLGA) NPs as carriers for fluorofenidone (AKF) to improve the antifibrotic efficacy of this drug in the lung. Spd-AKF-PLGA NPs were prepared and functionalized by modified solvent evaporation with Spd and polyethylene glycol (PEG)-PLGA groups. The size of Spd-AKF-PLGA NPs was 172.5±4.3 nm. AKF release from NPs was shown to fit the Higuchi model. A549 cellular uptake of an Spd–coumarin (Cou)-6-PLGA NP group was found to be almost twice as high as that of the Cou-6-PLGA NP group. Free Spd and difluoromethylornithine (DFMO) were preincubated in A549 cells to prove uptake of Spd-Cou-6-PLGA NPs via a polyamine-transport system. As a result, the uptake of Spd-Cou-6-PLGA NPs significantly decreased with increased Spd concentrations in incubation. At higher Spd concentrations of 50 and 500 µM, uptake of Spd-Cou-6-PLGA NPs reduced 0.34- and 0.49-fold from that without Spd pretreatment. After pretreatment with DFMO for 36 hours, cellular uptake of Spd-Cou-6-PLGA NPs reached 1.26-fold compared to the untreated DFMO group. In a biodistribution study, the drug-targeting index of Spd-AKF-PLGA NPs in the lung was 3.62- and 4.66-fold that of AKF-PLGA NPs and AKF solution, respectively. This suggested that Spd-AKF-PLGA NPs accumulated effectively in the lung. Lung-histopathology changes and collagen deposition were observed by H&E staining and Masson staining in an efficacy study. In the Spd-AKF-PLGA NP group, damage was further improved compared to the AKF-PLGA NP group and AKF-solution group. The results indicated that Spd-AKF-PLGA NPs are able to be effective nanocarriers for anti–pulmonary fibrosis therapy.
研究领域:
药学
·
肺病学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC PLANT BIOLOGY
·
2017
·Vol. 17
·期 1
·1-16
·
IF 3.964
Huang Yutao,Lin Cheng,He Fei,Li Zhan,Guan Yajing,Hu Qijuan,Hu Jin
Background The low seed vigor and poor field emergence are main factors that restricting the extension of sweet corn in China. Spermidine (Spd) plays an important role in plant growth and development, but little is known about the effect of Spd on sweet corn seed germination. Therefore the effect of exogenous Spd on seed germination and physiological and biochemical changes during seed imbibition of Xiantian No.5 were investigated in this study.Results Spd soaking treatment not only improved seed germination percentage but also significantly enhanced seed vigor which was indicated by higher germination index, vigor index, shoot heights and dry weights of shoot and root compared with the control; while exogenous CHA, the biosynthesis inhibitor of Spd, significantly inhibited seed germination and declined seed vigor. Spd application significantly increased endogenous Spd, gibberellins and ethylene contents and simultaneously reduced ABA concentration in embryos during seed imbibition. In addition, the effects of exogenous Spd on H2O2 and MDA productions were also analyzed. Enhanced H2O2 concentration was observed in Spd-treated seed embryo, while no significant difference of MDA level in seed embryo was observed between Spd treatment and control. However, the lower H2O2 and significantly higher MDA contents than control were detected in CHA-treated seed embryos.Conclusion sThe results suggested that Spd contributing to fast seed germination and high seed vigor of sweet corn might be closely related with the metabolism of hormones including gibberellins, ABA and ethylene, and with the increase of H2O2 in the radical produced partly from Spd oxidation. In addition, Spd might play an important role in cell membrane integrity maintaining.
研究领域:
植物生理学
·
农业科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
·
2023
·
IF 4.3
Keren Xiao,He Cheng,Yumeng Chen,Luting Ren,Qiaojuan Zhang,Qimeng Wang,Nan Cheng,Wenjing Hong,Zhiyi Yao
For some small biomolecules with simple structures, it is difficult to achieve rapid detection because they lack strong interactions with probes. To solve this problem, we have developed an approach based on perylene diimide derivatives combining an in-situ pre-modification technique. In this strategy, the nucleophilic reaction of o-phthalaldehyde (OPA) was used to enhance the non-covalent interactions between the analyte and probe. This method was utilized for sensing glutathione (GSH) and spermidine (SPD) and had the characteristics of fast response, wide detection range, and high selectivity. Moreover, it has been validated with real samples and the detection mechanism was investigated systematically. To the best of our knowledge, this is the first attempt to apply perylene diimide derivatives to the detection of some biological small molecules by an in-situ pre-modification method.
研究领域:
分析化学
·
生物化学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）