Plants-Basel
·
2024
·Vol. 13
·期 4
·543
·
IF 4
Long Lu,Xinyu Chen,Qinyan Tan,Wenqian Li,Yanyan Sun,Zaoli Zhang,Yuanyuan Song,Rensen Zeng
Aluminum toxicity poses a significant constraint on crop production in acidic soils. While phytohormones are recognized for their pivotal role in mediating plant responses to aluminum stress, the specific involvement of gibberellin (GA) in regulating aluminum tolerance remains unexplored. In this study, we demonstrate that external GA exacerbates the inhibitory impact of aluminum stress on root growth of rice seedlings, concurrently promoting reactive oxygen species (ROS) accumulation. Furthermore, rice plants overexpressing the GA synthesis geneSD1exhibit enhanced sensitivity to aluminum stress. In contrast, theslr1gain-of-function mutant, characterized by impeded GA signaling, displays enhanced tolerance to aluminum stress, suggesting the negative regulatory role of GA in rice resistance to aluminum-induced toxicity. We also reveal that GA application suppresses the expression of crucial aluminum tolerance genes in rice, includingAl resistance transcription factor 1(ART1),Nramp aluminum transporter 1(OsNramp4), andSensitive to Aluminum 1(SAL1). Conversely, theslr1mutant exhibits up-regulated expression of these genes compared to the wild type. In summary, our results shed light on the inhibitory effect of GA in rice resistance to aluminum stress, contributing to a theoretical foundation for unraveling the intricate mechanisms of plant hormones in regulating aluminum tolerance.
研究领域:
植物学
·
遗传学
·
植物生理学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Xin Shen,Yiqun Xia,Hui Lu,Peisen Zheng,Junqi Wang,Yinghua Chen,Chenxin Xu,Chenyu Qiu,Yafei Zhang,Zhongxiang Xiao,Peng Zou,Ri Cui,Daoyong Ni
Thioredoxin reductase 1 (TrxR1) has emerged as a promising target for cancer therapy. In our previous research, we discovered several new TrxR1 inhibitors and found that they all have excellent anti-tumor activity. At the same time, we found these TrxR1 inhibitors all lead to an increase in AKT phosphorylation in cancer cells, but the detailed role of AKT phosphorylation in TrxR1 inhibitor-mediated cell death remains unclear. In this study, we identified the combination of AKT and TrxR1 inhibitor displayed a strong synergistic effect in colon cancer cells. Furthermore, we demonstrated that the synergistic effect of auranofin (TrxR1 inhibitor) and MK-2206 (AKT inhibitor) was caused by ROS accumulation. Importantly, we found that ATM inhibitor KU-55933 can block the increase of AKT phosphorylation caused by auranofin, and exhibited a synergistic effect with auranofin. Taken together, our study demonstrated that the activation of ATM/AKT pathway is a compensatory mechanism to cope with ROS accumulation induced by TrxR1 inhibitor, and synergistic targeting of TrxR1 and ATM/AKT pathway is a promising strategy for treating colon cancer.
研究领域:
肿瘤学
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药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Yushun Chang,Jie Lin,Bo Yang,Yuxuan Shen,Weijun Zhao,Hao Shen,Quan Yang,Haowen Lu,Xiujun Cai,Yifan Wang,Wen Hua
Background Aloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, exhibits anticancer activity in several malignancies, but its efficacy and mechanisms in gallbladder cancer (GBC) remain undefined. Methods Human GBC cell lines (GBCs) were treated with ALO and assessed for viability, colony formation, 5-Ethynyl-2′-deoxyuridine (EdU) incorporation and apoptosis. Autophagic flux and related signaling were evaluated by western blotting and immunofluorescence. In vivo antitumor activity was determined in a nude mouse xenograft model. Results ALO markedly inhibited the proliferation ability of GBCs and disrupted autophagosome–lysosome fusion, leading to reactive oxygen species (ROS) accumulation and apoptosis. Furthermore, ALO induced DNA damage and nuclear release of double-stranded DNA (dsDNA) to cytoplasm, leading to cyclic-GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING)-mediated interferon (IFN) pathway activation and enhancing natural killer cells (NK cells) activation in vitro. In vivo, ALO reduced subcutaneous GBCs xenograft volume and weight and, along with increased cleaved caspase-3 and BAX expression in tumor tissues, confirming tumor cell apoptosis. Conclusions These findings indicate that ALO may serve as a novel therapeutic candidate for gallbladder cancer by inhibiting autophagic flux to induce ROS-mediated apoptosis while activating the cGAS–STING–IFN pathway to enhance antitumor immunity.
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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免疫学
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转化医学
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细胞信号转导
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 11
·e70681
·
IF 4.2
Yao Chen,Heqi Dai,Fei Mao,Yangbai Li,Ruizhi Feng,Yun Qian
Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in women of reproductive age. However, the underlying molecular mechanism remains unclear. In this study, we employed RNA sequencing analysis to identify differentially expressed protein‐coding genes and long noncoding RNA (lncRNA) expression profiles in granulosa cells from women with and without PCOS. It was established that the level of NONHSAT233728.1 was diminished in women with PCOS. The present study demonstrated the role of NONHSAT233728.1 in granulosa cells from patients with PCOS and further investigated the potential mechanism of NONHSAT233728.1 in the KGN cell line. Additionally, the knockdown of NONHSAT233728.1 has been observed to promote cell apoptosis, inhibit cell proliferation, promote mitochondrial dysfunction, and inflammation. Western blot analyses confirmed that phospho‐extracellular regulated protein kinases (ERK)1/2 were decreased following lnc‐NONHSAT233728.1 knockdown. Consequently, we propose that ROS accumulation activates the endogenous mitochondrial apoptosis pathway, leading to granulosa cell apoptosis via the MEK/ERK1/2 pathway, which contributes to follicular atresia. We observed a negative correlation between NONHSAT233728.1 and both LH levels and the LH/FSH ratio. These findings indicate that lncRNA NONHSAT233728.1 is linked to the pathogenesis of PCOS and offer new insights into its underlying mechanisms. Through isolation and transcriptomic profiling of granulosa cells, we identified the functional significance of lncRNA NONHSAT233728.1 in polycystic ovary syndrome (PCOS) pathogenesis. Knockdown of lncRNA NONHSAT233728.1 in granulosa cells elevated ROS levels, reduced the Bcl2/Bax ratio, downregulated phospho‐ERK1/2, and increased IL‐8 secretion. These results demonstrate ROS‐mediated mitochondrial apoptosis via MEK/ERK1/2 suppression, alongside inhibited proliferation and enhanced inflammation, consistent with follicular atresia in PCOS. Negative correlations between NONHSAT233728.1 and LH/FSH ratios further support its pathogenic role.
研究领域:
生殖医学
·
分子生物学
·
内分泌学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Yuhao Wu,Junke Wang,Tianxin Zhao,Yuexin Wei,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di-(2-ethylhexyl) phthalate (DEHP), one of the most commonly used endocrine-disrupting chemicals, has been shown to cause reproductive dysfunction in humans and animal models. However, very few studies have investigated the impact of DEHP at the post-transcriptional level in mouse testes, and the underlying mechanisms remain unclear. In the present research, TM3 Leydig cells were treated with 200 µM phthalic acid mono-2-ethylhexyl ester (MEHP, bio-metabolite of DEHP), and then the mRNA and lncRNA sequencing of TM3 Leydig cells was performed. Mice were exposed prepubertally to 0 or 500 mg DEHP/kg/day. RNA sequencing of mouse testes was performed to verify the RNA-seq results in vitro . The expression patterns of relevant genes and proteins were verified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. DEHP and MEHP exposure led to testicular damage and accelerated cell aging via ROS accumulation. RNA sequencing analyses indicated that FOXO signaling and longevity regulation pathways were activated in resistance to ROS accumulation. FOXO signaling and longevity regulation pathway-related genes and proteins were also activated. By constructing a competing endogenous RNA (ceRNA) network, we observed that the ceRNA network might play a role in regulating FOXO signaling and longevity regulation pathways in response to excessive ROS accumulation and cell aging. In summary, our data here suggests that the ceRNA network may play a role in regulating FOXO signaling and longevity pathways in response to DEHP exposure in mouse testes.
研究领域:
生殖生物学
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毒理学
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分子生物学
·
基因组学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Qianqian Zhao,Min Gu,Mengnan Ni,Jinyu Li,Ting Wu,Senlin Zhu,Yupeng Zhou,Yawen Lu,Xiaolin Li,Huae Xu,Meiping Lu
Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa mediated by immunoglobulin E (IgE) after exposure to allergens. The bothersome symptoms of AR, such as runny nose and nasal congestion, affect millions of people worldwide. Ipratropium Bromide (IB), commonly used in clinical practice for treating AR, requires frequent administration through nasal spray and may cause significant irritation to the nasal mucosa. The induction of ROS is closely related to the initiation and symptoms of AR, and ROS will continue to accumulate during the onset of AR. To address these challenges, we have designed a drug delivery system that can be administered in liquid form and rapidly crosslink into a ROS-responsive gel in the nasal cavity. This system enables sustained ROS responsive release of IB in a high-concentration ROS environment at AR lesions, thereby alleviating AR symptoms. The gel demonstrated prolonged release of IB for up to 24 hours in rats. In the treatment of AR rat models, it improved their symptoms, reduced the expression of various inflammatory factors, suppressed MUC5AC protein expression, and decreased mucus secretion through a ROS responsive IB release pattern. Overall, this system holds promise as a better option for AR treatment and may inspire the design of nanogel-based nasal drug delivery systems.
研究领域:
药学
·
药物递送
·
过敏与免疫学
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生物医学工程
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DOI
PubMed
高影响因子
Colloid and Interface Science Communications
·
2025
·
IF 4.7
Shouguang Wang,Xiaofei Zhang,Dunmin Zhuang,Lina Dong,Bo Li
Objective Breast cancer remains a global health challenge due to limitations of conventional therapies, such as drug resistance and systemic toxicity. This study aimed to develop a novel synergistic chemo-immunotherapy platform by constructing Mn 2+ -coordinated oxidized hyaluronic acid (OHA)-based nanoparticles co-loaded with phloretin (PHL) (OHA@Lys/PHL Mn 2+ ). Methods A nanosystem was engineered using oxidized hyaluronic acid (OHA) modified with lysine (Lys) to co-encapsulate PHL and Mn 2+ ions. The anti-tumor efficacy was evaluated in vitro (4 T-1 breast cancer cells) and in vivo (4 T-1 tumor-bearing mice), including assessments of proliferation inhibition, apoptosis induction, reactive oxygen species (ROS) accumulation, DNA damage, cGAS-STING pathway activation, and dendritic cell (DC) maturation. Combination therapy with cisplatin (CDDP) was also investigated. Results OHA@Lys/PHL Mn 2+ achieved 80.3 % cell viability inhibition on 4 T-1 cells. Combined with CDDP, it further suppressed proliferation, induced apoptosis, and enhanced ROS accumulation. Mechanistically, the nanosystem induced DNA double-strand damage and activated the cGAS-STING pathway. In vivo , OHA@Lys/PHL Mn 2+ monotherapy showed significant tumor inhibition (46.4 %, p < 0.001). Combination with CDDP achieved near-complete tumor suppression (86.7 % inhibition) and reduced lung metastasis. The in vivo mechanism results indicated that nanosystem triggered DNA damage, activated cGAS-STING signaling, and significantly promoted DC maturation (48.5 % vs. 28.2 % in controls). Conclusion This strategy offers a promising and clinically translatable approach for advanced breast cancer treatment.
研究领域:
纳米医学
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肿瘤学
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药学
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免疫治疗
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药物递送系统
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生物化学
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分子生物学
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产品关联
DOI
高影响因子
TRANSITION METAL CHEMISTRY
·
2018
·Vol. 43
·期 2
·149-159
·
IF 1.261
Chen Jincan,Zhang Yao,Li Baojun,Li Guodong,Jie Xinming,Cui Ying,Zou Zhilin,Huang Xiaofeng,Qu Jiaoyue,Chen Lanmei
Two ruthenium complexes [Ru(MeIm) 4 (bpy)] 2+ ( Ru1 , MeIm = 1-methylimidazole, bpy = 2,2′-bipyridine) and [Ru(Im) 4 (bpy)] 2+ ( Ru2 , Im = imidazole) with the same PF
− 6
counter-ion but different lipophilicities were synthesized and characterized and as potent anticancer agents. The relationships between cellular uptake, localization and molecular action mechanisms of these complexes were elucidated. The results showed that Ru1 with higher log P o/w exhibited faster cellular uptake rates, but lower anticancer activity than Ru2 . In addition, Ru1 predominantly accumulated in the mitochondria and cytoplasm, and induced G0/G1 cell cycle arrest, whereas the more hydrophilic Ru2 tended to localize and accumulate in the cell nucleus and mitochondria. Further mechanism studies indicated that Ru2 caused cell cycle arrest at S phase by regulating cell cycle related proteins and induced apoptosis in A549 cells through DNA damage, cellular ROS accumulation, activation of the caspase pathway and mitochondrial dysfunction.
研究领域:
化学
·
药理学
·
癌症研究
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细胞生物学
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产品关联
DOI
高影响因子
Stress Biology
·
2023
·Vol. 3
·期 1
·1-17
·
IF 0
Duan Kaili,Shen Qifang,Wang Yu,Xiang Ping,Shi Yutong,Yang Chenfei,Jiang Cong,Wang Guanghui,Xu Jin-Rong,Zhang Xue
Plant hormones are important for regulating growth, development, and plant-pathogen interactions. Some of them are inhibitory to growth of fungal pathogens but the underlying mechanism is not clear. In this study, we found that hyphal growth of Fusarium graminearum was significantly reduced by high concentrations of IAA and its metabolically stable analogue 2,4-dichlorophenoxyacetic acid (2,4-D). Besides inhibitory effects on growth rate, treatments with 2,4-D also caused significant reduction in conidiation, conidium germination, and germ tube growth. Treatments with 2,4-D had no obvious effect on sexual reproduction but significantly reduced TRI gene expression, toxisome formation, and DON production. More importantly, treatments with 2,4-D were inhibitory to infection structure formation and pathogenesis at concentrations higher than 100 µM. The presence of 1000 µM 2,4-D almost completely inhibited plant infection and invasive growth. In F. graminearum , 2,4-D induced ROS accumulation and FgHog1 activation but reduced the phosphorylation level of Gpmk1 MAP kinase. Metabolomics analysis showed that the accumulation of a number of metabolites such as glycerol and arabitol was increased by 2,4-D treatment in the wild type but not in the Fghog1 mutant. Transformants expressing the dominant active FgPBS2 S451D T455D allele were less sensitive to 2,4-D and had elevated levels of intracellular glycerol and arabitol induced by 2,4-D in PH-1. Taken together, our results showed that treatments with 2,4-D interfere with two important MAP kinase pathways and are inhibitory to hyphal growth, DON biosynthesis, and plant infection in F. graminearum .
研究领域:
植物病理学
·
分子生物学
·
植物激素
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DOI
FOOD CHEMISTRY
·
2024
·
IF 8.5
Jia-ping Ke,Jia-Yi Li,Zi Yang,Hao-Yue Wu,Jing-Ya Yu,Yi Yang,Chen-Hui Chen,Peng Zhou,Fang Hua,Wei Wang,Fenglin Hu,Gang-Xiu Chu,Xiao-Chun Wan,Guan-Hu Bao
Tea drinking impacts aging and aging-related diseases. However, knowledge of anti-aging molecules other than the major catechins in complex tea extracts remains limited. Here we used Caenorhabditis elegans to analyze the longevity effects of tea extracts and constituents comprehensively. We found that the hot water extract of green tea prolonged lifespan and heathspan. Further, the MeOH fraction prolonged lifespan significantly longer than other fractions. Correlation analysis between mass spectroscopic data and anti-aging activity suggests that ester-type catechins (ETCs) are the major anti-aging components, including 4 common ETCs, 6 phenylpropanoid-substituted ester-type catechins (PSECs), 5 cinnamoylated catechins (CCs), 7 ester-type flavoalkaloids (ETFs), and 4 cinnamoylated flavoalkaloids (CFs). CFs (200 μM) are the strongest anti-aging ETCs (with the longest 73% lifespan extension). Green tea hot water extracts and ETCs improved healthspan by enhancing stress resistance and reducing ROS accumulation. The mechanistic study suggests that they work by multiple pathways. Moreover, ETCs modulated gut microbial homeostasis , increased the content of short-chain fatty acids, and reduced fat content. Altogether, our study provides new evidence for the anti-aging benefits of green tea and insights into a deep understanding of the chemical truth and multi-target mechanism.
研究领域:
衰老研究
·
生物化学
·
药理学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Wenqian Zhang,Kangkang Zha,Yuan Xiong,Weixian Hu,Lang Chen,Ze Lin,Chenyan Yu,Wu Zhou,Faqi Cao,Hankun Hu,Bobin Mi,Guohui Liu
The diabetic wounds remain to be unsettled clinically, with chronic wounds characterized by drug-resistant bacterial infections, compromised angiogenesis and oxidative damage to the microenvironment. To ameliorate oxidative stress and applying antioxidant treatment in the wound site, we explore the function of folliculin-interacting protein 1 (FNIP1), a mitochondrial gatekeeper protein works to alter mitochondrial morphology, reduce oxidative phosphorylation and protect cells from unwarranted ROS accumulation. And our in vitro experiments showed the effects of FNIP1 in ameliorating oxidative stress and rescued impaired angiogenesis of HUVECs in high glucose environment. To realize the drug delivery and local regulation of FNIP1 in diabetic wound sites, a novel designed glucose-responsive HA-PBA-FA/EN106 hydrogel is introduced for improving diabetic wound healing. Due to the dynamic phenylboronate ester structure with a phenylboronic acid group between hyaluronic acid (HA) and phenylboronic acid (PBA), the hydrogel is able to realize a glucose-responsive release of drugs. Fulvic acid (FA) is added in the hydrogel, which not only severs as crosslinking agent but also provides antibacterial and anti-inflammatory abilities. Moreover, the release of FEM1b-FNIP1 axis inhibitor EN106 ameliorated oxidative stress and stimulated angiogenesis through FEM1b-FNIP1 axis regulation. These in vivo and in vitro results demonstrated that accelerated diabetic wounds repair with the use of the HA-PBA-FA/EN106 hydrogel, which may provide a promising strategy for chronic diabetic wound repair.
研究领域:
药理学
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生物医学工程
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伤口愈合
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糖尿病
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材料科学
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DOI
PubMed
高影响因子
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