Cell Death & Disease
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2025
·Vol. 16
·期 1
·1-11
·
IF 9.6
Chu Xiufeng,Zhang Ting,Bukhari Ihtisham,Hu Mei,Xu Jixuan,Xing Yamin,Liang Xinfeng,Zhang Zisen,Zheng Pengyuan
Gasdermin D (GSDMD) is a critical pyroptosis mediator, consisting of one N-terminal pore-forming domain and one C-terminal auto-inhibitory domain. The free N-terminal domain (GD-NT), which is released through caspase-1/11 cleavage, exhibits distinct features from the full-length GSDMD (GD-FL), including oligomerization, membrane translocation, and pore-formation. However, the underlying mechanisms are not well elucidated. Here, we found that GD-NT, but not GD-FL, was massively ubiquitinated in cells. The K63-linked polyubiquitination of GD-NT at Lys236/237 (human/mouse), catalyzed by TRAF1, directly prompted its membrane translocation and pore-formation during pyroptosis. Inhibition of GD-NT ubiquitination via site-directed mutations or the UBA1 inhibitor PYR-41 suppressed cell death in several pyroptosis cell models. Additionally, applying PYR-41 in septic mice efficiently suppressed the release of IL-18 and TNFα. Thus, GD-NT ubiquitination is a key regulatory mechanism controlling its membrane localization and activation, which may provide a novel target for modulating immune activity in pyroptosis-related diseases.
研究领域:
免疫学
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细胞生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Libo Zhu,Zhen Zhang,Quanjun Liu
With the development in DNA self-assembly technology, DNA origami nanostructures have been widely applied in biomedical research. Solid-state nanopores represent an emerging single-molecule sensing platform for studying nanostructures with arbitrary dimensions and physical characteristics, including DNA origami. Here, we employed relatively narrow silicon nitride nanopores to detect the deformation and translocation of DNA origami nanoplates with dimensions of approximately 60 × 54 nm. We performed translocation experiments using three nanopore diameters that are all smaller than the plat dimensions. Analysis of current blockade signals and the representative events reveals three types of translocation orientations for the nanoplates. Furthermore, by studying the electrical signal characteristics (current change and dwell time) for the different diameter pores, we obtained information about the translocation behaviors for the DNA nanoplates through different constrictions. Our investigation provides an approach to analyze the deformation and translocation of DNA origami structures.
研究领域:
生物物理学
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纳米技术
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单分子检测
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DOI
PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Yixuan Liu,Qi Sun,Chengfei Zhang,Min Ding,Cheng Wang,Qian Zheng,Zhijie Ma,Haojun Xu,Guoren Zhou,Xiaoming Wang,Zhangjun Cheng,Hongping Xia
Summary The liver is the main site of colorectal cancer (CRC) metastasis. Tumor-associated macrophages (TAMs) play a key role in tumor metastasis. Therefore, modulating the function of tumor-associated macrophages is a potential therapeutic strategy to control tumor metastasis. We found in vivo experiments that the activation of STING inhibited CRC liver metastasis in model mice and affected the macrophage phenotype in the tumor microenvironment. Mechanistically, STING affects TAM polarization and regulates macrophage function through IRG1. And STING activates IRG1 to promote the nuclear translocation of TFEB, affecting the ability of macrophages to suppress tumor metastasis.Therefore, this study highlights the critical role of the STING-IRG1 axis on TAM reprogramming and its role in the process of tumor liver metastasis, which may provide a promising therapeutic strategy for CRC liver metastasis.
研究领域:
肿瘤学
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免疫学
·
分子生物学
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DOI
PubMed
高影响因子
TALANTA
·
2015
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IF 3.545
Lu Hu,Panjie Zhang,Wanyu Shan,Xuan Wang,Songqing Li,Wenfeng Zhou,Haixiang Gao
A novel dispersion liquid–liquid microextraction method based on the solidification of sedimentary ionic liquids (SSIL-DLLME), in which an in situ metathesis reaction forms an ionic liquid (IL) extraction phase, was developed to determine four pyrethroid insecticides (i.e., permethrin, cyhalothrin , fenpropathrin , and transfluthrin) in water followed by separation using high-performance liquid chromatography. In the developed method, in situ DLLME was used to enhance the extraction efficiency and yield. After centrifugation, the extraction solvent, tributyldodecylphosphonium hexafluorophosphate ([P 44412 ][PF 6 ]), was easily collected by solidification in the bottom of the tube. The effects of various experimental parameters, the quantity of tributyldodecylphosphonium bromide ([P 44412 ]Br), the molar ratio of [P 44412 ]Br to potassium hexafluorophosphate (KPF 6 ), the ionic strength , the temperature of the sample solution, and the centrifugation time, were optimized using a Plackett–Burman design to identify the significant factors that affected the extraction efficiency. These significant factors were then optimized using a central composite design. Under the optimized conditions, the recoveries of the four pyrethroid insecticides at four spiked levels ranged from 87.1% to 101.7%, with relative standard deviations (RSDs) ranging from 0.1% to 5.5%. At concentration levels between 1 and 500 µg/L, good linearity was obtained, with coefficients of determination greater than 0.9995. The limits of detection (LODs) for the four pyrethroid insecticides were in the range of 0.71–1.54 µg/L. The developed method was then successfully used for the determination of pyrethroid insecticides in environmental samples.
研究领域:
分析化学
·
环境科学
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DOI
高影响因子
Bioengineered
·
2021
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IF 3.269
Bo Li,Xianyi Liu,Guogang Wu,Jiawen Liu,Shouliang Cai,Fuxin Wang,Chunyu Yang,Jisheng Liu
Colorectal cancer (CRC) is a global public health issue with increasing prevalence. MicroRNA-934 (miR-934) is a kind of non-coding RNA involved in the regulation of diverse cancers. Though previous researches have revealed part of association between miR-934 and CRC, the role of miR-934 in CRC pathogenesis has not been completely explored yet. In this study, we aim to investigate the effect of miR-934 on cell proliferation, migration, invasion and angiogenesis in CRC. Accordingly, miR-934 was found to be over-expressed in SW480 and HCT116 cells, two typical CRC cell lines. Meanwhile, miR-934 knockdown significantly inhibited cell proliferation and induced cell cycle arrest in SW480 and HCT116 cells. It was further validated that miR-934 knockdown displayed an inhibitory effect on cell migration and invasion in SW480 and HCT116 cells. Additionally, miR-934 deficiency markedly decreased VEGF expression in SW480 and HCT116 cells and suppressed capability of CRC cells to promote tube formation in vascular endothelial cells, which suggests the pro-angiogenesis role of miR-934 in vitro. Dual luciferase reporter assay further showed that miR-934 directly bound to B-cell translocation gene 2 (BTG2). BTG2 knockdown reversed the inhibitory effect of miR-934 silencing on cell proliferation, migration, invasion, and angiogenesis in SW480 and HCT116 cells. In summary, this study suggests that miR-934 facilitates CRC progression by targeting BTG2, and further highlights the role of miR-934 in pathogenesis of CRC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2025
·
IF 1.2
Junling Zhu,Rilian Lai,Qin Zheng,Shuying Huang,Shenghua Hu,Zhangfei Xu,Huixia Sun
1. To study the effects of calycosin on palmitic acid-induced HepG2 cells, as well as the potential mechanisms of action.2. Potential targets of calycosin for the alleviation of insulin resistance were predicted by network pharmacology. Glucose concentration in the culture medium was determined by the GOD-POD method. The model of insulin resistance was established by palmitic acid-induced HepG2 cells. Effects of palmitic acid and calycosin on HepG2 cell activity were determined using an MTT assay kit. The expression levels of AKT1 and FOXO3a were detected by western blot.The expression level of hsa-miR-324-3p was detected by RT-qPCR. Dual luciferase reporter assay to detect targeting of AKT1 by hsa-miR-324-3p.3. AKT1 was predicted and validated as a potential target of calycosin for treatment of insulin resistance. The model of insulin resistance was successfully established by palmitic acid-induced HepG2 cells. Up-regulation of AKT1 expression inhibits FOXO3a entry into the nucleus. Calycosian was demonstrated to concentration-dependently increase the sensitivity of insulin resistance cells to insulin. The hsa-miR-324-3p was proven to exist in insulin-resistant cells. Hsa-miR-324-3p was found to target AKT1 involved in the alleviation of insulin resistance.4. Calycosin inhibits FOXO3a nuclear translocation by regulating the hsa-miR-324-3p/AKT pathway, thus alleviating insulin resistance.
研究领域:
药理学
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分子生物学
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内分泌学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·
IF 15.7
Hu Xuewen,Zhou Tiantian,Cui Tiansi,Du Yuanjiao,Song Chunyu,Chang Weiping,Xiong Juan,Qin Jichao,Deng Lin,Ji Wei-Ke
Sigma Non-Opioid Intracellular Receptor 1 (SigmaR1) is a member of the sigma family of receptors that interacts with a variety of psychotomimetic drugs and is involved in a wide range of cellular and physiological functions. Despite its increasing importance in human physiology and disease, the subcellular localization of SigmaR1 and its molecular function remain poorly defined. Using endogenous tagging and cell fractionation, we show that SigmaR1 is a type II integral ER membrane protein that is specifically enriched at ER sheets. A short region at the N-terminus of SigmaR1 promotes its ER-sheet localization. Importantly, our biochemical studies demonstrate that SigmaR1 directly interacts with components of the translocon complex including TRAPα and Nicalin. In addition, we found that a β-barrel at the C-terminal of SigmaR1 binds phosphatidylcholine (PC), and the binding of PC strengthens the association of SigmaR1 with the translocon complex. SigmaR1 knockout systematically impaired cellular protein and lipid homeostasis, resulting in accumulation of lipid droplets in hepatocytes. Collectively, we propose that SigmaR1 is an auxiliary translocon factor that binds lipids to regulate protein and lipid droplet homeostasis, which may underlie the broad and vital roles of SigmaR1 in physiology and disease.
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DOI
PubMed
高影响因子
Cells
·
2022
·Vol. 11
·期 23
·3856
·
IF 7.666
Bin Liu,Hui Chen
The aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) belong to the bHLH-PAS (basic Helix–Loop–Helix–Period/ARNT/Single-minded) family of transcription factors, which participate in the sensing and transmitting stimuli of exogenous and endogenous chemical substances, and subsequently activates genes transcription involved in various detoxification and physiological functions. However, they have not been identified inDendroctonus armandi,and their roles in the detoxification metabolism are unclear. In the present study,AhRandARNTofD. armandiwere characterized. Spatiotemporal expression profiling indicated thatDaAhRandDaARNTwere highly expressed in the adult and larval stages ofD. armandiand mainly expressed in the midgut and Malpighian tubules of adults. Additionally, the expression ofDaAhRandDaARNTsignificantly increased after exposure to (−)-?-pinene, (+)-3-carene, and (±)-limonene. SilencingDaAhRandDaARNTincreased the susceptibility ofD. armandito (−)-?-pinene, (+)-3-carene, and (±)-limonene, and the activities of detoxification enzyme were also remarkably reduced. Moreover,DaCYP6DF1andDaGSTs2were significantly down-regulated after injections ofdsAhRanddsARNTin the male and female adults, with the expression ofDaCYP6DF1decreasing by higher than 70%. The present study revealed that the transcription factorsAhRandARNTofD. armandiwere induced by terpenoids and participated in the regulation ofDaCYP6DF1 expression, which was associated withD. armandi’s susceptibility to (−)-?-pinene and (±)-limonene. These results may provide a theoretical basis for the integrated control ofD. armandiand improve our comprehension of insect toxicology.Keywords:Dendroctonus armandi;AhR;ARNT;detoxification metabolism;transcriptional regulation
研究领域:
昆虫学
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分子生物学
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毒理学
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DOI
PubMed
高影响因子
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
·
2025
·Vol. 41
·期 10
·1-12
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IF 4.2
Sun Ying,Hua Qijing,Cai Yinglin,Dong Yamin,Xiao Yiwen,Bao Jianyin,Zhu Du,Liu Bin,Gao Boliang
Metal ions critically regulate microbial secondary metabolism. This study investigated the regulatory roles of metal ions in Shiraia sp. Slf14, an endophytic fungus with exceptional perylenequinone (PQ) biosynthesis capacity. Among eight ions tested, Na⁺, K⁺, Mg²⁺, and high Ca²⁺ (1.0 g/L) markedly enhanced PQ yields, while Mn²⁺, Cu²⁺, Zn²⁺, and Fe³⁺ (≥ 0.5 g/L) exerted strong inhibition. Na⁺ emerged as the optimal elicitor, boosting production to 504.82 ± 8.62 mg/L (+ 57.96%) at 1.0 g/L without cytotoxicity. Na⁺ exhibited concentration- and time-dependent biphasic regulation. Critical innovation was achieved at 4 g/L Na⁺ added on day 4 (early-log phase), maximizing total PQ yield (1836.95 ± 45.21 mg/L, 5.75 × control), while concentrations > 12 g/L or late addition (≥ day 8) suppressed biosynthesis. Component-specific sensitivities were observed among five PQs. Furthermore, Na⁺ activated the calcineurin pathway: stress-induced Cam/Cna triggered calcineurin-mediated Crz1 nuclear translocation, upregulating key PQ genes ( pksI , omef , hydroxylase ). Concurrent induction of ena1 (Na⁺ exporter) and Ca²⁺-ATPase maintained ion homeostasis. In conclusion, our work pointed out monovalent cations (Na⁺/K⁺) as potent PQ biosynthetic stimulators in filamentous fungi and establish the Na⁺-calcineurin-PQ axis, offering a scalable strategy to overcome production bottlenecks in pharmaceutical PQ manufacturing.
研究领域:
微生物学
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真菌生物学
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次级代谢产物
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信号转导
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药物生物技术
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分子生理学
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天然产物化学
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DOI
PubMed
高影响因子
FASEB JOURNAL
·
2022
·Vol. 36
·期 10
·e22530
·
IF 5.834
Chengyu Yang,Yang Liu,Ziyan Wang,Minmin Lin,Chao Liu
Despite the best treatment, approximately 10% of fractures still face undesirable repair and result in delayed unions or non-unions. Dynamic mechanical stimulation promotes bone formation, when applied at the correct time frame, with optimal loading magnitude, frequency, and repetition. Controlled mechanical loading significantly increases osteogenic cells during the matrix deposition phase of bone repair. In the bone defect, the blood vessel network guides the initial bone formation activities. A unique blood vessel subtype (Type H) exists in bone, which expresses high levels of CD31 and endomucin, and functions to couple angiogenesis and osteogenesis. However, how this form of controlled mechanical loading regulates the Type H vessels and promotes bone formation is still not clear. Sphingosine 1-phosphate (S1P) participates in the bone anabolic process and is a key regulator of the blood vessel. Its receptor, sphingosine 1-phosphate receptor 1 (S1Pr1), is a mechanosensitive protein that regulates vascular integrity. Therefore, we hypothesis that controlled anabolic mechanical loading promotes bone repair by acting on Type H vessels. To study the effect of S1Pr1 on loading induced-bone repair, we utilized a stabilized tibial defect model, which allows for the application of anabolic mechanical loading. Mechanical loading upregulated S1Pr1 within the entire defect, with up to 80% expressed in blood vessels, as observed by deep tissue imaging. Additionally, S1Pr1 antagonism by W146 inhibited the anabolic effects of mechanical loading. We showed that mechanical loading or activating S1Pr1 could induce YAP nuclear translocation, a key regulator in the cell's mechanical response, in endothelial cells (ECs) in vitro. Inhibition of S1Pr1 in endothelial cells by siRNA reduced loading-induced YAP nuclear translocation and expressions of angiogenic genes. In vivo, YAP nuclear translocation in Type H vessels was up-regulated after mechanical loading but was inhibited by antagonizing S1Pr1. S1Pr1 agonist, FTY720, increased bone volume and Type H vessel volume, similar to that of mechanical stimulation. In conclusion, controlled anabolic mechanical loading enhanced bone formation mainly through Type H vessels in a S1Pr1-dependent manner.
研究领域:
骨科
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再生医学
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生物力学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NEUROTOXICITY RESEARCH
·
2022
·Vol. 40
·期 2
·596-604
·
IF 3.978
Wang Fei,Li Wu-lin,Shen Li-juan,Jiang Ting-ting,Xia Jian-jun,You Da-li,Hu Shan-you,Wang Li,Wu Xiao
Intracerebral hemorrhage (ICH) is the deadliest type of stroke. Oxidative stress was considered to play an important role in ICH-induced secondary injury. Crocin, the main compound isolated from Crocus sativus L., possesses a potential anti-oxidative function in many types of diseases including ICH. In the current study, the protective role of crocin in ICH-induced brain injury was investigated in the ICH model. The ICH-induced brain edema and neurological deficits were analyzed by brain edema measurement and neurological testing. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity and the content of malondialdehyde (MDA) were assessed by a total superoxide dismutase assay kit. The expressions of ferroptosis-related genes were verified by quantitative real-time PCR (qPCR) and western blotting. The ICH-induced brain edema and neurological deficits were significantly decreased after treatment with crocin. Moreover, the SOD and GSH-px activities were obviously increased in the ICH with crocin-treated group compared with the ICH group, while the content of MDA was markedly decreased after treatment with crocin. Crocin inhibited ferroptosis of neuron cells, as evidenced by increased Fe 2+ concentration and the expression of GPX4, FTH1, and SLC7A11. Mechanistically, crocin treatment increased the expression and nuclear translocation of Nrf2. Our data suggest that crocin alleviates intracerebral hemorrhage–induced neuronal ferroptosis by facilitating Nrf2 nuclear translocation.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
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IF 7.2
Li Liang,Weiliang Sun,Xiaoxuan Wei,Li Wang,Huaqiang Ruan,Junchuan Zhang,Suyan Li,Bi Zhao,Mengshi Li,Zhengwen Cai,Jie'an Huang
Chinese herb Radix sophorae tonkinensis extract oxymatrine shows anticancer effects. This study evaluated the role of oxymatrine in colorectal cancer (CRC) and the underlying molecular events in vitro and in vivo. CRC cells were treated with different doses of oxymatrine to assess cell viability, reactive oxygen species production, gene expression, and gene alterations. Meanwhile, mouse xenograft and liver metastasis models were used to assess the effects of oxymatrine using histology examination, transmission electron microscopy, and Western blot, respectively. Our results showed that oxymatrine treatment triggered CRC cell mitophagy to inhibit CRC cell growth, migration, invasion, and metastasis in vitro and in vivo. At the gene level, oxymatrine inhibited LRPPRC to promote Parkin translocation into the mitochondria and reduce the mitophagy-activated NLRP3 inflammasome. Thus, oxymatrine had an anticancer activity through LRPPRC inhibition, mitophagy induction, and NLRP3 inflammasome suppression in the CRC cell xenograft and liver metastasis models. In conclusion, the study demonstrates the oxymatrine anti- CRC activity through its unique role in regulating CRC cell mitophagy and NLRP3 inflammasome levels in vitro and in vivo.
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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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）