INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 13
·7413
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IF 6.208
Yuanyuan Li,Daming Xiao,Shujun Li,Zhijun Chen,Shouxin Liu,Jian Li
Fluorescent materials based on aggregation-induced emission luminogens (AIEgens) have unique advantages for in situ and real-time monitoring of biomolecules and biological processes because of their high luminescence intensity and resistance to photobleaching. Unfortunately, many AIEgens require time-consuming and expensive syntheses, and the presence of residual toxic reagents reduces their biocompatibility. Herein,[email protected]nanoparticles ([email protected]), which have a clear core–shell structure, were prepared by redox reaction of quercetin (QC), a polyphenolic compound widely obtained from plants, including those used as foods, and silver ions.[email protected]show both aggregation-induced luminescence and the distinct plasma scattering of silver nanoparticles, as well as good resistance to photobleaching and biocompatibility. The[email protected]were successfully used for cytoplasmic labeling of living cells and for computerized tomography imaging in tumor-bearing mice, demonstrating their potential for clinical applications.Keywords:quercetin;silver;self-assembling nanoparticles;aggregation-induced emission luminogens;bioimaging
研究领域:
纳米技术
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生物医学工程
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材料科学
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生物学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2020
·Vol. 21
·期 12
·4336
·
IF 4.556
Jingjue Zeng,Muhammad Salman Haider,Junbo Huang,Yanshuai Xu,Tariq Pervaiz,Jiao Feng,Huan Zheng,Jianmin Tao
The glycogen synthase kinase 3/shaggy kinase (GSK3) is a serine/threonine kinase that plays important roles in brassinosteroid signaling, abiotic stress responses, cell division, and elongation, etc. In this study, we characterized seven grape GSK3 genes, showing high similarities with homologs from other species includingArabidopsis, white pear, apple, orange, and peach. Gene chip microarray data derived from an online database revealed very diverse developmental and tissue-specific expression patterns ofVvSKs.VvSK3andVvSK7showed much higher expression levels in almost every tissue compared with other members.VvSK7was highly enriched in young tissues like berries before the veraison stage, young leaves and green stems, etc., but immediately downregulated after these tissues entered maturation or senescence phases. Prediction of cis-elements inVvSKpromoters indicated thatVvSKsmight be sensitive to light stimulation, which is further confirmed by the qPCR data. Constitutive overexpression ofVvSK7inArabidopsisleads to dwarf plants that resembles BR-deficient mutants. The photosynthetic rate was significantly reduced in these plants, even though they accumulated more chlorophyll in leaves. Transient overexpression ofVvSKsin tomatoes delayed the fruit ripening process, consistent with the observation in grapevine which blocksVvSKsby EBR- or BIKININ-promoted berry expansion and soluble solids accumulation. Data presented in the current study may serve as a theoretical basis for the future application of BRs or related compounds in quality grape production.Keywords:GSK3;grapes;evolutionary analysis;light response;photosynthesis;ripening
研究领域:
植物学
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遗传学
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植物生理学
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Cell Chemical Biology
·
2020
·
IF 7.739
Bo Zhang,Yan Wang,Shenlong Huang,Jiaqi Sun,Min Wang,Wenxiao Ma,Yanbo You,Ling Wu,Jin Hu,Wei Song,Xudong Liu,Shengjie Li,Hua Chen,Guisheng Zhang,Lihe Zhang,Demin Zhou,Lingjun Li,Xuan Zhang
Summary Chimeric antigen receptor (CAR)-T-based therapeutics are a breakthrough in cancer treatment; however, they are hampered by constitutive activation, which leads to worrisome side effects. Engineering CAR-T cells to be as tightly controllable as possible remains a topic of ongoing investigation. Here, we report a photoswitchable approach that uses a mediator for the at-will regulation of CAR-T cells. This mediator carries dual folate and fluorescein isothiocyanate moieties tethered by an ortho-nitrobenzyl ester photocleavable linker. CAR-T cells were shown to be highly cytotoxic to targeted cells only in the presence of the mediator and acted in a dose-dependent manner. The toxicity of CAR-T cells can be rapidly terminated by cleavage of the mediator, and the effects of CAR-T cells can be activated again by resupplementation with the mediator without compromising tumor therapy. The approach described here provides a direction for enhancing the controllability of CAR-T cells and can likely be applied in other immunotherapies.
研究领域:
免疫疗法
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癌症研究
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分子生物学
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生物医学工程
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Human Cell
·
2023
·Vol. 36
·期 3
·987-996
·
IF 4.3
Yiou Wang,Zhihong Wang,Shibai Zhu,Shanni Li,Wenwei Qian
The dysregulation of microRNAs plays a critical role in the development of rheumatoid arthritis (RA). This study aims to explore the functional significance of miR-326 in RA. The RT-qPCR results showed that miR-326 was downregulated in synovial tissues of RA patients and RA fibroblast-like synoviocytes (RA-FLS). We found that miR-326 could target and reduce the expression of inhibitor of DNA binding 1 (Id1). MTT assay and flow cytometry were conducted to explore the biological function of miR-326. Our data revealed that the upregulation of miR-326 suppressed cell proliferation and induced apoptosis in RA-FLS. In collagen-induced arthritis mice, intraarticular injection of lentivirus carrying miR-326 overexpression vectors could reduce the arthritis score and attenuate synovial inflammation and cartilage destruction. We also found that long non-coding RNA-Ewing sarcoma-associated transcript 1 (lncRNA-EWSAT1) was significantly increased in RA synovial tissues and RA-FLS. The RNA immunoprecipitation and RNA pull-down assay indicated that lncRNA-EWSAT1 directly bound and negatively regulated the expression of miR-326. Knockdown of lncRNA-EWSAT1 could upregulate miR-326 expression and attenuate its proliferation inhibition and apoptosis induction effect in RA-FLS. In conclusion, the lncRNA-EWSAT1/miR-326 axis might provide a novel therapeutic target in the treatment of RA.
研究领域:
免疫学
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分子生物学
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风湿病学
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CHEMICO-BIOLOGICAL INTERACTIONS
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2026
·
IF 5.2
Wenzhi Wu,Xiaohai Chen,Weiyi Zhang,Haoxin Fu,Jie Chen,Chenchen Qian,Saili Xie,Congcong Zeng
Sleep disorders, particularly insomnia, are highly prevalent worldwide, and melatonin is widely used therapeutically as a key regulator of the sleep-wake cycle. This study aimed to investigate the inhibitory effect of apatinib on melatonin metabolism and its underlying mechanism. We elucidated the effect of apatinib on the metabolism of melatonin using rat liver microsomes (RLM) and human liver microsomes (HLM) and recombinant human CYP1A2 (rCYP1A2), complemented by pharmacokinetics in rats and molecular docking. In vitro , apatinib showed non-competitive inhibition in RLM (IC 50 = 15.85 μΜ) and competitive inhibition in HLM (IC 50 = 5.10 μΜ) and rCYP1A2 (IC 50 = 3.60 μΜ). IC 50 shift analysis yielded a shift ratio of 1.26 in RLM, indicating that apatinib exhibited non-time-dependent inhibition on melatonin metabolism. In vivo , apatinib markedly increased melatonin exposure with AUC (area under the curve) increased by approximately 2.8-fold (P < 0.05) and decreased clearance by 70.39% (P < 0.05), while significantly reducing the exposure of 6-hydroxymelatonin (the main metabolite of melatonin). Furthermore, molecular docking simulations revealed that both melatonin and apatinib were bound to the active pocket of CYP1A2, sharing interactions with residues Thr124 and Leu497. Overall, apatinib inhibited CYP1A2-mediated metabolism of melatonin in vitro and increased melatonin exposure in vivo , suggesting a potential clinically relevant interaction that may warrant caution and individualized dosing/monitoring when co-administered. However, the findings are limited by the use of rat pharmacokinetics and in vitro systems, and require confirmation in human clinical studies.
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JOURNAL OF FLUORESCENCE
·
2011
·Vol. 22
·期 2
·699-706
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IF 1.966
Chen Haiyan,Cui Sisi,Tu Zhenzhen,Gu Yueqing,Chi Xuemei
CdHgTe/SiO 2 nanoparticles were prepared by SiO 2 capping on the surface of CdHgTe QDs. The characteristics, such as optical spectra, photostability, size and cell toxicity were investigated. The dynamic distribution of CdHgTe/SiO 2 nanoparticles was in vivo monitored by near infrared fluorescence imaging system. CdHgTe/SiO 2 nanoparticles acted as a novel fluorescence probe have a maximum fluorescence emission of 785 nm and high photo-stability. The hydrodynamic diameter of CdHgTe/SiO 2 nanoparticles could be adjusted to 122.3 nm. Compared to CdHgTe QDs, inhibitory effects of CdHgTe/SiO 2 nanoparticles on proliferation of HCT116 cells decreased to a certain extent. CdHgTe/SiO 2 nanoparticles had their specific dynamic distribution behavior, which provided new perspectives for bio-distribution of nanoparticles.
研究领域:
纳米技术
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生物医学成像
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毒理学
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纳米医学
·
分子探针
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ACS Synthetic Biology
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2026
·
IF 4.5
Ruiying Zhu,Zehua Bao
Genetic diversification serves as the foundation for in vivo molecular evolution. The fusion of a cytidine deaminase with T7 RNA polymerase (MutaT7) enables efficient diversification of DNA sequences downstream of the T7 promoter in model microbial hosts E. coli and S. cerevisiae. Vibrio natriegens, currently the fastest-growing nonpathogenic bacterium with a doubling time half that of E. coli, emerged as a promising alternative chassis for synthetic biology. Here, we report the establishment of MutaT7 in V. natriegens (dubbed VnMutaT7), achieving rapid evolution of the model protein TEM-1 to confer high-level ceftazidime resistance in just 36 h. This work establishes the potential of V. natriegens as an accelerated platform for protein engineering.
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EXPERIMENTAL AND MOLECULAR MEDICINE
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2023
·Vol. 55
·期 1
·183-195
·
IF 12.8
Wu Zhuhua,Zhu Li,Nie Xinran,Wei Li,Qi Yong
Pulmonary hypertension (PH) is a life-threatening cardiopulmonary disease characterized by pulmonary vascular remodeling. Excessive growth and migration of pulmonary artery smooth muscle cells (PASMCs) are believed to be major contributors to pulmonary vascular remodeling. Ubiquitin-specific protease 15 (USP15) is a vital deubiquitinase that has been shown to be critically involved in many pathologies. However, the effect of USP15 on PH has not yet been explored. In this study, the upregulation of USP15 was identified in the lungs of PH patients, mice with SU5416/hypoxia (SuHx)-induced PH and rats with monocrotaline (MCT)-induced PH. Moreover, adeno-associated virus-mediated functional loss of USP15 markedly alleviated PH exacerbation in SuHx-induced mice and MCT-induced rats. In addition, the abnormal upregulation and nuclear translocation of YAP1/TAZ was validated after PH modeling. Human pulmonary artery smooth muscle cells (hPASMCs) were exposed to hypoxia to mimic PH in vitro, and USP15 knockdown significantly inhibited cell proliferation, migration, and YAP1/TAZ signaling in hypoxic hPASMCs. Rescue assays further suggested that USP15 promoted hPASMC proliferation and migration in a YAP1/TAZ-dependent manner. Coimmunoprecipitation assays indicated that USP15 could interact with YAP1, while TAZ bound to USP15 after hypoxia treatment. We further determined that USP15 stabilized YAP1 by inhibiting the K48-linked ubiquitination of YAP1. In summary, our findings reveal the regulatory role of USP15 in PH progression and provide novel insights into the pathogenesis of PH.
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ACS Applied Materials & Interfaces
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2023
·
IF 9.5
Aihui Wang,Hongyan Li,Hao Feng,Huimin Qiu,Rimei Huang,Yiqin Wang,Shichen Ji,Hong Liang,Xing-Can Shen,Bang-Ping Jiang
Natural biopolymers can be controllably in situ synthesized in organisms and play important roles in biological activities. Inspired by this, the manipulation of in situ biosynthesis of functional polymers in vivo will be an important way to obtain materials for meeting biological requirements. Herein, in situ biosynthesis of functional conjugated polymer at the tumor site was achieved via the utilization of specific tumor microenvironment (TME) characteristics for the first time. Specially, a water-soluble aniline dimer derivative (N-(3-sulfopropyl) p-aminodiphenylamine, SPA) was artfully in situ polymerized into polySPA (PSPA) nanoparticles at the tumor site, which was activated via the catalysis of hydrogen peroxide (H2O2) overexpressed in TME to produce hydroxyl radical (•OH) by coinjected horseradish peroxidase (HRP). Benefiting from outstanding near-infrared (NIR)-II absorption of PSPA, the in situ polymerization process can be validly monitored by photoacoustic (PA) signal at the NIR-II region. Meanwhile, in situ polymerization would induce the size of polymeric materials from small to large, improving the distribution and retention of PSPA at the tumor site. On the combination of NIR-II absorption of PSPA and the size variation induced by polymerization, such polymerization can be applied for tumor-specific NIR-II light mediated PA image and photothermal inhibition of tumors, enhancing the precision and efficacy of tumor phototheranostics. Therefore, the present work opens the way to manipulate TME-activated in situ biosynthesis of functional conjugated polymer at the tumor site for overcoming formidable challenges in tumor theranostics.
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CHEMOSPHERE
·
2023
·
IF 8.8
Xiaorong Wu,Shiqi Li,Meijia Zhang,Shengjun Bai,Yangyue Ni,Qiaoqiao Xu,Yun Fan,Chuncheng Lu,Zhipeng Xu,Chenbo Ji,Guizhen Du,Yufeng Qin
Bisphenol AP (BPAP), a structural analog of bisphenol A (BPA), has been widely detected in environment and biota. BPAP was reported to interfere with hormone and metabolism, while limited data were available about its effects on neurobehavior, especially exposure to it during early-life time. A mouse model of early-life BPAP exposure was established to evaluate the long-term neurobehaviors in offspring . Collectively, early-life BPAP exposure caused anxiety-like behaviors and impaired learning and memory in adult offspring. Through brain bulk RNA-sequencing (RNA-seq), we found differential expressed genes were enriched in pathways related to behaviors and neurodevelopment, which were consistent with the observed phenotype. Besides, single-nucleus RNA-sequencing (snRNA-seq) showed BPAP exposure altered the transcriptome of microglia in hippocampus. Mechanistically, BPAP exposure induced inflammations in hippocampus through upregulating Iba-1 and activating the microglia. In addition, we observed that BPAP exposure could activate peripheral immunity and promote proportion of macrophages and activation of dendritic cells in the offspring. In conclusion, early-life exposure to BPAP impaired neurobehaviors in adult offspring accompanied with excessive activation of hippocampal microglia. Our findings provide new clues to the underlying mechanisms of BPAP's neurotoxic effects and therefore more cautions should be taken about BPAP.
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ENVIRONMENTAL POLLUTION
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2022
·
IF 9.988
Caihong Wang,Zihong Pan,Yuanxiang Jin
Chlorinated polyfluorinated ether sulfonate (F–53 B) is a distinct substitute for perfluorooctane sulphonate. It has been reported to be biologically toxic to mammals, causing enteric toxicity, liver toxicity and neurotoxicity. However, studies about the effects of F–53 B on patients with gastrointestinal diseases such as inflammatory bowel disease are very limited. In this study, whether the toxic impacts of F–53 B on the gut and liver can be exacerbated in mice with colitis was explored. The sensitivity of mice with acute colitis caused by dextran sulfate sodium salt (DSS) to F–53 B was compared with that of healthy mice. The mice were administered water containing F–53 B at doses of 10 and 100 μg/L sequentially for two weeks, respectively. F–53 B exposure exacerbated DSS-induced colonic inflammation, including inducing shortening of colon length, inflammatory cell infiltration and more severe histopathological symptoms. In addition, F–53 B administration significantly increased the levels of inflammatory cytokines, including interleukin (IL)-1, IL-6 and tumour necrosis factor-α, in the plasma of mice with enteritis compared with control group. F–53 B impaired intestinal integrity of mice with colitis by downregulating Claudin-1 and antimicrobial peptide-related genes while elevating serum lipopolysaccharide levels. In addition, in mice with colitis, F–53 B increased the levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, aspartate aminotransferase, and alanine aminotransferase, resulted in more severe liver inflammation and increased the level of genes related to the Gasdermin D-mediated pyrolysis . Conclusively, our results indicated that F–53 B delayed the self-healing of ulcerative colitis (UC) and caused liver inflammation in mice. This study provided some new insights into the health risks of F–53 B and raises concerns about the health of individuals with UC.
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Lipids in Health and Disease
·
2023
·Vol. 22
·期 1
·1-14
·
IF 4.5
Tan Lunbo,Ouyang Zijun,Chen Zhilong,Sun Fen,Guo Haichun,Wang Feng,Mulder Monique,Sun Yuan,Lu Xifeng,Zhang Jian V.,Danser A. H. Jan,Verdonk Koen,Fan Xiujun,Yang Qing
Background The adipokine chemerin regulates adipogenesis and the metabolic function of both adipocytes and liver. Chemerin is elevated in preeclamptic women, and overexpression of chemerin in placental trophoblasts induces preeclampsia-like symptoms in mice. Preeclampsia is known to be accompanied by dyslipidemia, albeit via unknown mechanisms. Here, we hypothesized that chemerin might be a contributor to dyslipidemia. Methods Serum lipid fractions as well as lipid-related genes and proteins were determined in pregnant mice with chemerin overexpression in placental trophoblasts and chemerin-overexpressing human trophoblasts. In addition, a phospholipidomics analysis was performed in chemerin-overexpressing trophoblasts. Results Overexpression of chemerin in trophoblasts increased the circulating and placental levels of cholesterol rather than triglycerides. It also increased the serum levels of lysophosphatidic acid, high-density lipoprotein cholesterol (HDL-C), and and low-density lipoprotein cholesterol (LDL-C), and induced placental lipid accumulation. Mechanistically, chemerin upregulated the levels of peroxisome proliferator-activated receptor g, fatty acid-binding protein 4, adiponectin, sterol regulatory element-binding protein 1 and 2, and the ratio of phosphorylated extracellular signal-regulated protein kinase (ERK)1/2 / total ERK1/2 in the placenta of mice and human trophoblasts. Furthermore, chemerin overexpression in human trophoblasts increased the production of lysophospholipids and phospholipids, particularly lysophosphatidylethanolamine. Conclusions Overexpression of placental chemerin production disrupts trophoblast lipid metabolism, thereby potentially contributing to dyslipidemia in preeclampsia.
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