CELL BIOLOGY AND TOXICOLOGY
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2024
·Vol. 40
·期 1
·1-18
·
IF 5.3
Yang Ye,He Runze,Li Dongxiao,Mu Tianli,Kuang Ziteng,Wang Min
Zinc finger protein 384 (ZNF384) is a highly conserved transcribed gene associated with the development of multiple tumors, however, its role and mechanism in serous ovarian cancer (SOC) are unknown. We first confirmed that ZNF384 was abnormally highly expressed in SOC tissues by bioinformatics analysis and immunohistochemistry. We further used lentivirus packaging and transfection techniques to construct ZNF384 overexpression or knockdown cell lines, and through a series of cell function experiments, gradually verified that ZNF384 promoted a series of malignant behaviors of SOC cell proliferation, migration, and invasion. By establishing a xenotransplantation model in nude mice, it was confirmed that ZNF384 promoted the progress of SOC in vivo. Mechanistically, Overexpression of ZNF384 enhanced the transcriptional activity of Lin-28 homolog B (LIN28B), which promoted the malignant behavior of SOC cells. In addition, LIN28B could regulate the expression of the downstream factor ubiquitin D (UBD) in SOC cells, further promoting the development of SOC. This study shows that ZNF384 aggravates the malignant behavior of SOC cells through the LIN28B/UBD axis, which may be used as a diagnostic biomarker for patients with SOC. Graphical abstract
研究领域:
肿瘤学
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分子生物学
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遗传学
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF PATHOLOGY
·
2024
·
IF 4.7
N.I.N.G. HAN,N.A. YU,L.I. YU
Diabetic retinopathy (DR) is the major ocular complication of diabetes mellitus caused by chronic hyperglycemia, which leads to incurable blindness. Currently, the effectiveness of therapeutic interventions is limited. This study aimed to investigate the function of piezo-type mechanosensitive ion channel component 1 (PIEZO1) and its potential regulatory mechanism in DR progression. The results showed that PIEZO1 expression was upregulated in the retinal tissues of streptozotocin-induced diabetic mice and high glucose (HG)-triggered Müller cells. Functionally, the knockdown of PIEZO1 improves the abnormal retinal function of diabetic mice and impedes inflammatory cytokine secretion and gliosis of Müller cells under HG conditions. Mechanistic investigations utilizing RIP-qPCR, MeRIP-qPCR, and luciferase reporter assays demonstrated that PIEZO1 was a downstream target of methyltransferase-like 3 (METTL3). These studies revealed that METTL3-mediated N6-methyladenosine (m6A) modification within the coding sequence of PIEZO1 mRNA significantly shortened its half-life. In HG-stimulated cells, there was a negative regulatory relationship between PIEZO1 and YTH domain family 2 (YTHDF2), a recognized m6A reader. The loss of YTHDF2 resulted in an extended half-life of PIEZO1 in cells with overexpression of METTL3, indicating that the effect of METTL3 on the mRNA stability of PIEZO1 was dependent on YTHDF2. Taken together, this study demonstrated the protective role of the PIEZO1 silencing in DR development, and the degradation of PIEZO1 mRNA is accelerated by METTL3/YTHDF2-mediated m6A modification.
研究领域:
分子生物学
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细胞生物学
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神经科学
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糖尿病研究
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眼科学
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产品关联
DOI
PubMed
高影响因子
Biomarker Research
·
2024
·Vol. 12
·期 1
·1-16
·
IF 9.5
Wang Zhen,Liu Zhongwen,Zhou Pan,Niu Xiaona,Sun Zhengdao,He Huan,Zhu Zunmin
Background Megakaryocytic differentiation is a complicated process regulated by a series of transcription factors in a context- and stage-dependent manner. Recent studies have suggested that krüppel-like transcription factor 2 (KLF2) is involved in the control of embryonic erythroid precursor cell differentiation and maturation. However, the function and mechanism of KLF2 in regulating megakaryocytic differentiation remain unclear. Methods The expression patterns of krüppel-like transcription factors (KLFs) during megakaryocytic differentiation were identified from public databases. Phorbol 12-myristate 13-acetate (PMA) treatment of the myeloid-erythroid-leukemic cell lines K562 and HEL were used as cellular megakaryocytic differentiation models. A lentiviral transduction system was utilized to achieve the goal of amplifying or reducing KLF2. The expression of KLF2 was examined using real-time PCR and western blot. The impact of KLF2 on the megakaryocytic differentiation of K562 cells was examined by flow cytometry, Giemsa staining, Phalloidin staining and western blot. RNA-sequencing (RNA-seq) and chromatin immunoprecipitation-sequencing (ChIP-seq) technologies were used to identify the KLF2-regulated targets. Results KLF2 is increased in the maturation process of megakaryocytes. KLF2 overexpression accelerated the PMA-induced megakaryocytic differentiation, as reflected by an increased percentage of CD41/CD61 cells, an increased number of polyploid cells, and an elevated expression of P21 and P27. KLF2 knockdown exhibited the opposite results, indicating that KLF2 knockdown suppressed the megakaryocytic differentiation. Further, combination of the RNA-seq and ChIP-seq results suggested that chimerin 1 (CHN1) and potassium voltage-gated channel subfamily Q member 5 (KCNQ5) may be target genes regulated of KLF2. Both CHN1 and KCNQ5 knockdown could block the megakaryocytic differentiation to some content. Conclusion This study implicated a regulatory role of KLF2 in megakaryocytic differentiation, which may suggest KLF2 as a target for illness with abnormal megakaryocytic differentiation.
研究领域:
血液学
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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
EXPERIMENTAL CELL RESEARCH
·
2024
·
IF 3.3
Wei Shen,Xuzhong Zhang,Min Tang,Wei Chen,Ying Wang,Haoquan Zhou
Septic brain injury is a serious disease of the central nervous system that involves inflammation. Kelch repeat and BTB domain containing 7 (KBTBD7), an E3 ubiquitin ligase, is demonstrated to facilitate the pathological changes of various diseases, but its impact on septic brain injury is unclear. In this study, a rat model of septic brain injury was induced by cecal ligation and puncture (CLP). The neurobehavioral score and survival rate of CLP group were worse than those of sham group. In addition, CLP was found to evoke microglia activation, increase inflammation, induce the activation of NLRP3 inflammasome and NF-κB signaling pathway, and upregulate KBTBD7 expression. Immunofluorescence revealed strong positive KBTBD7 staining in CLP rat microglia. Furthermore, primary microglia were exposed to lipopolysaccharide (LPS) to explore the role and mechanism of KBTBD7. The results showed that KBTBD7 expression was increased in LPS-treated microglia. Knockdown of KBTBD7 markedly inhibited LPS-induced proinflammatory cytokine release, as well as the activation of NLRP3 inflammasome and NF-κB signaling pathway. The downstream molecular mechanism of KBTBD7 was then mined. Notably, co-immunoprecipitation (co-IP) results confirmed that KBTBD7 was a novel interacting protein of KLF transcription factor 15 (KLF15) and acted as an E3 ubiquitin ligase that catalyzed the ubiquitination degradation of KLF15 through the ubiquitin-proteasome system. Moreover, recovery experiment data suggested that KLF15 knockdown abolished the anti-inflammatory role of KBTBD7 knockdown in microglia, implying that KLF15 influenced the function of KBTBD7. Taken together, our results reveal a novel KBTBD7-KLF15 signal transduction pathway involved in septic brain injury and provide a potential therapeutic strategy for its treatment.
研究领域:
神经科学
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免疫学
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Small
·
2024
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IF 13
Mengmeng Zhang,Mingzhu Lu,Yimin Gong,Yannan Yang,Junfei Song,Jianing Li,Zhenxia Chen,Yun Ling,Yaming Zhou
Precise integration of diverse therapeutic approaches into nanomaterials is the key to the development of multimodal synergistic cancer therapy. In this work, tadpole-like carbon nanotubes with Fe nanoparticle encapsulated at the head and Zn single-atom anchored on the body (Fe@CNT-Zn) is precisely designed and facilely prepared via one-pot carbonization. In vitro studies revealed the integration of chemotherapy (CT), chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT) in Fe@CNT-Zn as well as the near-infrared light (NIR)-responsive cascade therapeutic efficacy. Furthermore, in vivo studies demonstrated the NIR-triggered cascade-amplifying synergistic cancer therapy in a B16 tumor-bearing mouse model. The results not only showcased the Fe@CNT-Zn as a potential tetramodal therapeutic platform, but also demonstrated a proof-of-concept on metal–organic framework-based “one stone for multiple birds” strategy for in situ functionalization of carbon materials.
研究领域:
生物医学工程
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纳米医学
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肿瘤治疗
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产品关联
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY COMMUNICATIONS
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2024
·
IF 4.4
Han Song,Jiasheng Fan,Shengkai Liu,Boyu Chen,Jin Huang,Yujie Fu,Zhiguo Liu
In this study, we synthesized DOX-loaded H-ZIF-8@CaCO 3 -PEG nanocarrier, which combined with calcium overload and photothermal therapy (PTT) for synergistic therapy. The nanocarrier comprised a PEG modified calcium carbonate (CaCO 3 ) shell and a hollow imidazolate zeolite skeleton (H-ZIF-8) core, in which the chemotherapy drug doxorubicin hydrochloride (DOX) and photosensitizer indocyanine green (ICG) were simultaneously co-loaded. In vitro cellular experiments revealed that the lethality of DOX&ICG@H-ZIF-8@CaCO 3 -PEG against tumor cells was significantly higher than that of the single chemotherapy owing to the combination with chemotherapy and photothermal therapy as well as calcium overloading. This drug-loaded nanocarrier exhibits notable characteristics such as exceptional stability, elevated drug loading capacity and efficient release of the loaded drug, which provides a promising perspective for efficient synergistic therapy.
研究领域:
纳米技术
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药学
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癌症治疗
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产品关联
DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2024
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IF 4.3
Wen-Jie Mao,Tian-Tian Wang,Lin Chen,Lei Zhang,Shan Li
Tyramine signaling amplification (TSA) technology is generally applied in immunofluorescence, enzyme-linked immunoassays, in situ hybridization techniques, etc. Successful amplification of fluoresence signals cannot be achieved without excellent fluorescent dyes. BODIPY fluorophore is an ideal probe for cell fluorescence imaging, but pristine BODIPY cannot be direct used in the TSA system. In the paper, the new red-shifted tyramide-conjugated BODIPY ( BDP-B/C/D ) was synthesized via the Knoevenagel condensation reaction, which based on the tyramide-conjugated BODIPY (BDP-A). The synthesized dyes were combined with tyramine to obtain which could be used as a fluorescent substrate for enzymatic reaction of TSA. By using the selected substrate ( BDP-C ) in TSA, we found it to be more sensitive than the commercial dye 594 styramide for the detection of low-abundance antigen proteins.
研究领域:
生物化学
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细胞生物学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
·
IF 9.4
Hezhong Jiang,Wenlan Fang,Shiqi Xu,Haimeng Luo,Dongqiu Li,Yuan Liu,Zhijun Zeng,Yan Tong,Long Zhao
In current clinical practice, the presence of biofilms poses a significant challenge in the effective elimination of bacterial infections because of the physical and chemical barriers formed by biofilms, which offer persistent protection to bacteria. Here, we developed hollow mesoporous polydopamine (hMP) nanoparticles (NPs) loaded with luteolin (Lu) as a quorum sensing inhibitor, which were further coated with hyaluronic acid (HA) shells to create hMP-Lu@HA NPs. We observed that upon reaching the infection site, the HA shells underwent initial degradation by the hyaluronidase enzyme present in the bacterial infection's microenvironment to expose the hMP-Lu NPs. Subsequently, Lu was released in response to the acidic conditions characteristic of bacterial infections, which effectively hindered and dispersed the biofilm. Moreover, when subjected to near-infrared irradiation, the robust photothermal conversion effect of hMP NPs accelerated the release of Lu and disrupted the integrity of the biofilms by localized heating. This dual action enhanced the eradication of the biofilm infection. Importantly, hMP-Lu@HA NPs also promoted tissue regeneration and healing at the implantation site, concurrently addressing biofilm infection. Taken together, this nanosystem, combined with mild-temperature photothermal therapy and quorum sensing inhibition strategy, holds significant potential for applications in the treatment of implantation-associated infections.
研究领域:
纳米技术
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生物医学工程
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药学
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传染病学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
·Vol. 13
·期 7
·2533-2548
·
IF 5.7
Mingbo Wu,Dong Li,Yao Liu,Xiaomiao Ruan,Jingwen Yang,Zegang Li,Siyi Chen,Xin Yang,Wenwu Ling
Piezocatalytic therapy is an emerging therapeutic strategy for eradicating drug-resistant bacteria, but suffers from insufficient piezoelectricity and catalytic active site availability. Herein, Bi-vacancies (BiV) and corona polarization were introduced to BiOBr nanosheets to create a BiOBr-BiVP nanoplatform for piezocatalytic antibacterial therapy. This meticulously tailored strategy strengthens the built-in electric field of nanosheets, enhancing piezoelectric potential and charge density and boosting charge separation and migration efficiency. Meanwhile, BiV adeptly adjust the band structure and increase reaction sites. Ultrasonication of nanosheets continuously enables the generation of reactive oxygen species (ROS) and CO, facilitating almost 100% broad-spectrum antibacterial efficacy. BiOBr-BiVP nanosheets demonstrate full bacterial eradication and accelerate wound healing through simultaneous regulation of inflammatory factors, facilitation of collagen deposition, and promotion of angiogenesis. Overall, this ultrasonic-triggered piezocatalytic nanoplatform combines BiV and the corona polarization strategy, providing a robust strategy for amplifying piezocatalytic mediated ROS/CO generation for drug-resistant bacterial eradication.
研究领域:
材料科学
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生物医学工程
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微生物学
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产品关联
DOI
PubMed
高影响因子
Research
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2024
·
IF 8.5
Hao Liu,Ke Huang,Hao Zhang,Xiaohui Liu,Hui Jiang,Xuemei Wang
Achieving antitumor immunotherapy based on hybridization of multiple types of inactivated cells has attracted a lot of attention. However, the hybridized cells of disordered structure could result in the shedding of antigens and their transfer to immune cells, which suppresses tumor immunity through trogocytosis. Here, we report a strategy for in situ solidification of tumor whole cell by biomineralization for sustained stimulation of antitumor immunity. The near-infrared light was used to accelerate the breaking of Au=P bonds in auranofin, and the exposed Au atoms biomineralize at the secondary structure (β-corner) of the protein to form Au nanocrystals with in situ protein coronas in tumor cells. Au nanocrystals are anchored to the tumor cells through protein coronas, which fixes the morphology and antigens of whole tumor cells, rendering them physiologically inactive. Interestingly, this solidified tumor cell prevents immune cells from undergoing trogocytosis, which inhibits proximal and distal tumor growth. Thus, this study presents the strategy of solidified cells and its potential application in tumor immunotherapy.
研究领域:
肿瘤免疫学
·
生物医学工程
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Congling Yang,Qianying Guo,Xinchun Wang,Hongmei Chen,Huan Tan,Bo Feng,Jie Weng
Multi-responsive drug-delivery systems have been widely explored to enable specific delivery to target sites. Here, interleukin-4 (IL-4), an anti-inflammatory cytokine, is first encapsulated in situ inside a zeolitic imidazolate framework (ZIF-8) to form IL-4@ZIF-8, which is subsequently coated with a diselenide block copolymer to obtain IL-4@ZIF-8@Se-Se-polymer. This delivery system enables redox-responsive release of IL-4 by the diselenide copolymer and a pH-triggered release by ZIF-8. Moreover, IL-4 release is precisely controlled stepwise by the stimuli response, with the dissociation of the diselenide copolymer, and breakdown of the ZIF-8 structure. The targeted release property of the IL-4@ZIF-8@Se-Se-polymer endows the materials with efficient macrophage immune regulation, as systematically demonstrated in vitro. This study provides an effective example of the delivery and on-demand release of IL-4, and may find promising applications in tissue engineering for the management of inflammation.
研究领域:
生物材料学
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免疫学
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Heliyon
·
2024
·
IF 3.4
Chongchong Liu,Jiangyan Sun,Xiaoming Shen,Shefang Li,Sha Luo,Na Chen,Yunke Zhang
Epilepsy is a chronic neurological disorder. Drug-resistant epilepsy (DRE) accounts for about one-third of epilepsy patients worldwide. Peimine, a main active component of Fritillaria, has been reported to show anti-inflammatory effects. However, its potential therapeutic role in DRE is not yet fully understood. In this work, a DRE rat model was established by injecting 1 μg kainic acid (KA), followed by a 250 mg/kg administration of valproic acid (VPA) from day 4–31. Rats were treated with different doses of peimine (2.5 mg/kg, 5 mg/kg and 10 mg/kg) daily from day 32–62. In vitro, BV-2 microglia were exposed to different doses of peimine (7.5 μg/ml, 15 μg/ml, and 30 μg/ml) in presence of LPS. The aim of this study was to investigate the potential therapeutic effects of peimine on DRE. The results showed that peimine efficiently suppressed the KA-induced epileptic behaviors of rats in a dose-dependent manner, as recorded by electroencephalography. Furthermore, peimine ameliorated hippocampal neuron injury in DRE rats, and promoted an M1-to-M2 microglial phenotype shift in a dose-dependent manner. Mechanistically, peimine inhibited the TLR4/NF-κB/HIF-1α signaling pathway both in vivo and in vitro. Additionally, peimine suppressed the apoptosis of primary neurons induced by LPS-treated microglia. In conclusion, peimine augments the microglial polarization towards an M2 phenotype by inhibiting the TLR4/NF-κB/HIF-1α signaling pathway, thereby attenuating DRE.
研究领域:
神经病学
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药理学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）