EXPERIMENTAL ANIMALS
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2023
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IF 2.4
Hong-Bo YANG,Ying LI,Xiu-Hai LI,Qing-Ming YAN,Xian-Zhang HAN,Jian CAO,Hong-Peng SANG,Jin-Long LI
Spinal cord injury (SCI) is a devastating disease characterized by neuronal apoptosis. Gli-similar 3 (GLIS3), a transcriptional factor, was involved in cell apoptosis and associated with the transcription of downstream target genes related to neuronal function. However, the function of GLIS3 in SCI remains unknown. Therefore, we used the mouse model of SCI to explore the role of GLIS3 in SCI. The results showed that GLIS3 expression was significantly increased in spinal cord tissues of SCI mice, and GLIS3 overexpression promoted the functional recovery, reserved histological changes, and inhibited neuronal apoptosis after SCI. Through online tools, the potential target genes of GLIS3 were analyzed and we found that Mps One Binder Kinase Activator 1b (MOB1b) had a strong association with SCI among these genes. MOB1b is a core component of Hippo signaling pathway, which was reported to inhibit cell apoptosis. MOB1b expression was significantly increased in mice at 7 days post-SCI and GLIS3 overexpression further increased its expression. Dual-luciferase reporter assay revealed that GLIS3 bound to the promoter of MOB1b and promoted its transcription. In conclusion, our findings reveal that the compensatory increase of GLIS3 promotes functional recovery after SCI through inhibiting neuronal apoptosis by transcriptionally regulating MOB1b. Our study provides a novel target for functional recovery after SCI.
研究领域:
神经科学
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分子生物学
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转录调控
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DOI
PubMed
高影响因子
Biomedical Materials
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2023
·Vol. 18
·期 5
·055024
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IF 4
Lihong Qiao,Xiaoxia Li,Chuanqi Wei,Zhongjun Li,Shisong Han,Du Cheng
Chemodynamic therapy (CDT) is a rising technology for cancer therapy by converting intracellular hydrogen peroxide (H2O2) into hydroxyl radical (•OH) via transition-metal-containing nanoparticles (NPs) catalysis reaction (i.e. Fenton reaction) to kill tumor cells. Highly efficient Fenton reaction and favorable delivery of the catalytic NPs 'nanoenzyme' are the key for successful treatment of cancer. In this work, we developed a novel nanoenzyme MnFe2O4@GFP for in vitro and in vivo antitumor therapy. A new MnFe2O4 nanoparticle containing two transition-metal-element Fe and Mn was synthesized for enhanced Fenton reaction and used to co-deliver protein with high biocompatibility through post-modification with dopamine polymerization, green fluorescent protein adsorption, and PEG coating. The enrichment of H2O2 and glutathione (GSH) in tumor tissue provided a favorable microenvironment for in situ generation of toxic free radicals. Fe3+ and GSH triggered a redox reaction to produce Fe2+, which in turn catalyzed H2O2 into •OH, with the consumption of antioxidant GSH. By combining Fe3+ with another catalyzer, the catalytic efficiency of the nanoenzyme were greatly improved. Consequently, the nanoenzyme showed efficient antitumor ability both in vitro and in vivo. Thus, the multifunctional CDT nanoenzyme platform shows great promising for antitumor therapy through the combination of catalyzers Fe3+ and Mn2+ and codelivery of protein cargo.
研究领域:
生物医学工程
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癌症治疗
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纳米医学
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DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
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2023
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IF 3.9
Yan Nan,Wang Zhengdong,Li Zhou,Zheng Yang,Chang Nan,Xu Kangjie,Wang Qian,Duan Xiaoxu
This study aimed to examine the immuntoxic effects of arsenic in the nervous system. Our results showed that arsenic increased corticocerebral and hippocampal weights ( p < 0.05). Morris water maze tests revealed that arsenic significantly increased the time spent in latency to platform on the fourth day in 50 mg/L arsenic exposure and the fifth day in 25 and 50 mg/L arsenic exposure, as well as reduced the path length in target quadrant, time spent in target quadrant, and crossing times of the platform ( p < 0.05). Hematoxylin–eosin staining showed that the vacuolated degeneration and pyknosis was found in the cerebral cortex and hippocampus of arsenic-treated mice. The mRNA levels of corticocerebral and hippocampal brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were decreased in the 50 mg/L arsenic-treated group ( p < 0.05). In addition, immunofluorescence staining showed that 25 and 50 mg/L arsenic all increased the expression of CD11b and glial fibrillary acidic protein (GFAP) in the cerebral cortex and hippocampus ( p < 0.05). Arsenic markedly raised antigen-presenting molecule MHCII and CD40 mRNA levels in the cerebral cortex and hippocampus and upregulated the cell chemokine receptor 5 (CCR5) and CCR7 mRNA levels in the cerebral cortex at the 50 mg/L arsenic group, and increased the CCR7 mRNA levels in the hippocampus at the 25 and 50 mg/L arsenic groups ( p < 0.05). Arsenic activated the nucleotide-binding domain-like receptor protein-3 (NLRP3) inflammasome, and enhanced its upstream promoter NF-κB protein level and downstream regulators IL-18 mRNA levels. Collectively, these results provide new evidences for the neuro-immune toxicity of arsenic. Graphical abstract
研究领域:
神经毒理学
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免疫毒理学
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神经科学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Kai Yue,Chao Yang,Yu You,Xueying Wang,Xinxin Zhang
Background A good understanding of the adhesion behaviors of the nanocarriers in microvessels in chemo-hyperthermia synergistic therapy is conducive to nanocarrier design for targeted drug delivery.Methods In this study, we constructed an artificial blood vessel system using gelatins with a complete endothelial monolayer formed on the inner vessel wall. The numbers of adhered NPs under different conditions were measured, as well as the interaction forces between the arginine–glycine–aspartic acid (RGD) ligands and endothelial cells.Results The experimental results on the adhesion of ligand–coated nanoparticles (NPs) with different sizes and morphologies in the blood vessel verified that the gelatin-based artificial vessel possessed good cytocompatibility and mechanical properties, which are suitable for the investigation on NP adhesion characteristics in microvessels. When the temperature deviated from 37 °C, an increase or decrease in temperature resulted in a decrease in the number of adhered NPs, but the margination probability of NP adhesion increased at high temperatures due to the enhanced Brownian movement and flow disturbance. It is found that the effect of cooling was less than that of heating according to the observed changes in cell morphology and a decrease in cell activity under the static and perfusion culture conditions within the temperature range of 25 °C–43 °C. Furthermore, the measurement results of change in the RGD ligand-cell interaction with temperature showed good agreement with those in the number of adhered NPs.Conclusion The Findings suggest that designing ligands that can bind to the receptor and are least susceptible to temperature variation can be an effective means to enhance drug retention.
研究领域:
生物医学工程
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纳米医学
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细胞生物学
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DOI
PubMed
高影响因子
MICROVASCULAR RESEARCH
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2023
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IF 3.1
Yushu Liu,Dong Wang,Yimin Jin,Guifang Sun,Qi Lou,Hong Wang,Weimin Li
Atrial fibrillation (AF) is a cardiac disease characterized by disordered atrial electrical activity. Atrial inflammation and fibrosis are involved in AF progression. Costunolide (COS) is a sesquiterpene lactone containing anti-inflammatory and anti-fibrotic activities. This study aims to explore the underlying mechanisms by which COS protects against AF. Male C57BL/6 mice (8- to 10-week-old) were infused with angiotensin (Ang) II for 3 weeks. Meanwhile, different doses of COS (COS-L: 10 mg/kg, COS-H: 20 mg/kg) were administered to mice by intragastric treatment. The results showed irregular and rapid heart rates in Ang II-treated mice. Moreover, the levels of inflammatory cytokines and fibrotic factors were elevated in mice. COS triggered a reduction of Ang II-induced inflammation and fibrosis, which conferred a protective effect. Mechanistically, mitochondrial dysfunction with mitochondrial respiration inhibition and aberrant ATP levels were observed after Ang II treatment. Moreover, Ang-II-induced excessive reactive oxygen species caused oxidative stress, which was further aggravated by inhibiting Nrf2 nuclear translocation. Importantly, COS diminished these Ang-II-mediated effects in mice. In conclusion, COS attenuated inflammation and fibrosis in Ang-II-treated mice by alleviating mitochondrial dysfunction and oxidative stress. Our findings represent a potential therapeutic option for AF treatment.
研究领域:
心脏病学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
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2023
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IF 8.6
Pengyu Zang,Yaqian Du,Chenghao Yu,Dan Yang,Shili Gai,Lili Feng,Shikai Liu,Piaoping Yang,Jun Lin
The newly developed thermoelectric dynamic therapy (TEDT) may not only solve the problem that photothermal therapy (PTT) is limited by the overexpression of heat shock proteins (HSPs) in tumor cells but also improve the killing effect through a dynamic process. Here, we propose photothermal-driven TEDT based on Ag–Ag2S nanoparticles that integrate Ag2S with Ag+ vacancies (VAg) and Ag in a Janus structure. VAg and Ag optimize the band structure and thermoelectric properties of Ag2S, and additional electrons from the introduction of Ag enhance the PTT effect and facilitates the construction of a significant thermoelectric field for electron–hole migration in the reverse direction, thereby markedly enhancing the TEDT effect. Furthermore, the generated VAg can also serve as a hole trap to suppress electron–hole recombination to promote 1O2 production, which inactivates HSPs to produce positive feedback on PTT, leading to better antitumor efficacy. The combined photothermal–thermoelectric therapeutic properties of Ag–Ag2S were verified from both in vivo and in vitro perspectives using ESR, UV–visible spectroscopy, cellular experiments, simulated tumor models, and other experiments.
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物医学工程
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产品关联
DOI
高影响因子
Journal of Natural Medicines
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2023
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IF 3.3
He Dongjie,Song Yanli,Xiao Huidongzi,Shi Shaoqi,Song Hongyan,Cui Tianwei,Ni Tingting,Wang Jing,Ren Xingxing,Wei Aiwu
Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels, which could promote focal angiogenesis to exert neuroprotection. However, there was no report that verified the exact effects of LIG on endometrial angiogenesis and the pregnancy outcomes. To explore the effects of LIG on low endometrial receptivity (LER) and angiogenesis, pregnancy rats were assigned into Control (saline treatment), LER (hydroxyurea-adrenaline treatment), LIG 20 mg/kg and LIG 40 mg/kg groups. Hematoxylin and eosin (H&E) staining was performed to evaluate endometrial morphology. Quantitative real-time PCR, immunofluorescence staining, western blot and immunohistochemistry staining were employed to assess the expression of endometrial receptivity factors and angiogenesis-related gene/protein, respectively. RNA sequencing was used to analyze the effects of LIG on LER caused by Kidney deficiency and blood stasis. We found that endometrial thickness and the implanted embryo number were substantially reduced in the hydroxyurea-adrenaline-treated pregnancy rats. At the same time, the gene and protein expressions of ERα, LIF, VEGFA and CD31 in the endometrium were markedly reduced, while the expressions of MUC1, E-cadherin were increased in the LER group. Administration of LIG raised the endometrial thickness and implanted embryos, as well as reversed the expressions of these factors. Collectively, our findings revealed that LIG could facilitate embryo implantation via recovery of the endometrium receptivity and promotion of endometrial angiogenesis.
研究领域:
药理学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Aihua Xu,Yang Yang,Yang Shao,Manyu Jiang,Yongxin Sun,Bo Feng
Neuronal apoptosis and inflammation exacerbate the secondary injury after spinal cord injury (SCI). Four and a half domains 2 (FHL2) is a multifunctional scaffold protein with tissue- and cell-type specific effects on the regulation of inflammation, but its role in SCI remains unclear. The T10 mouse spinal cord contusion model was established, and the mice were immediately injected with lentiviruses carrying FHL2 shRNA after SCI. The results showed that FHL2 expression was increased following SCI, and then gradually decreased. Moreover, FHL2 depletion aggravated functional impairment, neuronal necrosis, and enlarged lesion cavity areas in the injured spinal cord. FHL2 deficiency facilitated neuronal apoptosis by elevating cleaved caspase 3/9 expression, neuroinflammation by regulating microglia polarization, and bone loss. Indeed, FHL2 deficiency increased the secretion of TNF-α and IL-6, M1 microglia polarization, and the activation of STAT1 pathway but decreased the secretion of IL-10 and IL-4, M2 microglia polarization, and the activation of the STAT6 pathway in the spinal cord. In vitro , FHL2 silencing promoted LPS + IFN-γ-induced microglia M1 polarization through activating the STAT1 pathway and alleviated IL-4-induced microglia M2 polarization via inhibiting the STAT6 pathway. FHL2 positively regulated the expression of poly (ADP-ribose) polymerase family member 14 (PARP14) by promoting its transcription. PARP14 overexpression inhibited FHL2 silencing-induced microglia M1 polarization and relieved the inhibitory effect of FHL2 silencing on microglia M2 polarization. Collectively, the study suggests that FHL2 reduces the microglia M1/M2 polarization-mediated inflammation via PARP14-dependent STAT1/6 pathway and thereby improves functional recovery after SCI.
研究领域:
神经科学
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炎症
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Zhenzhen Feng,Gui Chen,Min Zhong,Ling Lin,Ziyi Mai,Yan Tang,Guimei Chen,Wen Ma,Guang Li,Yuanyuan Yang,Zhiqiang Yu,Meng Yu
Pyroptosis is an inflammatory form of programmed cell death (PCD) that is regulated by the Gasdermin protein family in response to various stimuli, playing a critical role in the development of tumor therapy strategies. However, cancers are generally known to escape from PCD via immunosuppressive pathways or other resistant mechanisms. In this study, an acid-responsive Fe/Mn bimetal-organic framework nanosystem carrying metal ions and immune adjuvant R848 (FeMn@R@H) was designed for combining pyroptosis and augmented immunotherapy. The FeMn@R@H would be triggered to disintegrate and release Fe 3+ and Mn 2+ ions in response to the acidic tumor microenvironment (TME), thereby initiating Fenton-like reactions for ROS-mediated pyroptosis. On the one hand, the pyroptosis-caused cell rupture would induce the release of proinflammatory cytokines and immunogenic constituents from tumor cells, further resulting in immunogenic cell death (ICD) to promote antitumor immune responses. On the other hand, the co-delivered R848 could reverse suppressive tumor immune microenvironment (TIME) and induce inflammatory responses by activating the TLR7/8 pathway. In conclusion, this tumor-specific therapy system can co-deliver metal ions and R848 to tumor tissues to perform pyroptosis-mediated PCD and augmented anti-tumor immunotherapy.
研究领域:
癌症生物学
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纳米技术
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免疫治疗
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药学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2023
·
IF 3.9
Yinzhong Chen,Wei Guo,Weizhao Lu,Xiucheng Guo,Weilu Gao,Zongsheng Yin
Osteoarthritis (OA), the most common joint disease, is characterized by inflammation and cartilage degradation. Previous studies illustrated that Smad nuclear-interacting protein 1 (SNIP1) is an inhibitor of the TGF-β signal transduction pathway and SNIP1 has been reported as an anti-inflammatory factor. This study aimed to explore the role of SNIP1 in OA progression. In this study, the SNIP1 expression was evaluated in OA human and OA mice tissue and interleukin-1 beta (IL-1β)-induced chondrocytes . The Safranin-O (SO) staining and osteoarthritis research society international (OARSI) scoring system was used to evaluate cartilage injury. The gain- and loss-of-function studies for SNIP1 were performed in chondrocytes. The SNIP1 overexpression adenovirus was injected into mice by intra-articular injection. The SNIP1 expression was decreased in OA patients, OA mice, and IL-1β-stimulated chondrocytes. The cartilage injury of medial meniscus-induced OA (DMM-OA) mice at 8 weeks showed more severe than that at 4 weeks. The expression of SNIP1 was lower at 8 weeks than that at 4 weeks. In IL-1β-stimulated chondrocytes, SNIP1 overexpression reduced the expression of TNF-α and IL-6, alleviated ECM degradation, reduced the phosphorylation levels of p65 and IκBα , and decreased the p65 level in nuclear. Moreover, overexpression of SNIP1 alleviated cartilage injury in DMM-OA mice. In brief, our study suggested that SNIP1 alleviated OA and repressed inflammation by inhibiting the activation of NF-κB. This study might provide a new insight into OA treatment.
研究领域:
风湿病学
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分子生物学
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炎症
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软骨生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOTECHNOLOGY
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2023
·
IF 2.6
Lv Chen-Guang,Cheng Yao,Zhang Lei,Wu Guo-Gang,Liang Chun-Yan,Tao Zuo,Chen Bo
BC (breast cancer) is the leading cause of cancer death in women. Exosome component 2 (EXOSC2), an RNA exosome component, is elevated in BC tissues and may relate to BC carcinogenesis. In this work, the high EXOSC2 expression was correlated with TNM (Tumor Node Metastasis) stage. Moreover, overexpression of EXOSC2 enhanced tumorigenic capacity of BC cells via facilitating cell proliferation and cell cycle progression, increasing migration and angiogenesis, as well as exacerbating xenograft formation in vivo. Whereas, EXOSC2 knockdown showed anti-cancer effects, including inhibition of cell proliferation and angiogenesis. Mechanistically, EXOSC2 activated the wnt/β-catenin pathway, which was also abolished by EXOSC2 knockdown. In addition, there were m6A methylation modification sites in the mRNA of EXOSC2. WTAP (Wilms tumor 1-associated protein) bound to EXOSC2 mRNA and increased its m6A methylation, resulting in extending the half-life of EXOSC2 mRNA. Luciferase data also confirmed that WTAP enhanced EXOSC2 mRNA stability through binding with the 3′-UTR containing m6A sites. Furthermore, WTAP silencing exhibited cancer-inhibiting effects on cell viability, cell cycle progression and tube formation, which was effectively reversed by EXOSC2 overexpression. In conclusion, our results demonstrate that EXOSC2 promotes the malignant behaviors of BC cells via activating the wnt/β-catenin pathway. In addition, EXOSC2 mediates the function of WTAP which contributes to the m6A modification of EXOSC2. Totally, this study suggested that EXOSC2 mediated the pro-tumor role of WTAP via activating the wnt/β-catenin signal.
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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癌症生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 44
·10728-10737
·
IF 7
Guangdong Yang,Jiajing Liu,Zhong Zhang,Li Yuan,Hongye Tian,Xingbin Yang
Phycocyanin, a macromolecular protein known for its robust fluorescence, proves to be highly suitable for verifying the successful deposition of imprinted layers. In this study, an acid-propelled magnetic micromotor was successfully fabricated by utilizing surface imprinting and self-propelled nanomotor technology to achieve selective loading and capture of targets such as phycocyanin for future applications in environmental monitoring and precision drug delivery in vivo. This micromotor features a distinct recognition layer achieved through a template electrodeposition method. The outermost imprint layer of the micromotor was meticulously crafted using poly(3,4-ethylenedioxythiophene)/poly(sodium-4-styrenesulfonate) in the presence of a template, while the Pt layer serves as the supportive foundation, the Ni layer acts as the magnetic guidance component, and the innermost layer consists of metal Zn. In acidic environments, the Zn reacts to generate bubbles, which propels the micromotor's motion. The micromotor was comprehensively characterized using techniques such as scanning electron microscopy. Findings highlight the exceptional self-propulsion of the Zn-based micromotor, which is a fusion of molecular imprinting and micromotor technologies. This innovative design achieves an impressive maximum velocity of approximately 100 μm s−1, as well as commendable magnetic steering performance. Furthermore, the micromotor demonstrates the ability to imprint target protein through the imprint layer, enabling selective recognition and capture for transport of specific phycocyanin. In vitro cytotoxicity tests have also demonstrated that the micromotors are non-toxic to cells. This breakthrough concept offers a novel avenue for realizing targeted capture and transport of specific nutrients within the human gastric environment.
研究领域:
生物材料学
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纳米技术
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环境科学
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药物递送
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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）