JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·Vol. 24
·期 1
·914
·
IF 15
Li Chenhao,Zhang Chao,Zhang Chuanqi,Duan Shiyu,Zhang Jiali,Wang Hongyue
AKI-to-CKD progression is shaped by sustained tubular stress, ferroptosis-related iron imbalance, and oxidative injury. To target this process, we developed an MHY1485-loaded molybdenum oxide (MoOx) nanozyme coated with a pH-responsive phenylboronic acid-polyethylene glycol-phenylboronic acid (PBA-PEG-PBA) polymer (MHY@MO@PPP). We tested whether this platform could weaken the ferroptosis-associated injury loop and delay AKI-to-CKD transition through regulation of the Fe 2+ -mechanistic target of rapamycin complex 1 (mTORC1)-glutathione peroxidase 4 (GPX4) axis. Material properties were examined by dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Biological activity was assessed in erastin-induced ferroptotic human renal proximal tubular epithelial (HK-2) cells and in a C57BL/6 mouse unilateral ischemia-reperfusion injury (UIRI) model. MHY@MO@PPP showed stimulus-responsive MHY1485 release under simulated lesion-like conditions, lowered reactive oxygen species (ROS), lipid peroxidation, and free Fe 2+ , restored mitochondrial function, and improved cell survival. Mechanistic assays showed increased p-mTOR and GPX4 expression with reduced autophagy-related stress, supporting attenuation of the ferroptosis-related feedback state. Proteomic analysis and functional intervention experiments further implicated the Fe 2+ -mTORC1-GPX4 axis in the protective response. In vivo, MHY@MO@PPP improved renal function and reduced renal tissue injury and fibrosis. These findings support a nanozyme-based strategy that combines catalytic redox regulation with pathway modulation to mitigate AKI-to-CKD progression. Graphical abstract
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DOI
高影响因子
Frontiers in Immunology
·
2017
·
IF 6.429
Ren Wenkai,Yin Jie,Xiao Hao,Chen Shuai,Liu Gang,Tan Bie,Li Nengzhang,Peng Yuanyi,Li Tiejun,Zeng Benhua,Li Wenxia,Wei Hong,Yin Zhinan,Wu Guoyao,Hardwidge Philip R.,Yin Yulong
Intestinal microbiota has critical importance in pathogenesis of intestinal infection; however, the role of intestinal microbiota in intestinal immunity during enterotoxigenic Escherichia coli (ETEC) infection is poorly understood. The present study tested the hypothesis that the intestinal microbiota is associated with intestinal interleukin-17 (IL-17) expression in response to ETEC infection. Here, we found ETEC infection induced expression of intestinal IL-17 and dysbiosis of intestinal microbiota, increasing abundance of γ-aminobutyric acid (GABA)-producing Lactococcus lactis subsp. lactis. Antibiotics treatment in mice lowered the expression of intestinal IL-17 during ETEC infection, while GABA or L. lactis subsp. lactis administration restored the expression of intestinal IL-17. L. lactis subsp. lactis administration also promoted expression of intestinal IL-17 in germ-free mice during ETEC infection. GABA enhanced intestinal IL-17 expression in the context of ETEC infection through activating mechanistic target of rapamycin complex 1 (mTORC1)-ribosomal protein S6 kinase 1 (S6K1) signaling. GABA–mTORC1 signaling also affected intestinal IL-17 expression in response to Citrobacter rodentium infection and in drug-induced model of intestinal inflammation. These findings highlight the importance of intestinal GABA signaling in intestinal IL-17 expression during intestinal infection and indicate the potential of intestinal microbiota-GABA signaling in IL-17-associated intestinal diseases.
研究领域:
微生物学
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免疫学
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病理学
·
分子生物学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Bo Chen,Jibing Wang,Xing Jin,Xin Wang,Zhangling Fan,Yuxin Zhang,Xuehan Sang,Zhaoxiang Meng
In the macrophage-specific mTORC1 signaling activation model, the synovial macrophages polarized toward M1, thus aggravating synovitis and progression of OA. Therefore, intra-articular injection of rapamycin, a classical mTORC1 inhibitor, may show great potential for alleviating synovitis and delaying cartilage destruction in osteoarthritis (OA). However, the durable retention of drugs in the joint cavity is still a critical issue to be addressed. Herein, we crosslinked the Poloxamer 407 and hyaluronic acid (P-HA) to prepare an injectable and thermo-responsive drug delivery system to durably retain rapamycin and dramatically magnify their therapeutic effects in OA management. The prepared P-HA hydrogel showed excellent biocompatibility with chondrocytes and fibroblasts, as well as possessed sustained rapamycin release profiles for 14 days. Intra-articular injection of this rapamycin-incorporated P-HA hydrogel indicated a positively effect on inducing the polarization of synovial macrophages from M1 to M2 phenotype and reducing synovial inflammation in OA. This strategy significantly decreased the pro-inflammatory cytokines ( e.g. , TNF-α, IL-1β, and IL-6) and increased the anti-inflammatory cytokine ( e.g. , IL-10) expression in the synovial tissues and synovial fluid. As a result, intra-articular injection of rapamycin-incorporated P-HA hydrogel significantly prevented cartilage destruction by inducing cartilage matrix formation, which suggesting a great potential for the management of OA.
研究领域:
药理学
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生物医学工程
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骨科
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免疫学
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DOI
高影响因子
Signal Transduction and Targeted Therapy
·
2025
·Vol. 10
·期 1
·1-20
·
IF 52.7
Ma Xiao,Chen Jiao,Wang Fang,Fan Xinzou,Li Zhenhong,Liang Hantian,Cheng Hao,Nan Fang,Lin Yubin,Song Xiaoshuang,Zhang Jianan,Gao Fan,Zhang Wei,Jin Wenwen,Zhang Huiyuan,Tong Jiyu,Jiang Hong,Zhou Xikun,Zou Qiang,Hu Hongbo,Tong Aiping,Chen WanJun,Zhang Dunfang
The intake of sugars, especially glucose and fructose, has significantly increased with the change of lifestyle. Excessive intake of sugar has been proven to be associated with tumors and inflammatory diseases. Fructose directly mediates innate immune responses; however, whether it can directly regulate T-cell immunity remains unknown. We show that high fructose consumption accelerates the development of inflammatory bowel disease (IBD) by promoting the generation of T helper 1 (Th1) and T helper 17 (Th17) cells. It was demonstrated that fructose promotes the differentiation of Th1 and Th17 cells directly by enhancing mechanistic target of rapamycin complex 1 (mTORC1) activation through the glutamine metabolism-dependent pathway. Reactive oxygen species (ROS)-induced activation of transforming growth factor-β (TGF-β) is also involved in fructose-induced Th17 cell generation. Moreover, metformin can reverse Th1 and Th17 cell generation induced by fructose by suppressing mTORC1 activation and reducing ROS-mediated TGF-β activation. Finally, we identified metformin as an in vivo therapeutic drug for relieving high fructose consumption-induced T-cell inflammation and colitis aggravation. Our study revealed a previously unknown adverse effect of high fructose consumption in disrupting immune homeostasis and exacerbating IBD by directly promoting T-cell immunity, and showed metformin is a potential therapeutic for reversing the T cell immune imbalance caused by long-term high fructose consumption.
研究领域:
免疫学
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营养学
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细胞生物学
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代谢
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胃肠病学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2019
·Vol. 108
·期 1
·30-38
·
IF 3.221
Rui Ma,Zhen-Gang Ma,Jin-Lai Gao,Yu Tai,Lan-Jun Li,Hai-Bin Zhu,Li Li,De-Li Dong,Zhi-Jie Sun
Niclosamide is an antihelminthic drug. Recent studies show that niclosamide exerts antitumor activity through inhibiting multiple signals including Wnt/β-catenin, mTORC1, signal transducer and activator of transcription 3, NF-κB, notch signals; however, the insolubility and poor bioavailability limits its potential clinic use, the aim of the present work is to synthesize an injectable pegylated niclosamide (polyethylene glycol-modified niclosamide) and investigate its antitumor activity in vitro and in vivo. The pegylated niclosamide (mPEG5000-Nic) was synthesized and the chemical structure was identified by Fourier transform infrared spectra and 1 H nuclear magnetic resonance spectra. The antitumor activity was evaluated in CT26 and HCT116 colon cancer cells in vitro and nude mouse xenograft model of CT26 cells in vivo. The water solubility of niclosamide in mPEG5000-Nic was significantly increased. Niclosamide could be released from mPEG5000-Nic nanoparticles in PBS solution. mPEG5000-Nic inhibited the cell viability of CT26 and HCT116 cells in vitro. No animal death was observed in mice with intraperitoneal injection of mPEG5000-Nic (equivalent to 1000 mg/kg niclosamide) within 24 hr, indicating that mPEG5000-Nic was less toxic. In nude mouse, xenograft model of CT26 colon carcinoma, intraperitoneal injection of mPEG5000-Nic (equivalent to niclosamide 50 mg/kg) inhibited tumor growth but had no effect on animal body weight and heart, liver, kidney, and lung weight in vivo. Meanwhile, in the same model, intraperitoneal injection of the positive clinic drug 5-fluorouracil not only inhibited the tumor growth, but also reduced the animal body weight. Our study demonstrates that pegylated niclosamide is novel niclosamide delivery system with clinical perspective for cancer therapy.
研究领域:
药理学
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肿瘤学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL PHYSIOLOGY
·
2021
·Vol. 106
·期 4
·958-971
·
IF 2.969
Xia Yan,Xuli Gao,Qiaohua Niu,Xin Peng,Jie Zhang,Xiufeng Ma,Yanhong Wei,Huiping Wang,Yunfang Gao,Hui Chang
New Findings What is the central question of this study? The aim was to investigate whether diaphragm hypertrophy and gastrocnemius atrophy during hibernation of Daurian ground squirrels involve differential regulation of protein metabolism and regeneration. What is the main finding and its importance? We clarified the differences in protein metabolism and muscle regenerative potential in the diaphragm and gastrocnemius of hibernating ground squirrels, reflecting the different adaptability of muscles. Are differences in the regulation of protein metabolism and regeneration involved in the different phenotypic adaptation mechanisms of muscle hypertrophy and atrophy in hibernators? Two fast-type muscles (diaphragm and gastrocnemius) in summer active and hibernating Daurian ground squirrels were selected to detect changes in cross-sectional area (CSA) and protein expression indicative of protein synthesis metabolism (protein expression of P-Akt, P-mTORC1, P-S6K1 and P-4E-BP1), protein degradation metabolism (MuRF1, atrogin-1, calpain-1, calpain-2, calpastatin, desmin, troponin T, Beclin1 and LC3-II) and muscle regeneration (MyoD, myogenin and myostatin). In the hibernation group compared with the summer active group, the CSA of the diaphragm muscle increased significantly by 26.1%, whereas the CSA of the gastrocnemius muscle decreased significantly by 20.4%. Our study also indicated that increased protein synthesis, decreased protein degradation and increased muscle regenerative potential contributed to diaphragm muscle hypertrophy, whereas decreased protein synthesis, increased protein degradation and decreased muscle regenerative potential contributed to gastrocnemius muscle atrophy. In conclusion, the differences in muscle regeneration and regulatory pattern of protein metabolism might contribute to the different adaptive changes observed in the diaphragm and gastrocnemius muscles of ground squirrels.
研究领域:
生理学
·
生物化学
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分子生物学
·
动物学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）