Microbiome
·
2023
·Vol. 11
·期 1
·1-13
·
IF 15.5
Ma Jie,Zhou Miao,Song Zehe,Deng Yuankun,Xia Siting,Li Yunxia,Huang Xingguo,Xiao Dingfu,Yin Yulong,Yin Jie
Background Compared to that of bacteria, the role of gut fungi in obesity development remains unknown. Results Here, alterations in gut fungal biodiversity and composition were confirmed in obese pig models and high-fat diet (HFD)-fed mice. Antifungal drugs improved diet-induced obesity, while fungal reconstruction by cohousing or fecal microbiota transplantation maintained the obese phenotype in HFD-fed mice. Fungal profiling identified 5 fungal species associated with obesity. Specifically, Ascomycota _sp. and Microascaceae_ sp. were reduced in obese mice and negatively correlated with fat content. Oral supplementation with fungi was sufficient to prevent and treat diet-induced obesity. Clec7a , which is involved in fungal recognition, was highly expressed in HFD-fed mice. The Clec7a agonist accelerated diet-induced obesity, while Clec7a deficieny in mice resulted in resistance to diet-induced obesity and blocked the anti-obese effect of antifungal drugs and fungi. Conclusions Taken together, these results indicate that gut fungi/ Clec7a signaling is involved in diet-induced obesity and may have therapeutic implications as a biomarker for metabolic dysregulation in humans.
Video Abstract
研究领域:
微生物学
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代谢生物学
·
免疫学
✓ 已验证
DOI
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2023
·
IF 6.2
Xue-Yun Chen,Si-Ning Feng,Yin Bao,Yu-Xin Zhou,Fang Ba
Parkinson's disease (PD) is a neurodegenerative disease. Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic tool in PD. High-throughput sequencing was performed to screen potential therapeutic targets in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. The candidate gene, Clec7a, was screened out and validated. Clec7a is a pattern recognition receptor involved in neuroinflammation. The higher expression of Clec7a was observed in the substantia nigra (SN) and striatum of PD rats with dopaminergic neurons damage and was mainly localized in the microglial. Adeno-associated virus (AAV)-mediated specific knockdown of Clec7a in microglial alleviated 6-OHDA induced motor deficits and nigrostriatal dopaminergic neuron damage of rats, as evidenced by the increase of tyrosine hydroxylase (TH) -positive neurons in SN, as well as dopaminergic nerve fibers in the striatum. Clec7a knockdown restrained the neuroinflammation by suppressing inflammatory factors (IFN-γ, TNF-α, IL-1β, IL-18, and IL-6) release in SN, which might result from enhanced Arg-1 expression (M2 polarization) and defective inducible nitric oxide synthase (iNOS) expression (M1 polarization). The same phenomena were also observed in the LPS inflammatory rat model of PD. In vitro, α-synuclein fibrils induced upregulation of Clec7a expression and microglia polarization to a pro-inflammatory state of BV2 cells, leading to increased release of cytokines. However, Clec7a knockdown reversed those changes and induced a shift to an anti-inflammatory phenotype in BV2 cells. In conclusion, our study suggested that Clec7a was involved in PD pathogenesis, and its inhibition might protect rats from PD by depressing neuroinflammation through microglial polarization.
研究领域:
神经科学
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神经退行性疾病
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治疗干预
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炎症
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2026
·
IF 2.8
Zhu Zhonglian,Chang Jiankang,Gao Xubin,Wang Zhaodong,Duan Keyou,Guan Jianzhong
Excessive inflammation driven by macrophage phenotype imbalance is a key pathological barrier hindering neural repair after spinal cord injury (SCI). Here, methacryloyl gelatin hydrogel (GelMA) loaded with natural anti-inflammatory agent resveratrol (Res) was designed and synthesized. Scanning electron microscopy (SEM), x-ray diffraction (XRD), fourier-transform infrared spectroscopy (FT-IR), Ultraviolet (UV) and rheological characterization confirmed that Res-loaded GelMA hydrogel (Res@GelMA) was successfully synthesized. High-Performance Liquid Chromatography (HPLC) analysis demonstrated sustained Res release. CCK8 and cell adhesion experiments confirmed that Res@GelMA treatment did not affect the cell function of RAW264.7 and had good cell compatibility. Flow cytometry, Enzyme-Linked Immunosorbent Assay (ELISA) and western blot assays revealed that Res@GelMA treatment promoted RAW264.7 to M2 polarization, while reducing the levels of inflammatory factors (IL-1β, IL-6, TNF-α) and down-regulating the expression of IL-1R1/MyD88/TNFR1 inflammatory signaling proteins. Transcriptome sequencing combined with functional screening identified C-type lectin receptor Clec7a as a key target gene regulated by Res@GelMA. Importantly, knockdown of Clec7a and Res@GelMA were both anti-inflammatory, promoted M2 polarization, and blocked the activation of the TLR2/TLR4-p38 MAPK signaling axis. In the SCI mouse model, local implantation of Res@GelMA significantly improved tissue pathological damage and enhanced motor function recovery compared with free Res or blank GelMA. In addition, Res@GelMA achieved systemic anti-inflammation by downregulating the Clec7a-TLR-p38 pathway in the injured area and promoting M2 polarization. This study developed an anti-inflammatory hydrogel material that can regulate the phenotype of macrophages, laying a theoretical and technical foundation for the development of neural repair strategies targeting the inflammatory microenvironment.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 12.4
Chongzheng Yan,Zhichao Kong,Yuxue Pan,Zhipeng Fu,Kun Han,Xiaotian Zhao,Jing Zhang,Longyu Bo,Weiyi Sun,Jinxin Gao,Xianghui Dong,Zuolin Zheng,Xiao Yue,Peng Sun,Xinyi Jiang,Chen Chen
Chimeric antigen receptor microglia (CAR-M)-mediated amyloid-β oligomers (AβO) phagocytosis shows great promise in Alzheimer's disease (AD) treatment, however, the limited AβO degradation of CAR-M compromises their anti-AβO potency. This work here reports an in situ engineered agonistic anti-C-type lectin domain containing 7 A (CLEC7A) nanobody to accelerate AβO degradation of CAR-M, augmenting their anti-AβO efficacy. Specifically, with the intranasal-delivered microglia-targeting lipid nanoparticles (LNP), this work generates an AβO-specific degradation-potentiated CAR-M by introducing dual mRNAs encoding AβO-specific CAR and anti-CLEC7A nanobody into the cerebral microglia. These data show that these engineered CAR-M exhibited superior phagocytic function and promoted intracellular AβO degradation via activating CLEC7A-spleen tyrosine kinase (SYK) signaling pathway through the local secretion of anti-CLEC7A nanobody. In the APP/PS1 mouse model of AD, these in situ reprogrammed CAR-M significantly reduced cerebral Aβ levels, suppressed neuroinflammation, and restored cognitive function. In sum, these findings demonstrate that potentiating AβO degradation within CAR-M effectively alleviates AD pathology, providing a promising therapeutic strategy for AD with broad application in other neurodegenerative diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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