ACS Nano
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2024
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IF 15.8
Yuan Xu,Xin An,Lei Liu,Xinran Cao,Zhanfeng Wu,Wang Jia,Jiacheng Sun,Haoyu Wang,Jiawei Huo,Zihao Sun,Mingming Zhen,Chunru Wang,Chunli Bai
Endotoxemia is a life-threatening multiple organ failure disease caused by bacterial endotoxin infection. Unfortunately, current single-target therapy strategies have failed to prevent the progression of endotoxemia. Here, we reported that alanine fullerene redox modulator (AFRM) remodeled the intestinal microenvironment for multiple targets endotoxemia mitigation by suppressing inflammatory macrophages, inhibiting macrophage pyroptosis, and repairing epithelial cell barrier integrity. Specifically, AFRM exhibited broad-spectrum and self-cascade redox regulation properties with superoxide dismutase (SOD)-like enzyme, peroxidase (POD)-like enzyme activity, and hydroxyl radical (•OH) scavenging ability. Guided by proteomics, we demonstrated that AFRM regulated macrophage redox homeostasis and down-regulated LPS/TLR4/NF-κB and MAPK/ERK signaling pathways to suppress inflammatory hyperactivation. Of note, AFRM could attenuate inflammation-induced macrophage pyroptosis via inhibiting the activation of gasdermin D (GSDMD). In addition, our results revealed that AFRM could restore extracellular matrix and cell-tight junction proteins and protect the epithelial cell barrier integrity by regulating extracellular redox homeostasis. Consequently, AFRM inhibited systemic inflammation and potentiated intestinal epithelial barrier damage repair during endotoxemia in mice. Together, our work suggested that fullerene based self-cascade redox modulator has the potential in the management of endotoxemia through synergistically remodeling the inflammation and epithelial barriers in the intestinal microenvironment.
研究领域:
药理学
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免疫学
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病理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Zian Mao,Liu Yang,Yishan Lv,Yuchi Chen,Mingyuan Zhou,Chengnan Fang,Bingqi Zhu,Fangmei Zhou,Zhishan Ding
A novel acidic glucuronogalactomannan (STHP-5) was isolated from the aboveground part of Tetrastigma hemsleyanum Diels et Gilg with a molecular weight of 3.225 × 10 5 kDa. Analysis of chain conformation showed STHP-5 was approximately a random coil chain. STHP-5 was composed mainly of galactose, mannose, and glucuronic acid. Linkages of glycosides were measured via methylation analysis and verified by NMR. Based on the structural characterization, the repeat unit of STHP-5 was proposed. In vitro, STHP-5 induced the production of nitric oxide (NO) and secretion of IL-6, MCP-1, and TNF-α in RAW264.7 cells, indicating STHP-5 had stimulatory activity on macrophages. STHP-5 was proven to function as a TLR4 agonist by inducing the secretion of secreted embryonic alkaline phosphatase (SEAP) in HEK-Blue™-hTLR4 cells. The TLR4 activation capacity was quantitatively measured via EC50, and it showed purified polysaccharides had stronger effects (lower EC50) on activating TLR4 compared with crude polysaccharides. In conclusion, our findings suggest STHP-5 may be a novel immunomodulator.
研究领域:
药理学
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免疫学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Hongping Wan,Kai Deng,Zhengqun Huang,Yunhan Yang,Bo Jing,Yumei Feng,Yuanfeng Li,Yong Liu,Mingqin Lu,Xinghong Zhao
Despite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan–catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS-CoV-2 spike protein receptor-binding domain (RBD) and toll-like receptor (TLR)9 agonist unmethylated cytosine-guanine (CpG) motif, forming uniform virus-like nanoparticles (Ssp-Chic-RBD-CpG) via electrostatic and covalent interactions. Ssp-Chic-RBD-CpG, mimicking the morphology and function of inactive virions, effectively prolongs the retention time of RBD in the nasal mucosa by 3.92-fold compared to RBD alone, enhances the maturation of dendritic cells (DCs), and facilitates the antigen trafficking to the draining lymph nodes, which subsequently induces a stronger mucosal immunity. Mechanistically, the enhanced chemokine chemokine (C-C motif) ligand 20 (CCL20)-driven DCs recruitment and maturation by Ssp-Chic-RBD-CpG are evidenced by a cell co-culture model. In addition, the overexpression of TLR4/9 and activation of MYD88/NF-κB signaling pathway in activation of DCs are observed. Proof of principle is obtained for RBD, but similar delivery mechanisms can be applied in other protein-based subunit vaccines as well when intranasal administration is needed.
研究领域:
纳米技术
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免疫学
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疫苗开发
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分子生物学
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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
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Jinyan Gu,Lianzhu Lin,Mouming Zhao
Due to the difficulty in obtaining highly branched rhamnogalacturonan-I (RG-I) type pectin, the relationship between the extent of RG-I branching (EB) of pectin and prebiotic/immunomodulatory activity has not been systematically investigated. Moreover, it is only possible to establish a structure–activity relationship using pectin that is highly purified and accurately characterized. In this study, a homogeneous highly branched RG-I type pectin (LBP-P4, a final product) with dual proliferative effects on Bifidobacterium and macrophage was effectively purified for the first time using enzyme hydrolysis combined with ultrafiltration. The RG-I content and EB of LBP-P4 reached 97.32 and 77.12, respectively. Its two branches were composed of arabinan and arabinogalactan-II, containing → 5)-Araf-(1→, →3)-Araf-(1→, →3,6)-Galp-(1→ and →6)-Galp-(1→ residues). The structure–activity relationship analysis indicated that strong prebiotic/immunomodulatory activity of LBP-P4 was depended on its high EB, which was further confirmed by the molecular docking simulation between low/high branched pectin with β-1,6-galactosidase, α-l-arabinanase, and Toll-like receptor 4 (TLR4).
研究领域:
食品科学
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生物化学
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免疫学
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微生物学
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药学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Kunmei Xie,Feibiao Wang,Yue Yang,Shoujie Pan,Junyao Wang,Nan Xiao,Xinyan Wang,Zhihao Ma,Xiaolong Xu,Zibo Dong
Sepsis-associated acute liver injury (ALI) is a deadly condition resulting from a systemic inflammatory response to liver cell damage and malfunction. Monotropein (MON) belongs to the iris group of compounds extracted from the natural product Mollen dae officinalis radix, which has strong anti-inflammatory and antioxidant pharmacological effects. The purpose of this study was to elucidate the underlying mechanism of MON in the treatment of sepsis ALI. In this study, an in vivo caecal ligation puncture (CLP)-induced ALI model and in vitro LPS-stimulated AML12 cells and RAW264.7 cells model were established. Additionally, a variety of experimental techniques, including CCK8, H&E staining, DHE probe labelling, biochemical, QPCR, and Western blotting and blocking tests, were used to explore the role of MON in ALI. The results showed that MON improved liver morphological abnormalities, oedema, histopathological injury, and elevated ALT and AST, providing a protective effect against ALI. MON reduced CYP2E1 expression, alleviated oxidative stress (downregulation of MDA levels and upregulation of GSH, CAT, and T-AOC levels) and ROS accumulation with the involvement of the NRF2-Keap-1 pathway. MON inhibited inflammation via the TLR4/NF-κB/NLRP3 inflammasome pathway. In addition, it activated the Akt (Ser473)/GSK3β (Ser9)/Fyn pathway and accelerated NRF2 nuclear accumulation; MK-2206 blockade reversed the NRF2 nuclear accumulation and anti-inflammatory function of MON. MON also restricted the mitochondrial apoptosis pathway, a process specifically blocked by MK-2206. In summary, we concluded that MON alleviated septic ALI by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3β (Ser9)/Fyn/NRF2 pathway.
研究领域:
药理学
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免疫学
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分子生物学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Yuan Chen,Yi Zhou,Jinhan Cai,Jiayi Xu,Chenwei Hu,Huiyue Chen,Yirui Hong,Nanyi Pan,Yujie Jiang,Chenhui Zhou,Hua Wei,Zhipeng Xu,Lin Liu,Xiang Wu,Wei Cui
Post-operative cognitive dysfunction (POCD) is a multi-etiological symptom mainly occurred in elderly people after surgery. The activation of retinoic acid receptor α (RARα), a transcriptional factor, was previously predicated to be negatively associated with the occurrence of POCD. However, the mechanisms underlying anti-POCD effects of RARα were still unclear. In this study, AM580, a selective agonist of RARα, and all-trans-retinoic acid (ATRA), a pan agonist of RAR, significantly alleviated cognitive dysfunction and increased the expression of RARα in elderly mice after surgery, which was decreased by RO41-5253, an antagonist of RARα. A bioinformatic study further predicted that the activation of RARα might produce anti-POCD effects via the restoration of synaptic proteins. Both agonists inhibited the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and the phosphorylation of nuclear factor kappa-B (NF-κB), leading to the prevention of microglial over-activation and pro-inflammatory cytokines secretion in the hippocampal regions of elderly mice after surgery. Moreover, AM580 and ATRA increased the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95), and the phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element binding protein (CREB). All these results suggested that the activation of RARα prevented surgery-induced cognitive impairments via the inhibition of neuroinflammation by the reduction of the TLR4/Myd88/NF-κB pathway and the restoration of synaptic proteins by the activation of the BDNF/ERK/CREB pathway, providing a further support that RARα could be developed as a therapeutic target for POCD.
研究领域:
神经科学
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药理学
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老年医学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Qiaoling Zhao,Fei Yang,Qiuyan Pu,Rui Zhao,Su Jiang,Yunping Tang
The protective effects of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS, 50 or 100 mg/kg) on bisphenol A (BPA)-induced intestinal damage were assessed. The biochemical indices, pathological examination, non-targeted metabolomics integrated with gut microbiota analysis, and immunofluorescence analysis were used to investigate the protective effects of DHA-PS and its underlying regulatory mechanism. The DHA-PS treatment improved the pathology of intestinal tract and increased the expression levels of Claudin-1, Occludin, and ZO-1. In addition, the DHA-PS treatment also notably decreased the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and increased the antioxidant enzymes activities. Moreover, DHA-PS treatment increased the relative abundances of Akkermansia, Alistipes, Butyricicoccus, Coriobacteriaceae_ UCG-002 , Enterorhabdus , and Lachnospiraceae_ UCG-006. DHA-PS treatment alleviated BPA-induced intestinal damage by regulating the kynurenine pathway of tryptophan, lipid, and arachidonic acid metabolisms. Overall, this study suggested that DHA-PS could alleviate BPA-induced intestinal damage by enhancing the intestinal barrier integrity, improving gut microbial composition and metabolites, and inhibiting the TLR4/NF-κB pathways.
研究领域:
营养学
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药理学
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微生物学
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代谢组学
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毒理学
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产品关联
DOI
高影响因子
Food & Function
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2024
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IF 5.1
Fenfen Wei,Huibin Jiang,Chuang Zhu,Lingyue Zhong,Zihan Lin,Yan Wu,Lihua Song
A high-fat diet (HFD) is associated with various adverse health outcomes, including cognitive impairment and an elevated risk of neurodegenerative conditions. This relationship is partially attributed to the influence of an HFD on the gut microbiota. The objective of this research was to evaluate the neuroprotective benefits of co-fermented black barley and quinoa with Lactobacillus (FG) against cognitive impairments triggered by an HFD and to investigate the microbiota-gut–brain axis mechanisms involved. C57BL/6J mice were randomized into four groups: the normal control group (NC, n = 10), the high-fat diet group (HFD, n = 10), the high-fat diet group supplemented with FG (HFG, 10 mL per kg BW, n = 10), and the high-fat diet group supplemented with Lactobacillus (HFL, 10 mL per kg BW, n = 10). Our results showed that the FG intervention enhanced the behavioral and locomotor skills of the mice, elevated the levels of dopamine (DA) and norepinephrine (NPI) in brain tissues, and alleviated synaptic ultrastructural damage in the hippocampus. Furthermore, FG intervention was observed to exert a protective effect on both the blood–brain barrier and the colonic barrier, as evidenced by an increase in the mRNA levels of Zona occludens-1 (ZO-1), Claudin-4, and Occludin in the hippocampus and colon. These beneficial effects may be attributed to FG's regulation of gut microbiota dysbiosis, which involves the restoration of intestinal flora diversity, reduction of the Firmicutes/Bacteroidetes (F/B) ratio, and a decrease in the levels of pro-inflammatory bacteria such as s_Escherichia coli E and g_Escherichia; moreover, there was an increase in the abundances of anti-inflammatory bacteria, such as s_Bacteroides thetaiotaomicron and s_Parabacteroides goldsteinii. Metagenomic analysis revealed that the FG treatment downregulated the lipopolysaccharide (LPS) pathway and upregulated neurotransmitter biosynthetic pathways. These probiotic effects of FG resulted in reduced production and “leakage” of LPS and decreased mRNA expression of Toll-like receptor 4 (Tlr4), cluster of differentiation 14 (CD14), and myeloid differentiation factor 88 (Myd88) in hippocampal and colon tissues. Consequently, a reduction was observed in the levels of inflammatory cytokines in the serum, hippocampus, and colon, along with suppression of the immunoreactivity of microglia and astrocytes. Our results suggest that FG may serve as an intervention strategy for preventing cognitive impairments caused by an HFD.
研究领域:
营养神经科学
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微生物组研究
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神经免疫学
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胃肠科学
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宏基因组学
✓ 已验证
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）