Bioactive Materials
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2025
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IF 20.3
Meng Zeng,Ping Deng,Qian Yang,Jie Hu,Jixiang Li,Qi Tang,Xiaoyan Pu,Liangke Zhang
Excessive accumulation of reactive oxygen and nitrogen species (RONS) exacerbates inflammatory responses and contributes to the progression of psoriasis. In particular, ROS activate the STAT3 pathway, inducing abnormal proliferation of keratinocytes and aggravating local inflammation. Moreover, interactions between macrophages and keratinocytes can further exacerbate disease progression. However, current therapeutic strategies have limited efficacy due to poor transdermal permeability and insufficient target specificity. To address these limitations, we have developed a machine learning (ML)-guided framework that integrates virtual screening, experimental validation, and mechanistic analysis into the design of transdermal ionic liquids (ILs). Using this approach, we successfully identified highly efficient transdermal ILs and developed a composite ionic liquids (CIL) delivery system capable of releasing H 2 S. This CIL platform enables the co-delivery of the APTSTAT3-9R peptide and catalase (CAT) directly to psoriatic lesions, implementing a dual therapeutic strategy: (1) inhibition of STAT3 phosphorylation to suppress keratinocyte hyperproliferation, and (2) regulation of redox homeostasis and macrophage polarization via local release of H 2 S and CAT. In vivo studies have shown that CIL@CA can effectively alleviate IMQ-induced psoriasis symptoms in mice. In this study, a novel ML-driven ILs-based drug delivery system was developed, offering a promising strategy for the treatment of inflammatory skin diseases.
研究领域:
皮肤病学
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药物递送系统
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分子生物学
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免疫调节
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纳米医学
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转化医学
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药剂学
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高影响因子
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
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2026
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IF 3.4
Yanliang Li,Siqiang Niu,Haipeng Wang,Jianhua Li
Gemcitabine (GEM) resistance remains a major challenge in the treatment of gallbladder cancer (GBC). This study investigated the synergistic effect of curcumin (CUR) combined with the probiotic Lactobacillus rhamnosus GG (LGG) in reversing chemoresistance through modulation of the gut microbiota. In GEM-resistant GBC-SD cells, the CUR–LGG combination significantly inhibited cell proliferation, suppressed migration and invasion, and induced apoptosis, as demonstrated by CCK-8, wound healing, Transwell, and flow cytometry assays. Western blot analysis revealed corresponding regulation of proliferation markers (Ki67, PCNA), apoptosis-related proteins (Bcl-2, Bax, cleaved Caspase-3), and epithelial–mesenchymal transition markers. In xenograft models, the combined treatment markedly suppressed tumor growth and altered gut microbial composition, increasing beneficial bacteria ( Lactobacillus , Bifidobacterium ) while reducing pathogenic taxa. LC–MS analysis further demonstrated restoration of bile acid homeostasis, characterized by elevated primary bile acids (GCA, CDCA) and decreased secondary bile acids (DCA, LCA). Mechanistically, the intervention significantly inhibited PI3K/AKT signaling, as confirmed by Western blot and immunohistochemistry. Bioinformatic analysis further identified PI3K/AKT as a central regulatory pathway. These findings indicate that probiotic-assisted CUR therapy reverses GEM resistance by remodeling the gut microbiota and its metabolic outputs, thereby suppressing oncogenic signaling pathways. This strategy provides a promising microbiota-based approach for improving therapeutic outcomes in GBC.
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BIOCHEMICAL PHARMACOLOGY
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2026
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IF 6.5
Huimin Qiu,Xinqi Tan,Quan Sheng,Na Yang,Chunming Jiang,Lulu Wang
Metabolic dysfunction-associated steatohepatitis (MASH) frequently induces renal injury, forming a “liver-kidney axis” vicious cycle. Current therapies primarily target hepatic lesions, failing to interrupt the cross-organ injury cascade, creating an urgent need for novel strategies. To explore dapagliflozin’s therapeutic efficacy and core mechanism in MASH and associated renal injury, we utilized in vitro models (free fatty acid [FFA]-induced HepG2 hepatocyte MASH model, HK2 renal tubular epithelial cell injury model, Transwell co-culture system) and an in vivo MASH mouse model induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Results showed dapagliflozin dose-dependently improved dysregulated lipid metabolism, suppressed inflammation, and alleviated fibrosis in vitro and in mouse liver/kidney tissues, while upregulating SIRT1/PPARα and downregulating SREBP-1c to restore lipid homeostasis. Molecularly, dapagliflozin specifically bound to ferroptosis key regulator solute carrier family 7 member 11 (SLC7A11), upregulated its abnormally reduced expression, and inhibited PI3K/AKT pathway hyperactivation—an effect mediated via a “liver-kidney axis” paracrine mechanism with β-hydroxybutyrate (β-HB) as the key mediator. Additionally, SLC7A11 knockdown in cells conversely confirmed that the lipid-lowering effect of dapagliflozin is mediated by SLC7A11.Collectively, dapagliflozin forms hydrogen bonds with SLC7A11, modulates the SIRT1/PPARα/SREBP-1c axis, and inhibits PI3K/AKT, thereby exerting therapeutic effects on MASH and associated renal injury.
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Food Science and Human Wellness
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2023
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IF 7
Qihong Jiang,Lin Chen,Rui Wang,Yin Chen,Shanggui Deng,Guoxin Shen,Shulai Liu,Xingwei Xiang
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease threatening human health. We investigated the effects of Tegillarca granosa polysaccharide (TGP) and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin. TGP (5.1 × 10 3 Da) was composed of mannose, glucosamine, rhamnose, glucuronic acid, galactosamine, glucose, galactose, xylose, and fucose. It could significantly alleviate weight loss, reduce fasting blood glucose levels, reverse dyslipidemia, reduce liver damage from oxidative stress, and improve insulin sensitivity. RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance. TGP increased the abundance of Allobaculum , Akkermansia , and Bifidobacterium , restored the microbiota abundance in the intestinal tracts of mice with T2DM, and promoted short-chain fatty acid production. This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.
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MOLECULAR NEUROBIOLOGY
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2023
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IF 5.1
Wu Yuhan,Zhu Zhanpeng,Lan Tian,Li Shuhan,Li Ye,Wang Changmin,Feng Yabo,Mao Xueqin,Yu Shuyan
Depression is a common psychological disease with high morbidity and mortality. Recently, the involvement of synaptic plasticity in the pathogenesis of depression has shed light on the direction of developing novel antidepressants. Levomilnacipran is a newly approved medication for the treatment of adult major depressive disorder. However, the detailed mechanisms underlying its antidepressant-like effects have yet to be illuminated. In this study, we aimed to investigate the role of levomilnacipran in regulating synaptic plasticity and explore the possible molecular mechanisms of its antidepressant effects using a rat model of depression induced by lipopolysaccharide (LPS). The results demonstrated that levomilnacipran (30 mg/kg, i.p.) significantly ameliorated depression-like behaviors in rats, alleviated the dysregulation of synaptic plasticity, and suppressed neuroinflammation within hippocampus induced by LPS-treatment. Levomilnacipran increased the expression of postsynaptic dense 95 (PSD-95) and synaptophysin (Syn) and reversed the imbalance between pro- and anti-inflammatory cytokines within hippocampus of depressed rats. Additionally, levomilnacipran elevated expression level of brain-derived neurotrophic factor (BDNF), accompanied by increased tyrosine kinase B (TrkB), phosphorylated phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR). Taken together, these results suggest that levomilnacipran may exert antidepressant effects via upregulating BDNF/TrkB mediated PI3K/Akt/mTOR signaling pathway to improve synaptic plasticity. These findings reveal potential mechanisms for the antidepressant effects of levomilnacipran and offer new insights into the treatments for depression. Graphical Abstract
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高影响因子
Biomaterials Science
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2019
·Vol. 7
·期 12
·5054-5067
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IF 5.251
Tiantian Zuo,Jing Li,Jun Zhang,Liang Sun,Xiao Liang,Jie Yang,Qi Shen
As the principal reason for the inducement of high mortality, tumor metastasis is regulated by different pathways owing to its complexity and multistep process. In order to inhibit the proliferation and metastasis of human breast cancer simultaneously, controlling the codelivery of chemotherapeutics and pathway inhibitors precisely has been considered as a high-potential strategy to accurately eliminate tumor metastasis. In this study, polymer PLGA-p-PEI-DA was synthesised and automatically assembled into a cascade “trinity” response drug delivery system, i.e., PPP-DA/NPs (PLGA: poly(lactin-co-glycolic acid), PEI: polyethyleneimine, DA: 2,3-dimethylmaleic anhydride). In the tumor microenvironment, PPP-DA/NPs could remove the outer DA molecules via the pH-sensitive hydrolysis of β-carboxylic amide bonded with DA and PEI. Then, PPP-DA/NPs were broken up owing to the enzymatically cleavable GFLGF (Gly-Phe-Leu-Gly-Phe) linker. The structure of the polymer and the properties of PPP-DA/NPs were evaluated in detail. Moreover, studies on the antitumor metastasis efficiency and antitumor mechanism of PPP-DA/NPs were carried out in detail. As demonstrated in this study, PPP-DA/NPs could reverse the potential in pH 6.8 PBS and showed elevated cellular uptake efficiency. Moreover, PPP-DA/NPs exhibited strong antitumor metastasis ability in vitro and in vivo. The tumor inhibiting rate (TIR) of PPP-DA/NPs (68.4%) was significantly higher than that of docetaxel (DTX) (5.9%). The antitumor mechanistic studies confirmed that PPP-DA/NPs could down-regulate the expressions of Akt, MMP-9 and pro-caspase-3/9 protein, as indicated by western blot analysis. This multifunctional drug delivery system (DDS) is highly selective and effective in inhibiting tumor metastasis, which shows a great potential in inventing smart nanocarriers for targeted tumor-metastasis therapy.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2018
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IF 2.297
Yunzhi Yin,Yiyue Wang,Jun Zhang,Jing Li,Jingjing Chen,Qi Shen
Docetaxel (DTX) is one kind of well-known anticancer drugs against tumors. GDC0941 was used to inhibit PI3K/Akt signal pathway and improve anti-tumor activity. PLGA-PEG-R7 (poly lactic-co-glycolic acid polyethylene glycol bending with cell penetrating peptide R7)/poly sulfadimethoxine-Folate nanoparticles (R7/PSD-Fol NPs) were made to load DTX and GDC0941 simultaneously. In vitro, the release capacity of DTX and GDC0941 inside nanoparticles was determined and both drugs could release from nanoparticles to 70% within 48h. The result of flow cytometry showed that GDC0941 had no interference on cell uptake and R7/PSD-Fol NPs could enhance MCF-7 cells uptake the most significantly. In cell colony study, GDC0941 could further improve the anti-tumor effect of DTX and inhibit the formation of cell clones on the basis of enhancing the uptake of R7/PSD-Fol NPs. The capability of cell colony formation was as follows: DTX > DTX + GDC0941 > R7 NPs > R7/PSD-Fol NPs. The expression of cell apoptosis proteins treated with R7/PSD-Fol NPs was the lowest. The addition of GDC0941 could decrease the full-length content of apoptotic proteins caspase-3 and caspase-9. In vivo, pharmacokinetic parameters results showed us that GDC0941 had no interference on pharmacokinetic study. Main pharmacokinetic parameters of DTX suspension and R7/PSD-Folate NPs suspension showed significant differences.
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NEUROSCIENCE LETTERS
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2017
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IF 2.18
Bing Chun Yan,Hui Shen,Yuanyuan Zhang,Xiaolu Zhu,Jie Wang,Pei Xu,Dan Jiang,Xing Yu
Levetiracetam (LEV), a second-generation antiepileptic drug, is commonly prescribed to treat certain types of seizures. Few studies have investigated the effects of LEV on hippocampal neurogenesis and its related mechanisms. In the present study, we investigated the effects of LEV on cell proliferation and neuronal differentiation in the mouse hippocampal dentate gyrus (DG). We here demonstrate a dose-dependent increase in Ki-67-immunoreactive cells in the subgranular zone of the DG in LEV-treated mice, and doublecortin-immunoreactive cells were also significantly increased in the hippocampal DG of mice treated with LEV. The above results indicate that LEV could improve cell proliferation and neuroblast differentiation in the hippocampus. In addition, we also found that LEV treatment improved superoxide dismutase (SOD)2, catalase and Gpx-1 levels and increased phosphatidylinositol 3-kinase (PI3K) and phosphorylated Akt protein levels in the hippocampus. Further investigation of the molecular mechanisms underlying these effects revealed that PC12 cell was blocked by a pharmacological inhibitor of PI3K (LY294002), and that LEV treatment rapidly activated PI3K/Akt and SOD2, catalase and Gpx-1. In brief, our results indicate that LEV enhanced cell proliferation and neuroblast differentiation by increasing the expression of antioxidants and PI3K and the level of phosphorylated Akt in the mouse hippocampus.
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PHYTOMEDICINE
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2022
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IF 6.656
Zichen Luo,Weichen Xu,Tianjie Yuan,Chen Shi,Tianzi Jin,Ying Chong,Jianjian Ji,Lili Lin,Jianya Xu,Ying Zhang,An Kang,Wei Zhou,Tong Xie,Liuqing Di,Jinjun Shan
Background Increasing hepatic insulin signaling is found to be an important mechanism of Platycodon grandiflorus root to alleviate metabolic syndrome (MetS) symptoms such as insulin resistance, obesity, hyperlipidemia and hepatic steatosis , but the details are not yet clear. Since the main constituents of Platycodon grandiflorus root were hard to be absorbed by gastrointestinal tract , getting opportunity to interact with gut microbiota , we speculate the gut microorganisms may mediate its effect. Purpose Our work aimed to confirm the critical role of gut microbes in the intervention of Platycodon grandiflorus root extract (PRE) on MetS, and investigate the mechanism. Methods Biochemical analyses, glucose tolerance test and hepatic lipidomics analysis were used to evaluate the anti-MetS effect of PRE on high fat diet (HFD) fed mice. Perform 16S rDNA analysis, qPCR analysis and in vitro co-incubation experiment to study its effect on gut microbes, followed by fecal microbiota transplantation (FMT) experiment and antibiotics intervention experiment. Also, the effect of Akkermansia muciniphila treatment on HFD mice was investigated. Results PRE alleviated lipid accumulation and insulin resistance in HFD mice and remodeled the fecal microbiome . It also increased the gene expression of colonic tight junction proteins , alleviated metabolic endotoxemia and inflammation, so that reduced TNF-α induced hepatic JNK-dependent IRS-1 serine phosphorylation and the impairment of PI3K/PIP3/Akt insulin signaling pathway. A. muciniphila was one of the most significantly enriched microbes by PRE treatment, and its administration to HFD mice showed similar effects to PRE, repairing the gut barrier and activating hepatic PI3K/PIP3/Akt pathway. Finally, anti-MetS effect of PRE could be delivered to FMT recipients, and PRE could not further attenuate MetS in gut microbiota depleted mice. Conclusion We demonstrated for the first time that PRE alleviated MetS in a gut microbiota dependent manner, and found activation of hepatic insulin signaling mediated by gut A. muciniphila was a potential mechanism of it.
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Journal of Oleo Science
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2022
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IF 1.628
Runzhou Sun,Ruixin Xiao,Pengfei Lv,Feifei Guo,Yanling Gong,Meixing Yan
Pink lotus essential oil (PLEO) is the volatile components extracted from lotus flowers and there are few relevant research. The purpose of this study was to observe the effect of PLEO on NAFLD in vitro model and its possible mechanism. The ingredients of PLEO were determined by gas chromatography-mass spectrometry (GS-MS) and its lipid-lowering and hepatoprotective activities were investigated. HepG2 cells were treated with free fatty acid (FFA) to establish a cell model of NAFLD. Cell viability was evaluated by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Total cholesterol (TC), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were determined by Enzyme-Linked Immune Sorbent Assay (ELISA). Oil red O staining was performed to observe the lipid accumulation in the HepG2 cells. Lipid metabolism enzymes including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), stearoyl-CoA desaturase 1 (SCD-1), and carnitine palmitoyltransferase-1 (CPT-1), insulin signaling pathways including phosphatidylinositol 3 kinase (PI3K) and protein kinase B Akt, inflammatory signaling pathways such as nuclear factor kappa-B (NF-κB), were determined by Western blotting. There were 46 components determined in PLEO with many terpenoids compounds. PLEO decreased TC and TG contents in the FFA-treated HepG2 cells. Furthermore, PLEO inhibited TNF-α, IL-6 and IL-1β excretion, decreased NF-κB, FAS, ACC and SCD-1 while increased phosphorylation of NF-κB, PI3K, Akt, and CPT-1 expression. It is the first time to reveal that PLEO alleviates FFA-induced steatosis in HepG2 cells by regulating lipid metabolism, inhibiting inflammatory response, and improving insulin sensitivity.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2022
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IF 7.129
Tianmeng Zhang,Zhuhua Dong,Feixue Liu,Enzhuang Pan,Nana He,Fenfen Ma,Guanglu Wang,Yan Wang,Jingquan Dong
Avermectin, a "low toxicity insecticide", has been widely used in recent years, but its non-target toxicity, especially to aquatic organisms, has been neglected. In this study, we evaluated the neurotoxic effects of avermectin on carp by establishing a 96 h avermectin acute toxicity test, and its possible mechanism was discussed. The 96 h LC 50 of avermectin in carp was found to be 24.04 μg/L. Therefore, 3.005 μg/L and 12.02 μg/L were used as the low-dose and high-dose groups, respectively, to investigate the neurotoxic effects of avermectin on carp. The results of high-performance liquid chromatography (HPLC) analysis showed that avermectin accumulated in the carp brain. Histopathological observation and immunohistochemical analysis (IHC) of TNF-α and Bax showed that avermectin exposure led to inflammatory cell infiltration and neuronal necrosis. The mRNA levels of tight junction genes and the IHC results of ZO-1 and Occludin showed that the structure of the blood-brain barrier (BBB) was destroyed. Biochemical analysis showed that avermectin induced the accumulation of MDA in the brain and decreased the activity of antioxidant enzymes CAT and SOD, leading to oxidative stress. In addition, avermectin induces brain inflammation by activating NF-κB pathway and releasing inflammatory factors IL-1β, IL-6, TNF-α and iNOS. TEM and TUNEL assays showed that exposure to avermectin induced apoptosis in brain. what is more, the expression of apoptosis-related genes and proteins suggested that avermectin-induced apoptosis may be associated with inhibition of the PI3K/Akt signaling pathway. This study also showed that avermectin-induced NF-κB signaling activation was partially dependent on its upstream PI3K/Akt signaling pathway. Therefore, this study concludes that avermectin can induce neurotoxicity in carp by disrupting the blood-brain barrier structure and generating oxidative stress, inflammation, and apoptosis and that NF-κB and PI3K/Akt signaling pathways are involved in this process.
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FOOD RESEARCH INTERNATIONAL
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2021
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IF 6.475
Ting Xia,Chang-Shun Liu,Yan-Nan Hu,Zhen-Ye Luo,Fei-Long Chen,Li-Xia Yuan,Xiao-Mei Tan
Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years. Coix seed (CS) as a homologous substance of traditional Chinese medicine and food, its polysaccharides can improve the symptoms of patients with metabolic disorders. Since most plant polysaccharides are difficult to digest and absorb, we hypothesized that Coix seed polysaccharides (CSP) exert hypoglycemic effects through the gut. In this study, the underlying mechanisms regulating hypoglycemic effects of CSP on a T2DM mouse model were investigated. After treatment with CSP, serum insulin and high-density lipoprotein cholesterol levels were increased, while total cholesterol, triglycerides and low-density lipoprotein cholesterol levels were decreased in T2DM mice. In addition, CSP treatment helped repair the intestinal barrier and modulated the gut microbial composition in T2DM mice, mainly facilitating the growth of short-chain fatty acid (SCFA)-producing bacteria, Spearman’s analysis revealed these bacteria were positively related with the hypoglycemic efficacy of CSP. Colonic transcriptome analysis indicated the hypoglycemic effect of CSP was associated with the activation of the IGF1/PI3K/AKT signaling pathway. Correlative analysis revealed that this activation may result from the increase of SCFAs-producing bacteria by CSP. GC–MS detection verified that CSP treatment increased fecal SCFAs levels. Molecular docking revealed that SCFAs could bind with IGF1, PI3K, and AKT. Our findings demonstrated that CSP treatment modulates gut microbial composition, especially of the SCFAs-producing bacteria, activates the IGF1/PI3K/AKT signaling pathways, and exhibits hypoglycemic efficacy.
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危险品化学品经营许可证（带存储）