INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Junxian Hu,Yibo Zhu,Xiaoxiao Li,Zeyu Pang,Xiangwei Li,Huilin Zhang,Yiyang Wang,Pei Li,Qiang Zhou
Medical and conservative treatments for intervertebral disc degeneration (IDD) primarily focus on alleviating symptoms. However, effective curative therapies that promote disc regeneration remain lacking. Recent advancements in disc repair materials offer a potential solution, but identifying effective cytokines for regeneration and developing efficient drug delivery systems are crucial for success. This study demonstrated a negative correlation between AQP3 expression levels and the extent of disc degeneration induced by mechanical overload, as evidenced in both in vivo and in vitro models, suggesting that AQP3 is a key regulator of intervertebral disc (IVD) homeostasis. Moreover, the overexpression of AQP3 or exogenous AQP3 protein significantly repaired degenerated IVDs. As a membrane protein, exogenous AQP3 is challenging for cells to recognize and internalize. To address this issue, we designed liposomes to encapsulate AQP3 and incorporated them into GelMA (AQP3-lipo@GelMA) for targeted repair of IDD resulting from high mechanical pressure. The encapsulation of AQP3 in liposomes improved cellular recognition and uptake, thereby enhancing its functionality at the cell membrane. Additionally, AQP3 within this material inhibited the binding of integrins to sialic acid-binding proteins (IBSP), which subsequently reduced the expression of the downstream integrin αVβ3. This cascade effect indirectly activated the AKT pathway, promoting the survival of NP cells. In vivo experiments, we found that AQP3-lipo@GelMA had an efficient function of repairing degenerated intervertebral disc. This study introduced AQP3-lipo@GelMA as a promising material for clinical applications in IVD repair.
研究领域:
再生医学
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骨科
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生物材料科学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2025
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IF 4.8
Dandan Zhou,Xiaoxiao Li,Wencun Liu,Mingjun Zhang,Ying Cheng,Zhousong Xu,Jian Gao,Yiyang Wang
Liver cancer, a highly aggressive malignancy, continues to present significant challenges in therapeutic management due to its pronounced chemoresistance. This resistance, which undermines the efficacy of conventional chemotherapy and targeted therapies, is driven by multifaceted mechanisms, with increasing emphasis placed on the protective role of the tumor microenvironment (TME). The hepatocellular carcinoma extracellular matrix (ECM), a primary non-cellular component of the TME, has emerged as a critical regulator in cancer progression and drug resistance, particularly in hepatocellular carcinoma cell (HCC). In this study, a hybrid biomimetic hydrogel was engineered by integrating decellularized hepatocellular carcinoma matrix (DHCM) with gelatin methacrylate (GelMA) precursors. This composite DHCM/GelMA hydrogel was designed to replicate the physicochemical and functional properties of the hepatocellular carcinoma ECM, thereby offering a biomimetic platform to explore the interactions between HCCs and their microenvironment. Leveraging a custom-designed microfluidic 3D printing platform, we achieved high-throughput fabrication of HCC-encapsulated DHCM/GelMA microgels, characterized by enhanced uniformity, biocompatibility, and scalability. These microgels facilitated the construction of hepatocellular carcinoma microtissues, which were subsequently employed for chemoresistance studies. Our findings revealed that DHCM/GelMA microgels closely mimic the hepatocellular carcinoma tumor microenvironment, effectively recapitulating key features of ECM-mediated drug resistance. Mechanistic studies further demonstrated that DHCM significantly upregulates the expression of Aquaporin 3 (AQP3) in the encapsulated HCCs. This upregulation potentially activates mTOR signaling-associated autophagy pathways, thereby enhancing chemoresistance in HCCs. These biomimetic models provide a robust and versatile platform for studying the underlying mechanisms of drug resistance and evaluating therapeutic interventions. This innovative approach highlights the potential of DHCM/GelMA microgels as a transformative tool in cancer-associated tissue engineering and anticancer drug screening. By enabling detailed investigations into the role of ECM in chemoresistance, this study contributes to advancing therapeutic research and offers promising strategies to overcome drug resistance, ultimately improving clinical outcomes in liver cancer treatment.
研究领域:
生物医学工程
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肿瘤学
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药理学
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DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
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2026
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IF 3.9
Zhen-ye Luo,Zhe Chen,Feng-lin Zhang,Chang-shun Liu,Fei-long Chen,Ze-zhong Zheng,Xiao-mei Tan
Bacterial diarrhea involves colonic water absorption dysfunction and gut microbiota disruption. Gegen Qinlian decoction (GQD) is clinically used to treat infectious diarrhea, yet its mechanisms remain incompletely understood. This study aimed to investigate how GQD modulates gut microbiota and enhances colonic water absorption in E. coli -induced diarrhea. Using an E. coli -induced piglet diarrhea model together with a rat colonic perfusion model, results show that GQD alleviates diarrhea-associated intestinal injury and inflammation and improves colonic water absorption. Mechanistically, GQD was associated with increased colonic aquaporin-3 (AQP3) expression and attenuation of the cAMP-protein kinase A-cystic fibrosis transmembrane conductance regulator (cAMP-PKA-CFTR) secretory signaling axis. 16S rRNA sequencing indicated enrichment of Lactobacillus amylovorus after GQD treatment, and administration of L. amylovorus partially reproduced the anti-diarrheal phenotype and transport-related signaling changes. In vitro assays further suggested that GQD suppresses E. coli growth while promoting L. amylovorus metabolic activity, and molecular docking provided hypothesis-generating predictions of candidate phytochemicals and bacterial targets. Overall, GQD may improve bacterial dysbiosis by enriching L. amylovorus and inhibiting E. coli , thereby restoring colonic water transport via the cAMP/CFTR/AQP3 pathway and ultimately improving bacterial diarrhea.
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DOI
高影响因子
Food Bioscience
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2026
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IF 6.2
Xiao Qiang,Mengyuan Gao,Zongshuo Li,Weidong Li
SQLE is a potential functional food for alleviating spleen deficiency syndrome. • SQLE contains diverse bioactive compounds with flavonoids as major components. • SQLE restores gut microbiota homeostasis and promotes SCFAs production. • SQLE improves spleen deficiency via the PI3K/Akt/NF-κB/AQP3 signaling pathway. Spleen deficiency syndrome (SDS) manifests as impaired digestive function, fatigue, and metabolic issues, which are closely associated with dysbiosis of the gut microbiota. Shen-Qi-Ling extract (SQLE) is a natural extract prepared from food-medicine homologous resources, primarily consisting of Codonopsis pilosula , Astragalus membranaceus , and Poria cocos . However, the bioactive constituents and mechanisms by which it alleviates SDS remain unclear. In this study, we systematically characterized the chemical constituents of SQLE and elucidated its potential mechanisms of action against SDS in mice. Using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) analysis, 137 compounds were identified in SQLE, with flavonoids being the most abundant, followed by coumarins, phenylpropanoids, and organic acids. Molecular docking analysis indicated that SQLE might have a spleen-strengthening effect. Treatment with SQLE, particularly SQLE-M, significantly enhanced intestinal absorption, exercise performance, tissue damage, and oxidative stress. Moreover, SQLE-M restored gut microbial homeostasis, increased the relative abundance of potentially beneficial bacteria, and promoted the production of short-chain fatty acids (SCFAs). Notably, SQLE-M normalized the intestinal barrier dysfunction and metabolic disorders by activating the PI3K/Akt signaling pathway, inhibiting NF-κB-mediated inflammatory responses, and upregulating aquaporin 3 (AQP3) expression. Collectively, SQLE mitigates SDS, which may be associated with alterations in the gut microbiota-metabolite axis and the PI3K/Akt/NF-κB/AQP3 signaling pathway, offering new perspectives for developing spleen-strengthening functional foods derived from food-medicine homologous resources. Download: Download high-res image (462KB) Download: Download full-size image
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DOI
高影响因子
BMC MICROBIOLOGY
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2024
·Vol. 24
·期 1
·1-13
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IF 4
Tang Shuai,Li Jia,Li Yi,Du Haitao,Zhu Wenya,Zhang Ru,Wan Jun
Saccharomyces boulardii (S. boulardii) is a fungal probiotic used to treat digestive disorders. However, the mechanism(s) by which S. boulardii affects the small intestine remains unclear. Here, we aimed to explore the effects of S. boulardii on the small intestine and the underlying mechanisms in mice with loperamide-induced constipation. While S. boulardii administration did not fully reverse the alterations in loperamide-induced defecation parameters, it altered the small intestinal floral composition toward a community conducive to alleviate constipation. Moreover, S. boulardii up-regulated the expression of tyrosine-protein kinase Kit (c-Kit), aquaporin 3 (AQP3), interleukin (IL)-10, myosin light chain kinase (MLCK), and phosphorylated myosin light chain 20 (P-MLC20), while concurrently down-regulating the expression levels of inducible nitric oxide synthase (iNOS), p65, and IL-17 A. These alterations indicate a discernible effect of small intestinal water reabsorption, inflammatory factor levels, and smooth muscle contraction. Saccharomyces boulardii also positively regulated small intestinal metabolite levels, such as fructose 6-phosphate, dihomo-alpha-linolenic acid, and 3-(4-hydroxyphenyl) lactate, and participated in metabolic pathways such as arginine biosynthesis, linoleic acid metabolism, and protein digestion and absorption. While not fully reversing defecation changes, Saccharomyces boulardii alters intestinal flora, up-regulates key proteins affecting water reabsorption and inflammation, and positively influences metabolic pathways. Our study provides serves as a basis for further studies on the application of S. boulardii in the treatment of intestinal disorders.
研究领域:
胃肠病学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
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