Food Bioscience
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2024
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IF 4.8
Zetong Cheng,Cheng Yao,Zhihao Chen,Kun Hu,Pinhuang Luo,Kewei Liu,Tian-Ao Zhang,Jiajun Hu,Min-Tian Gao
Strobilanthes cusia is a traditional Chinese medicinal herb containing indole alkaloids, key bioactive components responsible for its pharmacological effects. However, there has been limited research regarding S. cusia compositional impact on antimicrobial properties. This study centered around the hydrolysis and oxidative condensation reactions of indican, aiming to investigate the influence of its intermediate, indoxyl, on pathogenic bacteria growth and biofilm formation. A notable inhibitory effect of indoxyl on Staphylococcus aureus biofilm formation was found. High-performance liquid chromatography and transmission electron microscopy confirmed that indoxyl disrupted the membrane structure of biofilm cells, causing a disturbance in cellular redox balance. These findings suggest that the oxidative reaction of indoxyl within cells could be a prominent factor affecting cell viability. Simultaneously, a portion of indoxyl oxidized externally to form indigo, which did not affect intracellular activities but rather disrupted the biofilm structure. The concept of “compositional changes” enriches the understanding of antimicrobial properties of S. cusia , offering novel approaches for effectively inhibiting pathogenic microorganisms.
研究领域:
药用植物学
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微生物学
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药物化学
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DOI
高影响因子
ORAL DISEASES
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2024
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IF 2.9
Huiwen Chen,Yining Zhou,Yingli Liu,Wei Zhou,Lina Xu,Dihua Shang,Jing Ni,Zhongchen Song
Objectives The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients. Materials and Methods Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro-CT. MC3T3-E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis-related factors were detected. RT-PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation. Results Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3-E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS. Conclusions IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3-E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.
研究领域:
牙科学
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肾病学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
JCI Insight
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2022
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IF 9.484
Jing Yang,Hongxia Li,Chi Zhang,Yafeng Zhou
There is a high prevalence of ventricular arrhythmias related to sudden cardiac death in patients with chronic kidney disease (CKD). To explored the possible mechanism of CKD-related ventricular arrhythmias, a CKD rat model was created, and indoxyl sulfate (IS) was further used in vivo and in vitro. This project used the following methods: patch clamp, electrocardiogram, and some molecular biology experimental techniques. IS was found to be significantly elevated in the serum of CKD rats. Interestingly, the expression levels of the fast transient outward potassium current–related (I to,f -related) proteins (Kv4.2, Kv4.3, and KChIP2) in the heart of CKD rats and rats treated with IS decreased. IS dose-dependently reduced I to,f density, accompanied by the decreases in Kv4.2, Kv4.3, and KChIP2 proteins in vitro. IS also prolonged the action potential duration and QT interval, and paroxysmal ventricular tachycardia could be induced by IS. In-depth studies have shown that ROS/p38MAPK, ROS–p44/42 MAPK, and NF-κB signaling pathways play key roles in the reduction of I to,f density and I to,f -related proteins caused by IS. These data suggest that IS reduces I to,f -related proteins and I to,f density by activating ROS/MAPK and NF-κB signaling pathways, and the action potential duration and QT interval are subsequently prolonged, which contributes to increasing the susceptibility to arrhythmia in CKD.
研究领域:
心脏病学
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肾病学
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分子生物学
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电生理学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Xinyu Zhang,Sufang Li,Tingru Lin,Liangying Gan,Li Zhu,Li Zuo
Background Cardiovascular events remain the leading cause of mortality in chronic kidney disease (CKD). Pegmolesatide(P), a novel long-acting EPO receptor modulator, shows cardiovascular benefits in clinical studies. This study aims to demonstrate Pegmolesatide suppressed the formation of EPOR-CD131 heterodimer and to explore its cardioprotective mechanisms against indoxyl sulfate (IS)-induced cardiomyocyte hypertrophy. Methods H9c2 cardiomyocytes were assigned to different treatment groups (vehicle, IS, IS+P, P) and RNA sequencing was performed to identify dysregulated signaling pathways. Mechanistic exploration groups supplemented with CD131 agonist ARA290, STAT3 activator Colivelin, or STAT3 inhibitor Stattic for rescue experiments. Analyses included real-time qPCR/Western blot for cardiac hypertrophy markers and EPOR-CD131/JAK2/STAT3 axis components, phalloidin staining for cell size and co-immunoprecipitation (Co-IP) for EPOR-CD131 heterodimerization. Results Pegmolesatide significantly attenuated IS-induced cardiomyocyte hypertrophy, as evidenced by suppressed expression of cardiac hypertrophy markers (ANP, BNP, and β-MHC), reduced cell surface area, and improved cytoskeletal organization( P < 0.05). Mechanistically, Pegmolesatide upregulated EPOR expression while suppressing CD131 expression and activation of the JAK2/STAT3 signaling. Co-IP analysis demonstrated that Pegmolesatide suppressed the formation of EPOR-CD131 heterodimer. Functional rescue experiments showed that the cardioprotective effects of Pegmolesatide were reversed by CD131 agonist ARA290 or STAT3 activator Colivelin. Notably, combined treatment with ARA290 and STAT3 inhibitor Stattic partially restored its anti-hypertrophic activity. Conclusion Pegmolesatide exerts protective effects against IS-induced cardiomyocyte hypertrophy by inhibiting the EPOR-CD131/JAK2/STAT3 signaling axis. It may be a promising strategy for CKD-related cardiovascular complications.
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Lian Xiao,Hu Di,Zhang Ruilong,Niu Helin
Indoxyl sulfate (IS), a protein-bound uremic toxin implicated in chronic kidney disease (CKD) progression and extrarenal pathologies, necessitates the development of accessible monitoring tools for point-of-care diagnostics. To address this challenge, we engineered a portable fluorescent capsule device by encapsulating an antenna-effect-enhanced europium metal–organic gel (EuMOG) within a biocompatible alginate matrix. This innovative sensor exhibits specific ratiometric fluorescence modulation toward IS via a photoinduced electron transfer (PET) mechanism, wherein IS binding triggers a distinct emission shift: quenching of Eu3+ red emission (619 nm) with concurrent 29-fold enhancement of ligand-centered blue emission (393 nm). Significantly, the capsule achieves ultrasensitive detection with record-low detection limits of 1.9 ppb in urine and 43.61 ppm in serum─surpassing conventional methods by orders of magnitude─while maintaining selectivity against structurally similar metabolites (e.g., uric acid, creatinine) and physiological interferents in complex matrices. The visually discernible pink-to-blue transition under UV light enables instrument-free, real-time semiquantification within 16 min, as validated by linear ratiometric responses across clinically relevant IS concentrations (1–900 μM, R2 = 0.996). The integration of room-temperature synthesis, dynamic capsule dissolution kinetics, and PET-driven specificity establishes a paradigm shift toward deployable CKD diagnostics, particularly for resource-limited settings.
研究领域:
生物医学工程
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分析化学
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医学诊断
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材料科学
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生物化学
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肾病学
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产品关联
DOI
PubMed
高影响因子
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