Matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) play important roles in the progression of renal interstitial fibrosis (RIF). There is an increasing demand to construct a novel method for the simultaneous detection of MMP-9 and MMP-2 to monitor the progression of RIF. Herein, a strategy based on the nanoplatform composed of the polydopamine nanosphere and fluorescence-labeled aptamers is developed to simultaneously detect MMP-9 and MMP-2 with DNase-I-assisted recycling signal amplification. In the light of tracing the recovered fluorescence intensity at 520 and 610 nm upon adding MMP-9 and MMP-2, the increased fluorescence intensity is linear to the different concentrations of MMP-9 and MMP-2 with the detection limits of 9.6 and 25.6 pg/mL for MMP-9 and MMP-2, respectively. More intriguingly, the results of unilateral ureteral obstruction mice show that the concentration of MMP-9 in urine is increased with the extension of ligation time while the concentration of MMP-2 is reversed, indicating that the ratio of MMP-9 to MMP-2 could be considered as the potential urinary biomarker to evaluate the progress of RIF and the therapeutic effect of Huangkui capsule on RIF. Therefore, this study provides a paradigmatic strategy for the simultaneous detection of the dual markers of RIF, which is promising for the auxiliary clinical diagnosis and assessment of the prognosis of chronic kidney disease.

No abstract

Background: Pulmonary fibrosis (PF) is a devastating interstitial lung disease and characterized by an abnormal accumulation of extracellular matrix (ECM). Nintedanib (NDN) and pirfenidone are two approved therapies for PF, but their potential side-effects have been reported. Recently, the use of natural supplements for PF is attracting attention. Alpha-mangostin (α-MG) is an active xanthone-type compound isolated from the nutritious fruit mangosteen. Purpose: In the present study, the potential effect and underlying mechanism of α-MG were evaluated in bleomycin (BLM)-induced PF and activated primary lung fibroblasts (PLFs). Methods: Histopathological changes and collagen deposition were analyzed via hematoxylin-eosin staining and Masson staining, the expression of nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX4) involved in oxidative stress in lung tissues was analyzed by immunochemistry staining. The expressions of α-smooth muscle actin (α-SMA), collagen I (Col I), p-adenosine 5′-monophosphate-activated protein kinase (AMPK)/AMPK, and NOX4 were detected by Western blot, immunofluorescence or RT-PCR, and effects of α-MG on cell viability were detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. Results: In vivo results demonstrated that α-MG treatment (10 mg/kg/day) significantly ameliorated BLM-induced deposition of ECM in lung tissues. Moreover, α-MG could inhibit protein expressions of α-SMA and Col I as well as its mRNA levels. In addition, α-MG also significantly inhibited transforming growth factor-β1/Smad2/3 pathway and regulated the protein expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in lung tissues. In vitro results demonstrated that α-MG significantly increased p-AMPK/AMPK but reduced the protein expression level of α-SMA and Col I as well as NOX4 in activated PLFs. Further study demonstrated that these improvement effects were significantly blocked by compound C. Conclusion: α-MG treatment significantly decreased oxidative stress in lungs partly by activating AMPK mediated signaling pathway in BLM-induced PF and activated PLFs and decreased the deposition of ECM. The present study provides pharmacological evidence to support therapeutic application of α-MG in the treatment of PF.

No abstract

No abstract