CONTEXTDiabetic nephropathy (DN) is a major complication of diabetes mellitus and is the leading cause of kidney disease in patients undergoing renal replacement therapy. DN is associated with an increased risk of death in patients with diabetes. Conventional therapy for DN includes intensive control of blood glucose level and blood pressure and renin-angiotensin system blockade. However, this approach has limited treatment effects on DN. Therefore, identifying novel drugs to delay the progression of DN is urgently needed. Proanthocyanidin (PA) has been shown to exert potentially beneficial effects on DN. However, the protective mechanism and efficacy are yet to be elucidated.OBJECTIVEThis study evaluates the efficacy and potential mechanisms of PA in animal models of DN.METHODSPreclinical studies were searched from Chinese National Knowledge Infrastructure, PubMed, Web of Science, Embase, and Google Scholar databases, with the search deadline of August 2023. Keywords ('diabetic nephropathies', 'nephropathies, diabetic', 'diabetic kidney diseases', 'proanthocyanidin', 'anthocyanidin polymers', 'procyanidins', 'animal*', 'rat', and 'mice') were used to search the databases. RevMan 5.3 was used for statistical analysis.RESULTSA total of 22 studies involving 538 animals were included in this analysis. The pooled results indicated that PA therapy significantly improved kidney function and reduced proteinuria and blood glucose levels. The protective mechanism of PA was associated with anti-inflammatory, antioxidant, antifibrotic, and antiapoptotic effects; inhibition of endoplasmic reticulum stress; and alleviation of mitochondrial dysfunction and dyslipidemia.CONCLUSIONThese findings suggest that PA alleviates DN by mediating multiple targets and pathways.

01 Dec 2024·Journal of the Mechanical Behavior of Biomedical Materials

Promotion effect of proanthocyanidin on dentin remineralization via the polymer induced liquid precursor process

Article

Author: Chen, Chaoqun ; Lai, Haiyan ; Song, Pingping ; Gu, Xinhua

Proanthocyanidin (PA) has demonstrated promise as a dental biomodifier for maintaining dentin collagen integrity, yet there is limited evidence regarding its efficacy in dentin repair. The aim of this study was to investigate the effect of PA on dentin remineralization through the polymer induced liquid precursor (PILP) process, as well as to assess the mechanical properties of the restored dentin. Demineralized dentin was treated with a PA-contained remineralization medium, resulting in the formation of PA-amorphous calcium phosphate (ACP) nanoparticles via the PILP process. The kinetics and microstructure of remineralized dentin were examined through the use of Fourier transform infrared spectroscopy(FTIR), attenuated total reflectance-FTIR, scanning electron microscopy, transmission electron microscopy. The results showed that the application of PA facilitated the process of dentin remineralization, achieving completion within 48 h, demonstrating a notable reduction in time required. Following remineralization, the mechanical properties of the dentin exhibited an elastic modulus of 15.89 ± 1.70 GPa and a hardness of 0.47 ± 0.08 GPa, which were similar to those of natural dentin. These findings suggest that combining PA with the PILP process can promote dentin remineralization and improve its mechanical properties, offering a promising new approach for dentin repair in clinical practice.

01 Nov 2024·International Endodontic Journal

Proanthocyanidin surface preconditioning of dental pulp stem cell spheroids enhances dimensional stability and biomineralization in vitro

Article

Author: Dissanayaka, Waruna Lakmal ; Yang, Shengyan ; Leung, Andy Yu Pan ; Wang, Zheng ; Yiu, Cynthia Kar Yung

AbstractAimLack of adequate mechanical strength and progressive shrinkage over time remain challenges in scaffold‐free microtissue‐based dental pulp regeneration. Surface collagen cross‐linking holds the promise to enhance the mechanical stability of microtissue constructs and trigger biological regulations. In this study, we proposed a novel strategy for surface preconditioning microtissues using a natural collagen cross‐linker, proanthocyanidin (PA). We evaluated its effects on cell viability, tissue integrity, and biomineralization of dental pulp stem cell (DPSCs)‐derived 3D cell spheroids.MethodologyMicrotissue and macrotissue spheroids were fabricated from DPSCs and incubated with PA solution for surface collagen cross‐linking. Microtissue viability was examined by live/dead staining and 3‐(4,5‐dimethylthiazol‐2‐yl)−2,5‐diphenyltetrazolium bromide (MTT) assay, with transverse dimension change monitored. Microtissue surface stiffness was measured by an atomic force microscope (AFM). PA‐preconditioned microtissues and macrotissues were cultured under basal or osteogenic conditions. Immunofluorescence staining of PA‐preconditioned microtissues was performed to detect dentin sialophosphoprotein (DSPP) and F‐actin expressions. PA‐preconditioned macrotissues were subjected to histological analysis, including haematoxylin–eosin (HE), alizarin red, and Masson trichrome staining. Immunohistochemistry staining was used to detect alkaline phosphatase (ALP) and dentin matrix acidic phosphoprotein 1 (DMP‐1) expressions.ResultsPA preconditioning had no adverse effects on microtissue spheroid viability and increased surface stiffness. It reduced dimensional shrinkage for over 7 days in microtissues and induced a larger transverse‐section area in the macrotissue. PA preconditioning enhanced collagen formation, mineralized nodule formation, and elevated ALP and DMP‐1 expressions in macrotissues. Additionally, PA preconditioning induced higher F‐actin and DSPP expression in microtissues, while inhibition of F‐actin activity by cytochalasin B attenuated PA‐induced dimensional change and DSPP upregulation.ConclusionPA surface preconditioning of DPSCs spheroids demonstrates excellent biocompatibility while effectively enhancing tissue structure stability and promoting biomineralization. This strategy strengthens tissue integrity in DPSC‐derived spheroids and amplifies osteogenic differentiation potential, advancing scaffold‐free tissue engineering applications in regenerative dentistry.

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Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Preclinical	CN	Nanjing Medical University	28 Oct 2020

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