Atrial natriuretic peptide (ANP) activity deficiency contributes to salt-sensitive hypertension in humans and mice. However, the role of ileal microbiota in salt sensitivity in ANP deficiency-related cardiac injury has not been investigated yet. This study used ANP−/− mice to analyze the role of the salt-sensitive ileal microbiome on cardiac injury. ANP−/− mice showed an increase in blood pressure (BP), the heart weight/body weight (HW/BW) ratio, and cardiac hypertrophy compared with wild-type (WT) mice. ANP deficiency did not impact the histological structure but reduced occludin expression in the ileum. Antibiotics significantly relieved BP and cardiac hypertrophy in ANP−/− mice. A high-salt diet (HSD) increased BP, the HW/BW ratio, and cardiac hypertrophy/fibrosis in WT and ANP−/− mice, and an HSD treatment in ANP−/− mice exacerbated these cardiac parameters. The HSD markedly decreased muscularis layer thickening, villus length, and numbers of Paneth and goblet cells in the ileum of WT and ANP−/− mice. Furthermore, the HSD increased the level of TLR4 and IL-1β in ANP−/− mice ileum compared with WT mice. Antibiotics reduced the HW/BW ratio, cardiac hypertrophy/fibrosis, and the level of TLR4 and IL-1β in the ileum, and rescued the muscularis layer thickening, villus length, and numbers of Paneth and goblet cells in the ileum of HSD-ANP−/− mice. Importantly, ANP deficiency induced the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum on the NSD diet, which was only observed in HSD-induced WT mice but not in WT mice on the NSD. Besides, the HSD significantly enhanced the sum of the percentage of the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum of ANP−/− mice. Ileal microbiota transfer (IMT) from ANP−/− mice to healthy C57BL/6J mice drove Lactobacillus johnsonii and Lactobacillus reuteri colonization in the ileum, which manifested an increase in BP, the HW/BW ratio, cardiac hypertrophy, and ileal pathology compared with IMT from WT mice. The HSD in C57BL/6J mice with IMT from ANP−/− mice drove the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum and further exacerbated the cardiac and ileal pathology. Our results suggest that salt-sensitive ileal microbiota is probably related to ANP deficiency-induced cardiac injury.
Methylene blue (MB)- or Curcumin (Cur)-based photodynamic therapy (PDT) has been used as an adjunctive treatment for periodontitis. Its actual clinical efficacy is still in question because the lack of oxygen in a deep periodontal pocket might reduce the PDT efficacy. We aim to investigate the effect of oxygen on PDT efficacy and to examine if the addition of hydrogen peroxide (HP) could improve PDT performance anaerobically. To this end, we cultured 48 h saliva-derived multi-species biofilms and treated the biofilms with 25 µM MB or 40 µM Cur, HP (0.001%, 0.01% and 0.1%), light (L-450 nm or L-660 nm), or combinations thereof under ambient air or strictly anaerobic conditions. MB- and Cur-PDTs significantly reduced biofilm viability in air but not under anaerobic conditions. HP at 0.1% significantly enhanced the killing efficacies of both MB- and Cur-PDTs anaerobically. The killing efficacy of Cur-PDT combined with 0.1% HP was higher anaerobically than in air. However, this was not the case for MB-PDT combined with 0.1% HP. In conclusion, this study demonstrated that the biofilm killing efficacies of MB- and Cur-PDTs diminished when there was no oxygen. HP at 0.1% can enhance the efficacy of PDT performed anaerobically, but the level of enhancement is photosensitizer-dependent.
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