Amphibian-derived peptide RL-RF10 ameliorates paraquat-induced pulmonary fibrosis injury.

Pulmonary fibrosis is the result of dysfunctional repair after lung tissue injury, characterized by fibroblast proliferation and massive extracellular matrix aggregation. Once fibrotic lesions develop, effective treatment is difficult, with few drugs currently available. Here, we identified a short cyclic decapeptide RL-RF10 derived from frog skin secretions as a potential novel lead molecule for the amelioration of pulmonary fibrosis. In vivo experiments indicated that RL-RF10 treatment ameliorated lung histopathological damage and fibrogenesis after paraquat (PQ) induction in a concentration-dependent manner. On day 7, bronchoalveolar lavage fluid assays performed on mice showed that RL-RF10 exerted anti-inflammatory effects by decreasing the expression of inflammation-related factors, including transforming growth factor-ß1 (TGF-ß1) and tumor necrosis factor-α, in lung tissue. In addition, RL-RF10 down-regulated the levels of collagen I, collagen III, and vimentin, while increasing the expression of E-cadherin to inhibit epithelial-mesenchymal transition. Further research demonstrated that the SMAD2/3 signaling pathway, which is strongly linked to TGF-ß1, played a critical function in enhancing the pulmonary fibrosis relief achieved by RL-RF10. Both in vivo and in vitro assays showed that RL-RF10 treatment led to a significant reduction in the phosphorylation levels of SMAD2 and SMAD3 following PQ induction. Overall, we investigated the protective effects and underlying mechanisms of the RL-RF10 peptide against pulmonary fibrosis and demonstrated its potential as a novel therapeutic drug candidate for the treatment of pulmonary fibrotic diseases.

The Antivirulence Activity of Umbelliferone and Its Protective Effect against A. hydrophila-Infected Grass Carp.

A. hydrophila is an important pathogen that mainly harms aquatic animals and has exhibited resistance to a variety of antibiotics. Here, to seek an effective alternative for antibiotics, the effects of umbelliferone (UM) at sub-MICs on A. hydrophila virulence factors and the quorum-sensing system were studied. Subsequently, RNA sequencing was employed to explore the potential mechanisms for the antivirulence activity of umbelliferone. Meanwhile, the protective effect of umbelliferone on grass carp infected with A. hydrophila was studied in vivo. Our results indicated that umbelliferone could significantly inhibit A. hydrophila virulence such as hemolysis, biofilm formation, swimming and swarming motility, and their quorum-sensing signals AHL and AI-2. Transcriptomic analysis showed that umbelliferone downregulated expression levels of genes related to exotoxin, the secretory system (T2SS and T6SS), iron uptake, etc. Animal studies demonstrated that umbelliferone could significantly improve the survival of grass carps infected with A. hydrophila, reduce the bacterial load in the various tissues, and ameliorate cardiac, splenic, and hepatopancreas injury. Collectively, umbelliferone can reduce the pathogenicity of A. hydrophila and is a potential drug for treating A. hydrophila infection.

New Rice-Derived Short Peptide Potently Alleviated Hyperuricemia Induced by Potassium Oxonate in Rats.

Gout that caused by hyperuricemia affects human health seriously and more efficient drugs are urgently required clinically. In this study, a novel peptide named RDP1 (AAAAGAKAR, 785.91 Da) was identified from the extract of shelled fruits of Oryza sativa. Our results demonstrated that RDP1 (the minimum effective concentration is 10 µg/kg) could significantly reduce the serum uric acid and creatinine and alleviate hyperuricemic nephropathy in rats by intragastric administration. RDP1 inhibited xanthine oxidase, which also was verified at the animal level. Results from molecular docking indicated that RDP1 can inhibit uric acid formation by occupying the binding site of xanthine oxidase to xanthine. Besides, RDP1 showed no toxicity on rats and was stable in several temperatures, demonstrating its advantages for transportation. This research was the first discovery of antihyperuricemic peptide from the shelled fruits of O. Sativa and provided a new candidate for the development of hypouricemic drugs.

Edaphic Conditions Regulate Denitrification Directly and Indirectly by Altering Denitrifier Abundance in Wetlands along the Han River, China.

Riparian wetlands play a critical role in retaining nitrogen (N) from upland runoff and improving river water quality, mainly through biological processes such as soil denitrification. However, the relative contribution of abiotic and biotic factors to riparian denitrification capacity remains elusive. Here we report the spatiotemporal dynamics of potential and unamended soil denitrification rates in 20 wetlands along the Han River, an important water source in central China. We also quantified the abundance of soil denitrifying microorganisms using nirK and nirS genes. Results showed that soil denitrification rates were significantly different between riparian and reservoir shoreline wetlands, but not between mountain and lowland wetlands. In addition, soil denitrification rates showed strong seasonality, with higher values in August (summer) and April (spring) but lower values in January (winter). The potential and unamended denitrification rates were positively correlated with edaphic conditions (moisture and carbon concentration), denitrifier abundance, and plant species richness. Path analysis further revealed that edaphic conditions could regulate denitrification rates both directly and indirectly through their effects on denitrifier abundance. Our findings highlight that not only environmental factors, but also biotic factors including denitrifying microorganisms and standing vegetation, play an important role in regulating denitrification rate and N removal capacity in riparian wetlands.

Distribution, source identification, and ecological risk assessment of heavy metals in wetland soils of a river-reservoir system.

The majority of rivers in the world have been dammed, and over 45,000 large reservoirs have been constructed for multiple purposes. Riparian and reservoir shorelines are the two most important wetland types in a dammed river. To date, few studies have concerned the heavy metal pollution in wetland soils of these river-reservoir systems. In this study, we measured the concentrations of ten heavy metals (Ba, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sr, and Zn) in surface soils collected from riparian and reservoir shorelines along the Han River in different seasons. Our results found that the Co, Cu, and Ni concentrations in riparian wetlands were significantly lower than those in reservoir shorelines. In riparian wetlands, only soil Sr concentration significantly increased after summer and autumn submergence. Multivariate statistical analyses demonstrated that Ba and Cd might originate from industrial and mining sources, whereas Sr and Mn predominantly originated from natural rock weathering. The ecological risk assessment analysis indicated that both riparian and reservoir shorelines along the Han River in China exhibited a moderate ecological risk in soil heavy metals. The upper Han River basin is the water resource area of China's Middle Route of the South-to-North Water Transfer Project. Therefore, to control the contamination of heavy metals in wetland soils, more efforts should be focused on reducing the discharge of mining and industrial pollutants into the riparian and reservoir shorelines.