Peptide NCTX15 derived from spider toxin gland effectively relieves hyperuricemia in mice.

Hyperuricemia is a clinical disease characterized by a continuous increase in uric acid (UA) due to purine metabolism disorder. As current drug treatments are limited, it is imperative to explore new drugs that offer better safety and efficacy. In this study, Nephila clavata toxin gland homogenates were isolated and purified by exclusion chromatography and high-performance liquid chromatography, resulting in the identification and isolation of a short peptide (NCTX15) with the sequence 'QSGHTFK'. Analysis showed that NCTX15 exhibited no cytotoxicity in mouse macrophages or toxic and hemolytic activity in mice. Notably, NCTX15 inhibited UA production by down-regulating urate transporter 1 and glucose transporter 9 and up-regulating organic anion transporter 1, thus promoting UA excretion. In addition, NCTX15 alleviated the inflammatory response and renal injury by inhibiting the expression of inflammatory factors interleukin-6, interleukin-1ß, tumor necrosis factor alpha, NLR family, pyrin domain-containing 3, and pyroptosis-related factor gasdermin D. These results indicate that NCTX15 displayed urate-lowering, anti-inflammatory, and analgesic effects. As the first urate-reducing short peptide isolated from a spider toxin gland homogenate, NCTX15 exhibits considerable potential as a novel drug molecule for anti-gout and hyperuricemia treatment.

The long-term effects of microplastics on soil organomineral complexes and bacterial communities from controlled-release fertilizer residual coating.

Controlled-release fertilizer (CRF) was applied widely in China as an efficient utilization strategy for improving grain yield and reducing the nitrogen contamination. However, it was indeterminate to know the impacts of inevitably imported plastic into the soil on sustainable development. After ten-year fixed-site experiment, the visible residual coating microplastics were separated from the soil to measure their changes, then the long-term effects of CRF application (theoretical microplastic content 0.018-0.151 g kg-1 soil) on soil architecture and bacterial communities were evaluated. Based on soil organomineral complexes (OMC) distribution experiments and soil 16S rRNA sequence analysis, residual coating microplastics had no significant impact on soil architecture and limited effects on soil bacteria, but became the specific microbial habitat. The nitrogen rate and nitrogen release mode affected sand- and silt-grade OMC, and nitrogen rate impacted soil bacteria communities. The residual coating, small inert particles, is safe for soil OMC and bacterial communities in agricultural soil. Due to the effectiveness of CRF on reducing environmental pollution, CRF is considered as a favorable measure to the sustainable agricultural development in Shandong Province, China.

The beneficial roles of poisonous skin secretions in survival strategies of the odorous frog Odorrana andersonii.

The evolution of predatory, anti-predatory, and defensive strategies regarding environmental adaptation in animals is of significant research interest. In particular, amphibians, who represent a transition between aquatic and terrestrial vertebrates, play an important role in animal evolution. The bioactive skin secretions of amphibians are of specific interest due to their involvement in the crucial physiological functions of amphibian skin. We previously isolated and identified several bioactive peptides, including those showing antioxidant, antimicrobial, and wound-healing properties, from the skin secretions of the odorous frog species Odorrana andersonii. Currently, however, the biological significance of skin secretions in O. andersonii survival remains unclear. Here, we studied the biological significance of skin glands and secretions in regard to environmental adaptations of O. andersonii. Our research found that O. andersonii may secrete and excrete bioactive secretions through many glands (peptides and proteins as the main components in glands) distributed in the skin. The skin secretions not only displayed toxicity but also showed antioxidant, antibacterial, and repair promoting activities, suggesting that they play a protective role in O. andersonii when facing environmental threats. These bioactive skin secretions appear to act as a chemical survival strategy in O. andersonii, allowing the species to gain advantages in survival behavior.

A short peptide potentially promotes the healing of skin wound.

Skin wound, a common form of skin damage in daily life, remains a serious challenge in clinical treatment. Bioactive peptides with high efficiency have been considered as potential therapeutic candidates for wound healing. In this report, a novel short linear peptide, with mature peptide sequence of 'GLLSGINAEWPC' and no obvious similarity with other known bioactive peptides, was identified by genomic method from the skin of odorous frog, Odorrana andersonii Our results suggested that OA-GL12 (OA: abbreviation of species (O. andersonii), GL: two initial amino acids, 12: peptide length) obviously accelerated the scratch-healing of keratinocytes and human fibroblasts in a time- and concentration-dependent manner. Meanwhile, OA-GL12 showed significant effect in promoting the wound healing on the full-thickness skin wound model. Inflammatory assay results demonstrated that OA-GL12 induced the secretion of tumor necrosis factor (TNF) and transforming growth factor ß1 (TGF-ß1) on murine macrophage cell line (RAW264.7), which might explain the powerful accelerating capacity of wound healing. Moreover, results also indicated that epidermal growth factor receptor (EGFR) was involved in the mechanisms underlying the scratch-healing promoting activity of OA-GL12. In addition, OA-GL12 showed obvious free radical scavenging activity. Results supported that OA-GL12 did not exert risk in acute toxicity, hemolytic activity, and direct antibacterial activity. The remarkable effect of OA-GL12 on promoting wound healing verified in this research made it potential to be a novel template for the development of wound healing-promoting agents.

Accelerated Wound Healing Induced by a Novel Amphibian Peptide (OA-FF10).

BACKGROUND: Despite the continued development of modern medicine, chronic wounds are still a critical issue in clinical treatment, placing a great physiological, psychological, and financial burden on patients. Researchers have investigated many methods to solve this problem, with bioactive peptides gaining increasing attention due to their considerable advantages and diverse functions, as well as low cost, simple storage, and easy transportation. METHODS: In this research, a novel peptide (named OA-FF10) was identified from the skin secretions of the odorous frog species Odorrana andersonii. The sequence of mature OA-FF10 was "FFTTSCRSGC", which was produced by the post-translational processing of a 61-residue prepropeptide. RESULTS: Similar to most frog peptides, OA-FF10 showed an intramolecular disulfide bridge at the C-terminus. OA-FF10 demonstrated no antibacterial, antioxidant, hemolytic, or acute toxic activity, but promoted wound healing and proliferation of human keratinocytes (HaCaT) both time- and dose-dependently. Furthermore, while OA-FF10 had no effect on wound healing of Human Skin Fibroblasts (HSF), it did accelerate healing in a full-thickness skin-wound mouse model. CONCLUSION: Our research revealed the strong wound-healing activity of OA-FF10 in vivo and in vitro, thus providing a new candidate for the development of novel wound-healing drugs.

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.

Author Correction: Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

OA-GL21, a novel bioactive peptide from Odorrana andersonii, accelerated the healing of skin wounds.

Nowadays, the number of chronic trauma cases caused by a variety of factors such as the world's population-ageing and chronic diseases is increasing steadily, and thus effective treatment for chronic wounds has become a severe clinical challenge, which also burdens the patient both physically and financially. Therefore, it is urgent to develop new drugs to accelerate the healing of wounds. Bioactive peptides, which are relatively low cost, easy to produce, store and transport, have become an excellent choice. In this research, we identified a novel peptide OA-GL21, with an amino acid sequence of 'GLLSGHYGRVVSTQSGHYGRG', from the skin secretions of Odorrana andersonii Our results showed that OA-GL21 exerted the ability to promote wound healing of human keratinocytes (HaCaT) and human fibroblasts in a dose- and time-denpendent manner. However, OA-GL21 had no significant effect on the proliferation of these two cells. Significantly, OA-GL21 showed obvious ability to promote wound healing in the full-thickness skin wound model in dose- and scar-free manners. Further studies showed that OA-GL21 had no direct antibacterial, hemolytic, and acute toxic activity; it had weak antioxidant activities but high stability. In conclusion, this research proved the promoting effects of OA-GL21 on cellular and animal wounds, and thus provided a new peptide template for the development of wound-repairing drugs.

Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing.

Cathelicidins play pivotal roles in host defense. The discovery of novel cathelicidins is important research; however, despite the identification of many cathelicidins in vertebrates, few have been reported in amphibians. Here we identified a novel cathelicidin (named cathelicidin-OA1) from the skin of an amphibian species, Odorrana andersonii. Produced by posttranslational processing of a 198-residue prepropeptide, cathelicidin-OA1 presented an amino acid sequence of 'IGRDPTWSHLAASCLKCIFDDLPKTHN' and a molecular mass of 3038.5 Da. Functional analysis showed that, unlike other cathelicidins, cathelicidin-OA1 demonstrated no direct microbe-killing, acute toxicity and hemolytic activity, but did exhibit antioxidant activity. Importantly, cathelicidin-OA1 accelerated wound healing against human keratinocytes (HaCaT) and skin fibroblasts (HSF) in both time- and dose-dependent manners. Notably, cathelicidin-OA1 also showed wound-healing promotion in a mouse model with full-thickness skin wounds, accelerating re-epithelialization and granulation tissue formation by enhancing the recruitment of macrophages to the wound site, inducing HaCaT cell proliferation and HSF cell migration. This is the first cathelicidin identified from an amphibian that shows potent wound-healing activity. These results will help in the development of new types of wound-healing agents and in our understanding of the biological functions of cathelicidins.