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.

Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis.

Background: Wound management of diabetic foot ulcers (DFUs) is a complex and challenging task, and existing strategies fail to meet clinical needs. Therefore, it is important to develop novel drug candidates and discover new therapeutic targets. However, reports on peptides as molecular probes for resolving issues related to DFUs remain rare. This study utilized peptide RL-QN15 as an exogenous molecular probe to investigate the underlying mechanism of endogenous non-coding RNA in DFU wound healing. The aim was to generate novel insights for the clinical management of DFUs and identify potential drug targets. Methods: We investigated the wound-healing efficiency of peptide RL-QN15 under diabetic conditions using in vitro and in vivo experimental models. RNA sequencing, in vitro transfection, quantitative real-time polymerase chain reaction, western blotting, dual luciferase reporter gene detection, in vitro cell scratches, and cell proliferation and migration assays were performed to explore the potential mechanism underlying the promoting effects of RL-QN15 on DFU repair. Results: Peptide RL-QN15 enhanced the migration and proliferation of human immortalized keratinocytes (HaCaT cells) in a high-glucose environment and accelerated wound healing in a DFU rat model. Based on results from RNA sequencing, we defined a new microRNA (miR-4482-3p) related to the promotion of wound healing. The bioactivity of miR-4482-3p was verified by inhibiting and overexpressing miR-4482-3p. Inhibition of miR-4482-3p enhanced the migration and proliferation ability of HaCaT cells as well as the expression of vascular endothelial growth factor B (VEGFB). RL-QN15 also promoted the migration and proliferation ability of HaCaT cells, and VEGFB expression was mediated via inhibition of miR-4482-3p expression by the p38 mitogen-activated protein kinase (p38MAPK) and smad3 signaling pathways. Conclusions: RL-QN15 is an effective molecule for the treatment of DFUs, with the underlying mechanism related to the inhibition of miR-4482-3p expression via the p38MAPK and smad3 signaling pathways, ultimately promoting re-epithelialization, angiogenesis and wound healing. This study provides a theoretical basis for the clinical application of RL-QN15 as a molecular probe in promoting DFU wound healing.

Peptide OA-VI12 restrains melanogenesis in B16 cells and C57B/6 mouse ear skin via the miR-122-5p/Mitf/Tyr axis.

Excessive melanogenesis leads to hyperpigmentation, which is one of the common skin conditions in humans. Existing whitening cosmetics cannot meet market needs due to their inherent limitations. Thus, the development of novel skin-whitening agents continues to be a challenge. The peptide OA-VI12 from the skin of amphibians at high altitude has attracted attention due to its remarkable anti light damage activity. However, whether OA-VI12 has the skin-whitening effect of inhibiting melanogenesis is still. Mouse melanoma cells (B16) were used to study the effect of OA-VI12 on cell viability and melanin content. The pigmentation model of C57B/6 mouse ear skin was induced by UVB and treated with OA-VI12. Melanin staining was used to observe the degree of pigmentation. MicroRNA sequencing, quantitative real-time PCR (qRT-PCR), immunofluorescence analysis and Western blot were used to detect the change of factor expression. Double luciferase gene report experiment was used to prove the regulatory relationship between miRNA and target genes. OA-VI12 has no effect on the viability of B16 cells in the concentration range of 1-100 µM and significantly inhibits the melanin content of B16 cells. Topical application of OA-VI12, which exerted transdermal potency, prevented UVB-induced pigmentation of ear skin. MicroRNA sequencing and double luciferase reporter analysis results showed that miR-122-5p, which directly regulated microphthalmia-associated transcription factor (Mitf), had significantly different expression before and after treatment with OA-VI12. Mitf is a simple helix loop and leucine zipper transcription factor that regulates tyrosinase (Tyr) expression by binding to the M-box promoter element of Tyr. qRT-PCR, immunofluorescence analysis and Western blot showed that OA-VI12 up-regulated the expression of miR-122-5p and inhibited the expression of Mitf and Tyr. The effects of OA-VI12 on melanogenesis inhibition in vitro and in vivo may involve the miR-122-5p/Mitf/tyr axis. OA-VI12 represents the first report on a natural amphibian-derived peptide with skin-whitening capacity and the first report of miR-122-5p as a target for regulating melanogenesis, thereby demonstrating its potential as a novel skin-whitening agent and highlighting amphibian-derived peptides as an underdeveloped resource.

miR-186-5p targets TGFßR2 to inhibit RAW264.7 cell migration and proliferation during mouse skin wound healing.

BACKGROUND: Active peptides play a vital role in the development of new drugs and the identification and discovery of drug targets. As the first reported native peptide homodimer with pro-regenerative potency, OA-GP11d could potentially be used as a novel molecular probe to help elucidate the molecular mechanism of skin wound repair and provide new drug targets. METHODS: Bioinformatics analysis and luciferase assay were adopted to determine microRNAs (miRNAs) and its target. The prohealing potency of the miRNA was determined by MTS and a Transwell experiment against mouse macrophages. Enzyme-linked immunosorbent assay, realtime polymerase chain reaction, and western blotting were performed to explore the molecular mechanisms. RESULTS: In this study, OA-GP11d was shown to induce Mus musculus microRNA-186-5p (mmu-miR-186-5p) down-regulation. Results showed that miR-186-5p had a negative effect on macrophage migration and proliferation as well as a targeted and negative effect on TGF-ß type II receptor (TGFßR2) expression and an inhibitory effect on activation of the downstream SMAD family member 2 (Smad2) and protein-p38 kinase signaling pathways. Importantly, delivery of a miR-186-5p mimic delayed skin wound healing in mice. CONCLUSION: miR-186-5p regulated macrophage migration and proliferation to delay wound healing through the TGFßR2/Smad2/p38 molecular axes, thus providing a promising new pro-repair drug target.

A frog peptide provides new strategies for the intervention against skin wound healing.

BACKGROUND: Amphibian derived pro-healing peptides as molecular probes might provide a promising strategy for development of drug candidates and elucidation of cellular and molecular mechanisms of skin wound healing. A novel skin amphibian peptide, OA-RD17, was tested for modulation of cellular and molecular mechanisms associated with skin wound healing. METHODS: Cell scratch, cell proliferation, trans-well, and colony formation assays were used to explore the pro-healing ability of peptide OA-RD17 and microRNA-632 (miR-632). Then, the therapeutic effects of OA-RD17 and miR-632 were assessed in mice, diabetic patient ex vivo skin wounds and SD rats. Moreover, hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence staining were performed to detect skin wound tissue regeneration, inflammatory factors expression, and macrophage polarization. Finally, RNA sequencing, molecular docking, co-localization, dual luciferase reporter, real-time quantitative reverse transcription PCR (RT-qPCR), and Western blotting were used to explore the mechanism of OA-RD17 and miR-632 on facilitating skin wound healing. RESULTS: The non-toxic peptide (OA-RD17) promoted macrophage proliferation and migration by activating MAPK and suppressed inflammation by inhibiting NF-κB. In keratinocytes, OA-RD17 inhibited excessive inflammation, and activated MAPK via the Toll-like receptor 4 (TLR4) to promote proliferation and migration, as well as up-regulate the expression of miR-632, which targeted GSK3ß to activate Wnt/ß-catenin to boost proliferation and migration in a positive feedback manner. Notably, OA-RD17 promoted transition from the inflammatory to proliferative stage, accelerated epidermal and granulation regeneration, and exhibited therapeutic effects on mouse and diabetic patient ex vivo skin wounds. MiR-632 activated Wnt/ß-catenin to promote full-thickness skin wound healing in rats. CONCLUSIONS: OA-RD17 exhibited promising therapeutic effects on mice (full-thickness, deep second-degree burns), and ex vivo skin wounds in diabetic patients by regulating macrophages proliferation, migration, and polarization (MAPK, NF-κB), and keratinocytes proliferation and migration (TLR4/MAPK/miR-632/Wnt/ß-catenin molecular axis). Moreover, miR-632 also activated Wnt/ß-catenin to promote full-thickness skin wound healing in rats. Notably, our results indicate that OA-RD17 and miR-632 are promising pro-healing drug candidates.

OL-FS13 Alleviates Cerebral Ischemia-reperfusion Injury by Inhibiting miR-21-3p Expression.

BACKGROUND: OL-FS13, a neuroprotective peptide derived from Odorrana livida, can alleviate cerebral ischemia-reperfusion (CI/R) injury, although the specific underlying mechanism remains to be further explored. OBJECTIVE: The effect of miR-21-3p on the neural-protective effects of OL-FS13 was examined. METHODS: In this study, the multiple genome sequencing analysis, double luciferase experiment, RT-qPCR, and Western blotting were used to explore the mechanism of OL-FS13. RESULTS: Showed that over-expression of miR-21-3p against the protective effects of OL-FS13 on oxygen- glucose deprivation/re-oxygenation (OGD/R)-damaged pheochromocytoma (PC12) cells and in CI/R-injured rats. miR-21-3p was then found to target calcium/calmodulin-dependent protein kinase 2 (CAMKK2), and its overexpression inhibited the expression of CAMKK2 and phosphorylation of its downstream adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), thereby inhibiting the therapeutic effects of OL-FS13 on OGD/R and CI/R. Inhibition of CAMKK2 also antagonized up-regulated of nuclear factor erythroid 2-related factor 2 (Nrf-2) by OL-FS13, thereby abolishing the antioxidant activity of the peptide. CONCLUSION: Our results showed that OL-FS13 alleviated OGD/R and CI/R by inhibiting miR-21-3p to activate the CAMKK2/AMPK/Nrf-2 axis.

A new peptide, VD11, promotes structural and functional recovery after spinal cord injury.

The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury. It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury. Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue. While amphibians have a pronounced ability to regenerate the spinal cord, few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury. Here we report for the first time the successful identification and isolation of a new polypeptide, VD11 (amino acid sequence: VDELWPPWLPC), from the spinal cord of an endemic Chinese amphibian (Odorrana schmackeri). In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide, as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia. In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury, alleviated pathological damage, and promoted axonal regeneration. Furthermore, RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways. In summary, we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury.

A short peptide exerts neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis.

BACKGROUND: Despite considerable efforts, ischemic stroke (IS) remains a challenging clinical problem. Therefore, the discovery of effective therapeutic and targeted drugs based on the underlying molecular mechanism is crucial for effective IS treatment. METHODS: A cDNA-encoding peptide was cloned from RNA extracted from Rana limnocharis skin, and the mature amino acid sequence was predicted and synthesized. Hemolysis and acute toxicity of the peptide were tested. Furthermore, its neuroprotective properties were evaluated using a middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in neuron-like PC12 cells. The underlying molecular mechanisms were explored using microRNA (miRNA) sequencing, quantitative real-time polymerase chain reaction, dual-luciferase reporter gene assay, and western blotting. RESULTS: A new peptide (NP1) with an amino acid sequence of 'FLPAAICLVIKTC' was identified. NP1 showed no obvious toxicities in vivo and in vitro and was able to cross the blood-brain barrier. Intraperitoneal administration of NP1 (10 nmol/kg) effectively reduced the volume of cerebral infarction and relieved neurological dysfunction in MCAO/R model rats. Moreover, NP1 significantly alleviated the decrease in viability and increase in apoptosis of neuron-like PC12 cells induced by OGD/R. NP1 effectively suppressed inflammation by reducing interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels in vitro and in vivo. Furthermore, NP1 up-regulated the expression of miR-6328, which, in turn, down-regulated kappa B kinase ß (IKKß). IKKß reduced the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65) and inhibitor of NF-κB (I-κB), thereby inhibiting activation of the NF-κB pathway. CONCLUSIONS: The newly discovered non-toxic peptide NP1 ('FLPAAICLVIKTC') exerted neuroprotective effects on cerebral ischemia-reperfusion injury by reducing inflammation via the miR-6328/IKKß/NF-κB axis. Our findings not only provide an exogenous peptide drug candidate and endogenous small nucleic acid drug candidate but also a new drug target for the treatment of IS. This study highlights the importance of peptides in the development of new drugs, elucidation of pathological mechanisms, and discovery of new drug targets.

Peptide RL-QN15 promotes regeneration of epidermal nerve fibers and recovery of sensory function in diabetic skin wounds.

Epidermal nerve fiber regeneration and sensory function are severely impaired in skin wounds of diabetic patients. To date, however, research on post-traumatic nerve regeneration and sensory reconstruction remains scarce, and effective clinical therapeutics are lacking. In the current study, localized treatment with RL-QN15, considered as a drug candidate for intervention in skin wounds in our previous research, accelerated the healing of full-thickness dorsal skin wounds in diabetic mice and footpad skin wounds in diabetic rats. Interestingly, nerve density and axonal plasticity in the skin wounds of diabetic rats and mice, as well as plantar sensitivity in diabetic rats, were markedly enhanced by RL-QN15 treatment. Furthermore, RL-QN15 promoted the proliferation, migration, and axonal length of neuron-like PC12 cells, which was likely associated with activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway. The therapeutic effects of RL-QN15 were partially reduced by blocking the PI3K/Akt signaling pathway with the inhibitor LY294002. Thus, RL-QN15 showed positive therapeutic effects on the distribution of epidermal nerve fibers and stimulated the recovery of sensory function after cutaneous injury. This study lays a solid foundation for the development of RL-QN15 peptide-based therapeutics against diabetic skin wounds.

Scorpion venom peptide HsTx2 suppressed PTZ-induced seizures in mice via the circ_0001293/miR-8114/TGF-ß2 axis.

BACKGROUND: Due to the complexity of the mechanisms involved in epileptogenesis, the available antiseizure drugs (ASDs) do not meet clinical needs; hence, both the discovery of new ASDs and the elucidation of novel molecular mechanisms are very important. METHODS: BALB/c mice were utilized to establish an epilepsy model induced by pentylenetetrazol (PTZ) administration. The peptide HsTx2 was administered for treatment. Primary astrocyte culture, immunofluorescence staining, RNA sequencing, identification and quantification of mouse circRNAs, cell transfection, bioinformatics and luciferase reporter analyses, enzyme-linked immunosorbent assay, RNA extraction and reverse transcription-quantitative PCR, Western blot and cell viability assays were used to explore the potential mechanism of HsTx2 via the circ_0001293/miR-8114/TGF-ß2 axis. RESULTS: The scorpion venom peptide HsTx2 showed an anti-epilepsy effect, reduced the inflammatory response, and improved the circular RNA circ_0001293 expression decrease caused by PTZ in the mouse brain. Mechanistically, in astrocytes, circ_0001293 acted as a sponge of endogenous microRNA-8114 (miR-8114), which targets transforming growth factor-beta 2 (TGF-ß2). The knockdown of circ_0001293, overexpression of miR-8114, and downregulation of TGF-ß2 all reversed the anti-inflammatory effects and the influence of HsTx2 on the MAPK and NF-κB signaling pathways in astrocytes. Moreover, both circ_0001293 knockdown and miR-8114 overexpression reversed the beneficial effects of HsTx2 on inflammation, epilepsy progression, and the MAPK and NF-κB signaling pathways in vivo. CONCLUSIONS: HsTx2 suppressed PTZ-induced epilepsy by ameliorating inflammation in astrocytes via the circ_0001293/miR-8114/TGF-ß2 axis. Our results emphasized that the use of exogenous peptide molecular probes as a novel type of ASD, as well as to explore the novel endogenous noncoding RNA-mediated mechanisms of epilepsy, might be a promising research area.

Improving the performance for flip-chip AlGaN-based deep ultraviolet light-emitting diodes using surface textured Ga-face n-AlGaN.

Low light extraction efficiency (LEE), high forward voltage and severe self-heating effect greatly affect the performance for AlGaN-based deep ultraviolet light-emitting diodes (DUV LEDs). In this work, surface-textured Ga-face n-AlGaN is fabricated low-costly using self-assembled SiO2 nanosphere as hard mask. The experimental results manifest that when compared with conventional DUV LEDs, the optical power, the forward voltage and the thermal characteristics for the DUV LEDs with surface-textured Ga-face n-AlGaN are improved obviously. It is because the surface-textured Ga-face n-AlGaN between mesa and the n-electrode can be used as the scattering center for trapped light, and this leads to the enhanced LEE. Furthermore, thanks to the surface-textured n-AlGaN under the n-electrode, the n-type ohmic contact area can be increased effectively. Therefore, the n-type ohmic contact resistance can be reduced and the better heat dissipation can be attained for the proposed flip-chip DUV LED.

Peptide OM-LV20 protects astrocytes against oxidative stress via the 'PAC1R/JNK/TPH1' axis.

Stroke can lead to severe nerve injury and debilitation, resulting in considerable social and economic burdens. Due to the high complexity of post-injury repair mechanisms, drugs approved for use in stroke are extremely scarce, and thus, the discovery of new antistroke drugs and targets is critical. Tryptophan hydroxylase 1 (TPH1) is involved in a variety of mental and neurobehavioral processes, but its effects on stroke have not yet been reported. Here, we used primary astrocyte culture, quantitative real-time PCR, double immunofluorescence assay, lentiviral infection, cell viability analysis, Western blotting, and other biochemical experiments to explore the protective mechanism of peptide OM-LV20, which previously exhibited neuroprotective effects in rats after ischemic stroke via a mechanism that may involve TPH1. First, we showed that TPH1 was expressed in rat astrocytes. Next, we determined that OM-LV20 impacted expression changes of TPH1 in CTX-TNA2 cells and exhibited a protective effect on the decrease in cell viability and catalase (CAT) levels induced by hydrogen peroxide. Importantly, we also found that TPH1 expression induced by OM-LV20 may be related to the level of change in the pituitary adenylate cyclase-activating peptide type 1 receptor (PAC1R) and to the JNK signaling pathways, thereby exerting a protective effect on astrocytes against oxidative stress. The protective effects of OM-LV20 likely occur via the 'PAC1R/JNK/TPH1' axis, thus highlighting TPH1 as a novel antistroke drug target.

Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-ß1/Smad axis.

Background: Amphibian-derived peptides exhibit considerable potential in the discovery and development of new therapeutic interventions for clinically challenging chronic skin wounds. MicroRNAs (miRNAs) are also considered promising targets for the development of effective therapies against skin wounds. However, further research in this field is anticipated. This study aims to identify and provide a new peptide drug candidate, as well as to explore the underlying miRNA mechanisms and possible miRNA drug target for skin wound healing. Methods: A combination of Edman degradation, mass spectrometry and cDNA cloning were adopted to determine the amino acid sequence of a peptide that was fractionated from the secretion of Odorrana andersonii frog skin using gel-filtration and reversed-phase high-performance liquid chromatography. The toxicity of the peptide was evaluated by Calcein-AM/propidium iodide (PI) double staining against human keratinocytes (HaCaT cells), hemolytic activity against mice blood cells and acute toxicity against mice. The stability of the peptide in plasma was also evaluated. The prohealing potency of the peptide was determined by MTS, scratch healing and a Transwell experiment against HaCaT cells, full-thickness injury wounds and scald wounds in the dorsal skin of mice. miRNA transcriptome sequencing analysis, enzyme-linked immunosorbent assay, real-time polymerase chain reaction and western blotting were performed to explore the molecular mechanisms. Results: A novel peptide homodimer (named OA-GL17d) that contains a disulfide bond between the 16th cysteine residue of the peptide monomer and the sequence 'GLFKWHPRCGEEQSMWT' was identified. Analysis showed that OA-GL17d exhibited no hemolytic activity or acute toxicity, but effectively promoted keratinocyte proliferation and migration and strongly stimulated the repair of full-thickness injury wounds and scald wounds in the dorsal skin of mice. Mechanistically, OA-GL17d decreased the level of miR-663a to increase the level of transforming growth factor-ß1 (TGF-ß1) and activate the subsequent TGF-ß1/Smad signaling pathway, thereby resulting in accelerated skin wound re-epithelialization and granular tissue formation. Conclusions: Our results suggest that OA-GL17d is a new peptide drug candidate for skin wound repair. This study emphasizes the importance of exogenous peptides as molecular probes for exploring competing endogenous RNA mechanisms and indicates that miR-663a may be an effective target for promoting skin repair.

OL-FS13 alleviates experimental cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion (I/R) is the main cause of neurological injury after stroke. However, existing treatments for I/R injury are relatively poor, and relevant drugs need to be further explored. Amphibians have received increasing attention as a resource bank of bioactive peptides. However, reports on neuroprotective peptides from amphibians remain extremely rare. Here, we identified a new neuroprotective peptide (OL-FS13, amino acid sequence: FSLLLTWWRRRVC) from the odorous frog species Odorrana livida using a constructed cDNA library. OL-FS13 significantly improving infarct volume, behavioral and histological abnormalities in rats, and also showed neuroprotective activities in PC12 cell (by oxygen glucose deprivation/reoxygenation, OGD/R). Mechanistically, OL-FS13 increased the level of antioxidative enzymes to resist oxidative stress and alleviated endoplasmic reticulum (ER) stress induced by I/R and OGD/R. The use of ML385 (Nrf2 inhibitor) indicated that OL-FS13 relieved nerve damage caused by oxidative and ER stress by increasing the nuclear displacement of Nrf2. Collectively, this research provides a novel drug candidate for the clinical cerebral I/R curation.

Zn2+ Cross-Linked Alginate Carrying Hollow Silica Nanoparticles Loaded with RL-QN15 Peptides Provides Promising Treatment for Chronic Skin Wounds.

Chronic and non-healing wounds pose a great challenge to clinical management and patients. Many studies have explored novel interventions against skin wounds, with bioactive peptides, nanoparticles, and hydrogels arousing considerable attention regarding their therapeutic potential. In this study, the prohealing peptide RL-QN15 was loaded into hollow silica nanoparticles (HSNs), with these HSN@RL-QN15 nanocomposites then combined with zinc alginate (ZA) gels to obtain HSN@RL-QN15/ZA hydrogel. The characteristics, biological properties, and safety profiles of the hydrogel composites were then evaluated. Results showed that the hydrogel had good porosity, hemocompatibility, biocompatibility, and broad-spectrum antimicrobial activity, with the slow release of loaded RL-QN15. Further analysis indicated that the hydrogel promoted skin cell proliferation and keratinocyte scratch repair, regulated angiogenesis, reduced inflammation, and accelerated re-epithelialization and granulation tissue formation, resulting in the rapid healing of both full-thickness skin wounds and methicillin-resistant Staphylococcus aureus biofilm-infected chronic wounds in mice. This peptide-based hydrogel provides a novel intervention for the treatment of chronic skin wounds and shows promise as a wound dressing in the field of tissue regeneration.

Short Hexapeptide Optimized from Rice-Derived Peptide 1 Shows Promising Anti-hyperuricemia Activities.

Plant-derived peptides are a treasure trove for new-generation anti-hyperuricemia drugs. In the current study, we optimized a short hexapeptide rice-derived peptide 1 (RDP1)-M3 (AAAAGA) according to the anti-hyperuricemia RDP1 peptide identified from rice in our previous research. Results showed that RDP1-M3 exerted better hyperuricemia-alleviating and xanthine oxidase (XOD)-inhibiting potency in mice than RDP1. The biodistribution of RDP1-M3 was also analyzed. RDP1-M3 directly decreased XOD and uric acid levels in vivo and in vitro. In addition, RDP1-M3 reduced the expression of urate transporter 1 and glucose transporter 9, increased the level of organic anion transporter 1, reduced the expression of NOD-like receptor superfamily pyrin 3 inflammasomes, and reduced the levels of interleukin-1ß and tumor necrosis factor-α of hyperuricemic mice. Thus, our results indicated that the optimized short hexapeptide RDP1-M3 may be a candidate drug for anti-hyperuricemia.

A new peptide originated from amphibian skin alleviates the ultraviolet B-induced skin photodamage.

Although amphibian-derived bioactive peptides have attracted increasing attention for their potential use in the treatment of photodamage, research is still in its infancy. In this study, we obtained a new antioxidant peptide, named OA-GI13 (GIWAPWPPRAGLC), from the skin of the odorous frog Odorrana andersonii and determined its effects on ultraviolet B (UVB)-induced skin photodamage as well as its possible molecular mechanisms. Results showed that OA-GI13 directly scavenged free radicals, maintained the viability of hydrogen peroxide-challenged keratinocytes, promoted the release of superoxide dismutase, catalase, and glutathione, and reduced the level of lactate dehydrogenase. Furthermore, topical application of OA-GI13 in mice alleviated dorsal skin erythema and edema and protected the skin against UVB irradiation by increasing antioxidant levels and decreasing peroxide, malondialdehyde, and 8-hydroxydeoxyguanosine levels. OA-GI13 also alleviated oxidative stress injury in vivo and in vitro, possibly by inhibiting p38 protein phosphorylation. Our study confirmed the anti-photodamage effects of this novel amphibian-derived peptide, thus providing a new molecule for the development of drugs and topical agents for the treatment of skin photodamage.

Amphibian-derived peptide homodimer promotes regeneration of skin wounds.

Despite the increasing treatments in skin wound repair, existing therapeutic drugs cannot meet current needs. As such, skin wound repair remains a considerable clinical challenge, and thus the discovery of new pro-healing agents is crucial. Here, we identified the first naturally occurring peptide homodimer named as OA-GP11 dimer (OA-GP11d) from Odorrana andersonii (odorous frog) through the combinational methods of peptidomics and genomics. OA-GP11d was linked by the intramolecular disulfide formed by the 10th cysteine residues from the monomer of peptide with sequence of GPLSGINAECM, which effectively promoted the repair of full-thickness and burn wounds in mice. The underlying molecular mechanisms revealed that OA-GP11d not only accelerated the migration and cell-scratch healing of mouse keratinocytes, but also activated the mitogen-activated protein kinases (MAPKs) signaling pathway (phosphorylation of p38 and ERK subgroups) in immortalized human keratinocytes (HaCaT). Besides, OA-GP11d reduced the phosphorylation of nuclear factor-κB (NF-κB) and inhibitor of NF-κB (I-κB) induced by lipopolysaccharide stimulation in mouse macrophages, and inhibited the release of associated inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6. OA-GP11d is the first identified naturally occurring peptide dimer with significant pro-healing potency. Our results highlight the importance of amphibians as a source of novel pro-healing agents and suggest OA-GP11d as a potential new pro-regenerative drug candidate.

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.

Mesoporous polydopamine nanoparticles carrying peptide RL-QN15 show potential for skin wound therapy.

BACKGROUND: Skin wound healing remains a considerable clinical challenge, thus stressing the urgent need for the development of new interventions to promote repair. Recent researches indicate that both peptides and nanoparticles may be potential therapies for the treatment of skin wounds. METHODS: In the current study, the mesoporous polydopamine (MPDA) nanoparticles were prepared and the peptide RL-QN15 that was previously identified from amphibian skin secretions and exhibited significant potential as a novel prohealing agent was successfully loaded onto the MPDA nanoparticles, which was confirmed by results of analysis of scanning electron microscopy and fourier transform infrared spectroscopy. The encapsulation efficiency and sustained release rate of RL-QN15 from the nanocomposites were determined. The prohealing potency of nanocomposites were evaluated by full-thickness injured wounds in both mice and swine and burn wounds in mice. RESULTS: Our results indicated that, compared with RL-QN15 alone, the prohealing potency of nanocomposites of MPDA and RL-QN15 in the full-thickness injured wounds and burn wounds in mice was increased by up to 50 times through the slow release of RL-QN15. Moreover, the load on the MPDA obviously increased the prohealing activities of RL-QN15 in full-thickness injured wounds in swine. In addition, the obvious increase in the prohealing potency of nanocomposites of MPDA and RL-QN15 was also proved by the results from histological analysis. CONCLUSIONS: Based on our knowledge, this is the first research to report that the load of MPDA nanoparticles could significantly increase the prohealing potency of peptide and hence highlighted the promising potential of MPDA nanoparticles-carrying peptide RL-QN15 for skin wound therapy.