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Abstract: Peptide agents are regarded as potential candidates for overcoming the life-threatening resistance of pathogenic microorganisms to classic antibiotics. Accordingly, a peptidomic and genomic investigation of natural antimicrobial peptides (AMPs) can provide structure–functional information for designing peptide antibiotics with therapeutic potential. In the present study, we identified nine AMPs from the venom gland of the wasp Vespa tropica using combined methods of peptidomics and genomics. These AMPs were classified into two different families based on sequence similarity, mastoparan and vespid chemotactic peptides (VCPs), and thus named mastoparan-VT1 to -VT7, VCP-VT1 and -VT2. Among these nine AMPs, mastoparan-VT1 and VCP-VT1 are identical to peptides from other wasps. These AMPs exerted broad-spectrum antimicrobial activity against standard and clinically isolated strains of bacteria. In addition, they showed weak hemolytic activity toward human erythrocytes. Our results reveal that identical AMPs are widely distributed in different wasp venoms and might provide templates for the development of novel peptide antibiotics. [Copyright &y& Elsevier]

Abstract: The characterization of new natural antimicrobial peptides (AMPs) can help to solve the serious problem of bacterial resistance to currently used antibiotics. In the current study, we analyzed two families of AMPs from the Chinese torrent frog Amolops jingdongensis with a range of bioactivities. The first family of peptides, named jindongenin-1a, is 24 amino acids in length; a BLAST search of jindongenin-1a revealed no sequence similarity with other AMPs. The second family consists of two peptides containing 29 amino acid residues each. These peptides have high sequence similarity with the AMPs of palustrin-2 and are therefore designated palustrin-2AJ1 and palustrin-2AJ2. The cDNA sequences encoding these AMPs have been cloned and the deduced protein sequence of each AMP has been determined by protein sequencing. Sequence and structural analysis showed that each precursor is composed of a putative signal peptide, an N-terminal spacer, a processing site and a disulfide-bridged heptapeptide segment at the C-terminus. We synthesized jindongenin-1a and palustrin-AJ1 to test their antimicrobial, hemolytic, antioxidative and cytotoxic activities. These two peptides showed broad-spectrum antimicrobial activity to standard and clinically isolated strains of bacteria. In addition, they exhibited weak hemolytic activity to human and rabbit erythrocytes under our experimental conditions. Moreover, these peptides also displayed cytotoxic activity against the K562 and HT29 mammalian cell lines and low anti-oxidant activity. These findings provide helpful insight that will be useful in the design of anti-infective peptide agents. [Copyright &y& Elsevier]

Melasma is a common skin disease induced by an increase in the content of melanin in the skin, which also causes serious physical and mental harm to patients. In this research, a novel peptide (Nigrocin-OA27) from Odorrana andersonii is shown to exert a whitening effect on C57 mice pigmentation model. The peptide also demonstrated non-toxic and antioxidant capacity, and can significantly reduce melanin content in B16 cells. Topical application effectively delivered Nigrocin-OA27 to skin's epidermal and dermal layers and exhibited significant preventive and whitening effects on the UVB-induced ear pigmentation model in C57 mice. The whitening mechanism of Nigrocin-OA27 may be related to reduced levels of the microphthalmia-associated transcription factor and the key enzyme for melanogenesis-tyrosinase (TYR). Nigrocin-OA27 also inhibited the catalytic activity by adhering to the active core of TYR, thereby reducing melanin formation and deposition. In conclusion, Nigrocin-OA27 may be a potentially effective external agent to treat melasma by inhibiting aberrant skin melanin synthesis. • A novel peptide Nigrocin-OA27 from amphibians exerted a whitening effect. • Nigrocin-OA27 can deliver to the epidermal and dermal layers of the skin. • The whitening mechanism may be related to the reduce of TYR and MITF levels. [ABSTRACT FROM AUTHOR]

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-β1 (TGF-β1) 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-β1, 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. [Display omitted] • RL-RF10, a frog skin peptide, shows promise for treating pulmonary fibrosis. • This peptide down-regulates collagen levels and inhibits epithelial-mesenchymal transition, potentially preventing fibrosis progression. • RL-RF10's mechanism of action involves inhibiting the SMAD2/3 signaling pathway. [ABSTRACT FROM AUTHOR]

The potential application of anti-inflammatory and analgesic compounds in medication and therapeutic care have become of increasing interest. We purified and characterized two novel analgesic and anti-inflammatory peptides, VQ-5 and AQ-5, from the coelomic fluid of the earthworm ( Eisenia foetida ). Their primary structures were determined as VSSVQ and AMADQ, respectively. Both peptides, especially AQ-5, exhibited analgesic activity in mouse models of persistent neuropathic pain and inflammation. AQ-5 also inhibited tumor necrosis factor alpha and cyclooxygenase-2 production. The mitogen-activated protein kinase signaling pathway, which is involved in analgesic and anti-inflammatory functions, was inhibited by AQ-5. Thus, the analgesic and anti-inflammatory effects of these peptides, especially AQ-5, demonstrated their potential as candidates for the development of novel analgesic medicines. [ABSTRACT FROM AUTHOR]

[Display omitted] • HPDAlR&ZA (a new zinc alginate hydrogel embedded with hollow dopamine nanoparticles (HPDA) loaded with potent pro-healing peptide RL-QN15) promotes cells proliferation, as well as migration and angiogenesis and accelerates the healing rate of chronic skin wounds in diabetes mice. • HPDAlR&ZA modulates the expression of cytokines from macrophages. • HPDAlR&ZA resists the inflammatory response by rapidly polarizing M1 macrophages to M2 macrophages, thereby reconstructing blood supply, increasing collagen deposition, and accelerating diabetic wound repair and skin regeneration. Chronic wound healing remains a considerable clinical challenge worldwide. We previously identified a pro-regenerative agent, i.e., hollow dopamine nanoparticles (HPDA) loaded with potent pro-healing peptide RL-QN15 (HPDAlR), with significant skin wound healing activity. In the current study, in consideration of clinical application, we successfully prepared a new zinc alginate hydrogel embedded with HPDAlR (HPDAlR&ZA) to treat diabetic wounds. HPDAlR&ZA exhibited no obvious toxicity against keratinocytes, human umbilical vein endothelial cells (HUVECs), human skin fibroblasts (HSFs), and mice. HPDAlR&ZA significantly promoted keratinocyte, HUVEC, and HSF proliferation, as well as HUVEC migration and angiogenesis. HPDAlR&ZA also modulated the expression of cytokines from macrophages. Diabetic mouse full-thickness skin wound and diabetic patient in vitro skin wound models showed that HPDAlR&ZA resisted the inflammatory response by rapidly polarizing M1 macrophages to M2 macrophages, thereby reconstructing blood supply, increasing collagen deposition, and accelerating diabetic wound repair and skin regeneration. In summary, HPDAlR&ZA is a biodegradable hydrogel wound dressing and an efficient treatment strategy for diabetic wound repair, with strong anti-oxidant, anti-inflammatory, and pro-angiogenic features. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) is a major pathogen-associated pattern molecule that can initiate lethal sepsis. Bioactive peptides in amphibian skin secretions, especially antimicrobial peptides, are essential components of the host immune system and help fight the microbial invasion. In this study, two peptides: peptide 1 (KINRKGPRPPG) and peptide 2 (INRKGPRPPG) were isolated, from skin secretions of the Chinese red belly frog (Bombina maxima). After stimulation with LPS, peptide 1 showed direct LPS-binding activity, low cytotoxicity, immunoregulatory functions in vitro , and neutralizing LPS effects in animal models. Thus, natural peptide 1 exhibits potential as an ideal candidate against LPS. • The peptide 1 (KINRKGPRPPG) and peptide 2 (INRKGPRPPG) were isolated from skin secretions of Bombina maxima. • The peptide 1 showed direct lipopolysaccharide-binding activity, low cytotoxity, immunoregulatory functions in vitro. • The peptide 1 could neutralize lipopolysaccharide effects in animal models. • The peptide 1 exhibits an ideal candidate against lipopolysaccharide. [ABSTRACT FROM AUTHOR]

Borosilicate glass–ceramics precursors with varying compositional ratios in the CaO–SiO 2 –B 2 O 3 (CBS) system were synthesized by sol–gel method. The precursors were calcined at 1200 °C for 2 h to form glass powders. The glass–ceramics were prepared by overlaying glass slurries on the substrates before sintering at different temperatures. The as-prepared glasses and glass–ceramics were characterized by differential scanning calorimetry and X-ray diffraction. The crystallization activation energies ( E c ) were calculated using the Kissinger method from DSC results. The morphology and crystallization behavior of the glass–ceramics were monitored by scanning electron microscopy. Both glass transition and crystallization temperatures decreased, however, the metastable zone increased. The E c values of CBS glasses and glass–ceramics were 254.1, 173.2 and 164.4 kJ/mol with increasing B 2 O 3 content, whereas that of the calcined G3 glass was 104.9 kJ/mol. Finally, the coatings were prepared at a low temperature (700 °C). The crystals that grew on the surface of multilayer coatings demonstrated heterogeneous surface nucleation and crystallization after heat-treatment from 700 °C to 850 °C for 4 h. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • A new active peptide was identified from odorana andersonii named OA-GI13. • The peptide OA-GI13 showed significantly antioxidant effects in vivo and in vitro. • OA-GI13 resisted skin photodamage by maintaining the balance of oxidation system. • The other potentially mechanism was related with phosphorylated p38 protein inhibition. • This research provided a new molecule to treat skin photodamage. [ABSTRACT FROM AUTHOR]

[Display omitted] • Chronic VNS ameliorated the frequency and duration of seizures. • The neuronal loss of hippocampal was significantly reduced after chronic VNS treatment. • The expression of inflammatory cytokines might be involved in anti-epileptic effect of VNS. An increasing number of observations have indicated that the activation of inflammatory processes is involved in the pathogenesis of epilepsy. As an effective adjunctive therapy for medically intractable seizures, vagus nerve stimulation (VNS) is thought to interact with the inflammatory process to play an antiepileptic role. In this study, we examined the levels of multiple cytokine in focal brain tissue and peripheral blood to determine whether the antiepileptic effect of chronic VNS is related to the expression of cytokines. We observed that the frequency and duration of seizures significantly decreased in epileptic rats after two weeks of chronic VNS treatment. Pathological staining showed that the number of neural cells in the hippocampus was higher in the Epi + VNS group than in the Epi group, indicating that chronic VNS had a significant neuroprotective effect on epileptic rats. After comparing the expression of 9 cytokines, we found that the levels of the proinflammatory cytokines IL-6, IL-1β and CXCL-1 in the hippocampus were significantly increased in the Epi group, while these cytokines were significantly decreased in the Epi + VNS group. Moreover, the level of the anti-inflammatory cytokine IL-13 was found to be reduced in Epi rats, while its levels were increased after VNS treatment. However, these changes in cytokine expression were not found in the hypothalamus or peripheral blood. These results suggest that the antiepileptic mechanism of VNS may work by inhibiting the activation of inflammatory processes in the epileptogenic focus. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Our research has identified a naturally occurring peptide homodimer with excellent ability to promote wound repair. • Peptide homodimer (OA-GP11d) activates MAPKs signaling pathway and inhibits NFKB. • Our results suggest OA-GP11d as a potential novelpro-regenerative drug candidate. [ABSTRACT FROM AUTHOR]

Exposure to the toxic herbicide paraquat (PQ) can lead to the active absorption and enrichment of alveolar epithelial cells, resulting in pulmonary fibrosis and respiratory failure. At present, no effective clinical treatment is available. Notably, however, patients infected with human acquired immunodeficiency virus (HIV) (with T lymphocyte deficiency) do not show pulmonary fibrosis after PQ poisoning, suggesting that T lymphocytes may be involved in the occurrence and pathological development of lung fibers following PQ exposure, although relevant studies remain limited. Here, we found that the degree of pulmonary fibrosis induced by intragastric administration of PQ in congenital immunodeficiency BALB/C (nu/nu) nude (T lymphocyte loss) mice was lower than that in normal mice. However, pulmonary fibrosis was aggravated after transplantation of BALB/C (nu/nu) T lymphocytes into congenital immunodeficiency mice. This study is the first to report on the involvement of T lymphocytes in the occurrence and pathological development of lung fibers induced by PQ exposure. Thus, T cells may be an important cellular target for the clinical treatment of pulmonary fibrosis caused by PQ. • We report on the involvement of T lymphocytes in the occurrence and pathological development of PQ-induced lung fibrosis. • PQ-induced pulmonary fibrosis was lower in T lymphocyte-deficient nude mice than in normal mice. • Pulmonary fibrosis was aggravated after transplantation of BALB/C (nu/nu) T lymphocytes into congenital immunodeficient mice. • T cells may be an important cellular target for the clinical treatment of pulmonary fibrosis caused by PQ poisoning. [ABSTRACT FROM AUTHOR]

• In this research, we identify a new peptide (OM-GL15) from the skin of the Odorrana margaretae. • The experimental results show that OM-GL15 can inhibit the expression of p53 protein. • OM-GL15 inhibit the mitochondrial apoptosis pathway mediated by caspase-9 and caspase-3. • OM-GL15 has potential application value in the development of anti-UVB skin photodamage drugs. Although the application potential of amphibian skin-derived active peptides in alleviating ultraviolet B (UVB)-induced damage has attracted increasing attention, research remains in its infancy. In this study, a new peptide (OM-GL15, GLLSGHYGRASPVAC) was identified from the skin of the green odorous frog (Odorrana margaretae). Results showed that OM-GL15 scavenged free radicals (2,2′-diazo-bis-3-ethylbenzothiazoline-6-sulfonic acid and 1,1-diphenyl-2-trinitrophenylhydrazine) and reduced Fe3+ to Fe2+. Moreover, topical administration of OM-GL15 significantly alleviated UVB-induced skin photodamage in mice. Exploration of the underlying mechanisms further showed that OM-GL15 exerted antioxidant potency. Specifically, the peptide reduced the levels of lipid peroxidation and malondialdehyde and protected epidermal cells from UVB-induced apoptosis by inhibiting DNA damage via down-regulation of p53, caspase-3, caspase-9, and Bax and up-regulation of Bcl-2. Our results highlight the potential application of amphibian skin-derived peptides in protection against UVB-induced photodamage and provide a novel peptide candidate for the development of anti-photodamage agents. [ABSTRACT FROM AUTHOR]

With increasing demand, the development of new natural antioxidants has become a primary direction of scientific research. We previously identified a short gene-encoded peptide (OA-VI12) from Odorrana andersonii frog skin secretions that exerted direct scavenging capacity against free radicals, suggesting a possible function in protecting skin against photodamage caused by their high-altitude habitat. In the current research, we examined the effects of OA-VI12 on both UVB-irradiation and hydrogen peroxide-induced oxidative stress models established with human immortalized keratinocytes. In addition, we identified the differentially expressed genes (DEGs) in the oxidative stress and OA-VI12 groups and further performed transcriptome as well as functional and pathway enrichment analyses. Results showed that OA-VI12 protected cell viability, promoted the release of catalase, and decreased the levels of lactate dehydrogenase and reactive oxygen species. Moreover, the peptide promoted the production of superoxide dismutase and glutathione, alleviated epidermis and dermis thickness, and decreased the production of light spots and collagen fibers in skin from the photo-injured mouse model. Kyoto Encyclopedia of Genes and Genomes analysis showed mitogen-activated protein kinase (MAPK) to be the most abundant signaling pathway. Gene Ontology (GO) analysis indicated that the top 55 significantly enriched GO terms mainly involved cellular processes, parts, and binding. These results revealed the beneficial role of the small molecule gene-encoding antioxidant peptide (OA-VI12) and its potential application as a protective agent against photodamage. [ABSTRACT FROM AUTHOR]