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Clinical fungal infections always cause a negative impact on human health. Moreover, during the interaction of pathogenic fungi with the environment and host, many biologically active substances are produced. Here, we report a new toxin-like defensin of purlisin derived from a clinical pathogenic isolate of Purpureocillium lilacinum. The analysis of its genomic and mRNA sequences revealed an open reading frame of 444 bp without introns. The deduced precursor peptide was composed of 147 amino acids, and the mature peptide were identified at protein level by LC-ESI-Q-TOF-MS/MS. After posttranslational processing, the precursor peptide of purlisin was split into two independent peptides. The two mature defensins, purlisin-NT and purlisin-CT, are consisting of 36 and 38 amino acid residues, which can form three and four intramolecular disulfide bonds, respectively. The results of circular dichroism and homology modeling revealed that they adopted a representative cysteine-stabilized α-helical and β-sheet motif. The purlisin-NT showed a dose-dependent selective inhibition of immune-related hKv1.3 target channel with IC50 value of 0.2 ± 0.04 μM but no obvious antibacterial activity, while the purlisin-CT displayed antimicrobial activities against gram-positive bacteria as well as clinical isolates of MRSA and low affinities for potassium channels. Our findings suggest that purlisin-NT with immunosuppressive effects and purlisin-CT possessing antibacterial activities are adapted to the survival and pathogenicity of clinical P lilacinumis. Moreover, they can also be used as templates for the design of novel antibacterial peptide and immunosuppressive agents.

Background Tick bites severely threaten human health because they allow the transmission of many deadly pathogens, including viruses, bacteria, protozoa, and helminths. Pruritus is a leading symptom of tick bites, but its molecular and neural bases remain elusive. Objectives This study sought to discover potent drugs and targets for the specific prevention and treatment of tick bite–induced pruritus and arthropod-related itch. Methods We used live-cell calcium imaging, patch-clamp recordings, and genetic ablation and evaluated mouse behavior to investigate the molecular and neural bases of tick bite–induced pruritus. Results We found that 2 tick salivary peptides, IP defensin 1 (IPDef1) and IR defensin 2 (IRDef2), induced itch in mice. IPDef1 was further revealed to have a stronger pruritogenic potential than IRDef2 and to induce pruritus in a histamine-independent manner. IPDef1 evoked itch by activating mouse MrgprC11 and human MRGPRX1 on dorsal root ganglion neurons. IPDef1-activated MrgprC11/X1 signaling sensitized downstream ion channel TRPV1 on dorsal root ganglion neurons. Moreover, IPDef1 also activated mouse MrgprB2 and its ortholog human MRGPRX2 selectively expressed on mast cells, inducing the release of inflammatory cytokines and driving acute inflammation in mice, although mast cell activation did not contribute to oxidated IPDef1–induced itch. Conclusions Our study identifies tick salivary peptides as a new class of pruritogens that initiate itch through MrgprC11/X1-TRPV1 signaling in pruritoceptors. Our work will provide potential drug targets for the prevention and treatment of pruritus induced by the bites or stings of tick and maybe other arthropods.

Virus entry into cells is the initial stage of infection and involves multiple steps, and interfering viral entry represents potential antiviral approaches. Ion channels are pore-forming membrane proteins controlling cellular ion homeostasis and regulating many physiological processes, but their roles during viral infection have rarely been explored. Here, the functional Kv1.3 ion channel was found to be expressed in human hepatic cells and tissues. The Kv1.3 was then revealed to restrict HCV entry via inhibiting endosome acidification-mediated viral membrane fusion. The Kv1.3 was also demonstrated to inhibit DENV and ZIKV with an endosome acidification-dependent entry, but have no effect on SeV with a neutral pH penetration. A Kv1.3 antagonist PAP-1 treatment accelerated animal death in ZIKV-infected Ifnar1-/- mice. Moreover, Kv1.3-deletion was found to promote weight loss and reduce survival rate in ZIKV-infected Kv1.3-/- mice. Altogether, the Kv1.3 ion channel behaves as a host factor restricting viral entry. These findings broaden understanding about ion channel biology.

Rationale With the development of endoscopic techniques, endoscopic therapy began to play an important role in the management of esophageal hemangiomas. Patients concerns A large esophageal submucosal tumor (2.5 cm), which was suspected to be an esophageal hemangioma, was diagnosed in a 50-year-old woman. Diagnosis Esophageal hemangioma INTERVENTIONS:: Endoscopic submucosal dissection was performed for tumor removal. Outcomes Histopathological results revealed hemangioma. No complication or recurrence was observed in the 17-month follow-up period. Lessons Our successful experience showed that endoscopic submucosal dissection is an effective and a safe approach to treat large esophageal hemangiomas (2.5 cm).

Scorpion venom contains diverse bioactive peptides that can recognize and interact with membrane proteins such as ion channels. These natural toxins are believed to be useful tools for exploring the structure and function of ion channels. In this study, we characterized a K+-channel toxin gene, ImKTx96, from the venom gland cDNA library of the scorpion Isometrus maculates. The peptide deduced from the ImKTx96 precursor nucleotide sequence contains a signal peptide of 27 amino acid residues and a mature peptide of 29 residues with three disulfide bridges. Multiple sequence alignment indicated that ImKTx96 is similar with the scorpion toxins that typically target K+-channels. The recombined ImKTx96 peptide (rImKTx96) was expressed in the Escherichia coli system, and purified by GST-affinity chromatography and RP-HPLC. Results from whole-cell patch-clamp experiments revealed that rImKTx96 can inhibit the current of the Kv1.2 ion channel expressed in HEK293 cells. The 3D structure of ImKTx96 was constructed by molecular modeling, and the complex formed by ImKTx96 interacting with the Kv1.2 ion channel was obtained by molecular docking. Based on its structural features and pharmacological functions, ImKTx96 was identified as one member of K+-channel scorpion toxin α-KTx10 group and may be useful as a molecular probe for investigating the structure and function of the Kv1.2 ion channel.

The effective treatment of autoimmune diseases remains a challenge. Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a new therapeutic target for treating autoimmune disease. Consequently, Kv1.3 channel-inhibiting venom-derived peptides are a prospective resource for new drug discovery and clinical application. Area covered: Preclinical and clinical studies have produced a wealth of information on Kv1.3 channel-inhibiting venom-derived peptides, especially from venomous scorpions and sea anemones. This review highlights the advances in screening and design of these peptides with diverse structures and potencies. It focuses on representative strategies for improving peptide selectivity and discusses the preclinical research on those venom-derived peptides as well as their clinical developmental status. Expert opinion: Encouraging results indicate that peptides isolated from the venom of venomous animals are a large resource for discovering immunomodulators that act on Kv1.3 channels. Since the structural diversity of venom-derived peptides determines the variety of their pharmacological activities, the design and optimization of venom-peptides for improved Kv1.3 channel-specificity has been advanced through some representative strategies, such as peptide chemical modification, amino acid residue truncation and binding interface modulation. These advances should further accelerate research, development and the future clinical application of venom-derived peptides selectively targeting Kv1.3 channels.

Background Hepatitis B virus (HBV) infection causes acute and chronic liver disease, ultimately leading to the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Phospholipase A2 group IIA (PLA2G2A) plays important roles in the development and progression of many tumors. Thus far, there have been no reports on the association between HBV and PLA2G2A. The present study investigated the effect of HBV infection on PLA2G2A expression and its application in the diagnosis of HBV-related diseases. Methods Serum levels of PLA2G2A in 308 HBV-infected patients and 185 healthy controls were measured using an enzyme-linked immunosorbent assay (ELISA). The difference in serum levels of PLA2G2A was analyzed among chronic hepatitis B (CHB), LC, and HCC patients. PLA2G2A mRNA and protein expression in HepG2 and HepG2.2.15 cells carrying the integrated HBV genome were measured using reverse transcription polymerase chain reaction (RT-PCR) and western blot assays. The HBV infectious clone pHBV1.3, the control plasmid pBlue-ks and PLA2G2A gene promoter were transfected into HepG2 and HepG2.2.15 cells. After transfection, the luciferase activity was measured in the cells. PLA2G2A mRNA and protein expression levels were examined using RT-PCR and western blot assays. Results The serum levels of PLA2G2A were 258.3 ± 20.3ng/dl in the healthy controls and 329.0 ± 22.5ng/dl, 385.4 ± 29.3ng/dl and 459.2 ± 38.6ng/dl in the CHB, LC, and HCC patients, respectively. Statistical analyses revealed significantly higher serum levels of PLA2G2A in CHB, LC, and HCC patients than in the healthy controls (P LC > CHB group. High serum PLA2G2A levels in HCC patients were associated with a lower prevalence of lymph node metastasis and a lower TNM stage. HepG2.2.15 cells carrying the HBV genome expressed higher levels of PLA2G2A mRNA and protein than the HepG2 cells. In addition, HBV triggered PLA2G2A promoter activity and enhanced PLA2G2A mRNA and protein expression compared to the empty vector pBlue-ks. Conclusion HBV can upregulate the expression of PLA2G2A, and serum levels of PLA2G2A are associated with the progression of HBV-related diseases.