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Antitumor-analgesic peptide（AGAP）is a novel recombinant polypeptide. The primary study showed that AGAP 1.0 mg/kg exhibited strong analgesic and antitumor effects. The tail vein administration of AGAP potently reduced pain behaviors in mice induced by intraplantar injection of formalin or intraperitoneal injection of acetic acid, without affecting basal pain perception. To further assess the mechanisms of AGAP, the effects of AGAP on sodium channels were assessed using the whole-cell patch clamp recordings in dorsal root ganglia (DRG) neurons. The results showed that AGAP (3-1000 nM) inhibited the sodium currents in small-diameter DRG neurons in a dose-dependent manner. 1000 nM AGAP could inhibit the current density-voltage relationship curve of sodium channels in a voltage-dependent manner and negatively shift the activation curves. 1000 nM AGAP could reduce the tetrodotoxin-resistant (TTX-R) sodium currents by 42.8% in small-diameter DRG neurons. Further analysis revealed that AGAP potently inhibited NaV1.8 currents by 59.4%, and negatively shifted the activation and inactivation kinetics. 1000 nM AGAP also reduced the NaV1.9 currents by 33.7%, but had no significant effect on activation and inactivation kinetics. Thus, our results demonstrated that submicromolar concentrations of AGAP inhibited TTX-R sodium channel in rat small-diameter DRG neurons. It is concluded that these new results may better explain, at least in part, the analgesic properties of this polypeptide.

In this paper, we firstly reported a C-type lectin cDNA clone of1029 bps from the larvae of A. Pernyi (Ap-CTL) using PCR andRACE techniques. The full-length cDNA contains an openreading frame encoding 308 amino acid residues which hastwo different carbohydrate-recognition domains (CRDs) arrangedin tandem. To investigate the biological activities in theinnate immunity, recombinant Ap-CTL was expressed in E. coliwith a 6-histidine at the amino-terminus (Ap-rCTL). Besidesacted as a broad-spectrum recognition protein binding to awide range of PAMPs and microorganisms, Ap-rCTL also hadthe ability to recognize and trigger the agglutination of bacteriaand fungi. In the proPO activation assay, Ap-rCTL specificallyrestored the PO activity of hemolymph blocked by anti-Ap-rCTL antibody in the presence of different PAMPs ormicroorganisms. In summary, Ap-rCTL plays an important rolein insect innate immunity as an pattern recognition protein.[BMB Reports 2013; 46(7): 358-363]

Pattern recognition receptors are known to participate in theactivation of Prophenoloxidase system. In this study, a1,3-β-D-glucan recognition protein was detected for the firsttime in Antheraea pernyi larvae (Ap-βGRP). Ap-βGRP waspurified to 99.9% homogeneity from the hemolymph usingtraditional chromatographic methods. Ap-βGRP specificallybind 1,3-β-D-glucan and yeast, but not E. coli or M. luteus.The 1,3-β-D-glucan dependent phenoloxidase (PO) activity ofthe hemolymph inhibited by anti-Ap-βGRP antibody could berecovered by addition of purified Ap-βGRP. These resultsdemonstrate that Ap-βGRP acts as a biosensor of 1,3-β-Dglucanto trigger the Prophenoloxidase system. A trace mountof 1,3-β-D-glucan or Ap-βGRP alone was unable to trigger theproPO system, but they both did. Ap-βGRP was specificallydegraded following the activation of proPO with 1,3-β-Dglucan.These results indicate the variation in the amount ofAp-βGRP after specific immune challenge in A. pernyihemolymph is an important regulation mechanism to immuneresponse. [BMB Reports 2013; 46(5): 264-269]

Non-steroidal Anti-inflammatory Drugs (NSAIDs) are widely used because of their excellent anti-inflammatory and analgesic effects. However, NSAIDs could cause certain cardiac side effects, such as myocardial infarction, heart failure, atrial fibrillation, arrhythmia and sudden cardiac death. Therefore, meloxicam, nimesulide, piroxicam, and diclofenac were selected and the whole cell patch clamp technique was used to investigate the electrophysiological regulatory effects of them on the sodium channel hNav1.5 and potassium channel hKv11.1, which were closely associated to the biotoxicity of cardiac, and to explore the potential cardiac risk mechanism. The results showed that the four NSAIDs could inhibit the peak currents of hNav1.5 and hKv11.1. Furthermore, the four NSAIDs could affect both the activation and inactivation processes of hNav1.5 with I–V curves left-shifted to hyperpolarized direction in activation phase. These data indicate that the inhibition effects of Nav1.5 and Kv11.1 by meloxicam, nimesulide, piroxicam, and diclofenac might contribute to their potential cardiac risk. These findings provide a basis for the discovery of other potential cardiac risk targets for NSAIDs. [Display omitted] • NSAIDs act as inhibitors of hNav1.5 and hERG. • Nav1.5 and hERG might be involved in the cardiac side effects of NSAIDs. • Diclofenac showed the least inhibition effects on both hNav1.5 and hERG channels. • Minor perturbations of piroxicam and meloxicam lead to major changes in hNav1.5. [ABSTRACT FROM AUTHOR]

Utilization of the intestinal lymphatic pathway will allow extraordinary gains in lymph and tumors cascade-targeted delivery of oral drugs and awakening the innate/adaptive immunity of the body and the lesion microenvironment, in addition to improving oral bioavailability relative to other means of delivery of oral drugs. Here, inspired by the specific invasion route of intestinal microorganisms, we pioneered an immune-awakening Saccharomyces -inspired mesoporous silicon nanoparticle (yMSN) for the ingenious cascade-targeted delivery of therapeutic cancer vaccines and antitumor drugs to lymph and tumors via the intestinal lymphatic pathway. Encouragingly, yMSN high-loaded tumor-specific antigens (OVA, 11.9%) and anti-tumor drugs (Len, 28.6%) with high stability, namely Len/OVA/yMSN, efficiently co-delivered OVA and Len to their desired target sites. Moreover, yMSN concomitantly awakened the innate antitumor immunity of dendritic cells and macrophages, strengthening vaccine-induced adaptive immune responses and reversing macrophage-associated immunosuppression in the tumor microenvironment. Surprisingly, Len/OVA/yMSN treatment resulted in excellent synergistic antitumor efficacy and long-term antitumor memory in OVA-Hepa1-6-bearing mice. This high-performance nanocarrier provides a novel approach for lesion-targeting delivery of oral drugs accompanied with awakening of the innate/adaptive immunity of the lesion environment, and also represents a novel path for the oral delivery of diverse therapeutic agents targeting other lymph-mediated diseases., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Scorpion toxins can kill other animals by inducing paralysis and arrhythmia, which limits the potential applications of these agents in the clinical management of diseases. Antitumor-analgesic peptide (AGAP), purified from Buthus martensii Karsch, has been proved to possess analgesic and antitumor activities. Trp 38 , a conserved aromatic residue of AGAP, might play an important role in mediating AGAP activities according to the sequence and homology-modeling analyses. Therefore, an AGAP mutant, W38G, was generated, and effects of both AGAP and the mutant W38G were examined by whole-cell patch clamp techniques on the sodium channels hNa v 1.4 and hNa v 1.5, which were closely associated with the biotoxicity of skeletal and cardiac muscles, respectively. The data showed that both W38G and AGAP inhibited the peak currents of hNa v 1.4 and hNa v 1.5; however, W38G induced a much weaker inhibition of both channels than AGAP. Accordingly, W38G exhibited much less toxic effect on both skeletal and cardiac muscles than AGAP in vivo The analgesic activity of W38G and AGAP were verified in vivo as well, and W38G retained analgesic activity similar to AGAP. Inhibition to both Na v 1.7 and Na v 1.8 was involved in the analgesic mechanism of AGAP and W38G. These findings indicated that Trp 38 was a key amino acid involved in the biotoxicity of AGAP, and the AGAP mutant W38G might be a safer alternative for clinical application because it retains the analgesic efficacy with less toxicity to skeletal and cardiac muscles., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

White spot syndrome virus (WSSV) is a major pathogen of cultivated shrimp, but its host range includes a large number of crustaceans. In this investigation, Artemia franciscana was tested for susceptibility to WSSV by the oral route. Both instars and adults were challenged, and the presence of WSSV was followed through to reproductive cysts and offspring using PCR. WSSV caused a much lower cumulative mortality in Artemia than in cultivated shrimp by 10 d post-challenge. Instars, adults and reproductive cysts were PCR positive. However, the virus was undetectable by PCR in nauplii that had hatched from PCR-positive reproductive cysts. The data indicate that WSSV or WSSV genomic DNA can be vertically transmitted from WSSV-PCR-positive instars to reproductive cysts, but this DNA is removed during hatching.