Research diversity and advances in simultaneous removal of multi-mycotoxin.

被引量：- 发表：1970

Obscure properties of a traditional herb Pittosporum neelgherrense used to treat snakebite envenoming against Daboia russelli venoms.

In tropical nations, snakebite envenomation is a significant public health issue with negative human and social effects. This is due to three factors: 1) more species of the most hazardous snakes are present; 2) emergency medical assistance is not readily available; and 3) inadequate health care. The problems caused by snakebite envenomation have been partially resolved by immunotherapy. An extensive collection of medicinal herbs is recognized to have antivenomous properties in traditional medicine. However, very few species have undergone scientific investigation, and even fewer have had their active components separated and structurally and functionally defined. In this work, the anti-venom potential of hot and cold aqueous extracts from Pittosporum neelgherrense is evaluated using an in-vitro model. The experimental results showed that 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-(11.20), 1-Undecanol (16.38), Lauryl acetate (18.25), and Cyclotridecane (19.14) were phytochemical substances whose chemical structures were recognized by GCMS. The Direct and Indirect hemorrhagic activity was found to be completely neutralized by P. neelgherrense extract (44.61% hot plant extract & 55.38% cold plant extract) and the zone (2.4 mm), respectively. The neutralization of venoms was indicated by the zone (0.5-0.9 cm) of hydrolysis production of proteolytic activity. Additionally, the results of the gelatine liquefaction study demonstrated that clot formation was not triggered by venom at low concentrations (50:50) but was instead brought on by higher concentrations. The present study suggested that the neutralization of venom by hot water extracts of P. neelgherrense is a potentially therapeutic application.

被引量：- 发表：1970

Yangzheng mixture reversed EMT against hepatocellular carcinoma metastasis via NF-κB/NLRP3/β-catenin pathway.

Yangzheng mixture has been used as an adjuvant tumor therapy as a traditional Chinese medicine in clinical. However, less is known about the activity of Yangzheng mixture. In our study, we explored the anti-tumor activity of Yangzheng mixture for HCC in vitro and in vivo. The effects of Yangzheng mixture on HCC biological behaviors were assessed using colony formation assay, EdU staining, cell cycle assay, Annexin V/PI staining, and wound healing assay. Migration and invasion of HCC cells were further evaluated via transwell assays, while molecular mechanisms were investigated through western blotting and immunofluorescence staining. Additionally, the anticancer effect of Yangzheng mixture in vivo were examined using H22 xenograft and H22 metastatic hepatocellular carcinoma models. Our results revealed that Yangzheng mixture inhibited colony formation, EdU incorporation, cell migration, and invasion, while arresting cell cycle at the G2-M phase in Bel-7402 and SMMC-7721 cells. Mechanistic studies demonstrated that Yangzheng mixture showed a markedly inhibition on Bel-7402 and SMMC-7721 cells with higher NLRP3 expression. We further confirmed that Yangzheng mixture could activate NLRP3 inflammasome through NF-κB by western blotting and immunofluorescence staining. Additionally, Yangzheng mixture inhibited β-catenin nucleus translocation and reversed EMT process. In vivo, the H22 xenograft model depicted that Yangzheng mixture significantly reduced tumor size and weight compared with control. Moreover, H22 lung metastasis model showed that Yangzheng mixture significantly inhibited liver cancer cell spreading to lungs in mice. Overall, our finding revealed that Yangzheng mixture inhibited HCC proliferation and migration in vitro and in vivo by reversing EMT via NF-κB/NLRP3/β-catenin pathway. These results may serve new therapeutic evidences for Yangzheng mixture application in clinical.

被引量：- 发表：1970

Structure-aided function assignment to the transcriptomic conopeptide Am931.

Implementation of the next-generation technologies for gene sequencing of venom duct transcriptome has provided a large number of peptide sequences of marine cone snails. Emerging technologies on computational platforms are now rapidly evolving for the accurate predictions of the 3D structure of the polypeptide using the primary sequence. The current report aims to integrate the information derived from these two technologies to develop the concept of structure-aided function assignment of Conus peptides. The proof of the concept was demonstrated using the transcriptomic peptide Am931 of C. amadis. The 3D structure of Am931 was computed using Density Functional Theory (DFT) and the quality of the predicted structure was confirmed using 2D NMR spectroscopy of the corresponding synthetic peptide. The computed structure of Am931 aligns with the active site motif of thioredoxins, possess catalytic disulfide conformation of (+, -)AntiRHHook and selectively modulate the N-terminal Cys3 thiol. These structural features indicate that Am931 may act as a disulfide isomerase and modulate the oxidative folding of conotoxins. Synthetic peptide Am931 provides proof-of-function by exhibiting catalytic activity on the oxidative folding of α-conotoxin ImI and improving the yield of native globular fold. The approach of integration of new technologies in the Conus peptide research may help to accelerate the discovery pipeline of new/improved conotoxin functional.

被引量：- 发表：1970

V-ToCs (Venom Toxin Clustering): A tool for the investigation of sequence and structure similarities in snake venom toxins.

Recently, there has been a major push toward the development of next-generation treatments against snakebite envenoming. However, unlike current antivenoms that rely on animal-derived polyclonal antibodies, most of these novel approaches are reliant on an in-depth understanding of the over 2000 known snake venom toxins. Indeed, by identifying similarities (i.e., conserved epitopes) across these different toxins, it is possible to design cross-reactive treatments, such as broadly-neutralising antibodies, that target these similarities. Therefore, in this project, we built an automated pipeline that generates sequence and structural distance matrices and homology trees across all available snake venom toxin sequences and structures. To facilitate analysis, we also developed a user-friendly and high-throughput visualisation tool, coined "Venom TOxin CluStering" (V-ToCs). This tool allows researchers to easily investigate sequence and structure patterns in snake venom toxins for a wide array of purposes, such as elucidating toxin evolution, and will also hopefully help guide the discovery and development of increasingly broadly-neutralising antivenoms in the near future.

被引量：- 发表：1970