International Journal of Peptide Research and Therapeutics最新文献

Liver cancer is a worldwide issue that also affects the Malaysian population. The occurrence is closely related to risk factors like chronic infections and environmental exposures. Due to the toxicity of conventional therapeutic drugs for liver cancer, bioactive peptides have emerged as a popular alternative anticancer agent. Although the full-length pardaxin from Pardachirus marmoratus was proven with anticancer effects, its concurrent haemolytic effects are yet to be resolved. Therefore, this study utilized in silico and in vitro analyses to assess cytotoxic effects induced by the shortened pardaxin derivatives. The in silico findings led to the discovery of a series of shortened pardaxin derivatives with 13 amino acids, where single residue replacement prediction by bioinformatics tools was done on the shortened sequences. Among the top five shortened derivatives, the derivative where amino acid threonine was replaced by proline, was identified as the most potential candidate, namely LL13. The LL13 peptide was predicted with improved anticancer effects, non-toxic, and alleviated haemolytic effects as compared to its parental peptide. The subsequent cytotoxicity testing further validated its selective toxicity against liver cancer cells, HepG2 cells, with relatively lower killing effects on the normal cells, Vero cells. These in vitro findings validated the in silico predictions and also indicated that this peptide has potential as an anticancer drug with selective targeting capabilities. In conclusion, this study has highlighted the potential of using a combination of in silico and in vitro approaches to discover potentially shortened peptides as a novel therapeutic option for liver cancer treatment.

FOXM1 is a crucial oncogenic transcription factor involved in almost all cancer hallmark pathways across all cancer types. Our previous work had found that FOXM1 targeted peptide P201 can strongly inhibit the growth of cancer cells including the liver cancer HCCLM3 cells. In addition, by RNA-seq of HCCLM3 cells treated with MCP-1, an anticancer peptide optimized from P201, ALOXE3, a key feature of ferroptosis was significantly elevated while FOXM1 was down-regulated, we wonder if the cell death of HCCLM3 induced by MCP-1 was associated with ferroptosis. Also, the relationship between FOXM1 and ferroptosis was less understood. Hence, in this study, we explore the effect of MCP-1 on ferroptosis and establish the associations among MCP-1, FOXM1 and ALOXE3 in HCCLM3 cells. The results showed that MCP-1 can significantly induce the elevated expression of ALOXE3, while the other important ferroptosis features including GSH, GPX4,ROS and total iron in HCCLM3 cells were all expectedly regulated. Also, ferrostatin-1, a specific inhibitor for ferroptosis, can reverse the cell death of HCCLM3 cells when co-administrated with MCP-1. TCGA database hepatocellular carcinoma gene expression analysis showed that FOXM1 was negative-related to ALOXE3 and further confirmed by the results of siRNA knockdown of FOXM1 in HCCLM3 cells. Moreover, the co-expressed genes analysis for FOXM1 and ALOXE3 revealed that many of them were closely involved in the regulation of ferroptosis. Taken together, we discovered and confirmed the induction of ferroptosis by MCP-1 in liver cancer HCCLM3 cells and primarily established the associations among MCP-1, FOXM1 and ALOXE3.

Dengue, a significant mosquito-borne disease, presents a global health challenge with limited treatment options. Recently, there have been estimates of 390 million dengue infections annually worldwide. Thus, Dengue viruses (DENV) continue to result in a severe burden on human health all over the world. Here, we are introducing the Anti-Dengue Peptide Database (ADPDB) as a comprehensive knowledgebase dedicated to anti-dengue peptides, aiming to aid research and development efforts against the dengue virus. ADPDB consolidates information on antimicrobial peptides (AMPs) exhibiting anti-dengue activity, sourced from extensive literature curation. The database provides a user-friendly interface offering functionalities such as simple and advanced search options, data retrieval, and customizable reports. Currently housing 606 peptide entries, ADPDB encompasses peptides from various sources, including natural and synthetic origins. Name, sequence, source, target, mode of action (MoA), length, IC50, toxicity, hemolytic activity of peptides are meticulously curated, facilitating insights into their therapeutic potential. Notably, ADPDB addresses the gap in specialized databases focusing on anti-DENV peptides, aligning with the growing interest in peptide-based therapeutics. The database enables researchers, pharmaceutical industries, and clinicians to explore peptide candidates, study structure-activity relationships, and accelerate drug discovery processes. By leveraging bioinformatics-driven approaches, ADPDB aims to advance the understanding and development of peptide-based interventions against dengue. This resource is accessible via any web browser at URL: https://bblserver.org.in/adpdb/.

Graphical abstract

Graphical abstract of ADPDB (for the creation of graphical abstract, we have used the image of dengue virus (PDB ID: 1K4R by Kuhn et al in Structure of dengue virus: implications for flavivirus organization, maturation, and fusion, Cell, 108(5):717–725, 2002), image of arenicin-1 AMP (PDB ID: 2JSB by Andrä et al in Structure and mode of action of the antimicrobial peptide arenicin, Biochem J, 410(1):113–122, 2008), and image of an PubMed article (PMID: 29200948 by Chew MiawFang et al in Peptides as therapeutic agents for dengue virus, Int J Med Sci 14(13):1342–1359, 2017). The remaining images are generated and incorporated by us).

A robust strategy is imperative to counteract multi-resistant pathogens within the oral cavity and mitigate the occurrence of dental-related diseases. According to the recent Global Oral Health Status Report (2022), over 3.5 billion individuals worldwide have been affected, with more than 2 billion experiencing permanent tooth caries. Despite employing various techniques to combat oral pathogens, these microbes persistently proliferate, culminating in biofilm formation that exhibits resistance to conventional antibiotics. Moreover, there is a notable surge in the rate of implant failure attributable to peri-implantitis. Peptide therapy emerges as a promising and enduring solution, demonstrating adaptability to diverse techniques. The pivotal technique involving Antimicrobial peptides (AMPs) orchestrates damage to the extracellular matrix, encompassing the glucan matrix, disrupting microbial content, and inducing pathogen demise. Notably, AMPs actively participate in the intricate process of oral tissue healing. Nanofibers, characterized by their multifaceted properties and robust mechanical capacity, facilitate protracted drug delivery and manifest optimal biocompatibility. This inherent attribute stimulates the application of AMPs, thereby augmenting healing durations and ensuring sustained therapeutic efficacy against oral diseases. The primary focus of this review centers on Antimicrobial peptides (AMPs) integrated into Nanofibers, offering a comprehensive clinical solution to diverse dental-mediated diseases. The exploration of various AMPs and their modes of action, coupled with the efficacy of peptide durability, sets the stage for futuristic enhancements in oral health therapeutics.

This bibliometric analysis delves into the latest research on protein hydrolysates from fish, examining its potential to contain various bioactive peptides and other functional compounds that benefit overall health. The study also explores publication trends of fish protein hydrolysates from 2019 to 2023, revealing a total of 564 related articles with an annual growth rate of 6%. Notably, countries such as China, Spain, India, and Norway lead the way in contributing to the field of fish protein hydrolyzate. The top journal in this area is Marine Drugs published by the Multidisciplinary Digital Publishing Institute (MDPI). The most frequently cited studies focus on the development and application of food ingredients, bioactive properties, enzyme use, food allergy prevention, and peptide characterization in relation to fishery products and protein hydrolysates. Keyword analysis highlights functional properties, bioactive peptides, biological activity, and cell proliferation as key areas of interest. Overall, these findings suggest that functional properties, bioactive peptides, and cell proliferation remain promising topic for future research and development.

Antimicrobial peptides (AMPs) are small cationic or amphipathic molecules that are produced by both prokaryotic and eukaryotic species. The latest findings in the field of dermatology point to the potential significance of AMPs in the battle against skin microbial infections. AMPs additionally function as multifunctional immune effectors, promoting angiogenesis, wound healing, and the production of cytokines and chemokines. In human skin, AMPs such as β-defensin, S100, and cathelicidin are primarily secreted by keratinocytes, neutrophils, sebocytes, or sweat glands. These substances are either produced continuously or expressed in reaction to certain inflammatory stimuli, thus playing a role in the development of various skin diseases in humans. Furthermore, in contrast to other human skin conditions, the level of AMP synthesis decreases as the disease progresses. In this review, we provide data supporting the role of AMPs as natural mediators of dermatological problems, as well as their potential for being used as therapeutic agents in the treatment of skin diseases.

Nowadays, design of cytotoxic agents based on microbial toxins is attracted for researchers. Pertussis-like toxin subunit A (PltA) of typhoid toxin is ADP-ribosyl transferase and had the cytotoxicity and cell arrest property in G2/M phase of human cancer cell line. To translocate and its increase to the cells, PltA requires the cell penetrating part. Here, the catalytic PltA (named Typh) was attached to Tat peptide as a cell penetrating agent and expressed as a new recombinant fusion protein (named Tat-Typh) in E. coli BL21. After that, recombinant Tat-Typh was purified using Ni + chromatography column and confirmed by western blotting. Finally, its cytotoxicity effects and cell penetration activity were evaluated by, MTT assay, Annexin-V/PI staining and western blotting methods, respectively. Our results showed that Tat-Typh had the significant cytotoxic effect at 25, 50, 150 and 200 µg/mL concentrations (P < 0.05). In addition, cell treating with 50 µg/mL Tat-Typh was resulted in to increase the percentage of necrotic cells compared to control groups (P < 0.05). Moreover, binding of Tat fragment to Typh protein caused to increase the speed of entry of Tat-Typh to cells compared to Typh alone. In conclusion, it is observed that Tat-Typh protein is able to increase the cell penetration properties of catalytic Pertussis-like toxin subunit A and has the cytotoxic effects on lung cancer cell line.

Amphiphilic cationic peptide (ACP) is a widely studied biofilm-active peptide that has great potential in cancer treatment. However, poor stability, a short half-life, and complex preparation pose significant challenges for practical therapeutic applications. In the current investigation, the amphiphilic peptide Melittin (Mel), recognized for its powerful anticancer properties, was chosen from natural and synthetic ACP, and integrated into a nanostructure by utilizing polyhydroxyalkanoate (PHA) microspheres as carriers to produce Mel-loaded PHA microspheres (Mel@PHA-PhaC). Mel@PHA-PhaC nanostructure was self-assembled in Escherichia coli, simplifying its preparation and making it more convenient and high-yield. Mel@PHA-PhaC were spherical, with a particle size of approximately 300 nm, as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The concentration of Mel in Mel@PHA-PhaC was 4 μg/mg. Mel@PHA-PhaC still maintained good stability after being treated with pancreatic enzymes. Furthermore, in vitro experiments demonstrated that Mel@PHA-PhaC enhanced the inhibitory effect on cancer cells compared to free Mel. This study provides insights and guidelines for the development and utilization of peptide delivery systems using PHA microspheres to create stable and improved peptides for cancer therapy.

Antimicrobial peptides (AMPs) are promising candidates for the development of new drugs. However, thorough studies on the toxicity of these molecules are scarce, which is a gap, as host toxicity is one of the main reasons for nonapproval of the drug by regulatory agencies. This work aimed to evaluate the toxicity of three AMPs isolated from Capsicum annuum leaves, named CaCPin-II, CaCDef-like and CaCLTP2. The AMP toxicological profile was evaluated by in vitro cytotoxicity against mammalian cells and systemic in vivo toxicity using Galleria mellonella larvae as study model. AMP cytotoxicity was evaluated in a broad panel of human cell lines, namely, vascular endothelium, cervical adenocarcinoma, prostatic epithelium, mammary epithelium and fibroblasts, and in murine macrophages. Cell viability was evaluated through metabolic activity, a gold standard method for assessing viability due to the speed, robustness and reliability of the results. To elucidate the toxicity mechanism of the peptides, their ability to bind to the cell surface and to permeabilize membranes was evaluated by measuring the zeta potential and the absorption of the SYTOX® Green fluorescent probe, respectively. The AMPs did not decrease cell viability or permeabilize the membranes of the cell lines at the tested concentrations. Only CaCLTP2 had the ability to interact with the cell surface, but it was not able to permeabilize them. The in vivo systemic toxicity was evaluated by the survival rate of the G. mellonella larvae inoculated with peptides. CaCPin-II showed in vivo toxicity, as the larval survival rate after the test was 60% lower than that of the controls. The results suggest that these peptides have potential as antimicrobial agents because they have low or no toxicity to mammalian cells and can serve as a framework for drug development.