Human amniotic mesenchymal stem cell-islet organoids enhance the efficiency of islet engraftment in a mouse diabetes model.

AIMS: Despite islet transplantation has proved a great potential to become the standard therapy for type 1 diabetes mellitus (T1DM), this approach remains limited by ischemia, hypoxia, and poor revascularization in early post-transplant period as well as inflammation and life-long host immune rejection. Here, we investigate the potential and mechanism of human amniotic mesenchymal stem cells (hAMSCs)-islet organoid to improve the efficiency of islet engraftment in immunocompetent T1DM mice. MAIN METHODS: We generated the hAMSC-islet organoid structure through culturing the mixture of hAMSCs and islets on 3-dimensional-agarose microwells. Flow cytometry, whole-body fluorescent imaging, immunofluorescence, Calcein-AM/PI staining, ELISA, and qPCR were used to assess the potential and mechanism of shielding hAMSCs to improve the efficiency of islet transplantation. KEY FINDINGS: Transplant of hAMSC-islet organoids results in remarkably better glycemic control, an enhanced glucose tolerance, and a higher ß cell mass in vivo compared with control islets. Our results show that hAMSCs shielding provides an immune privileged microenvironment for islets and promotes graft revascularization in vivo. In addition, hAMSC-islet organoids show higher viability and reduced dysfunction after exposure to hypoxia and inflammatory cytokines in vitro. Finally, our results show that shielding with hAMSCs leads to the activation of PKA-CREB-IRS2-PI3K and PKA-PDX1 signaling pathways, up-regulation of SIL1 mRNA levels, and down-regulation of MT1 mRNA levels in ß cells, which ultimately promotes the synthesis, folding and secretion of insulin, respectively. SIGNIFICANCE: hAMSC-islet organoids can evidently increase the efficiency of islet engraftment and might develop into a promising alternative for the clinical treatment of T1DM.

Development of a novel hybrid antimicrobial peptide for enhancing antimicrobial spectrum and potency against food-borne pathogens.

AIMS: To address the increasingly serious challenge of the transmission of foodbrone pathogens in the food chain. METHODS AND RESULTS: In this study, we employed rational design strategies, including truncation, amino acid substitution, and heterozygosity, to generate seven engineered peptides with α-helical structure, cationic property, and amphipathic characteristics based on the original Abhisin template. Among them, as the hybird antimicrobial peptide (AMP), AM exhibits exceptional stability, minimal toxicity, as well as broad-spectrum and potent antimicrobial activity against foodborne pathogens. Besides, it was observed that the electrostatic incorporation demonstrates by AM results in its primary targeting and disruption of the cell wall and membrane of Escherichia coli O157: H7 (EHEC) and methicillin-resistant Staphylococcus aureus (MRSA), resulting in membrane perforation and enhanced permeability. Additionally, AM effectively counteracts the deleterious effects of lipopolysaccharide, eradicating biofilms and ultimately inducing the demise of both food spoilage and pathogenic microorganisms. CONCLUSIONS: The findings highlight the significant potential of AM as a highly promising candidate for a novel food preservative and its great importance in the design and optimization of AMP-related agents.

The inhibitory action of lactocin 63 on deterioration of seabass (Lateolabrax japonicus) during chilled storage.

BACKGROUND: The bacteriocins, particularly derived from lactic acid bacteria, currently exhibit potential as a promising food preservative owing to their low toxicity and potent antimicrobial activity. This study aimed to evaluate the efficacy of lactocin 63, produced by Lactobacillus coryniformis, in inhibiting the deterioration of Lateolabrax japonicas during chilled storage, while also investigating its underlying inhibitory mechanism. The measurement of total viable count, biogenic amines, and volatile organic compounds were conducted, along with high-throughput sequencing and sensory evaluation. RESULTS: The findings demonstrated that treatment with lactocin 63 resulted in a notable retardation of bacterial growth in L. japonicas fish fillet during refrigerated storage compared with the water-treated and nisin-treated groups. Moreover, lactocin 63 effectively maintained the microbial flora balance in the fish fillet and inhibited the proliferation and metabolic activity of specific spoilage microorganisms, particularly Shewanella, Pseudomonas, and Acinetobacter. Furthermore, the production of unacceptable volatile organic compounds (e.g. 1-octen-3-ol, hexanal, nonanal), as well as the biogenic amines derived from the bacterial metabolism, could be hindered, thus preventing the degradation in the quality of fish fillets and sustaining relatively high sensory quality. CONCLUSION: The results of this study provide valuable theoretical support for the development and application of lactocin 63, or other bacteriocins derived from lactic acid bacteria, as potential bio-preservatives in aquatic food. © 2024 Society of Chemical Industry.

Rational Design and Antimicrobial Potency Assessment of Abaecin Analogues.

The widespread and escalating emergence of multidrug resistance is now recognized as one of the most severe global threats to human health. To address the urgent issue of drug-resistant bacteria and the limitation of effective clinical treatments, antimicrobial peptides (AMPs) have been developed as promising substituents of conventional antibiotics. In this study, rational design strategies were employed to acquire seven cationic and α-helical engineered peptides based on the original template of Abaecin. After investigation, we found that AC7 (LLRRWKKLFKKIIRWPRPLPNPGH) demonstrated potent and broad-spectrum antimicrobial activity. Additionally, it demonstrated low cytotoxicity and hemolysis while maintaining good stability. Notably, AC7 displays the antibacterial mechanism with superior abilities in cell membrane disruption and potential DNA binding in vitro, as well as effectively disrupting biofilms. Moreover, the murine skin wound model infected with drug-resistant Pseudomonas aeruginosa was employed to evaluate the anti-infective efficacy and therapeutic potential of AC7. It was observed that AC7 displays a remarkable capacity to inhibit wound colonization, reduce levels of inflammatory cytokines (TNF-α) and inflammatory cells (white blood cells (WBC), monocytes (MONO), lymphocytes (LYMPH), neutrophils (GRAN)), promote the levels of IL-10 and VEGF, and enhance wound healing. Overall, these findings demonstrate the potential of AC7 as a viable alternative to traditional antibiotics.

Rational design of Abhisin-like peptides enables generation of potent antimicrobial activity against pathogens.

Infections caused by pathogens can be a significant challenge in wound healing, particularly when antimicrobial resistance is a factor. This can pose a serious threat to human health and well-being. In this scenario, it is imperative to explore novel antimicrobial agents to fight against multi-drug resistant (MDR) pathogenic bacteria. This study employed rational design strategies, including truncation, amino acid replacement, and heterozygosity, to obtain seven α-helical, cationic, and engineered peptides based on the original template of Abhisin. Among the analogs of Abhisin, AB7 displayed broad-spectrum and potent antimicrobial activity, superior targeting of membranes and DNA, and the ability to disrupt biofilms and anti-endotoxins in vitro. Additionally, we evaluated the anti-infection ability of AB7 using a murine skin wound model infected with methicillin-resistant Staphylococcus aureus (MRSA) and found that AB7 displayed negligible toxicity both in vitro and in vivo. Furthermore, AB7 exhibited desirable therapeutic efficacy by reducing bacterial burden and pro-inflammatory mediators, modulating cytokines, promoting wound healing, and enhancing angiogenesis. These results highlight the potential of AB7 as a promising candidate for a new antibiotic. KEY POINTS: • A α-helical, cationic, and engineered peptide AB7 was obtained based on Abhisin. • AB7 exhibited potent antimicrobial activity and multiple bactericidal actions. • AB7 effectively treated infected skin wounds in mice.