Nanovaccines: An effective therapeutic approach for cancer therapy.

Cancer vaccines hold considerable promise for the immunotherapy of solid tumors. Nanomedicine offers several strategies for enhancing vaccine effectiveness. In particular, molecular or (sub) cellular vaccines can be delivered to the target lymphoid tissues and cells by nanocarriers and nanoplatforms to increase the potency and durability of antitumor immunity and minimize negative side effects. Nanovaccines use nanoparticles (NPs) as carriers and/or adjuvants, offering the advantages of optimal nanoscale size, high stability, ample antigen loading, high immunogenicity, tunable antigen presentation, increased retention in lymph nodes, and immunity promotion. To induce antitumor immunity, cancer vaccines rely on tumor antigens, which are administered in the form of entire cells, peptides, nucleic acids, extracellular vesicles (EVs), or cell membrane-encapsulated NPs. Ideal cancer vaccines stimulate both humoral and cellular immunity while overcoming tumor-induced immune suppression. Herein, we review the key properties of nanovaccines for cancer immunotherapy and highlight the recent advances in their development based on the structure and composition of various (including synthetic and semi (biogenic) nanocarriers. Moreover, we discuss tumor cell-derived vaccines (including those based on whole-tumor-cell components, EVs, cell membrane-encapsulated NPs, and hybrid membrane-coated NPs), nanovaccine action mechanisms, and the challenges of immunocancer therapy and their translation to clinical applications.

Antibacterial and antibiofilm effects of Pseudomonas aeruginosa derived outer membrane vesicles against Streptococcus mutans.

Antimicrobial resistance (AMR) is a serious and most urgent global threat to human health. AMR is one of today's biggest difficulties in the health system and has the potential to harm people at any stage of life, making it a severe public health issue. There must be fewer antimicrobial medicines available to treat diseases given the rise in antibiotic-resistant organisms. If no new drugs are created or discovered, it is predicted that there won't be any effective antibiotics accessible by 2050. In most cases, Streptococcus increased antibiotic resistance by forming biofilms, which account for around 80 % of all microbial infections in humans. This highlights the need to look for new strategies to manage diseases that are resistant to antibiotics. Therefore, development alternative, biocompatible and high efficacy new strategies are essential to overcome drug resistance. Recently, bacterial derived extracellular vesicles have been applied to tackle infection and reduce the emergence of drug resistance. Therefore, the objective of the current study was designed to assess the antibacterial and antibiofilm potential of outer membrane vesicles (OMVs) derived from Pseudomonas aeruginosa againstStreptococcus mutans. According to the findings of this investigation, the pure P. aeruginosa outer membrane vesicles (PAOMVs) display a size of 100 nm. S. mutans treated with PAOMVs showed significant antibacterial and antibiofilm activity. The mechanistic studies revealed that PAOMVs induce cell death through excessive generation of reactive oxygen species and imbalance of redox leads to lipid peroxidation, decreased level of antioxidant markers including glutathione, superoxide dismutase and catalase. Further this study confirmed that PAOMVs significantly impairs metabolic activity through inhibiting lactate dehydrogenase activity (LDH), adenosine triphosphate (ATP) production, leakage of proteins and sugars. Interestingly, combination of sub-lethal concentrations of PAOMVs and antibiotics enhances cell death and biofilm formation of S. mutans. Altogether, this work, may serve as an important basis for further evaluation of PAOMVs as novel therapeutic agents against bacterial infections.

Multitargeted pharmacokinetics, molecular docking and network pharmacology-based identification of effective phytocompounds from Sauropus androgynus (L.) Merr for inflammation and cancer treatment.

According to worldwide health data, cancer, and inflammatory illnesses are on the rise and are among the most common causes of death. Across the world, these types of health problems are now considered top priorities for government health organizations. Hence, this study aimed to investigate medicinal plants' potential for treating cancer and inflammatory disorders. This network pharmacology analysis aims to learn more about the potential targets and mechanisms of action for the bioactive ingredients in Sauropus androgynus (L.) Merr L. The compound-target network and protein-protein interaction analysis were built using the STRING database. Using Network Analyst, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes, pathway enrichment was performed on the hub genes. 1-hexadecanol was shown to inhibit drug-metabolizing enzymes in a pharmacokinetic investigation. Those samples of 1-hexadecanol were found to be 1-hexadecanol (BBB 0.783), GI High, Pgp Substrate Yes, CYP2C19 Inhibitor Yes, CYP2D6 Yes, and HI -89.803. The intermolecular binding energies for 1-hexadecanol (4-DRI, -8.2 kcal/mol) are evaluated. These results from a study on S. androgynus used molecular docking and network pharmacology to gain insight into the prime target genes and potential mechanisms identified for AKT1, mTOR, AR, PPID, FKBP5, and NR3C1. The PI3K-Akt signalling pathway has become an important regulatory node in various pathological processes requiring coordinated actions. Stability and favourable conformations have been resolved by considering nonbonding interactions such as electrostatic and hydrogen bonds in MD simulations of the perfect molecules using the Desmond package. Thus, using an appropriate platform of network pharmacology, molecular docking, and in vitro experiments, this study provides for the first time a clearer knowledge of the anti-cancer and anti-inflammatory molecular bioactivities of S. androgynus. Further in vitro and in vivo confirmations are strongly needed to determine the efficacy and therapeutic effects of 1-hexadecanol in the biological process.Communicated by Ramaswamy H. Sarma.

Postbiotics: Functional Food Materials and Therapeutic Agents for Cancer, Diabetes, and Inflammatory Diseases.

Postbiotics are (i) "soluble factors secreted by live bacteria, or released after bacterial lysis, such as enzymes, peptides, teichoic acids, peptidoglycan-derived muropeptides, polysaccharides, cell-surface proteins and organic acids"; (ii) "non-viable metabolites produced by microorganisms that exert biological effects on the hosts"; and (iii) "compounds produced by microorganisms, released from food components or microbial constituents, including non-viable cells that, when administered in adequate amounts, promote health and wellbeing". A probiotic- and prebiotic-rich diet ensures an adequate supply of these vital nutrients. During the anaerobic fermentation of organic nutrients, such as prebiotics, postbiotics act as a benevolent bioactive molecule matrix. Postbiotics can be used as functional components in the food industry by offering a number of advantages, such as being added to foods that are harmful to probiotic survival. Postbiotic supplements have grown in popularity in the food, cosmetic, and healthcare industries because of their numerous health advantages. Their classification depends on various factors, including the type of microorganism, structural composition, and physiological functions. This review offers a succinct introduction to postbiotics while discussing their salient features and classification, production, purification, characterization, biological functions, and applications in the food industry. Furthermore, their therapeutic mechanisms as antibacterial, antiviral, antioxidant, anticancer, anti-diabetic, and anti-inflammatory agents are elucidated.

Interaction of azadirachtin with the lipid-binding domain: Suppression of lipid transportation in the silkworm, Bombyx mori.

This study investigates the effects of the insect growth regulator azadirachtin on lipid transportation to the ovary of the silkworm, Bombyx mori. Lipids are hydrophobic in nature and require a carrier for circulation in the blood. Protein-lipid interactions play a vital role in lipid transport, thereby keeping the system balanced. In general, lipids bind to lipoproteins in a specific region called the lipid-binding domain (LBD). In this study, B. mori apolipophorin amino acid sequences were retrieved from NCBI and the LBD was identified. The LBD structure was predicted by (PS)2 and validated in ProSA. The LBD structure was docked with DMPC, POPC and sphingomyelin by SwissDock, each binding with GLN 171, ASN 162, and ASN 160 and 162, respectively. Interestingly, azadirachtin binds with ASN 160 and 162 and GLN 171, which shows that lipids and azadirachtin are binding with the same amino acid residues in the LBD. Later, this result was confirmed with wet lab work using a fluorescent phospholipid probe. Azadirachtin binding with the LBD was indirectly proportional to the fluorescent lipid binding. These results suggest that azadirachtin binds with the LBD instead of the lipids and interrupts the protein-lipid interaction, leading to the suppression of lipid transportation to the ovary.