Cathelicidins are a family of antimicrobial peptides (AMPs) with broad-spectrum activity and immunomodulatory functions. Among them, the only human cathelicidin LL-37 has garnered significant interest due to its potent antimicrobial, antiviral, antifungal, antiparasitic, and antitumor properties. However, the clinical application of LL-37 is hindered by several limitations, including low proteolytic stability, cytotoxicity, and high production costs. To overcome these challenges, a wide range of design strategies have been employed to modify LL-37 and improve its therapeutic potential. LL-37-based analogs represent promising candidates for the development of next-generation antimicrobial and immunomodulatory therapies. Despite significant progress, further research is required to optimize peptide design, ensure cost-effective production, and validate long-term safety and efficacy. Advances in computational modeling, high-throughput screening, and nanotechnology will play an important role in the translation of modified cathelicidins into clinical practice. This review summarizes key strategies of chemical and structural modifications of LL-37 aimed at enhancing its functional properties. Particular attention is given to truncated and retro-analogs, which preserve or improve biological activity while exhibiting reduced toxicity and increased proteolytic resistance. Furthermore, we highlight the use of nanoscale delivery systems, which facilitate targeted delivery, prolong peptide half-life, and mitigate cytotoxic effects.

Single nucleotide polymorphisms (SNPs) are now considered as the most perspective and convenient markers for studies of genetic basis of multifactorial diseases. Fast development of technologies for exact screening of a large volume of genetic information and construction of genomic maps of SNP-markers promote the development of innovative diagnostic systems on the basis of significant SNP for an estimation of individual genetic risk of development of various diseases. This review considers the basic aspects of genetics of diabetes mellitus type 1 and 2 and an opportunity to use SNP as markers for the estimation of individual genetic predisposition to this disease.

Diabetic foot ulcers (DFU) are among the most severe complications of diabetes, resulting from a combination of metabolic dysregulation, vascular insufficiency, neuropathy, chronic inflammation, and impaired tissue repair, whereas diabetic foot infection (DFI) may develop within this compromised wound environment and frequently involves polymicrobial communities and biofilms. This review evaluates the mechanistic and translational basis for the use of antimicrobial peptides (AMP) in DFU and DFI, with emphasis on the diabetic wound microenvironment, polymicrobial ecology, endogenous AMP dysregulation, mechanisms of action, therapeutic development, and barriers to clinical translation. Hyperglycemia, ischemia, oxidative and proteolytic stress, and impaired innate immunity sustain inflammation, delay tissue repair, and promote microbial persistence. These conditions may also complicate antibiotic treatment through impaired tissue exposure and biofilm-associated tolerance. Depending on the peptide and experimental context, AMP may provide direct antimicrobial or antibiofilm activity and may also exert immunomodulatory or pro-reparative effects involving inflammatory signaling, angiogenesis, keratinocyte and fibroblast migration, and re-epithelialization. Approaches under investigation include engineered peptides, combination regimens, and local biomaterial-based platforms, including hydrogels, dressings, scaffolds, and nanoparticle-conjugated systems. Clinical translation remains constrained by proteolytic instability, potential host-tissue toxicity, limited selectivity, limited predictive value of preclinical models, heterogeneous clinical populations, nonstandardized endpoints, and manufacturing and regulatory requirements. Preclinical evidence supports further evaluation of approaches for local delivery of AMP, whereas clinical evidence in DFU and DFI remains limited and heterogeneous, with no AMP-based intervention yet demonstrating sufficiently consistent clinical benefit to support routine use.

Adenosine-to-inosine RNA editing is one of the most common types of RNA editing, a posttranscriptional modification made by special enzymes. We present a proteomic study on this phenomenon for Drosophila melanogaster. Three proteome data sets were used in the study: two taken from public repository and the third one obtained here. A customized protein sequence database was generated using results of genome-wide adenosine-to-inosine RNA studies and applied for identifying the edited proteins. The total number of 68 edited peptides belonging to 59 proteins was identified in all data sets. Eight of them being shared between the whole insect, head and brain proteomes. Seven edited sites belonging to synaptic vesicle and membrane trafficking proteins were selected for validation by orthogonal analysis by Multiple Reaction Monitoring. Five editing events in cpx, Syx1A, Cadps, CG4587 and EndoA were validated in fruit fly brain tissue at the proteome level using isotopically labeled standards. Ratios of unedited-to-edited proteoforms varied from 35:1 (Syx1A) to 1:2 (EndoA). Lys-137 to Glu editing of endophilin A may have functional consequences for its interaction to membrane. The work demonstrates the feasibility to identify the RNA editing event at the proteome level using shotgun proteomics and customized edited protein database.