Antimicrobial resistance (AMR) has emerged as one of the most pressing global health challenges of our time. Alarming projections of increasing mortality from resistant infections highlight the urgent need for innovative solutions. While many candidates have shown promise in preliminary studies, they often encounter challenges in terms of efficacy and safety during clinical translation. This review examines cutting-edge approaches to combat AMR, with a focus on engineered antimicrobial peptides, functionalized nanoparticles, and advanced genomic therapies, including Clustered Regularly Interspaced Short Palindromic Repeats-associated proteins (CRISPR-Cas systems) and phage therapy. Recent advancements in these fields are critically analyzed, with a focus on their mechanisms of action, therapeutic potential, and current limitations. Emphasis is given to strategies targeting biofilm disruption and quorum sensing interference, which address key mechanisms of resistance. By synthesizing current knowledge, this work provides researchers with a comprehensive framework for developing next-generation antimicrobials, highlighting the most promising approaches for overcoming AMR through rational drug design and targeted therapies. Ultimately, this review aims to bridge the gap between experimental innovation and clinical application, providing valuable insights for developing effective and resistance-proof antimicrobial agents.

Wound healing is a dynamic process involving distinct phases that are regulated by cellular and molecular interactions. This review explores the fundamental mechanisms involved in wound healing, including the roles of cytokines and growth factors within the local microenvironment, with a particular focus on antimicrobial peptides (AMPs) as immune modulators and therapeutic agents in chronic wounds. Notably, AMPs such as LL-37 have been shown to reduce biofilm density by up to 60%, highlighting their dual role in both modulating host immune responses and combating persistent bacterial infections. It further examines emerging technologies that are transforming the field, extending beyond traditional biological mechanisms to innovations such as smart dressings, 3D bioprinting, AI-driven therapies, regenerative medicine, gene therapy, and organoid models. Additionally, the review addresses strategies to overcome bacterial biofilms and highlights promising approaches including biomaterials, nanomedicine, gene therapy, peptide-loaded nanoparticles, and the application of organoids as advanced platforms for studying and enhancing wound repair.

Background: Metastatic melanoma stands out as the most lethal form of skin cancer because of its high propensity to spread and its remarkable resistance to treatment methods. Methods: In this review article, we address the incidence of melanoma worldwide and its staging phases. We thoroughly investigate the different melanomas and their associated risk factors. In addition, we underscore the principal therapeutic goals and pharmacological methods that are currently used in the treatment of melanoma. Results: The implementation of targeted therapies has contributed to improving the approach to patients. However, because of the emergence of resistance early in treatment, overall survival and progression-free periods continue to be limited. Conclusions: We provide new insights into plant serine protease inhibitor therapeutics, supporting high-throughput drug screening soon, and seeking a complementary approach to explain crucial mechanisms associated with melanoma.

Background/Objectives: Cancer is one of the leading causes of death worldwide, and skin cancer is especially prevalent and lethal in Brazil. Despite advancements in treatment, there is still a need for new anticancer agents that are effective, selective, and less toxic. This study aimed to evaluate the cytotoxic and therapeutic potential of the peptide PEPAD. Methods: The cytotoxicity of PEPAD was assessed by MTT assay in murine melanoma (B16F10-Nex2), human melanoma (SK-MEL-28), breast (MCF-7), and cervical (HeLa) cancer cell lines. Selectivity was evaluated in healthy cells (RAW 264.7 and FN1). Morphological changes were analyzed by microscopy. Cell migration was assessed using scratch assays. Apoptotic features were evaluated using MitoTracker Deep Red, NucBlue, CaspACETM labeling, and flow cytometry. Immunogenic cell death was investigated by calreticulin and HMGB1 release. Molecular dynamics simulations explored peptide structure and interaction with lipid membranes. Results: PEPAD showed IC₅₀ values of 7.4 µM and 18 µM in B16F10-Nex2 and SK-MEL-28 cells, respectively, and >60 µM in MCF-7 and HeLa cells. Low toxicity was observed in healthy cells (IC₅₀ > 56 µM), indicating high selectivity. Apoptotic morphology and reduced cell migration were observed. Flow cytometry and fluorescence probes confirmed apoptosis and mitochondrial swelling. Calreticulin and HMGB1 release indicated immunogenic cell death. Simulations showed that PEPAD maintains a stable α-helical conformation and interacts with membranes. Conclusions: These findings highlight PEPAD’s selective cytotoxicity and its potential as an anticancer agent with apoptotic and immunogenic properties, making it a promising candidate for therapeutic development.

Cancer therapy remains limited by drug resistance and poor selectivity, while inflammation-driven tumor progression further complicates treatment outcomes. Antimicrobial peptides (AMPs) have emerged as promising therapeutic alternatives due to their multifunctional properties. In this study, we investigated the anticancer and immunomodulatory activities of KI17, a rationally designed peptide derived from GL18, a peptide fragment identified from the talisin protein of Talisia esculenta. KI17 exhibited dose-dependent antiproliferative effects against murine and human melanoma (B16F10-Nex2, SK-MEL-2, A375) and cervical cancer (HeLa) cell lines, while displaying reduced cytotoxicity toward non-tumoral BV-2 microglial cells, resulting in a favorable selectivity index. Mechanistic analyses revealed that KI17 induces morphological alterations, mitochondrial dysfunction, caspase activation, and late-stage apoptosis, together with G0/G1 cell cycle arrest accompanied by accumulation of the Sub-G0 population, indicating coordinated regulation of cell death and cell cycle progression. KI17 effectively suppressed lipopolysaccharide (LPS)-induced microglial activation, markedly reducing pro-inflammatory cytokine and nitric oxide production without compromising cell viability. These biological activities are consistent with the peptide’s optimized physicochemical features, including increased cationicity, amphipathicity, and α-helical folding. Overall, our findings demonstrate that KI17 combines selective anticancer activity with potent immunomodulatory effects, highlighting its potential as a bioinspired peptide for further preclinical development in cancer therapy.

Snake venoms are rich sources of molecules with pharmacological potential, with approximately 90% of their composition consisting of proteins and peptides responsible for their biological activities. These proteins are classified as enzymatic or non-enzymatic. Enzymatic proteins function as catalysts in regulatory chemical reactions, whereas non-enzymatic proteins, despite lacking catalytic activity, play essential roles in physiological processes. Lectins are non-enzymatic proteins of non-immune origin characterized by carbohydrate- and glycoprotein-binding domains, enabling their ability to agglutinate erythrocytes. C-type lectins and C-type lectin-like proteins are commonly found in snake venoms and are associated with hemostatic disturbances, particularly bleeding and coagulation disorders. This review provides a comprehensive analysis of studies published over the past decade on lectins isolated from snake venom, addressing their definitions, classifications, structural characteristics, and mechanisms of action, as well as their relevance in biotechnological applications. Although progress has been made in elucidating their pharmacological properties, most studies have focused on plant lectins. In contrast, research on snake venom lectins remains limited, particularly regarding their heterologous activities. This gap, especially compared to other venom-derived molecules, highlights the need to further expand research on this class of proteins.