RESUMEN
Tuberculosis (TB) is a global threat, affecting one-quarter of the world's population. The World Health Organization (WHO) reports that 6 million people die annually due to chronic illnesses, a statistic that includes TB-related deaths. This high mortality is attributed to factors such as the emergence of drug-resistant strains and the exceptional survival mechanisms of Mycobacterium tuberculosis (MTB). Recently, microRNAs (miRNAs) have garnered attention for their crucial role in TB pathogenesis, surpassing typical small RNAs (sRNA) in their ability to alter the host's immune response. For instance, miR-155, miR-125b, and miR-29a have been identified as key players in the immune response to MTB, particularly in modulating macrophages, T cells, and cytokine production. While sRNAs are restricted to within cells, exo-miRNAs are secreted from MTB-infected macrophages. These exo-miRNAs modify the function of surrounding cells to favor the bacterium, perpetuating the infection cycle. Another significant aspect is that the expression of these miRNAs affects specific genes and pathways involved in immune functions, suggesting their potential use in diagnosing TB and as therapeutic targets. This review compiles existing information on the immunomodulatory function of exosomal miRNAs from MTB, particularly focusing on disease progression and the scientific potential of this approach compared to existing diagnostic techniques. Thus, the aim of the study is to understand the role of exosomal miRNAs in TB and to explore their potential for developing novel diagnostic and therapeutic methods.
RESUMEN
Long-term inflammatory skin disease atopic dermatitis is characterized by dry skin, itching, and eczematous lesions. During inflammation skin barrier protein impairment promotes S. aureus colonisation in the inflamed skin, worsening AD patient's clinical condition. Proteomic analysis revealed the presence of several immune evasion proteins and virulence factors in S. aureus extracellular vesicles (EVs), suggesting a possible role for these proteins in the pathophysiology of atopic dermatitis. The objective of this study is to assess the efficacy of a wall fragment obtained from a patented strain of C. acnes DSM28251 (c40) and its combination with a mucopolysaccharide carrier (HAc40) in counteract the pathogenic potential of EVs produced by S. aureus ATCC 14458. Results obtained from in vitro studies on HaCaT keratinocyte cells showed that HAc40 and c40 treatment significantly altered the size and pathogenicity of S. aureus EVs. Specifically, EVs grew larger, potentially reducing their ability to interact with the target cells and decreasing cytotoxicity. Additionally, the overexpression of the tight junctions mRNA zona occludens 1 (ZO1) and claudin 1 (CLDN1) following EVs exposure was decreased by HAc40 and c40 treatment, indicating a protective effect on the epidermal barrier's function. These findings demonstrate how Hac40 and c40 may mitigate the harmful effects of S. aureus EVs. Further investigation is needed to elucidate the exact mechanisms underlying this interaction and explore the potential clinical utility of c40 and its mucopolysaccharide carrier conjugate HAc40 in managing atopic dermatitis.
RESUMEN
The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance.