Fibroblasts are among the most abundant cell types in the human body, playing crucial roles in numerous physiological processes, including the structural maintenance of the dermis, production of extracellular matrix components, and mediation of inflammatory responses. Despite their importance, fibroblasts remain one of the least characterized cell populations. The advent of single-cell analysis techniques, particularly single-cell RNA sequencing (scRNA-seq) and fluorescence-activated cell sorting (FACS), has enabled detailed investigations into fibroblast biology. In this study, we present an extensive analysis of fibroblast surface markers suitable for cell sorting and subsequent functional studies. We reviewed over three thousand research articles describing fibroblast populations and their markers, characterizing and comparing subtypes based on their surface markers, as well as their intra- and extracellular proteins. Our detailed analysis identified a variety of distinct fibroblast subpopulations, each with unique markers, characteristics dependent on their location, and the physiological or pathophysiological environment. These findings underscore the diversity of fibroblasts as a cellular population and could lead to the development of novel diagnostic and therapeutic tools.

Diverse chemical and pharmacological strategies are currently being explored to minimize the unwanted side effects of currently used opioid analgesics while achieving effective pain relief. The use of multitarget ligands with activity at more than one receptor represents a promising therapeutic approach. We recently reported a bifunctional peptide-based hybrid LENART01 combining dermorphin and ranatensin pharmacophores, which displays activity to the mu-opioid receptor (MOR) and dopamine D2 receptor (D2R) in rat brains and spinal cords. In this study, we investigated the in vitro binding and functional activities to the human MOR and the in vivo pharmacology of LENART01 in mice after subcutaneous administration. In vitro binding assays showed LENART01 to bind and be selective to the human MOR over the other opioid receptor subtypes and delta, kappa and nociceptin receptors. In the [³⁵S]GTPγS binding assay, LENART01 acted as a potent and full agonist to the human MOR. In mice, LENART01 produced dose-dependent antinociceptive effects in formalin-induced inflammatory pain, with increased potency than morphine. Antinociceptive effects were reversed by naloxone, indicating MOR activation in vivo. Behavioral studies also demonstrated LENART01’s properties to induce less adverse effects without locomotor dysfunction and withdrawal syndrome compared to conventional opioid analgesics, such as morphine. LENART01 is the first peptide-based MOR-D2R ligand known to date and the first dual MOR-dopamine D2R ligand for which in vivo pharmacology is reported with antinociceptive efficacy and reduced opioid-related side effects. Our current findings may pave the way to new pain therapeutics with limited side effects in acute and chronic use.

Neuroinfections caused by herpesviruses, mainly by HHV-1, represent a significant problem for modern medicine due to the small number of therapeutic substances available in the pharmaceutical sector. Furthermore, HHV-1 infection has been linked to neurodegenerative processes such as Alzheimer’s disease, which justifies the search for new effective therapies. The development of nanotechnology opens up new possibilities for the treatment of neuroinflammation. Gold and silver nanoparticles are gaining popularity, and the number of clinical trials involving metallic nanoparticles is constantly increasing. This paper reviews the research on gold and silver nanoparticles and their potential use in the treatment of herpesvirus neuroinfection.

Hashimoto’s thyroiditis (HT) is a chronic autoimmune thyroid disease in which natural product-derived compounds may influence both immune-mediated injury and thyroid-specific physiology. This critical narrative review integrated molecular, cellular, animal, and human evidence using a dual-axis framework: H1, covering anti-inflammatory, immunomodulatory, antioxidant, and cytoprotective effects; and H2, covering direct effects on thyroid peroxidase, sodium–iodide symporter activity, thyroglobulin, thyroid-specific gene expression, and hormone synthesis. PubMed/MEDLINE, Scopus, and Web of Science searches identified 687 records; after deduplication, 356 unique publications were screened and 79 were retained for final synthesis. Human evidence was limited to three independent HT trials evaluating curcumin, Nigella sativa, and genistein. These studies reported preliminary immunological and/or biochemical thyroid-function signals, including changes in thyroid autoantibodies, inflammatory markers, TSH, or thyroid hormones. Reductions in TPOAb or TgAb are surrogate immunological outcomes and should not be interpreted as evidence of disease modification. None of the available trials established preservation of thyroid functional reserve, prevention or delay of hypothyroidism, reduced levothyroxine requirements, or improvement in patient-important outcomes. Preclinical studies supported biological plausibility but also identified direct thyroid modulation whose clinical relevance depends on exposure and context. Natural products should currently be regarded as investigational adjuncts rather than established disease-modifying therapies.