Endometriosis is a common gynecological disease defined by the presence of endometrial-like tissue outside the uterus, most frequently on the pelvic viscera and ovaries, which is associated with pelvic pains and infertility. It is an inflammatory disorder with some features of autoimmunity. It is accepted that ectopic endometriotic tissue originates from endometrial cells exfoliated during menstruation and disseminating into the peritoneum by retrograde menstrual blood flow. It is assumed that the survival of endometriotic cells in the peritoneal cavity may be partially due to their abrogated elimination by natural killer (NK) cells. The decrease of NK cell cytotoxic activity in endometriosis is associated with an increased expression of some inhibitory NK cell receptors. It may be also related to the expression of human leukocyte antigen G (HLA-G), a ligand for inhibitory leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) receptors. The downregulated cytotoxic activity of NK cells may be due to inhibitory cytokines present in the peritoneal milieu of patients with endometriosis. The role of NK cell receptors and their ligands in endometriosis is also confirmed by genetic association studies. Thus, endometriosis may be a subject of immunotherapy by blocking NK cell negative control checkpoints including inhibitory NK cell receptors. Immunotherapies with genetically modified NK cells also cannot be excluded.
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.
ABCA4 gene mutations are the cause of a spectrum of ABCA4 retinopathies, and the most common juvenile macular degeneration is called Stargardt disease. ABCA4 has previously been observed almost exclusively in the retina. Therefore, studying the functional consequences of ABCA4 variants has required advanced molecular analysis techniques. The aim of the present study was to evaluate whether human hair follicles may be used for molecular analysis of the ABCA4 gene splice-site variants in patients with ABCA4 retinopathies. We assessed ABCA4 expression in hair follicles and skin at mRNA and protein levels by means of real-time PCR and Western blot analyses, respectively. We performed cDNA sequencing to reveal the presence of full-length ABCA4 transcripts and analyzed ABCA4 transcripts from three patients with Stargardt disease carrying different splice-site ABCA4 variants: c.5312+1G>A, c.5312+2T>G and c.5836-3C>A. cDNA analysis revealed that c.5312+1G>A, c.5312+2T>G variants led to the skipping of exon 37, and the c.5836-3C>A variant resulted in the insertion of 30 nucleotides into the transcript. Our results strongly argue for the use of hair follicles as a model for the molecular analysis of the pathogenicity of ABCA4 variants in patients with ABCA4 retinopathies.
Despite the progress in early diagnostic and available treatments, pancreatic cancer remains one of the deadliest cancers. Therefore, there is an urgent need for novel anticancer agents with a good safety profile, particularly in terms of possible side-effects. Recently dopaminergic receptors have been widely studied as they were proven to play an important role in cancer progression. Although various synthetic compounds are known for their interactions with the dopaminergic system, peptides have recently made a great comeback. This is because peptides are relatively safe, easy to correct in terms of the improvement of their physicochemical and biological properties, and easy to predict. This paper aims to evaluate the anticancer activity of a naturally existing peptide—ranatensin, toward three different pancreatic cancer cell lines. Additionally, since there is no sufficient information confirming the exact character of the interaction between ranatensin and dopaminergic receptors, we provide, for the first time, binding properties of the compound to such receptors.
Advancements in single-cell analyzis technologies, particularly single-cell RNA sequencing (scRNA-seq) and Fluorescence-Activated Cell Sorting (FACS), have enabled the analyzis of cellular diversity by providing resolutions that were not available previously. These methods enable the simultaneous analyzis of thousands of individual transcriptomes, facilitating the classification of cells into distinct subpopulations, based on transcriptomic differences, adding a new level of complexity to biomolecular and medical research. Fibroblasts, despite being one of the most abundant cell types in the human body and forming the structural backbone of tissues and organs, remained poorly characterized for a long time. This is largely due to the high morphological similarity between different types of fibroblasts and the lack of specific markers to identify distinct subpopulations. Once thought to be cells responsible solely for the synthesis of extracellular matrix (ECM) components, fibroblasts are now recognized as active participants in diverse physiological processes, including inflammation and antimicrobial responses. However, defining the molecular profile of fibroblast subpopulations remains a significant challenge. In this comprehensive review, which is based on over two thousand research articles, we focus on the identification and characterization of fibroblast subpopulations and their specific surface markers, with an emphasis on their potential as molecular targets for selective cell isolation. By analyzing surface markers, alongside intra- and extracellular protein profiles, we identified multiple fibroblast subtypes within the female reproductive system. These subtypes exhibit distinct molecular signatures and functional attributes, shaped by their anatomical localization and the surrounding physiological or pathological conditions. Our findings underscore the heterogeneity of fibroblasts and their diverse roles in various biological contexts. This improved understanding of fibroblast subpopulations paves the way for innovative diagnostic and therapeutic strategies, offering the potential for precision targeting of specific fibroblast subsets in clinical applications.