NLRP3 Inflammasome as a Potentially New Therapeutic Target of Mesenchymal Stem Cells and Their Exosomes in the Treatment of Inflammatory Eye Diseases.

Due to their potent immunoregulatory and angio-modulatory properties, mesenchymal stem cells (MSCs) and their exosomes (MSC-Exos) have emerged as potential game-changers in regenerative ophthalmology, particularly for the personalized treatment of inflammatory diseases. MSCs suppress detrimental immune responses in the eyes and alleviate ongoing inflammation in ocular tissues by modulating the phenotype and function of all immune cells that play pathogenic roles in the development and progression of inflammatory eye diseases. MSC-Exos, due to their nano-sized dimension and lipid envelope, easily bypass all barriers in the eyes and deliver MSC-sourced bioactive compounds directly to target cells. Although MSCs and their exosomes offer a novel approach to treating immune cell-driven eye diseases, further research is needed to optimize their therapeutic efficacy. A significant number of experimental studies is currently focused on the delineation of intracellular targets, which crucially contribute to the immunosuppressive and anti-inflammatory effects of MSCs and MSC-Exos. The activation of NLRP3 inflammasome induces programmed cell death of epithelial cells, induces the generation of inflammatory phenotypes in eye-infiltrated immune cells, and enhances the expression of adhesion molecules on ECs facilitating the recruitment of circulating leukocytes in injured and inflamed eyes. In this review article, we summarize current knowledge about signaling pathways that are responsible for NLRP3 inflammasome-driven intraocular inflammation and we emphasize molecular mechanisms that regulate MSC-based modulation of NLRP3-driven signaling in eye-infiltrated immune cells, providing evidence that NLRP3 inflammasome should be considered a potentially new therapeutic target for MSCs and MSC-Exo-based treatment of inflammatory eye diseases.

New software for collecting data from the organized cervical cancer screening program in Serbia. Are we on the threshold of a new screening registry? - A multicentric study.

PURPOSE: The purpose of this study was to present the Screening Registry and the results of organized cervical cancer screening program (OCCSP) in the Republic of Serbia using a database made as an output model, linked with the Screening Registry. METHODS: Data were respectively collected over a onemonth period from 3 state primary health care centers (and related hospitals/clinical center) in central Serbia in which OCCSP was conducted. The sample consisted of women of the target population (25 to 64 years old) who responded the call for Pap test. RESULTS: The most frequent abnormal cytological diagnosis was in the 38-50 years age group, and consisted of atypical squamous cells of undetermined significance - ASCUS (7.5%) and low grade squamous intraepithelial lesions - L-SIL (7.3%). The most frequent abnormal colposcopic finding in the youngest age group of women (25-37 years) was iodine negative epithelium (35.7%) and in the group of women aged 38-50 and 51-64 years acid-white epithelium. The most common histopathological diagnosis was L-SIL. Positive predictive value of colposcopy in relation to the Pap test was 0.64 (95% CI=0.56-0.70). Interrater agreement (between cytotechnicians and supervisors) measured by the Cohen's coefficient was 0.94 (95% CI=0.91 to 0.97), but between cytology (supervisors) and pathology findings it was 0.83 (95% CI = 0.67 to 0.99). CONCLUSION: The existence of a screening registry contributes to a better epidemiological surveillance of a screening program, and to a possibility for development of various epidemiological researches.