Peripheral Blood Mononuclear Cell-Related Biomarkers in Schizophrenia.

INTRODUCTION: Schizophrenia is a severe mental illness causing significant impairment in personal, family, social, educational, occupational, and other important areas of life. While there is no widely accepted endophenotype, peripheral blood cells may serve as an accessible model of intracellular changes in schizophrenia. METHODS: We reviewed the literature on the query "peripheral blood mononuclear cells AND schizophrenia" in Medline (Pubmed), selecting studies that searched for specific biomarkers of schizophrenia. We considered both diagnostic biomarkers and biomarkers of therapeutic response, specific schizophrenia disorders or differential diagnostic biomarkers. RESULTS: We retrieved 41 articles matching the search criteria, among which were studies that considered changes in the production of pro-inflammatory and anti-inflammatory markers, proteins, receptors, enzyme activity, and gene expression as potential biomarkers. CONCLUSION: Approaches analysing a biological axis or a group of related biomarkers may hold the greatest promise for identifying schizophrenia. In addition, pharmacological status, smoking status, inflammatory markers and glucose metabolites, the presence of comorbidities should be considered. Certain biomarkers, while not specific for the diagnosis of schizophrenia, may indicate the prognosis and effectiveness of treatment in the established diagnosis.

A pilot study to assess the performance of a rapid ultrasound particle agglutination method for the detection of HIV antibodies.

Anti-HIV antibody screening and confirmatory tests include rapid diagnostics tests (RDT), which have limited sensitivity, and high-sensitivity ELISA and western blot tests, which are laborious and require technical proficiency. Thus, there is an unmet need for novel rapid, simple, and highly sensitive tests. A pilot study was conducted to assess the performance of a recently developed ultrasound particle agglutination (UPA) method for high-sensitivity HIV antibody detection using 51 confirmed positive and 310 presumably negative plasma samples, and 6 commercially available anti-HIV-1 seroconversion panels (total 56 members). Optimal cutoff value of the UPA method was determined by receiver operating characteristics (ROC) analysis, providing clinical sensitivity and specificity of 100% and 98.1%, respectively. The performance characteristics of UPA, compared with those of some established RDT's and ELISA tests using HIV seroconversion panels, showed 2 days earlier HIV antibody detection than other RDT's and 2nd-generation ELISA, and at approximately the same time as 3rd-generation ELISA. The preliminary analysis of the UPA method performance characteristics showed that it meets the minimum requirements of the WHO guidelines for RDTs as first-line assays. This pilot study paves the way for more detailed validation studies of the UPA method for HIV antibody detection in clinical practice.

3D Bioprinting of Hyaline Articular Cartilage: Biopolymers, Hydrogels, and Bioinks.

The musculoskeletal system, consisting of bones and cartilage of various types, muscles, ligaments, and tendons, is the basis of the human body. However, many pathological conditions caused by aging, lifestyle, disease, or trauma can damage its elements and lead to severe disfunction and significant worsening in the quality of life. Due to its structure and function, articular (hyaline) cartilage is the most susceptible to damage. Articular cartilage is a non-vascular tissue with constrained self-regeneration capabilities. Additionally, treatment methods, which have proven efficacy in stopping its degradation and promoting regeneration, still do not exist. Conservative treatment and physical therapy only relieve the symptoms associated with cartilage destruction, and traditional surgical interventions to repair defects or endoprosthetics are not without serious drawbacks. Thus, articular cartilage damage remains an urgent and actual problem requiring the development of new treatment approaches. The emergence of biofabrication technologies, including three-dimensional (3D) bioprinting, at the end of the 20th century, allowed reconstructive interventions to get a second wind. Three-dimensional bioprinting creates volume constraints that mimic the structure and function of natural tissue due to the combinations of biomaterials, living cells, and signal molecules to create. In our case-hyaline cartilage. Several approaches to articular cartilage biofabrication have been developed to date, including the promising technology of 3D bioprinting. This review represents the main achievements of such research direction and describes the technological processes and the necessary biomaterials, cell cultures, and signal molecules. Special attention is given to the basic materials for 3D bioprinting-hydrogels and bioinks, as well as the biopolymers underlying the indicated products.

Rheumatoid Arthritis: Applicability of Ready-to-Use Human Cartilaginous Cells for Screening of Compounds with TNF-Alpha Inhibitory Activity.

In the context of modern drug discovery, there is an obvious advantage to designing phenotypic bioassays based on human disease-relevant cells that express disease-relevant markers. The specific aim of the study was to develop a convenient and reliable method for screening compounds with Tumor Necrosis Factor-alpha (TNF-α) inhibitory activity. This assay was developed using cryopreserved ready-to-use cartilage-derived cells isolated from juvenile donors diagnosed with polydactyly. It has been demonstrated that all donor (10 donors) cells were able to respond to TNF-α treatment by increased secretion of pro-inflammatory cytokine IL-6 into subcultural medium. Inhibition of TNF-α using commercially available TNF-α inhibitor etanercept resulted in a dose-dependent decrease in IL-6 production which was measured by Enzyme-Linked Immunosorbent Assay (ELISA). TNF-α dependent IL-6 production was detected in the cells after both their prolonged cultivation in vitro (≥20 passages) and cryopreservation. This phenotypic bioassay based on ready-to-use primary human cells was developed for detection of novel TNF-α inhibitory compounds and profiling of biosimilar drugs.

A rapid ultrasound particle agglutination method for HIV antibody detection: Comparison with conventional rapid HIV tests.

We present the results of the feasibility and preliminary studies on analytical performance of a rapid test for detection of human immunodeficiency virus (HIV) antibodies in human serum or plasma that is an important advance in detecting HIV infection. Current methods for rapid testing of antibodies against HIV are qualitative and exhibit poor sensitivity (limit of detection). In this paper, we describe an ultrasound particle agglutination (UPA) method that leads to a significant increase of the sensitivity of conventional latex agglutination tests for HIV antibody detection in human serum or plasma. The UPA method is based on the use of: 1) a dual mode ultrasound, wherein a first single-frequency mode is used to accelerate the latex agglutination process, and then a second swept-frequency mode of sonication is used to disintegrate non-specifically bound aggregates; and 2) a numerical assessment of results of the agglutination process. The numerical assessment is carried out by optical detection and analysis of moving patterns in the resonator cell during the swept-frequency mode. The single-step UPA method is rapid and more sensitive than the three commercial rapid HIV test kits analyzed in the study: analytical sensitivity of the new UPA method was found to be 510-, 115-, and 80-fold higher than that for Capillus™, Multispot™ and Uni-Gold™ Recombigen HIV antibody rapid test kits, respectively. The newly developed UPA method opens up additional possibilities for detection of a number of clinically significant markers in point-of-care settings.

Protein self-organization patterns in dried serum reveal changes in B-cell disorders.

BACKGROUND: Detection of serum monoclonal proteins is a common laboratory analysis used in the evaluation of patients with B-cell disorders. Since many individuals with elevated immunoglobulin have no symptoms, it is important to have simple methods for initial screening of patients with suspected B-cell disorders. METHODS: Samples of serum from healthy donors and from patients with elevated immunoglobulin levels were tested using a technology named Droplet MicroChromatography (DMC). DMC was developed at Artann Laboratories (West Trenton, New Jersey, USA) for the rapid assessment of changes in the composition of serum. DMC is based on the dynamics of the sediment pattern formation during drying of a fluid microdroplet. RESULTS: Results of this pilot study confirm the hypothesis that the pattern formation created by drying droplets of serum would differ between normal samples and those containing monoclonal proteins. Reproducible differences in the patterns formed by the two types of specimens are shown. Strong correlation between abnormally elevated levels of immunoglobulins in the serum of myeloma patients and the patterns formed by drying droplets of serum indicates that the DMC technique may be suitable for semi-quantitative analysis of serum samples. We also demonstrate that computer identification of the drying droplet structure and dynamics is a tractable issue. CONCLUSIONS: DMC has significant diagnostic potential and can serve as a basis for development of a simple, rapid, and inexpensive method for initial screening of patients suspected of having multiple myeloma and other pathologies of lymphoid origin that are associated with the overproduction of monoclonal immunoglobulins. The DMC test requires only approximately 1 microL of serum and could therefore be performed in any facility where it is safe to work with serum.