Serum cytokines levels in patients with myocardial infarction with non-obstructive and obstructive coronary arteries

Aim. To compare the concentrations of proinflammatory and anti-inflammatory cytokines in patients with myocardial infarction with non-obstructive (MINOCA) and obstructive coronary arteries (MIOCA) in the early postinfarction period and after 1-year follow-up.Material and methods. The study included 40 patients with myocardial infarction (experimental group, 19 patients; control group, 21 patients). Three (15,7%) patients with diagnosed acute myocarditis were excluded from the final analysis. Blood samples were taken upon admission, on the 2nd, 4th and 7th days from hospitalization, and also after 1-year follow-up. Twenty-three parameters were analyzed using multiplex analysis and the Multiplex Instrument FLEXMAP 3D system (Luminex Corporation), as well as the MILLIPLEX map Human Cytokine/ Chemokine Panel II.Results. According to multiplex analysis of blood serum of the studied groups, a comparable increase in proinflammatory cytokines CCL-15, CCL-26, CCL-27 in the early postinfarction period and after 1-year follow-up, as well as antiinflammatory and regenerative cytokines CXCL-12, TPO in the early postinfarction period and after 1-year follow-up. In patients with MINOCA, higher concentrations of the following proinflammatory cytokines were determined: IL-16 upon admission (p=0,03), IL-20 on days 2 and 4 of the early postinfarction period (p=0,005 and p = 0.03), as well as CCL-15 on days 4 and 7 (p=0,05 and p=0,02). After 1-year follow-up, among the proinflammatory cytokines, a greater increase in CCL-21 (p=0,02) was noted in the patients of experimental group. Also, in patients with MINOCA, a greater increase in TPO was determined upon admission and on the 2nd day (p=0,02 and p=0,02), SCF — on the 7th day and after 1-year follow-up (p=0,04 and p=0,04), and LIF on the 4th day of early postinfarction period (p=0,007). In contrast, MIOCA patients showed a greater increase in CXCL-12 levels upon admission (p=0,04). At the same time, patients with MINOCA showed a higher level of C-reactive protein on the 1st day, as well as a higher relative monocyte count after 1-year follow-up.Conclusion. Despite a comparable increase in the cytokines CCL-8, CCL-13, CCL26, CCL-27 in patients of both groups, in patients with MINOCA there was a greater increase in proinflammatory cytokines IL-16, IL-20, CCL-15, CCL-21, and also CXCL-12, LIF, TPO, SCF, which have anti-inflammatory and regenerative activity. After 1 year follow-up, MINOCA patients showed a significant increase in CCL-21 and SCF, with a comparable increase in other proinflammatory cytokines in patients of both groups. A greater increase in proinflammatory cytokines in patients with MINOCA may indicate a more aggressive atherosclerosis course and lead to plaque destabilization followed by ischemic event.

759 Single-Cell Proteogenomics (Cite-seq) analysis of cGAS-STING pathway activation alone and in combination with nivolumab using a patient-derived 3D ex vivo tumoroid platform

BackgroundThe tumor immune microenvironment comprises a heterogeneous collection of adaptive and innate immune cells that play a critical role in immune evasion and response to immunotherapeutic agents. cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway results in activation of various immune cells promoting innate immunity in addition to senescence of cancer cells. However, the mechanisms involved in response and resistance to cGAS-STING pathway activation is not well understood. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we explored immunological heterogeneity of tumor microenvironment in colorectal cancer and analyzed transcriptional and compositional changes of the immune landscape in response to cGAS-STING pathway activation alone and in combination with a PD-1 inhibitor nivolumab.MethodsAll human tumor samples were obtained with proper patient consent and IRB approval. Fresh patient tumor tissue was processed to generate uniform sized live 3D tumoroids measuring 150 µm in size. Treatment groups included a STING agonist, ADU-S100, alone or in combination with nivolumab. Here, we applied multi-modal CITE-seq profiling using the 10X Genomics platform to interrogate cellular responses to ex vivo treatment. Culture supernatants were collected for multiplex analysis of cytokine release in media. Additionally, flow cytometry was used to assess the activation profile of resident immune cells.ResultsMultimodal analysis of transcriptomes or proteomics at the single-cell level provided an unprecedented view of cellular diversity and enabled better understanding of how activation of STING pathway alone and in combination with nivolumab affects the TME in colorectal cancer. Flow cytometric analysis of immune cell populations isolated from 3D tumoroids demonstrated treatment mediated activation of tumor resident T-cells and changes in the innate immune cells, which coincided with marked changes in pro-and anti-inflammatory cytokine profiles determined by multiplex analysis.ConclusionsThese results demonstrate that the 3D-EXplore ex vivo tumoroid model provides a unique platform to assess the efficacy of immunotherapeutic agents and to develop novel therapeutic combinations. Furthermore, implementation of this platform in the clinical studies may also allow identifying clinically relevant biomarkers to enable the most effective treatment strategies for individual patients.

Comparing phonological and orthographic networks: A multiplex analysis

The complexity of natural language can be explored by means of multiplex analyses at different scales, from single words to groups of words or sentence levels. Here, we plan to investigate a multiplex word-level network, which comprises an orthographic and a phonological network defined in terms of distance similarity. We systematically compare basic structural network properties to determine similarities and differences between them, as well as their combination in a multiplex configuration. As a natural extension of our work, we plan to evaluate the preservation of the structural network properties and information-based quantities from the following perspectives: (i) presence of similarities across 12 natural languages from 4 linguistic families (Romance, Germanic, Slavic and Uralic), (ii) increase of the size of the number of words (corpus) from 104 to 50 × 103, and (iii) robustness of the networks. Our preliminary findings reinforce the idea of common organizational properties among natural languages. Once concluded, will contribute to the characterization of similarities and differences in the orthographic and phonological perspectives of language networks at a word-level.

Fiber bundle based chemiluminescence array detection

Chemiluminescence (CL) is a dominated technology in clinical diagnosis. In order to meet increasing demand for sensitive and simultaneous detection of chemiluminescence from multiple samples, the development of multiplex analysis...