MODERN DATA ABOUT THE MECHANISMS OF IMMUNE DYSFUNCTION IN CASE OF INJURY OF THE INTERIOR PART OF THE EYEBALL

AbstractA remarkable family of discrete sets which has recently attracted the attention of the discrete geometry community is the family of convex polyominoes, that are the discrete counterpart of Euclidean convex sets, and combine the constraints of convexity and connectedness. In this paper we study the problem of their reconstruction from orthogonal projections, relying on the approach defined by Barcucci et al. (Theor Comput Sci 155(2):321–347, 1996). In particular, during the reconstruction process it may be necessary to expand a convex subset of the interior part of the polyomino, say the polyomino kernel, by adding points at specific positions of its contour, without losing its convexity. To reach this goal we consider convexity in terms of certain combinatorial properties of the boundary word encoding the polyomino. So, we first show some conditions that allow us to extend the kernel maintaining the convexity. Then, we provide examples where the addition of one or two points causes a loss of convexity, which can be restored by adding other points, whose number and positions cannot be determined a priori.

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High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19

Therapeutic Advances in Infectious Disease ◽

10.1177/20499361211034065 ◽

2021 ◽

Vol 8 ◽

pp. 204993612110340

Author(s):

Malgorzata Karawajczyk ◽

Lena Douhan Håkansson ◽

Miklos Lipcsey ◽

Michael Hultström ◽

Karlis Pauksens ◽

...

Keyword(s):

Adhesion Molecules ◽

Mean Fluorescence Intensity ◽

Immune Dysfunction ◽

Severe Form ◽

Receptor Expression ◽

Future Research ◽

Early Biomarkers ◽

Severe Stage ◽

Activated Neutrophils ◽

Edta Blood

Background and Aims: The pronounced neutrophilia observed in patients with coronavirus disease 2019 (COVID-19) infections suggests a role for these leukocytes in the pathology of the disease. Monocyte and neutrophil expression of CD64 and CD11b have been reported as early biomarkers to detect infections. The aim of this study was to study the expression of receptors for IgG (CD64) and adhesion molecules (CD11b, CD15s, CD65, CD162, CD66b) on neutrophils and monocytes in patients with severe COVID-19 after admission to an intensive care unit (ICU). Methods: The expression of receptors was analyzed using flow cytometry. EDTA blood from 23 patients with confirmed COVID-19 infection was sampled within 48 h of admission to the ICU. Leukocytes were labeled with antibodies to CD11b, CD15s, CD65s, CD162, CD64, and CD66b. Expression of receptors was reported as mean fluorescence intensity (MFI) or the percentage of cells expressing receptors. Results: Results are presented as comparison of COVID-19 patients with the healthy group and the receptor expression as MFI. Neutrophil receptors CD64 (2.5 versus 0.5) and CD66b (44.5 versus 34) were increased and CD15 decreased (21.6 versus 28.3) when CD65 (6.6 versus 4.4), CD162 (21.3 versus 21.1) and CD11b (10.5 versus 12) were in the same range. Monocytes receptors CD64 (30.5 versus 16.6), CD11b (18.7 versus 9.8), and CD162 (38.6 versus 36.5) were increased and CD15 decreased (10.3 versus 17.9); CD65 were in the same range (2.3 versus 1.96). Conclusion: Monocytes and neutrophils are activated during severe COVID-19 infection as shown by strong upregulation of CD64. High monocyte and neutrophil CD64 can be an indicator of a severe form of COVID19. The adhesion molecules (CD11b, CD162, CD65, and CD15) are not upregulated on otherwise activated neutrophils, which might lead to relative impairment of tissue migration. Low adhesion profile of neutrophils suggests immune dysfunction of neutrophils. Monocytes maintain upregulation of some adhesion molecules (CD11b, CD162) suggesting the persistence of an increased ability to migrate into tissues, even during a severe stage of COVID-19. Future research should focus on CD64 and CD11b kinetics in the context of prognosis.

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A Review of Repurposed Cancer Drugs in Clinical Trials for Potential Treatment of COVID-19

Pharmaceutics ◽

10.3390/pharmaceutics13060815 ◽

2021 ◽

Vol 13 (6) ◽

pp. 815

Author(s):

Bárbara Costa ◽

Nuno Vale

Keyword(s):

Clinical Trials ◽

Anticancer Drugs ◽

Clinical Management ◽

Scientific Discovery ◽

Immune Dysfunction ◽

Potential Treatment ◽

Medical Treatments ◽

Prevention And Treatment ◽

Rapid Pace ◽

Effective Drugs

The pandemic of the coronavirus disease 2019 (COVID-19) represents an unprecedented challenge to identify effective drugs for prevention and treatment. While the world’s attention is focused on news of COVID-19 vaccine updates, clinical management still requires improvement. Due to the similarity of cancer-induced inflammation, immune dysfunction, and coagulopathy to COVID-19, anticancer drugs, such as Interferon, Pembrolizumab or Bicalutamide, are already being tested in clinical trials for repurposing, alone or in combination. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected, clinicians need effective medical treatments for this infection.

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Cell subtypes and immune dysfunction in peritoneal fluid of endometriosis revealed by single-cell RNA-sequencing

Cell & Bioscience ◽

10.1186/s13578-021-00613-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Gen Zou ◽

Jianzhang Wang ◽

Xinxin Xu ◽

Ping Xu ◽

Libo Zhu ◽

...

Keyword(s):

Dendritic Cells ◽

Single Cell ◽

Natural Killer ◽

Rna Sequencing ◽

Peritoneal Cavity ◽

Immune Cells ◽

Peritoneal Fluid ◽

Control Sample ◽

Immune Dysfunction ◽

Single Cell Rna Sequencing

Abstract Background Endometriosis is a refractory and recurrent disease and it affects nearly 10% of reproductive-aged women and 40% of infertile patients. The commonly accepted theory for endometriosis is retrograde menstruation where endometrial tissues invade into peritoneal cavity and fail to be cleared due to immune dysfunction. Therefore, the comprehensive understanding of immunologic microenvironment of peritoneal cavity deserves further investigation for the previous studies mainly focus on one or several immune cells. Results High-quality transcriptomes were from peritoneal fluid samples of patients with endometriosis and control, and firstly subjected to 10 × genomics single-cell RNA-sequencing. We acquired the single-cell transcriptomes of 10,280 cells from endometriosis sample and 7250 cells from control sample with an average of approximately 63,000 reads per cell. A comprehensive map of overall cells in peritoneal fluid was first exhibited. We unveiled the heterogeneity of immune cells and discovered new cell subtypes including T cell receptor positive (TCR+) macrophages, proliferating macrophages and natural killer dendritic cells in peritoneal fluid, which was further verified by double immunofluorescence staining and flow cytometry. Pseudo-time analysis showed that the response of macrophages to the menstrual debris might follow the certain differentiation trajectory after endometrial tissues invaded into the peritoneal cavity, that is, from antigen presentation to pro-inflammation, then to chemotaxis and phagocytosis. Our analyses also mirrored the dysfunctions of immune cells including decreased phagocytosis and cytotoxic activity and elevated pro-inflammatory and chemotactic effects in endometriosis. Conclusion TCR+ macrophages, proliferating macrophages and natural killer dendritic cells are firstly reported in human peritoneal fluid. Our results also revealed that immune dysfunction happens in peritoneal fluid of endometriosis, which may be responsible for the residues of invaded menstrual debris. It provided a large-scale and high-dimensional characterization of peritoneal microenvironment and offered a useful resource for future development of immunotherapy.

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Immunosenescence: potential causes and strategies for reversal

Biochemical Society Transactions ◽

10.1042/bst0280250 ◽

2000 ◽

Vol 28 (2) ◽

pp. 250-254 ◽

Cited By ~ 33

Author(s):

R. Aspinall ◽

D. Andrew

Keyword(s):

T Cell ◽

Immune Dysfunction ◽

Careful Analysis ◽

Experimental Therapy ◽

Thymic Involution ◽

Interleukin 7 ◽

Cell Pool ◽

Age Related ◽

Peripheral T Cells ◽

Laboratory Investigations

Age-related deterioration in immune function has been recognized in many species. In humans the clinical manifestation of such immune dysfunction is age-related increases in the susceptibility to certain infections and in the incidence of some autoimmune disease and certain cancers. Laboratory investigations reveal age-related changes in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signalling function and in replicative ability following stimulus with antigen, mitogens or anti-CD3 antibody. These changes in the properties of peripheral T cells are thought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymic microenvironment linked to a reduction in the level of available interleukin 7. Treatment with interleukin 7 leads to a reversal of thymic atrophy with increased thymopoiesis. This provides the potential to reverse the immune dysfunction seen in the peripheral T cell pool by replacing old cells with new output generated in the thymus. Problems to overcome in order for such an experimental therapy to be successful require careful analysis in order to provide an optimal strategy to ensure that new T cell emigrants from the thymus have a broad range of specificities and are able to enter the peripheral T cell pool.

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