Search

The paper presents the results of metrological tests and measurements of dimensional accuracy of models manufactured using the photo-curing additive technology of POLYJET MATRIX - PJM. The material from which the samples were manufactured was a liquid polymer resin with the commercial name MED610, which is characterized by a high degree of biocompatibility, which increases the validity of the research in medical and dental applications. The key parameter considered was the location of digital CAD models in selected places of the virtual building platform and it influence of dimensional accuracy. The research results showed a clear impact of the arrangement of models on the building platform on the accuracy of the produced models, both in terms of external and internal diameters. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the pro-phagocytic phenotype of macrophages in SSc and other rheumatic diseases by examining their activation, signaling pathways, and treatment responses, with the goal of uncovering mechanisms that drive enhanced phagocytosis., Methods: Single-cell RNA sequencing (scRNA-seq) datasets (GSE138669/GSE212109) from skin and lung macrophages of healthy controls and SSc patients were analyzed. Human monocyte-derived macrophages (hMDM) were differentiated from CD14+ monocytes from healthy controls, SSc, RA, PsA, and axSpA patients. In selected experiments, hMDMs were pretreated with 0.1 μM nintedanib. Phagocytic activity was quantified using pHrodo bioparticles and flow cytometry. Macrophage surface markers were evaluated by flow cytometry, NF-κB signaling by Western blot, and gene expression by RT-qPCR., Results: Analysis of scRNA-seq datasets revealed a pro-phagocytic signature in SSc-affected organs. SSc macrophages, particularly the FCGR3A  hi cluster in skin, exhibited elevated expression of FCGR genes and enriched FcγR-mediated phagocytosis pathways, accompanied by pro-inflammatory markers. This phenotype extended to FCN1  hi lung macrophages in SSc patients with interstitial lung disease, indicating a systemic pro-inflammatory and phagocytic profile. hMDMs from SSc, RA, and PsA patients demonstrated enhanced phagocytic activity in vitro. Elevated FcγRI and FcγRII levels were identified as key drivers of increased phagocytic activity and subsequent IL-6-driven inflammation. Nintedanib showed reduction in FcγRI expression, suggesting its potential therapeutic benefit in attenuating the phagocytic process., Conclusion: This study highlights FcγR-expressing macrophages as drivers of phagocytosis and inflammatory responses in SSc. Dysregulated activation of these macrophages could lead to persistent inflammation and fibrosis in rheumatic diseases, highlighting new potential therapeutic approaches., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

The aim of this work was to investigate the possibility of doping copper sulfide Cu 2 S with selected fifth-group elements, potentially having a positive effect on the thermoelectric properties of the resulting materials. For the selected model structures, theoretical calculations and an analysis of the electronic structure and changes in the enthalpy of formation due to doping were performed using the WIEN2k package employing the Full-Potential Linearized Augmented Plane Wave (FP-LAPW) method within density functional theory (DFT) formalism. Polycrystalline materials with the nominal composition of Cu 32 S 15 X 1 ( X = P, As, Sb, Bi) were synthesized in quartz ampoules, then sintered using the spark plasma sintering (SPS) technique and "SPS melting" method. The chemical and phase compositions of the obtained sinters were studied by X-Ray diffraction (XRD) and scanning electron microscopy (SEM). Additionally, investigations of thermoelectric properties, i.e., electrical conductivity, Seebeck coefficient and thermal conductivity in the temperature range 300-920 K, were performed. The results of this study indicate that only phosphorus is successfully incorporated into the Cu₂S structure.

Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells; induced tumor regressions; and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.

Self-stigma beliefs are common among people with visible chronic skin diseases and can negatively affect their quality of life and psychosocial wellbeing. Hence, evidence-based interventions are urgently needed. The objective for this systematic review was to summarize research on available interventions and evaluate their benefits and limitations. Following PRISMA guidelines, we conducted an electronic database search of four databases (EMBASE, PsycINFO, PubMed, Web of Science). Studies were eligible if they (a) investigated interventions to reduce self-stigma in adults with chronic skin disease, (b) were original empirical articles, and (c) were written in English or German. Two independent reviewers conducted the abstract and full text screening as well as data extraction. The quality of the included studies was evaluated using the Critical Appraisal Skills Programme checklists. The initial search yielded 5811 abstracts; of which, 23 records were eligible. Studies addressed a broad range of skin conditions, and interventions ranged from social skills training, counselling and self-help to psychosocial and behavioural interventions. Overall, interventions had mostly positive effects on self-stigma and related constructs. However, the study quality was heterogeneous, and further efforts to develop, thoroughly evaluate and implement interventions tackling self-stigma in multiple skin conditions and languages are warranted.

The article presents the results of tribological research of sample models manufactured using three separate 3D printing technologies: selective laser sintering-SLS, photo-curing of liquid polymer resins-PolyJet Matrix (PJM) and fused deposition modeling-FDM. The impact of process parameters (printing direction, layer thickness, and energy density for SLS) on tribological properties was assessed through linear wear and coefficient of friction. The research was carried out to assess the possibility of using 3D printing for the quick manufacturing of casting models, which has a significant impact on shortening the time of implementation for mass production of the casting process. The research results proved the possibility of controlling the technological process in a manner allowing to produce models with controlled properties, including tribological parameters. In addition, the results for three additive technologies and different materials were compared by using the same friction parameters., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

In connection with the growing demand of the medical and medicine-related industry for materials exhibiting biocompatible properties used as part of three-dimensional (3D) printing additive technologies. The article presents research results concerning rheological and selected mechanical properties of a modern, photocurable MED610 resin, which is also used mainly in medicine, as well as dentistry. The article also shows extensive results of testing bending stress relaxation and creep, as well as the tensile strength of samples created with the PolyJet Matrix (PJM) technology. The authors used various sample types, including ones of unique shape and a hexagonal cellular structure. The analysis of the impact of element orientation on the working platform of the machine (3D printer) on the obtained test results (so-called printing direction-Pd) was also taken into account as a key technological parameter of the 3D printing process. Experimental rheological curves were matched with theoretical curves resulting from the application of a five-parameter Maxwell-Wiechert (M-W) model in the case of stress relaxation and a five-parameter Kelvin-Voigt model for creep. Very good matches were achieved, mean coefficients Chi 2  = 0.9956 for matching the five-parameter M-W model and mean coefficients R 2  = 0.9956 for matching the five-parameter M-W model and mean coefficients Chi 2  = 0.000006 and R 2  = 0.9992 enable recommending the obtained results to be used for various engineering calculations, especially computer simulations. Moreover, the use of relaxation curves can significantly increase the construction capabilities within the design process, which includes the MED610 material., Competing Interests: No competing financial interests exist., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Fibrotic changes in the myocardium and cardiac arrhythmias represent fatal complications in systemic sclerosis (SSc), however the underlying mechanisms remain elusive. Mice overexpressing transcription factor Fosl-2 (Fosl-2 tg ) represent animal model of SSc. Fosl-2 tg mice showed interstitial cardiac fibrosis, disorganized connexin-43/40 in intercalated discs and deregulated expression of genes controlling conduction system, and developed higher heart rate (HR), prolonged QT intervals, arrhythmias with prevalence of premature ventricular contractions, ventricular tachycardias, II-degree atrio-ventricular blocks and reduced HR variability. Following stimulation with isoproterenol Fosl-2 tg mice showed impaired HR response. In contrast to Fosl-2 tg , immunodeficient Rag2 -/- Fosl-2 tg mice were protected from enhanced myocardial fibrosis and ECG abnormalities. Transcriptomics analysis demonstrated that Fosl-2-overexpression was responsible for profibrotic signature of cardiac fibroblasts, whereas inflammatory component in Fosl-2 tg mice activated their fibrotic and arrhythmogenic phenotype. In human cardiac fibroblasts FOSL-2-overexpression enhanced myofibroblast signature under proinflammatory or profibrotic stimuli. These results demonstrate that under immunofibrotic conditions transcription factor Fosl-2 exaggerates myocardial fibrosis, arrhythmias and aberrant response to stress., (© 2023. The Author(s).)

This paper presents the metrological quality and mechanical properties of models in the form of hook holders manufactured from MED610 polymer material using PolyJet Matrix (PJM) technology. Measurements in the dimensional and shape analysis were made using the optical method with a microscope. The mechanical test was estimated by static tensile testing of the fabricated parts. A comprehensive approach to both the analysis of test results based on standardized samples and real hook models makes the presented results of great scientific and engineering value and creates the possibility of practical use in the medical industry, which has not been so comprehensively presented in the currently published research papers. Analyzing the results of measurements of the geometrical characteristics of the elements, it can be concluded that the PolyJet Matrix 3D printing technology has demonstrated a high level of precision in manufacturing the prototype parts. The static tensile test of samples, taking into account the printing directions, showed a high anisotropy of mechanical properties. The results of both strength and simulation tests indicate that it is necessary to assume a relatively high safety factor, the value of which depends on the direction of printing, which, in the case of such a responsible medical application, is very important.

Objective: Systemic sclerosis (SSc) is characterized by dysregulation of type I interferon (IFN) signaling. CD52 is known for its immunosuppressive functions in T cells. This study was undertaken to investigate the role of CD52 in monocyte adhesion and type I IFN signaling in patients with SSc., Methods: Transcriptome profiles of circulating CD14+ monocytes from patients with limited cutaneous SSc (lcSSc), patients with diffuse cutaneous SSc (dcSSs), and healthy controls were analyzed by RNA sequencing. Levels of CD52, CD11b/integrin αΜ, and CD18/integrin β2 in whole blood were assessed by flow cytometry. CD52 expression was analyzed in relation to disease phenotype (early, lcSSc, dcSSc) and autoantibody profiles. The impact of overexpression, knockdown, and antibody blocking of CD52 was analyzed by gene and protein expression assays and functional assays., Results: Pathway enrichment analysis indicated an increase in adhesion- and type I IFN-related genes in monocytes from SSc patients. These cells displayed up-regulated expression of CD11b/CD18, reduced expression of CD52, and enhanced adhesion to intercellular adhesion molecule 1 and endothelial cells. Changes in CD52 expression were consistent with the SSc subtypes, as well as with immunosuppressive treatments, autoantibody profiles, and monocyte adhesion properties in patients with SSc. Overexpression of CD52 led to decreased levels of CD18 and monocyte adhesion, while knockdown of CD52 increased monocyte adhesion. Experiments with the humanized anti-CD52 monoclonal antibody alemtuzumab in blood samples from healthy controls increased monocyte adhesion and CD11b/CD18 expression, and enhanced type I IFN responses. Monocytic CD52 expression was up-regulated by interleukin-4 (IL-4)/IL-13 via the STAT6 pathway, and was down-regulated by lipopolysaccharide and IFNs α, β, and γ in a JAK1 and histone deacetylase IIa (HDAC IIa)-dependent manner., Conclusion: Down-regulation of the antiadhesion CD52 antigen in CD14+ monocytes represents a novel mechanism in the pathogenesis of SSc. Targeting of the IFN-HDAC-CD52 axis in monocytes might represent a new therapeutic option for patients with early SSc., (© 2021, American College of Rheumatology.)

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by overproduction of extracellular matrix (ECM) and multiorgan fibrosis. Animal studies pointed to bone marrow-derived cells as a potential source of pathological ECM-producing cells in immunofibrotic disorders. So far, involvement of monocytes and macrophages in the fibrogenesis of SSc remains poorly understood., Methods and Results: Immunohistochemistry analysis showed accumulation of CD14 + monocytes in the collagen-rich areas, as well as increased amount of alpha smooth muscle actin (αSMA)-positive fibroblasts, CD68 + and mannose-R + macrophages in the heart and lungs of SSc patients. The full genome transcriptomics analyses of CD14 + blood monocytes revealed dysregulation in cytoskeleton rearrangement, ECM remodeling, including elevated FN1 (gene encoding fibronectin) expression and TGF-β signalling pathway in SSc patients. In addition, single cell RNA sequencing analysis of tissue-resident CD14 + pulmonary macrophages demonstrated activated profibrotic signature with the elevated FN1 expression in SSc patients with interstitial lung disease. Peripheral blood CD14 + monocytes obtained from either healthy subjects or SSc patients exposed to profibrotic treatment with profibrotic cytokines TGF-β, IL-4, IL-10, and IL-13 increased production of type I collagen, fibronectin, and αSMA. In addition, CD14 + monocytes co-cultured with dermal fibroblasts obtained from SSc patients or healthy individuals acquired a spindle shape and further enhanced production of profibrotic markers. Pharmacological blockade of the TGF-β signalling pathway with SD208 (TGF-β receptor type I inhibitor), SIS3 (Smad3 inhibitor) or (5Z)-7-oxozeaenol (TGF-β-activated kinase 1 inhibitor) ameliorated fibronectin levels and type I collagen secretion., Conclusions: Our findings identified activated profibrotic signature with elevated production of profibrotic fibronectin in CD14 + monocytes and CD14 + pulmonary macrophages in SSc and highlighted the capability of CD14 + monocytes to acquire a profibrotic phenotype. Taking together, tissue-infiltrating CD14 + monocytes/macrophages can be considered as ECM producers in SSc pathogenesis., Competing Interests: OD had consultancy relationship and/or has received research funding from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi, UCBin the area of potential treatments of scleroderma and its complications. In addition, OD has a patent mir-29 for the treatment of systemic sclerosis issued (US8247389, EP2331143). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rudnik, Hukara, Kocherova, Jordan, Schniering, Milleret, Ehrbar, Klingel, Feghali-Bostwick, Distler, Błyszczuk and Kania.)

Systemic sclerosis (SSc) is an autoimmune fibrotic disease of unknown aetiology that is characterized by vascular changes in the skin and visceral organs. Autologous haematopoietic stem cell transplantation can improve skin and organ fibrosis in patients with progressive disease and a high risk of organ failure, indicating that cells originating in the bone marrow are important contributors to the pathogenesis of SSc. Animal studies also indicate a pivotal function of myeloid cells in the development of fibrosis leading to changes in the tissue architecture and dysfunction in multiple organs such as the heart, lungs, liver and kidney. In this Review, we summarize current knowledge about the function of myeloid cells in fibrogenesis that occurs in patients with SSc. Targeted therapies currently in clinical studies for SSc might affect myeloid cell-related pathways. Therefore, myeloid cells might be used as cellular biomarkers of disease through the application of high-dimensional techniques such as mass cytometry and single-cell RNA sequencing.

WNT signaling plays an important role in fibrotic processes in the heart. Recently, exosomes have been proposed as novel extracellular transporters for WNT proteins. In this study, we analyzed whether WNT3a and WNT5a carried by exosomes could activate downstream molecular pathways in human cardiac fibroblasts. Exosomes were isolated from conditioned medium of control, WNT3a- and WNT5a-producing L cells by differential ultracentrifugations. Obtained exosomes showed size ranging between 20⁻150 nm and expressed exosomal markers ALG-2-interacting protein X (ALIX) and CD63. Treatment with WNT3a-rich exosomes inhibited activity of glycogen synthase kinase 3β (GSK3β), induced nuclear translocation of β-catenin, and activated T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcription factors as well as expression of WNT/β-catenin responsive genes in cardiac fibroblasts, but did not coactivate extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and activator protein 1 (AP-1) signaling pathways. In contrast, exosomes produced by WNT5a-producing L cells failed to activate β-catenin-dependent response, but successfully triggered phosphorylation of ERK1/2 and JNK and stimulated IL-6 production. In conclusion, exosomes containing WNT proteins can functionally contribute to cardiac fibrosis by activating profibrotic WNT pathways on cardiac fibroblasts and may represent a novel mechanism of spreading profibrotic signals in the heart.

The concept of "illness's social course" can be approached from two stand-points. We can trace both the way the social world shapes the course of an illness and the way an illness' symptoms shape the social world. The purpose of this study is to locate the specific illness of love melancholy in a specific historical and social context, namely that of France and England in the late sixteenth and early seventeenth centuries, in order to explain the intense discussion on the disorder during that period. This attempt is done with respect to the two dimensions of the concept of "illness' social course" and in the light of constructivist commentary on psychological disorders, which regards them as local stress idioms shaped by a specific social and cultural context.

Monoclonal antibodies (McAb) 2AH10, specifically reacting with protein preparations having mol. wt. of 18 and 38 kD and not interacting with brucellar lipopolysaccharide (LPS) and protein-polysaccharide antigen, have been obtained. As shown with the use of McAb 2AH10, Brucella spp. and Yersinia enterocolitica O:9 possess common antigenic determinants, localized not only in the area of their LPS, which is generally known, but also in the area of their outer cell-wall proteins with mol. wt. 18 and 38 kD. The sensitivity of the solid-phase enzyme immunoassay and the latex agglutination test with the use of McAb 2AH10 is essentially higher in the detection of B. abortus and B. suis, than B. melitensis and B. rangiferi, as well as Y. enterocolitica O:9. Essential differences observed in the detected concentrations of different Brucella species and Y. enterocolitica O:9 are seemingly linked with different expression of specific antigenic determinants, detected with the use of McAb 2AH10 in the corpuscular antigens under study.

Significant data on the dynamics of globulin production in guinea pigs in the process of immunogenesis after the injection of Francisella tularensis vaccine strain or conjugated brucellosis vaccine have been obtained by means of immunofluorescence and the enzyme immunoassay. The number of globulin-producing cells in lymphoid organs (the spleen, regional and remote lymph nodes) differs, depending on the injected antigen. The relationship between the character of immunomorphological changes in lymphoid organs and the dynamics of the increase of antibody titers in the peripheral blood of the animals after their immunization with conjugated brucellosis vaccine and the injection of avirulent F. tularensis has been established.

Female rats that had been subjected to a moderate treadmill running program were compared with sedentary animals on the basis of heart weight, selected biochemical measurements, and heart function. Exercised animals maintained normal growth rate, and cardiac hypertrophy was not present. Left ventricular RNA, DNA, and cytochrome c levels were unchanged. Heart functional measurements obtained in situ were similar in sedentary and exercised animals under control conditions. When subjected to sustained (1-3 days) aortic constriction pressure overload, exercised animals maintained or increased myocardial contractility. Contractility was depressed in sedentary animals. Both sedentary and exercised animals increased left ventricular end diastolic pressure without changing contractility during acute (1-3 min) pressure overload. However, exercised animals were able to fully regain normal cardiac output when the acute overload was relieved. Cardiac output remained approximately 10% below control in sedentary animals. The improved ability of previously exercised animals to withstand pressure overload appears to be due to alterations in adaptation rather than preliminary augmentation of metabolism or function.

The approbation of the enzyme immunoassay in the study of diverse field material (corpses of animals, ectoparasites, soil, feces of birds of prey, etc.) for the presence of Yersinia pestis contamination has shown the advantages of this assay over the existing serological tests: the passive hemagglutination test and the antigen (or antibody) neutralization test. The use of the immunoperoxidase preparation obtained on the basis of staphylococcal protein A makes it possible to detect antibodies to Y. pestis in animals of various species known to be the main carriers, as well as less important ones, in the natural foci of plague in Siberia. The enzyme immunoassay is recommended for use in the study of not only active natural foci, but also territories, dangerous with respect to plague, as well as for controlling the state of such territories after the realization of relevant sanitation measures.

Plasma of healthy persons and intact animals contains antibodies to blood coagulation factors IIa and Xa of autologous origin demonstrated by passive hemagglutination and ELISA. During fibrin formation, autoantibodies are bound and thus are not detectable in the serum. The importance of the facts described for hemostasis control is discussed.