Myeloid CD169/Siglec1: An immunoregulatory biomarker in viral disease.

CD169, also known as Siglec1 or Sialoadhesin (Sn), is a surface adhesion molecule on human myeloid cells. Being part of the Siglec family, it acts as a receptor for sialylated molecular structures, which are found among various pathogenic and non-pathogenic ligands. Recent data suggest that CD169 may represent a promising new biomarker in acute respiratory and non-respiratory viral infections, such as SARS-CoV-2, Respiratory syncytial virus (RSV) and Human immunodeficiency virus (HIV). Therein lies a great potential to sufficiently differentiate viral from bacterial infection, which has been an incessant challenge in the clinical management of infectious disease. CD169 equips myeloid cells with functions, reaching far beyond pathogen elimination. In fact, CD169 seems to crosslink innate and adaptive immunity by antigen presentation and consecutive pathogen elimination, embodying a substantial pillar of immunoregulation. Yet, our knowledge about the kinetics, mechanisms of induction, signaling pathways and its precise role in host-pathogen interaction remains largely obscure. In this review, we describe the role of CD169 as a potentially novel diagnostic biomarker for respiratory viral infection by evaluating its strengths and weaknesses and considering host factors that are involved in pathogenesis of virus infection. Finally, this brief review aims to point out shortcomings of available evidence, thus, guiding future work revolving the topic.

Pregnancy in patients with multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disorder that affects ~2.5 million people globally. Women of reproductive age are highly susceptible to this disease. This study aims to explore the association between MS and pregnancy. Articles related to the topic under investigation were identified; the search terms included "pregnancy", "multiple sclerosis", "MS", and "women". Only articles published between 2010 and 2020 were included in the review. This review shows that researchers have attempted to explore the link between pregnancy and MS, and the results from previous studies indicate that pregnancy reduces the risk of MS relapse. However, evidence suggesting that pregnancy can affect the long-term progression of MS is lacking. The research results also indicate that MS does not increase the risk of maternal and fetal complications. MS remains a serious autoimmune disorder that affects many women worldwide. The data gathered during this review indicate that a significant correlation exists between pregnancy and MS relapse rates. The findings presented in this review can aid in the management of MS during pregnancy. Furthermore, these research results provide vital insights that caregivers can use to monitor patients with MS during pregnancy.

Neuronal Antibodies and Associated Syndromes.

INTRODUCTION: Multiple well-recognized conditions, such as Lambert-Eaton myasthenic syndrome (LEMS) and myasthenia gravis (MG), have been associated with neuronal antibodies. MATERIALS AND METHODS: A search was performed using Embase, PubMed, and CINAHL. An initial search of each database was conducted using keywords and terms related to the aim of the current review. Additional articles were obtained by examining the reference lists and citations in the selected records. RESULTS: The studies identified through the search process used different designs and methods to explore neuronal antibodies and associated syndromes. Previous studies have shown that neurological and psychiatric disorders can be mediated and influenced by various antibodies. The identification of autoantibodies can help with the accurate diagnosis of conditions and commencement of early treatment. DISCUSSION: A review of selected studies identified in the literature implicated that classic anti-neuronal antibodies, such as anti-Ri and anti-Hu, play a role in the development of neurological diseases. More recent studies have indicated that other novel antibodies act on neuronal cell surface antigens to contribute to the development of neurological disorders. CONCLUSION: Existing research provides evidence revealing a spectrum of antibodies linked to the development and progression of neurological diseases. However, further antibody testing and studies should be performed to validate the relationship between conditions and antibodies.

Impact of B cells to the pathophysiology of multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a chronic autoimmune disorder that affects the central nervous system and compromises the health and well-being of millions of people worldwide. B cells have been linked to MS and its progression. This review aimed to determine the role of B cells in MS development. METHODS: Articles used in this review were obtained from PubMed, LILACS, and EBSCO. The search terms and phrases included "multiple sclerosis," "MS," "B-Cells," "pathogenesis," and "development." Original research studies and articles on MS and B cells published between 2007 and 2018 were included. RESULTS: Results from the selected articles showed a significant connection between B cell groups and MS. B cells act as a significant source of plasma cells, which generate antibodies while also regulating autoimmune processes and T cell production. In addition, B cells regulate the release of molecules that affect the proinflammatory actions of other immune cells. DISCUSSION: B cells play key roles in immune system functioning and MS. The findings of this review illustrate the complex nature of B cell actions, their effects on the autoimmune system, and the method by which they contribute to MS pathogenesis. CONCLUSION: Previous research implicates biological, genetic, and environmental factors in MS pathogenesis. This review suggests that B cells contribute to MS development and advancement by influencing and regulating autoimmune processes such as T cell production and APC activity.

Gut-brain axis biochemical signalling from the gastrointestinal tract to the central nervous system: gut dysbiosis and altered brain function.

BACKGROUND: The gut-brain axis facilitates a critical bidirectional link and communication between the brain and the gut. Recent studies have highlighted the significance of interactions in the gut-brain axis, with a particular focus on intestinal functions, the nervous system and the brain. Furthermore, researchers have examined the effects of the gut microbiome on mental health and psychiatric well-being.The present study reviewed published evidence to explore the concept of the gut-brain axis. AIMS: This systematic review investigated the relationship between human brain function and the gut-brain axis. METHODS: To achieve these objectives, peer-reviewed articles on the gut-brain axis were identified in various electronic databases, including PubMed, MEDLINE, CIHAHL, Web of Science and PsycINFO. RESULTS: Data obtained from previous studies showed that the gut-brain axis links various peripheral intestinal functions to brain centres through a broad range of processes and pathways, such as endocrine signalling and immune system activation. Researchers have found that the vagus nerve drives bidirectional communication between the various systems in the gut-brain axis. In humans, the signals are transmitted from the liminal environment to the central nervous system. CONCLUSIONS: The communication that occurs in the gut-brain axis can alter brain function and trigger various psychiatric conditions, such as schizophrenia and depression. Thus, elucidation of the gut-brain axis is critical for the management of certain psychiatric and mental disorders.

The H3K4 methyltransferase Setd1b is essential for hematopoietic stem and progenitor cell homeostasis in mice.

Hematopoietic stem cells require MLL1, which is one of six Set1/Trithorax-type histone 3 lysine 4 (H3K4) methyltransferases in mammals and clinically the most important leukemia gene. Here, we add to emerging evidence that all six H3K4 methyltransferases play essential roles in the hematopoietic system by showing that conditional mutagenesis of Setd1b in adult mice provoked aberrant homeostasis of hematopoietic stem and progenitor cells (HSPCs). Using both ubiquitous and hematopoietic-specific deletion strategies, the loss of Setd1b resulted in peripheral thrombo- and lymphocytopenia, multilineage dysplasia, myeloid-biased extramedullary hematopoiesis in the spleen, and lethality. By transplantation experiments and expression profiling, we determined that Setd1b is autonomously required in the hematopoietic lineages where it regulates key lineage specification components, including Cebpa, Gata1, and Klf1. Altogether, these data imply that the Set1/Trithorax-type epigenetic machinery sustains different aspects of hematopoiesis and constitutes a second framework additional to the transcription factor hierarchy of hematopoietic homeostasis.

Activation of CD4 and CD8 T cell receptors and regulatory T cells in response to human proteins.

This study assessed in detail the influence of four different human proteins on the activation of CD4+ and CD8+ T lymphocytes and on the formation of regulatory T cells. Human whole-blood samples were incubated with four different human proteins. The effects of these proteins on the downstream immune-system response, on the expression of extracellular activation markers on and intracellular cytokines in T lymphocytes, and on the number of regulatory T cells (T-reg cells) were investigated via flow cytometry. Incubation with ß-actin or glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which are cytoplasmic proteins, increased the expression of both extracellular activation markers (CD69 and HLA-DR) and intracellular cytokines but did not significantly affect the number of T-reg cells. In contrast, incubation with human albumin or insulin, which are serum proteins, reduced both extracellular activation markers and intracellular cytokine expression and subsequently increased the number of T-reg cells. These findings may help to explain the etiological basis of autoimmune diseases.

Multiple Sclerosis and Schizophrenia.

The psychiatric and neurological aspects of health may present methodological challenges in the diagnosis and treatment of disease. This is especially true for patients whose symptoms indicate the coexistence of multiple sclerosis (MS) and schizophrenia (SCZ). These cases raise critical questions regarding the relationship between the mind and the brain. Studies have noted that patients with MS have an increased risk of developing SCZ or bipolar disorder (BD). It is suggested here that MS and a subgroup of SCZ have similar etiologies. Factors such as gender, ethnicity, geography and season also have an influence on the occurrence of MS and SCZ. This paper aims to examine the differences and similarities between SCZ and MS. For this purpose, scientific papers examining various factors associated with these disorders were reviewed, and similarities and differences in genetic, immunological, seasonal, geographical, and gender-related risk factors and limited similarities in ethnic factors between the two diseases were identified. The findings suggest that subgroups of these two diseases may belong to the same class of disorders.

The impact of uric acid on long-term mortality in patients with asymptomatic carotid atherosclerotic disease.

BACKGROUND: Serum uric acid (SUA) has been discussed to be related to cardiovascular (CV) disease and outcome. We investigated whether levels of SUA predict long-term mortality in neurologically asymptomatic patients with carotid atherosclerotic disease. METHODS: We prospectively studied 959 consecutive patients with carotid atherosclerosis as evaluated by duplex Doppler sonography for all-cause and CV death, respectively. RESULTS: During a median follow-up time of 6.3 years (interquartile range [IQR], 5.4-7.1 years), 246 deaths (25.7%), including 160 CV deaths (16.7%), were recorded. Median baseline SUA levels were 5.9 mg/dL (IQR, 5.0-7.0 mg/dL). SUA was significantly associated with all-cause death and CV death. Adjusted hazard ratios (HRs) for an increase of 1 mg/dL of SUA levels were 1.12 (95% confidence interval [CI], 1.04-1.21; P = .003) and 1.20 (95% CI, 1.11-1.30; P < .001) for all-cause and CV death, respectively. Quartiles of SUA levels showed a significant association with CV mortality (log-rank P = .002). For CV death, adjusted HRs for quartiles of increasing SUA levels were 1.45 (95% CI, .87-2.43), 1.44 (95% CI, .85-2.46), and 2.26 (95% CI, 1.36-3.76; P < .01), compared with the lowest quartile, respectively. Patients with baseline carotid stenosis of more than 50% and/or increased levels of SUA (≥median) had an approximately 2-fold increase in risk of (CV) death, compared with patients with carotid narrowing of less than 50% and/or SUA levels less than the median (P < .001). CONCLUSIONS: Levels of SUA represent independent predictors for CV mortality in a cohort of patients with asymptomatic carotid atherosclerosis.

Technology and new fluorescence flow cytometry parameters in hematological analyzers.

BACKGROUND: Modern hematological analyzers offer a series of new tests in addition to the differential blood cell count. Here, we provide a short overview of the technique and the new tests included in the hematological analyzers manufactured by the company Sysmex (Kobe, Japan). As introduced here, the resulting new extended blood cell count allows for the quantification of DNA- and RNA-rich, activated and/or precursor leukocyte subpopulations. METHODS: To compare the different methods of blood cell counting, repetitive cell counting is carried out by hematological experts using microscopy and using the XE-5000 hematological analyzer. RESULTS: The hematological analyzer delivers more-accurate results with respect to normal cells but microscopy is suited better to recognize and count pathological cells. CONCLUSION: With the new hematological analyzers, several new hematological tests are made available as screening tools that were not possible previously using standard cell-counting procedures.

Novel parameters of extended complete blood cell count under fluorescence flow cytometry in patients with sepsis.

BACKGROUND: We first describe a patient who developed urosepsis from an ordinary urinary tract infection. In this case, the new hematological parameters of immature leukocytes, that is, the high-fluorescence lymphocyte cell (HFLC) and immature granulocyte (IG) counts peaked early, whereas the established infection parameters, that is, C-reactive protein (CRP) and total white blood cell count showed less dynamic regarding infection and therapy. METHODS: To investigate this phenomenon in greater detail, the novel parameters HFLC and IG counts are investigated retrospectively in a cohort of 38 patients who were admitted to the anesthesia intensive care unit. Three groups of patients have been analyzed and compared: patients without signs of infection, patients with limited infections, and patients with sepsis. Data were collected with a Sysmex XE-5000 hematological analyzer. RESULTS: In patients (n = 22) without any signs of infection, both values are very low. In patients with limited local infections (n = 10), moderate elevations of the IG and HFLC counts are seen. In patients with sepsis (n = 6), the IG and HFLC counts are significantly higher. CONCLUSION: The total IG count seems to be useful for distinguishing a septic patient from a nonseptic (P < 0.004). Hematological parameters have the advantage of being measured easily during routine blood cell analysis.

Deregulated expression of urokinase and its inhibitor type 1 in prostate cancer cells: role of epigenetic mechanisms.

Plasminogen activator inhibitor-1 (PAI-1) and urokinase-type plasminogen activator (uPA) play a crucial role in cancer progression. In the present study we examined the regulation of PAI-1 and uPA expressions in normal prostate epithelial cells (PrEC) and the prostate cancer cell lines LNCaP, DU-145, and PC-3. The antigen and mRNA levels of PAI-1 were down-regulated in cancer cells, especially in LNCaP and DU-145. In the presence of proinflammatory cytokines, an increase of PAI-1 mRNA levels was observed in PrEC, LNCaP and PC-3, but not in DU-145 cells. Treatment with demethylating agent, 5-aza-2'-deoxycytidine increased the level of PAI-1 transcript in DU-145 cells and restored the inducing effect of cytokines on PAI-1 expression. An aberrant methylation of PAI-1 promoter in DU-145 and LNCaP cells was shown by methylation-sensitive high resolution melting (MS-HRM) analysis. PAI-1 methylation was also significantly increased in tumor samples (23.2±1.7%) in comparison to adjacent non-tumor tissue (6.0±0.8%). Furthermore, the expression of uPA was increased in high invasive cell lines DU-145 and PC-3 in comparison to PrEC and low invasive LNCaP cells. MS-HRM analysis revealed aberrant methylation of uPA promoter in LNCaP cells, but not in PrEC, DU-145 and PC-3 cells, as well as in normal and prostate cancer tissue samples. In conclusion, the study shows that PAI-1 and uPA expressions were changed in opposite directions in high invasive prostate cancer cell lines resulting in a strong decrease of PAI-1/uPA ratio, which may indicate a shift towards proteolytic activities. Methylation of the PAI-1 gene is suggested as one of the molecular mechanisms involved in the cancer-associated down-regulation of the PAI-1 expression.

Sequence variability and sequence evolution: an explanation of molecular polymorphisms and why many molecular structures can be preserved although they are not predominant.

The existence of many processes that regulate RNA expression poses a challenge to the idea that the cell is the culmination of a highly efficient interplay of individual proteins, each with specific, highly specialized functions. It will be demonstrated here the extent to which the cell may undergo evolutionary processes that also occur in the macrocosmos, specifically with reference to the rules of mutation and preservation. These molecular evolutionary processes could facilitate a better understanding of the development of molecular structures and the functioning of the cell and could give an explanation of the molecular polymorphisms and also explain why many molecular structures can be preserved although they are not predominant.

Measurement of T cell activation after 16-hr in vitro stimulation with concanavalin A.

A flow cytometry assay that can be used to directly determine the proportion of activated T lymphocytes in human whole blood samples after stimulation with concanavalin A is presented here. Human whole blood is incubated with fluorescently labeled antibodies (against CD3, CD4, CD8, and CD69), erythrocytes are then lysed, and the samples are analyzed using a flow cytometer. The assay presented is able to differentiate between CD4+ and CD8+ T lymphocytes. Thus, it is possible to quantify both lymphocyte populations in parallel, as well as the respective proportions of activated T lymphocytes, all from one sample. An additional advantage of this assay is that it was developed to assay whole blood, thereby reducing the likelihood of introducing pre-analytic error and facilitating the calculation of quantitative ratios. Thus, the method can be used for both in vitro and ex vivo experiments.

Protective autoimmunity and protein localization.

The influence of the immune system was originally thought to be harmful regarding injuries and infarctions of the brain. Recently, there has been increasing evidence for the protective, positive effects of cells of the immune system on brain tissue. From an evolutionary biology standpoint, this hypothesis is more compelling than viewing the immune system only as a harmful influence. Herein we emphasize how physiological activation of immune cells following tissue damage and/or by infarcts of brain tissue can lead to an activation of T-lymphocytes. These activated T-lymphocytes are then regarded to perform several protective effects.

In vitro model for the activation of CD4 and CD8 T cell receptors.

Previously, most models that sought to explain the misregulation of immune cell function assumed molecular similarities between the disease-causing pathogens and the host's proteins. In recent time several different models have been proposed and in this study, these concepts are compared to a new hypothesis proposing another explanation for this immune dysregulation: the possibility that the mislocalization of proteins may be responsible for autoimmune activity. Based on this hypothesis, proteins are recognized as self or non-self depending on where they appear in sufficiently high concentrations. To examine this new idea, the intracellular human proteins beta-actin, GAPDH, and hemoglobin as well as the extracellular human proteins insulin and albumin, were added to human whole blood samples. After an incubation period, the activation of whole-blood T lymphocytes in the samples was measured. The observed activation pattern of the T lymphocytes fit well with the proposed hypothesis. Therefore, these data suggest that protein mislocalization and/or errors within protein trafficking might be important in the development of autoimmune diseases.

Error calculation for the PSA quotient.

OBJECTIVE: Prostate specific antigen (PSA) assays have significant measurement errors, but the error associated with the PSA quotient (free to total PSA) often remains unknown. METHODS: We used both Gaussian error calculation and measurement of imprecision to investigate the level of error associated with the PSA quotient. RESULTS: Surprisingly, we found that the error of the PSA quotient at low levels is markedly smaller than that of the total PSA value. CONCLUSIONS: The PSA quotient should be calculated and considered as a clinically relevant value.