Background: Growing body of evidence suggests that the pathogenesis of Alzheimer’s disease (AD), a progressing neurodegenerative condition, is not limited to the neuronal compartment, but also involves various immunological mechanisms. Insoluble Aβ aggregates in the brain can induce the activation of microglia, resulting in the synthesis of proinflammatory mediators, which further can stimulate astrocytic expression of YKL-40. Therefore, the aim of the current review is to present up-to-date data about the role of YKL-40 as a biomarker of AD as well as the possibility of therapeutic strategies targeting neuroinflammation.Objective/Methods: We searched PubMed articles for the terms “YKL-40”, “neurodegeneration”, “neuroinflammation” and “Alzheimer’s disease”, and included papers focusing on this review’s scope.Results:Recent studies indicate that CSF concentrations of YKL-40 were significantly higher in AD patients than in cognitively normal individuals and correlated with dementia biomarkers, such as tau proteins and amyloid beta. Determination of YKL-40 CSF concentration may be also helpful in differentiation between types of dementia and in the distinction of patients in the stable phase of MCI from those who progressed to dementia. Moreover, significantly increased levels of YKL-40 mRNA were found in AD brains in comparison with non-demented controls. Additionally, it was suggested that anti-inflammatory treatment might relief the symptoms of AD and slow its progression.Conclusion: Based on the recent knowledge, YKL-40 might be useful as a possible biomarker in the diagnosis and prognosis of AD. Modulation of risk factors and targeting of immune mechanisms, including systemic inflammation could lead to future preventive or therapeutic strategies for AD.
Alzheimer’s disease (AD) is one of the most frequent neurodegenerative diseases affecting more than 35 million people in the world, and its incidence is estimated to triple by 2050. Alzheimer’s disease is an age-related disease characterized by the progressive loss of memory and cognitive function, caused by the unstoppable neurodegeneration and brain atrophy. Current AD treatments only relieve the symptoms. The first molecular signs of the disease identified decades ago and were related to the tau neurofibrillary tangles and the β amyloid plaques. Despite the considerable progress in the diagnostic field, there is no certain knowledge of the specific biomarkers reflecting molecular mechanisms that trigger the symptoms of the disease. Therefore, there is an enormous need to find biomarkers useful for early diagnosis, before the first symptoms appear, and develop new therapeutic targets, which would guarantee improving patients’ quality of life. Researchers from all around the world are looking for biomarkers that can be identified in different biological fluids such as plasma, serum, and cerebrospinal fluid, specific for Alzheimer’s disease. In this review, we would like to resume some of the most interesting discovery in pathological mechanisms underlying Alzheimer’s disease and promising biomarkers.
Introduction. Since colorectal cancer (CRC) is the second most commonly diagnosed malignancy in Europe and third worldwide, novel biomarkers for diagnosing the disease are critically needed. Objectives. According to our knowledge, the present study is the first to evaluate the clinical usefulness of serum CXCL-8 (C-X-C motif chemokine 8) in the diagnosis and progression of CRC compared to classical tumor marker CEA (carcinoembryonic antigen) and marker of inflammation CRP (C-reactive protein). Patients and Methods. The study included 59 CRC patients and 46 healthy volunteers. Serum levels of selected proteins were measured using ELISA (enzyme-linked immunosorbent assay), CMIA (chemiluminescent microparticle immunoassay), and immunoturbidimetric methods. Results. Serum concentrations of CXCL-8, similarly to those of the classical tumor marker CEA and inflammatory state marker CRP, were significantly higher in CRC patients than in healthy controls. There were statistically significant differences in CXCL-8 concentrations between tumor stages, as established by the Kruskal–Wallis test and confirmed by the post hoc Dwass–Steele–Critchlow–Fligner test. CXCL-8 levels were also significantly elevated in CRC patients with distant metastases compared to patients in the subgroup without metastases. Diagnostic sensitivity, predictive values for negative results (NPV), and AUC (area under the Receiver Operating Characteristic Curve—ROC curve) of CXCL-8 were higher than those of CEA, while diagnostic specificity and predictive values for positive results (PPV) of CXCL-8 were higher than those of CRP. Conclusions. Our findings indicate greater utility of CXCL-8 in comparison to the classical tumor marker CEA in the diagnosis of CRC. Moreover, serum CXCL-8 might be a potential biomarker of colorectal cancer progression.
Calcium ions are crucial in the process of information transmission and integration in the central nervous system (CNS). These ions participate not only in intracellular mechanisms but also in intercellular processes. The changes in the concentration of Ca2 + ions modulate synaptic transmission, whereas neuronal activity induces calcium ion waves. Disturbed calcium homeostasis is thought to be one of the main features in the pathophysiology of Alzheimer's disease (AD), and AD pathogenesis is closely connected to Ca2 + signaling pathways. The effects of changes in neuronal Ca2 + are mediated by neuronal calcium sensor (NCS) proteins. It has been revealed that NCS proteins, with special attention to visinin-like protein 1 (VILIP-1), might have a connection to the etiology of AD. In the CNS, VILIP-1 influences the intracellular neuronal signaling pathways involved in synaptic plasticity, such as cyclic nucleotide cascades and nicotinergic signaling. This particular protein is implicated in calcium-mediated neuronal injury as well. VILIP-1 also participates in the pathological mechanisms of altered Ca2 + homeostasis, leading to neuronal loss. These findings confirm the utility of VILIP-1 as a useful biomarker of neuronal injury. Moreover, VILIP-1 plays a vital role in linking calcium-mediated neurotoxicity and AD-type pathological changes. The disruption of Ca2 + homeostasis caused by AD-type neurodegeneration may result in the damage of VILIP-1-containing neurons in the brain, leading to increased cerebrospinal fluid levels of VILIP-1. Thus, the aim of this overview is to describe the relationships of the NCS protein VILIP-1 with the pathogenetic factors of AD and neurodegenerative processes, as well as its potential clinical usefulness as a biomarker of AD. Moreover, we describe the current and probable therapeutic strategies for AD, targeting calcium-signaling pathways and VILIP-1.
Introduction Novel biomarkers are critically needed to improve the management of patients with pancreatic cancer (PC). Objectives We aimed to evaluate the clinical usefulness of serum CXCL8 in relation to its specific receptor CXCR2 in the diagnosis and prediction of PC compared with classic tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) and C-reactive protein (CRP). Patients and methods The study included 76 subjects: 42 patients with PC and 34 healthy volunteers. Serum protein levels were measured by immunological methods. Results Serum CXCL8 and CXCR2 concentrations were significantly higher in PC patients compared with healthy controls, similarly to classic tumor markers and CRP. CXCL8 levels were significantly elevated in patients with lymph node metastasis compared with individuals without nodal involvement. The diagnostic sensitivity, accuracy, negative predictive value, and areas under the receiver operating characteristic curves for CXCL8 were higher than those for CXCR2, CRP, CA 19-9, and CEA. Moreover, serum CXCL8 was the only significant predictor of PC risk. Conclusions Our findings indicate the significance of the CXCL8-CXCR2 axis in the pathogenesis of PC. Serum CXCL8 is emerging as the strongest candidate for a potential PC biomarker among all proteins tested.
Every year, almost 2 million people develop colorectal cancer (CRC), which makes it the fourth most common malignancy worldwide. It is also estimated that approximately 48% of CRC patients will die from the disease. Thus, noninvasive and accurate methods for early detection and prevention of CRC are sorely needed. It is suggested that C-X-C motif ligand 1 (CXCL1) and C-X-C motif ligand 8 (CXCL8) as well as their cognate receptors can mediate tumor growth, proliferation, survival, neoangiogenesis and metastasis of malignant cells, including CRC. However, little is known about the clinical significance of these proteins as potential biomarkers for CRC. Therefore, in our review, we performed a comprehensive literature search using the PubMed database to identify original articles that investigated whether CXCL1 and CXCL8 and their receptors play a role in CRC pathogenesis. In summary, our review highlighted the potential significance of CXCL1/CXCR2 and CXCL8/CXCR1,-2 in the diagnosis and progression of CRC as well as indicated their potential therapeutic significance. However, given the non-specific nature of analyzed chemokines and a small number of studies concerning the assessment of blood concentration of these proteins in CRC patients, investigations need to be continued in the future before selected chemokines could be established as biomarkers for CRC.
Introduction:The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. Methods:We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. Results:The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis.Discussion: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.
Our findings indicate that YKL-40 may contribute to decreased stability and increased permeability of BBB in AD patients. It is assumed that YKL-40 is implicated in the development of brain barriers, although its precise mechanism of action in the BBB disruption remains unrevealed. Further studies on larger groups of patients are required to confirm our hypothesis.
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