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1.
Platelet extracellular vesicles in COVID-19: Potential markers and makers.
Puhm, F, Flamand, L, Boilard, E
Journal of leukocyte biology. 2022;(1):63-74
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Abstract
Platelets and platelet extracellular vesicles (pEV) are at the crossroads of coagulation and immunity. Extracellular vesicles are messengers that not only transmit signals between cells, but also provide information about the status of their cell of origin. Thus, pEVs have potential as both biomarkers of platelet activation and contributors to pathology. Coronavirus Disease-19 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a complex disease affecting multiple organs and is characterized by a high degree of inflammation and risk of thrombosis in some patients. In this review, we introduce pEVs as valuable biomarkers in disease with a special focus on their potential as predictors of and contributors to COVID-19.
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State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer's disease.
Hampel, H, Shaw, LM, Aisen, P, Chen, C, LleĆ³, A, Iwatsubo, T, Iwata, A, Yamada, M, Ikeuchi, T, Jia, J, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022;(1):159-177
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Abstract
Recent advances in developing disease-modifying therapies (DMT) for Alzheimer's disease (AD), and the recognition that AD pathophysiology emerges decades before clinical symptoms, necessitate a paradigm shift of health-care systems toward biomarker-guided early detection, diagnosis, and therapeutic decision-making. Appropriate incorporation of cerebrospinal fluid biomarker analysis in clinical practice is an essential step toward system readiness for accommodating the demand of AD diagnosis and proper use of DMTs-once they become available. However, the use of lumbar puncture (LP) in individuals with suspected neurodegenerative diseases such as AD is inconsistent, and the perception of its utility and safety differs considerably among medical specialties as well as among regions and countries. This review describes the state-of-the-art evidence concerning the safety profile of LP in older adults, discusses the risk factors for LP-associated adverse events, and provides recommendations and an outlook for optimized use and global implementation of LP in individuals with suspected AD.
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Disease Prognostic Biomarkers in Inflammatory Bowel Diseases-A Reality Check.
Zilbauer, M, Heuschkel, R
Journal of Crohn's & colitis. 2022;(1):162-165
Abstract
Inflammatory bowel diseases [IBD] such as Crohn's disease [CD] and ulcerative colitis [UC] are complex conditions presenting with a wide range of phenotypes. Given major variation in disease severity and outcomes as well as response to existing therapies, a personalised treatment approach stands the chance of improving the overall disease outcome as well as minimising potentially harmful side effects. However, disease activity or distribution at the point of diagnosis are poor predictors of future disease outcome. Hence, the urgent need to develop biomarkers that could either predict the overall disease course [i.e., disease prognostic biomarkers] or the response to individual therapies [i.e., disease predictive biomarkers]. Despite the widely accepted need for such biomarkers to improve the management of IBD patients, their development has proven to be challenging for a number of reasons. Based on our own experience in this field, we perform a reality check on existing evidence, discuss main challenges, and outline future perspectives.
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Status of biomarkers for the identification of stable or vulnerable plaques in atherosclerosis.
Lubrano, V, Balzan, S
Clinical science (London, England : 1979). 2021;(16):1981-1997
Abstract
Atherosclerosis is a systemic inflammation of the arteries characterized by atherosclerotic plaque due to the accumulation of lipids, inflammatory cells, apoptotic cells, calcium and extracellular matrix (ECM) proteins. Stable plaques present a chronic inflammatory infiltration, whereas vulnerable plaques present an 'active' inflammation involved in the thinning of the fibrous cap that predisposes to plaque rupture. Several complex biological cellular processes lead plaques to evolve from stable to vulnerable predisposing them to rupture and thrombosis. In this review, we analyze some emerging circulating biomarkers related to inflammation, ECM and lipid infiltration, angiogenesis, metalloproteinases and microRNA (miRNA), as possible diagnostic and prognostic indicators of plaque vulnerability.
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Diagnostic potential and future directions of matrix metalloproteinases as biomarkers in gingival crevicular fluid of oral and systemic diseases.
Zhang, F, Liu, E, Radaic, A, Yu, X, Yang, S, Yu, C, Xiao, S, Ye, C
International journal of biological macromolecules. 2021;:180-196
Abstract
Gingival crevicular fluid (GCF) is a physiological fluid and an inflammatory serum exudate derived from the gingival plexus of blood vessels and mixed with host tissues and subgingival plaque flows. In addition to proteins, GCF contains a diverse population of cells, including desquamated epithelial cells, cytokines, electrolytes, and bacteria from adjacent plaques. Recently, matrix metalloproteinases(MMPs), which are endopeptidases that are active against extracellular macromolecules, in GCF have been revealed as potential utility biomarkers for the diagnosis and follow-up of oral and systemic diseases, thereby facilitating the early evaluation of malignancy risk and the monitoring of disease progression and treatment response. Tissue inhibitors of metalloproteinases (TIMPs) are specific inhibitors of matrixins that participate in the regulation of local activities of MMPs in tissues. This review provides an overview of the latest findings on the diagnostic and prognostic values of MMPs and TIMPs in GCF of oral and systemic diseases, including periodontal disease, pulpitis, peri-implantitis and cardiovascular disease as well as the extraction, detection and analytical methods for GCF.
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Salivary Biomarkers of Oxidative Stress and Inflammation in Stroke Patients: From Basic Research to Clinical Practice.
Maciejczyk, M, Bielas, M, Zalewska, A, Gerreth, K
Oxidative medicine and cellular longevity. 2021;:5545330
Abstract
Cerebral stroke is a serious worldwide health problem, as can be seen by the global epidemic of the disease. In this disorder, when the blood flow is compromised by ruptures or blocked arteries, sudden death of neurons is observed as a result of a lack of oxygen and nutrients. Numerous severe problems and frequent complications also exist in stroke patients; therefore, there is an urgent need to develop new therapeutic, diagnostic, and prognostic methods for the disease. At present, the diagnosis of stroke is based on a neurological examination, medical history, and neuroimaging, due to the fact that rapid and noninvasive diagnostic tests are unavailable. Nevertheless, oxidative stress and inflammation are considered key factors in stroke pathogenesis. Oxygen free radicals are responsible for oxidation of lipids, proteins, and DNA/RNA, which in turn contributes to oxidative damage of the brain. Toxic products of the oxidation reactions act cytostatically on the cell by damaging cell membranes and leading to neuronal death by apoptosis or necrosis. Thus, it seems that redox/inflammatory biomarkers might be used in the diagnosis of the disease. Nowadays, saliva is of increasing interest in clinical laboratory medicine. Redox biomarkers could be obtained easily, noninvasively, cheaply, and stress-free from saliva. This minireview is aimed at presenting the current knowledge concerning the use of salivary biomarkers of oxidative stress and inflammation in the diagnosis and prognosis of stroke.
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CGMS and Glycemic Variability, Relevance in Clinical Research to Evaluate Interventions in T2D, a Literature Review.
Breyton, AE, Lambert-Porcheron, S, Laville, M, Vinoy, S, Nazare, JA
Frontiers in endocrinology. 2021;:666008
Abstract
Glycemic variability (GV) appears today as an integral component of glucose homeostasis for the management of type 2 diabetes (T2D). This review aims at investigating the use and relevance of GV parameters in interventional and observational studies for glucose control management in T2D. It will first focus on the relationships between GV parameters measured by continuous glucose monitoring system (CGMS) and glycemic control and T2D-associated complications markers. The second part will be dedicated to the analysis of GV parameters from CGMS as outcomes in interventional studies (pharmacological, nutritional, physical activity) aimed at improving glycemic control in patients with T2D. From 243 articles first identified, 63 articles were included (27 for the first part and 38 for the second part). For both analyses, the majority of the identified studies were pharmacological. Lifestyle studies (including nutritional and physical activity-based studies, N-AP) were poorly represented. Concerning the relationships of GV parameters with those for glycemic control and T2D related-complications, the standard deviation (SD), the coefficient of variation (CV), the mean blood glucose (MBG), and the mean amplitude of the glycemic excursions (MAGEs) were the most studied, showing strong relationships, in particular with HbA1c. Regarding the use and relevance of GV as an outcome in interventional studies, in pharmacological ones, SD, MAGE, MBG, and time in range (TIR) were the GV parameters used as main criteria in most studies, showing significant improvement after intervention, in parallel or not with glycemic control parameters' (HbA1c, FBG, and PPBG) improvement. In N-AP studies, the same results were observed for SD, MAGE, and TIR. Despite the small number of N-AP studies addressing both GV and glycemic control parameters compared to pharmacological ones, N-AP studies have shown promising results on GV parameters and would require more in-depth work. Evaluating CGMS-GV parameters as outcomes in interventional studies may provide a more integrative dimension of glucose control than the standard postprandial follow-up. GV appears to be a key component of T2D dysglycemia, and some parameters such as MAGE, SD, or TIR could be used routinely in addition to classical markers of glycemic control such as HbA1c, fasting, or postprandial glycemia.
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Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing. A Review.
Alehagen, U, Opstad, TB, Alexander, J, Larsson, A, Aaseth, J
Biomolecules. 2021;(10)
Abstract
Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1-3), glutathione peroxidases (GPX1-4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.a., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1-4 and TXNRD1-3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress. In this review, we highlight the role of adequate Se status for human ageing and prevention of age-related diseases, and further its proposed role in preservation of telomere length in middle-aged and elderly individuals.
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The Evolving Landscape of Biomarkers in Celiac Disease: Leading the Way to Clinical Development.
Smithson, G, Siegelman, J, Oki, T, Maxwell, JR, Leffler, DA
Frontiers in immunology. 2021;:665756
Abstract
Celiac disease is a common immune-mediated disease characterized by abnormal T-cell responses to gluten. For many patients, symptoms and intestinal damage can be controlled by a gluten-free diet, but, for some, this approach is not enough, and celiac disease progresses, with serious medical consequences. Multiple therapies are now under development, increasing the need for biomarkers that allow identification of specific patient populations and monitoring of therapeutic activity and durability. The advantage of identifying biomarkers in celiac disease is that the underlying pathways driving disease are well characterized and the histological, cellular, and serological changes with gluten response have been defined in gluten challenge studies. However, there is room for improvement. Biomarkers that measure histological changes require duodenal biopsies and are invasive. Less invasive peripheral blood cell and cytokine biomarkers are transient and dependent upon gluten challenge. Here, we discuss established biomarkers and new approaches for biomarkers that may overcome current limitations.
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A Scoping Review on Lipocalin-2 and Its Role in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma.
Krizanac, M, Mass Sanchez, PB, Weiskirchen, R, Asimakopoulos, A
International journal of molecular sciences. 2021;(6)
Abstract
Excess calorie intake and a sedentary lifestyle have made non-alcoholic fatty liver disease (NAFLD) one of the fastest growing forms of liver disease of the modern world. It is characterized by abnormal accumulation of fat in the liver and can range from simple steatosis and non-alcoholic steatohepatitis (NASH) to cirrhosis as well as development of hepatocellular carcinoma (HCC). Biopsy is the golden standard for the diagnosis and differentiation of all NAFLD stages, but its invasiveness poses a risk for patients, which is why new, non-invasive ways of diagnostics ought to be discovered. Lipocalin-2 (LCN2), which is a part of the lipocalin transport protein family, is a protein formally known for its role in iron transport and in inflammatory response. However, in recent years, its implication in the pathogenesis of NAFLD has become apparent. LCN2 shows significant upregulation in several benign and malignant liver diseases, making it a good candidate for the NAFLD biomarker or even a therapeutic target. What makes LCN2 more interesting to study is the fact that it is overexpressed in HCC development induced by chronic NASH, which is one of the primary causes of cancer-related deaths. However, to this day, neither its role as a biomarker for NAFLD nor the molecular mechanisms of its implication in NAFLD pathogenesis have been completely elucidated. This review aims to gather and closely dissect the current knowledge about, sometimes conflicting, evidence on LCN2 as a biomarker for NAFLD, its involvement in NAFLD, and NAFLD-HCC related pathogenesis, while comparing it to the findings in similar pathologies.