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Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies.

A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, rece

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… Chitotriosidase was found to be the human analogue of chitinases from lower organisms (Rao et al. 2005 ). The enzyme hydrolyzes chitin, the natural polymer of beta-1,4 N-acetylglucosamine, is a member of the large chitinase protein family created by gene duplications (Bussink et al. 2007 ). … Besides chitotriosidase, the chitinase protein family includes one other active enzyme—AMCase (Boot et al. 2001 )—and several inactive lectins (Bussink et al. 2007 ; Renkema et al. 1998 ). …

Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus.

OBJECTIVES: Scrub typhus is endemic in the Asia-Pacific region. Mortality is high even with treatment, and further knowledge of the immune response during this infection is needed. This study was aimed at comparing plasma levels of monocyte/macrophage and endothelial related inflammatory markers in patients and controls in South India and to explore a possible correlation to disease severity and clinical outcome. METHODS: Plasma levels of ALCAM, VCAM-1, sCD163, sCD14, YKL-40 and MIF were measured in scrub typhus patients (n = 129), healthy controls (n = 31) and in infectious disease controls

YKL-40-gene polymorphism affects acute cellular rejection and fibrosis progression after transplantation for hepatitis C virus-induced liver disease.

BACKGROUND AND AIM: The development of end-stage graft disease is suspected to be partially determined by an individual genetic background. The aim of our study was to determine the prevalence of YKL-40-gene polymorphism in hepatitis C virus (HCV)-positive patients and its impact on the incidence of acute cellular rejection (ACR), graft fibrosis and antiviral treatment response. METHODS: A total of 149 patients, who underwent liver transplantation for HCV-induced liver disease, were genotyped for YKL-40 (rs4950928; G/C) by TaqMan Genotyping Assay. The results were correlated with 616 post-tra

Биомаркеры сыворотки и цереброспиновой жидкости в качестве предсказателей когнитивного расстройства при множественном склерозе: систематический обзор продольных исследований.

Множественный склероз (MS) — хроническое аутоиммунное заболевание центральной нервной системы, характеризующееся воспалением, обезвоживанием, глиозом и нейронной потерей. Когнитивные расстройства являются частью клинического представления, а также на ранних стадиях с коэффициентом распространенности: 40 в адрес 65% и тесно связаны с низким качеством жизни. В последние годы достижения в области молекулярных биомаркеров способствовали повышению точности когнитивной диагностики и выявлению объектов, подверженных риску развития когнитивных расстройств. Сосредоточив внимание на продольных исследова

[Pathological changes and macrophage polarization in the liver and spleen of mice infected with Angiostrongylus cantonensis].

OBJECTIVE: To investigate the temporal changes in pathological damage and macrophage polarization in liver and spleen tissues of mice infected with Angiostrongylus cantonensis, and to preliminarily unravel the peripheral immune responses during the early stage of A. cantonensis infection. METHODS: Forty female BALB/c mice at ages of 6 to 8 weeks were randomly divided into four groups, including the control group and 7-, 14-, and 21-day infection groups, with 10 mice in each group. Each mouse in the infection groups was inoculated with 30 third-stage (L3) larvae of A. cantonensis by oral gavag

A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure.

OBJECTIVE: To investigate whether the Multi-Biomarker Disease Activity (MBDA) score predicts optimal add-on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX-IRs). METHODS: We analyzed data from 157 MTX-IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28-ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who were randomized to receive triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) versus MTX plus infliximab. The MBDA score as a predictor of the subsequent DAS28-based response to each se

Флюидные биомаркеры в демиелионирующих синдромах: прошлое, настоящее и перспективы.

По-прежнему продолжается работа над диагностическим алгоритмом демиелионирующих расстройств центральной нервной системы, а также поиск идеальных биомаркеров. Так называемый "идеальный" биомаркер должен обеспечивать точное различие между наиболее распространенными демиелионирующими патологиями ЦНС и подтипами одной и той же патологии (например, переход от релапсирующего многоразового склероза к вторичному прогрессивному фенотипу). Достижения в области технологии способствовали проведению этого исследования, и в нижеследующих разделах мы всесторонне проанализируем большинство из них, охарактериз

Pretreatment multi-biomarker disease activity score and radiographic progression in early RA: results from the SWEFOT trial.

OBJECTIVES: Prediction of radiographic progression (RP) in early rheumatoid arthritis (eRA) would be very useful for optimal choice among available therapies. We evaluated a multi-biomarker disease activity (MBDA) score, based on 12 serum biomarkers as a baseline predictor for 1-year RP in eRA. METHODS: Baseline disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), disease activity score based on C-reactive protein (DAS28-CRP), CRP, MBDA scores and DAS28-ESR at 3 months were analysed for 235 patients with eRA from the Swedish Farmacotherapy (SWEFOT) clinical trial. RP wa

Нынешние проблемы, связанные со вторичным прогрессивным множественным склерозом: диагностика, выявление активности и лечение.

Примерно 50% диагностировали повторное склерозное склерозное излучение (RRMS), переходя к вторичному прогрессивному множественным склерозу (SPMS) в течение 20 лет после возникновения болезни. Однако ранняя диагностика СМПС и эффективное лечение по-прежнему являются важными клиническими проблемами. Отсутствие установленных диагностических критериев часто приводит к задержкам с определением СМПС. Кроме того, для прогрессивных форм MS имеется ограниченный доступ к методам лечения, позволяющим сглаживать заболевания (DMT), и эти методы требуют подтверждения активности заболеваний, которая должна б

Targeting large middle molecules: Clinical implications of expanded hemodialysis in hemodialysis care.

End-stage kidney disease (ESKD) presents a major clinical burden, with maintenance hemodialysis (HD) patients facing high cardiovascular mortality and impaired quality of life (QoL). Despite advances from low-flux to high-flux HD and the introduction of hemodiafiltration (HDF), clearance of large middle molecules (LMMs >25 kDa) remains inadequate. These molecules contribute to inflammation, oxidative stress, atherogenesis, and mineral-bone disorders, all of which worsen patient outcomes. Expanded hemodialysis (HDx), utilizing medium cutoff membranes, represents a novel approach that combines d

Clonal ZEB1-Driven Mesenchymal Transition Promotes Targetable Oncologic Antiangiogenic Therapy Resistance.

Glioblastoma (GBM) responses to bevacizumab are invariably transient with acquired resistance. We profiled paired patient specimens and bevacizumab-resistant xenograft models pre- and post-resistance toward the primary goal of identifying regulators whose targeting could prolong the therapeutic window, and the secondary goal of identifying biomarkers of therapeutic window closure. Bevacizumab-resistant patient specimens and xenografts exhibited decreased vessel density and increased hypoxia versus pre-resistance, suggesting that resistance occurs despite effective therapeutic devascularization

Glycoprotein Non-Metastatic Protein B: An Emerging Biomarker for Lysosomal Dysfunction in Macrophages.

Several diseases are caused by inherited defects in lysosomes, the so-called lysosomal storage disorders (LSDs). In some of these LSDs, tissue macrophages transform into prominent storage cells, as is the case in Gaucher disease. Here, macrophages become the characteristic Gaucher cells filled with lysosomes laden with glucosylceramide, because of their impaired enzymatic degradation. Biomarkers of Gaucher cells were actively searched, particularly after the development of costly therapies based on enzyme supplementation and substrate reduction. Proteins selectively expressed by storage macrop

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… Implications for specific inhibitor design and function of mammalian chitinase-like lectins. J. Biol. Chem. 2002;277:25537–25544. doi: 10.1074/jbc.M201636200. 71. Boven L.A., van Meurs M., Boot R.G., Mehta A., Boon L., Aerts J.M., Laman J.D. … The Biology of the Gaucher Cell: The Cradle of Human Chitinases. Int. Rev. Cytol. 2006;252:71–128. doi: 10.1016/S0074-7696(06)52001-7. 74. Bussink A.P., Speijer D., Aerts J.M.F.G., Boot R.G. Evolution of mammalian chitinase(-like) members of family 18 glycosyl hydrolases. …

[Dynamics of eosinophil infiltration and microglia activation in brain tissues of mice infected with Angiostrongylus cantonensis].

OBJECTIVE: To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. METHODS: Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control gr

Нейродегенеративные биомаркеры при множественном склерозе: на стыке между исследованиями и клинической практикой.

Множественный склероз (MS) — хроническое аутоиммунное расстройство, характеризующееся воспалением, обезвоживанием и нейродегенерацией в центральной нервной системе (CNS). Хотя подстрекательские компоненты MS были тщательно изучены, прогрессивный нейродегенеративный аспект по-прежнему является одним из важнейших факторов, способствующих долгосрочной инвалидности. Поэтому выявление и проверка биомаркеров, связанных с нейродегенеративными процессами, имеют важнейшее значение для улучшения диагностики, прогнозирования и мониторинга лечения. В рамках этого обзора изучаются цереброспинные жидкости (

Ixazomib Improves Bone Remodeling and Counteracts sonic Hedgehog signaling Inhibition Mediated by Myeloma Cells.

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of plasma cells (PC) in the bone marrow (BM), leading to bone loss and BM failure. Osteolytic bone disease is a common manifestation observed in MM patients and represents the most severe cause of morbidity, leading to progressive skeletal damage and disabilities. Pathogenetic mechanisms of MM bone disease are closely linked to PCs and osteoclast (OCs) hyperactivity, coupled with defective osteoblasts (OBs) function that is unable to counteract bone resorption. The aim of the present study was to investigate t

Biomaterials from the sea: Future building blocks for biomedical applications.

Marine resources have tremendous potential for developing high-value biomaterials. The last decade has seen an increasing number of biomaterials that originate from marine organisms. This field is rapidly evolving. Marine biomaterials experience several periods of discovery and development ranging from coralline bone graft to polysaccharide-based biomaterials. The latter are represented by chitin and chitosan, marine-derived collagen, and composites of different organisms of marine origin. The diversity of marine natural products, their properties and applications are discussed thoroughly in t

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… 158 ] [ 159 ] Alkaline protease | marine Psychrobacter Aureobasidium pullulan Bacillus mojavensis A21 Pseudoalteromonas sp | Protease | Peptide hydrolases | [ 160 ] [ 161 ] Extracellular phospholipase C | marine streptomycete Pseudoalteromonas sp | Lipases | Hydrolyze different oils | [ 162 ] [ 163 ] Chitinase … Inhibition of microbial chitinases via these halogenated compounds are highly relevant [ 314 ]. From an economical perspective, demosponge-derived chitin-bromotyrosine hybrid scaffolds are easily available. …

Correlation Between Serum Tumor Marker Levels and Connective Tissue Disease-Related Interstitial Lung Disease.

OBJECTIVE: The main aims of this study were to explore the relationships between serum tumor markers and connective tissue disease-related interstitial lung disease (CTD-ILD) and to evaluate the clinical value of tumor markers for investigating interstitial lung disease (ILD) in patients with connective tissue disease (CTD). METHODS: The study included 235 patients with CTD (90 CTD without ILDs, 145 CTD-ILD). Clinical information and the levels of inflammatory and tumor markers, including carbohydrate antigen (CA) 19-9, CA125, carcinoembryonic antigen (CEA), CA153, and cytokeratin 19 fragment

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BackgroundThis study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets.MethodsTotal RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)

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… Another gene of interest, CHI3L1 (chitinase 3-like 1), a member of the glycoside hydrolase 18 family, has been shown to regulate osteoclast differentiation and bone resorption [ 30–34 ]. … Determination of chitinases family during osteoclastogenesis. Bone. 2014;61:55–63. doi: 10.1016/j.bone.2014.01.005. 32. Jin T, He P, Yang R, et al. CHI3L1 promotes Staphylococcus aureus -induced osteomyelitis by activating p38/MAPK and Smad signaling pathways. …

Expanded haemodialysis: news from the field.

Expanded haemodialysis (HDx) has emerged as a promising solution to improve haemodialysis effectiveness. A medium cut-off membrane allows the removal of a wider range of uraemic toxins. However, little is known about the potential interesting applications of HDx therapy. Feedback from the first routine use of HDx therapy under real-life conditions in European facilities was excellent for priming and rinse back. There was no adverse event after 5191 HDx treatments. Patients suffering from itching, restless legs syndrome, persistent asthenia or malnourishment could benefit from HDx therapy. More

Эпигенетические достижения в педиатрическом многоразовом склерозе: ДНК-метилирование примечательно участие Эпштейна-Барра заражённых вирусом и принимающих иммунных сетей.

СПРАВОЧНАЯ ИНФОРМАЦИЯ И ЦЕЛИ: Педиатрический множественный склероз (PedMS) предоставляет уникальную возможность для изучения патогенеза MS с учетом короткого интервала между воздействием на окружающую среду и возникновением заболеваний. Цель этого исследования состояла в том, чтобы выявить различные метилированные регионы (ДМР), которые способствуют взаимодействию между экологическими факторами и геномными факторами на ранних этапах заболевания. В этом многоцентровом исследовании мы проанализировали периферическую ДНК крови. 175 Итальянские предметы122 Пациенты педиатрии, 53 - здоровый контрол