PNLIPRP1 Hypermethylation in Exocrine Pancreas Links Type 2 Diabetes and Cholesterol Metabolism.

We postulated that type 2 diabetes (T2D) predisposes patients to exocrine pancreatic diseases through (epi)genetic mechanisms. We explored the methylome (using MethylationEPIC arrays) of the exocrine pancreas in 141 donors, assessing the impact of T2D. An epigenome-wide association study of T2D identified hypermethylation in an enhancer of the pancreatic lipase-related protein 1 (PNLIPRP1) gene, associated with decreased PNLIPRP1 expression.

Preservation of urine specimens for metabolic evaluation of recurrent urinary stone formers.

Objectives: Stability of concentrations of urinary stone-related metabolites was analyzed from samples of recurrent urinary stone formers to assess necessity and effectiveness of urine acidification during collection and storage.

Methods: First-morning urine was collected from 20 adult calcium-stone forming patients at Tomas Bata Hospital in the Czech Republic. Urine samples were analyzed for calcium, magnesium, inorganic phosphate, uric acid, sodium, potassium, chloride, citrate, oxalate, and urine particles.

Reduction in Xenogeneic Epitopes on Porcine Endothelial Cells by Periodate Oxidation.

Background: Patterns of humoral immune responses represent a major hurdle in terms of pig-to-human xenotransplantation approaches. The best-known xenogeneic glycan antigens present in pigs are the αGal (Galili antigen) and the non-human sialic acid Neu5Gc. As there are further differences between porcine and human cellular surface glycosylation, a much broader range of glycan epitopes with xeno-reactive relevance can be anticipated.

Exploring the effect of APOE ε4 on biomarkers of neurodegeneration in Alzheimer's disease.

Background And Aims: This study aims to assess the association between APOE genotype and biomarkers of neurodegeneration in Alzheimer's disease (AD).

Methods: We performed a retrospective observational study at the University Hospital "P. Giaccone" in Palermo, Italy.

Exploring dose-response variability and relative severity assessment in STZ-induced diabetes male NSG mice.

NSG mice are among the most immunodeficient mouse model being used in various scientific branches. In diabetelogical research diabetic NSG mice are an important asset as a xenotransplantation model for human pancreatic islets or pluripotent stem cell-derived islets. The treatment with the beta cell toxin streptozotocin is the standard procedure for triggering a chemically induced diabetes.

Evaluation of core Biomarkers of Alzheimer's disease in saliva and plasma measured by chemiluminescent enzyme immunoassays on a fully automated platform.

Cerebrospinal fluid (CSF) core biomarkers of Alzheimer's disease (AD), including amyloid peptide beta-42 (Aβ42), Aβ42/40 ratio, and phosphorylated tau (pTau), are precious tools for supporting AD diagnosis. However, their use in clinical practice is limited due to the invasiveness of CSF collection. Thus, there is intensive research to find alternative, noninvasive, and widely accessible biological matrices to measure AD core biomarkers.

Predictive Value of the sFlt-1/PlGF Ratio and Interleukin-6 for the Presence of Placental Lesions in Spontaneous Preterm Labor with Intact Membranes with Delivery within 7 Days.

Introduction: The aim of the study was to identify predictive values of the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio and interleukin (IL)-6, assessed with a clinically available method in a large-volume biochemistry laboratory, in maternal blood, amniotic fluid, and umbilical cord blood for the presence of the placental lesions consistent with maternal vascular malperfusion (MVM) and acute histological chorioamnionitis (HCA), respectively.

Methods: This retrospective study included 92 women with preterm labor with intact membranes (PTL) delivered within 7 days of admission with gestational ages between 22+0 and 34+6 weeks. The sFlt-1/PlGF ratio and IL-6 were assessed in stored samples of maternal serum, amniotic fluid, and umbilical cord serum using Elecsys® sFlt-1, PlGF, and IL-6 immunoassays.

Understanding the value of monocyte distribution width (MDW) in acutely ill medical patients presenting to the emergency department: a prospective single center evaluation.

The monocyte distribution width (MDW) has emerged as a promising biomarker for accurate and early identification of patients with potentially life-threatening infections. Here we tested the diagnostic performance of MDW in adult patients requiring hospital admission for community-acquired infections and sepsis, evaluated sources of heterogeneity in the estimates of diagnostic accuracy, and assessed the meaning of MDW in a patient population presenting to the emergency department (ED) for acute non-infectious conditions. 1925 consecutive patients were categorized into three groups: non-infection (n = 1507), infection (n = 316), and sepsis/septic shock (n = 102).

Transition transferases prime bacterial capsule polymerization.

Capsules are long-chain carbohydrate polymers that envelop the surfaces of many bacteria, protecting them from host immune responses. Capsule biosynthesis enzymes are potential drug targets and valuable biotechnological tools for generating vaccine antigens. Despite their importance, it remains unknown how structurally variable capsule polymers of Gram-negative pathogens are linked to the conserved glycolipid anchoring these virulence factors to the bacterial membrane.

The fate of intracellular S1P regulates lipid droplet turnover and lipotoxicity in pancreatic beta-cells.

Lipotoxicity has been considered the main cause of pancreatic beta-cell failure during type 2 diabetes development. Lipid droplets (LD) are believed to regulate the beta-cell sensitivity to free fatty acids (FFA), but the underlying molecular mechanisms are largely unclear. Accumulating evidence points, however, to an important role of intracellular sphingosine-1-phosphate (S1P) metabolism in lipotoxicity-mediated disturbances of beta-cell function.

Sialic acids on T cells are crucial for their maintenance and survival.

Sialic acids are found as terminal sugars on glycan structures on cellular surfaces. T cells carry these sialoglycans abundantly, and they are thought to serve multiple functions in cell adhesion, cell migration, and protection from complement attack. We studied the role of sialoglycans on T cells in a mouse model with a T cell-specific deletion of cytidine monophosphate-sialic acid synthase (CMAS), the enzyme that is crucial for the synthesis of sialoglycans.

Ectodomain shedding of PLA2R1 is mediated by the metalloproteases ADAM10 and ADAM17.

Phospholipase A2 receptor 1 (PLA2R1) is a 180-kDa transmembrane protein that plays a role in inflammation and cancer and is the major autoantigen in membranous nephropathy, a rare but severe autoimmune kidney disease. A soluble form of PLA2R1 has been detected in mouse and human serum. It is likely produced by proteolytic shedding of membrane-bound PLA2R1 but the mechanism is unknown.

Clinical usefulness of presepsin and monocyte distribution width (MDW) kinetic for predicting mortality in critically ill patients in intensive care unit.

Background: In this study, we explored the accuracy of two new sepsis biomarkers, monocyte distribution width (MDW) and presepsin (PSP), compared to traditional ones, C-reactive protein (CRP) and Procalcitonin (PCT), to identify sepsis and predict intra-hospital mortality by analyzing their kinetic at different time points during hospitalization stay.

Methods: We enrolled 104 patients admitted to the intensive care unit (ICU) of University Hospital "Paolo Giaccone", Palermo. Among these, 30 (29%) had a clinical diagnosis of sepsis.

Macrophage- and CD4+ T cell-derived SIV differ in glycosylation, infectivity and neutralization sensitivity.

The human immunodeficiency virus (HIV) envelope protein (Env) mediates viral entry into host cells and is the primary target for the humoral immune response. Env is extensively glycosylated, and these glycans shield underlying epitopes from neutralizing antibodies. The glycosylation of Env is influenced by the type of host cell in which the virus is produced.

The final part of the CRESS trilogy - how to evaluate the quality of stability studies.

High quality laboratory results are critical for patient management. However, poor sample quality can impact these results and patient safety. To ensure reliable and accurate results laboratories must be aware of each analyte's stability under various storage conditions and matrices to guarantee correct and dependable outcomes.

Conserved cysteines prevent C-mannosylation of mucin Cys domains.

Mucins are major components of the mucus. Besides the highly O-glycosylated tandem repeat domains, mucins contain Cys domains (CysDs). CysDs contain conserved disulfide-forming cysteine residues as well as a WxxW motif.

Non-esterified fatty acid palmitate facilitates oxidative endoplasmic reticulum stress and apoptosis of β-cells by upregulating ERO-1α expression.

Adipose tissue-derived non-esterified saturated long-chain fatty acid palmitate (PA) decisively contributes to β-cell demise in type 2 diabetes mellitus in part through the excessive generation of hydrogen peroxide (HO). The endoplasmic reticulum (ER) as the primary site of oxidative protein folding could represent a significant source of HO. Both ER-oxidoreductin-1 (ERO-1) isoenzymes, ERO-1α and ERO-1β, catalyse oxidative protein folding within the ER, generating equimolar amounts of HO for every disulphide bond formed.

Molecular Biomarkers of Neurodegenerative Disorders: A Practical Guide to Their Appropriate Use and Interpretation in Clinical Practice.

Neurodegenerative disorders (NDs) represent a group of different diseases characterized by the progressive degeneration and death of the nervous system's cells. The diagnosis is challenging, especially in the early stages, due to no specific clinical signs and symptoms. In this context, laboratory medicine could support clinicians in detecting and differentiating NDs.

Two cases with discrepancy in the quantitative cytological assessment of cerebrospinal fluid in neonatal samples using light microscopy in comparison with Sysmex XN-1000.

We present two cases from the neonatal department with cerebrospinal fluid examination. We revealed a striking discrepancy in polymorphonuclear (PMN) and mononuclear (MN) cell counts using conventional light microscopy in comparison with automated analyzer Sysmex XN-1000 (PMNs - 13 . 173x10/L, MNs - 200 .

Monocyte distribution width (MDW) kinetic for monitoring sepsis in intensive care unit.

Objectives: Monocyte distribution width (MDW) is a measure of monocyte anisocytosis. In this study, we assessed the role of MDW, in comparison to C-reactive protein (CRP), procalcitonin (PCT), and lactate, as a screening and prognostic biomarker of sepsis in intensive care unit (ICU) by longitudinally measuring it in the first 5 days of hospital stay.

Methods: We considered all consecutive patients admitted to the ICU.

The role of Killer immunoglobulin-like receptors (KIRs) in the genetic susceptibility to non-celiac wheat sensitivity (NCWS).

Objectives: Non-celiac wheat sensitivity (NCWS) is an emerging clinical condition characterized by gastrointestinal and extraintestinal symptoms following the ingestion of gluten-containing foods in patients without celiac disease (CD) or wheat allergy. Despite the great interest for NCWS, the genetic risk factors still need to be fully clarified. In this study, we first assessed the possible contribution of genes and KIR haplotypes on the genetic predisposition to NCWS.

Motor properties of Myosin 5c are modulated by tropomyosin isoforms and inhibited by pentabromopseudilin.

Myosin 5c (Myo5c) is a motor protein that is produced in epithelial and glandular tissues, where it plays an important role in secretory processes. Myo5c is composed of two heavy chains, each containing a generic motor domain, an elongated neck domain consisting of a single α-helix with six IQ motifs, each of which binds to a calmodulin (CaM) or a myosin light chain from the EF-hand protein family, a coiled-coil dimer-forming region and a carboxyl-terminal globular tail domain. Although Myo5c is a low duty cycle motor, when two or more Myo5c-heavy meromyosin (HMM) molecules are linked together, they move processively along actin filaments.