β-Secretase-1 (BACE1) plays a key role in the regulation of cerebral amyloid-β homeostasis, being involved in amyloidogenic and, as recently found, amyloidolytic pathways. Growing evidence indicates that increased serum BACE1 (sBACE1) activity might represent an early biomarker for Alzheimer's disease. Here, we tested the hypothesis that an increase in sBACE1 activity may already occur in individuals with subjective cognitive decline (SCD).
View Article and Find Full Text PDFParaoxonase 1 (PON1) and Paraoxonase 3 (PON3) are enzymes located on the surface of high-density lipoprotein (HDL) and share similar antioxidant properties, possibly modulated by other proteins such as Myeloperoxidase (MPO), which drives the shift from functional to dysfunctional HDL. PON1 has been extensively studied in relation to Alzheimer's Disease (AD), but the role of PON3 remains unknown. To fill this knowledge gap, the study analyzed PON3 protein levels and PON1-arylesterase activity in 99 AD patients, 100 patients with mild cognitive impairment (MCI), and 79 cognitively normal controls.
View Article and Find Full Text PDFIntroduction: The accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy.
View Article and Find Full Text PDFTransglutaminase 2 (TG2) performs many functions both under physiological and pathological conditions. In cancer, its expression is associated with aggressiveness, propensity to epithelial-mesenchymal transition, and metastasis. Since TG2 performs key functions both outside and inside the cell, using inhibitors with different membrane permeability we analyzed the changes in the transcriptome induced in two triple-negative cell lines (MDA-MB-436 and MDA-MB-231) with aggressive features.
View Article and Find Full Text PDFStudy Question: Does sperm DNA recover from damage in all men after 2 years from the end of cytotoxic treatments?
Summary Answer: The current indication of 2 years waiting time for seeking natural pregnancy after cytotoxic treatment may not be adequate for all men, since severe sperm DNA damage is present in a proportion of subjects even after this timeframe.
What Is Known Already: Data in the literature on sperm DNA fragmentation (SDF) in lymphoma patients after cytotoxic treatments are scarce. The largest longitudinal study evaluated paired pre- and post-therapy (up to 24 months) semen samples from 34 patients while one study performed a longer follow-up (36 months) in 10 patients.
The incidence of cancer increases with age and as family planning is being delayed, there is a growing number of cancer patients whose fertility may be affected by oncological treatments. International guidelines recommend that all reproductive age cancer patients, including adolescent patients, should be referred for fertility preservation consultation, and if necessary, fertility preservation procedures should be performed. Fertility preservation enables cancer survivors to offer a chance for biological parenthood after recovery.
View Article and Find Full Text PDFCancer impairs spermatogenesis, whereas results on sperm DNA integrity are controversial and no data are available about sperm oxidative stress. In cancer patients, we detected sperm DNA fragmentation (sDF) and both viable (ROS production in viable sperm fraction/viable spermatozoa) and total (ROS production in viable sperm fraction/total spermatozoa) oxidative stress. We found that cancer (22.
View Article and Find Full Text PDFBackground: Zonulin is involved in the integrity and functioning of both intestinal-epithelial barrier and blood-brain barrier (BBB) by regulating tight junction molecular assembly.
Aim: Since changes in microbiota and BBB may play a role in neurodegenerative disorders, we aimed to determine whether serum zonulin levels change in older patients affected by different types of dementia or mild cognitive impairment (MCI).
Methods: We evaluated serum zonulin levels in patients with late-onset AD (LOAD), vascular dementia (VAD), MIXED (AD + VAD) dementia, amnestic MCI, and in healthy controls.
Cumulating evidence links environmental toxicants, such as organophosphate (OP) pesticides, to the pathogenesis of Alzheimer's disease (AD). The calcium-dependent Paraoxonase 1 (PON1) can neutralize these toxicants with good catalytic efficiency, thus protecting from OP-induced biological damage. Although different previous studies have already partially described an association between PON1 activity and AD, this intriguing relationship has not yet been comprehensively examined.
View Article and Find Full Text PDFA wealth of evidence suggests that Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a relevant role in atherogenesis and inflammation, which in turn are associated with the risk of developing dementia. The aim of this study was to evaluate whether serum Lp-PLA2 activity might be an early and/or late biomarker for different forms of dementia. Serum Lp-PLA2 activity was assessed in older patients with mild cognitive impairment (MCI, = 166; median clinical follow-up = 29 months), Late-Onset Alzheimer's disease (LOAD, = 176), vascular dementia (VAD, = 43), dementia characterized by an overlap between LOAD and VAD (AD-VAD MIXED dementia) ( = 136), other dementia subtypes ( = 45), and cognitively normal controls ( = 151).
View Article and Find Full Text PDFIntroduction: Testicular germ cell tumor is the most frequent neoplasia in men of reproductive age, with a 5-year survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation, especially within the first year post-therapy. Data in the literature are heterogeneous concerning longer follow-up periods, and the large majority is limited to 2 years.
View Article and Find Full Text PDFBackground: In earlier studies, it has been observed that 8-week treatment with a novel nutraceutical compound (NC) containing low monacolin K dose, polymethoxyflavones, phenolic acids, flavonoids, and hydroxytyrosol improves lipid profile and endothelial function and reduces the level of oxidized low-density lipoprotein (oxLDL). We hypothesize that this effect might be, at least in part, explained by positive modulation exerted by the NC on the atheroprotective function of high-density lipoprotein (HDL).
Aim: This study aimed to evaluate whether the NC could influence determinants of HDL function.
Background: Increasing evidence indicates that β-secretase 1 (BACE1) activity and concentration in blood are candidate biomarkers for Alzheimer's disease (AD). Investigating potential demographic, biological, and clinical determinants of BACE1 in the blood matrix is the critical step to validate and qualify BACE1 bio-indicators for different contexts-of-use (CoU), such as risk assessment, early detection, diagnosis, prognosis, management of AD, and outcome of amyloid pathway targeted drugs.
Objectives: To evaluate the influence of age, sex, HDL-cholesterol and comorbidities (cardiovascular diseases, hypertension, diabetes) on circulating BACE-1 activity.
Accumulating evidence suggests that high consumption of natural antioxidants promotes health by reducing oxidative stress and, thus, the risk of developing cardiovascular diseases. Similarly, fermentation of natural compounds with lactic acid bacteria (LAB), such as , enhances their beneficial properties as regulators of the immune, digestive, and cardiovascular system. We investigated the effects of fermentation with on the antioxidant and immunomodulatory effects of Pushgay berries (, Ericaceae family) in human umbilical vein endothelial cells (HUVECs) and macrophage cell line RAW264.
View Article and Find Full Text PDFBackground: Beta-site APP cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in amyloid-β (Aβ) plaques formation. BACE1 activity is increased in brains of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and plasma levels of BACE1 appears to reflect those in the brains.
Objective: In this work, we investigated the role of serum BACE1 activity as biomarker for AD, estimating the diagnostic accuracy of the assay and assessing the correlation of BACE1 activity with levels of Aβ1 - 40, Aβ1 - 42, and Aβ40/42 ratio in serum, known biomarkers of brain amyloidosis.
Patients with acute respiratory failure (ARF) may need mechanical ventilation (MV), which can lead to diaphragmatic dysfunction and muscle wasting, thus making difficult the weaning from the ventilator. Currently, there are no biomarkers specific for respiratory muscle and their function can only be assessed trough ultrasound or other invasive methods. Previously, the fast and slow isoform of the skeletal troponin I (fsTnI and ssTnI, respectively) have shown to be specific markers of muscle damage in healthy volunteers.
View Article and Find Full Text PDFBeta-secretase 1 (BACE1) is considered as the key enzyme in amyloid-β formation. Previous works suggest that high BACE1 activity may be present in brain, cerebrospinal fluid and serum of patients with late-onset Alzheimer's disease (LOAD) as well as mild cognitive impairment (MCI). Therefore, we evaluated whether serum BACE1 activity increases in MCI patients and is associated with the progression from MCI to dementia.
View Article and Find Full Text PDFBackground: A wealth of experimental and epidemiological evidence suggest that Apolipoprotein A-I (ApoA-I), the main protein constituent of high-density lipoprotein (HDL), may protect against Alzheimer disease (AD). To investigate this potential role, we conducted a meta-analysis of the published studies on the relationship between serum ApoA-I and AD occurrence.
Methods: We screened MEDLINE, EMBASE, Web of Science, and Scopus, for cross-sectional studies published from inception to 1 March 2021, comparing the ApoA-I serum levels between patients with AD and cognitively normal controls.
Azoospermia affects 1% of men, and it can be due to: (i) hypothalamic-pituitary dysfunction, (ii) primary quantitative spermatogenic disturbances, (iii) urogenital duct obstruction. Known genetic factors contribute to all these categories, and genetic testing is part of the routine diagnostic workup of azoospermic men. The diagnostic yield of genetic tests in azoospermia is different in the different etiological categories, with the highest in Congenital Bilateral Absence of Vas Deferens (90%) and the lowest in Non-Obstructive Azoospermia (NOA) due to primary testicular failure (~30%).
View Article and Find Full Text PDFOxidative stress (OxS) has been linked to several pregnancy-related complications. Previous studies demonstrated that lactoferrin (LF) has the ability to modulate inflammation, OxS and the immune function. Therefore, we aimed to observe whether vaginal LF administration was able to decrease OxS in the amniotic fluid (AF) of pregnant women undergoing mid-trimester genetic amniocentesis.
View Article and Find Full Text PDFLate onset Alzheimer disease (LOAD) is traditionally considered as a separate disease from vascular dementia (VAD). However, growing evidence suggests that β-amyloid (Aβ) accumulation, that initiates LOAD-related neurodegeneration, is preceded by vascular events. Previous in vitro studies showed that β-secretase 1 (BACE1), the key-enzyme of amyloidogenesis, is upregulated by cerebrovascular insult; moreover, its activity is increased both in brain and serum of LOAD patients.
View Article and Find Full Text PDFType-2 diabetes (T2D) and its cardiovascular complications are related to sex. Increasing evidence suggests that paraoxonase 1 (PON1) activity, an antioxidant enzyme bound to high-density lipoproteins (HDL), is implicated in the onset and clinical progression of T2D. Since we previously showed that PON1 is a sexual dimorphic protein, we now investigated whether sex might impact the relationship between PON1 and this chronic disease.
View Article and Find Full Text PDFBackground Myeloperoxidase (MPO) is an enzyme with a recognized prognostic role in coronary artery disease (CAD), which is also emerging as a promising biomarker for cardiac risk stratification. However, the lack of a consensus method for its quantification has hindered its implementation in clinical practice. The aim of our work was to optimize an absolute sensitive assay for active MPO without external standards, to validate the method in the clinical context of CAD patients, and to estimate the enzyme specific activity.
View Article and Find Full Text PDFBeta-secretase (BACE1) is a key enzyme in the formation of amyloid-β; its activity/concentration is increased in brain and cerebrospinal fluid of patients with late-onset Alzheimer's disease (LOAD). Since BACE1 was found also in blood, we evaluated its potential as peripheral biomarker. To this aim, serum BACE1 activity was assessed in 115 subjects with LOAD and 151 controls.
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