Search Results (148)

Cancer diagnosis requires alternative techniques that allow for early, non-invasive, or minimally invasive identification. Traditional methods, like tissue biopsies, are highly invasive and can be traumatic for patients. Liquid biopsy, a less invasive option, detects cancer biomarkers in body fluids such as blood and urine. However, early-stage cancer often presents low biomarker levels, making sensitivity a challenge for integrating liquid biopsy into early diagnosis. Recent studies revealed that extracellular vesicles (EVs) secreted by cells are apt markers for liquid biopsy. Detecting extracellular vesicles (EVs) for liquid biopsy faces challenges like low sensitivity, EV subtype heterogeneity, and difficulty isolating pure populations. Label-free methods, such as plasmonic biosensors and Raman spectroscopy, offer potential solutions by enabling direct analysis without markers, improving accuracy, and reducing complexity. This review paper discusses current challenges in EV-based liquid biopsy for cancer diagnosis and prognosis. It addresses the effective use of microfluidics and nano-plasmonic approaches to address these challenges. Enhancing label-free EV detection in liquid biopsy could revolutionize early cancer diagnosis by offering non-invasive, cost-effective, and rapid testing. This could improve patient outcomes through personalized treatment and ease the burden on healthcare systems. Full article

A child’s exposure to arsenic (As) can begin in utero through placental transfer to the fetus. There is a growing body of epidemiologic evidence suggesting an association between As exposure and neuropsychological development. Therefore, our objective was to describe the consequences of maternal and/or childhood As exposure on children’s neuropsychological development. We conducted a scoping review with a systematic search of the PubMed, Scopus, EMBASE, Web of Science, and PsycINFO databases. We included studies that assessed the association between maternal and/or childhood As exposure and neuropsychological development in children up to an average of 12 years of age. A total of 77 studies were included, most of which were published between 2020 and 2024 (44.1%), conducted in the United States of America (18.2%) and Bangladesh (16.9%), and involved participants with a median age of 6.6 years. Most studies performed cross-sectional analyses (51.9%) and assessed exposure to elements other than As (64.9%). Childhood was the most frequently studied exposure window (57.2%), and urine was the most commonly used biomarker of exposure (58.4%), followed by blood or serum (32.3%). Cognition was the most frequently evaluated neuropsychological domain (94.8%), followed by psychomotor function (40.3%) and social–emotional function (29.9%). Most studies reported evidence of a negative impact of As exposure on children’s neuropsychological development (73.7%), while some found no changes (27.3%) and a few suggested an improvement (1.3%). An important limitation is that most studies measured total urinary As without speciation into inorganic versus organic forms, which limits the validity of dose–response conclusions based on total arsenic concentrations. This review highlights the potential deleterious neuropsychological effects of maternal and/or childhood As exposure while also identifying areas where the evidence remains inconclusive. Full article

Preterm delivery affects approximately 10% of pregnancies worldwide and remains a major clinical challenge due to the lack of reliable early predictive tools. Existing strategies are often invasive, relying on blood or amniotic fluid samples and requiring complex processing. In this study, we describe a novel non-invasive approach based on the multiplex detection of inflammatory cytokines in small urine volumes from pregnant women. To account for clinical and temporal variability, we applied Generalized Additive Models for Location, Scale, and Shape (GAMLSS) to adjust for gestational age at sampling and obstetric factors. Correlation network analyses revealed cytokine interactions that distinguished preterm from term deliveries, with macrophage-derived cytokines—MIP-1α, MIP-1β, IL-15, and IL-22—emerging as central nodes. These findings highlight the involvement of the IL-1 pathway in the pathophysiology of preterm labor. Furthermore, urinary IL-5 and IL-31 levels correlated positively with pregnancy duration, whereas IL-1β and IL-1Ra in urine and TNFα in amniotic fluid showed inverse associations. Altogether, this non-invasive methodology provides insight into immune dynamics during pregnancy and offers a foundation for future studies focused on biomarker discovery and mechanistic understanding of preterm birth. Full article

Simultaneous molecular recognition and quantification of at least four biomarkers in biological samples may contribute to early and fast diagnosis of illnesses such as cancer. The electrodes able to reliably perform on-site these tests are the stochastic sensors. Therefore, three novel 3D stochastic sensors employing carbon-based powders (graphite, graphene, nanographene) treated with N-(2-mercapto-1H-benzo[d]imidazole-5-yl) oleamide solution were used for screening tests of whole blood, gastric tumoral tissue, urine, and saliva for molecular recognition and quantification of CA12-5, CA72-4, HER1, and AFP. The best performance was achieved for the sensor based on graphene, when the highest sensitivities were recorded, on wide working concentration ranges of: 8.37 × 10⁻¹⁴–8.37 U mL⁻¹ for CA12-5, 4.00 × 10⁻¹¹–4.00 × 10⁻³ U mL⁻¹ for CA72-4, 3.90 × 10⁻¹⁶–3.90 × 10⁻⁶ g mL⁻¹ for HER1, and 3.00 × 10⁻²⁰–3.00 × 10⁻⁶ g mL⁻¹ for AFP. The wide linear concentration ranges cover levels of biomarkers found in gastric cancer patients from early to late stages. The recovery values were higher than 98.00 with %, RSD lower than 1.00%. Full article

Background/Objectives: Oxidative stress plays a pivotal role in skin aging and carcinogenesis. Phytochemicals such as sulforaphane (SF, from broccoli sprouts or seeds) or curcumin (CUR, from turmeric) can be highly protective against this stress. They each induce a suite of cytoprotective and antioxidant enzymes that are coordinately transcribed via the Keap1-Nrf2-ARE pathway in mammals, such as the prototypical cytoprotective enzyme NAD(P)H dehydrogenase 1 (NQO1). Methods: Eighteen healthy human volunteers (9 males, 9 females, aged 18–69. were randomized to receive daily glucoraphanin (GR), which is converted to SF upon ingestion (450 mg; 1 mmol), CUR (1000 mg; 2.7 mmol), or both (450 mg GR + 1000 mg CUR), as oral supplements. After 8 days of a diet low in both compounds, blood and urine were collected for compliance and biomarker measurements. Randomized spots on the buttock’s skin were exposed to 2 x M.E.D. of UVB, and punch biopsies were obtained 1 and 3 days later for biomarker and histological measurement. Erythema was measured with a chromameter daily for 3 consecutive days following UVB. The process was repeated after receiving oral supplements, both with and without UVB exposure. Results: Compared to baseline, each treatment (n = 6 for each) induced NQO1 mRNA levels in skin biopsies: 3.1-fold with GR, 3.3-fold with CUR, and 3.6-fold with the combination of GR and CUR. Across all treatments (n = 18), expression of the pro-inflammatory cytokines IL-1β and TNF-α were reduced, as were IL-6, IL-17, STING, and CYR61, though less robustly. Modulation of these biomarkers persisted, but was less pronounced, in biopsies taken following UV exposure. The presence of SF and its metabolites in the skin post-treatment was confirmed by examining 6 of 12 subjects who ingested GR. Supplement effects on erythema following UV exposure were not significant, and no significant changes were measured in the same biomarkers in blood cells (PBMC), or by counting dyskeratotic keratinocytes. Supplements were well tolerated and compliance was excellent. Conclusions: Oral GR and CUR are well tolerated and have for the first time been shown to result in increased expression of cytoprotective genes and reduced expression of inflammatory cytokine genes in human skin in vivo. This mechanism-based clinical study suggests that an antioxidant, anti-inflammatory, and cytoprotective benefit from these oral supplements is delivered to the skin in humans. Full article

Background: Consumers are increasingly interested in healthier, less processed food products, driving the meat industry to improve the quality and health benefits of its offerings. Growing concerns about additives and allergens have encouraged the replacement of these ingredients with natural alternatives, presenting both challenges and opportunities. However, consumer rejection of additives and the actual health effects of their replacement remain poorly understood. In previous work, two new meat products—cooked turkey breast and cooked ham—were developed, where additives and allergens were replaced with natural extracts. These products demonstrated potential health benefits in vitro, including improvements in protein quality and microbiota composition. Methods: This study assessed consumer perceptions of additives through a survey and evaluated the two new meat products in a double-blind, randomized clinical trial conducted over a 5-week period. Biomarkers of interest were measured in blood, faeces, and urine samples at baseline and at the end of this study. Additionally, a separate study tested the satiating effect of these products using VAS score surveys. Results: The additive perception survey revealed that consumers associate additive-free products with being more natural and less harmful to health, with differences observed based on age, gender, and knowledge of additives. In the clinical trial, both the intervention and control groups showed significant decreases in serum levels of ox-LDL and GPx, with no differences between the groups. However, significant differences between the groups were found in inflammation markers TNF-α and IL-1β. Furthermore, the intervention group exhibited a significant reduction in nitrate excretion and a decrease in nitrification-related gut bacteria. Finally, the reformulated products demonstrated a satiating effect, reducing hunger. Conclusions: These findings suggest that the new additive- and allergen-free reformulated meat products may offer potential oxidative and anti-inflammatory benefits to consumers. Full article

Down Syndrome or Trisomy 21 (T21) is a complex genetic disease characterized by the presence of an extra chromosome 21, which leads to multiple clinical features and manifestations that severely affect the patient’s quality of life. Various methods of prenatal screening have been developed over time, allowing informed decision-making. However, a common drawback of the current methods for detecting T21 is their invasive nature. Over the past years, mass-spectrometry-based omics technologies have become a key tool for discovering biomarkers for the prenatal screening of T21, particularly focusing on proteins, peptide sequences, or metabolites in samples, like amniotic fluid, umbilical cord blood, and others. Recently, there has been a noticeable shift towards using less invasive biological sample types (e.g., maternal serum, plasma, and urine) reflecting a growing interest in non-invasive methods for prenatal screening. These advances aim to improve the sensitivity and accuracy for T21 detection while reducing the risks associated with more invasive procedures. The first section of this paper offers an in-depth review of studies utilizing mass-spectrometry-based omics for the prenatal screening of T21. This part provides an overview of the methodologies employed and their key findings. Instead, the subsequent section offers a comprehensive examination of the differentially expressed proteins (DEPs) and metabolites (DEMs) reported in the literature in T21 prenatal screening. Additionally, pathway analysis is carried out to explore the biological pathways that these molecules are involved in and how they relate to the clinical features of the syndrome. These findings aim to guide future research in the field and foster the development of more advanced, less invasive prenatal screening techniques for T21. Full article

Background: Leucine rich α-2 glycoprotein (LRG) is a glycoprotein that is an acute-phase protein produced by neutrophils, macrophages, hepatocytes, and intestinal epithelial cells. This study aimed to determine the serum LRG (s-LRG) and urine LRG (u-LRG) expression levels in children with inflammatory bowel disease (IBD) and evaluated their correlation with clinical disease activity, other inflammatory markers, laboratory results, and endoscopic activity scoring. Methods: This prospective observational study was conducted at a tertiary centre and included children aged 2–18 years with IBD. Clinic activity scoring was used to assess clinical disease activity. Haemoglobin levels, platelet counts, albumin, C-reactive protein, and erythrocyte sedimentation rate were analysed in the blood sample. LRG levels were measured in both blood and urine samples. The endoscopic assessment was scored according to the simple endoscopic score and Mayo endoscopic score. Serum and urine LRG levels were measured using commercial enzyme-linked immunosorbent assay kits. Disease activation was defined based on clinical activity scoring, laboratory results, and endoscopic evaluation. The results were compared between the active IBD and remission groups. Results: Forty-two (50%) patients with active IBD and forty-two (50%) patients in remission were included in this study. The serum levels of LRG were elevated in the patients with active IBD compared with the levels in the patients with IBD in remission (p = 0.020). However, there was no difference in the u-LRG level between the two groups (p = 0.407). In patients with IBD, positive correlations were observed between s-LRG, platelet count, C-reactive protein (CRP), and the erythrocyte sedimentation rate. The serum LRG was negatively correlated with albumin and haemoglobin levels. Urine LRG was not correlated with s-LRG in any patients with IBD included or in patients with active IBD. The cutoff value for s- LRG (77.03 μg/mL) had a sensitivity and specificity of 40.4% (95% CI 25.6–56.7%) and 88.1% (95% CI 74.3–96.0%), respectively. It was found that s-LRG was a more significant parameter than CRP in predicting disease activation. Conclusions: This prospective study demonstrated that the s-LRG level is a useful biomarker for predicting disease activation in children with IBD and appears to be a more significant parameter than the CRP level. However, the u-LRG level is not effective in predicting disease activation in children with IBD. Full article

The 2024 Nobel Prize in Physiology or Medicine was awarded to the pioneers who reported that microRNAs (miRNAs) regulate and direct the switch between physiological and pathological pathways via their over- or underexpression. The discovery changed the medical landscape and there are many completed and on-going clinical studies based on miRNAs. MiRNAs occur at the femtomolar level in biological fluids and are typically quantified using amplification-based techniques. Experimental nanopores have illustrated potential for trace analysis including amplification-free miRNA quantification. We repurposed the MinION, the only commercially available nanopore array device, and developed unique probes and protocols to detect and measure miRNA copies in blood and urine. Here, we report that miRNA copies are proportional to the total RNA isolated from the biospecimen, and that three known miRNA cancer biomarkers, i.e., miR-21, miR-375, and miR-141, were more than 1.5-fold overexpressed in blood samples from breast, ovarian, prostate, pancreatic, lung, and colorectal cancer patients compared to healthy patients. In these cancer samples, miR-15b was not overexpressed, in agreement with earlier studies. In contrast to literature reports, sample variability was undetectable in this study. The potential and limitations of this ready-to-use MinION/Yenos platform for multiple-cancer early detection (MCED) using blood or urine are discussed. Full article

Innovative biosensor technologies are revolutionizing cancer detection by offering non-invasive, sensitive, and rapid diagnostic tools, addressing the limitations of conventional screening. Non-invasive samples like breath, saliva, urine, and sweat, analyzed using advanced technologies like electronic nose systems and AI, show promise for early detection and frequent monitoring, though validation is needed. AI integration enhances data analysis and personalization. While blood-based methods remain the gold standard, combining them with less invasive sample types like saliva or sweat, and using sensitive techniques, is a promising direction. Conventional methods (mammography, MRI, etc.) offer proven efficacy, but are costly and invasive. Innovative methods using biosensors offer reduced infrastructure needs, lower costs, and patient-friendly sampling. However, challenges remain in validation, standardization, and low biomarker concentrations. Integrating both methodologies could create a comprehensive framework, combining reliability with accessibility. Future research should focus on robust biosensor development, standardization, expanding application to other cancers, exploring less-studied samples like sweat, and improving affordability for wider adoption, especially in resource-limited settings. The future lies in integrating diverse approaches for more sensitive, specific, and patient-friendly screening, improving early detection and outcomes. Full article

Metal nanocomposites are rapidly emerging as a powerful platform for biosensing applications, particularly in the analysis of biological fluids. This review paper examines the recent advancements in the development and application of metal nanocomposites as biosensors for detecting various analytes in complex biological matrices such as blood, serum, urine, and saliva. We discuss the unique physicochemical properties of metal nanocomposites, including their high surface area, enhanced conductivity, and tunable optical and electrochemical characteristics, which contribute to their superior sensing capabilities. The review will cover various fabrication techniques, focusing on their impact on the sensitivity, selectivity, and stability of the resulting biosensors. Furthermore, we will analyze the diverse applications of these biosensors in the detection of disease biomarkers, environmental toxins, and therapeutic drugs within biological fluids. Finally, we will address the current challenges and future perspectives of this field, highlighting the potential for improved diagnostic tools and personalized medicine through the continued development of advanced metal nanocomposite-based biosensors. Full article

Human biomonitoring (HBM) is a critical scientific tool for assessing human exposure by quantifying chemicals and their metabolites in biological specimens such as blood and urine. This approach provides a comprehensive and accurate evaluation of internal exposures from diverse sources and exposure routes. In Ireland, establishing a national HBM programme requires a systematic chemical prioritisation process that aligns global frameworks with local public perceptions. This study integrates insights from international initiatives such as the European Joint Programme Human Biomonitoring for Europe (HBM4EU) and the Partnership for the Assessment of Risks from Chemicals (PARC)—along with HBM programmes from EU countries (Germany, France, Belgium, Norway, Slovenia, Czech Republic, and Sweden) and non-EU countries (US, Canada, South Korea, China, and New Zealand). In addition, a national survey was conducted to capture the perceptions of people in Ireland regarding chemicals of concern to develop a comprehensive priority list of chemicals and biomarkers. The broader chemical groups identified include heavy metals (lead, cadmium, mercury, arsenic, and chromium VI), plasticisers (phthalates), bisphenols, pesticides, flame retardants, PFASs (per- and polyfluoroalkyl substances), PAHs (polycyclic aromatic hydrocarbons), POPs (persistent organic compounds), VOCs (volatile organic compounds), and UV (ultraviolet) filters. This integrated, participatory approach provides a roadmap for a robust, adaptable chemical list that supports evidence-based policy decisions in HBM in Ireland and enhances public health outcomes. Full article

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a progressive degeneration in the neurons of the frontal cortex, spinal cord, and brainstem, altering the correct release of neurotransmitters. The disease affects every muscle in the body and could cause death three to five years after symptoms first occur. There is currently no efficient treatment to stop the disease’s progression. The lack of identification of potential therapeutic strategies is a consequence of the delayed diagnosis due to the absence of accurate ALS early biomarkers. Indeed, neurotransmitters altered in ALS are not measurable in body fluids at quantities that allow for testing, making their use as diagnostic tools a challenge. Contrarily, neuroproteins and neuropeptides are chemical messengers produced and released by neurons, and most of them have the potential to enter bodily fluids. To find out new possible ALS biomarkers, the research of neuropeptides and proteins is intensified using mass spectrometry and biochemical-based assays. Neuropeptides derived from the proVGF precursor protein act as signaling molecules within neurons. ProVGF and its derived peptides are expressed in the nervous and endocrine systems but are also widely distributed in body fluids such as blood, urine, and cerebrospinal fluid, making them viable options as disease biomarkers. To highlight the proVGF and its derived peptides’ major roles as ALS diagnostic biomarkers, this review provides an overview of the VGF peptide alterations in spinal cord and body fluids and outlines the limitations of the reported investigations. Full article

Deoxynivalenol (DON) and Alternaria toxins (ATs) are two common types of mycotoxins in food. Although they are physiologically toxic to animals and various cell lines, data related to the exposure risks and health effects in the human population were still limited, especially for ATs. In this study, we combined food consumption data and human biomonitoring data of 200 pregnant volunteers from different districts of Shanghai to assess the exposure to DON and ATs. In addition, correlations between food consumption and urinary DON and ATs levels, urine biomarkers, and blood indexes were analyzed by regression analysis. For DON, the exposure assessment of the probable daily intake (PDI) indicated that a portion (37.5%) of all participants exceeded the Tolerable Daily Intake (TDI) proposed for DON. For ATs, the PDI values estimated based on the urinary concentrations indicated that 2–100% of all participants exceeded the threshold of toxicological concern (TTC) values for ATs. In addition, we innovatively found some associations between exposure to ATs and abnormal uric acid and high-density lipoprotein cholesterol indexes by regression analysis. Despite the inevitable uncertainties, these results make an important contribution to the understanding of DON and ATs exposure risks and potential health hazards in the pregnant women population. Full article

Background/Objective: Cobalamin (B₁₂) deficiency is reported in 18% of adults with sickle cell disease (SCD) and only 10% without SCD; limited data are available on children. Diagnosing B₁₂ deficiency is challenging given the lack of an established gold standard method of assessment and the unique renal features of SCD. B₁₂ metabolism can be impacted by the clinical use of nitrous oxide gas (N₂O), which is a standard therapy for SCD pain in some European countries. In response to emerging reports of neurologic sequalae in patients with SCD receiving N₂O, we evaluated the prevalence of B₁₂ deficiency in children with SCD pain. Methods: Secondary analysis of prospective blood and urine samples in children aged 3–21 hospitalized with SCD pain. B₁₂ deficiency was defined as plasma methylmalonic acid (MMA) > 592 nmol/L or urine MMA/creatinine ≥ 2.2 mmol/mol. Results: Ninety-four children (13 ± 4 years, 54% female, 68% hemoglobin-SS, and 72% on hydroxyurea) were assessed. Further, 53% (50/94) had B₁₂ deficiency diagnosed by either urine, plasma, or both; 27% (25/94) were deficient based on urine; 39% (37/94) were deficient by plasma; and 13% (12/94) were deficient by both plasma and urine. Plasma MMA and urine MMA/creatinine did not correlate with hemoglobin or mean corpuscular volume. Conclusions: B₁₂ deficiency was common in children with SCD. The absence of a gold standard for diagnosing B₁₂ deficiency compounded with the reliability issues of testing modalities make it impractical to determine whether this is an over- or under-estimation of the true prevalence. Future studies to better understand the dynamics of B₁₂ metabolism during acute and steady states in SCD are warranted and could elucidate the influence of acute SCD pain on these biomarkers. Full article