Search Results (1,441)

Cancer is one of the major causes of death, and as it becomes more malignant, it becomes an intractable disease that is difficult to cure completely. Therefore, early detection is important to increase the survival rate. For this reason, testing with blood biomarkers is currently common. However, in order to accurately diagnose early-stage cancer, new biomarkers and diagnostic methods that enable highly accurate diagnosis are needed. This review summarizes recent studies on cancer biomarker detection. In particular, we focus on the analysis of volatile organic compounds (VOCs) in urine and the development of diagnostic methods using olfactory receptors in living organisms. Urinary samples from cancer patients contain a wide variety of VOCs, and the identification of cancer specific compounds is underway. It has also been found that the olfactory sense of organisms can distinguish cancer-specific odors, which may be applicable to cancer diagnosis. We explore the possibility of novel cancer biomarker candidates and novel diagnostic methods. Full article

This study aims to develop a protocol for respiratory disease-associated biomarker discovery by combining urine proteome studies with urinary exosome components analysis (i.e., miRNAs). To achieve this, urine was DTT treated to decrease uromodulin, then concentrated and ultracentrifuged. Proteomic analyses of exosome-free urine were performed using LC-MS/MS. Simultaneously, miRNA expression from urine exosomes was measured using either RTqPCR (pre-amplification) or nCounter Nanostring (non-amplication) analyses. We detected 548 different proteins in exosome-free urine samples (N = 5) with high confidence (FDR < 1%), many of them being expressed in different non-renal tissues. Specifically, lung-related proteins were overrepresented (Fold enrichment = 1.31; FDR = 0.0335) compared to whole human proteome, and 10–15% were already described as protein biomarkers for several pulmonary diseases. Urine proteins identified belong to several functional categories important in respiratory pathology. We could confirm the expression of miRNAs previously connected to respiratory diseases (i.e., miR-16-5p, miR-21-5p, miR-146a-5p, and miR-215-5p) in urine exosomes by RTqPCR. Finally, we detected 333 miRNAs using Nanostring, 15 of them up-regulated in T2^high asthma (N = 4) compared to T2^low asthma (N = 4) and healthy subjects (N = 4). Therefore, this protocol combining the urinary proteome (exosome free) with the study of urinary exosome components (i.e., miRNAs) holds great potential for molecular biomarker discovery of non-renal and particularly respiratory pathologies. Full article

Background: The current gold standards for diagnosing acute kidney injury (AKI) are an increase in serum creatinine and a decrease in urine output, which are inadequate for rapid diagnosis. Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein produced and secreted by injured kidney tubule epithelial cells, and can serve as an early urinary biomarker for AKI. ProNephro AKI (NGAL) is an immunoassay for the quantitative determination of NGAL in urine (uNGAL) that recently received FDA clearance. A multisite, cross-sectional study was conducted to establish reference intervals for uNGAL in apparently healthy individuals. Methods: Urine samples were collected from apparently healthy individuals aged ≥3 months who met all inclusion criteria and no exclusion criteria. Specimens were temporarily stored at room temperature or 2–8 °C, then transferred into urinalysis tubes before being frozen and shipped for testing. uNGAL testing was performed using the ProNephro AKI (NGAL) immunoassay on a Roche cobas c501 analyzer. Results: Of the 688 individuals screened, 677 were eligible, and 629 (91.4%) of those were deemed evaluable. The 95th and 97.5th percentile uNGAL values for all pediatric participants were below the clinical cutoff of 125 ng/mL. uNGAL values were statistically significantly higher for female vs. male participants in both adult (p = 0.003) and pediatric groups (p < 0.001), while differences were not statistically significant for age, site location, race, or ethnicity. Conclusions: This study provides normal reference intervals for uNGAL with the ProNephro AKI (NGAL) clinical chemistry immunoassay that may be useful for interpreting patient results. Full article

Traumatic brain injuries (TBIs) are a leading cause of mortality and morbidity, particularly in forensic settings where determining the cause of death and timing of injury is critical. Glial fibrillary acidic protein (GFAP), a biomarker specific to astrocytes, has emerged as a valuable tool in post-mortem analyses of TBI. A PRISMA-based literature search included studies examining GFAP in human post-mortem samples such as brain tissue, cerebrospinal fluid (CSF), serum, and urine. The results highlight that GFAP levels correlate with the severity of brain injury, survival interval, and pathological processes such as astrocyte damage and blood–brain barrier disruption. Immunohistochemistry, ELISA, and molecular techniques were commonly employed for GFAP analysis, with notable variability in protocols and thresholds among studies. GFAP demonstrated high diagnostic accuracy in distinguishing TBI-related deaths from other causes, particularly when analyzed in CSF and serum. Furthermore, emerging evidence supports its role in complementing other biomarkers, such as S100B and NFL, to improve diagnostic precision. However, the review also identifies significant methodological heterogeneity and gaps in standardization, which limit the generalizability of findings. Future research should focus on establishing standardized protocols, exploring biomarker combinations, and utilizing advanced molecular tools to enhance the forensic application of GFAP. Full article

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for causing the Coronavirus disease 2019 (COVID-19) outbreak. While mutations cause the emergence of new variants, the ancestral SARS-CoV-2 strain is unique among other strains. Methods: Various clinical parameters, the activity of cathepsin proteases, and the concentration of various proteins were measured in urine samples from COVID-19-negative participants and COVID-19-positive participants. Urinary extracellular vesicles (uEVs) were isolated from urine samples from the two groups and used for proteomic analysis and subsequent pathway analyses. Results: Activity levels of cathepsin S and L were greater in the urine of COVID-19-positive participants. The concentration of C-reactive protein, transmembrane serine protease 2, and klotho protein were significantly greater in the urine of COVID-19-positive participants. There was a greater amount of uEVs in the COVID-19 group and klotho protein was found to be enriched in uEVs from the COVID-19 group. Pathway analyses of the proteomics data showed most of the identified proteins were involved in signal transduction, stress response, protein metabolism, and transport. The identified proteins were predominantly associated with cellular membranes and with function of the cytoskeleton, enzyme regulation, and signal transduction. Conclusions: Taken together, our data identify novel urinary biomarkers that could be used to further investigate the long-term effects of SARS-CoV-2 infection. Full article

Exposure to ionizing radiation disrupts metabolic pathways and causes oxidative stress, which can lead to organ damage. In this study, urinary metabolites from mice exposed to high-dose and low-dose whole-body irradiation (WBI HDR, WBI LDR) or partial-body irradiation (PBI BM2.5) were analyzed using targeted and untargeted metabolomics approaches. Significant metabolic changes particularly in oxidative stress pathways were observed on Day 2 post-radiation. By Day 30, the WBI HDR group showed persistent metabolic dysregulation, while the WBI LDR and PBI BM2.5 groups were similar to control mice. Machine learning models identified metabolites that were predictive of the type of radiation exposure with high accuracy, highlighting their potential use as biomarkers for radiation damage and oxidative stress. Full article

Serious alcohol-associated hazards underscore the need to develop new biomarkers reflecting the biological changes caused by chronic alcohol use and predicting the risk of alcohol-related death. Oxidative stress is one mechanism of alcohol toxicity. The blood and urine redox status (total antioxidant capacity [TAC], total oxidative status [TOS], and oxidative stress index [OSI]) was assessed in 105 people who died a sudden death (controls), 47 people who died of alcohol overdose, and 102 people with alcohol dependency. TAC and TOS were determined utilizing the colorimetric method. Non-parametric tests were used for statistical analysis. Blood and urine TAC levels were significantly elevated in individuals both with alcohol dependency and alcohol poisoning compared with controls. TOS levels were elevated in the blood of both study groups compared with the control group, and significantly higher in patients with alcohol dependency compared with the group with alcohol poisoning. TAC in the blood highly correlated with blood alcohol content. Receiver operating characteristic (ROC) analysis showed that the blood TAC effectively discriminated between individuals with alcohol poisoning and alcohol dependency with high sensitivity and specificity. Our study confirmed impaired redox homeostasis in people with alcoholism and indicated the utility of TAC, TOS, and OSI as biomarkers of alcohol exposure. Full article

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has spurred an extraordinary scientific effort to better understand the disease’s pathophysiology and develop diagnostic and prognostic tools to guide more precise and effective clinical management. Among the biological samples analyzed for biomarker identification, urine stands out due to its low risk of infection, non-invasive collection, and suitability for frequent, large-volume sampling. Integrating data from omics studies with standard biochemical analyses offers a deeper and more comprehensive understanding of COVID-19. This review aims to provide a detailed summary of studies published to date that have applied omics and clinical analyses on urine samples to identify potential biomarkers for COVID-19. In July 2024, an advanced search was conducted in Web of Science using the query: “covid* (Topic) AND urine (Topic) AND metabol* (Topic)”. The search included results published up to 14 October 2024. The studies retrieved from this digital search were evaluated through a two-step screening process: first by reviewing titles and abstracts for eligibility, and then by retrieving and assessing the full texts of articles that met the specific criteria. The initial search retrieved 913 studies, of which 45 articles were ultimately included in this review. The most robust biomarkers identified include kynurenine, neopterin, total proteins, red blood cells, ACE2, citric acid, ketone bodies, hypoxanthine, amino acids, and glucose. The biological causes underlying these alterations reflect the multisystemic impact of COVID-19, highlighting key processes such as systemic inflammation, renal dysfunction, critical hypoxia, and metabolic stress. Full article

Extracellular vesicles (EVs) in cerebrospinal fluid (CSF) represent a valuable source of biomarkers for central nervous system (CNS) diseases, offering new pathways for diagnosis and monitoring. However, existing methods for isolating EVs from CSF often prove to be labor-intensive and reliant on specialized equipment, hindering their clinical application. In this study, we present a novel, clinically compatible method for isolating EVs from CSF. We optimized the use of ExoGAG, a commercially available reagent that has been tested in plasma, urine and semen, and compared it directly with differential ultracentrifugation using Western blotting, protein quantification, nanoparticle tracking analysis, and cryogenic electron microscopy. Additionally, we analyzed the presence of specific microRNAs (miRNAs) known to be present in CSF-derived EVs. Our data demonstrate that ExoGAG is an effective method for isolating EVs from CSF, yielding a higher amount of EVs compared to traditional ultracentrifugation methods, and with comparable levels of specific miRNAs. In conclusion, the use of ExoGAG in a clinical setting may facilitate the testing of biomarkers essential for tracking brain pathology in CNS diseases. Full article

Background/Objectives: Testicular germ cell tumors (TGCT) are common in young adult men and have high cure rates. Conventional serum tumor markers and imaging are not able to differentiate between histologic subtypes of the disease, which portend different prognoses and require distinct therapeutic strategies. Micro-RNAs (miRNAs) are small non-coding transcripts involved in the post-transcriptional regulation of gene expression, which have emerged as promising biomarkers in a variety of tumors. This study aimed to assess the potential of differentially expressed miRNAs in differential diagnosis and prognostication among TGCT patients with various histologic subtypes. Methods: Transcriptomic analysis of 134 patients from The Cancer Genome Atlas (TCGA)-TGCT database was conducted. miRNA differential expression analysis among seminomatous, embryonal carcinoma, mixed GCT, and teratoma was performed, followed by ROC curve analysis of the most significantly up- and downregulated miRNAs, respectively. Statistical associations of miRNA expression with AJCC stage were also investigated along with miRNA target network analysis and evaluation of miRNA detection in patients’ fluids. Results: Upregulation of seven miRNAs (hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-200a, hsa-mir-200b, hsa-mir-203b, hsa-mir-375, hsa-mir-582) and downregulation of seven additional miRNAs (hsa-mir-105-1, hsa-mir-105-2, hsa-mir-4433a, hsa-mir-548x, hsa-mir-5708, hsa-mir-6715a, hsa-mir-767) were identified. miRNAs displayed a high sensitivity/specificity of 0.94/1.0 (AUC = 0.98) for the upregulated and 0.97/0.94 (AUC = 0.96) for the downregulated signature. Deregulated expression of these miRNAs was significantly associated with AJCC stage and distant organ metastasis (p < 0.001), overall supporting their prognostic strength. Both signatures were detectable in body fluids, particularly urine. miRNA target network analysis supported the functional role of these miRNAs in the regulation of cancer-related processes such as cell proliferation via deregulation of pivotal oncogenes. Conclusions: These findings support the clinical value of two novel miRNA signatures in differential diagnosis and prognostic stratification of various histologic subtypes of TGCT, with potential treatment implications. Full article

Enzyme-based portable amperometric biosensors are precise and low-cost medical devices used for rapid cancer biomarker screening. Sarcosine (Sar) is an ideal biomarker for prostate cancer (PCa). Because human serum and urine contain complex interfering substances that can directly oxidize at the electrode surface, rapid Sar screening biosensors are relatively challenging and have rarely been reported. Therefore, highly sensitive and selective amperometric biosensors that enable real-time measurements within <1.0 min are needed. To achieve this, a chitosan–polyaniline polymer nanocomposite (CS–PANI NC), a carrier for dispersing mesoporous carbon (MC), was synthesized and modified on a screen-printed carbon electrode (SPCE) to detect hydrogen peroxide (H₂O₂). The sarcosine oxidase (SOx) enzyme-immobilized CS–PANI–MC-2 ternary NCs were referred to as supramolecular architectures (SMAs). The excellent electron transfer ability of the SMA-modified SPCE (SMA/SPCE) sensor enabled highly sensitive H₂O₂ detection for immediate trace Sar biomarker detection. Therefore, the system included an SMA/SPCE coupled to a portable potentiostat linked to a smartphone for data acquisition. The high catalytic activity, porous architecture, and sufficient biocompatibility of CS–PANI–MC ternary NCs enabled bioactivity retention and immobilized SOx stability. The fabricated biosensor exhibited a detection limit of 0.077 μM and sensitivity of 8.09 μA mM⁻¹ cm⁻² toward Sar, demonstrating great potential for use in rapid PCa screening. Full article

Background: Traditional methods of bladder cancer (BC) diagnosis include clinical examination, imaging, urine tests, cystoscopy, and biopsy. Due to the complexity of detection, diagnostic markers of bladder cancer measured in blood are still being sought. The pathogenesis of BC is complex and depends on many factors. However, the available literature data suggest that gasdermin D (GSDM D) has an influence in the pathogenesis of cancers. This study is the first that assesses the significance and diagnostic utility of serum GSDM D in bladder cancer. Methods: A total of 80 serum samples were obtained and analysed from healthy volunteers (C) and bladder cancer patients. The cancer patients were further classified into two groups, low-grade (LG) and high-grade (HG) bladder cancer, according to the TNM classification. The serum levels of GSDM D, CEA, and CA19-9 were assessed following the manufacturer’s instructions using immunoassay techniques. Results: The concentrations of GSDM D were nearly twice as high in the serum of BC patients compared to controls. Additionally, the median of GSDM D concentration was notably elevated in LG and HG bladder cancer than in C. In the total study group, the GSDM D concentration correlated with CRP and CEA levels. The diagnostic sensitivity of GSDM D was higher than that of CEA, but slightly lower in comparison to CA19-9. Moreover, the negative predictive value of GSDM D was the highest among all tested markers. The highest positive predictive value and diagnostic accuracy were observed for CEA, while the accuracy of GSDM D was comparable. GSDM D had an AUC value of 0.741, which was similar to the AUC value of CEA. Conclusions: GSDM D in serum appears to be a valuable diagnostic biomarker, especially when its measurement is used in conjunction with other markers such as CEA. Its high sensitivity makes it effective for the early detection of bladder cancer. Full article

Background/Objectives: Thus far, no studies have examined the relationship between fruit and vegetable (F and V) intake, urinary metabolite quantities, and weight change. Therefore, the aim of the current study was to explore changes in urinary metabolomic profiles during and after a 10-week weight loss intervention where participants were prescribed a high F and V diet (7 servings daily). Methods: Adults with overweight and obesity (n = 34) received medical nutrition therapy counselling to increase their F and V intakes to national targets (7 servings a day). Data collection included weight, dietary intake, and urine samples at baseline at week 2 and week 10. Urinary metabolite profiles were quantified using ¹H NMR spectroscopy. Machine learning statistical approaches were employed to identify novel urine-based metabolite biomarkers associated with high F and V diet patterns at weeks 2 and 10. Metabolic changes appearing in urine in response to diet were quantified using Metabolite Set Enrichment Analysis (MSEA). Results: Energy intake was significantly lower (p = 0.02) at week 10 compared with baseline. Total F and V intake was significantly higher at week 2 and week 10 (p < 0.05). In total, 123 urinary metabolites were quantified. At week 10, 21 metabolites showed significant changes relative to baseline. Of these, 11 metabolites also significantly changed at week 2. These overlapping metabolites were acetic acid, dimethylamine, choline, fumaric acid, glutamic acid, L-tyrosine, histidine, succinic acid, uracil, histamine, and 2-hydroxyglutarate. Ridge Classifier and Linear Discriminant Analysis provided best prediction accuracy values of 0.96 when metabolite level of baseline was compared to week 10. Conclusions: Urinary metabolites quantified represent potential candidate biomarkers of high F and V intake, associated with a reduction in energy intake. Further studies are needed to validate these findings in larger population studies. Full article

Pancreatic cancer is one of the most aggressive cancers with a very poor 5-year survival rate and reduced therapeutic options when diagnosed in an advanced stage. The dismal prognosis of pancreatic cancer has guided significant efforts to discover novel biomarkers in order to anticipate diagnosis, increasing the population of patients who can benefit from curative surgical treatment. CA 19-9 is the reference biomarker that supports the diagnosis and guides the response to treatments. However, it has significant limitations, a low specificity, and is inefficient as a screening tool. Several potential biomarkers have been discovered in the serum, urine, feces, and pancreatic juice of patients. However, most of this evidence needs further validation in larger cohorts. The advent of advanced omics sciences and liquid biopsy techniques has further enhanced this field of research. The aim of this review is to analyze the historical evolution of the research on novel biomarkers for the early diagnosis of pancreatic cancer, focusing on the current evidence for the most promising biomarkers from different body fluids and the novel trends in research, such as omics sciences and liquid biopsy, in order to favor the application of modern personalized medicine. Full article

Background/Objectives: Myostatin, primarily produced by skeletal muscle, inhibits muscle growth and promotes protein degradation. It has been implicated in conditions such as obesity, insulin resistance, and cardiovascular disease. However, its association with endothelial function in chronic kidney disease (CKD) patients remains unclear. This study aimed to investigate the relationship between serum myostatin levels and endothelial function in 136 non-dialysis CKD patients at stages 3–5. Methods: Fasting blood samples were collected to measure serum myostatin levels using enzyme-linked immunosorbent assay kits. Endothelial function was evaluated non-invasively by measuring the vascular reactivity index (VRI) with a digital thermal monitoring test. Results: VRI values were classified as poor (<1.0, n = 25, 18.4%), intermediate (1.0 to <2.0, n = 63, 46.3%), or good (≥2.0, n = 48, 35.3%). Factors associated with poor vascular reactivity included older age (p = 0.026), elevated serum blood urea nitrogen (p = 0.020), serum creatinine (p = 0.021), urine protein-to-creatinine ratio (UPCR, p = 0.013), and myostatin levels (p = 0.003), along with reduced estimated glomerular filtration rate (p = 0.015). Multivariate regression analysis identified older age, higher serum creatinine, and log-transformed myostatin levels as significant independent predictors of lower VRI. Conclusions: These findings suggest that myostatin may serve as a potential biomarker for endothelial dysfunction in CKD patients. Future large-scale, longitudinal studies are warranted to confirm and extend our preliminary findings. Full article