Currently, the only definitive method for diagnosing ovarian cancer involves histological examination of tissue obtained at time of surgery or by invasive biopsy. Blood has traditionally been the biofluid of choice in ovarian cancer biomarker discovery; however, there has been a growing interest in exploring urinary biomarkers, particularly as it is non-invasive. In this systematic review, we present the diagnostic accuracy of urinary biomarker candidates for the detection of ovarian cancer. A comprehensive literature search was performed using the MEDLINE/PubMed and EMBASE, up to 1 st April 2021. All included studies reported the diagnostic accuracy using sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. Risk of bias and applicability of included studies were assessed using the QUADAS-2 tool.
Twenty seven studies were included in the narrative synthesis. Protein/peptide biomarkers were most commonly described (n=18), with seven studies reporting composite scores of multiple protein-based targets. The most frequently described urinary protein biomarker was HE4 (n=5), with three studies reporting a sensitivity and specificity >80%. Epigenetic (n=1) and metabolomic/organic compound biomarkers (n=8) were less commonly described. Overall, six studies achieved a sensitivity and specificity of >90% and/or an AUC >0.9. Evaluation of urinary biomarkers for the detection of ovarian cancer is a dynamic and growing field. Currently, the most promising biomarkers are those that interrogate metabolomic pathways and organic compounds, or quantify multiple proteins. Such biomarkers require external validation in large, prospective observational studies before they can be implemented into clinical practice.
Rapid electrostatic DNA enrichment for sensitive detection of Trichomonas vaginalis in clinical urinary samples
Estimated to be the most common non-viral sexually transmitted infection globally, Trichomonas vaginalis (TV) can lead to pelvic inflammatory disease, pregnancy complications, and increased risk of acquiring and transmitting HIV. Once diagnosed, TV infection can be treated with oral antibiotics; however, infected individuals are often asymptomatic and do not seek treatment. The WHO and others have identified a need for point-of-care tests to expand access to TV testing and screening; ideal test characteristics include high sensitivity and specificity and the ability to use urine as a sample type, rather than invasively collected swab samples. Here, we report on a proof-of-concept prototype for rapid, electrostatic enrichment of DNA from urine samples and demonstrate the use of large volumes of urine to increase sensitivity of downstream nucleic acid amplification testing.
We developed an internally controlled thermophilic helicase-dependent amplification (tHDA) assay with lateral flow immunoassay readout and demonstrate that this tHDA assay can be performed directly on our DNA capture filter. We validated our method using clinical urine samples with qPCR-quantified TV loads. Using 62 clinical urine samples and a simple sample processing device, our tHDA assay displayed 96.6% sensitivity and 100% specificity. Our analytical limit of detection was found to be approximately 7 genomic equivalents of TV DNA per mL of sample when 1 mL of sample was tested, comparable to existing isothermal tests for TV. Using large-volume simulated samples (40 mL of buffered urine with spiked-in TV DNA), we also demonstrated that sensitivity could be improved 28-fold to 0.25 genomic equivalents of TV DNA per mL, with a sample processing time of only 2 minutes.
Nanomaterials-Based Urinary Extracellular Vesicles Isolation and Detection for Non-invasive Auxiliary Diagnosis of Prostate Cancer
Extracellular vesicles (EVs) are natural nanoparticles secreted by cells in the body and released into the extracellular environment. They are associated with various physiological or pathological processes, and considered as carriers in intercellular information transmission, so that EVs can be used as an important marker of liquid biopsy for disease diagnosis and prognosis. EVs are widely present in various body fluids, among which, urine is easy to obtain in large amount through non-invasive methods and has a small dynamic range of proteins, so it is a good object for studying EVs. However, most of the current isolation and detection of EVs still use traditional methods, which are of low purity, time consuming, and poor efficiency; therefore, more efficient and highly selective techniques are urgently needed. Recently, inspired by the nanoscale of EVs, platforms based on nanomaterials have been innovatively explored for isolation and detection of EVs from body fluids.
These newly developed nanotechnologies, with higher selectivity and sensitivity, greatly improve the precision of isolation target EVs from urine. This review focuses on the nanomaterials used in isolation and detection of urinary EVs, discusses the advantages and disadvantages between traditional methods and nanomaterials-based platforms, and presents urinary EV-derived biomarkers for prostate cancer (PCa) diagnosis. We aim to provide a reference for researchers who want to carry out studies about nanomaterial-based platforms to identify urinary EVs, and we hope to summarize the biomarkers in downstream analysis of urinary EVs for auxiliary diagnosis of PCa disease in detail.
Rational Design of Phe-BODIPY Amino Acids as Fluorogenic Building Blocks for Peptide-based Detection of Urinary Tract Candida Infections
Fungal infections caused by Candida species are among the most prevalent in hospitalized patients. However, current methods for the detection of Candida fungal cells in clinical samples rely on time-consuming assays that hamper rapid and reliable diagnosis. Herein, we describe the rational development of new Phe-BODIPY amino acids as small fluorogenic building blocks and their application to generate fluorescent antimicrobial peptides for rapid labelling of Candida cells in urine.
We have used computational methods to analyse the fluorogenic behaviour of BODIPY-substituted aromatic amino acids and performed bioactivity and confocal microscopy experiments in different strains to confirm the utility and versatility of peptides incorporating Phe-BODIPYs. Finally, we have designed a simple and sensitive fluorescence-based assay for the detection of Candida albicans in human urine samples.
Creatinine Urinary Detection Kit (2 Plate) |
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| K002-H1 | Arbor Assays | 2x96 well plates | 271 EUR |
Creatinine Urinary Detection Kit (10 Plate) |
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| K002-H5 | Arbor Assays | 10x96 well plates | 949 EUR |
Urine Creatinine Detection Kit |
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| SKT-200-192 | Stressmarq | 2 plates of 96 wells | 410.4 EUR |
Exosome Purification and Detection Kit (Urine) |
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| abx290027-25tests | Abbexa | 25 tests | 777.6 EUR |
NGAL (Detection Ab) |
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| abx019242-100ug | Abbexa | 100 ug | 777.6 EUR |
SEB Detection Kit |
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| 6030 | Chondrex | 1 kit | 663.78 EUR |
TLR Detection Set |
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| PSI-1806 | ProSci | 1 Set | 1627.8 EUR |
PD1 Detection Set |
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| SD8600 | ProSci | 1 Set | 537.9 EUR |
IRAK Detection Set |
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| PSI-1802 | ProSci | 1 Set | 884.4 EUR |
ORAI Detection Set |
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| PSI-1819 | ProSci | 1 Set | 1627.8 EUR |
Grik Detection Set |
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| PSI-1824 | ProSci | 1 Set | 1627.8 EUR |
LAG3 Detection Set |
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| SD8700 | ProSci | 1 Set | 569.4 EUR |
PDL1 Detection Set |
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| SD8500 | ProSci | 1 Set | 355.2 EUR |
4x Detection Buffer |
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| 79389 | BPS Bioscience | 10 ml | 195 EUR |
HMGB1 Detection Kit |
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| 6010 | Chondrex | 1 kit | 903.9 EUR |
OVA Detection ELISA |
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| 6032 | Chondrex | 1 kit | 663.78 EUR |
SAPAP Detection Set |
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| PSI-1826 | ProSci | 1 Set | 752.1 EUR |
TIGIT Detection Set |
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| SD8800 | ProSci | 1 Set | 569.4 EUR |
Detection Reagent A |
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| abx296004-120ul | Abbexa | 120 ul | 385.2 EUR |
Human Urinary oxalate(urinary oxalate) ELISA Kit |
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| QY-E05414 | Qayee Biotechnology | 96T | 433.2 EUR |
TnI (Detection) Antibody |
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| abx018057-100ug | Abbexa | 100 ug | 410.4 EUR |
PCT (Detection) Antibody |
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| 20-abx019248 | Abbexa |
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Ecl Detection Reagents |
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| RPN2105 | Scientific Laboratory Supplies | EACH | 724.8 EUR |
Ecl Detection Reagents |
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| RPN3004 | Scientific Laboratory Supplies | EACH | 582 EUR |
Apoptosis Detection Kit |
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| ANXVKB-100T | ImmunoStep | 100 test | 557.64 EUR |
Apoptosis Detection Kit |
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| ANXVKCFB-100T | ImmunoStep | 100 test | 495.24 EUR |
A Prospective Multicenter Trial to Evaluate Urinary Metabolomics for Non-invasive Detection of Renal Allograft Rejection (PARASOL): Study Protocol and Patient Recruitment
Background: In an earlier monocentric study, we have developed a novel non-invasive test system for the prediction of renal allograft rejection, based on the detection of a specific urine metabolite constellation. To further validate our results in a large real-world patient cohort, we designed a multicentric observational prospective study (PARASOL) including six independent European transplant centers. This article describes the study protocol and characteristics of recruited better patients as subjects.
Methods: Within the PARASOL study, urine samples were taken from renal transplant recipients when kidney biopsies were performed. According to the Banff classification, urine samples were assigned to a case group (renal allograft rejection), a control group (normal renal histology), or an additional group (kidney damage other than rejection).
Results: Between June 2017 and March 2020, 972 transplant recipients were included in the trial (1,230 urine samples and matched biopsies, respectively). Overall, 237 samples (19.3%) were assigned to the case group, 541 (44.0%) to the control group, and 452 (36.7%) samples to the additional group. About 65.9% were obtained from male patients, the mean age of transplant recipients participating in the study was 53.7 ± 13.8 years. The most frequently used immunosuppressive drugs were tacrolimus (92.8%), mycophenolate mofetil (88.0%), and steroids (79.3%). Antihypertensives and antidiabetics were used in 88.0 and 27.4% of the patients, respectively. Approximately 20.9% of patients showed the presence of circulating donor-specific anti-HLA IgG antibodies at time of biopsy. Most of the samples (51.1%) were collected within the first 6 months after transplantation, 48.0% were protocol biopsies, followed by event-driven (43.6%), and follow-up biopsies (8.5%). Over time the proportion of biopsies classified into the categories Banff 4 (T-cell-mediated rejection [TCMR]) and Banff 1 (normal tissue) decreased whereas Banff 2 (antibody-mediated rejection [ABMR]) and Banff 5I (mild interstitial fibrosis and tubular atrophy) increased to 84.2 and 74.5%, respectively, after 4 years post transplantation. Patients with rejection showed worse kidney function than patients without rejection.
Conclusion: The clinical characteristics of subjects recruited indicate a patient cohort typical for routine renal transplantation all over Europe. A typical shift from T-cellular early rejections episodes to later antibody mediated allograft damage over time after renal transplantation further strengthens the usefulness of our cohort for the evaluation of novel biomarkers for allograft damage.