Bladder cancer (BC) is characterized by high incidence and recurrence rates together with genomic instability and elevated mutation degree. Currently, cystoscopy combined with cytology is routinely used for diagnosis, prognosis and disease surveillance. Such an approach is often associated with several side effects, discomfort for the patient and high economic burden. Thus, there is an essential demand of non-invasive, sensitive, fast and inexpensive biomarkers for clinical management of BC patients. In this context, liquid biopsy represents a very promising tool that has been widely investigated over the last decade. Liquid biopsy will likely be at the basis of patient selection for precision medicine, both in terms of treatment choice and real-time monitoring of therapeutic effects. Several different urinary biomarkers have been proposed for liquid biopsy in BC, including DNA methylation and mutations, protein-based assays, non-coding RNAs and mRNA signatures. In this review, we summarized the state of the art on different available tests concerning their potential clinical applications for BC detection, prognosis, surveillance and response to therapy.

Mercury (Hg) is a global environmental pollutant that affects human and ecosystem health. With the aim of exploring the Hg-induced protein modifications, intact human erythrocytes were exposed to HgCl₂ (1–60 µM) and cytosolic and membrane proteins were analyzed by SDS-PAGE and AU-PAGE. A spectrofluorimetric assay for quantification of Reactive Oxygen Species (ROS) generation was also performed. Hg²⁺ exposure induces alterations in the electrophoretic profile of cytosolic proteins with a significant decrease in the intensity of the hemoglobin monomer, associated with the appearance of a 64 kDa band, identified as a mercurized tetrameric form. This protein decreases with increasing HgCl₂ concentrations and Hg-induced ROS formation. Moreover, it appears resistant to urea denaturation and it is only partially dissociated by exposure to dithiothreitol, likely due to additional protein–Hg interactions involved in aggregate formation. In addition, specific membrane proteins, including band 3 and cytoskeletal proteins 4.1 and 4.2, are affected by Hg²⁺-treatment. The findings reported provide new insights into the Hg-induced possible detrimental effects on erythrocyte physiology, mainly related to alterations in the oxygen binding capacity of hemoglobin as well as decreases in band 3-mediated anion exchange. Finally, modifications of cytoskeletal proteins 4.1 and 4.2 could contribute to the previously reported alteration in cell morphology.

Plant polyphenols, with broadly known antioxidant properties, represent very effective agents against environmental oxidative stressors, including mercury. This heavy metal irreversibly binds thiol groups, sequestering endogenous antioxidants, such as glutathione. Increased incidence of food-derived mercury is cause for concern, given the many severe downstream effects, ranging from kidney to cardiovascular diseases. Therefore, the possible beneficial properties of Feijoa sellowiana against mercury toxicity were tested using intact human red blood cells (RBC) incubated in the presence of HgCl₂. Here, we show that phenol-rich (10–200 µg/mL) extracts from the Feijoa sellowiana fruit potently protect against mercury-induced toxicity and oxidative stress. Peel and pulp extracts are both able to counteract the oxidative stress and thiol decrease induced in RBC by mercury treatment. Nonetheless, the peel extract had a greater protective effect compared to the pulp, although to a different extent for the different markers analyzed, which is at least partially due to the greater proportion and diversity of polyphenols in the peel. Furthermore, Fejioa sellowiana extracts also prevent mercury-induced morphological changes, which are known to enhance the pro-coagulant activity of these cells. These novel findings provide biochemical bases for the pharmacological use of Fejioa sellowiana-based functional foods in preventing and combating mercury-related illnesses.

The CD33 gene encodes for a member of the sialic-acid-binding immunoglobulin-type lectin (Siglec) family, and is one of the top-ranked Alzheimer’s disease (AD) risk genes identified by genome-wide association studies (GWAS). Many CD33 polymorphisms are associated with an increased risk of AD, but the function and potential mechanism of many CD33 single-nucleotide polymorphisms (SNPs) in promoting AD have yet to be elucidated. We recently identified the CD33 SNP rs2455069-A>G (R69G) in a familial form of dementia. Here, we demonstrate an association between the G allele of the rs2455069 gene variant and the presence of AD in a cohort of 195 patients from southern Italy. We carried out in silico analysis of the 3D structures of CD33 carrying the identified SNP to provide insights into its functional effect. Structural models of the CD33 variant carrying the R69G amino acid change were compared to the CD33 wild type, and used for the docking analysis using sialic acid as the ligand. Our analysis demonstrated that the CD33-R69G variant may bind sialic acid at additional binding sites compared to the wild type, thus potentially increasing its affinity/specificity for this molecule. Our results led to a new hypothesis of rs2455069-A>G SNP as a risk factor for AD, suggesting that a long-term cumulative effect of the CD33-R69G variant results from the binding of sialic acid, acting as an enhancer of the CD33 inhibitory effects on amyloid plaque degradation.

Bladder cancer is one of the most common cancers worldwide. Despite its high incidence, cystoscopy remains the currently used diagnostic gold standard, although it is invasive, expensive and has low sensitivity. As a result, the cancer diagnosis is mostly late, as it occurs following the presence of hematuria in urine, and population screening is not allowed. It would therefore be desirable to be able to act promptly in the early stage of the disease with the aid of biosensing. The use of devices/tools based on genetic assessments would be of great help in this field. However, the genetic differences between populations do not allow accurate analysis in the context of population screening. Current research is directed towards the discovery of universal biomarkers present in urine with the aim of providing an approach based on a non-invasive, easy-to-perform, rapid, and accurate test that can be widely used in clinical practice for the early diagnosis and follow-up of bladder cancer. An efficient biosensing device may have a disruptive impact in terms of patient health and disease management, contributing to a decrease in mortality rate, as well as easing the social and economic burden on the national healthcare system. Considering the advantage of accessing population screening for early diagnosis of cancer, the main challenges and future perspectives are critically discussed to address the research towards the selection of suitable biomarkers for the development of a very sensitive biosensor for bladder cancer.

Renal cell carcinoma, bladder cancer, and prostate cancer are the most widespread genitourinary tumors. Their treatment and diagnosis have significantly evolved over recent years, due to an increasing understanding of oncogenic factors and the molecular mechanisms involved. Using sophisticated genome sequencing technologies, the non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have all been implicated in the occurrence and progression of genitourinary cancers. Interestingly, DNA, protein, and RNA interactions with lncRNAs and other biological macromolecules drive some of these cancer phenotypes. Studies on the molecular mechanisms of lncRNAs have identified new functional markers that could be potentially useful as biomarkers for effective diagnosis and/or as targets for therapeutic intervention. This review focuses on the mechanisms underlying abnormal lncRNA expression in genitourinary tumors and discusses their role in diagnostics, prognosis, and treatment.