Urinary extracellular vesicles as potential biomarkers for urologic cancers: An overview of current methods and advances

Urologic cancers are a heterogeneous group of tumors, some of which have poor progno-sis. This is partly due to the unavailability of specific and sensitive diagnostic techniques and monitoring tests, ideally non-or minimally invasive. Hence, liquid biopsies are promising tools that have been gaining significant attention over the last decade. Among the different classes of bi-omarkers that can be isolated from biofluids, urinary extracellular vesicles (uEVs) are a promising low-invasive source of biomarkers, with the potential to improve cancer diagnosis and disease man-agement. Different techniques have been developed to isolate and characterize the cargo of these vesicles; however, no consensus has been reached, challenging the comparison among studies. This results in a vast number of studies portraying an extensive list of uEV-derived candidate biomarkers for urologic cancers, with the potential to improve clinical outcome; however, without significant validation. Herein, we review the current published research on miRNA and protein-derived uEV for prostate, bladder and kidney cancers, focusing on different uEV isolation methods, and its implications for biomarker studies.The APC was funded by CI-IPOP-PI27-FB-GEBC and TRIMARKCHIP (POCI-01-0145-FEDER-030831 and PTDC/BTM-TEC/30831/2017). VC received the support of a fellowship from “la Caixa” Foundation (ID 100010434). The fellowship code is LCF/BQ/DR20/11790013

Kinetics of optical properties of colorectal muscle during optical clearing

In this paper, we describe a simple and indirect method to evaluate the kinetics of the optical properties for biological tissues under optical clearing treatments. We use the theoretical formalism in this method to process experimental data obtained from colorectal muscle samples to evaluate and characterize the dehydration and refractive index matching mechanisms

Glucose diffusion in colorectal mucosa - a comparative study between normal and cancer tissues

Colorectal carcinoma is a major health concern worldwide and its high incidence and mortality require accurate screening methods. Following endoscopic examination, polyps must be removed for histopathological characterization. Aiming to contribute to the improvement of current endoscopy methods of colorectal carcinoma screening or even for future development of laser treatment procedures, we studied the diffusion properties of glucose and water in colorectal healthy and pathological mucosa. These parameters characterize the tissue dehydration and the refractive index matching mechanisms of optical clearing (OC). We used ex vivo tissues to measure the collimated transmittance spectra and thickness during treatments with OC solutions containing glucose in different concentrations. These time dependencies allowed for estimating the diffusion time and diffusion coefficient values of glucose and water in both types of tissues. The measured diffusion times for glucose in healthy and pathological mucosa samples were 299.2 ± 4.7 ?? s and 320.6 ± 10.6 ?? s for 40% and 35% glucose concentrations, respectively. Such a difference indicates a slower glucose diffusion in cancer tissues, which originate from their ability to trap far more glucose than healthy tissues. We have also found a higher free water content in cancerous tissue that is estimated as 64.4% instead of 59.4% for healthy mucosa

Kinetics of optical properties of human colorectal tissues during optical clearing: a comparative study between normal and pathological tissues

To characterize the optical clearing treatments in human colorectal tissues and possibly to differentiate between treatments of normal and pathological tissues, we have used a simple indirect method derived from Mie scattering theory to estimate the kinetics of the reduced scattering coefficient. A complementary method to estimate the kinetics of the scattering coefficient is also used so that the kinetics of the anisotropy factor and of the refractive index are also calculated. Both methods rely only on the thickness and collimated transmittance measurements made during treatment. The results indicate the expected time dependencies for the optical properties of both tissues: an increase in the refractive index and anisotropy factor and a decrease in the scattering coefficients. The similarity in the kinetics obtained for normal and pathological tissues indicates that optical clearing treatments can be applied also in pathological tissues to produce similar effects. The estimated time dependencies using experimental spectral data in the range from 400 to 1000 nm allowed us to compare the kinetics of the optical properties between different wavelengths.info:eu-repo/semantics/publishedVersio

numerical modelling and validation

Publisher Copyright: © 2023 The Author(s)This study investigates the Non-Destructive Testing (NDT) inspection of 3D-printed fibre-reinforced polymers, comparing the conventional Active Transient Thermography (ATT) technique with a novel variant known as Double Active Transient Thermography (DATT). Finite element models for the simulation of both inspection techniques are validated by evaluating two statistical measures to correlate the numerical results with the experimental responses. The thermal contrast obtained with DATT was approximately twice the one obtained with ATT, for all tested samples. Numerical models allowed an insight evaluation of the heat dissipation along the thickness of the specimens, specifically around the fibres and the defects. These validated numerical models evidenced a relevant tool to predict the results of thermal contrast and to optimize the inspection parameters.publishersversionpublishe

Diffuse reflectance and machine learning techniques to differentiate colorectal cancer ex vivo

In this study, we used machine learning techniques to reconstruct the wavelength dependence of the absorption coefficient of human normal and pathological colorectal mucosa tissues. Using only diffuse reflectance spectra from the ex vivo mucosa tissues as input to algorithms, several approaches were tried before obtaining good matching between the generated absorption coefficients and the ones previously calculated for the mucosa tissues from invasive experimental spectral measurements. Considering the optimized match for the results generated with the multilayer perceptron regression method, we were able to identify differentiated accumulation of lipofuscin in the absorption coefficient spectra of both mucosa tissues as we have done before with the corresponding results calculated directly from invasive measurements. Considering the random forest regressor algorithm, the estimated absorption coefficient spectra almost matched the ones previously calculated. By subtracting the absorption of lipofuscin from these spectra, we obtained similar hemoglobin ratios at 410/550 nm: 18.9-fold/9.3-fold for the healthy mucosa and 46.6-fold/24.2-fold for the pathological mucosa, while from direct calculations, those ratios were 19.7-fold/10.1-fold for the healthy mucosa and 33.1-fold/17.3-fold for the pathological mucosa. The higher values obtained in this study indicate a higher blood content in the pathological samples used to measure the diffuse reflectance spectra. In light of such accuracy and sensibility to the presence of hidden absorbers, with a different accumulation between healthy and pathological tissues, good perspectives become available to develop minimally invasive spectroscopy methods for in vivo early detection and monitoring of colorectal cancer.The application of machine learning methods to noninvasivelike diffuse reflectance spectra allowed us to reconstruct the absorption coefficient spectra of human healthy and pathological mucosa tissues from the colorectal wall. Consequently, we were able to obtain differentiated blood and pigment content in both tissues, which can be used for the development of new noninvasive diagnostic methods for colorectal cancer.The work of L. M. Oliveira was supported by the Portuguese Science Foundation (Grant No. FCT-UIDB/04730/2020). The work of V. V. Tuchin was supported by a grant of the Government of the Russian Federation (Registration No. 2020-220-08-2389).info:eu-repo/semantics/publishedVersio

Tissue Spectroscopy and Optical Clearing of Colorectal Mucosa in the Pursuit of New Cancer Diagnostic Approaches

In this paper we present three studies that demonstrate the applicability of spectroscopy methods and optical clearing treatments in pathology identification and monitoring. In the first study, by obtaining the absorption spectra of human healthy and pathological (adenocarcinoma) colorectal mucosa tissues, it was possible to identify a higher content of a pigment in the diseased tissues. This study also shows that machine learning methods can be used to reach the same differentiated results in vivo through diffuse reflectance spectroscopy. In the second study, the combination of collimated transmittance spectroscopy with optical clearing treatments allowed to obtain the diffusion coefficients of glucose in healthy and pathological colorectal mucosa as: Dglucose=5.8x10–7 cm2/s and Dglucose=4.4x10–7 cm2/s, respectively. This study also demonstrated that the diseased tissues contains about 5% more mobile water than the healthy tissues. The third study was performed to evaluate the protein dissociation mechanism of optical clearing. By treating both healthy and pathological colorectal mucosa tissues with 93%-glycerol, a protein dissociation rate of about 3 times higher was obtained for the pathological mucosa. All the discriminating parameters that result from these studies can be obtained in the in vivo situation through diffuse reflectance spectroscopy and further studies to evaluate their values in different stages of cancer progression are of great importance to develop disease monitoring protocols.The authors of the article knew well and communicated with Ekaterina Borisova for many years, especially Valery Tuchin and in recent years Luís Oliveira. We had many joint plans to organize conferences and joint research projects, but COVID-19 mercilessly interrupted our communication. We have lost a great scientist and a person with a huge soul, sociable, but at the same time modest and kind. We will always remember our warm meetings and fruitful work with Ekaterina. This research was supported by the Portuguese grant FCT-UIDB/04730/2020. VVT was supported by grant under the Decree of the Government of the Russian Federation No. 220 of 09 April 2010 (Agreement No. 075-15-2021-615 of 04 June 2021).info:eu-repo/semantics/publishedVersio

Androgens and low density lipoprotein-cholesterol interplay in modulating prostate cancer cell fate and metabolism

Background: Androgens, the known drivers of prostate cancer (PCa), have been indicated as important metabolic regulators with a relevant role in stimulating lipid metabolism. Also, the relationship between obesity and the aggressiveness of PCa has been established. However, it is unknown if the androgenic hormonal environment may alter the response of PCa cells to lipid availability. Purpose: The present study evaluated the effect of 5 alpha-dihydrotestosterone (DHT) in regulating lipid metabolism, and the interplay between this hormone and low-density lipoprotein (LDL)-cholesterol in modulating PCa cells fate.Methods: Non-neoplastic and neoplastic PCa cells were treated with 10 nM DHT, and the expression of fatty acids transporter, fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A) evaluated. PCa cells were also exposed to LDL (100 mu g/ml) in the presence or absence of DHT.Results: Treatment with DHT upregulated the expression of FASN and CPT1A in androgen-sensitive PCa cells. In contrast, LDL supplementation suppressed FASN expression regardless of the presence of DHT, whereas aug-menting CPT1A levels. Our results also showed that LDL-cholesterol increased PCa cells viability, proliferation, and migration dependently on the presence of DHT. Moreover, LDL and DHT synergistically enhanced the accumulation of lipid droplets in PCa cells.Conclusions: The obtained results show that androgens deregulate lipid metabolism and enhance the effects of LDL increasing PCa cells viability, proliferation and migration. The present findings support clinical data linking obesity with PCa and first implicate androgens in this relationship. Also, they sustain the application of phar-macological approaches targeting cholesterol availability and androgens signaling simultaneously.info:eu-repo/semantics/publishedVersio

Fast calculation of spectral optical properties and pigment content detection in human normal and pathological kidney

A fast calculation method was used to obtain the spectral optical properties of human normal and pathological (chromophobe renal cell carcinoma) kidney tissues. Using total transmittance, total reflectance and collimated transmittance spectra acquired from ex vivo kidney samples, the spectral optical properties of both tissues, namely the absorption, the scattering and the reduced scattering coefficients, as well as the scattering anisotropy, dispersion and light penetration depth, were calculated between 200 and 1000 nm. Analysis of the mean ab sorption coefficient spectra of the kidney tissues showed that both contain melanin and lipofuscin, and that 83 % of the melanin in the normal kidney converts into lipofuscin in the pathological kidney.info:eu-repo/semantics/publishedVersio