Association between estrogen receptors and GATA3 in bladder cancer: a systematic review and meta-analysis of their clinicopathological significance

Background: Estrogen receptors alpha (ERα) and beta (ERβ) and the cooperating protein GATA-binding factor 3 (GATA3) have been implicated in bladder carcinogenesis and tumour progression. GATA3 and ER have been functionally linked in the establishment of luminal fate in breast tissue, but to date their relationship in bladder cancer has not been established. This information will be useful to advance diagnostic and prognostic markers. Aim: To determine the relationship between the expression of ERα, ERβ and GATA3 in bladder cancer, disclose their prognostic and diagnostic value and their association with clinicopathological characteristics. Methods: A comprehensive literature search in PubMed database was performed for all immunohistochemical studies of ERα, ERβ and/or GATA3 in bladder cancer patients. We selected eligible studies in accordance with the PRISMA guidelines and evaluated methodological quality and risk of bias based on quality criteria from the reporting recommendations for tumour MARKer (REMARK) prognostic studies. Risk of bias assessment was performed using Review Manager 5. R software was used for all statistical analysis, the packages used were meta and dmetar for the standard meta-analysis, and netmeta for the network meta-analysis. Results: Thirteen studies were eligible for ERα, 5 for ERβ and 58 for GATA3 meta-analysis. Low grade tumours showed significantly lower ERα expression. GATA3 was widely expressed in bladder tumours, especially urothelial carcinomas, with higher expression of GATA3 in low grade and low stage tumours. Data was insufficient to determine the prognostic value of either ERα or ERβ, but GATA3-positivity was associated with higher recurrence free survival. A negative correlation between ERα or ERβ positivity and GATA3 expression was disclosed. Additionally, several sources of heterogeneity were identified, which can be used to improve future studies. Conclusion: The clinicopathological value of ERα and ERβ was inconclusive due to low availability of studies using validated antibodies. Still, this meta-analysis supports GATA3 as good prognostic marker. On the contrary, ERα-positivity was associated to higher grade tumours; while ERα and ERβ were inversely correlated with GATA3 expression. Considering that it has previously been shown that bladder cancer cell lines have functional ERs, this suggests that ERα could be activated in less differentiated cells and independently of GATA3. Therefore, a comprehensive analysis of ERα and ERβ expression in BlaCa supported by complete patient clinical history is required for the identification of BlaCa subtypes and subgroups of patients expressing ERα, to investigate if they could benefit from treatment with hormonal therapy. Systematic Review Registration: Prospero, CRD42021226836.publishe

Comparative Analysis of Viperidae Venoms Antibacterial Profile: a Short Communication for Proteomics

Bacterial infections involving multidrug-resistant strains are one of the ten leading causes of death and an important health problem in need for new antibacterial sources and agents. Herein, we tested and compared four snake venoms (Agkistrodon rhodostoma, Bothrops jararaca, B. atrox and Lachesis muta) against 10 Gram-positive and Gram-negative drug-resistant clinical bacteria strains to identify them as new sources of potential antibacterial molecules. Our data revealed that, as efficient as some antibiotics currently on the market (minimal inhibitory concentration (MIC) = 1–32 μg mL−1), A. rhodostoma and B. atrox venoms were active against Staphylococcus epidermidis and Enterococcus faecalis (MIC = 4.5 μg mL−1), while B. jararaca inhibited S. aureus growth (MIC = 13 μg ml−1). As genomic and proteomic technologies are improving and developing rapidly, our results suggested that A. rhodostoma, B. atrox and B. jararaca venoms and glands are feasible sources for searching antimicrobial prototypes for future design new antibiotics against drug-resistant clinical bacteria. They also point to an additional perspective to fully identify the pharmacological potential of these venoms by using different techniques

Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers.

Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of sterol derivatives are metabolized to active quinones that can modify DNA, which in other contexts can lead to breast and other cancers, helminth parasite associated sterols might induce tumor-like phenotypes in the target cells susceptible to helminth parasite associated cancers, i.e., urothelial cells of the bladder in the case of urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced cancers originate from parasite estrogen-host epithelial/urothelial cell chromosomal DNA adducts, and here we review recent findings that support this conjecture

Functional screening for the detection of β-glucosidase activity in a metagenomic library obtained from a compost sample

There is an increasing need to find novel and robust biocatalysts with promising features that compete with those currently available on the market. Composting is an extreme habitat of high microbiological diversity that represents a suitable source of lignocellulose-degrading enzymes, such as cellulases, hemicellulases and ligninases, properly active under harsh conditions. These enzymes can convert the recalcitrant structure of lignocellulose into valuable bioproducts with great biotechnological potential. -Glucosidases are glycoside hydrolases responsible for degrading cellulose, namely in the disruption of the final glycosidic bonds of short-chain oligosaccharides to obtain glucose. Metagenomics is an emerging cultureindependent technique that has proven effective in identifying new biocatalysts with better catalytic activity through the analysis of DNA extracted from a vast number of environments. The metagenomic analysis is divided into two main technologies: sequence- and functionalbased approach. Function-based screening aims to discover and identify new genes capable of producing biocompounds/biomolecules with new or improved functions. This screening is based on the detection and isolation of clones with a positive response to the desired phenotype when activity-based techniques are applied. In this study, high-molecular-weight DNA extracted from a compost sample was used to construct a fosmid metagenomic library. This library was evaluated through a functional screening to identify clones that expressed cellulase activity, specifically -glucosidase activity. The enzymatic activity was unravelled using esculin as substrate through the formation of a brown halo as a positive response (Figure 1). The functional screening was performed in 96-well microplates and the detection of - glucosidase activity was evaluated at different temperature (25-60 °C) and pH (4.5-9.5) conditions. It was possible to identify clones with the enzymatic activity of -glucosidase in almost all tested conditions, except at 60 °C. The best conditions for clone growth occur in a longer initial incubation time (3 days, 37 °C). On the other hand, the lower pH and incubation temperature favoured a faster detection of -glucosidase activity.The study received financial support from the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and the Project LIGNOZYMES (POCI-01-0145-FEDER-029773).info:eu-repo/semantics/publishedVersio

Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumour aggressiveness

Monocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladder tumors, namely their preponderance on the tumor stroma, remains to be elucidated. Thus, we evaluated the immunoexpression of MCTs in the different compartments of UBC tissue samples (n = 111), assessing the correlations among them and with the clinical and prognostic parameters. A significant decrease in positivity for MCT1 and MCT4 occurred from normoxic toward hypoxic regions. Significant associations were found between the expression of MCT4 in hypoxic tumor cells and in the tumor stroma. MCT1 staining in normoxic tumor areas, and MCT4 staining in hypoxic regions, in the tumor stroma and in the blood vessels were significantly associated with UBC aggressiveness. MCT4 concomitant positivity in hypoxic tumor cells and in the tumor stroma, as well as positivity in each of these regions concomitant with MCT1 positivity in normoxic tumor cells, was significantly associated with an unfavourable clinicopathological profile, and predicted lower overall survival rates among patients receiving platinum-based chemotherapy. Our results point to the existence of a multi-compartment metabolic model in UBC, providing evidence of a metabolic coupling between catabolic stromal and cancer cells' compartments, and the anabolic cancer cells. It is urgent to further explore the involvement of this metabolic coupling in UBC progression and chemoresistance.This study was supported by the Life and Health Sciences Research Institute (ICVS) from the School of Health Sciences of the University of Minho. JA received a postdoctoral fellowship from ICVS (reference ICVS-SSRL: ON.2 SR&TD Integrated Program, NORTE-07-0124-FEDER-000017).info:eu-repo/semantics/publishedVersio

Combining diversity queries and visual mining to improve content-based image retrieval systems: the DiVI method

This paper proposes a new approach to improve similarity queries with diversity, the Diversity and Visually-Interactive method (DiVI), which employs Visual Data Mining techniques in Content-Based Image Retrieval (CBIR) systems. DiVI empowers the user to understand how the measures of similarity and diversity affect their queries, as well as increases the relevance of CBIR results according to the user judgment. An overview of the image distribution in the database is shown to the user through multidimensional projection. The user interacts with the visual representation changing the projected space or the query parameters, according to his/her needs and previous knowledge. DiVI takes advantage of the users’ activity to transparently reduce the semantic gap faced by CBIR systems. Empirical evaluation show that DiVI increases the precision for querying by content and also increases the applicability and acceptance of similarity with diversity in CBIR systems.FAPESPCNPqCAPESRescuer Project (European Commission Grant 614154 and CNPq/MCTI Grant 490084/2013-3