Given the stochastic complexity of cancer diseases, the development of chemotherapeutic drugs is almost limited by problems of selectivity and side effects. Furthermore, an increasing number of protective approaches have been recently considered as the main way to limit these pathologies. Natural bioactive compounds, and particularly dietary phenolic compounds, showed major protective and therapeutic effects against different types of human cancers. Indeed, phenolic substances have functional groups that allow them to exert several anti-cancer mechanisms, such as the induction of apoptosis, autophagy, cell cycle arrest at different stages, and the inhibition of telomerase. In addition, in vivo studies show that these phenolic compounds also have anti-angiogenic effects via the inhibition of invasion and angiogenesis. Moreover, clinical studies have already highlighted certain phenolic compounds producing clinical effects alone, or in combination with drugs used in chemotherapy. In the present work, we present a major advance in research concerning the mechanisms of action of the different phenolic compounds that are contained in food medicinal plants, as well as evidence from the clinical trials that focus on them.

The hypermethylation status of the promoter region of the breast cancer 1 (BRCA1), a well-known tumor suppressor gene, has been extensively investigated in the last two decades as a potential biomarker for breast cancer. In this retrospective study, we investigated the prevalence of BRCA1 promoter methylation in 84 human breast tissues, and we correlated this epigenetic silencing with the clinical and histopathological parameters of breast cancer. We used methylation-specific PCR (MSP) to analyze BRCA1 promoter hypermethylation in 48 malignant breast tumors (MBTs), 15 normal adjacent tissues (NATs), and 21 benign breast lesions (BBLs). The results showed that BRCA1 promoter hypermethylation was higher in MBTs (20/48; 41.67%) and NATs (7/15; 46.67%) compared to BBLs (4/21; 19.05%). The high percentage of BRCA1 hypermethylation in the histologically normal adjacent tissues to the tumors (NATs) suggests the involvement of this epigenetic silencing as a potential biomarker of the early genomic instability in NATs surrounding the tumors. The detection of BRCA1 promoter hypermethylation in BBLs reinforces this suggestion, knowing that a non-negligible rate of benign breast lesions was reported to evolve into cancer. Moreover, our results indicated that the BRCA1 promoter hypermethylated group of MBTs exhibited higher rates of aggressive features, as indicated by the SBR III grade (14/19; 73.68%), elevated Ki67 levels (13/16; 81.25%), and Her2 receptor overexpression (5/20; 25%). Finally, we observed a concordance (60%) in BRCA1 promoter hypermethylation status between malignant breast tumors and their paired histologically normal adjacent tissues. This study highlights the role of BRCA1 promoter hypermethylation as a potential useful biomarker of aggressiveness in MBTs and as an early marker of genomic instability in both histological NATs and BBLs.

The human gastrointestinal tract harbors a vast array of microorganisms, which play essential roles in maintaining metabolic balance and immune function. While bacteria dominate the gut microbiome, fungi represent a much smaller, often overlooked fraction. Despite their relatively low abundance, fungi may significantly influence both health and disease. Advances in next-generation sequencing, metagenomics, metatranscriptomics, metaproteomics, metabolomics, and computational biology have provided novel opportunities to study the gut mycobiome, shedding light on its composition, functional genes, and metabolite interactions. Emerging evidence links fungal dysbiosis to various diseases, including inflammatory bowel disease, colorectal cancer, metabolic disorders, and neurological conditions. The gut mycobiome also presents a promising avenue for precision medicine, particularly in biomarker discovery, disease diagnostics, and targeted therapeutics. Nonetheless, significant challenges remain in effectively integrating gut mycobiome knowledge into clinical practice. This review examines gut fungal microbiota, highlighting analytical methods, associations with human diseases, and its potential role in precision medicine. It also discusses pathways for clinical translation, particularly in diagnosis and treatment, while addressing key barriers to implementation.

The comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAF^V600E tumors compared to PTC-BRAF^wt tumors. However, a comparative analysis of NOX4 at the protein level in malignant and non-malignant tumors is missing. We explored NOX4 protein expression by immunohistochemistry staining in malignant tumors (28 classical forms of PTC (C-PTC), 17 follicular variants of PTC (F-PTC), and three anaplastic thyroid carcinomas (ATCs)) and in non-malignant tumors (six lymphocytic thyroiditis, four Graves’ disease, ten goiters, and 20 hyperplasias). We detected the BRAF^V600E mutation by Sanger sequencing and digital droplet PCR. The results show that NOX4 was found to be higher (score ≥ 2) in C-PTC (92.9%) compared to F-PTC (52.9%) and ATC (33.3%) concerning malignant tumors. Interestingly, all C-PTC-BRAF^V600E expressed a high score for NOX4 at the protein level, strengthening the positive correlation between the BRAF^V600E mutation and NOX4 expression. In addition, independent of the mutational status of BRAF, we observed that 90% of C-PTC infiltrating tumors showed high NOX4 expression, suggesting that NOX4 may be considered a complementary biomarker in PTC aggressiveness. Interestingly, NOX4 was highly expressed in non-malignant thyroid diseases with different subcellular localizations.

Background/Objectives: Y chromosome microdeletions in the azoospermia factor (AZF) regions are a major genetic cause of severe male infertility, yet their relationship with hormonal profiles in azoospermic men remains unclear. This study aimed to investigate AZF microdeletions and associated hormonal parameters in azoospermic patients. Methods: Azoospermic patients were screened for AZFa, AZFb, and AZFc microdeletions using multiplex real-time PCR targeting sequence-tagged site (STS) markers (sY84, sY127, and sY254). Patients were categorized into AZF-negative and AZF-positive groups, with the latter further stratified according to their deletion subtype. Serum follicle-stimulating hormone (FSH), testosterone, and inhibin B levels were measured. Hormonal parameters were compared between groups using the Mann–Whitney U test, and a logistic regression analysis was performed to evaluate associations between hormonal variables and AZF deletion status. Results: AZF microdeletions were detected in 18.7% (17/91) of patients. Patients without AZF deletions showed a median FSH level of 17.40 (7.12–31.27) IU/L. In contrast, AZFc deletion carriers exhibited an intermediate median FSH level of 21.10 (16.11–26.10) IU/L and lower median inhibin B concentrations (25.50 [25.25–26.00] pg/mL) compared with AZF-negative patients (56.00 [33.50–106.50] pg/mL). Median testosterone levels in AZFc patients (3.61 [2.87–4.35] ng/mL) remained within the expected physiological range. However, no statistically significant differences were observed between the AZF subgroups for age (p = 0.262), FSH (p = 0.506), testosterone (p = 0.615), or inhibin B (p = 0.524). The logistic regression analysis also showed no significant association between hormonal parameters and AZF deletion status. Conclusions: Hormonal parameters alone are insufficient to predict the presence of AZF microdeletions in azoospermic men. These findings highlight the importance of routine genetic screening for accurate diagnosis, clinical management, and reproductive counseling in male infertility.