High-risk human papillomavirus (HR-HPV) infection, followed by chronic inflammation and oxidative stress, is a major risk factor of male infertility. In this study, we explored the potential impact of high-risk (HR) HPV genotypes in single infection (SI) and multiple infections (MI) that promote CYP2E1 expression, oxidative damage and pro-inflammatory cytokines, possibly contributing to sperm damage and male infertility. Semen samples from 101 infertile military men were studied. We analyzed seminal parameters, namely, HPV genotyping, cytochrome P450 2E1 (CYP2E1), oxidative stress biomarkers (total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD)), lipid peroxidation (LPO), 8-hydroxiguanosine (8-OHdG) and pro-inflammatory cytokines (IFN-γ, IL-1β, IL-4, IL-6 and IL-8). Eighty-one men (80.2%, 81/101) were positive for HPV infection, and MI-HR-HPV was higher than SI-HR-HPV (63% vs. 37%). HPV-52 was the most frequently detected type (18.5%), followed by HPV-33 (11.1%), and the most frequent combination of genotypes detected was HPV-33,52 (11.1%), followed by HPV-18,31 (6.2%). The group with infected samples presented lower normal morphology and antioxidant levels compared to non-infected samples. In concordance, the infected group showed high levels of LPO, IFN-γ, IL-1β, IL-4 and IL-6 and downregulation of CAT and SOD enzymes. Interestingly, changes in motility B, low levels of TAC, overexpression of CYP2E1, LPO and IL-8 levels were higher in MI-HR-HPV than SI-HR-HPV, suggesting that HPV infection promotes a chronic inflammatory process and a toxic and oxidative microenvironment, which increases with MI-HPV infections.

Background: Cytochrome P4502E1 (CYP2E1) metabolizes environmental toxins, however, compound metabolism can produce oxidative stress, causing in-cell toxicity and sometimes transformation. Aim: To evaluate CYP2E1 gene expression and its effects in antioxidant defenses, and cell toxicity in printing workers. Methods: The hierarchical method of health and chemical risk was used to evaluate chemical exposure in workplace. Blood samples and buccal epithelial cells were obtained from printing workers, and workers without any history of occupational exposure to chemicals (control group). Gene expression of CYP2E1, and antioxidant enzymes Superoxide dismutase (SOD) and Catalase (CAT) from leukocytes were evaluated. Hematic analysis and cell-free DNA from plasma were analyzed. Frequencies of cells with micronuclei (MN) and nuclear abnormalities from buccal epithelial cells were explored. Results: Evaluation of chemical exposure in working place demonstrated that ethyl alcohol, isopropyl alcohol, and isophorone represent 91% of the accumulated potential risk. CYP2E1 expression showed a 2.5-fold overexpression in the printing workers compared to the control group. SOD expression showed a 0.5-fold lower level in the printing workers than the control group, and CAT expression showed no differences between groups. Lower red blood cell and platelet values were detected in the printing workers than in the control group, and cell-free DNA plasma concentration was 3-fold higher in the printing workers than in the control group. The printing workers showed a higher frequency of cells with MN and nuclear anomalies than the control group. Conclusion: CYP2E1 overexpression triggers antioxidant defenses and toxic cell effects in printing workers.

Breast cancer is the most common malignancy in women around the world. Intratumor and intertumoral heterogeneity persist in mammary tumors. Therefore, the identification of biomarkers is essential for the treatment of this malignancy. This study analyzed 28,143 genes expressed in 49 breast cancer cell lines using a Weighted Gene Co-expression network analysis to determine specific target proteins for Basal A, Basal B, Luminal A, Luminal B and HER2 ampl breast cancer subtypes. Sixty-five modules were identified, of which five were characterized as having a high correlation with breast cancer subtypes. Genes overexpressed in the tumor were found to participate in the following mechanisms: regulation of the apoptotic process, transcriptional regulation, angiogenesis, signaling, and cellular survival. In particular, we identified the following genes, considered as hubs: IFIT3, an inhibitor of viral and cellular processes; ETS1, a transcription factor involved in cell death and tumorigenesis; ENSG00000259723 lncRNA, expressed in cancers; AL033519.3 a hypothetical gene; and TMEM86A, important for regulating keratinocyte membrane properties, considered as a key in Basal A, Basal B, Luminal A, Luminal B and HER2 ampl breast cancer subtypes, respectively. The modules and genes identified in this work can be used to identify possible biomarkers or therapeutic targets in different breast cancer subtypes.