Insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) are signaling adaptor proteins that participate in canonical pathways, where insulin cascade activation occurs, as well as in non-canonical pathways, in which phosphorylation of substrates is carried out by a diverse array of receptors including integrins, cytokines, steroid hormones, and others. IRS proteins are subject to a spectrum of post-translational modifications essential for their activation, encompassing phosphorylation events in distinct tyrosine, serine, and threonine residues. Tyrosine residue phosphorylation is intricately linked to the activation of the insulin receptor cascade and its interaction with SH2 domains within a spectrum of proteins, including PI3K. Conversely, serine residue phosphorylation assumes a different function, serving to attenuate the effects of insulin. In this review, we have identified over 50 serine residues within IRS-1 that have been reported to undergo phosphorylation orchestrated by a spectrum of kinases, thereby engendering the activation or inhibition of different signaling pathways. Furthermore, we delineate the phosphorylation of over 10 distinct tyrosine residues at IRS-1 or IRS-2 in response to insulin, a process essential for signal transduction and the subsequent activation of PI3K.

The human papillomavirus (HPV) is recognized as the main etiologic agent associated with cervical cancer. HPVs are epitheliotropic, and the ones that infect the mucous membranes are classified into low-risk (LR) and high-risk (HR) types. LR-HPVs produce benign lesions, whereas HR-HPVs produce lesions that may progress to cancer. HR-HPV types 16 and 18 are the most frequently found in cervical cancer worldwide. E6 and E7 are the major HPV oncogenic proteins, and they have been profusely studied. Moreover, it has been shown that the HPV16 E5 (16E5) oncoprotein generates transformation, although the molecular mechanisms through which it carries out its activity have not been well defined. In contrast to E6 and E7, the E5 open reading frame is lost during the integration of the episomal HPV DNA into the cellular genome. This suggests that E5 acts at the early stages of the transformation process. In this review, we focused on the biochemical characteristics and functions of the HPV E5 oncoprotein, mainly on its association with growth factor receptors and other cellular proteins. Knowledge of the HPV E5 biology is important to understand the role of this oncoprotein in maintaining the viral cycle through the modulation of proliferation, differentiation, and apoptosis, as well as the alteration of other processes, such as survival, adhesion, migration, and invasion during early carcinogenesis. Finally, we summarized recent research that uses the E5 oncoprotein as a therapeutic target, promising a novel approach to the treatment of cervical cancer in its early stages.

Human papillomavirus (HPV) infection is associated with precancerous lesions and cancer of the genital tract both in women and men. The high incidence of cervical cancer worldwide focused the research on this infection mainly in women and to a lesser extent in men. In this review, we summarized epidemiological, immunological, and diagnostic data associated with HPV and cancer in men. We presented an overview of the main characteristics of HPV and infection in men that are associated with different types of cancer but also associated with male infertility. Men are considered important vectors of HPV transmission to women; therefore, identifying the sexual and social behavioral risk factors associated with HPV infection in men is critical to understand the etiology of the disease. It is also essential to describe how the immune response develops in men during HPV infection or when vaccinated, since this knowledge could help to control the viral transmission to women, decreasing the incidence of cervical cancer, but also could reduce other HPV-associated cancers among men who have sex with men (MSM). Finally, we summarized the methods used over time to detect and genotype HPV genomes, as well as some diagnostic tests that use cellular and viral biomarkers that were identified in HPV-related cancers.

Insulin signaling plays an important role in the development and progression of cancer since it is involved in proliferation and migration processes. It has been shown that the A isoform of the insulin receptor (IR-A) is often overexpressed, and its stimulation induces changes in the expression of the insulin receptor substrates (IRS-1 and IRS-2), which are expressed differently in the different types of cancer. We study the participation of the insulin substrates IRS-1 and IRS-2 in the insulin signaling pathway in response to insulin and their involvement in the proliferation and migration of the cervical cancer cell line. Our results showed that under basal conditions, the IR-A isoform was predominantly expressed. Stimulation of HeLa cells with 50 nM insulin led to the phosphorylation of IR-A, showing a statistically significant increase at 30 min (p ≤ 0.05). Stimulation of HeLa cells with insulin induces PI3K and AKT phosphorylation through the activation of IRS2, but not IRS1. While PI3K reached the highest level at 30 min after treatment (p ≤ 0.05), AKT had the highest levels from 15 min (p ≤ 0.05) and remained constant for 6 h. ERK1 and ERK2 expression was also observed, but only ERK2 was phosphorylated in a time-dependent manner, reaching a maximum peak 5 min after insulin stimulation. Although no effect on cell proliferation was observed, insulin stimulation of HeLa cells markedly promoted cell migration.

Antibodies against the Human Papillomavirus (HPV) L1 protein are associated with past infections and related to the evolution of the disease, whereas antibodies against L1 Virus-Like Particles (VLPs) are used to follow the neutralizing antibody response in vaccinated women. In this study, serum antibodies against conformational (VLPs) and linear epitopes of HPV16/18 L1 protein were assessed to distinguish HPV-vaccinated women from those naturally infected or those with uterine cervical lesions. The VLPs-16/18 were generated in baculovirus, and L1 proteins were obtained from denatured VLPs. Serum antibodies against VLPs and L1 proteins were evaluated by ELISA. The ELISA-VLPs and ELISA-L1 16/18 assays were validated with a vaccinated women group by ROC analysis and the regression analysis to distinguish the different populations of female patients. The anti-VLPs-16/18 and anti-L1-16/18 antibodies effectively detect vaccinated women (AUC = 1.0/0.79, and 0.94/0.84, respectively). The regression analysis showed that anti-VLPs-16/18 and anti-L1-16/18 antibodies were associated with the vaccinated group (OR = 2.11 × 10⁸/16.50 and 536.0/49.2, respectively). However, only the anti-L1-16 antibodies were associated with the high-grade lesions and cervical cancer (CIN3/CC) group (OR = 12.18). In conclusion, our results suggest that anti-VLPs-16/18 antibodies are effective and type-specific to detect HPV-vaccinated women, but anti-L1-16 antibodies better differentiate the CIN3/CC group. However, a larger population study is needed to validate these results.

Introduction: Dengue is currently the most widespread vector-borne disease, and its transmission has been intensively studied in endemic/hyperendemic localities. However, to obtain a complete picture of dengue transmission, it is necessary to study nonendemic localities. Imported dengue cases have been reported in Mexico City, and the presence of eggs of the vector Aedes aegypti has been detected. Methodology: In the present study, we determined the prevalence of IgG antibodies against Dengue virus in four city boroughs via random cluster sampling in individuals aged 5-35 years. Results: The weighted seroprevalence rate was 1.90% (95% CI 0.75-4.75) at Xochimilco, 1.81% (95% CI 0.64-5.00) at Venustiano Carranza, 1.81% (95% CI 0.54-5.83) at Tlahuac, and 5.48% (95% CI 1.96-14.43) at Gustavo A Madero; seropositivity was concentrated in the adult group, many of whom lived in dengue-endemic localities. The distribution of seroprevalence in the four boroughs is very homogeneous and unrelated to the number of vector eggs in the borough. Conclusions: These data suggest that there is still no autochthonous transmission of dengue in Mexico City. However, it is important to note that the structural conditions of the dwellings in these boroughs, which offer minimal barriers to vector infestation, could facilitate the establishment of local transmission under favorable conditions.