Janaina Cristiana de Oliveira Crispim

Müllerian duct anomalies (MDAs) are a heterogeneous group of congenital malformations that result from defects in the formation, fusion, or canalization (the process by which a solid cord of cells ...

Objectives: This study aimed to characterise the local cytokine milieu in the cervicovaginal environment of women with HSIL compared with healthy controls. Methods: In this case–control study, cervical samples were collected from 84 women aged 20–49 years, including 57 patients with histologically confirmed HSIL and 27 healthy controls. Levels of IL‐2, IL‐4, IL‐6, IL‐10, TNF, IFN‐γ and IL‐17A were quantified in cervicovaginal lavage fluid using a Cytometric Bead Array. Cytokine ratios were calculated to assess the balance between pro‐inflammatory and regulatory immune responses. Statistical comparisons between groups were performed using the Mann–Whitney test. Results: Women with HSIL exhibited significantly lower concentrations of TNF ( p = 0.030) and IL‐2 ( p = 0.010) compared with controls. Correspondingly, the TNF/IL‐10 ( p = 0.018) and TNF/IL‐4 ( p = 0.032) ratios were markedly decreased, suggesting impaired Th1‐mediated immune activation. No significant differences were observed for IL‐17A levels or IL‐17A/IL‐6 ratios, suggesting that Th17‐associated soluble mediators may not be the predominant drivers of the observed immunomodulation in this context, although broader Th17 involvement cannot be excluded. Conclusions: HSIL is characterised by reduced TNF and IL‐2 expression and a suppressed TNF/IL‐10 and TNF/IL‐4 balance, revealing a shift towards an immunoregulatory profile independent of Th17 activity. This cytokine signature suggests an immune milieu favouring lesion persistence and provides a potential framework for developing cytokine‐based biomarkers and immunotherapeutic strategies in HPV‐associated cervical disease.

Breast cancer is the leading cause of cancer death among Brazilian women, yet mortality estimates are often underestimated due to ill-defined causes, incomplete diagnoses, underreporting, and data quality limitations. Using national mortality data from 2000 to 2023, we examined the spatial distribution of breast cancer mortality among women aged 20 years and older, comparing uncorrected and adjusted estimates. Adjustments were applied to correct ill-defined causes, incomplete diagnoses, underreporting, and other data quality limitations using methods developed by the World Health Organization and the Brazilian Institute of Geography and Statistics (IBGE). Age-standardized mortality rates were calculated for five time periods using the World Health Organization (WHO) standard population, and spatial patterns were analyzed using choropleth maps, Moran I, and Local Indicators of Spatial Association (LISA). A total of 328,319 breast cancer deaths were reported, increasing to 385,068 (+ 17.3%) after adjustment. Corrections had the greatest effect in the North and Northeast in 2000–2004 (up to + 69.9%), but declined substantially over time. Mortality remained consistently higher in wealthier regions, while adjustments revealed underestimation in historically underserved areas. These findings reveal enduring geographic inequalities in breast cancer mortality and underscore the urgent need for targeted interventions and improved surveillance systems.

Cervical cancer is a leading cause of morbidity and mortality among women, particularly in low- and middle-income countries. Early detection through routine Pap smear screening is essential to prevent disease progression. The COVID-19 pandemic severely disrupted healthcare services worldwide, including cancer screening programs. This study aimed to evaluate the impact of the COVID-19 pandemic on cervical cancer screening in Brazil. A nationwide retrospective population-based study was conducted using data from the Cancer Information System (SISCAN) of Brazil’s public health system (SUS). Data from 2018–2019 (pre-pandemic) were compared to 2020–2021 (pandemic period) regarding the number of Pap smear tests performed, regional distribution, and diagnostic outcomes. Furthermore, data from 2022–2023 were incorporated to evaluate the volume of cytopathological exams performed in the post-pandemic context. Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and repeated measures ANOVA with Bonferroni correction. A significant reduction in Pap smear testing was observed nationwide during the pandemic (p < 0.01), with variations across regions. Despite fewer screenings, there was an increase in unsatisfactory exams and a rise in adenocarcinoma and atypical findings in some regions. In contrast, the post-pandemic period showed a significant recovery in the number of exams, reaching volumes comparable to those observed before the pandemic (p < 0.05). The COVID-19 pandemic substantially reduced cervical cancer screening coverage in Brazil, highlighting structural vulnerabilities in the healthcare system. Strengthening organized screening programs is essential to mitigate the long-term impact of these disruptions.

Cervical cancer, a leading cancer among women, is strongly associated with Human Papillomavirus infection, but host genetic factors also contribute to the progression from high-grade squamous intraepithelial lesions (HSIL) to invasive cancer. Interleukin-10 (IL-10), an immunosuppressive cytokine, may influence susceptibility to HSIL and cervical cancer through genetic variations. This study aimed to compare IL-10 gene promoter polymorphisms, -1082 A > G and − 819T > C, in women diagnosed with HSIL or cervical cancer and those with negative for intraepithelial lesion or malignancy (NILM). In this case-control study, 309 women were analyzed, including 142 with HSIL or cervical cancer and 167 controls with NILM. Blood samples were collected for DNA extraction and genotyping of polymorphisms through PCR amplification. Statistical analyses included comparisons of genotype and allele frequencies, haplotype frequency, and assessments of Hardy-Weinberg equilibrium and linkage disequilibrium. The mean age was 33.4 years for cases and 41.7 years for controls (p < 0.05). For the − 1082 A > G polymorphism, the GG genotype was significantly associated with a decreased risk of HSIL and cervical cancer (p = 0.0266, OR = 0.35). Recessive model (GG vs. AA + AG) confirmed this association (p = 0.0045, OR = 0.29). AC/GC diplotype was associated with a 2-fold increased risk of cervical lesions. Further studies are needed to confirm our results.

Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, associated with genetic and environmental factors, including microRNA (miRNA) gene polymorphisms. Objective: To evaluate the association between miRNA gene polymorphisms and PCOS. Search Strategy: PubMed, Embase, Web of Science, and Scopus databases were searched to September 2024, using MeSH terms including “MicroRNAs”, “Polymorphism, Single Nucleotide,” and “Polycystic Ovary Syndrome”. Selection Criteria: Case–control studies investigating the relationship between miRNA gene polymorphism and PCOS were included. Data Collection and Analysis: Two researchers collected the data independently. The risk of bias was assessed using the Newcastle‐Ottawa Scale (NOS). Data synthesis was performed using RevMan 5.4, and the strength of the evidence was evaluated using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Main Results: Five case–control studies were included in the systematic review, encompassing 985 patients with PCOS and 1004 healthy controls. The meta‐analysis included data from 870 PCOS patients and 889 controls. The GG genotype of miR‐146a rs2910164 was significantly associated with a protective effect against PCOS, while the GC and CC genotypes were linked to increased PCOS risk. In contrast, the TT genotype of miR‐196a‐2 rs11614913 was associated with heightened PCOS susceptibility. However, the certainty of evidence supporting these associations was low, indicating that the true effects may differ from the observed estimates. Conclusion: miRNA polymorphisms, specifically the GG genotype of miR‐146a rs2910164 and the GC, CC, and TT genotypes of miR‐196a‐2 rs11614913 seem to be associated with an increased risk of PCOS, warranting further large‐scale studies to validate these associations.

Cervical cancer remains a significant global health concern, causing more than 300,000 deaths annually. Erythrina velutina, a tree native to north-eastern Brazil, contains bioactive alkaloids with potential anticancer properties. This study aimed to characterize the alkaloid-enriched fraction of Erythrina velutina leaves and investigate the effects of the alkaloid erythraline on apoptosis and cell cycle in SiHa cervical cancer cells. Using Gas Chromatography–Mass Spectrometry (GC-MS), six alkaloids, including erythraline, were identified. Cytotoxicity was assessed through proliferation assays on SiHa cells and peripheral blood mononuclear cells (PBMCs). Apoptosis and cell cycle analyses were performed using flow cytometry, and in silico virtual screening identified potential protein targets of erythraline. Erythraline showed time- and concentration-dependent inhibitory effects on SiHa cell proliferation, with significant cytotoxicity observed at 50 µg/mL. Morphological changes, chromatin condensation, and increased apoptotic cell percentages confirmed the induction of caspase-independent apoptosis. Erythraline also induced G2/M cell cycle arrest, with 22% of cells in the G2/M phase compared with 7.25% in the untreated controls. In silico analysis identified polyamine oxidase, pyruvate kinase M2, and tankyrase as potential targets that contribute to the antitumor activity of erythraline. These findings suggest that erythraline is a promising candidate for anticancer therapy, warranting further investigation.

The clinical application of exosomal microRNAs as diagnostic biomarkers presents a promising approach for identifying potential markers of endometriosis. We conducted a systematic review of case–control studies to investigate exosomal microRNAs as epigenetic biomarkers potentially involved in the pathogenesis of endometriosis. A comprehensive literature search was performed across PubMed, Embase, Web of Science, and Scopus databases, yielding 702 studies, with 12 meeting the inclusion criteria after screening and full-text review. These studies included 191 women with confirmed endometriosis and 169 healthy controls. Quality assessment using the Newcastle–Ottawa Scale indicated a moderate quality across studies, with a common score of 5/9. In total, 668 exosomal microRNAs were found to be significantly differentially expressed between endometriosis patients and controls. In serum samples, 119 exosomal microRNAs were differentially expressed, with miR-22-3p, miR-320a, miR-320b, and miR-1273g-3p reported in more than one study. In endometrial tissue samples, miR-200c-3p and miR-425-5p were identified in more than one study, with miR-200c-3p consistently upregulated. Bioinformatic analysis indicated that these exosomal microRNAs are involved in key signaling pathways such as PI3K/Akt, MAPK, and TGF-β, which are associated with cell proliferation, migration, and inflammation. Despite these promising findings, variability in exosomal microRNA expression patterns across studies underscores the need for standardized methods and validation in large-scale, ethnically diverse cohorts. Future research should focus on rigorous validation studies to establish clinically relevant exosomal microRNAs for early diagnosis and improved patient outcomes.

Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by hyperglycemia and insulin resistance, with unclear genetic mechanisms. The specific involvement of proinflammatory cytokines, including IL-17A, and the immuno-tolerogenic HLA-G remains poorly understood in GDM. We aimed to explore the associations of three polymorphisms, IL-17A -197G>A (rs2275913), IL-17RA -947A>G (rs4819554), and HLA-G 14-bp insertion/deletion (indel), with GDM risk in a Brazilian population. We conducted a case-control study (79 GDM cases and 79 controls). Genetic polymorphisms were analyzed using PCR–RFLP, with DNA extracted using the Salting-out procedure. Significant associations were identified between -197G>A rs2275913 and HLA-G 14-bp indel polymorphisms in both codominant and recessive models. The IL-17A rs2275913 AA genotype was associated with a nearly ten-fold increased risk of GDM in both the codominant (p = 0.021, OR 9.89, 95% CI: 1.63–59.92) and recessive models (p = 0.006, OR 9.33, 95% CI: 1.57–55.38). Similarly, the HLA-G 14-bp Ins/Ins genotype was associated with an increased risk in both the codominant (p = 0.026, OR 3.34, 95% CI: 0.98–11.41) and recessive models (p = 0.010, OR 4.20, 95% CI: 1.36–12.96). IL-17RA polymorphism showed no significant associations. The study findings highlight the potential genetic and immune factors associated with GDM, particularly the -197G>A rs2275913 and HLA-G 14-bp indel polymorphisms. Further functional characterization is warranted to uncover the mechanism of genotype–phenotype association.