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Employing machine learning for identifying antifungal compounds against Candida albicans
(2025) Souza, Dienny Rodrigues de; Silva, Lívia do Carmo; Silva, Kleber Santiago Freitas e; Jesus, Fabrício Silva de; Oliveira, Amanda Alves de; Neves, Bruno Junior; Pereira, Maristela
Aims To evaluate the efficacy of a machine learning approach in developing classification and regression models for antifungal activity against Candida albicans. Materials & methods Utilized RF, SVM, and LightGBM algorithms to screen the eMolecules® library. Selected 17 virtual hits for in vitro assays. Results Eleven compounds showed activity against C. albicans. Compounds 1 and 17 inhibited C. albicans at 0.51 µM and 0.071 µM, respectively. Conclusions The RF model proved effective for virtual screening, demonstrating the success of the physicochemical classification and regression model in identifying new antifungal molecules against C. albicans. Plain Language Summary This study aimed to test a machine learning method for identifying substances that can combat Candida albicans, a type of fungus. The researchers utilized computer programs, including RF, SVM, and LightGBM, to analyze a large dataset of compounds. They selected 17 compounds for further testing in the lab. Of these, 11 compounds showed activity against C. albicans, and two compounds (1 and 17) could inhibit the fungus’ growth at very low concentrations. The results demonstrate that the machine learning model effectively identified new potential antifungal substances. This could aid in the development of more effective treatments for fungal infections.
Protein recognition is chiefly mediated by the CDR2 region in TREM2 - an in silico characterization
(2025) Dantas, Pedro Henrique dos Santos; Matos, Amanda de Oliveira; Contreras Colmenares, Mike Telemaco; Costa, Vinícius Alexandre Fiaia; Felice, Andrei Giacchetto; Carmo Neto, José Rodrigues do; Soares, Siomar de Castro; Sales, Marcelle Figueira Marques da Silva; Neves, Bruno Junior; Campos, Helioswilton Sales
The Triggering Receptor Expressed on Myeloid cells 2 (TREM2) is an immune receptor with three complementarity-determining regions (CDR1-3) that primarily interact with the receptor's ligands. Aside from its role in reducing inflammation, enhancing phagocytosis, and contributing to cellular maturation and survival, TREM2 also contributes to the pathophysiology of neurodegenerative disorders, cancer, and metabolic diseases. Therefore, understanding how the receptor interacts with its ligands is essential to mitigate its adverse effects and/or to foster the development of new therapeutic approaches. Thus, our research focused on understanding the interactions between TREM2 and its protein ligands: APOA1, APOA2, APOE3, APOE4, APOJ, C1q, Galectin-3, cyclophilin A, Heat shock protein 60 (HSP60), IL-34, IL-4, the SARS-CoV-2 membrane protein and the cholera toxin subunit B, TDP-43 using in silico methods, such as molecular docking and molecular dynamics simulations. TREM2 showed a higher affinity and stability with HSP60, APOA2, Cyclophilin A, Galectin-3, TDP-43 and C1q when compared to the other protein ligands. Notably, our data suggest that TREM2 interacts with its ligands predominantly through the CDR2 region by the following residues: N68, L69, W70, L71, L72, F74 and R76. Our findings indicate that the CDR2 region can be a crucial target for the development of inhibitory or agonistic approaches targeting the receptor's activity.
Exploring the orphan immune receptor TREM2 and its non-protein ligands: in silico characterization
(2025) Dantas, Pedro Henrique dos Santos; Costa, Vinícius Alexandre Fiaia; Felice, Andrei Giacchetto; Sousa, Eduarda Guimarães; Matos, Amanda de Oliveira; Soares, Siomar de Castro; Sales, Marcelle Figueira Marques da Silva; Neves, Bruno Junior; Campos, Helioswilton Sales de
The triggering receptor expressed on myeloid cells 2 (TREM2) is an immunoreceptor that interacts with a wide range of non-protein ligands, and it has been implicated in infectious and non-infectious diseases. However, there is a limited understanding on how this receptor interacts with non-protein ligands and the potential of such information to develop new therapeutic drugs. Therefore, our study aimed to elucidate the interactions between TREM2 and its non-protein ligands. First, we searched PubChem and Protein Data Bank (PDB) for TREM2 structures and their corresponding non-protein ligands. Subsequently, these structures were employed in molecular docking and MM/GBSA simulations with the Maestro software and molecular dynamics in GROMACS software. TREM2 was subsequently subjected to druggable site prediction using CavityPlus and receptor-based drug repositioning via the DrugRep server. TREM2 interacts with high affinity with its 12 non-protein ligands, with affinity values ranging from −33.01 kcal/mol for phosphatidylserine to −80.87 kcal/mol for cardiolipin (CLP). In molecular dynamics simulations, homodimeric TREM2 bound more stably to its lipid ligands, such as CLP and PSF, whereas it was unstable when unbound. The interactions between the receptor and its non-protein ligands were driven by the complementarity determining regions (CDR) 1 and 2, that are present in the hydrophobic and positively charged regions, highlighting that the Y38–R98 region is fundamental for drugs targeting TREM2. Our data underscore the significance of TREM2's CDRs in recognizing its ligands, suggesting they as promising targets for prospective drug design studies.
Modulation of the endocannabinoid system by (S)-ketamine in an animal model of depression
(2025) Silva, Nicole Rodrigues da; Arjmand, Shokouh; Domingos, Luana Barreto; Chaves Filho, Adriano José Maia; Mottin, Melina; Gregório, Caroline Cristiano Real; Waszkiewicz, Anna L.; Nunes, Pedro Henrique Gobira; Ferraro, Alessio Nicola; Andrade, Carolina Horta
Ketamine (KET) is recognized as rapid-acting antidepressant, but its mechanisms of action remain elusive. Considering the role of endocannabinoids (eCB) in stress and depression, we investigated if S-KET antidepressant effects involve the regulation of the eCB system using an established rat model of depression based on selective breeding: the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL). S-KET (15 mg/kg) effects were assessed in rats exposed to the open field and forced swimming test (FST), followed by analysis of the eCB signaling in the rat prefrontal cortex (PFC), a brain region involved in depression neurobiology. Changes in eCB receptors and enzymes were assessed at mRNA and protein levels (qPCR and western blot), CB1 binding ([3H]SR141716A autoradiography) and endocannabinoid content (lipidomics). The results demonstrated that the depressive behavior in FSL was negatively correlated with 2-AG levels, which were restored upon acute S-KET treatment. Although S-KET decreased CB1 and FAAH gene expression in FSL, there were no significant changes at protein levels. [3H]SR141716A binding to CB1 receptors was increased by S-KET and in silico analysis suggested that it binds to CB1, CB2, GPR55 and FAAH. Overall, S-KET effects correlated with an increased endocannabinoid signaling in the PFC, but systemic treatment with rimonabant failed to block its behavioral effects. Altogether, our results indicate that S-KET facilitates eCB signaling in the PFC of FSL. The inability of rimonabant to block the antidepressant effect of S-KET highlights the complexity of its interaction with the ECS, warranting further investigation into the molecular pathways.
QSAR-Lit: a no-code platform for predictive QSAR model development - from data curation to virtual screening
(2025) Silva, Igor Henrique Sanches; Oliveira, Francisco Lucas Feitosa de; Lemos, Jade Milhomem; Mendonça, Sabrina Silva; Cabral, Ester Souza Victoria Ferreira; Moreira Filho, José Teófilo; Gil, Henric Pietro Vicente; Neves, Bruno Junior; Braga, Rodolpho de Campos
The development of predictive quantitative structure-activity relationship (QSAR) models using machine learning (ML) algorithms has become increasingly feasible due to the growing availability of chemical libraries with experimental data. These models can accelerate the drug discovery process and reduce failure rates by enabling data-driven decision-making. However, existing standalone software often lacks several critical components necessary for effective data preparation and modeling. Here, we introduce QSAR-Lit, an innovative, no-code, and comprehensive workflow designed for curating chemical and biological data, generating QSAR models, and performing virtual screening through an interactive Python-based Streamlit dashboard. The QSAR model development process begins with data curation, collecting and cleaning data on chemical structures and their biological activities. The next step is model building, where the curated data is used to train and optimize QSAR models. Finally, QSAR-Lit provides virtual screening, allowing QSAR models to predict the activity of new chemical structures. This application efficiently screens libraries of chemical compounds, assisting researchers in identifying and prioritizing potential candidates for further investigation.
Structure-based identification of non-covalent prolyl oligopeptidase 80 inhibitors targeting Trypanosoma cruzi cell entry
(2025) Costa, Vinícius Alexandre Fiaia; Motta, Flávia da Silva Nader; Carvalho, Alexandra Maria dos Santos; Melo, Felipe da Silva Mendonça de; Mottin, Melina; Charneau, Sébastien Olivier; Grellier, Philippe; Santana, Jaime Martins de; Charneau, Izabela Marques Dourado Bastos; Neves, Bruno Junior
Chagas disease remains a persistent public health challenge due to the limited efficacy and significant toxicity of current pharmacological treatments. This highlights the urgent need for novel drugs with innovative mechanisms of action, specifically targeting cell infection pathways. The prolyl oligopeptidase of Trypanosoma cruzi (POPTc80) has emerged as a promising target for developing inhibitors to block the parasite’s infection process. In this study, we developed a robust structurebased virtual screening pipeline to discover potent POPTc80 inhibitors. The customized protocol integrated structural analysis of the 3D structure of POPTc80 and enrichment analysis of molecular docking and shape-based models to optimize the selection of potential inhibitors. After optimization, a large-scale virtual screening of 1.3 million compounds prioritized 19 putative hits for experimental validation. Nine of these compounds demonstrated inhibitory activity at nanomolar concentrations. The most potent inhibitors�LC-44 (Ki = 0.175 μM), LC-45 (Ki = 0.054 μM), LC-46 (Ki = 0.513 μM), LC-50 (Ki = 0.44 μM), LC-53 (Ki = 0.158 μM), and LC-55 (Ki = 0.83 μM)�demonstrated superior inhibitory activity, consistent with the competitive inhibition mechanism predicted by our computational protocol. Subsequently, a phenotypic assay confirmed their ability to effectively inhibit T. cruzi entry into host cells in a dose-dependent manner, further validating their mechanism of action. These findings establish these compounds as promising chemical scaffolds for prospective hit-to-lead optimization, offering a unique opportunity to develop novel, mechanismdriven therapeutics targeting a critical step in the parasite’s infection process.
TREM-1 as a potential coreceptor in norovirus pathogenesis: insights from transcriptomic analysis and molecular docking
(2025) Contreras Colmenares, Mike Telemaco; Matos, Amanda de Oliveira; Dantas, Pedro Henrique dos Santos; Carmo Neto, José Rodrigues do; Neves, Bruno Junior; Gardinassi, Luiz Gustavo Araujo; Sales, Marcelle Figueira Marques da Silva; Campos, Helioswilton Sales
: Norovirus (NoV) is a major cause of acute diarrheal disease in humans. However, due to complications in cultivating this virus, bioinformatics aids in elucidating the virus−host relationship. One of the molecules that has been associated with the burden of viral diseases is TREM-1, mainly due to its role in amplifying the inflammatory response. Thus, we hypothesized that TREM-1 may be involved in NoV infection. Analysis of public transcriptomic data sets showed an increased expression of Trem1 and Trem3 during murine NoV (MNoV) infection. Then, molecular docking was performed between murine TREM-1 and the P domain of the MNoV VP1 protein. The viral antigenic segment C′−D′ was recognized by the murine TREM-1 CDR1 region. Subsequently, based on phylogenetic criteria, NoV VP1 proteins from the GII.4 genotype sequenced in different years (1987, 2010, 2012, 2014, 2016, and 2019) were modeled. Using docking and molecular dynamics simulations, a stable interaction was observed between the human TREM-1 Ig-like domain and the conserved S and P segments of the NoV VP1 protein. Notably, this interaction was conserved over the years and was mainly dictated by the TREM-1 CDR3 region. Also, coexpression between Trem1 with genes involved in apoptosis and pyroptosis pathways was surveyed during viral infection by MNoV. It was found that Trem1 is primarily expressed with genes from the pyroptosis pathway. These simulations strongly suggest the involvement of TREM-1 in NoV pathogenesis and its potential contribution as a coreceptor
Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women
(2016) Castro Sobrinho, Juçara Maria de; Santos, Silvia Helena Rabelo dos; Alves, Rosane Ribeiro Figueiredo; Derchain, Sophie Françoise Mauricette; Sarian, Luis Otávio Zanatta; Moraes, Denise da Rocha Pitta Lima de; Campos, Elisabete A.; Zeferino, Luiz Carlos
Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV-infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ≥20% of clue cells. Present inflammatory response was defined as ≥30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06–3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06–3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06–3.47), BV (OR: 3.54 95% CI 1.62–7.73) and IR (OR: 6.33 95% CI 3.06–13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26–0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64–9.29) and IR (OR: 6.43 95% CI 2.92–14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV-positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia.
Human papillomavirus in oral cavity and oropharynx carcinomas in the central region of Brazil
(2017) Petito, Guilherme; Carneiro, Megmar Aparecida dos Santos; Santos, Silvia Helena Rabelo dos; Silva, Antonio Márcio Teodoro Cordeiro; Alencar, Rita de Cássia Gonçalves de; Gontijo, Antonio Paulo Machado; Saddi, Vera Aparecida
Introduction: Molecular studies about carcinomas of the oral cavity and oropharynx demon strate the presence of human papilomavirus genome in these tumors, reinforcing the participation of human papilomavirus in oral carcinogenesis. Objectives: This study aimed to determine the prevalence of human papilomavirus and geno type distribution of HPV16 and HPV18 in oral cavity and oropharynx carcinomas, as well as their association with clinical characteristics of the tumors. Methods: This is a retrospective study, with clinical data collected from 82 patients. Human papilomavirus detection was conducted on specimens of oral cavity and oropharynx carcinomas included in paraffin blocks. Patients were assisted in a cancer reference center, in the central region of Brazil, between 2005 and 2007. Polymerase chain reaction was used for the detection and genotyping of human papilomavirus. Results: Among the patients evaluated, 78% were male. The average age of the group was about 58 years. Risk factors, such as smoking (78%) and alcohol consumption (70.8%) were recorded for the group. HPV DNA was detected in 21 cases (25.6%; 95% confidence interval 16.9---36.6) of which 33.3% were HPV16 and 14.3% were HPV18. The presence of lymph node metastases and registered deaths were less frequent in human papilomavirus positive tumors, suggesting a better prognosis for these cases; however, the differences between the groups were not statistically significant.
Strong SOD2 expression and HPV-16/18 positivity are independent events in cervical cancer
(2018) Santos, Silvia Helena Rabelo dos; Termini, Lara; Pierulivo, Enrique Mario Boccardo; Derchain, Sophie Françoise Mauricette; Longatto Filho, Adhemar; Andreoli, Maria Antonieta Avilla; Costa, Maria Cecília; Nunes, Rafaella Almeida Lima; Andrade, Liliana Aparecida Lucci de Angelo; Villa, Luisa Lina
Human papillomavirus and anal cancer: prevalence, genotype distribution, and prognosis aspects from midwestern region of Brazil
(2019) Libera, Larisse Silva Dalla; Carvalho, Keila Patrícia Almeida de; Ramos, Jessica Enocencio Porto; Cabral, Lázara Alyne Oliveira; Alencar, Rita de Cássia Gonçalves de; Villa, Luísa Lina; Alves, Rosane Ribeiro Figueiredo; Santos, Silvia Helena Rabelo dos; Carneiro, Megmar Aparecida dos Santos; Saddi, Vera Aparecida
d. Approximately 90% of all anal cancers are associated with human papillomavirus (HPV), especially high-risk genotypes such as HPVs 16 and 18. Objective. To investigate the clinical and prognostic aspects of anal cancers associated with the presence, as well as the genotypic distribution of human papillomavirus (HPV). Methods. A retrospective study carried out over a 10-year period, using clinical and molecular data, with PCR analysis and reverse hybridization (INNO LIPA kit), in anal cancers. ,e data analysis was done using descriptive univariate statistics, and the survival curves were made using the Kaplan–Meier and log-rank methods. Results. Of the 81 formalin-fixed and paraffin-embedded specimens, HPV prevalence was 69% and was significantly higher in squamous cell carcinomas (SCC) than in other anal tumors (p � 0.0001). Female patients had a higher prevalence of HPV (p � 0.01). Multiple infections were detected in 14.3% of cases. ,e most prevalent genotypes were HPVs 16, 33, and 18. ,e overall survival at 60 months was 44.3%, and the prognostic factors included gender (p � 0.008) with greater survival for men (52.9%) in comparison to women (29.6%), histological type (p � 0.01), SCC (54.4%), adenocarcinomas (37.5%), other carcinomas (14.2%), and the presence of distant metastasis (p � 0.01). Survival was not influenced by the presence of HPV (p � 0.54). Conclusions. ,e association of HPV to anal cancer was found in this study, especially in SCC. However, the presence of HPV did not influence the prognosis of patients with anal cancer.
Swainsonine, an alpha-mannosidase inhibitor, may worsen cervical cancer progression through the increase in myeloid derived suppressor cells population
(2019) Silveira, Caio Raony Farina; Manzine, Marcella Cipelli Carolina; Santos, Silvia Helena Rabelo dos; Zeferino, Luiz Carlos; Rodríguez Rodríguez, Gretel; Assis, Josiane Betim de; Herbster, Suellen da Silva Gomes; Bernadinelli, Isabel; Laginha, Fábio Martins
Cervical cancer, caused by high oncogenic risk Human Papillomavirus (HPV) infection, con tinues to be a public health problem, mainly in developing countries. Using peptide phage display as a tool to identify potential molecular targets in HPV associated tumors, we identi fied α-mannosidase, among other enriched sequences. This enzyme is expressed in both tumor and inflammatory compartment of the tumor microenvironment. Several studies in experimental models have shown that its inhibition by swainsonine (SW) led to inhibition of tumor growth and metastasis directly and indirectly, through activation of macrophages and NK cells, promoting anti-tumor activity. Therefore, the aim of this work was to test if swainso nine treatment could modulate anti-tumor immune responses and therefore interfere in HPV associated tumor growth. Validation of our biopanning results showed that cervical tumors, both tumor cells and leukocytes, expressed α-mannosidase. Ex vivo experiments with tumor associated macrophages showed that SW could partially modulate macrophage phe notype, decreasing CCL2 secretion and impairing IL-10 and IL-6 upregulation, which prompted us to proceed to in vivo tests. However, in vivo, SW treatment increased tumor growth. Investigation of the mechanisms leading to this result showed that SW treatment significantly induced the accumulation of myeloid derived suppressor cells in the spleen of tumor bearing mice, which inhibited T cell activation. Our results suggested that SW contrib utes to cervical cancer progression by favoring proliferation and accumulation of myeloid cells in the spleen, thus exacerbating these tumors systemic effects on the immune system, therefore facilitating tumor growth.
Tumoral and stromal expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2, and VEGFA in cervical cancer patient survival: a competing risk analysis
(2016) Martins, Jordana Maria Azevedo; Santos, Silvia Helena Rabelo dos; Westin, Maria Cristina do Amaral; Zeferino, Luiz Carlos
Background Human papillomavirus and Chlamydia trachomatis share the same route of sexual transmission and possess similar risk factors, indicating that coinfection may act synergistically in the induction of epithelial cell abnormalities. Objective This study aimed to determine the prevalence of human papillomavirus and Chlamydia trachomatis in adolescents and young women and identify factors associated with coinfection. Study Design This cross-sectional study included 276 female participants, aged 15–24 years, who were sexually active. Interviews were conducted and cervical specimens were collected for cervical smears and molecular tests. All cervical specimens were tested for 27 human papillomavirus genotypes by polymerase chain reaction amplification and hybridization to a human papillomavirus linear array. Detection of Chlamydia trachomatis was performed by polymerase chain reaction using primers directed to the region encoding the cryptic plasmid. Bivariate and multivariate analyses were performed to evaluate the factors associated with coinfection with human papillomavirus and Chlamydia trachomatis. The odds ratio, the adjusted odds ratio, and the 95% confidence interval were calculated. Results The prevalence of infection by Chlamydia trachomatis and human papillomavirus was 9.1% (95% confidence interval, 5.61–12.4) and 47.1% (95% confidence interval, 41.0–53.2), respectively. The prevalence of coinfection with human papillomavirus and Chlamydia trachomatis was 5.8% (95% confidence interval, 3.3–9.2); coinfection with 1 human papillomavirus type was 3.3% (95% confidence interval, 1.5–6.1) and with multiple types was 2.5% (95% confidence interval, 1.0–5.2). The prevalence of cytological abnormalities was 12.3% (95% confidence interval, 8.6–16.79). Human papillomavirus infections of high oncogenic risk were more prevalent (85.4%). Factors independently associated with coinfection of human papillomavirus/Chlamydia trachomatis obtained by multivariate analysis were the initiation of sexual activity under 16 years of age with an an odds ratio of 4.9 (95% confidence interval, 1.0–23.63; P = .05) and cytological abnormalities with an odds ratio of 10.7 (95% confidence interval, 1.9–59.5; P = .01), which indicates there is risk for the detection of cytological abnormalities in adolescents and young women coinfected with human papillomavirus/Chlamydia trachomatis. Conclusion The prevalence of coinfection among our study population was of a magnitude that warrants attention by public health services. Adolescents and young women should be monitored for Chlamydia trachomatis infection and vaccinated against human papillomavirus. The association between cytological abnormalities and coinfection with human papillomavirus and Chlamydia trachomatis indicates the potential synergistic role of these infections in carcinogenesis of the cervix.
Three Prime Repair Exonuclease 1 (TREX1) expression correlates with cervical cancer cells growth in vitro and disease progression in vivo
(2019) Abjaude, Bruna Prati Walason da Silva; Morale, Lara Termini Mirian Galliote; Herbster, Suellen da Silva Gomes; Longatto Filho, Adhemar; Nunes, Rafaella Almeida Lima; Córdoba Camacho, Lizeth Carolina; Santos, Silvia Helena Rabelo dos; Zeferino, Luiz Carlos; Aguayo, Francisco; Boccardo Pierulivo, Enrique Mario
Alterations in specifc DNA damage repair mechanisms in the presence of human papillomavirus (HPV) infection have been described in diferent experimental models. However, the global efect of HPV on the expression of genes involved in these pathways has not been analyzed in detail. In the present study, we compared the expression profle of 135 genes involved in DNA damage repair among primary human keratinocytes (PHK), HPV-positive (SiHa and HeLa) and HPV-negative (C33A) cervical cancer derived cell lines. We identifed 9 genes which expression pattern distinguishes HPV-positive tumor cell lines from C33A. Moreover, we observed that Three Prime Repair Exonuclease 1 (TREX1) expression is upregulated exclusively in HPV-transformed cell lines and PHK expressing HPV16 E6 and E7 oncogenes. We demonstrated that TREX1 silencing greatly afects tumor cells clonogenic and anchorage independent growth potential. We showed that this efect is associated with p53 upregulation, accumulation of subG1 cells, and requires the expression of E7 from high-risk HPV types. Finally, we observed an increase in TREX1 levels in precancerous lesions, squamous carcinomas and adenocarcinomas clinical samples. Altogether, our results indicate that TREX1 upregulation is important for cervical tumor cells growth and may contribute with tumor establishment and progression.
Prevalence and factors associated with coinfection of human papillomavirus and Chlamydia trachomatis in adolescents and young women
(2016) Nonato, Dejan Rodrigues; Alves, Rosane Ribeiro Figueiredo; Ribeiro, Andrea Alves; Saddi, Vera Aparecida; Segati, Kelly Deyse; Carvalho, Keila Patrícia Almeida de; Lima, Yanna Andressa Ramos de; D'Alessandro, Walmirton Bezerra; Santos, Silvia Helena Rabelo dos
Background Human papillomavirus and Chlamydia trachomatis share the same route of sexual transmission and possess similar risk factors, indicating that coinfection may act synergistically in the induction of epithelial cell abnormalities. Objective This study aimed to determine the prevalence of human papillomavirus and Chlamydia trachomatis in adolescents and young women and identify factors associated with coinfection. Study Design This cross-sectional study included 276 female participants, aged 15–24 years, who were sexually active. Interviews were conducted and cervical specimens were collected for cervical smears and molecular tests. All cervical specimens were tested for 27 human papillomavirus genotypes by polymerase chain reaction amplification and hybridization to a human papillomavirus linear array. Detection of Chlamydia trachomatis was performed by polymerase chain reaction using primers directed to the region encoding the cryptic plasmid. Bivariate and multivariate analyses were performed to evaluate the factors associated with coinfection with human papillomavirus and Chlamydia trachomatis. The odds ratio, the adjusted odds ratio, and the 95% confidence interval were calculated. Results The prevalence of infection by Chlamydia trachomatis and human papillomavirus was 9.1% (95% confidence interval, 5.61–12.4) and 47.1% (95% confidence interval, 41.0–53.2), respectively. The prevalence of coinfection with human papillomavirus and Chlamydia trachomatis was 5.8% (95% confidence interval, 3.3–9.2); coinfection with 1 human papillomavirus type was 3.3% (95% confidence interval, 1.5–6.1) and with multiple types was 2.5% (95% confidence interval, 1.0–5.2). The prevalence of cytological abnormalities was 12.3% (95% confidence interval, 8.6–16.79). Human papillomavirus infections of high oncogenic risk were more prevalent (85.4%). Factors independently associated with coinfection of human papillomavirus/Chlamydia trachomatis obtained by multivariate analysis were the initiation of sexual activity under 16 years of age with an an odds ratio of 4.9 (95% confidence interval, 1.0–23.63; P = .05) and cytological abnormalities with an odds ratio of 10.7 (95% confidence interval, 1.9–59.5; P = .01), which indicates there is risk for the detection of cytological abnormalities in adolescents and young women coinfected with human papillomavirus/Chlamydia trachomatis. Conclusion The prevalence of coinfection among our study population was of a magnitude that warrants attention by public health services. Adolescents and young women should be monitored for Chlamydia trachomatis infection and vaccinated against human papillomavirus. The association between cytological abnormalities and coinfection with human papillomavirus and Chlamydia trachomatis indicates the potential synergistic role of these infections in carcinogenesis of the cervix.
Internal quality control indicators in cervical cytopathology of a university laboratory
(2018) Cardoso Filho, Leonardo Izidório; Tavares, Suelene Brito do Nascimento; Batista, Maria de Lourdes Siqueira; Passos, Eva Nayssa dos; Araújo, N. L. A. S.; Martins, Jordana Maria Azevedo; Ribeiro, Andrea Alves; Santos, Silvia Helena Rabelo dos
Introduction To evaluate the internal quality control indicators and quality management programme in a university cytopathology laboratory. Methods All results of conventional cervical smears tests (taken from the SISCAN, the Brazilian cervical cancer screening system) of women aged ≥15 years at the time of Papanicolaou smear specimen collection during January 2007-December 2014 were included. The final results of the cytopathology were classified in accordance with the Bethesda System. The variables included in the database were the woman's name, date of birth, and age at the time of sampling (15-30, 31-40 and older than 40 years). Results In this period, 50 286 cytopathology examinations were carried out. Of these, 44 386 (91.34%) were negative for malignancy or unsatisfactory and 4209 (8.66%) presented epithelial abnormalities. The percentage of the tests consistent with atypical squamous cells (ASC) between satisfactory examinations was 4.12%; the percentage of tests compatible with ASC among abnormal examinations was 47.87%; the ASC/squamous intraepithelial lesion) ratio was 0.97 and the percentage of high-grade squamous intraepithelial lesion among satisfactory tests was 2.21%, and the 5-year retrospective review identified 4.97% of false-negative results. Conclusion All rates obtained were consistent over the years and within the recommended values by Federal Regulation of Brazil. This demonstrates the efficacy of our established internal quality monitoring and continuing education, reflecting the commitment of the team involved in the release of smear reports.
Bacterial vaginosis, representation of endocervical and/or metaplastic cells, and cytological abnormalities in different age groups: association study
(2020) Passos, Eva Nayssa do; Ribeiro, Andrea Alves; Tavares, Suelene Brito do Nascimento; Souza, Nadja Lindany Alves de; Batista, Maria de Lourdes Siqueira; Cardoso Filho, Leonardo Izidório; Aquino, Érika Carvalho de; Santos, Silvia Helena Rabelo dos
Background Studies have indicated that bacterial vaginosis (BV) might be a cofactor for the acquisition and persistence of high-risk papillomavirus, enabling the development of cytological abnormalities. The presence of endocervical and metaplastic cells makes the smear more adequate for the detection of these abnormalities once these cell types are representative of the transformation zone, a site of increased susceptibility to viral infection. Methods The purpose of this study was to evaluate the patterns of vaginal microbiota, the representation of endocervical and/or metaplastic cells, and the detection of cytological abnormalities in cervical smears from women 15 to 64 years old. Results from satisfactory cytological smears performed in a laboratory school from the Federal University of Goiás were analyzed. The degree of association between the categorical variables was evaluated by the χ2 test, Fisher's Exact test, and stratified analysis through the estimation of the prevalence ratio, with 95% confidence intervals and 5% statistical significance level (P < .05). Results The global prevalence of BV and cytological abnormalities was 22.02% and 8.21%, respectively. BV and the representation of endocervical and/or metaplastic cells were independently associated with the detection of high-grade cytological abnormalities in the cervical smears of women between 25 and 64 years old. Conclusions BV and representation of endocervical and/or metaplastic cells were independently associated with the detection of high-grade cytological abnormalities reinforcing the importance of specimen adequacy and microbiota in the cervical microenvironment.
QSAR-Driven design and discovery of novel compounds with antiplasmodial and transmission blocking activities
(2018) Lima, Marília Nunes do Nascimento; Melo Filho, Cleber Camilo do; Cassiano, Gustavo Capatti; Neves, Bruno Junior; Alves, Vinícius de Medeiros; Braga, Rodolpho de Campos; Cravo, Pedro Vitor Lemos; Muratov, Eugene; Paim, Juliana Calit; Bargieri, Daniel Youssef; Costa, Fabio Trindade Maranhão; Andrade, Carolina Horta
Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium, affecting more than 200 million people worldwide every year and leading to about a half million deaths. Malaria parasites of humans have evolved resistance to all current antimalarial drugs, urging for the discovery of new effective compounds. Given that the inhibition of deoxyuridine triphosphatase of Plasmodium falciparum (PfdUTPase) induces wrong insertions in plasmodial DNA and consequently leading the parasite to death, this enzyme is considered an attractive antimalarial drug target. Using a combi-QSAR (quantitative structure-activity relationship) approach followed by virtual screening and in vitro experimental evaluation, we report herein the discovery of novel chemical scaffolds with in vitro potency against asexual blood stages of both P. falciparum multidrug-resistant and sensitive strains and against sporogonic development of P. berghei. We developed 2D- and 3D-QSAR models using a series of nucleosides reported in the literature as PfdUTPase inhibitors. The best models were combined in a consensus approach and used for virtual screening of the ChemBridge database, leading to the identification of five new virtual PfdUTPase inhibitors. Further in vitro testing on P. falciparum multidrug-resistant (W2) and sensitive (3D7) parasites showed that compounds LabMol-144 and LabMol-146 demonstrated fair activity against both strains and presented good selectivity versus mammalian cells. In addition, LabMol-144 showed good in vitro inhibition of P. berghei ookinete formation, demonstrating that hit-to-lead optimization based on this compound may also lead to new antimalarials with transmission blocking activity.
Development of Web and mobile applications for chemical toxicity prediction
(2018) Alves, Vinícius de Medeiros; Braga, Rodolpho de Campos; Muratov, Eugene; Andrade, Carolina Horta
Computational tools are recognized to provide high-quality predictions for the assessment of chemical toxicity. In the recent years, mobile devices have become ubiquitous, allowing for the development of innovative and useful models implemented as chemical software applications. Here, we will briefly discuss this recent uptick in the development of web-based and mobile applications for chemical problems, focusing on best practices, development, usage and interpretation. As an example, we also describe two innovative apps (Pred-hERG and Pred-Skin) for chemical toxicity prediction developed in our laboratory. These applications are based on predictive quantitative structure-activity relationships (QSAR) models developed using the largest publicly available datasets of structurally diverse compounds. The developed tools ensure both highly accurate predictions and easy interpretation of the models, allowing users to discriminate potential toxicants and to purpose structural modifications to design safer chemicals.
Quimioinformática: uma introdução
(2018) Alves, Vinícius de Medeiros; Braga, Rodolpho de Campos; Muratova, Eugene; Andrade, Carolina Horta
Cheminformatics is an interdisciplinary field between chemistry and informatics, which has evolved considerably since its inception in the 1960s. Initially, the cheminformatics community dealt primarily with practical and technical aspects of chemical structure representation, manipulation, and processing, while modern research explores a new role: the exploration and interpretation of large chemical databases and the discovery of new compounds with desired activity and safety profiles. Despite the recent release of several hallmark reviews addressing methods and application of cheminformatics written in Portuguese, so far there are no scientific articles presenting cheminformatics research to the Brazilian scientific community yet. To address this gap, we aim to introduce the field of cheminformatics to both students and researchers in a simple and didactic way by narrating important historical facts and contextualizing information within the scope of various applications.

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