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Background/Objectives: To analyze the spatial distribution of HPV vaccination coverage in relation to sociodemographic variables in a state of Southern Brazil. Methods: This was an ecological, retrospective study with secondary data from the Department of Information Technology of the Unified Health System/Ministry of Health from 2015 to 2022. The cohort method was used to calculate vaccination coverage. Geographically weighted regression was used for the independent variables. Results: There was a 22.04% reduction in vaccination between the first and second doses. Coverage with the first dose of the vaccine reached 95.17% for the female population, 64.67% for the male population, and 79.57% for both sexes. In 50.62% of cities, coverage exceeded 90% for both sexes. In 80.45% of cities, the recommended coverage for females was achieved. The variable municipal performance was positively significant for the increase in vaccination coverage in 45.45% of the regions for girls, 18.18% for boys, and 36.36% for both sexes. The family health strategy variable was significant in 9.09% of the regions for girls and both sexes. The education variable showed an inverse significance for girls in 40.90%, for boys in 18.18%, and for both sexes in 36.36% of the regions. Conclusions: HPV vaccination declined between the first and second doses, with high first-dose coverage among females and moderate coverage among males. Municipal performance notably impacted coverage, particularly for girls. The family health strategy was relevant in specific regions, while educational factors had a variable effect. Addressing these variables may enhance vaccination coverage and minimize the gap between doses.

Background: The coronavirus 2019 (COVID-19) pandemic impacted cancer health care in several countries, with delays in the detection and treatment of breast and cervical cancer. The objective of this study is to analyze and compare the screening, diagnosis and treatment of breast and cervical cancer in the pre-COVID period and during the COVID-19 period., Methods: Cross-sectional study with secondary data collected from the Mortality Information System (SIM), Hospital Information System (SIH), Ambulatory Information System (SIA) and the Oncology Panel (PO) of breast cancer notifications with ICD C50.0 to C50.9 and cervix ICD C53.0 to C53.9, The analyzed period before the pandemic was from March 1 to October 1, 2019, and during the pandemic from March 1 to October 1, 2020. The period from 2013 to 2022 was also analyzed with the same information, including the number of diagnoses, treatments, and deaths from breast cancer and cervical cancer. The study population consisted of Brazilian women aged 25 to 70 years. In order to compare categorical variables between periods, the Chi-Square or Fisher's Exact tests, and Mann-Whitney U tests were applied, and the Poisson Regression model was applied to model the number of reported cases of COVID-19 and the amount of procedures., Results: There was a decrease in the number of mammograms and cytopathological exams during COVID-19, as well as a decrease in cases of breast and cervical cancer. The Poisson regression showed that the increase in the number of COVID-19 cases caused a decrease in the number of breast cytopathological examinations, cervical-vaginal cytopathological examinations/microflora and screening, diagnosis, initiation of treatment for breast cancer and deaths from this disease. Meanwhile, in some regions of Brazil, as the number of Covid-19 increased, there was a significantly increase in the number of mammograms performed and cervical cancer diagnoses., Conclusions: The COVID-19 period in 2020 significantly impacted screening, diagnosis, treatment for breast and cervical cancer., (© 2024. The Author(s).)

Introduction: Despite the evidence that photodynamic therapy (PDT) associated with chemotherapy presents great potential to overcome the limitations of monotherapy, little is known about the current status of this combination against cervical cancer. This systematic review aimed to address the currently available advances in combining PDT and chemotherapy in different research models and clinical trials of cervical cancer., Methods: We conducted a systematic review based on PRISMA Statement and Open Science Framework review protocol using PubMed, Web of Science, Embase, Scopus, LILACS, and Cochrane databases. We selected original articles focusing on 'Uterine Cervical Neoplasms' and 'Photochemotherapy and Chemotherapy' published in the last 10 years. The risk of bias in the studies was assessed using the CONSORT and SYRCLE tools., Results: Twenty-three original articles were included, focusing on HeLa cells, derived from endocervical adenocarcinoma and on combinations of several chemotherapeutics. Most of the combinations used modern drug delivery systems for improved simultaneous delivery and presented promising results with increased cytotoxicity compared to monotherapy., Conclusion: Despite the scarcity of animal studies and the absence of clinical studies, the combination of chemotherapy with PDT presents a potential option for cervical cancer therapy requiring additional studies., Osf Registration: https://doi.org/10.17605/OSF.IO/WPHN5 [Figure: see text].

Background: Breast cancer is the most commonly diagnosed cancer among women worldwide with limited treatment options. Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is one of the main constituents of Brazilian propolis presenting different activities, including antitumoral effects against various types of cancer., Objective: We evaluated the antitumoral potential and mechanisms of action of artepillin C against two distinct human breast cancer cell lines, MCF-7 and MDA-MB-231, to explore a new therapeutic candidate., Methods: Cell viability was assessed by MTT assay and the long-term cytotoxicity was performed by clonogenic assay. The morphological changes were observed by light microscopy, analysis of cell death pathway by Annexin V FITC/propidium iodide (PI), lactate dehydrogenase (LDH) by colorimetry, DNA fragmentation by agarose gel and senescence by β-galactosidase. Detection of total reactive oxygen species (ROS) by fluorescence microscopy and determination of mitochondrial transmembrane potential by flow cytometry were also performed., Results: Artepillin C presented a strong and dose-time-dependent cytotoxic effect on MCF-7 and MDA-MB-231 cell lines, with cytotoxicity more evident in MCF-7. In both cancer cell lines, the clonogenic potential was significantly reduced and the morphology of the cells was changed. The treatment also induced death by necrosis and late apoptosis in MCF-7 and MDA-MB-231 and induced cell senescence in MCF-7. Also, artepillin C increased total ROS in both cancer cells and decreased mitochondrial membrane potential in MDA-MB-231 cells., Conclusion: Artepillin C presented antitumoral potential in two human breast cancer cell lines, MCF-7, and MDA-MB-231, suggesting a new promising option for the treatment and/or chemopreventive strategy for breast cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course., Methods: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site., Discussion: Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines., (© 2023. The Author(s).)

Despite the options available for breast cancer (BC) therapy, several adverse effects and resistance limit the success of the treatment. Furthermore, the use of a single drug is associated with a high failure rate. We investigated through a systematic review the in vitro effects of the combination between conventional drugs and bioactive compounds derived from cinnamic acid in BC treatment. The information was acquired from the following databases: PubMed, Web of Science, Embase, Scopus, Lilacs and Cochrane library. We focused on "Cinnamates", "Drug Combinations" and "Breast neoplasms" for publications dating between January 2012 and December 2022, based on the PRISMA statement. The references of the articles were carefully reviewed. Finally, nine eligible studies were included. The majority of these studies were performed using MCF-7, MDA-MB-231, MDA-MB-468 and BT-20 cell lines and the combination between cisplatin, paclitaxel, doxorubicin, tamoxifen, dactolisib and veliparib, with caffeic acid phenethyl ester, eugenol, 3-caffeoylquinic acid, salvianolic acid A, ferulic acid, caffeic acid, rosmarinic acid and ursolic acid. The combination improved overall conventional drug effects, with increased cytotoxicity, antimigratory effect and reversing resistance. Combining conventional drugs with bioactive compounds derived from cinnamic acid could emerge as a privileged scaffold for establishing new treatment options for different BC types.

Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity., (© 2022. The Author(s).)

Objective: Breast cancer (BC) currently has no effective treatment especially for the highly aggressive and metastatic triple negative breast cancer (TNBC). Here, we investigated the antitumoral and antimigratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against TNBC cell line MDA-MB-231 compared to a nontumorigenic human breast ductal cell line (MCF-10A)., Methods: The phototoxicity/cytotoxicity was assessed by MTT assay, long-term cytotoxicity by clonogenic assay, cell uptake, subcellular distribution, and cellular oxidative stress by fluorescence microscopy, cell death with annexin V-FITC/propidium iodide, PDT mechanism using sodium azide and D-mannitol, and cell migration by wound-healing assay., Results: The treatment promoted phototoxic effect on tumor cell line in a dose-dependent and selective manner. Internalization of F127/HYP was efficient and accumulation occurred in the endoplasmic reticulum and mitochondria, resulting in cellular oxidative stress mainly by the type II mechanism, induced by necrosis. Furthermore, F127/HYP decreased colony formation and reduced the cell migration ability in MDA-MB-231 cells., Conclusion: Our results suggest a potentially useful role of F127/HYP micelles as a platform for HYP delivery to more specifically and effectively treat TNBC.

Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China's Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients' overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.

Thermosensitive bioadhesive formulations can display increased retention time, skin permeation, and improve the topical therapy of many drugs. Acne is an inflammatory process triggered by several factors like the proliferation of the bacteria Propionibacterium acnes . Aiming for a new alternative treatment with a natural source, propolis displays great potential due to its antibiotic, anti-inflammatory, and healing properties. This study describes the development of bioadhesive thermoresponsive platform with cellulose derivatives and poloxamer 407 for propolis skin delivery. Propolis ethanolic extract (PES) was added to the formulations with sodium carboxymethylcellulose (CMC) or hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (Polox). The formulations were characterized as rheology, bioadhesion, and mechanical analysis. The selected formulations were investigated as in vitro propolis release, cytotoxicity, ex vivo skin permeation by Fourier Transform Infrared Photoacoustic Spectroscopy, and the activity against P. acnes . Formulations showed suitable sol-gel transition temperature, shear-thinning behavior, and texture profile. CMC presence decreased the cohesiveness and adhesiveness of formulations. Polox/HPMC/PES system displayed less cytotoxicity, modified propolis release governed by anomalous transport, skin permeation, and activity against P. acnes . These results indicate important advantages in the topical treatment of acne and suggest a potential formulation for clinical evaluation.

Cervical cancer is one of the most common causes of cancer-related deaths in women worldwide. Despite advances in current therapies, women with advanced or recurrent disease present poor prognosis. Photodynamic therapy (PDT) has emerged as an effective therapeutic alternative to treat oncological diseases such as cervical cancer. Phthalocyanines (Pcs) are considered good photosensitizers (PS) for PDT, although most of them present high levels of aggregation and are lipophilic. Despite many investigations and encouraging results, Pcs have not been approved as PS for PDT of invasive cervical cancer yet. This review presents an overview on the pathophysiology of cervical cancer and summarizes the most recent developments on the physicochemical properties of Pcs and biological results obtained both in vitro in tumor-bearing mice and in clinical tests reported in the last five years. Current evidence indicates that Pcs have potential as pharmaceutical agents for anti-cervical cancer therapy. The authors firmly believe that Pc-based formulations could emerge as a privileged scaffold for the establishment of lead compounds for PDT against different types of cervical cancer.

In melanomas, therapy resistance can arise due to a combination of genetic, epigenetic and phenotypic mechanisms. Due to its crucial role in DNA supercoil relaxation, TOP1 is often considered an essential chemotherapeutic target in cancer. However, how TOP1 expression and activity might differ in therapy sensitive versus resistant cell types is unknown. Here we show that TOP1 expression is increased in metastatic melanoma and correlates with an invasive gene expression signature. More specifically, TOP1 expression is highest in cells with the lowest expression of MITF, a key regulator of melanoma biology. Notably, TOP1 and DNA Single-Strand Break Repair genes are downregulated in BRAFi- and BRAFi/MEKi-resistant cells and TOP1 inhibition decreases invasion markers only in BRAFi/MEKi-resistant cells. Thus, we show three different phenotypes related to TOP1 levels: i) non-malignant cells with low TOP1 levels; ii) metastatic cells with high TOP1 levels and high invasiveness; and iii) BRAFi- and BRAFi/MEKi-resistant cells with low TOP1 levels and high invasiveness. Together, these results highlight the potential role of TOP1 in melanoma progression and resistance., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: The present report investigated the rates of coinfections between high-rik human papillomavirus (hrHPV) and the most important human mycoplasmas including Mycoplasma hominis, M. genitalium, Ureaplasma urealyticum and U. parvum in cervical samples of asymptomatic brazilian population., Methods: Were included a total of 283 women aged 25-64 years screened by Papanicolaou smears for determining cervical abnormalities, single-target polymerase chain reaction (PCR) and real-time PCR (rt-PCR) for hrHPV and mycoplasmas, respectively., Results: A total of 273 (94.5%) women were negative for intraepithelial lesions or malignancy cytology (NILM) and 10 (3.5%) presented abnormal cytology, all low-grade intraepithelial lesions (LSIL). The prevalence of hrHPV was 12.7% and 53.7% for mycoplasmas. U. parvum was the most frequently bacteria detected, followed by Mycoplasma hominis and U. urealyticum. M. genitalium was not detected. Women positive for U. parvum presented a 5-fold increased risk of LSIL (OR = 5.33; 95% CI = 1.09-26.04, P = 0.02) and co-infections between U. parvum and hrHPV increased the risk for LSIL (OR = 3.88; 95% CI = 1.75-8.58, P = 0.0003). However, these associations were not dependent on the concentration of the bacteria., Conclusion: Our results reinforced the hypothesis that some mycoplasmas may play a role as cofactors in HPV-mediated cervical carcinogenesis, at least in some populations., .

Sexually transmitted infections (STIs) represent a global health problem with variable prevalence depending on the geographical region and the type of population. Human papillomavirus (HPV) encompasses widespread virus types related to cervical carcinogenesis. The present study investigated the molecular prevalence of HPV and seven other important STIs in asymptomatic women working or studying at a Brazilian university. A secondary aim was to assess cytological abnormalities associated with HPV and other STIs coinfections. We recruited 210 women from a Brazilian university. HPV was detected using a single-round polymerase chain reaction (sPCR) followed by a viral genotyping by restriction fragment length polymorphism (RFLP-PCR). The presence of seven STIs: Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, Mycoplasma genitalium, herpes simplex virus (HSV)-1 and HSV-2 was detected by multiplex PCR (M-PCR). Furthermore, cytological findings and epidemiological characteristics were evaluated.The mean age of the participants was 27.1 years old. HPV prevalence was 33.8%, and HPV16 was the most frequently detected papillomavirus genotype. Moreover, multiple HPV infections were common (42.2%). We detected at least one STI agent in 11.4% of the tested women, most frequently C. trachomatis (6.7%). Among HPV-positive women, 14.1% were coinfected with other STI agents. Cytological abnormalities were observed in 9.5% of smears, and HPV-DNA, high-risk HPV (HR-HPV), HPV16 and HPV multiple infections were associated with abnormal cytological findings. There was a high prevalence of HPV, and C. trachomatis was the most prevalent STI agent, with low rates of cytological abnormalities. These findings highlight the need of timely STI diagnosis in young asymptomatic women and of a public policy design for STI prevention.

SARS-CoV-2 is an enveloped non-segmented positive-sense RNA virus, classified as a beta coronavirus, responsible for the COVID-19 pandemic. Angiotensin-converting enzyme 2 (ACE2), reported as a SARS-CoV-2 receptor, is expressed in different human tissues (lung, intestine, and kidney) and in the testis, ovaries, uterus, and vagina. This suggests a potential risk to the human reproductive tract in COVID-19 patients. In addition, SARS-CoV-2 RNA has been detected in the blood, urine, facial/anal swabs, semen, and vaginal secretion, suggesting other potential means of transmission. However, little has been reported about SARS-CoV-2 infection in the male and nonpregnant female reproductive tracts, which may provide direct evidence on sexual transmission and fertility problems. Therefore, we focused this narrative review mainly on the distribution of ACE2 and SARS-CoV-2 positivity in the male and nonpregnant female reproductive tracts, providing an overview of the potential threat of COVID-19 to reproductive health and sexual transmission.

Indoleamine 2,3-dioxygenase (IDO) is associated with the progression of many types of tumors, including melanoma. However, there is limited information about IDO modulation on tumor cell itself and the effect of BRAF inhibitor (BRAFi) treatment and resistance. Herein, IDO expression was analyzed in different stages of melanoma development and progression linked to BRAFi resistance. IDO expression was increased in primary and metastatic melanomas from patients' biopsies, especially in the immune cells infiltrate. Using a bioinformatics approach, we also identified an increase in the IDO mRNA in the vertical growth and metastatic phases of melanoma. Using in silico analyses, we found that IDO mRNA was increased in BRAFi resistance. In an in vitro model, IDO expression and activity induced by interferon-gamma (IFNγ) in sensitive melanoma cells was decreased by BRAFi treatment. However, cells that became resistant to BRAFi presented random IDO expression levels. Also, we identified that treatment with the IDO inhibitor, 1-methyltryptophan (1-MT), was able to reduce clonogenicity for parental and BRAFi-resistant cells. In conclusion, our results support the hypothesis that the decreased IDO expression in tumor cells is one of the many additional outcomes contributing to the therapeutic effects of BRAFi. Still, the IDO production changeability by the BRAFi-resistant cells reiterates the complexity of the response arising from resistance, making it not possible, at this stage, to associate IDO expression in tumor cells with resistance. On the other hand, the maintenance of 1-MT off-target effect endorses its use as an adjuvant treatment of melanoma that has become BRAFi-resistant., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

At present, cervical cancer is the fourth leading cause of cancer among women worldwide with no effective treatment options. In this study we aimed to evaluate the efficacy of hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) photodynamic therapy (PDT) in a comprehensive panel of human cervical cancer-derived cell lines, including HeLa (HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and 18-positive), and C33A (HPV-negative), compared to a nontumorigenic human epithelial cell line (HaCaT). Were investigated: (i) cell cytotoxicity and phototoxicity, cellular uptake and subcellular distribution; (ii) cell death pathway and cellular oxidative stress; (iii) migration and invasion. Our results showed that HYP/P123 micelles had effective and selective time- and dose-dependent phototoxic effects on cervical cancer cells but not in HaCaT. Moreover, HYP/P123 micelles accumulated in endoplasmic reticulum, mitochondria and lysosomes, resulting in photodynamic cell death mainly by necrosis. HYP/P123 induced cellular oxidative stress mainly via type II mechanism of PDT and inhibited cancer cell migration and invasion mainly via MMP-2 inhibition. Taken together, our results indicate a potentially useful role of HYP/P123 micelles as a platform for HYP delivery to more specifically and effectively treat cervical cancers through PDT, suggesting they are worthy for in vivo preclinical evaluations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

Background: Despite the demonstrated role of human Papillomavirus (HPV) in the etiology of cervical cancer and the strong evidence suggesting the importance of HPV in the development of oropharyngeal cancer, several aspects of the interrelationship between HPV infection in both body sites remain unknown, specifically in female human immunodeficiency virus (HIV)-positive (HIV+) patients. We aimed to assess the prevalence, distribution, and concordance of cervical and oral HPV in HIV+ women and matched HIV-negative (HIV-) controls in Brazil., Material and Methods: Cervical and endocervical samples for cytological screening and HPV detection and oral samples were collected from 115 HIV+ women using highly active antiretroviral therapy (HAART) and 139 HIV-matched controls (HIV-) in Maringá City, Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding HIV infection were obtained from the patients' medical records. HPV detection and typing were performed using the Kit Multiplex XGEN Multi HPV Chip HS12., Results: HIV infection was well controlled in this cohort, but women who exhibited detectable HIV loads were significantly associated with HPV-positive status overall ( P  = 0.03) and in cervical mucosa ( P  = 0.01). HIV+ women had significantly more abnormal cytological findings ( P  = 0.04) than HIV- women. Of the 115 HIV+ women, 48.7% were positive for cervical and/or oral HPV DNA; of the 139 HIV- women, 41% were positive for cervical and/or oral HPV ( P  = 0.25). Both HIV+ and HIV- women had a statistically higher prevalence of cervical HPV infection than oral infection. The concurrent HPV infection in two anatomical sites was similar in HIV+ and HIV- women; however, HPV type concordance was not observed. HPV type distribution was different between the anatomical sites in both groups, and HIV+ women presented less common types, mainly in oral mucosa., Conclusion: Our data support the importance of testing HPV infection in HIV+ women, even when the HIV infection is well controlled. Prospective studies are required to better understand the natural history of HPV infection in both anatomical sites, specifically in HIV+ women., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

This review provides a general overview on the positivity and persistence of Zika virus (ZIKV) in female genital tract (FGT) of non-pregnant women and animals, as well as in cell cultures, and its influence on FGT health. We performed a systematic review based on the PRISMA statement to identify studies focused on "Zika virus" and "non-pregnant female" in PubMed, Embase, Scopus Scholar and Web of Knowledge databases of full-text papers and abstracts published in English, with no restrictions regarding the initial date of publication, up to August 2019. Our search terms yielded 625 records, that were 108 after removal of duplicates, leaving 517 items for title and abstract reviews. Of these, 475 did not meet the inclusion criteria, leaving 42 records for full-text review and resulting in the exclusion of 6 additional records. The remaining 36 met our inclusion criteria. Variations were observed regarding the presence and persistence of ZIKV in lower and upper genital samples. However, the FGT was the place in which ZIKV RNA has been detected, sometimes for relatively long periods, even after the clearance from blood and urine. In addition to the vagina and cervix, the endometrium, uterus and ovary (oocytes and follicles) could also be involved in persistent ZIKV infections. Further prospective studies are needed to assess the effect of ZIKV on FGT health.

Background: Breast cancer is the most relevant type of cancer and the second cause of cancer- related deaths among women in general. Currently, there is no effective treatment for breast cancer although advances in its initial diagnosis and treatment are available. Therefore, the value of novel anti-tumor therapeutic modalities remains an immediate unmet need in clinical practice. Following our previous work regarding the properties of the Pluronics with different photosensitizers (PS) for photodynamic therapy (PDT), in this study we aimed to evaluate the efficacy of supersaturated hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) against breast cancer cells (MCF-7) and non-tumorigenic breast cells (MCF-10A)., Methods: Cell internalization and subcellular distribution of HYP/P123 was confirmed by fluorescence microscopy. The phototoxicity and citototoxicity of HYP/P123 was assessed by trypan blue exclusion assay in the presence and absence of light. Long-term cytotoxicity was performed by clonogenic assay. Cell migration was determined by the wound-healing assay. Apoptosis and necrosis assays were performed by annexin VFITC/ propidium Iodide (PI) by fluorescence microscopy., Results: Our results showed that HYP/P123 micelles had high stability and high rates of binding to cells, which resulted in the selective internalization in MCF-7, indicating their potential to permeate the membrane of these cells. Moreover, HYP/P123 micelles accumulated in mitochondria and endoplasmic reticulum organelles, resulting in the photodynamic cell death by necrosis. Additionally, HYP/P123 micelles showed effective and selective time- and dose dependent phototoxic effects on MCF-7 cells but little damage to MCF-10A cells. HYP/P123 micelles inhibited the generation of cellular colonies, indicating a possible capability to prevent the recurrence of breast cancer. We also demonstrated that HYP/P123 micelles inhibit the migration of tumor cells, possibly by decreasing their ability to form metastases., Conclusion: Taken together, the results presented here indicate a potentially useful role of HYP/P123 micelles as a platform for HYP delivery to more specifically and effectively treat human breast cancers through photodynamic therapy, suggesting they are worthy for in vivo preclinical evaluations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Human papillomavirus (HPV) infection is the central factor for cervical cancer, whereas epithelial immune mechanisms contribute to the progression of HPV infection and its associated lesions. The authors evaluated the expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) in cervicovaginal samples from women with normal cervical epithelium or with different degrees of squamous intraepithelial lesions (SILs) and cervical cancer., Methods: IDO expression was analyzed by immunocytochemistry in liquid-based cytology samples from 165 women, of whom 42 had cervical changes subclassified as low-grade SIL (n = 6), high-grade SIL (n = 30), or squamous cell carcinoma (SCC) (n = 6), and 123 had negative Papanicolaou smears. IDO and TDO expression also were analyzed by immunohistochemistry, and HPV and other genital pathogens were evaluated by polymerase chain reaction analysis., Results: Low IDO expression was observed in normal cervical epithelium irrespective of HPV status. Increased numbers of IDO-positive squamous cells and IDO-positive leukocytes were observed in women with SIL or SCC. TDO expression was detected in leukocytes infiltrating the stroma around intraepithelial or invasive cervical lesions. Higher IDO levels were detected in organotypic epithelial cultures established from keratinocytes transduced with the HPV16 E6/E7 oncoproteins., Conclusions: The upregulation of IDO expression in leukocytes and squamous cells in HPV-associated SIL and SCC suggests that immunosuppressive mechanisms involving tryptophan metabolism may have a role in cervical carcinogenesis. Although previous studies have suggested the role of IDO in HPV pathogenesis, this is the first evidence of TDO involvement in the process. Furthermore, the current data emphasize the role of leukocytes, especially neutrophil-like cells, as an IDO source., (© 2019 American Cancer Society.)

Research Question: Is there an association between the presence of sexually transmitted pathogens in the lower (LGT) and upper (UGT) female genital tract with endometriosis and infertility?, Design: Case-control study with 60 women submitted to gynaecological laparoscopic surgery. Samples from the UGT and LGT were collected and analysed by single polymerase chain reaction (PCR) for human papillomavirus (HPV) and by multiplex PCR for other sexually transmitted infections (STI). Patients were initially divided into two clinical groups: infertile patients (n = 25) with conjugal infertility and fertile control patients (n = 35). After the surgical findings patients were further divided for additional analysis: an endometriosis group (n = 29) and non-endometriosis control group (n = 31)., Results: Sixty per cent of patients were positive for DNA-HPV in some of the genital tract sites sampled. Infertile patients were associated with high-risk HPV (hrHPV) positivity in the UGT sites (P = 0.027). The endometriosis group was associated with hrHPV positivity in the LGT and UGT sites (P = 0.0002 and P = 0.03, respectively). Only hrHPV types were detected in the UGT in both groups. It may be that there is a hrHPV infection continuum, from LGT to UGT, in infertile and endometriosis patients. No association was observed among the other seven STI studied., Conclusions: This study shows both an association between hrHPV infections in the UGT with infertility and endometriosis, and a possible hrHPV infection continuum, from LGT to UGT. Larger studies are needed to fully investigate the role of hrHPV as a cause of endometriosis and infertility., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Zika virus (ZIKV) is a re-emerging mosquito-transmitted flavivirus associated with congenital abnormalities in newborns and with Guillain-Barré syndrome in adults. The virus can also be sexually transmitted and can persist in the male genital tract. Studies evaluating the kinetics of ZIKV in seminal shedding of men who have been infected, as well as in animal and cellular models of infection, have shown that, in addition to the testis and epididymis, the prostate and seminal vesicles could also be involved in persistent ZIKV infection. Additionally, some studies have reported that men infected with ZIKV can present with genitourinary symptoms such as haematospermia, prostatitis, painful ejaculation, penile discharge, and oligospermia; however, little is known about the effect of ZIKV on fertility. Understanding the mechanisms that underlie persistent ZIKV infections in men is crucial to developing guidelines, effective vaccines, and therapies.

Most cervical cancers occur in women who do not participate in cervical-cancer screening. We therefore evaluated adherence to screening for clinic-based Pap testing, self-collected sampling for HPV testing, and choice of the 2 among 483 unscreened/underscreened women in Brazil. Three public Basic Health Units (BHU) were each randomly assigned to three arms: (i) Pap testing at the BHU ( N = 160), (ii) "Self&HPV" (self-collection for HPV testing) ( N = 161), and (iii) "Choice" between self-collection and HPV testing and Pap test at the local BHU ( N = 162). The theory-based (PEN-3 and Health Belief Model) intervention in all three arms was implemented by trained Community Health Workers (CHW) at participants' home. With the first invitation, 60.0% in the Pap arm, 95.1% [154 of 161 (95.7%) who selected Self&HPV and 0 of 1 (0.0%) who selected Pap] in the Choice arm, and 100% in the Self&HPV arm completed screening. By the second invitation to choose a method of screening in the Choice arm, 100% completed screening. After three invitations, 75.0% of women in the Pap arm completed screening. Adherence to screening differed by study arm ( P < 0.001). In conclusion, Self&HPV testing is a promising strategy for unscreened/underscreened women who are recalcitrant or unable to undergo clinic-based cervical screening to complement the screening modality used in the general population. In Brazil, where Pap testing is recommended for routine cervical screening, training CHWs in behavior change strategies and offering Self&HPV or Choice could greatly improve screening population coverage by reaching the unscreened/underscreened populations., (©2019 American Association for Cancer Research.)

Zika virus (ZIKV) infection is an emerging public health problem, associated with increased risk for Guillain-Barré syndrome and adverse fetal outcomes, including congenital microcephaly. Zika virus sexual transmission is known, but detection of the virus in different parts of the female reproductive tract is not well established. In this case report, we describe prolonged detection of ZIKV RNA in the vaginal secretion and endocervical mucosa from a Brazilian woman convalescent to ZIKV infection. A viral load of 2 × 10 2 copies/mL was detected up to 31 days after symptom onset in both samples. Other biological fluids, including whole blood, plasma, serum, urine, and saliva samples, were negative for ZIKV RNA. These findings advance the understanding of ZIKV infection and provide data for additional testing strategies.

To access the possibility that key markers of bacterial vaginosis (KM-BV) could affect seminal parameters and thus fertility a prospective cohort study was designed (a) to develop rapid and sensitive multiplex polymerase chain reaction (M-PCR) assays to screen 13 key markers of bacterial vaginosis (KM-BV) in semen specimens, (b) to determine the prevalence of KM-BV in semen from randomized male partners of couples seeking fertility evaluation. A total of 229 semen samples were included in the study from males who visited the Sperm Analysis Section of Brazil between October 2015 and March 2016. Eligible men were 18 years or older and had a semen analysis due fertility evaluation (after failing to conceive with their partner after 1 year of unprotected intercourse). Basic seminal parameters were analyzed, and KM-BV was detected by M-PCR assays. M-PCR assays clearly distinguished 13 KM-BV in 146 semen samples (63.8%), mainly Gardnerella vaginalis (50.7%). Some important associations occurred between the presence of KM-BV in semen and changes in seminal parameters. KM-BV is commonly present in the semen of males seeking fertility evaluation and could potentially play significant roles in male subfertility and/or infertility.

Background: Human papillomavirus (HPV) infection is associated with cervical cancer; however, it is controversial whether it is involved in non-cervical genital cancers. Objective: This study aimed to evaluate articles on the prevalence of HPV in penile cancer, vulvar cancer, colorectal cancer, prostate cancer and anal canal cancer in studies conducted in Brazil. Methods: The study was conducted in accordance with the Preferred Reporting of Systematic Reviews and Meta-Analysis Statement. Comprehensive searches for HPV and cancer for the years 2006 to 2016 were conducted in two databases (PubMed and Web of Knowledge) and Google Scholar system. We also tracked the references of all eligible articles to identify additional non-captured publications through online surveys. Results: Eighteen studies, with a combined sample size of 1,552 patients were analyzed. The overall prevalence of HPV was 43% (95% CI: 36–51%; p < 0.001). The pooled prevalence of HPV in penile cancer was 42% (95% CI: 32–55%; p < 0.001), in colorectal cancer it was 67% (95% CI: 64–70%; p < 0.001) and in vulvar cancer 43% (95% CI: 34–55%; p < 0.001). HPV 16 was the most prevalent in all sites evaluated, with prevalence estimated at 54% (95% CI: 44–66%; p < 0.001), followed by genotypes 33 (21%; 95% CI: 17–28; p < 0.001), 6 (15%; 95% CI: 8–26%; p < 0.001), 11 (13%; 95% CI: 5–32%; p < 0.001) and 18 (12%; 95% CI: 7–22%; p < 0.001), respectively. The pooled prevalence of single infection was 82% and infection by multiple genotypes of HPV was 22%. Conclusion: Our study demonstrated a high prevalence of HPV in non-cervical genital cancers in Brazil, with predominance of genotype 16, providing evidence for the need for preventive and control measures to avoid future harm to the population., (Creative Commons Attribution License)

Cervical cancer is the fourth most common cancer that affects women, mainly through human papilloma virus (HPV) infection with high-risk HPV16 and HPV18. The present study investigated the in vitro anticancer activity and mechanism of action of a proanthocyanidin polymer-rich fraction of Stryphnodendron adstringens (F2) in cervical cancer cell lines, including HeLa (HPV18-positive), SiHa (HPV16-positive), and C33A (HPV-negative) cells, and also evaluated in vivo anticancer activity. In vitro , cell viability was determined by the MTT assay. Cell migration was determined by the wound healing assay. The mechanism of action was investigated by performing ultrastructural analysis and evaluating reactive oxygen species (ROS) production, mitochondrial metabolism, lipoperoxidation, BCL-2 family expression, caspase expression, and DNA and cell membrane integrity. In vivo activity was evaluated using the murine Ehrlich solid tumor model. F2 time- and dose-dependently reduced cell viability and significantly inhibited the migration of cervical cancer cells. HeLa and SiHa cells treated with F2 (IC 50 ) exhibited intense oxidative stress (i.e., increase in ROS and decrease in antioxidant species) and mitochondrial damage (i.e., mitochondrial membrane potential depolarization and a reduction of intracellular levels of adenosine triphosphate). Increases in the Bax/BCL-2 ratio and caspase 9 and caspase 3 expression, were observed, with DNA damage that was sufficient to trigger mitochondria-dependent apoptosis. Cell membrane disruption was observed in C33A cells (IC 50 and IC 90 ) and HeLa and SiHa cells (IC 90 ), indicating progress to late apoptosis/necrosis. The inhibition of ROS production by N -acetylcysteine significantly suppressed oxidative stress in all three cell lines. In vivo , F2 significantly reduced tumor volume and weight of the Ehrlich solid tumor, and significantly increased lipoperoxidation, indicating that F2 also induces oxidative stress in the in vivo model. These findings indicate that the proanthocyanidin polymer-rich fraction of S. adstringens may be a potential chemotherapeutic candidate for cancer treatment.

Currently, there is a strong global trend towards the development of in vitro models to replace the use of animals in safety evaluation tests. Reconstructed Human Epidermis (RHE) models have been employed as an alternative method to animal testing of skin corrosion and irritation potential of chemical compounds. However, the consequences of an absence of the dermal compartment in these models should be considered since the cross-talk between fibroblasts and keratinocytes is fundamental for promoting proper epidermal stratification, homeostasis, inflammatory response and wound healing. In this study, we compare in-house developed models of Reconstructed Human Epidermis (i.e. USP-RHE) and full thickness skin (i.e. USP-FTS) regarding their response when submitted to skin corrosion assays, based on Guideline 431 (OECD). The results show that both models correctly classified the four substances tested (2-phenylethyl bromide, benzylacetone, lactic acid, octanoic acid) as corrosive or non-corrosive. Furthermore, we have demonstrated higher cell viability of the USP-FTS model compared to the USP-RHE model, a sign of its improved barrier function, following the exposure to the substances test on the corrosion assay. This emphasizes the importance of employing in vitro models that are more physiologically relevant and that better mimic the in vivo situation for the toxicological screening of substances., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To assess the possibility that herpes simplex virus (HSV) infection could affect seminal parameters, we (1) standardize and validate a multiplex polymerase chain reaction (M-PCR) assay to detect HSV-1 and HSV-2 in semen, and (2) determine the prevalence of HSV-1/-2 in the semen of randomized male partners of couples seeking fertility evaluation., Materials and Methods: A total of 279 semen samples were included in the study from men who visited the Sperm Analysis Section of São Camilo Laboratory of Maringá, Brazil, between November 2014 and July 2015. Eligible men were 18 years or older and had a semen analysis due fertility evaluation (after failing to conceive with their partner after 1 year of unprotected intercourse). Basic seminal parameters were analyzed, and HSV-1 and HSV-2 were detected by M-PCR., Results: The M-PCR assay clearly distinguished and identified 2 HSV types in semen samples. HSV in total was detected in 10.7% of samples, of which 7.5% had HSV-1 exclusively and 3.2% had HSV-2 exclusively. We detected a significant association of HSV-2 infection with hematospermia and with a lower mean seminal volume, and between HSV-1 infection and a lower mean sperm count., Conclusion: These findings suggest that the male partners of infertile couples with HSV infections may have changes on the 2 equally important components of semen, spermatozoa and seminal fluid, which may influence fertility. Further studies enrolling a larger number of patients are necessary to confirm these data and to elucidate the clinical relevance of HSV presence in semen., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is the main bioactive component of Brazilian green propolis, and possesses, among other things, anticancer properties. However, to the best of our knowledge, there are no studies of artepillin C in cervical cancer., Method: To explore a new therapeutic candidate for cervical cancer, we have evaluated the effects of artepillin C on cellular viability in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16- and 18-positive) and C33A (HPV-negative) cells compared to a spontaneously immortalized human epithelial cell line (HaCaT)., Results: Our results demonstrated that artepillin C had a selective effect on cellular viability and could induce apoptosis possibly by intrinsic pathway, likely a result of oxidative stress, in all cancer-derived cell lines but not in HaCaT. Additionally, artepillin C was able to inhibit the migration and invasion of cancer cells., Conclusion: Thus, artepillin C appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV types., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To evaluate screening by the Papanicolaou smear (Pap) and the frequency of cervical abnormalities in the age range recommended by the Brazilian programme for prevention and control of cervical cancer (CC) in the years 2012 and 2013 in a high prevalence city. Methods: This retrospective study covered results of Pap examinations performed on women aged ≥12 years residing in urban areas of the city of Maringá, Paraná in Brazil. The examinations were performed in the years 2012 and 2013 for the System of Public Health (SPH) which maintains a city database. The age ranges were grouped as recommended into <15-24, 25-64, and >64 years. Results: A total 40,866 women were screened, 19,606 in 2012 and 21,260 in 2013. The Pap exams performed for the age range 25-64 years accounted for 80.7% of the total in 2012 and 80.3% in 2013 (p=0.13), while those for <15 to 24 years accounted for 11.7% and 11.3%, respectively. There were more tests performed in the >64 years age group in 2013 (8.46%) than in 2012 (7.52%) (p<0.001). A total of 1,354 (3.31%) women presented with abnormal test results, with atypical squamous cells of undetermined significance (ASC-US) as the most prevalent finding (2.12%) in 2012, while in 2013 it was LSIL (1.56%) (p<0.001 for both). Women with ASC-US showed a lower mean age than did those with other lesions in both years. Conclusions: This study detected a significant expansion of women screened for CC in age ranges not recommended by the Brazilian government., (Creative Commons Attribution License)

Purpose: Vulvovaginal candidiasis (VVC) is one of the most frequent female genital disorders and Candida glabrata is the second most common agent. Current study was aimed to study the susceptibility to antifungal agents of C. glabrata isolated from vaginal samples and some virulence attributes in order to better understand why this species is emerging as the main VVC agents., Methods: A total of 60 C. glabrata vaginal isolates were included in this study. Firstly they were screened by susceptibility tests to antifungal agents. The isolates that showed sensitivity or resistance to fluconazole were evaluated for their virulence potential, including ability to adhere to polystyrene and vaginal ring, cell surface hydrophobicity (CSH) and capacity to form biofilm., Results: Candida glabrata isolates varied significantly in adherence capacity, biofilm formation and CSH. However, it was possible to observe that isolates resistant to fluconazole adhered more efficiently to the vaginal ring and were statistically more able to form biofilm., Conclusion: These results allow hypothesizing that C. glabrata is an emergent agent in VVC probably because the treatment with fluconazole selects this species. But once adhered, yeasts remain on biotic or abiotic surfaces causing colonization or VVC symptomatology.

Different models of reconstructed human epidermis (RHE) are currently validated to assess skin irritation in vitro and ultimately to the animal replacement of the Draize test. The development of a new RHE model is a challenge for many laboratories, representing a potential gain of autonomy and improvement of technological knowledge. The Organization for Economic Co-operation and Development (OECD) encourages the development of new models and, for this purpose, offers a thorough guideline on quality control parameters (OECD TG 439 performance standards). This work aimed to develop an RHE model (i.e. USP-RHE) for in vitro skin irritation assays, following the OECD TG 439. The developed model presents a well-differentiated epidermis similar to the Validated Reference Methods (VRM) and to native human epidermis. Quality parameters, i.e. optical density of negative control, tissue integrity and barrier function, were similar to VRM and in accordance with OECD TG 439. Moreover, the USP-RHE model was shown to have 85,7% of specificity (6/7), 100% of sensitivity (6/6) and 92,3% of accuracy (12/13) when compared to in vivo UN GHS classification. The within-laboratory reproducibility was 92.3% (12/13). Thus, we demonstrated that USP-RHE model attends to all OECD TG 439 performance standards and is ready to be used by private and public laboratories and companies for future validation studies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The photodynamic properties of Hypericin (Hyp) may be used as an alternative treatment for malignancies of the lower gastrointestinal tract and for the prevention of surgical-site infection; however, its use in photodynamic therapy has been limited because of its poor hydrosolubility. Therefore, in order to improve its water solubility and its photodynamic effect, Hyp was encapsulated in Pluronic P123 (P123) and the photodynamic effects against intestinal and epidermal bacteria and against two lineages of intestinal colon carcinoma cells were investigated. Two response surface methods (RSM) were used to achieve the best in vitro photodynamic activity against Enterococcus faecalis, Escherichia coli and Staphylococcus aureus: in the first (full 2 3 RSM), Hyp concentration (HC*), incubation time (IT*) and LED-light time (LT*) were considered as the independent variables and E. faecalis inhibition as the dependent variable. In the second (full 3 2 RSM), Hyp concentration (HC*) and P123 concentration (CC*) were considered as independent variables and E. faecalis, E. coli and S. aureus inhibition as dependent variables. The optimized experimental conditions achieved were: Hyp concentration=37.5μmol/L; P123 concentration=21.5 μmol/L and 6.3J/cm 2 , which resulted in 2.86±0.12 and 2.30±0.31CFU log-reductions of E. faecalis and S. aureus. No effect was seen against E. coli. The cytotoxic effects of Hyp/P123 were also investigated for Caco-2 and HT-29 intestinal colon carcinoma cells at Hyp/P123 concentrations of 1, 0.5, 0.25 and 0.1μmol/L for Caco-2 cells and 4, 3, 2 and 1μmol/L for HT-29 cells. The cytotoxic concentrations for 50% (CC 50 ) and 90% (CC 90 ) of Hyp/P123 were 0.443 and 0.870μmol/L for Caco-2 cells and 1.4 and 2.84μmol/L for HT-29 cells. The P123 nanocarrier played a significant role in the permeation of Hyp through the cell membrane leading to significant cell death, and showed itself to be a promising photosensitizer for PDT that could be suitable for the treatment of colonic diseases since it is effective against positive Gram bacteria and intestinal colon carcinoma cells., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Several studies have addressed the impact of viral infections on male infertility. However, it is still unknown whether human papillomavirus (HPV) can alter seminal parameters. The aim of this study was to determine the prevalence of HPV in the semen of male partners of couples seeking fertility evaluation. Additionally, we assessed the possibility that HPV infections affect seminal parameters. A total of 229 semen samples were collected from men in the Sperm Analysis Section of São Camilo Laboratory of Maringá, Brazil, between October 2015 and March 2016. Basic seminal parameters were analyzed, and HPV was detected and genotyped by polymerase chain reaction. HPV DNA was detected in 16.6% of samples. Of these, 10.5% had single type HPV infections, 6.1% had multiple HPV infections, 5.7% had exclusively high-risk HPV, and 6.1% had exclusively low-risk HPV. Samples positive for single and multiple types of HPV were associated with abnormal viscosity, and samples positive for multiple HPV types were also associated with hypospermia, higher pH, and increased leukocyte numbers. These findings suggest that the male partners of infertile couples with seminal HPV infections may have prostate disturbances indicative of glandular dysfunction, which may influence fertility.

Vulvovaginal candidiasis (VVC) in HIV-infected (HIV+) women is a serious public health problem. However, little is known about the virulence mechanisms of vaginal Candida albicans from HIV+ women in the post-highly active antiretroviral therapy (HAART) era. Here, we report a comparative analysis of the expression of key virulence factors and genetic variability of 26 vaginal C. albicans strains isolated from HIV+ women undergoing HAART and 18 from HIV-uninfected (HIV-) women. In general, we observed that C. albicans from HIV+ women receiving HAART showed lower expression of virulence factors compared with C. albicans from HIV- women, except for the proteinase activity which is highly expressed. The results in HIV-women further suggest that virulence factors appear to be expressed in response to the yeast stress, in the presence of an adequate immune response. Furthermore, the RAPD results showed a high heterogeneity among isolates from both groups of women. These findings in HIV+ women using HAART will help to improve the monitoring of vaginal yeast infections and the quality of life of patients.

The field of redox biology has changed tremendously over the past 20 years. Formerly regarded as bi-products of the aerobic metabolism exclusively involved in tissue damage, reactive oxygen species (ROS) are now recognized as active participants of cell signaling events in health and in disease. In this sense, ROS and the more recently defined reactive nitrogen species (RNS) are, just like hormones and second messengers, acting as fundamental orchestrators of cell signaling pathways. The chemical modification of enzymes by ROS and RNS (that result in functional enzymatic alterations) accounts for a considerable fraction of the transient and persistent perturbations imposed by variations in oxidant levels. Upregulation of ROS and RNS in response to stress is a common cellular response that foments adaptation to a variety of physiologic alterations (hypoxia, hyperoxia, starvation, and cytokine production). Frequently, these are beneficial and increase the organisms' resistance against subsequent acute stress (preconditioning). Differently, the sustained ROS/RNS-dependent rerouting of signaling produces irreversible alterations in cellular functioning, often leading to pathogenic events. Thus, the duration and reversibility of protein oxidations define whether complex organisms remain "electronically" healthy. Among the 20 essential amino acids, four are particularly susceptible to oxidation: cysteine, methionine, tyrosine, and tryptophan. Here, we will critically review the mechanisms, implications, and repair systems involved in the redox modifications of these residues in proteins while analyzing well-characterized prototypic examples. Occasionally, we will discuss potential consequences of amino acid oxidation and speculate on the biologic necessity for such events in the context of adaptative redox signaling. © 2014 IUBMB Life, 66(3):167-181, 2014., (© 2014 International Union of Biochemistry and Molecular Biology.)