Search

Objective: The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis., Methods: The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes., Results: This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated., Conclusions: In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest and funding disclosures., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Microplastic studies hold a low explored potential for citizen science and environmental education, but methodological issues challenge data produced by non-specialists. We compared microplastic abundance and diversity in the red tilapia Oreochromis niloticus recovered by untrained students with those recovered by researchers that have experience of three years studying the incorporation of this pollutant by aquatic organisms. Seven students dissected 80 specimens and performed digestion of digestive tract in hydrogen peroxide. The solution was filtered and inspected under a stereomicroscope by the students and by two expert researchers. A control treatment consisted of 80 samples handled only by experts. The students overestimated the abundance of fibers and fragments. Striking differences in abundance and richness of microplastics were verified between the fish dissected by students and by expert researchers. Therefore, citizen science projects involving the uptake of microplastics by fish should provide training until a satisfactory level of expertise is reached., 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 © 2023 Elsevier Ltd. All rights reserved.)

FOXO3a dysregulation is frequently implicated in tumorigenesis, and its inhibition can occur by several molecular mechanisms. Among these, post-transcriptional suppression by miRNAs has been associated with various cancers initiation. Here, we assessed the expression profiles of the most relevant miRNAs for breast tumorigenesis, using Luminal A (LA) and Triple-Negative (TN) breast cancer from Brazilian patients, by the quantitative real time-PCR method. Their potential prognostic role for the patients was also evaluated. We identified the miRNAs miR-96-5p and miR-182-5p, de-scribed as negative regulators of FOXO3A, with differential expression both in LA and TN tumors when compared to normal tissue. The miR-96-5p and miR-182-5p miRNAs were upregulated in LA (7.82 times, p < 0.005; 6.12 times, p < 0.005, respectively) and TN breast cancer samples (9.42 times, p < 0.0001; 8.51 times, p < 0.0001) compared to normal tissues. The samples with higher miR-96-5p and miR-182-5p expression (FR ≥ 4) were submitted for FOXO3a immunostaining. Reduced protein detection was observed in all of the tumors compared to normal tissues. The most prominent miRNA expression and FOXO3a protein suppression were observed in TN samples (p < 0.001), indicating the relevant role of these molecules in this tumor biology and clinical behavior. Our results corroborate the literature regarding to the relevance of FOXO3a in the breast cancer, and they open new perspectives for alternative target therapy options for Brazilian patients expressing both FOXO3a and its regulatory miRNAs., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Density functional theory (DFT) calculations were used to study the superoxide dismutase (SOD) mimic activity of two Cu 2+ complexes with ligands derived from 8-hydroxyquinoline (8-HQ). Electron-donating and -withdrawing substituent groups were inserted into the structures to verify changes in the reactivity. The theoretical parameters obtained were compared and validated with the experimental data available. The results showed that the reduction process occurs with greater participation of the 8-HQ ligand and the oxidation step occurs with participation of the copper atom in the complexes, where the electron received during the reduction step is used to reduce the Cu 2+ to Cu + . The calculated electronic affinity showed good correlation with the experimental mimetic activity, and the analysis of this property, of total charge and of molecular orbitals indicated an increase in the mimetic activity with the insertion of electron-withdrawing substituent groups in the structures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: The present study aimed to contribute to the catalog of genetic mutations involved in the carcinogenic processes of uterine sarcomas (USs) and carcinosarcomas (UCSs), which may assist in the accurate diagnosis of, and selection of treatment regimens for, these conditions., Methods: We performed gene-targeted next-generation sequencing (NGS) of 409 cancer-related genes in 15 US (7 uterine leiomyosarcoma [ULMS], 7 endometrial stromal sarcoma [ESS], 1 adenosarcoma [ADS]), 5 UCS, and 3 uterine leiomyoma (ULM) samples. Quality, frequency, and functional filters were applied to select putative somatic variants., Results: Among the 23 samples evaluated in this study, 42 loss-of-function (LOF) mutations and 111 missense mutations were detected, with a total of 153 mutations. Among them, 66 mutations were observed in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. TP53 (48%), ATM (22%), and PIK3CA (17%) were the most frequently mutated genes. With respect to specific tumor subtypes, ESS showed mutations in the PDE4DIP, IGTA10, and DST genes, UCS exhibited mutations in ERBB4, and ULMS showed exclusive alterations in NOTCH2 and HER2. Mutations in the KMT2A gene were observed exclusively in ULM and ULMS. In silico pathway analyses demonstrated that many genes mutated in ULMS and ESS have functions associated with the cellular response to hypoxia and cellular response to peptide hormone stimulus. In UCS and ADS, genes with most alterations have functions associated with phosphatidylinositol kinase activity and glycerophospholipid metabolic process., Conclusion: This preliminary study observed pathogenic mutations in US and UCS samples. Further studies with a larger cohort and functional analyses will foster the development of a precision medicine-based approach for the treatment of US and UCS.

The white garland-lily rhizomes represent a potential source for starch extraction. Thus, the present study aimed to contribute with new data about the starch extraction yield and to characterize the chemical-structural, thermal and technological properties of the white garland-lily starch. The rhizomes harvested in the dry season presented greater starch yields (22.0 g 100 g -1 ) than in the early summer (6.9 ± 0.5 g 100 g -1 ) (d.b). The starch presented adequate purity (97.67 g 100 g -1 ), the granules were flat, with the thickness varying from 2 to 6 μm and length between 12 and 38 μm, and they showed no birefringence. They presented an amylose content of 59.16 g 100 g -1 , crystallinity of 19.30% and type B starch. The C13 CP/MAS spectrum presented an amorphous pattern although indicating a transition to type V. This was a product with moderate swelling power and a high gelatinization peak temperature (76.78 °C). The extraction of white garland-lily starch is feasible in the dry season when it has chemical-structural, thermal and technological properties suitable for use in the food industry, related to its high amorphous starch content., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Selenium (Se) is essential to humans and animals due to its antioxidant properties. Although it is not considered an essential nutrient for higher plants. Many studies show that Se in low concentrations (up to 0.5 mg kg -1 ) provides beneficial effects to non-hyperaccumulating plants by participating in antioxidant defense systems and enhancing tolerance to abiotic stress. Therefore, this study aimed to evaluate the effects of Se application rates on rice plants under different soil water conditions. The experiment was conducted on an Oxisol using four Se rates (0, 0.5, 1.0 and 2.0 mg kg -1 ) and two soil water conditions (irrigated and water deficit). Selenium application via soil up to 0.5 mg kg -1 increased the plant height, chlorophyll index, sulfur and copper accumulation in shoots, carbon dioxide assimilation, superoxide dismutase (EC 1.15.1.1) activity and decreased the hydrogen peroxide concentration in rice leaves. The accumulation of Se in shoot biomass and Se concentration in seeds increased linearly with the applied rates. Water deficit strongly decreased the plant growth and yield. However, rice plants treated with Se showed higher net photosynthesis, water use efficiency and antioxidant system. This study provides useful information about the roles of Se in protecting rice plants from water deficit stress., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Eye closure sensitivity (ECS) has been described as a reflex trait in juvenile myoclonic epilepsy (JME). However, there is no consensus regarding its significance on prognosis. The aim of this study is to clarify the long-term impact of ECS documented by a clinical interview and a video-EEG neuropsychological protocol (VNPP) in a series of 133 JME patients., Methods: Data from 22 JME patients with ECS confirmed by a VNPP (Group 1) were compared with those of 20 JME patients without any reflex traits (Group 2). They were followed for a mean of 8.21 years (SD=±5.044). The frequency of seizures was assessed using a diary. Except for photosensitivity (PS), any other reflex traits occurrence, drugs/alcohol abuse intake, noncompliance, and Jeavons syndrome, were considered exclusion criteria., Results: Group 1 had a lower age at epilepsy onset (p = 0.028), higher incidence of febrile seizures (13.6%), and familial history of epilepsy (p = 0.023). Only 18.2% had self-perception of eyelid myoclonia (EM) (kappa coefficient = 0.193), which persisted in 77.3% of patients. Limb myoclonia, tonic-clonic seizures (TCS) and/or myoclonic-tonic-clonic seizures (MTCS), as well as absences were more frequent (p = 0.015; p = 0.013; p = 0.011, respectively) in Group 1. PS did not influenced frequency of EM (p = 1.0), absences (p = 0.648), or TCS/MTCS (p = 0.934). Psychiatric comorbidities were not different between groups., Conclusions: ECS is related to a worse outcome regarding control of all seizure types, persistence of EM, and higher frequency of limb myoclonia, as well as the total number of TCS and/or MTCS., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives:: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol., Methods:: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis., Results:: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor., Conclusions:: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

Purpose: Juvenile myoclonic epilepsy (JME) is a heterogeneous syndrome in which seizures can be precipitated not only by non-specific factors, such as sleep deprivation and stress, but also by specific stimuli, such as photic stimuli, eye-closure, praxis, and language. The presence of these reflex traits may indicate the hyperexcitability of different cortical areas, which may be reflected in patients' neuropsychological deficit profile. The objective of our study is to investigate the possible relations between JME endophenotypes and patients' cognitive performance., Methods: 61 JME patients were divided into four groups: no reflex traits (group 1, 20 patients); praxis induction (group 2, 13); eye-closure and/or photosensitivity (group 3, 17); and a combination of different reflex traits (group 4, 11). Neuropsychological performance was compared between JME subgroups. 60 healthy controls were used to calculate z-scores. Patients also underwent psychiatric assessment. We controlled the clinical variables, e.g. age at epilepsy onset, frequency of myoclonic seizures, total and sedative drug load, setting them as covariables for the ANOVA analysis., Results: Praxis induction was more common in males (p=0.018) and groups with reflex traits (2, 3, and 4) presented higher rates of persistent myoclonia, polytherapy, clonazepam use (group 3), and more frequent psychiatric comorbidities. Group 4 patients performed worse in Trail Making Test B than the patients in group 1. These findings were independent of clinical variables., Conclusion: JME patients with a combination of praxis induction and eye-closure/photosensitivity had greater executive dysfunction, revealing an association between reflex ictogenic mechanisms and cognitive performance., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: In a recent phase 2 clinical trial in spinocerebellar ataxia type 3/Machado Joseph disease (SCA3/MJD), a neurogenetic disorder without specific therapy, benefits of lithium carbonate were found only on secondary efficacy outcomes, all related to ataxic features. In order to help designing future studies, we further analyzed the trial data searching for treatment response modifiers and metric properties of spinocerebellar ataxia (SCA) scales., Methods: Efficacy analysis was performed with the Neurological Examination Score for the Assessment of Spinocerebellar Ataxia (NESSCA) and the Scale for the Assessment and Rating of Ataxia (SARA) subscores and with the subgroup of patients with independent gait according to the 8-meter walking-time (8MW). Interactions of clinical/molecular findings with treatment response, minimally important differences (MIDs), and sample size estimations for NESSCA, SARA, Spinocerebellar Ataxia Functional Index (SCAFI) and Composite Cerebellar Functional Score (CCFS) were evaluated., Results: 62 SCA3/MJD patients had been randomly assigned (1:1) for the double-blind, placebo-controlled trial. While cerebellar NESSCA (range: 0-7 points) differed between groups 0.64 points (95% CI 0.23 to 1.05, p<0.001) over the whole 48weeks of study, favoring lithium, no effect was found on non-ataxia subscores. Among patients able to perform the 8MW on baseline, NESSCA (p=0.010) and SCAFI (p=0.015) differed between groups favoring lithium. Finally, estimated sample sizes for the scales were provided., Conclusion: Lithium efficacy on cerebellar NESSCA, and on SCAFI and CCFS in the primary analysis, together with the lack of effect on non-ataxia features suggests that lithium should be tested in phase 3 trials in SCA3/MJD and that ataxia scales should be preferred to multisystem neurological instruments as the primary outcome. The inclusion of early stage patients is advisable in future clinical trials in SCA3/MJD., Trial Registration: clinicaltrials.gov identifier: NCT01096082., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Juvenile myoclonic epilepsy (JME) is a heterogeneous syndrome with seizures presenting typical fluctuation in diurnal cycle and relation with awakening. Few publications have approached clinical expressions of praxis induction (PI) in the nosology of JME as well as its impact on outcome. The aim of this study is to characterize PI as the only reflex trait in JME and its relation with prognosis., Method: JME with PI reported on a questionnaire and confirmed by video-EEG testing (Group 1, 20 patients) were compared with JME without any reflex epileptic trait (Group 2, 25 patients) and followed for a mean of 7.82 years (SD=3.98). Circadian distribution and frequency of seizures were assessed in a diary. Patients also had psychiatric evaluation., Results: Prevalence of PI was 20/133 (15%) JME patients, and was predominant in males (1.5 male: 1 female; OR 13; p=0.042). Among Group 1 patients, only 2/20 presented seizures exclusively in the morning (p=0.013), and none, exclusively on awakening (p<0.001). PI patients had worse prognosis regarding control of myocloni (p=0.02) and absences (p=0.01); only 7/20 (35.0%) could be treated with VPA in monotherapy (p=0.01). At the last follow-up, 2/20 (10.0%) of Group 1 and 10 (40.0%) of Group 2 patients were free of all three seizure types (p=0.02). Even though relative risk of stress as a precipitant of seizures increased 3.82 times in Group 1, psychiatric comorbidities were not different between groups., Conclusion: PI reflex trait in JME is related to seizures without preferential circadian occurrence and reduced response to antiepileptic drugs., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Aim: To evaluate the prognostic importance of MGMT and PTEN concerning their correlation with other prognostic factors evaluated by immunohistochemistry (IHC) and the molecular phenotype of breast cancers., Methods: IHC for estrogen and progesterone receptors, HER2, Ki67, p53, p63, e-cadherin, EGFR, CK5, CK14, MGMT and PTEN was performed on 200 breast tumors. Basal-like and luminal breast carcinomas were defined by the IHC evaluation of these markers. Fluorescent in situ hybridization (FISH) was performed for PTEN and HER2 analysis using the Vysis PTEN and HER2 DNA probe kits (Abbott™). RT-PCR was performed to evaluate gene expressions of MGMT and PTEN in frozen tissue of 59/200 cases., Results: 147/200 cases were triple-negative (73.5%), 47/147 were basal-like carcinomas (31.9%). 53 cases (26.5%) were luminal-like type A or B. 56 (93.3%) and 46 samples (76.6%) expressed lower levels of MGMT and PTEN mRNA, respectively, compared with normal breast (p<0.001). There was a positive correlation between the IHC results and the RT-PCR values for MGMT and PTEN. Tumors with homozygotic deletion of PTEN expressed little or no mRNA or protein. Positive p53, high Ki67, and basal-like tumors expressed significant lower MGMT and PTEN., Conclusions: We hypothesize that MGMT and PTEN expressions have prognostic significance in breast cancer. Also, based on their predictive value of response to therapy, evaluating MGMT and PTEN and learning to interpret their patterns of immunoexpression will undoubtedly lead to a greater understanding of breast cancer and its treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To analyze glucose transporter 1 expression patterns in malignant tumors of various cell types and evaluate their diagnostic value by immunohistochemistry., Introduction: Glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans. Glucose transporter 1 is aberrantly expressed in several tumor types. Studies have implicated glucose transporter 1 expression as a prognostic and diagnostic marker in tumors, primarily in conjunction with positron emission tomography scan data., Methods: Immunohistochemistry for glucose transporter 1 was performed in tissue microarray slides, comprising 1955 samples of malignant neoplasm from different cell types., Results: Sarcomas, lymphomas, melanomas and hepatoblastomas did not express glucose transporter 1. Forty-seven per cent of prostate adenocarcinomas were positive, as were 29% of thyroid, 10% of gastric and 5% of breast adenocarcinomas. Thirty-six per cent of squamous cell carcinomas of the head and neck were positive, as were 42% of uterine cervix squamous cell carcinomas. Glioblastomas and retinoblastomas showed membranous glucose transporter 1 staining in 18.6% and 9.4% of all cases, respectively. Squamous cell carcinomas displayed membranous expression, whereas adenocarcinomas showed cytoplasmic glucose transporter 1 expression., Conclusion: Glucose transporter 1 showed variable expression in various tumor types. Its absence in sarcomas, melanomas, hepatoblastomas and lymphomas suggests that other glucose transporters mediate the glycolytic pathway in these tumors. The data suggest that glucose transporter 1 is a valuable immunohistochemical marker that can be used to identify patients for evaluation by positron emission tomography scan. The function of cytoplasmic glucose transporter 1 in adenocarcinomas must be further examined.

Squamous cell carcinoma of the oral cavity (OSCC) is a malignancy characterized by a high degree of local aggression and metastasis to cervical lymph nodes. Tetraspanins are proteins with functional roles in a wide array of cellular processes and are reported to be associated with tumor progression. The present study investigated the expression of the CD9, CD37, CD63, CD81 and CD82 tetraspanins in OSCC using immunohistochemistry (IHC) and quantitative Real Time-PCR (qRT-PCR). Tissue microarray (TMA) analysis of samples from 179 cases of OSCC and 10 normal samples oral mucosa were evaluated immunomorphologically. We analyzed CD9 and CD82 expression by qRT-PCR in 66 OSCC cases and 4 normal samples of oral mucosa. Expression of CD63, CD37 and CD81 was not detected in the samples studied. CD82 was downregulated or negative in 127 of 179 (80%) specimens; no correlation was observed between CD82 expression, clinicopathological parameters, disease-free survival and 5-year overall survival. CD9 expression was downregulated or negative in 75 of 129 (42%) OSCC samples. Loss of CD9 expression in OSCC samples correlated with the incidence of lymph node metastasis (p=0.017). Disease-free survival and the 5-year overall survival of patients with downregulated or negative CD9 expression were significantly lower than in patients with positive CD9 expression (p=0.010 and p=0.071, respectively). No correlation was found between CD9 or CD82 expression and clinicopathological parameters by qRT-PCR. Our results suggest that the downregulation or lack of expression of the CD9 protein might indicate a more aggressive of OSCC., ((c) 2009 Elsevier Ltd. All rights reserved.)

Paracoccidioides brasiliensis is the dimorphic fungus responsible for human paracoccidioidomycosis (PCM). We previously observed that P. brasiliensis isolates bearing highly polymorphic PbGP43 of genotype A (Pb2, Pb3 and Pb4) were phylogenetically distant from the others. The PbGP43 gene encodes an immune dominant diagnostic antigen (gp43), and its polymorphism reflects broader genetic diversity in the species. In the present study, we observed that isolates with PbGP43 of genotype A showed low virulence when inoculated in B10.A mice by the intraperitoneal, intratracheal and intravenous routes. In vitro studies detected sharp and prolonged down-regulation of PbGP43 in Pb3 (and not in Pb18 or Pb339) as a result of heat shock at 42 degrees C and temperature shift to prompt mycelium to yeast transition, which was, however, not disturbed. Differences in transcriptional regulation are possibly a consequence of mutations in the PbGP43 promoter region, which we here show to be more polymorphic in genotype A isolates. As opposed to Pb3's rapid adaptation to in vitro culture conditions after isolation from the lung, Pb12, the most aggressive isolate tested here, showed slow growth and phase transition in vitro. Interestingly, animals that were highly infected by Pb12 produced small amounts of anti-gp43 antibodies. That was apparently due to down-regulation in PbGP43 expression. We present the first evidence of transcriptional regulation of gp43 expression, but our results suggest that gene expression is also regulated at the protein and/or secretion levels.