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Talinum paniculatum (Jacq.) Gaertn. (Talinaceae), popularly known as "major gomes," is a Brazilian Cerrado plant used in traditional medicine and as a food source. Recent studies have demonstrated its diuretic effects. However, no studies have been performed on its effects on the reproductive system. Therefore, we aimed to investigate the effects of the ethanol-soluble fraction of T. paniculatum leaves (ESTP) on general toxicity and on the pubertal development of male and female Wistar rats. For this purpose, the uterotrophic and the pubertal assays were performed. In the uterotrophic test, female immature rats were treated for three consecutive days with 30, 100, or 300 mg/kg of ESTP. Uterus without luminal fluid was weighed and the relative weight calculated. For the pubertal assay, male and female immature rats were submitted to 30-day treatment with 30 or 300 mg/kg of ESTP. Clinical signs of toxicity, biochemical, and histopathological parameters were evaluated. ESTP treatment did not promote estrogenic effects in female rats. In the pubertal test, no daily signs of toxicity or weight loss were observed. Moreover, ESTP did not affect the onset of vaginal opening and preputial separation and did not cause significant changes in biochemical parameters as well as in organ weight and histopathological analyses of animals. [ABSTRACT FROM AUTHOR]

Cerebrovascular disease (CVD) includes a range of conditions affecting the brain's blood vessels, which can result in reduced blood flow to brain tissue. The most common manifestation of CVD is stroke, the second leading cause of death and the third leading cause of disability worldwide. Major risk factors for CVD encompass gender, age, smoking, hypertension, diabetes, physical inactivity, obesity, alcohol consumption, and metabolic syndrome. Research suggests a link between telomere length and an increased risk of CVD, particularly in ischemic stroke cases. This review highlights key findings on the relationship between telomere length and CVD, underscoring its clinical importance. The analysis utilizes scientific literature from PubMed, Scopus, and SciELO up to 2024. Results show that shorter telomere length is associated with various types of CVD, including stroke, ischemic stroke, hemorrhagic stroke, and cardioembolic stroke. Some studies propose that telomere length measurement could be a valuable biomarker for CVD, potentially improving prevention, diagnosis, and management strategies., Competing Interests: Declarations Conflict of interest The authors declare no competing interests. Consent to participate Not applicable. Consent for publication Not applicable. Ethical approval Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: While COVID-19 vaccination has been shown to reduce the risk of severe illness, its impact on the occurrence of persistent symptoms in patients with mild Omicron infection remains uncertain. Our objective was to investigate whether COVID-19 vaccination reduces the occurrence of persistent COVID-19-related symptoms 3 months after mild Omicron infection., Methods: Multicenter prospective cohort study was conducted in Brazil between January 2022 and June 2023 when Omicron was predominant. Participants ≥ 18 years seeking outpatient care for symptomatic SARS-CoV-2 infection were enrolled. Complete vaccination included individuals who received the full primary series and any booster dose, while incomplete vaccination included those with incomplete primary series or no vaccination. The primary outcome was any persistent symptoms at 3 months. Secondary outcomes were organ system-specific persistent symptoms and the EQ-5D-3L utility score. All outcomes were assessed by means of structured telephone interviews 3 months after enrollment., Results: 1,067 patients were enrolled (median age, 39 years), of which 914 (871 completely vaccinated and 43 unvaccinated or incompletely vaccinated). Among the vaccinated participants the median time since the last vaccine dose was 145 (interquartile range, 106-251) days. A total of 388/1067 (36.9 %) had a prior infection at the time of study entry . The occurrence of overall persistent COVID-19-related symptoms at 3 months was 41.6 % (n = 362) among completely vaccinated and 44.2 % (n = 19) among unvaccinated or incompletely vaccinated patients (adjusted risk ratio [aRR], 0.87; 95 % confidence interval [CI], 0.61-1.23; p  = 0.43). Complete vaccination was associated with lower occurrence of mental health symptoms (aRR, 0.44; 95 % CI, 0.24-0.81; p  = 0.01). No differences were found in the occurrence of persistent symptoms in other specific domains, nor in EQ-5D-3L utility scores., Conclusions: This study was not able to identify a statistically significant protection of complete COVID-19 vaccination against any overall persistent symptoms at 3 months. Nevertheless, complete vaccination was associated with a lower occurrence of persistent mental health symptoms., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors MMR, FLS, GT, MMDS, DS, RRMS, RFCS, ESR, GPE, GSR, DM, JMBS, APM, CRI, GNS, JMN, HJMF, CVPS, ASS, CMD, CMS, JVP and IFS work at Hospital Moinhos de Vento, which received a research grant from the Brazilian Ministry of Health for the conduction of this study. RGR and MF had received research grants from the Brazilian Ministry of Health, Pfizer and MSD. All other authors declare that they have no conflict of interest. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The present systematic review, through the analysis of several studies, focused on attempting to answer the following question: Is the micronucleus assay suitable for genetic biomonitoring of workers exposed to anesthetic gases? We conducted searches in PubMed, SCOPUS and Web of Science to identify eligible articles on December, 2023. After screening the manuscript, a total of 18 articles were included in the review. In the quality assessment, a total of 12 studies were rated as strong, 3 studies were rated as moderate and 3 were rated as weak. Taken as a whole, the results suggest that occupational exposure to different anesthetic agents may induce genome damage and that the micronucleus assay appears to be a reliable and suitable DNA damage biomarker for professionals chronically exposed to anesthetics.

Cardiovascular diseases (CVDs) have a high mortality rate, and despite the several available therapeutic targets, non-response to antihypertensives remains a common problem. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are important classes of drugs recommended as first-line therapy for several CVDs. However, response to ACEIs and ARBs varies among treated patients. Pharmacogenomics assesses how an individual's genetic characteristics affect their likely response to drug therapy. Currently, numerous studies suggest that genetic polymorphisms may contribute to variability in drug response. Moreover, further studies evaluating gene-gene interactions within signaling pathways in response to antihypertensives might help to unravel potential genetic predictors for antihypertensive response. This review summarizes the pharmacogenetic data for ACEIs and ARBs in patients with CVD, and discusses the potential pharmacogenetics of these classes of antihypertensives in clinical practice. However, replication studies in different populations are needed. In addition, studies that evaluate gene-gene interactions that share signaling pathways in the response to antihypertensive drugs might facilitate the discovery of genetic predictors for antihypertensive response., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nothing to declare. If there are other authors, they 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 © 2024 Elsevier B.V. All rights reserved.)

Objective: To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5-11 years of age., Methods: This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5-11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated., Results: A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days)., Conclusion: In this study with children 5-11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference., Trial Registration Number: ClinicalTrials.gov number, NCT05403307 (https://classic., Clinicaltrials: gov/ct2/show/NCT05403307)., Competing Interests: Declaration of competing interest Rodrigues, Maltempi de Souza, Manfio, de Souza, Araujo, Cohen, Barbosa, Romeiro Silva, Sganzerla, Dias da Silva, Ferreira, Kunkel, Camargo, Sarturi, Guilhem, Oliveira, Lopes, Widmar, Barufi, Nunes da Silva, Gradia, Brandalize, Royer, Luiz, Baura, Abreu, and Poitevin report honoraria fee for working in this study from Hospital Moinhos de Vento. Rosa reports honoraria fee related to investigator activities from Pfizer, and research grants from Pfizer, MSD and Brazilian Ministry of Health. Falavigna reports honoraria fee related to investigator activities from Pfizer and MSD, consulting fees from Sanofi, Ultragenyx, Novartis, Alnylam, PTC and JCR, and honoraria for lectures from Janssen, Abbvie, Sanofi, Roche, Pfizer and Novartis.Valluri, Srivastava, Julião, Melone, Allen, Kyaw, Spinardi, Castillo, and McLaughlin are Pfizer empolyees. Kucharski, and Pedrotti have nothing to disclose., (Copyright © 2024. Published by Elsevier B.V.)

This study aimed to analyze whether taurine has a nootropic effect on short-term and long-term memory in a model of sporadic dementia of the Alzheimer's type (SDAT). Moreover, we evaluated the immunoreactivity and insulin receptor (IR) distribution and markers for neurons and glial cells in the hippocampus of rats with SDAT and treated with taurine. For this, Male Wistar rats received STZ (ICV, 3 mg/kg, bilateral, 5ul per site, aCFS vehicle) and were treated with taurine (100 mg/kg orally, 1 time per day, saline vehicle) for 25 days. The animals were divided into 4 groups: vehicle (VE), taurine (TAU), ICV-STZ (STZ) and ICV-STZ plus taurine (STZ + TAU). At the end of taurine treatment, short- and long-term memory were assessed by performance on object recognition and Y-maze tasks. Insulin receptor (IR) was evaluated by immunoperoxidase while mature neurons (NeuN), astrocytes (GFAP, S100B, SOX9), and microglia (Iba-1) were evaluated by immunofluorescence. STZ induced worse spatial and recognition memory (INDEX) in YM and ORT tasks. Taurine protected against STZ-induced memory impairment. SDAT reduced the population of mature neurons as well as increased astrocytic and microglial reactivity, and taurine protected against these STZ-induced effects, mainly in the CA1 region of the hippocampus. Taurine increases IR expression in the hippocampus, and protects against the reduction in the density of this receptor in CA1 induced by STZ. In conclusion, these findings demonstrate that taurine is able to enhance memory, up-regulates IR in the hippocampus, protects the neuron population, and reduces the astrogliosis found in SDAT., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Obesity is a big public health problem that claims several thousand lives every year. Bariatric surgery has arisen as a suitable procedure for treating obesity, particularly morbid obesity. Oxidative stress, genotoxicity, apoptosis, and inflammatory responses are recognized as the most important occurrences in carcinogenesis, as they actively contribute to the multistep process. This study aimed to briefly review the connection between oxidative stress, genotoxicity, apoptosis, and inflammation in obese patients undergoing bariatric surgery, focusing on its impact on carcinogenesis. Regarding oxidative stress, bariatric surgery may inhibit the synthesis of reactive oxygen species. Moreover, a significant reduction in the inflammatory status after weight loss surgery was not observed. Bariatric surgery prevents apoptosis in several tissues, but the maintenance of low body weight for long periods is mandatory for mitigating DNA damage. In conclusion, the association between bariatric surgery and cancer risk is still premature. However, further studies are yet needed to elucidate the real association between bariatric surgery and a reduced risk of cancer.

Introduction: Although some studies have reported the association between uric acid (UA) and hypertension, evidence on prehypertension is still lacking. Therefore, the objective of this study was to determine the levels of UA and other cardiovascular markers among prehypertensive and hypertensive patients and assess their risk for developing arterial hypertension., Methods: 157 individuals were recruited: 67 normotensive, 23 pre-hypertensive and 67 hypertensive. Blood samples were collected to measure biochemical parameters and anthropometric measurements and blood pressure were evaluated. We calculated the product of lipid accumulation and the visceral adiposity index to assess cardiovascular risk., Results: Our data showed an increase in UA levels in normotensives (4.9±1.3mg/dL), prehypertensives (5.2±1.3mg/dL) and hypertensives (5.9±1.6mg/dL) (p=0.004). We found a higher frequency of hyperuricemia in the hypertensive group (34.3%) than in the normotensive group (13.4%, p<0.05). Hypertensive volunteers had lower levels of HDL-C (p=0.004 and p=0.003) and higher body mass indexes (p<0.001 and p=0.007), glucose (p<0.001 and p=0.033), triglycerides (p=0.001 and p=0.005), visceral adiposity index (p<0.001 and p=0.002) and lipid accumulation product (p<0.001 and p=0.007) than normotensive and prehypertensive participants. We also observed that individuals with UA≥6.2mg/dL had an increased risk of hypertension of 4.77 (p=0.003) compared to individuals with levels≤4.3mg/dL., Conclusion: Our results showed that UA is associated with increased blood pressure and unfavorable changes in anthropometric and biochemical parameters, which represent risk factors for hypertension and cardiovascular diseases., (Copyright © 2024 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Arterial hypertension is characterized by systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg and its treatment consists of the use of antihypertensive drugs, as losartan and hydrochlorothiazide. Blood pressure is regulated by angiotensin-converting enzyme (ACE) and polymorphisms in the ACE gene are associated to a greater predisposition to hypertension and response to treatment. The aim of this study was to evaluate the association of genetic polymorphisms of ACE rs4363, rs4291 and rs4335 and the response to antihypertensive drugs in hypertensive patients from Ouro Preto/MG, Brazil. A case-control study was carried out with 87 hypertensive patients being treated with losartan and 75 with hydrochlorothiazide, who answered a questionnaire and had blood samples collected. Biochemical analyzes were performed on serum using UV/Vis spectrophotometry and identification of ACE variants rs4363, rs4291 and rs4335 was performed by real-time PCR using the TaqMan® system. Univariate logistic regression test was performed to compare categorical data in STATA 13.0 software. The results showed that there was an influence of ACE polymorphisms on the response to losartan, demonstrating that AT or TT genotypes of rs4291 were more frequent in the group of controlled AH (54.9%), indicating that these individuals are 2.8 times more likely to of being controlled AH (95% CI 1.12-6.80, p. =0.026) compared to those with AA genotype. In contrast, no influence of ACE polymorphisms on the response to hydrochlorothiazide was observed. In conclusion, the presence of the T allele of the rs4291 variant was associated to controled blood pressure when losartan was used as an antihypertensive agent. These results show the importance of pharmacogenetic studies to detect genetic characteristics, enabling therapeutic individuality and reducing costs for the healthcare system., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Cervical cancer is the fourth most commonly diagnosed cancer in women and is considered a preventable disease, as vaccination and screening programs effectively reduce its incidence and mortality rates. Disease physiopathology and malignant cell transformation is a complex process, but it is widely known that high-risk HPV (hrHPV) infection is a necessary risk factor for cancer development. Mitochondria, cell organelles with important bioenergetic and biosynthetic functions, are important for cell energy production, cell growth, and apoptosis. Mitochondrial DNA is a structure that is particularly susceptible to quantitative (mtDNA copy number variation) and qualitative (sequence variations) alterations that are associated with various types of cancer. Novel biomarkers with diagnostic and prognostic value in cervical cancer can be evaluated to provide higher specificity and complement hrHPV molecular testing, which is the most recommended method for primary screening. In accordance with this, this review aimed to assess mitochondrial alterations associated with cervical cancer in clinical cervicovaginal samples, in order to unravel their possible role as specific diagnostic and prognostic biomarkers for cervical malignancy, and also to guide the understanding of their involvement in carcinogenesis, HPV infection, and disease progression., (© 2024 Environmental Mutagenesis and Genomics Society.)

In a world with a rising use of pesticides, these chemicals, although designed to effectively control pests, pose potential threats to the environment and non-target organisms, including humans. Thus, this systematic review aims to investigate a possible association between genetic polymorphisms and susceptibility and genotoxicity in individuals occupationally exposed to pesticides. This review was conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A total of 14 carefully selected studies were thoroughly analyzed by two reviewers, who assigned scores based on previously set evaluation criteria. This study classified over half of the chosen studies as having moderate or strong quality, observing a correlation between certain genetic polymorphisms involved in xenobiotic metabolism and genotoxicity in workers exposed to pesticides. Results suggest that the genes associated with xenobiotic metabolism play a substantial role in determining individuals' susceptibility to genomic damage due to pesticide exposure, affecting both their peripheral blood and oral mucosa. This implies that individuals with specific genotypes may experience increased or decreased levels of DNA damage when exposed to these chemicals.

Cardiovascular diseases are the leading cause of death worldwide. They are non-transmissible diseases that affect the cardiovascular system and have different etiologies such as smoking, lipid disorders, diabetes, stress, sedentary lifestyle and genetic factors. To date, lncRNAs have been associated with increased susceptibility to the development of cardiovascular diseases such as hypertension, acute myocardial infarction, stroke, angina and heart failure. In this way, lncRNAs are becoming a very promising point for the prevention and diagnosis of cardiovascular diseases. Therefore, this review highlights the most important and recent discoveries about the mechanisms of action of the lncRNAs ANRIL, H19 and TUG1 and their clinical relevance in these pathologies. This may contribute to early detection of cardiovascular diseases in order to prevent the pathological phenotype from becoming established., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Quinones are chemical compounds produced from the oxidation of phenols. Among the quinones, naphthoquinones stand out as potential antitumor agents. Bladder tumour is the tenth most diagnosed in the world. Based on this, using a urothelial carcinoma cell line (T24), two naphthoquinones had their cytotoxicity tested by the MTT colorimetric method and were submitted to assays of clonogenic survival, morphology, cell cycle, cell migration and species reactive oxygen. The results showed 8-methoxy-α-lapachone and lausone presented selectivity indexes (19.5 and 28.0, respectively) for T24 cells. Moreover, the two naphthoquinones reduced the cell viability, interfered with the process of cell migration, changed the cell cycle kinectics and induced the production of species reactive oxygen (ROS). Additionaly, 8-methoxy-α-lapachone altered the morphology of the cells. In conclusion, the studied naphthoquinones showed potential antiproliferative effects in bladder cancer cells, interfering in cellular processes, possibly through oxidative stress.

Cancer still represents a serious public health problem and one of the main problems related to the worsening of this disease is the ability of some tumors to develop metastasis. In this work, we synthesized a new series of chalcones and isoxazoles derived from eugenol and analogues as molecular hybrids and these compounds were evaluated against different tumor cell lines. This structural pattern was designed considering the cytotoxic potential already known for eugenol, chalcones and isoxazoles. Notably, chalcones 7, 9, 10, and 11 displayed significant activity (4.2-14.5 µM) against two cancer cell lines, surpassing the potency of the control drug doxorubicin. The reaction of chalcones with hydroxylamine hydrochloride provided the corresponding isoxazoles that were inactive against these cancer cells. The dihydroeugenol chalcone 7 showed the most promising results, demonstrating higher potency against HepG2 (CC 50 : 4.2 µM) and TOV-21G (CC 50 : 7.2 µM). Chalcone 7 was also three times less toxic than doxorubicin considering HepG2 cells, with a selectivity index greater than 11. Further investigations including clonogenic survival, cell cycle progression and cell migration assays confirmed the compelling antitumoral potential of chalcone 7, as it reduced long-term survival due to DNA fragmentation, inducing cell death and inhibiting HepG2 cells migration. Moreover, in silico studies involving docking and molecular dynamics revealed a consistent binding mode of chalcone 7 with metalloproteinases, particularly MMP-9, shedding light on its potential mechanism of action related to anti-migratory effects. These significant findings suggest the inclusion of compound 7 as a promising candidate for future studies in the field of cancer therapeutics., 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.)

Background and Objectives: In order to detect genetic damage, different methods have been developed, such as micronuclei and comet assay. The comet assay presents some advantages when compared to the other aforementioned methods, including wide versatility, as any eukaryotic cell can be evaluated at an individual cellular level. In this context, the aim of this systematic review was designed to help further elucidate the following question: is the comet assay a suitable biomarker of in vivo oral carcinogenesis?, Material and Methods: The present systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Full manuscripts from 18 studies were carefully selected in this setting., Results: A total of 15 studies demonstrated positive findings for genotoxicity in peripheral blood or oral cells in patients with pre-malignant lesions or oral cancer. In the quality assessment of studies, 1 was classified as Strong, 5 were considered as Moderate, and 12 were classified as Weak., Conclusion: In summary, the comet assay can be a useful biomarker for oral carcinogenesis. However, further studies with more strict parameters are suggested (with less uncontrolled confounders) in order to increase findings reliability for diagnosis of oral potentially malignant lesions.

Resveratrol is a polyphenolic compound whose antitumor activity has been demonstrated in several types of cancer. However, there are few studies on its molecular mechanisms of action in bladder cancer. Therefore, we aimed to evaluate resveratrol activity in bladder tumour cells with different TP53 gene status. Cytotoxicity, cell proliferation, reactive oxygen species (ROS) production, cell migration, mutagenicity, and CDH1 , CTNNBIP1 , HAT1 , HDAC1 , MYC , and SMAD4 gene expression were evaluated. An increase in ROS after resveratrol treatment was accompanied by reduced cell viability and proliferation in all cell lines. In TP53 wild-type cells, the inhibition of cell migration was accompanied by CDH1 and SMAD4 modulation. In TP53 mutated cells, cell migration inhibition with CDH1 and CTNNB1P1 upregulation was observed. In conclusion, resveratrol has antiproliferative effect in bladder tumour cells and its mechanism of action occurred through ROS production, interference with cell cycle, and inhibition of cell migration, independent of TP53 status.

Due to the COVID-19 pandemic, the Higher Education Institutions had to suspend their on-site activities and adapt to the new scenario. Therefore, the objective of the research was to investigate the effects of the COVID-19 pandemic on the mental health of the academic community of a Brazilian public university. This is a cross-sectional study, at a Brazilian public university, that used the baseline data from a longitudinal study carried out with employees and students. Participants answered a self-administered and confidential questionnaire in online platform, composed of sociodemographic, economic, lifestyles and mental health issues. 1,353 students and 372 employees participated. The prevalence of anxiety disorder symptoms among students and employees was 46.12% and 17.47%, depression 54.62% and 22.85% and stress 47.45% and 22.58%, respectively. The co-occurrence of symptoms was 33.56% among university students and 10.75% among employees. Falling family income, having stopped smoking and negative self-rated health, during the COVID-19 pandemic, may be the reasons for the high prevalence of co-occurrence of anxiety, depression and stress disorders among the academic community.

This study was conducted with the aim of exploring the molecular and cellular mechanisms of action of the chrysin (natural flavonoid compound) on bladder tumour cell lines with different status of TP53 (RT4, 5637 and T24). The cells were treated with different concentrations of chrysin (20, 40, 60, 80 and 100 µM) to analyze the cell viability, nuclear division index, mutagenicity, apoptosis rates and expression of genes related to epigenetic events ( DNMT1 , HAT1 and HDAC1 ). Results showed that the treatment with chrysin reduced the cell viability and caused apoptosis, regardless TP53 . Moreover, in the TP53 -mutated cell lines, chrysin modulated the expression of the DNMT1 , HAT1 and HDAC1 epigenetic genes, which might be a plus to the death observed in the cells with p53 mutation.

Climacteric women often experience unfavorable metabolic changes. Consequently, identifying markers that may contribute to such undesirable changes is imperative. This study aimed to evaluate serum uric acid (UA) concentration and its association with metabolic and clinical parameters in climacteric women. We selected 672 women between 40 and 65 years and performed interviews, biochemical analyses, blood pressure, and anthropometric measurements. UA levels were determined using the enzymatic-colorimetric method. We compared variables according to the quartiles of UA using the Kruskal-Wallis test. The mean UA level was 4.9 ± 1.5 mg/dl, ranging from 2.0 to 11.6 mg/dl. We found that UA levels greater than 4.8 mg/dl were associated with adverse metabolic parameters in climacteric women. For all anthropometric and biochemical variables, we observed significantly better results in women who had lower UA levels (p < 0.05). Similarly, we observed a significant increase in blood pressure, frequency of metabolic syndrome, and cardiovascular risk as UA levels increased (p < 0.05). Our findings showed that climacteric women with high levels of UA were more likely to have adverse metabolic and clinical parameters than those with lower UA levels. Further studies may determine the causal relationship between UA and metabolic changes in climacteric women., (© 2023. The Author(s).)

Aim: We examined whether ADIPOQ (rs266729 and rs1501299) and NOS3 (rs3918226 and rs1799983) SNPs or the haplotypes formed by them, affect blood pressure (BP) control in 196 patients with adherence to antihypertensive therapy grouped into controlled (BP <140/90 mmHg) and uncontrolled (BP ≥140/90 mmHg) hypertension. Materials & methods: The average of the three most recent BP measurements was retrieved from the patients' electronic medical records. Adherence to antihypertensive therapy was evaluated using the Morisky-Green test. Haplotype frequencies were estimated using Haplo.stats. Multiple logistic/linear regression analyses were adjusted for the covariates ethnicity, dyslipidemia, obesity, cardiovascular disease and uric acid. Results: ADIPOQ rs266729 genotypes CG (additive model) and CG+GG (dominant model) were associated with uncontrolled hypertension and CG was associated with higher systolic BP and mean arterial pressure (p < 0.05). ADIPOQ haplotypes 'GT' and 'GG' were associated with uncontrolled hypertension and 'GT' was associated with higher diastolic BP and mean arterial pressure (p < 0.05). Conclusion: ADIPOQ SNPs and haplotypes affect BP control in hypertensive patients undergoing treatment.

Despite fine tuning voluntary movement as the most prominently studied function of the cerebellum, early human studies suggested cerebellar involvement emotion regulation. Since, the cerebellum has been associated with various mood and anxiety-related conditions. Research in animals provided evidence for cerebellar contributions to fear memory formation and extinction. Fear and anxiety can broadly be referred to as defensive states triggered by threat and characterized by multimodal adaptations such as behavioral and cardiac responses integrated into an intricately orchestrated defense reaction. This is mediated by an evolutionary conserved, highly interconnected network of defense-related structures with functional connections to the cerebellum. Projections from the deep cerebellar nucleus interpositus to the central amygdala interfere with retention of fear memory. Several studies uncovered tight functional connections between cerebellar deep nuclei and pyramis and the midbrain periaqueductal grey. Specifically, the fastigial nucleus sends direct projections to the ventrolateral PAG to mediate fear-evoked innate and learned freezing behavior. The cerebellum also regulates cardiovascular responses such as blood pressure and heart rate-effects dependent on connections with medullary cardiac regulatory structures. Because of the integrated, multimodal nature of defensive states, their adaptive regulation has to be highly dynamic to enable responding to a moving threatening stimulus. In this, predicting threat occurrence are crucial functions of calculating adequate responses. Based on its role in prediction error generation, its connectivity to limbic regions, and previous results on a role in fear learning, this review presents the cerebellum as a regulator of integrated cardio-behavioral defensive states., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 da Silva, Seiffert and Tovote.)

Long non-coding RNAs are frequently found to be dysregulated and are linked to carcinogenesis, aggressiveness, and chemoresistance in a variety of tumors. As expression levels of the JHDM1D gene and lncRNA JHDM1D-AS1 are altered in bladder tumors, we sought to use their combined expression to distinguish between low-and high-grade bladder tumors by RTq-PCR. In addition, we evaluated the functional role of JHDM1D-AS1 and its association with the modulation of gemcitabine sensitivity in high-grade bladder-tumor cells. J82 and UM-UC-3 cells were treated with siRNA- JHDM1D-AS1 and/or three concentrations of gemcitabine (0.39, 0.78, and 1.56 µM), and then submitted to cytotoxicity testing (XTT), clonogenic survival, cell cycle progression, cell morphology, and cell migration assays. When JHDM1D and JHDM1D-AS1 expression levels were used in combination, our findings indicated favorable prognostic value. Furthermore, the combined treatment resulted in greater cytotoxicity, a decrease in clone formation, G0/G1 cell cycle arrest, morphological alterations, and a reduction in cell migration capacity in both lineages compared to the treatments alone. Thus, silencing of JHDM1D-AS1 reduced the growth and proliferation of high-grade bladder-tumor cells and increased their sensitivity to gemcitabine treatment. In addition, the expression of JHDM1D/JHDM1D-AS1 indicated potential prognostic value in the progression of bladder tumors.

Introduction: The genetic component, including genes and their variants, plays a significant role in the pathophysiology of arterial hypertension (AH). Thus, clinical, epidemiological and genetic studies have been carried out to improve the understanding of disease mechanisms, improve diagnostic quality and contribute to prevention., Objective: To determine the association of risk factors, biochemical parameters and different ACE gene polymorphisms with AH., Method: The case-control study was carried out in the population of Ouro Preto, Brazil. The subjects answered a questionnaire containing clinical and sociodemographic data. The ACE gene polymorphisms rs4291, rs4363 and rs4335 were evaluated by real time-polymerase chain reaction (real-time PCR) in 310 people (155 hypertensive and 155 normotensive patients), in addition to biochemical parameters. A multivariate logistic regression model was used to identify factors associated with AH. Analysis of continuous variables was performed using the Kruskal-Wallis test to assess significance between groups and Dunn's post-test for multiple comparisons., Results: The results showed that AH was associated with age, education, smoking, obesity and high levels of triglycerides, sodium, glucose and uric acid. Regarding the biochemical parameters, in hypertensive patients, the rs4363 and rs4335 polymorphisms were associated with high levels of triglycerides, urea and glucose; the rs4291 polymorphism was associated with elevated urea and glucose levels. No association was detected between SNPs and HA., Conclusion: AH was associated with socioeconomic status, lifestyle habits and biochemical parameters. ACE polymorphisms may have influenced the levels of triglycerides, urea and glucose in hypertensive patients., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Bladder cancer is the 10th most common cancer worldwide. It is a heterogeneous disease, comprising several tumor subtypes with differences in histology, genomic aberrations, prognosis and sensitivity to anti-cancer treatments. Although the treatment of bladder cancer is based tumor classifications and gradings, patients have different clinical response. In recent years, long non-coding RNAs (lncRNAs) were associated with bladder cancer chemoresistance. Thus, lncRNAs seem to be promising targets in treatment of bladder cancer. This review highlights the recent findings concerning lncRNAs and their relevance to the chemoresistance of bladder cancer. This may provide a basis for exploiting more robust therapeutic approaches in the future.

Oral cancer is a disease with high incidence and mortality worldwide, and its treatment still needs to be improved. The search for new therapies using natural products is strongly supported, given the wide chemical range of these compounds. In addition, phytochemicals can exert antitumor activities by several mechanisms of action, including the modulation of non-coding RNAs. Thus, in this review, we discussed the role of non-coding RNAs, including circular RNAs, microRNAs, and long non-coding RNAs, in oral cancer and presented their potential as treatment targets using natural products. Some natural products capable of being used to treat oral cancer have been suggested., Competing Interests: Conflict of interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Sodium butyrate-loaded nanoparticles coated chitosan (NaBu-loaded nanoparticles/CS) were developed to treat the choroidal neovascularization in wet age-related macular degeneration (AMD). The nanoparticles were produced by double emulsification and solvent evaporation technique, optimized by experimental statistical design, characterized by analytical methods, investigated in terms of in vitro and in vivo ocular biocompatibility, and evaluated as an antiangiogenic system in vivo. The NaBu-loaded nanoparticles/CS were 311.1 ± 3.1 nm in diameter with a 0.208 ± 0.007 polydispersity index; had a +56.3 ± 2.6 mV zeta potential; showed a 92.3 % NaBu encapsulation efficiency; and sustained the drug release over 35 days. The NaBu-loaded nanoparticles/CS showed no toxicity to human retinal pigment epithelium cells (ARPE-19 cells); was not irritant to the chorioallantoic membrane (CAM); did not interfere in the integrity of the retinal layers of rat's eyes, as detected by the Optical Coherence Tomography and histopathology; and inhibited the angiogenesis in CAM assay. The NaBu-loaded nanoparticles/CS could be a therapeutic alternative to limit the neovascularization in AMD., 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 © 2022 Elsevier B.V. All rights reserved.)

Pollution of aquatic ecosystems is associated with the discharge of mainly industrial and urban effluents, which may cause damage to public health. This study aims to evaluate the cytotoxic, genotoxic, and mutagenic potential of surface water samples under the influence of different anthropogenic effluents in a human-derived liver cell line (HepG2). Samples were collected in Esteio and Sapucaia streams (Rio Grande do Sul; Brazil), which flow into the Sinos River, a source of water supply for more than one million people. Physicochemical and microbiological analyses were performed as well as an analysis of inorganic elements using the PIXE technique (Particle-Induced X-Ray Emission). The presence of pharmaceutical compounds and caffeine was evaluated by gas chromatography coupled to mass spectrometry. The cytotoxicity, genotoxicity, and mutagenicity of the samples were evaluated in HepG2 cells by cell viability assays, alkaline Comet Assay and Cytokinesis-block micronucleus (CBMN) assay. We verified alterations in the physicochemical and microbiological parameters and detected caffeine, diethyltoluamide, and different inorganic elements that corresponded to elements from domestic and industrial effluents and agricultural runoff. Although the samples in the concentration used were not cytotoxic, water samples from all sites induced DNA damage. However, it is difficult to attribute these damages to a specific substance since the factors are a complex mixture of different compounds. Despite this, it is observed that both urban and industrial contributions had a similar effect in the cells evaluated. Such results demonstrate the need to perform biomonitoring of surface waters under anthropogenic influence, especially those that flow into rivers that are a source of public supply water. We also highlight the need for research into emerging pollutants in these aquatic environments., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bladder cancer has a high incidence and recurrence rate among patients worldwide. This study aimed to evaluate the cytotoxic activity of fractions of Sambucus nigra L. flower extracts on bladder carcinoma cells (T24 cells) and human fibroblast cells (MRC-5). The butanolic fraction (F-BuOH) was characterized by UPLC-DAD-MS/MS and nine flavonoids were identified. Rutin was the major compound. The cytotoxic activity of this fraction was observed in the T24 cells but not in MRC-5 cells, indicating selectivity. F-BuOH was incorporated in micellar solutions of Pluronic® F127 and cytotoxic effect for T24 cells was observed again. In vitro assay demonstrated a controlled release of the fraction from the micelles. The results obtained showed that flavonoids are the possible responsible for cytotoxic activity in bladder carcinoma cells. In addition, micellar solutions act together to increase the action of the butanolic fraction.

The treatment of bladder cancer remains a challenge in clinical practice. Different chemotherapeutic protocols can be used; however, it is common to observe tumor recurrence and secondary effects that result in toxicity. Doxorubicin (DOX), one of the most effective anticancer agents used to treat bladder cancer, can cause chronic cardiotoxicity, limiting its use in clinical practice. Resveratrol (RES), a natural product with potential antitumor activity against bladder cancer, is associated with rapid metabolism and low bioavailability and needs to be combined with chemotherapeutic drugs to improve its use. Our study aimed to assess the therapeutic effect of a low concentration of DOX (2 µM) in combination with RES (150, 200 and 250 µM) on two bladder cancer cell lines. We investigated the mechanism of interaction between the drugs by performing cytotoxicity, clonogenic, oxidative stress, cell migration, cell morphology and nuclear division index (NDI) assays. Cytotoxicity evaluation revealed an additive interaction between RES and DOX for both cell lines. Additionally, the results of cell colony formation, oxidative stress, cell migration, cell morphology and NDI assays showed that a combination of DOX and RES was more effective than RES or DOX alone. In conclusion, a low concentration of DOX combined with RES could potentiate the antitumor effects of the drugs on bladder cancer cells, thus overcoming the secondary effects caused by DOX and the low bioavailability of resveratrol., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The broad pharmacological spectrum of plants is related to their secondary metabolism, which is responsible for the synthesis of different compounds that have multiple effects on cellular physiology. Among the biological effects presented by phytochemicals, their use for the prevention and treatment of cancer can be highlighted. This occurs due to several mechanisms of antitumor action demonstrated by these compounds, including regulation of the cell signaling pathways and inhibition of tumor growth. In this way, long non-coding RNAs (lncRNAs) appear to be promising targets for the treatment of cancer. Their deregulation has already been related to a variety of clinicalpathological parameters. However, the effects of secondary metabolites on lncRNAs are still restricted. For this reason, the present review aimed to gather data on phytochemicals with action on lncRNAs in order to confirm their possible antitumor potential. According to the literature, terpenoid and flavonoid are the main examples of secondary metabolites involved with lncRNAs activity. In addition, the lncRNAs H19, CASC2, HOTAIR, NKILA, CCAT1, MALAT1, AFAP1-AS1, MEG3, and CDKN2B-AS1 can be highlighted as important targets in the search for new anti-tumor agents since they act as modulating pathways related to cell proliferation, cell cycle, apoptosis, cell migration and invasion. Finally, challenges for the use of natural products as a commercial drug were also discussed. The low yield, selectivity index and undesirable pharmacokinetic parameters were emphasized as a difficulty for obtaining these compounds on a large scale and for improving the potency of its biological effect. However, the synthesis and/or development of formulations were suggested as a possible approach to solve these problems. All of these data together confirm the potential of secondary metabolites as a source of new anti-tumor agents acting on lncRNAs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of this study was to analyse the antitumor effect of the Cymbopogon densiflorus essential oil in silico and in vitro on bladder cancer cells RT4 and T24, with different TP53 status. The oil was extracted by hydrodistillation and the gas chromatography coupled to the mass spectrometry was used for characterisation. In silico analysis was carried out by Pass online software. Cytotoxicity, cell proliferation, cell cycle progression, apoptosis and wound healing assays were performed. Five major compounds were identified. In silico analysis showed that major compounds present high potential for antitumor activities. The treatment with C. densiflorus essential oil reduced cell viability of bladder cancer cells. Only in wild-type cells, the increase of apoptosis rates and the decrease of cell migration were observed. In conclusion, the C. densiflorus essential oil presents antitumor effects on TP53 wild-type and mutated bladder cancer cells, however, the mechanism of action is TP53 status-dependent.[Figure: see text].

Ethanolic (EB) extract and hexanic (SH) and hydromethanolic (SEM) sub-extracts of Humulus lupulus leaves were submitted to cytotoxicity evaluation and to phytochemical methods. The effect of EB and SEM on cellular cycle was evaluated by propidium iodide method and the phases were quantified through flow cytometry. The cytotoxicity assessment was done using T24 and MRC5 cells, with EB and SEM (25-1200 µg/mL). By means of UPLC-DAD-MS/MS data were identified the flavonoids astragaline, nicotiflorin, kaempferol-7- O -rutinoside, robinin, hyperin, rutin, quercetin-7- O -rutinoside and manghaslin. EB (800 µg/mL) and SEM (1200 µg/mL) reduces the T24 cell viability. These extracts at 25 µg/mL stimulate the growth of MRC5 cells, evidencing a selective cytotoxicity. After 24 h of the treatment with extracts was not observed cycle arrest of T24 cells. The bioactivity prediction of the flavonoids was evaluated in silico through in house Active-IT software and PASSonline which indicated potential activity as antitumoral, cytotoxic, anti-inflammatory, antiparasitic, antimicrobial, antiviral and others.

Aim: The aim of this review was to evaluate the scientific literature regarding the cytogenetic damage in oral exfoliated cells of adult patients submitted to panoramic X-ray., Materials and Methods: An extensive search of the literature was conducted on PubMed, Scopus and Web of Science databases for all studies published until April 2021 using combinations of the following keywords: "panoramic X-ray," "DNA damage," "genetic damage", "genotoxicity", "mutagenicity", cytotoxicity", "buccal cells", "oral mucosa", "tongue", "gingiva", "micronucleus assay", according to the PRISMA guidelines. All clinical studies in English language were included in the study. A total of 10 studies were identified., Results: As expected, the results regarding the cytogenetic damage induced by panoramic X-ray are conflicting. Some authors have demonstrated that panoramic X-ray induces mutagenesis in oral cells, whereas others did not. After reviewing the 10 studies, two were classified as strong, four were considered moderate, and four were considered weak, according to the quality assessment components of the Effective Public Health Practice Project (EPHPP). Meta-analysis data revealed a negative response related to mutagenicity in oral cells by panoramic X-ray., Conclusion: Taken together, this review failed to demonstrate the association between micronucleus frequency and panoramic X-ray., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic. The outbreak caused a worldwide impact, becoming a health threat to the general population and its professionals. To date, there are no specific antiviral treatments or vaccines for the COVID-19 infection, however, some drugs are being clinically tested. The use of these drugs on large scale raises great concern about their imminent environmental risk, since the elimination of these compounds by feces and urine associated with the inefficiency of sewage treatment plants in their removal can result in their persistence in the environment, putting in risk the health of humans and of other species. Thus, the goal of this work was to conduct a review of other studies that evaluated the presence of the drugs chloroquine, hydroxychloroquine, azithromycin, ivermectin, dexamethasone, remdesivir, favipiravir and some HIV antivirals in the environment. The research indicated the presence of these drugs in the environment in different regions, with concentration data that could serve as a basis for further comparative studies following the pandemic., Competing Interests: 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., (© 2021 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.)

The new severe acute respiratory syndrome coronavirus (SARS-CoV-2) recently emerged as a worrying pandemic, with many confirmed cases and deaths globally. Therefore, there is a clear need for identifying effective therapeutic options and a review of secondary metabolites related to Brazilian herbal medicines was performed as a strategy for the discovery of new antiviral agents. To confirm this potential, an in silico screening of the identified compounds identified was also evaluated. The review was performed by the PubMed database and the selected natural compounds were subjected to in silico analysis such as QSAR, molecular docking and ADMET. 497 secondary metabolites were identified from 23 species. The in silico assays indicated 19 potential anti-SARS-CoV-2 compounds, being triterpenes and phenolic compounds. The indicated compounds showed a high affinity with proteins considered as the main molecular targets against SARS-CoV-2 and parameters indicated low toxicity. In addition to Brazilian medicinal plants, these compounds can be found in other species and they can be a base for the synthesis of other anti-COVID-19 drugs. Therefore, this review is important to conduct researches that address the emerging need for drugs in COVID-19 treatment., (© 2021 John Wiley & Sons Ltd.)

Oral cancer is a very common tumor worldwide with high incidence and mortality. The treatment of oral cancer involves surgery, radio- and chemotherapy; however, high failure rates and toxicity are noticed. Thus, the search of new drugs aiming a more effective treatment is welcomed. Natural products present chemopreventive and anti-cancer effects. Resveratrol is a naturally occurring antioxidant that contains several health benefits, including anti-inflammatory and antiproliferative activities. This review discusses the different action mechanisms of resveratrol related in the in vitro and in vivo studies using models of oral cancer., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China and its spread worldwide has become one of the biggest health problem due to the lack of knowledge about an effective chemotherapy. Based on the current reality of the SARS-CoV-2 pandemic, this study aimed to make a review literature about potential anti-coronavirus natural compounds guided by an in silico study. In the first step, essential oils from native species found in the Brazilian herbal medicine market and Brazilian species that have already shown antiviral potential were used as source for the literature search and compounds selection. Among these compounds, 184 showed high antiviral potential against rhinovirus or picornavirus by quantitative structure-activity relationship analysis. ( E )-α-atlantone; 14-hydroxy-α-muurolene; allo-aromadendrene epoxide; amorpha-4,9-dien-2-ol; aristochene; azulenol; germacrene A; guaia-6,9-diene; hedycaryol; humulene epoxide II; α-amorphene; α-cadinene; α-calacorene and α-muurolene showed by a molecular docking study the best result for four target proteins that are essential for SARS-CoV-2 lifecycle. In addition, other parameters obtained for the selected compounds indicated low toxicity and showed good probability to achieve cell permeability and be used as a drug. These results guided the second literature search which included other species in addition to native Brazilian plants. The majority presence of any of these compounds was reported for essential oils from 45 species. In view of the few studies relating essential oils and antiviral activity, this review is important for future assays against the new coronavirus., Supplementary Information: The online version contains supplementary material available at 10.1007/s11101-021-09754-4., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2021.)

The Buccal Micronucleus Cytome Assay (BMCyt) has become an important biomonitoring tool for assessing cytogenetic damage in many studied populations. Each laboratory applies protocols that vary according to the method of collecting and preparing samples. Besides, Brazil is a country of great territorial extensions that received immigrants from various parts of the world with different genetic backgrounds. Therefore, the present study aimed to evaluate the inter-laboratory variation in scoring the same set of slides using the more comprehensive scoring criteria, to standardize the BMCyt protocol, to observe the basal alterations in populations of different Brazilian regions and to compare it with other places around the world. Our results showed that a valuable number of laboratories participated, ten laboratories from different regions of the country, for the validation of the BMCyt in human biomonitoring studies, resulting in the 804 healthy individuals. This was possible because we observed: a range of measures needs to be considered, such as the baseline frequency of DNA damage and cell death in non-exposed individuals; age when grouped showed an influence on DNA damage, although when evaluated by group we did not see an influence; association between smoking habit and all endpoints of the BMCyt (except karyolytic cells) was evident; the basal MN frequency, in the majority of groups, follows those around the world; and the BMCyt was confirmed as a good health status biomarker. We emphasize the need for constant discussions on the parameters of cell death due to greater difficulty among the analyzers., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Diclofenac is a non-steroidal anti-inflammatory drug widely used by the general population and, although generally contraindicated during pregnancy, it is also used by some pregnant women. This study investigated endocrine, reproductive and behavioral effects of diclofenac in male and female offspring rats exposed in utero from gestational days 10-20. Pregnant rats were treated with diclofenac at doses of 0.2, 1 and 5 mg/kg/day via oral gavage. Anogenital distance (AGD), number of nipples, and developmental landmarks of puberty onset - vaginal opening (VO), first estrus (FE) and preputial separation (PPS) - were evaluated in the offspring. At adulthood, behavioral and reproductive parameters were assessed. Male and female rats were tested in the elevated plus maze test to assess locomotor activity and anxiety-like behaviors, while male rats were also evaluated in the partner preference test. No significant effects were observed on AGD and number of nipples in both males and females. Diclofenac treatment induced an overall delay in developmental landmarks of puberty onset in male and female offspring, which reached statistical significance for PPS at the lowest diclofenac dose. Prenatal exposure to all tested doses abolished the preference of male rats for an estrous female, suggesting an impairment of brain masculinization. No changes were observed on male or female reproductive parameters at adulthood. Overall, our results indicate that prenatal exposure to therapeutically relevant doses of diclofenac may have an impact in the pubertal development of rats and negatively affect male partner preference behavior., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The antitumour activity of chrysin have been studied in several types of cancer cells. In urinary bladder cancer, its cytotoxic effects have already demonstrated; however, its mechanism of action is not completely understood and the role of tumour protein p53 (TP53) gene in these effects is unclear. In this study, we investigated the role of chrysin (10, 20, 40, 60 80 and 100 µM) in progression of bladder tumour cells with different status of the TP53 gene and different degrees of tumour (RT4, grade 1, TP53 wild type; 5637, grade 2, TP53 mutated and T24, grade 3, TP53 mutated). Results demonstrated that chrysin inhibited cell proliferation by increasing reactive oxygen species and DNA damage and inhibited cell migration in all cell lines. In TP53 wild-type cells, a sub-G1 apoptotic population was present. In mutated TP53 cells, chrysin caused arrest at the G2/M phase and morphological changes accompanied by downregulation of PLK1, SRC and HOXB3 genes. In addition, in Grade 2 cells, chrysin induced global DNA hypermethylation and, in the highest-grade cells, downregulated c-MYC, FGFR3 and mTOR gene expression. In conclusion, chrysin has antiproliferative and toxicogenetic activity in bladder tumour cells independently of TP53 status; however, the mechanisms of action are dependent on TP53 status., (© The Author(s) 2020. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ethnopharmacological Relevance: Plinia cauliflora (Mart.) Kausel (Myrtaceae) is popularly known as "jaboticaba" or "jaboticaba". The fruit is appreciated for both fresh consumption and the manufacture of jelly, juice, ice cream, fermented beverages, and liqueurs. The more widespread traditional use of the plant involves the treatment of diarrhea, which utilizes all parts of the plant, including the fruit peels., Aim of the Study: We sought to elucidate possible risks of the administration of an ethanol-soluble fraction that was obtained from an infusion of P. cauliflora fruit peels (SEIPC). We performed a series of experiments to evaluate possible toxicity, in which we administered SEIPC orally both acutely and repeatedly for 28 days. We also evaluated possible endocrine-disruptive and genotoxic effects in eukaryotic cells. The possible mutagenic activity of SEIPC was evaluated using reverse mutation (Ames) assays., Materials and Methods: SEIPC was produced and chemically characterized by LC-DAD-MS. Acute toxicity and behavioral and physiological alterations were evaluated in the modified Irwin test. Respiratory rate, arterial blood gas, electrocardiography, respiratory rate, heart rate, and blood pressure were evaluated, and hematological, biochemical, and histopathological analyses were performed after 28 days of oral treatment. The comet assay, mammalian erythrocyte micronucleus test, uterotrophic test, Hershberger bioassay, and AMES test were performed using appropriate protocols., Results: From SEIPC, ellagic acid and derivatives, flavonols and anthocyanidins, as well as citric acid and gallic acid, were annotated by LC-DAD-MS. We did not observed any significant toxic effects after acute or prolonged SEIPC treatment. No endocrine-disruptive or mutagenic effects were observed., Conclusions: The present study found that SEIPC did not cause any significant alterations of various corporeal systems, including cardiac electrical activity, body temperature, respiratory rate, and arterial pressure. No alterations of biochemical, hematological, or blood gas parameters were observed. SEIPC did not cause any perturbations of the endocrine system or mutagenic, cytotoxic, or genotoxic effects. These findings substantiate the safe clinical use of P. cauliflora., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Silibinin, a natural compound extracted from milk thistle, has demonstrated antitumor properties in urinary bladder cancer cells; however, the role of TP53 gene in these effects is unclear. In order to better understand the molecular and antiproliferative mechanisms of this compound, urinary bladder cancer cells with different TP53 gene status, RT4 (low-grade tumor, wild TP53 gene), 5637 (high-grade tumor, Grade 2, mutated TP53 gene), and T24 (high-grade tumor, Grade 3, mutated TP53 gene) were treated with several concentrations of silibinin (1, 5, 10, 50, 100, and 150 μM). Cytotoxicity, prooxidant effect, morphological changes, cell migration, cell cycle progression, global methylation profile, and relative expression of HOXB3, c-MYC, PLK1, SMAD4, SRC, HAT, HDAC, and RASSF1A genes were evaluated. The silibinin presented cytotoxic and prooxidant effects in the three cell lines. In mutated TP53 cells, significant interference in cell migration and cell cycle arrest at the G2/M phase was observed. Additionally, silibinin induced global DNA hypomethylation in the highest grade tumor cells. For wild-type TP53 cells, a sub-G1 apoptotic population was present. Furthermore, there was modulation of gene expression responsible for cell growth (SMAD and c-MYC), migration (SRC), cell cycle kinetics (PLK1), angiogenesis (HOXB3), and of genes associated with epigenetic events such as DNA acetylation (HAT) and deacetylation (HDAC). In conclusion, the silibinin inhibited the urinary bladder tumor cell proliferation independently of TP53 status; however, cell cycle effects, gene expression changes, and alteration of cell migration are dependent on TP53 status. © 2020 Wiley Periodicals, Inc., (© 2020 Wiley Periodicals, Inc.)

Reactive arthritis (ReA) with the classic triad of arthritis, conjunctivitis and urethritis, previously termed Reiter's syndrome, is a systemic illness, usually induced by genitourinary or gastrointestinal infections. However, it can be a rare complication of intravesical Bacillus Calmette-Guérin instillation (iBCG), a therapy prepared from attenuated strains of Mycobacterium bovis , a common and effective treatment for carcinoma in situ of the bladder (CisB). We report a case of a patient with CisB who developed ReA after iBCG. The symptoms resolved completely with corticosteroids. iBCG was stopped with no recurrence of carcinoma within 2 years., Learning Points: ReA is an aseptic arthritis, usually triggered by genitourinary or gastrointestinal infections, generally in individuals positive for HLA-B27.Septic arthritis and microcrystalline arthritis can mimic ReA and they must be ruled out with arthrocentesis.ReA may be considered as a complication in patients under iBCG., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interest, (© EFIM 2020.)

The etiology of multiple sclerosis (MS) is still not known, but the interaction of genetic, immunological, and environmental factors seem to be involved. This study aimed to investigate genetic alterations and the vitamin D status in patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS). A total of 53 patients (29 RRMS; 24 SPMS) and 25 healthy subjects were recruited to evaluate the micronucleated cell (MNC) frequency and nuclear abnormalities in the buccal mucosa, gene expression profiling in mononuclear cells, and plasmatic vitamin D concentration in the blood. Results showed a higher frequency of cells with karyorrhexis (SPMS) and lower frequencies of nuclear pyknosis (RRMS and SPMS) and karyolysis (SPMS) in patients with MS. Significant increase in the frequency of MNC was detected in the buccal mucosa of RRMS and SPMS patients. HIF1A, IL13, IL18, MYC, and TNF were differentially expressed in MS patients, and APP was overexpressed in cells of RRMS compared to SPMS patients. No relationship was observed between vitamin D level and the differentially expressed genes. In conclusion, the cytogenetic alterations in the buccal mucosa can be important indicators of genetic instability and degenerative processes in patients with MS. Furthermore, our data introduced novel biomarkers associated with the molecular pathogenesis of MS.

The antitumor activity of resveratrol, a polyphenolic compound found mainly in grapes, has been studied in several types of cancer. In bladder cancer, its antiproliferative effects have already been demonstrated; however, its mechanism of action is not completely understood. The aim of this study was to evaluate resveratrol antitumor activity (12.5, 25, 50, 100, 150, 200, and 250 μM) and its possible mechanisms of action in bladder tumor cells with different TP53 gene status (RT4, grade 1, TP53 wild type; 5637-grade 2 and T24-grade 3, TP53 mutated). Cell proliferation, clonogenic survival, morphological changes, cell cycle progression, apoptosis rates, genotoxicity, global methylation, immunocytochemistry for p53 and PCNA and relative expression profiles of the AKT, mTOR, RASSF1A, HOXB3, SRC, PLK1, and DNMT1 were evaluated. Resveratrol decreased cell proliferation and induced DNA damage in all cell lines. Regarding the long-term effects, resveratrol reduced the number of colonies in all cell lines; however, TP53 wild type cells were more resistant. Increased rates of apoptosis were found in the TP53 wild type cells and this was accompanied by AKT, mTOR, and SRC downregulation. In addition, the resveratrol antiproliferative effects in wild type TP53 cells were accompanied by modulation of the DNMT1 gene. In the TP53 mutated cells, cell cycle arrest at S phase with PLK1 downregulation was observed. Additionally, there was modulation of the HOXB3/RASSF1A pathway and nuclear PCNA reduction in the highest-grade cells. In conclusion, resveratrol has antiproliferative activity in bladder tumor cells; however, the mechanisms of action are dependent on TP53 status. Environ. Mol. Mutagen., 60:740-751, 2019. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)