•Exposure to EDCs is associated with global DNA demethylation in murine N2A neuroblastoma cells.•Adipocyte differentiation in vitro is accompanied by global DNA demethylation.•Flame retardant BDE47 ...increases adipocyte differentiation in murine 3T3-L1 cells.•TBT induces both global DNA demethylation and adipocyte differentiation in vitro.
Recent studies suggest that endocrine disrupting chemicals (EDCs) may form a risk factor for obesity by altering energy metabolism through epigenetic gene regulation. The goal of this study is to investigate the effects of a range of EDCs with putative obesogenic properties on global DNA methylation and adipocyte differentiation in vitro. Murine N2A and human SK-N-AS neuroblastoma cells and murine preadipocyte fibroblasts (3T3-L1) were exposed to tributyltin (TBT), diethylstilbestrol (DES), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153), hexachlorobenzene (HCB), hexabromocyclododecane (HBCD), 2,2′,4,4′-tetrabrominated diphenyl ether (BDE-47) , perfluorinated octyl acid (PFOA) and perfluorinated octyl sulfonate (PFOS). A modest decrease in global DNA methylation was observed in N2A cells exposed to 10μM DES, BPA, TCDD, BDE-47, PCB-153 and 1μM HCB, but no changes were found in the human SK-N-AS cells. We reveal for the first time that BDE-47 increases adipocyte differentiation in a dose-dependent manner (2.5–25μM). Adipocyte differentiation was also enhanced by TBT (⩾10nM) and BPA (>10μM) and inhibited by TCDD (⩾0.1nM). The other chemicals showed either modest or no effects on adipocyte differentiation at the concentrations tested (PFOA, PFOS and HBCD at 10μM; PCB-153, 3.4μM and HCB, 1μM). This study demonstrates that selected EDCs can induce functional changes in murine adipocyte differentiation in vitro which are accompanied by decreased global DNA methylation.
Perfluorooctanoic acid (PFOA) is known to cause developmental toxicity and is a suggested endocrine disrupting compound (EDC). Early life exposure to EDCs has been implicated in programming of the ...developing organism for chronic diseases later in life. Here we study perinatal metabolic programming by PFOA using an experimental design relevant for human exposure. C57BL/6JxFVB hybrid mice were exposed during gestation and lactation via maternal feed to seven low doses of PFOA at and below the NOAEL used for current risk assessment (3–3000 µg/kg body weight/day). After weaning, offspring were followed for 23–25 weeks without further exposure. Offspring showed a dose-dependent decrease in body weight from postnatal day 4 to adulthood. Growth under high fat diet in the last 4–6 weeks of follow-up was increased in male and decreased in female offspring. Both sexes showed increased liver weights, hepatic foci of cellular alterations and nuclear dysmorphology. In females, reductions in perigonadal and perirenal fat pad weights, serum triglycerides and cholesterol were also observed. Endocrine parameters, such as glucose tolerance, serum insulin and leptin, were not affected. In conclusion, our study with perinatal exposure to PFOA in mice produced metabolic effects in adult offspring. This is most likely due to disrupted programming of metabolic homeostasis, but the assayed endpoints did not provide a mechanistic explanation. The BMDL of the programming effects in our study is below the current point of departure used for calculation of the tolerable daily intake.
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•Four flavonoids were described for the first time in the Brosimum genus.•Two new flavonoids were isolated from the bark of B. parinarioides.•All isolated flavonoids were described ...for the first time in the Moraceae family.•The chemotaxonomic significance of flavonoids for Brosimum genus was discussed.
The objective of this study was to evaluate the effect of administering injectable progesterone (P4i) before a timed artificial insemination (TAI) protocol on the follicular growth, ovulation, and ...pregnancy rate of Bos taurus suckled cows. The effect of P4i administration before the TAI on the pregnancy rate (P/AI) was evaluated in 576 suckled Bos taurus cows at 30–90 days postpartum. In addition, the effect of P4i administration before TAI on follicular dynamics was evaluated in subgroup of 401 suckled Bos taurus cows. On Day −10 (D-10), cows were divided into two experimental groups (Control and P4i). In this moment, P4i cows received i.m. 150 mg of injectable long-action progesterone. After that, both experimental groups received a synchronization protocol (Day 0; D0) that consisted of administration i.m. of 2 mg of estradiol benzoate and a progesterone intravaginal insert on D0. On Day 8 (D8), the progesterone insert was removed, and the cows received 500 μg of cloprostenol, 400 IU of eCG, and 1 mg of estradiol cypionate. TAI was performed 48 h after the removal of the progesterone insert. The ultrasound exams were performed in a subgroup of cows on Days 0, 8, 10 and 12 to evaluate the diameter of the largest follicle, rate of follicular growth and risks of single and double ovulation. The pregnancy diagnosis was performed 30 days after TAI in all cows to determine the pregnancy rate. The diameter of the largest follicle, on D10 (P = 0.84), rate of follicular growth (P = 0.14), ovulation rate (P = 0.40) and double ovulation rates (P = 0.23) did not differ between experimental groups. The pregnancy rate was greater in the P4i group Control 46.2 % (133/288) vs. P4i 55.6 % (160/288); P = 0.03. The diameter of the largest follicles (LF) on D0 (Control 11.6 ± 0.2 vs. P4i 13.3 ± 0.3) was greater (P = 0.01) in the P4i group. In conclusion, injectable progesterone before the ovulation synchronization protocol increased the diameter of the largest follicle on the D0 and the pregnancy rate in multiparous Bos taurus suckled beef cows.
•Exposure to progesterone previous TAI increased P/AI in multiparous Bos taurus cows.•Multiparous Bos taurus cows in estrous in the TAI protocol have greater fertility.•Follicles on D0 and D8 were greater in cows pretreated with injectable progesterone.
TOXICOLOGICAL STRESS IN A HIGHLY IMPACTED RIVER FROM THE PORT ENVIRONMENT OF SANTOS, SP. There are many stilts and industry, which discharge sewage, domestic garbage and industrial effluents in the ...Pouca Saúde River from the port environment of Santos, São Paulo (SP) State. However, ecotoxicological studies in this river are rare. In this study, we seek to fill this gap by analyzing physicochemical, toxicological, and chemical conditions. Surface water and sediment samples were collected at 2 sampling sites with riparian community activities and industrial activities in the summer, autumn, winter and spring. The parameters analyzed were pH, alkalinity, turbidity, salinity, oils, greases, dissolved oxygen (DO), toxicological and cytotoxicity with mitotic index (MI) of onion roots using Allium cepa roots, and concentration of Pb, Zn, Hg, Ni and Cd. Our results showed alterations in the DO, turbidity, oils/greases and reduction of MI when compared to the respective control. Ni and Zn in sediment samples presented concentrations exceeding levels occasionally associated with adverse biological effects “threshold effect level”. These results suggested that the water quality of the Pouca Saúde River is influenced by both presences of heavy metals contamination and the seasons, i.e. by the tide. Thus, the toxic potential monitoring carried out in this study is of paramount importance to this river.
The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop ...and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones.
Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients.
Median (25-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO
/FiO
ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829-0.859), which was confirmed in the Brazilian (0.859 95% CI 0.833-0.885) and Spanish (0.894 95% CI 0.870-0.919) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/).
An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.
Cryptococcosis therapy is often limited by toxicity problems, antifungal tolerance, and high costs. Studies approaching chalcogen compounds, especially those containing selenium, have shown promising ...antifungal activity against pathogenic species. This work aimed to evaluate the
and
antifungal potential of organoselenium compounds against Cryptococcus neoformans. The lead compound LQA_78 had an inhibitory effect on C. neoformans planktonic cells and dispersed cells from mature biofilms at similar concentrations. The fungal growth inhibition led to an increase in budding cells arrested in the G
/M phase, but the compound did not significantly affect structural cell wall components or chitinase activity, an enzyme that regulates the dynamics of the cell wall. The compound also inhibited titan cell (Tc) and enlarged capsule yeast (NcC) growth and reduced the body diameter and capsule thickness associated with increased capsular permeability of both virulent morphotypes. LQA_78 also reduced fungal melanization through laccase activity inhibition. The fungicidal activity was observed at higher concentrations (16 to 64 μg/mL) and may be associated with augmented plasma membrane permeability, ROS production, and loss of mitochondrial membrane potential. While LQA_78 is a nonhemolytic compound, its cytotoxic effects were cell type dependent, exhibiting no toxicity on Galleria mellonella larvae at a dose ≤46.5 mg/kg. LQA_78 treatment of larvae infected with C. neoformans effectively reduced the fungal burden and inhibited virulent morphotype formation. To conclude, LQA_78 displays fungicidal action and inhibits virulence factors of C. neoformans. Our results highlight the potential use of LQA_78 as a lead molecule for developing novel pharmaceuticals for treating cryptococcosis.
This work presents an experimental current measurement set based on a Lead Zirconate Titanate (PZT) ceramic for AC (60 Hz) current measurement. The proposed device is built using a PZT rectangular ...plate ceramic with one fixed end. A permanent magnet is mounted to the other end of the plate. The interaction between a magnetic field (B) and the device creates a mechanical vibration. Due to the piezoelectric effect, a voltage is presented at the output terminals of the device. This output is proportional to the magnitude of the current flowing in the wire. We present experimental results of the AC 60 Hz current measurement on the 15–110 A. The good sensitivity of the device (approximately 20 mV/A) for a distance of 1.5 cm between device and the magnetic B-field source must be highlighted.
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