Artisanal Gem Mining in Brazil: Evaluation of Oxidative Stress and Genotoxicity Biomarkers.

This study was carried out in the district of Taquaral de Minas, in the municipality of Itinga, located in Jequitinhonha Valley, state of Minas Gerais, which is considered one of the largest yolk-producing regions in Brazil. Miners in gem extraction areas are prone to severe oxidative damage due to their increased exposure to toxic metals, as well as chemical, physical, and biological agents, resulting in diseases such as silicosis. Thus, this work aimed to evaluate occupational exposure in prospectors through biomonitoring techniques using a variety of biomarkers for oxidative stress, genotoxicity, and mutagenicity. Twenty-two miners and seventeen workers who were not occupationally exposed were recruited, totaling thirty-nine participants. The study was approved by the Research Ethics Committee of the Federal University of the Jequitinhonha and Mucuri Valleys. In this study, the levels of total peroxides, catalase activity, and microelements in plasma were evaluated. Additionally, environmental analysis was carried out through the Ames and Allium cepa tests. The results of the lipoperoxidation assessment were significant, with increased frequencies in exposed individuals compared to controls (p < 0.05), as determined by the Mann-Whitney test. Micronutrients in the blood showed lower concentrations in the group exposed to Fe and Se than in individuals not exposed to these elements. The results of the Ames test and Allium cepa test were statistically significant compared to the controls (p < 0.05), as determined by the Mann-Whitney test for genotoxicity and cytotoxicity. Thus, the results of the present study indicate possible environmental contamination and a potential risk to the health of miners, which suggests that further studies are important in the region.

Contribution of nanotechnology to greater efficiency in animal nutrition and production.

Feed costs present a major burden in animal production for human consumption, representing a key opportunity for cost reduction and profit improvement. Nanotechnology offers potential to increase productivity by creating higher-quality and safer products. The feed sector has benefited from the use of nanosystems to improve the stability and bioavailability of feed ingredients. The development of nanotechnology products for feed must consider the challenges raised by biological barriers as well as regulatory requirements. While some nanotechnology-based products are already commercially available for animal production, the exponential growth and application of these products requires further research ensuring their safety and the establishment of comprehensive legislative frameworks and regulatory guidelines. Thus, this article provides an overview of the current state of the art regarding nanotechnology solutions applied in feed, as well as the risks and opportunities aimed to help researchers and livestock producers.

Assessment of Health Risk and Presence of Metals in Water and Fish Samples from Doce River, Brazil, After Fundão Dam Collapse.

The rupture of the Fundão dam released about 50 million m3 of mining tailings in the Doce river basin. To assess the potential for environmental contamination and the risks of residual exposure of the human population generated by these tailings, water and fish samples from the Doce river were collected 25 days after the accident and analyzed the physicochemical parameters of the water and levels of metals by ICP-MS, in addition to the temporal variability of the concentration of these elements through other studies. This was the first study to carry out an assessment of the health risk associated with the consumption of fish contaminated by metals from the areas affected by the disaster. The values of turbidity (5460 NTU), electrical conductivity (74.8 µS cm-1), total dissolved solids (892 mg L-1) and total suspended solids (772 mg L-1) were above the maximum limit allowed by Brazilian legislation, due to the presence of large amounts of solid materials released after the dam rupture. The analysis of metals in water samples indicated high concentrations of Al (1,906.71 µg L-1), Mn (370.32 µg L-1), Fe (8,503.50 µg L-1) and Hg (34.25 µg L-1), while for the fish samples, only As (1,033.98 µg kg-1) and Hg (herbivorous: 505.32 µg kg-1; predatory: 1,184.09 µg kg-1) presented levels above those established by Brazilian legislation. The health risk assessment showed that the estimated daily intake for Hg was higher than the reference dose, reinforcing the need for monitoring the area affected by the disaster.

Arsenic in Mining Areas: Environmental Contamination Routes.

The emission and accumulation of toxic elements such as arsenic in various environmental compartments have become increasingly frequent primarily due to anthropogenic actions such as those observed in agricultural, industrial, and mining activities. An example of environmental arsenic contamination in Brazil exists in the city of Paracatu, MG, due to the operation of a gold mine. The aim of this work is to evaluate the routes and effects of arsenic contamination in environmental compartments (air, water, and soil) and environmental organisms (fish and vegetables) from mining regions as well as the trophic transfer of the element for a risk assessment of the population. In this study, high levels of arsenic were found in the waters of the Rico stream ranging from 4.05 µg/L during the summer season to 72.4 µg/L during the winter season. Moreover, the highest As concentration was 1.668 mg kg-1 in soil samples, which are influenced by seasonal variation and by proximity to the gold mine. Inorganic and organic arsenic species were found above the allowed limit in biological samples, indicating the transfer of arsenic found in the environment and demonstrating a great risk to the population exposed to this area. This study demonstrates the importance of environmental monitoring to diagnose contamination and encourage the search for new interventions and risk assessments for the population.

Artisanal Gem Mining in Brazil: A Source of Genotoxicity and Exposure to Toxic Elements.

Environmental and occupational exposure to toxic metals has led many people around the world to have serious health problems. Mining activities contribute to an increased risk of exposure to these elements. In this work, a study of environmental biomonitoring and routes of exposure to toxic metals in a region of artisanal mining was performed. This study was carried out in the district of Taquaral de Minas, located in the Jequitinhonha Valley in the state of Minas Gerais. The valley is one of the wealthiest and highest gem-producing areas in Brazil. Five artisanal mines were sampled (Bode, Pirineu, Pinheira, Lajedo, and Marmita). Several potentially toxic metals (Be, Zn, Mn, Ba Cd, Hg, and U) were investigated in the soils and dust over the rocks and the soils. Samples from 22 individuals occupationally exposed and 17 unexposed persons, who formed the reference group, were analyzed for trace elements by an inductively coupled plasma mass spectrometer. The genotoxicity was evaluated by the micronucleus test in buccal mucosa epithelial cells, where the following changes were scored: micronuclei (MN) binucleate (BN) cells and kariolytic (KL) cells. The MN test showed significantly increased frequencies in all alterations of exposed individuals compared to the controls (p < 0.05, Student's t-test). The urine analysis showed levels of Cr, Ni Ba, Pb, and As in the blood, which were higher than the ATSDR recommended levels. The association between the MN test and the trace element concentrations found in the blood and urine was significant (p < 0.05). The higher the number of years of working, the higher the concentrations in the blood were, due to chronic exposure. The results of the present study indicate environmental contamination and a potential risk to the health of miners, suggesting an intervention.

Adherens Junction Integrity Is a Critical Determinant of Sodium Iodide Symporter Residency at the Plasma Membrane of Thyroid Cells.

While most cases of differentiated thyroid carcinoma (DTC) are associated with a good prognosis, a significant number progress to advanced disease exhibiting aggressive clinical characteristics and often becoming refractory to radioactive iodine (RAI) treatment, the current gold-standard therapeutic option for metastatic disease. RAI-refractoriness is caused by defective functional expression of the sodium-iodide symporter (NIS), which is responsible for the active transport of iodide across the plasma membrane (PM) into thyroid follicles. NIS deficiency in these tumors often reflects a transcriptional impairment, but also its defective targeting and retention at the cells' PM. Using proteomics, we previously characterized an intracellular signaling pathway derived from SRC kinase that acts through the small GTPase RAC1 to recruit and bind the actin-anchoring adaptor EZRIN to NIS, regulating its retention at the PM of both non-transformed and cancer thyroid cells. Here, we describe how by reanalyzing the proteomics data, we identified cell-cell adhesion as the molecular event upstream the pathway involved in the anchoring and retention at the PM. We show that by interacting with NIS at the PM, adherens junction (AJ)-associated P120-catenin recruits and is phosphorylated by SRC, allowing it to recruit RAC1 to the complex. This enables SRC-phosphorylated VAV2 exchange factor to activate RAC1 GTPase, inducing NIS retention at the PM, thus increasing its abundance and function at the surface of thyroid cells. Our findings indicate that the loss of epithelial cell-cell adhesion may contribute to RAI refractoriness, indicating that in addition to stimulating NIS expression, successful resensitization therapies might require the employment of agents that improve cell-cell adhesion and NIS PM retention in refractory TC cells.

Degradation of Praguicide Disulfoton Using Nanocompost and Evaluation of Toxicological Effects.

Organophosphates (OPPs) are an important element of modern agriculture; however, because they are being used excessively, their residues are leaching and accumulating in the soil and groundwater, contaminating aquatic and terrestrial food chains. An important OPP called disulfoton is frequently used to eradicate pests from a wide range of crops, including Brazil's coffee crops. Additionally, it does not easily degrade in the environment, and as such, this compound can slowly build up in living organisms such as humans. Moreover, this compound has been classified as "extremely hazardous" by the World Health Organization. This study evaluated the degradation efficiency of disulfoton using a Fenton-like reaction catalyzed by magnetite nanoparticles and determined the toxicity of the by-products of the degradation process using the bioindicator Allium cepa. Further, the removal efficiency of disulfoton was determined to be 94% under optimal conditions. On the other hand, the Allium cepa bioassay showed different toxic, cytotoxic, genotoxic, and mutagenic outcomes even after the remediation process. In conclusion, the Fenton process catalyzed by magnetite nanoparticles presents great efficiency for the oxidation of disulfoton. However, it is important to highlight that the high degradation efficiency of the Fenton-based process was not sufficient to achieve detoxification of the samples.

Comparative analysis of origin and branches of phrenic nerve in the diaphragm of the crab-eating fox (Cerdocyon thous) and domestic dog (Canis lupus familiaris).

The crab-eating fox (Cerdocyon thous) is a canid widely distributed throughout South America, considered the only representative of the gender. There is a lack of information about anatomical aspects of the species, mainly regarded of nervous system anatomy. For clinical and surgical approaches of these animals, the domestic dog is adopted as anatomophysiological model. So, the aim of the present study was to analyse origin and branches of the phrenic nerve in the diaphragm of crab-eating fox compared to domestic dog. Four specimens of Cerdocyon thous and four of Canis lupus familiaris were used. The phrenic nerve originated from the ventral branches of the fifth (C5), sixth (C6) and seventh (C7) cervical spinal nerves. Phrenic nerves were distributed in the diaphragm as lumbocostal trunk and sternal branch (100%) in the crab-eating fox, and in costosternal trunk and lumbar branch (75%) and lumbocostal trunk and sternal branch (25%) in the domestic dog. In both species, the lumbar branch innervates the diaphragm pillars, the costal branch addresses all costal region, and the sternal branch distributes in the costal ventrolateral region and the sternal part of the diaphragm, to the left and to the right.

Determination of 14 trace elements in blood, serum and urine after environmental disaster in the Doce River basin: Relationship between mining waste and metal concentration in the population.

BACKGROUND: Exposure to chemical substances after an environmental disaster can cause both toxic effects and changes in the health status of people who live in or have proximity to environments of this nature, so that the concern with populations is growing. METHODS: In this cross-sectional study, blood, serum and urine samples were collected from 100 volunteers from Santo Antônio do Rio Doce, eight from Ilha das Pimentas and 50 from the control group; and analyzed by inductively coupled plasma mass spectrometry for biomonitoring of Al, As, Ba, Cd, Co, Cu, Cr, Fe, Hg, Mn, Ni, Se, Pb, Zn. In addition, a comprehensive questionnaire was applied to collect demographic and socioeconomic information, as well as lifestyle. RESULTS: The concentrations of As, Al, Cd, Ni and Mn were above the reference value in some biological matrices, with more pronounced exposure in Ilha das Pimentas. The concentrations of As, Cd, Cu, Co, Pb and Zn showed statistical differences regarding gender in the different biological matrices. The trace elements in the blood, serum and urine showed significant correlations when considering age and habits such as the consumption of cigarettes, alcoholic beverages and fish. The main correlations were observed between Co, Cr, Mn, Ni and Pb in the blood and cigarette consumption. CONCLUSION: This is the first study in these regions after the environmental disaster and confirmation of the diagnosis and health care of the participants should be promoted for clinical investigation and the eventual need for treatment. Human biomonitoring demonstrated high concentrations of some toxic elements, with more accentuated exposure in Ilha das Pimentas.

Analysis of NIS Plasma Membrane Interactors Discloses Key Regulation by a SRC/RAC1/PAK1/PIP5K/EZRIN Pathway with Potential Implications for Radioiodine Re-Sensitization Therapy in Thyroid Cancer.

The functional expression of the sodium-iodide symporter (NIS) at the membrane of differentiated thyroid cancer (DTC) cells is the cornerstone for the use of radioiodine (RAI) therapy in these malignancies. However, NIS gene expression is frequently downregulated in malignant thyroid tissue, and 30% to 50% of metastatic DTCs become refractory to RAI treatment, which dramatically decreases patient survival. Several strategies have been attempted to increase the NIS mRNA levels in refractory DTC cells, so as to re-sensitize refractory tumors to RAI. However, there are many RAI-refractory DTCs in which the NIS mRNA and protein levels are relatively abundant but only reduced levels of iodide uptake are detected, suggesting a posttranslational failure in the delivery of NIS to the plasma membrane (PM), or an impaired residency at the PM. Because little is known about the molecules and pathways regulating NIS delivery to, and residency at, the PM of thyroid cells, we here employed an intact-cell labeling/immunoprecipitation methodology to selectively purify NIS-containing macromolecular complexes from the PM. Using mass spectrometry, we characterized and compared the composition of NIS PM complexes to that of NIS complexes isolated from whole cell (WC) lysates. Applying gene ontology analysis to the obtained MS data, we found that while both the PM-NIS and WC-NIS datasets had in common a considerable number of proteins involved in vesicle transport and protein trafficking, the NIS PM complexes were particularly enriched in proteins associated with the regulation of the actin cytoskeleton. Through a systematic validation of the detected interactions by co-immunoprecipitation and Western blot, followed by the biochemical and functional characterization of the contribution of each interactor to NIS PM residency and iodide uptake, we were able to identify a pathway by which the PM localization and function of NIS depends on its binding to SRC kinase, which leads to the recruitment and activation of the small GTPase RAC1. RAC1 signals through PAK1 and PIP5K to promote ARP2/3-mediated actin polymerization, and the recruitment and binding of the actin anchoring protein EZRIN to NIS, promoting its residency and function at the PM of normal and TC cells. Besides providing novel insights into the regulation of NIS localization and function at the PM of TC cells, our results open new venues for therapeutic intervention in TC, namely the possibility of modulating abnormal SRC signaling in refractory TC from a proliferative/invasive effect to the re-sensitization of these tumors to RAI therapy by inducing NIS retention at the PM.

MAPK Inhibition Requires Active RAC1 Signaling to Effectively Improve Iodide Uptake by Thyroid Follicular Cells.

The Sodium/Iodide Symporter (NIS) is responsible for the active transport of iodide into thyroid follicular cells. Differentiated thyroid carcinomas (DTCs) usually preserve the functional expression of NIS, allowing the use of radioactive iodine (RAI) as the treatment of choice for metastatic disease. However, a significant proportion of patients with advanced forms of TC become refractory to RAI therapy and no effective therapeutic alternatives are available. Impaired iodide uptake is mainly caused by the defective functional expression of NIS, and this has been associated with several pathways linked to malignant transformation. MAPK signaling has emerged as one of the main pathways implicated in thyroid tumorigenesis, and its overactivation has been associated with the downregulation of NIS expression. Thus, several strategies have been developed to target the MAPK pathway attempting to increase iodide uptake in refractory DTC. However, MAPK inhibitors have had only partial success in restoring NIS expression and, in most cases, it remained insufficient to allow effective treatment with RAI. In a previous work, we have shown that the activity of the small GTPase RAC1 has a positive impact on TSH-induced NIS expression and iodide uptake in thyroid cells. RAC1 is a downstream effector of NRAS, but not of BRAF. Therefore, we hypothesized that the positive regulation induced by RAC1 on NIS could be a relevant signaling cue in the mechanism underlying the differential response to MEK inhibitors, observed between NRAS- and BRAF-mutant tumors. In the present study, we found that the recovery of NIS expression induced through MAPK pathway inhibition can be enhanced by potentiating RAC1 activity in thyroid cell systems. The negative impact on NIS expression induced by the MAPK-activating alterations, NRAS Q61R and BRAF V600E, was partially reversed by the presence of the MEK 1/2 inhibitors AZD6244 and CH5126766. Notably, the inhibition of RAC1 signaling partially blocked the positive impact of MEK inhibition on NIS expression in NRAS Q61R cells. Conversely, the presence of active RAC1 considerably improved the rescue of NIS expression in BRAF V600E thyroid cells treated with MEK inhibitors. Overall, our data support an important role for RAC1 signaling in enhancing MAPK inhibition in the context of RAI therapy in DTC, opening new opportunities for therapeutic intervention.

Spatiotemporal distribution and temporal trends of brucellosis and tuberculosis in water buffalo (Bubalus bubalis) in Brazil.

The buffalo herds in Brazil have been an alternative for increasing the economy in different biomes. For this reason, knowledge of the spatial distribution of diseases of mandatory notification in buffalo herds, such as brucellosis and tuberculosis, is essential to guarantee the quality of exported animal products, as well as assist in strategies of national control and eradication programs. In the present study, we aimed to evaluate the spatiotemporal distribution and temporal trends of brucellosis and tuberculosis in buffalo in Brazilian states between 2012-2019. During this period, 474 cases of brucellosis and 604 cases of tuberculosis were observed in buffalo in Brazil, with no significant differences between the total number of cases and incidence risk. The spatial distribution for the states was mostly heterogeneous, showing similarities of occurrences for both diseases in the south, north, and the states of Minas Gerais and Pernambuco. In the eight years evaluated, tuberculosis showed cyclical variation every 1-2 years; however, for brucellosis, there was a cyclical trend only between 2012-2015, with a significant decrease until 2018. Among Brazilian states, Pará had greater disease case numbers, with 34 % for brucellosis and 40.6 % for tuberculosis. Temporal trend analysis showed an increase for Pernambuco (annual percentage change [APC]: 21.0 [CI = 20.3; 21.8]), Paraná (APC: 27.1 [CI = 5.6; 53.0]), and Santa Catarina (APC: 10.4 [CI = 0.8; 21.0]) for brucellosis, and for tuberculosis, only for Santa Catarina state (APC: 24.1 [CI = 15.5; 33.3]). Spatiotemporally, there were four high-risk brucellosis clusters with a primary cluster, cluster A (relative risk [RRs] = 53.42, P < 0.001), involving the state of Amazonas between 2014-2015. For tuberculosis, there were three states of high risk, with a primary cluster, cluster E (RRs = 28.18, P < 0.001), involving the states of Pará, Roraima, Amazonas, Rondônia, and Acre in 2014. In conclusion, brucellosis and tuberculosis in buffalo in Brazil are heterogeneously distributed, with well-defined regions of high historical risk of infection. Among these regions, the states of Amazonas, Pará, Amapá, and Minas Gerais stand out due to the higher risk of infection for both brucellosis and tuberculosis, alerting Brazilian authorities to the need for disease control actions.

Iron Oxide Nanomaterials for the Removal of Cr(VI) and Pb(II) from Contaminated River After Mariana Mining Disaster.

If not properly treated, water contaminated with chromium (Cr(VI)) and lead (Pb(II)) can cause severe damage to health due to the accumulation of those toxic metals in the human body. Therefore, in this work, three iron oxides, i.e., δ-FeOOH, cystine-functionalized δ-FeOOH (Cys-δ-FeOOH), and Fe3O4, were synthesized and used as adsorbents for Cr(VI) and Pb(II) in water. The results indicated that the Cr(VI) is best adsorbed on cys-δ-FeOOH followed by δ-FeOOH and Fe3O4. It was because of the enhanced interaction between Cr(VI) and the cysteine functional groups on the δ-FeOOH surface. The Cr(VI) adsorption capacity of cys-δ-FeOOH, δ-FeOOH, and Fe3O4 was 217, 14, and 8 mg g-1, respectively. On the other hand, Pb(II) was preferentially adsorbed directly on δ-FeOOH achieving a maximum Pb(II) adsorption capacity of 174 mg g-1. The Pb(II) adsorption capacity of cys-δ-FeOOH and Fe3O4 was 97 and 74 mg g-1, respectively. The Cr(VI) adsorption on cys-δ-FeOOH was best described by the Langmuir-Freundlich model, whereas Pb(II) adsorption on δ-FeOOH followed the Langmuir model. Both Cr(VI) and Pb(II) adsorption on the adsorbents was well-fitted to pseudo-second-order kinetics. The Cr(VI) was more quickly adsorbed by cys-δ-FeOOH (h0 = 0.10 mg g-1 min-1) while the initial adsorption rate of Pb(II) onto δ-FeOOH was significantly faster (h0 = 16.34 mg g-1 min-1). Finally, the synthesized adsorbents were efficient to remove Cr(VI) and Pb(II) from water samples of the Doce river after the environmental disaster of Mariana city, Brazil, thus showing its applicability to remediate real water samples.

Purification of arsenic-contaminated water using iron molybdate filters and monitoring of their genotoxic, mutagenic, and cytotoxic effects through bioassays.

Environmental contamination has been a cause of concern worldwide, being aggravated by anthropogenic activities carried out without the correct disposal of toxic products in the various habitats on our planet. In Brazil, mining companies are responsible for the contamination of large river basins with toxic elements from mining activities. Among these elements, arsenic draws attention because it is highly carcinogenic and found in waters in concentrations above those recommended by regulatory agencies. Here, Fe2(MoO4)3 nanoparticles are synthesized and used as a filter medium in water purification systems contaminated with arsenic. The adsorption kinetics of arsenic by Fe2(MoO4)3 nanoparticles is fast, showing pseudo-second-order rate constants of 0.0044, 0.0080, and 0.0106 g mg-1 min-1 for As3+, As5+, and MMA, respectively. The adsorption isotherms are better adjusted with the Langmuir and Redlich-Peterson models, indicating that the arsenic adsorption occurs in monolayers on the Fe2(MoO4)3 surface. The Fe2(MoO4)3 adsorption capacities determined for the As3+, As5+, and MMA species are 16.1, 23.1, and 23.5 mg g-1, respectively. The Fe2(MoO4)3 filter is efficient in purifying arsenic-contaminated water, reducing its initial concentration from 1000 µg L-1 to levels close to zero. Biological tests indicate that Fe2(MoO4)3 nanoparticles and filtered water have no cytotoxic, genotoxic, and mutagenic risks to human life. Those results suggest that the Fe2(MoO4)3 filter can be used as an efficient and safe technology for the purification of water contaminated by arsenic.

Inflammatory Microenvironment Modulation of Alternative Splicing in Cancer: A Way to Adapt.

The relationship between inflammation and cancer has been long recognized by the medical and scientific community. In the last decades, it has returned to the forefront of clinical oncology since a wealth of knowledge has been gathered about the cells, cytokines and physiological processes that are central to both inflammation and cancer. It is now robustly established that chronic inflammation can induce certain cancers but also that solid tumors, in turn, can initiate and perpetuate local inflammatory processes that foster tumor growth and dissemination. Inflammation is the hallmark of the innate immune response to tissue damage or infection, but also mediates the activation, expansion and recruitment to the tissues of cells and antibodies of the adaptive immune system. The functional integration of both components of the immune response is crucial to identify and subdue tumor development, progression and dissemination. When this tight control goes awry, altered cells can avoid the immune surveillance and even subvert the innate immunity to promote their full oncogenic transformation. In this chapter, we make a general overview of the most recent data linking the inflammatory process to cancer. We start with the overall inflammatory cues and processes that influence the relationship between tumor and the microenvironment that surrounds it and follow the ever-increasing complexity of processes that end up producing subtle changes in the splicing of certain genes to ascertain survival advantage to cancer cells.

TNFα-mediated activation of NF-κB downregulates sodium-iodide symporter expression in thyroid cells.

The sodium-iodide symporter (NIS) mediates transport of iodide across the basolateral membrane of thyroid cells. NIS expression in thyroid cancer (TC) cells allows the use of radioactive iodine (RAI) as a diagnostic and therapeutic tool, being RAI therapy the systemic treatment of choice for metastatic disease. Still, a significant proportion of patients with advanced TC lose the ability to respond to RAI therapy and no effective alternative therapies are available. Defective NIS expression is the main reason for impaired iodide uptake in TC and NIS downregulation has been associated with several pathways linked to malignant transformation. NF-κB signaling is one of the pathways associated with TC. Interestingly, NIS expression can be negatively regulated by TNF-α, a bona fide activator of NF-κB with a central role in thyroid autoimmunity. This prompted us to clarify NF-kB's role in this process. We confirmed that TNF-α leads to downregulation of TSH-induced NIS expression in non-neoplastic thyroid follicular cell-derived models. Notably, a similar effect was observed when NF-κB activation was triggered independently of ligand-receptor specificity, using phorbol-myristate-acetate (PMA). TNF-α and PMA downregulation of NIS expression was reverted when NF-κB-dependent transcription was blocked, demonstrating the requirement for NF-kB activity. Additionally, TNF-α and PMA were shown to have a negative impact on TSH-induced iodide uptake, consistent with the observed transcriptional downregulation of NIS. Our data support the involvement of NF-κB-directed transcription in the modulation of NIS expression, where up- or down-regulation of NIS depends on the combined output to NF-κB of several converging pathways. A better understanding of the mechanisms underlying NIS expression in the context of normal thyroid physiology may guide the development of pharmacological strategies to increase the efficiency of iodide uptake. Such strategies would be extremely useful in improving the response to RAI therapy in refractory-TC.

Removal of mercury(II) from contaminated water by gold-functionalised Fe3O4 magnetic nanoparticles.

Fe3O4 nanoparticles were prepared by co-precipitation of Fe2+ and Fe3+ and then modified with Au to produce an effective adsorbent (Fe3O4/Au) for aqueous Hg(II) in contaminated water. Rietveld refinement on the XRD pattern confirmed that the Fe3O4/Au was synthesised. Mössbauer spectra exhibited broad and asymmetric resonance lines with two sextets which can be assigned to tetrahedral Fe3+; and octahedral Fe3+/Fe2+. The quantitative analysis of magnetite confirms that the sample shows around 3 wt.% Au and 97 wt.% partially oxidised Fe3O4. High surface area: 121 m2 g-1, average pore sizes: 6.3 nm and pore volume: 1.64 cm3 g-1. The kinetics data were better fitted with a pseudo-second-order and Dubinin-Radushkevich isotherm suggests the Hg(II) adsorption onto Fe3O4/Au nanoparticles was mainly by chemical adsorption forming complex with the Au metal immobilised on Fe3O4 surfaces. Adsorption capacity of 79.59 mg g-1. Ionic strength and co-existing ions had a slight influence on the adsorption capacity.

Isolation and characterization of bacteria from a brazilian gold mining area with a capacity of arsenic bioaccumulation.

In Paracatu, a city in Minas Gerais State (Brazil), the gold mineral extraction produces wastes that contribute to environmental contamination by arsenic. This work describes the evaluation of arsenic concentration from soil of a gold mining area in Paracatu and the selection of arsenic resistant bacteria. In the process of culturing enrichment, 38 bacterial strains were isolated and the minimum inhibitory concentration (MIC) was determined in solid medium for each strain. Three bacterial strains named P1C1Ib, P2Ic and P2IIB were resistant to 3000 mg L-1 of arsenite. Analysis of 16S rDNA gene sequences revealed that these bacteria belong to Bacillus cereus and Lysinibacillus boronitolerans species. After cultivation of the strains P1C1Ib, P2Ic and P2IIIb, 69.38%-71.88% of arsenite and 82.39%-85.72% of arsenate concentrations were reduced from the culture medium, suggesting the potential application of theses strains in bioremediation processes.

Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroid.

Thyroid cancer (TC) is the most common endocrine malignancy. The sodium-iodide symporter (NIS), responsible for active transport of iodide into thyroid cells, allows the use of radioactive iodine (RAI) as the systemic treatment of choice for TC metastatic disease. Still, patients with advanced forms of TC often lose the ability to respond to RAI therapy, which results in worse survival rates. We have shown that the overexpression of RAC1b, a tumor-related RAC1 splice variant, is associated with less favorable clinical outcomes in differentiated TCs derived from the follicular epithelial (DTCs). RAC1b overexpression is also significantly associated with the presence of MAPK-activating BRAFV600E mutation, which has been previously implicated in the loss of NIS expression. Here, we show that increased RAC1b levels are associated with NIS downregulation in DTCs and demonstrate that ectopic overexpression of RAC1b in non-transformed thyroid cells is sufficient to decrease TSH-induced NIS expression, antagonizing the positive effect of the canonically spliced RAC1 GTPase. Moreover, we clearly document for the first time in thyroid cells that both NIS expression and iodide uptake are hampered by RAC1 inhibition, highlighting the role of RAC1 in promoting TSH-induced NIS expression. Our findings support a role for RAC1 and RAC1b signaling in the regulation of NIS expression in thyroid cells and suggest that RAC1b in cooperation with other cancer-associated signaling cues may be implicated in the response of DTCs to RAI therapy.

Degradation of haloacetic acids with the Fenton-like and analysis by GC-MS: use of bioassays for monitoring of genotoxic, mutagenic and cytotoxic effects.

In this study, a method was developed to evaluate the degradation of haloacetic acids (HAAs) in water by a heterogenous Fenton-like process catalyzed by cobalt-doped magnetite nanoparticles (Fe3 - xCoxO4), extraction of the contaminants by liquid-liquid extraction (LLE), and analysis by gas chromatography-mass spectrometry (GC-MS). The developed method was efficient in the degradation of HAAs, with the following degradation values: 63%, 62%, 30%, 39%, 37%, 50%, 84%, 41%, and 79% for monochloroacetic acid, monobromoacetic acid, dichloroacetic acid, trichloroacetic acid, bromochloroacetic acid, dibromoacetic acid, bromodichloroacetic acid, dibromochloroacetic acid, and tribromoacetic acid compounds, respectively. Through the application of the Allium cepa test, the cytotoxicity, genotoxicity, and mutagenicity of HAAs were evaluated. The results confirm its genotoxic and mutagenic effects on Allium cepa meristematic cells. Through this study, it was possible to verify the effectiveness of the developed method and its potential as a proposal for environmental remediation.